Natural Treatment to get rid of Kidney Problems

Kidney Function Restoration Program

The All Natural Kidney Health & Kidney Function Restoration Program is a compilation of the best and most effective natural treatments for kidney disease from around the world. The system is meant to complement your usual medication and not to replace it. This easy to understand kidney disease program can help you make better-informed decisions about what is the right thing to do to support your kidney and return it to its former healthy state. The techniques shared in this program will help cure and retain your kidney back to its natural wellness. You may even be able to postpone or entirely avoid dialysis or a kidney transplant forever. The All Natural Kidney Health and Kidney Function Restoration Program contain zero filler and is fully backed by modern-day scientific research. Everything contained in this program is safe, natural, and with good safety profiles, proven case studies and doctor recommended. Many of the products including the diet, herbs, and supplements have been used safely in other countries for many years and in several hospitals in the United States. Continue reading...

Kidney Function Restoration Program Summary


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Immunosuppression For Kidney Transplantation

All kidney transplant recipients require life-long immunosuppression to prevent a T-cell alloimmune rejection response. Many immunosuppressive agents have been approved by the Federal Drug Administration (FDA), and several more are in phase 3 clinical trials. There are two broad classifications of immunosuppressive agents intravenous induction anti-rejection agents, and maintenance immunotherapy agents. There is no consensus as to the single best immunosuppressive protocol and each transplant program utilizes the various combinations of agents slightly differently. The goals of each of the programs are similar to prevent acute and chronic rejection, to minimize the toxicities of the agents, to minimize the rates of infection and malignancy, and to achieve the highest possible rates of patient and graft survival. A. Therapeutic Use of Immunosuppression in Kidney Transplantation

Outcomes Of Kidney Transplantation

The results of kidney transplantation are defined according to the specific endpoint studied. The broad endpoints include patient survival and renal allograft survival. More specific endpoints have been examined such as the incidence and severity of rejection episodes, quality of renal allograft function, hospitalizations, and even economic data. Outcomes may be reported from various sources including national databases or in multi-center trials, and single-center experiences. Over the past 15 years the results of kidney transplantation have steadily improved with appreciation of the medical nuances of each case, and the development of new immunosuppressive and antimicrobial agents.24 The outcome of kidney transplantation is influenced by many variables (Table 6.10). Some of these that will be discussed include donor source, degree of HLA mismatch, PRA level, race, etiology of renal disease, duration of pre-transplant dialysis therapy, delayed graft function, and the transplant center...

Impaired renal function

Progression of liver disease may result in hepatorenal syndrome. This is characterized by reduced glomerular filtration rate, hyponatremia with water intoxication, and almost complete sodium reabsorption. Since the main role of the kidney is excretion, the first dose of drugs used in renal failure is usually unchanged again, it is subsequent doses that may need modification. One exception is suxamethonium which should be used with extreme caution in acute renal failure because of the risk of hyperkalemia. Other effects of renal disease may also change drug effects. These may include the following

Contrast media nephropathy

Renal dysfunction following radiocontrast media is rare in patients with normal renal function but more common in those with renal disease, particularly diabetic nephropathy. The most important prophylactic measure against contrast nephropathy is maintenance of hydration. Risk of renal dysfunction is also reduced by using smaller volumes of contrast and avoiding repeated doses at short time intervals. Use of non-ionic contrast media is associated with less renal dysfunction in patients with pre-existing renal disease. Prophylaxis with mannitol, furosemide, dopamine, and ANP has had variable results.

Other causes of acute intrinsic renal failure

Other less common etiologies of ARF include acute allergic interstitial nephritis, characterized by inflammatory cell infiltration and interstitial edema. It is typically induced by antibiotics (penicillins, cephalosporins, and sulfonamides), diuretics (hydrochlorothiazide), non-steroidal anti-inflammatory drugs, allopurinol, and angiotensin-converting enzyme inhibitors (captopril). Renal artery or vein occlusion and glomerulonephritis may also reduce glomerular filtration rate and generate ARF, the etiology of which is often suspected by the clinical setting.

Acute renal failure

The term acute renal failure (ARF), like acute respiratory failure and congestive cardiac failure, simply and broadly defines a clinical syndrome. This syndrome is characterized by an abrupt decrease in glomerular filtration rate, a rapid deterioration in renal function, and the accumulation in blood of nitrogenous waste products. 1. Does this patient presenting with an elevated plasma urea and serum creatinine concentration have acute, rapidly progressive, or chronic renal failure 2. What is the etiology of this patient's acute renal failure 3. What investigations should be performed to confirm the diagnosis and establish an etiology Acute, rapidly progressive, or chronic renal failure The differentiation of acute from rapidly progressive or chronic renal failure is important because it helps in the etiological diagnosis and can usually be made on history alone. In most cases seen in the ICU, one is dealing with patients with known near-normal or moderately impaired renal function...

Prerenal renal or postrenal kidney failure

Acute renal failure is diminished renal blood flow (so-called prerenal ARF). This type of ARF can be induced by a variety of insults ranging from hemorrhage to septic A very accurate drug-intake history should be taken to assess the possibility of nephrotoxic ARF. Attention should be paid to the use of angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs, and antibiotics. The finding of eosinophils in the urine suggests a drug-induced allergic nephropathy. A full blood examination, including a blood film, and standard biochemical tests for electrolytes and liver function are mandatory. If there are clinical and laboratory features suggesting that ARF is due to parenchymal renal disease, several other investigations may become necessary. A markedly elevated sedimentation rate, an elevated or abnormally low white cell count in the absence of infection or the presence of eosinophilia, a blood film suggesting hemolysis, serological studies positive for...

Prerenal azotemia or established acute renal failure

In the context of a hypovolemic, hypotensive, or hypoxic insult, having excluded renal or postrenal cause of ARF, several authorities recommend the performance of biochemical investigations to help distinguish between so-called 'prerenal azotemia' (the kidney is underperfused and stressed but still functioning appropriately) and 'acute renal failure' (normal cell function has been lost because of the severity of the insult). These investigations typically include the following measurements Rarely, ARF can be confused with rapidly progressive or chronic renal failure. Clinical clues and some relatively simple investigations are usually sufficent to clarify the diagnosis.

Underdiagnosis of chronic renal failure

An individual's plasma creatinine concentration is determined by its production from skeletal muscle (dependent on age, gender, and ethnicity) and its renal clearance due mainly to glomerular filtration. The inverse relationship between plasma creatinine and glomerular filtration rate means that small increments to a near normal plasma level correspond to much larger decrements in glomerular filtration rate. For example, a doubling of plasma creatinine within the normal range (from 60 to 120 mol l) represents a halving of glomerular filtration rate. This subtle biochemical relationship and the absence of referable symptoms and signs means that cases of chronic renal failure may go unrecognized on the intensive care unit as easily as elsewhere.

Hemodialysis and hemofiltration

Hemodialysis and peritoneal dialysis, when required because of renal failure, are effective in reversing metabolic alkalosis if bicarbonate concentration is decreased and chloride concentration is increased in the dialysate. Similarly, continuous hemofiltration allows treatment of metabolic alkalosis by adapting the composition of solutions used to compensate fluid losses through the membrane. Metabolic alkalosis can be treated by other methods, so that these techniques are not required to correct the alkalosis in the absence of renal failure.

Kidney Transplantation

Although chronic dialysis improves live expectancy, kidney transplantation improves the quality of life. Therefore, kidney transplantation has now become a commonly performed and standardized surgical procedure. Patients with endstage renal disease but with otherwise normal life expectancy are good candidates for this procedure. The tolerable ischemic time for kidneys is up to 48 h, and therefore cadaveric kidney transplants are semi-elective procedures, while living-related kidney transplants are elective. Renal failure ultimately results in the uremic syndrome these patients are unable to regulate their volume status and composition of body fluids, leading to fluid overload, metabolic acidosis, and hyperkalemia. In addition, there is secondary organ dysfunction with neuropathy, anemia, platelet dysfunction, hypertension, congestive heart failure, pericardial or pleural effusions, muscle weakness, osteodystrophy, nausea, vomiting, and impaired cellular immunity. Candidates for renal...

Renal disorders Acute renal failure

Acute renal failure is an abrupt decrease in renal function sufficient to result in azotaemia retention of nitrogenous waste in the body. (79) Acute renal failure can result from a decrease of renal blood flow (prerenal azotaemia), intrinsic renal disease (renal azotaemia), or obstruction of urine flow (postrenal azotaemia). Prerenal azotaemia can be caused by renal arterial occlusion or a decrease in the effective blood volume (e.g. haemorrhage, fluid pooling, congestive heart failure, diarrhoea, massive diuresis). Intrinsic renal azotaemia is most commonly caused by acute tubular necrosis due to an acute ischaemic or nephrotoxic insult. Less commonly, renal azotaemia is caused by vasculitis, acute postinfectious glomerulonephritis, or drug-induced acute interstitial nephritis. Postrenal azotaemia is due to obstruction of the urine collecting system, as occurs with bladder outlet obstruction, bilateral ureteral obstruction, or ureteral obstruction in a solitary kidney. Medical...

Chronic renal failure

Chronic renal failure is a progressive and irreversible loss of renal function. (8 The most common aetiologies of renal insufficiency ultimately leading to endstage renal disease are diabetes, hypertension, and glomerulonephritis. Less frequent causes (less than 5 per cent) include interstitial nephritis, obstruction, collagen vascular disease, and AIDS-related aetiologies. Loss of up to 75 per cent of glomerular filtration rate does not usually result in pronounced clinical symptoms, as the remaining glomeruli adapt with hyperfiltration. Serum creatinine is a sensitive indicator of early, subclinical, chronic renal failure. For example, the doubling of serum creatinine from 0.7 to 1.4 mg dl signifies a loss of approximately 50 per cent of glomerular filtration rate, emphasizing the importance of early detection and prevention. Once renal insufficiency is established, there is a tendency for renal disease to progress regardless of the initial insult. Patients with chronic renal...

Acute renal failurediagnosis

Renal failure is defined as renal function inadequate to clear the waste products of metabolism despite the absence of or correction of haemodynamic or mechanical causes. Renal failure is suggested by Persistent oliguria may be a feature of acute renal failure but non-oliguric renal failure is not uncommon 2-3l of poor quality urine per day may occur despite an inadequate glomerular filtration rate. The prognosis is better if urine output is maintained. Clinical features may suggest the cause of renal failure and dictate further investigation. Acute tubular necrosis is a common aetiology in the critically ill (e.g. following hypovolaemia, extensive burns) but other causes must be borne in mind. In sepsis, the kidney often has a normal histological appearance. Anaemia implies chronic renal failure.

Postoperative renal failure

Risk factors include hypovolaemia, haemodynamic instability (particularly hypotension), major abdominal surgery in those 50 years, major surgery in jaundiced patients and biliary and other sepsis. Surgical procedures (particularly gynaecological) may be complicated by damage to the lower urinary tract with an obstructive nephropathy. Abdominal aortic aneurysm surgery may be associated with renal arterial disruption and should be investigated urgently with renography and possible arteriography or re-exploration.

Chronic Allograft Nephropathy

The past 15 years has seen a marked improvement in early graft survival. However, while later graft survival has not kept pace with the remarkable gains made in early (1 year) graft survival. The most common cause of late allograft loss is due to the process of chronic allograft nephropathy (formerly referred to as chronic rejection). Chronic allograft nephropathy can be defined as a chronic deterioration in renal function which cannot be explained by other known processes (e.g., acute rejection, recurrent disease) which is also accompanied by characteristic histologic lesions of interstitial fibrosis, vasculopathy, and glomerular sclerosis. The diagnosis of chronic allograft nephropathy (CAN) is therefore one of exclusion and it is important to search critically for treatable causes of the renal deterioration (particularly if the histologic lesions are nonspecific). The etiology of chronic allograft nephropathy has to this date not been fully elucidated. Both antigen dependent and...

IiiMembranoproliferative glomerulonephritis MPGN

Degree of proteinuria tends to follow disease activity and may completely resolve during full remission. vii. Diabetic nephropathy. Microalbuminuria is first sign of this condition. Because diabetic nephropathy usually takes many years to develop, this form of proteinuria is mostly seen in adolescents.

Factors Influencing Nutritional Status In Dialysis Patients

Approximately 40 of dialysis patients exhibit some degree of protein and energy malnutrition and this is associated with an increased risk of morbidity and mortality. In the Modification in Renal Disease Feasibility Study (MDRD) in which 840 patients were prospectively studied, 42 of CAPD patients and 30 of HD patients were considered to be malnourished (15). Contributing factors to protein energy malnutrition occurring in dialysed patients are shown in Table 15.1. Table 15.1 Factors implicated in protein-energy malnutrition in dialysis patients Uraemic symptoms can continue for upto three months after starting dialysis Dialysis-related effects Nutritional intake deteriorates with inadequate dialysis IHD and episodes of hypotension limiting dialysis time PVD can limit vascular access for HD Infections of vascular access in HD patients and peritonitis in PD

Energy Requirements for Dialysis Patients

Energy requirements to achieve neutral nitrogen balance in stable diabetic dialysis patients are similar to those of healthy non-diabetic adults (35kcal kg body weight), with lower requirements for subjects over 65 years of age (30-35kcal kg body weight) (19). Patients on CAPD receive part of their energy requirements from dialysate glucose (see below) (20). Table 15.3 A checklist for interpreting blood results of dialysis patients Table 15.3 A checklist for interpreting blood results of dialysis patients

Racial Priorities for Kidney Transplants

Some persons have suggested that the current system of allocating kidneys for transplant is biased against African Americans and should be changed to include race as a factor in determining allocation of organs (Ayres et al., 1993). Although African Americans disproportionately end up on dialysis with end-stage kidney disease, they receive disproportionately fewer of the kidneys available for transplant. A number of factors explain this difference, including the requirement of a close enough match between donor and recipient to ensure that the graft will take (Epstein et al., 2000). Because African Americans share fewer HLA antigens with whites, who are also the most frequent organ donors, they are often the poorest match and the most infrequently transplanted. As a result, some persons have suggested that the matching requirement be altered to enable more African Americans to obtain kidney transplants, or that African Americans be allocated a share of kidneys regardless of matching....

Timing the initiation of dialysis

Absolute indications for renal replacement therapy include intravascular volume overload unresponsive to diuretics, hyperkalemia, acidemia, and uremic symptoms (encephalopathy, pericarditis, bleeding diathesis). Although there is no consensus on the ideal timing to initiate dialysis in acute renal failure, it is generally accepted that treatment is initiated when a reversible component to the renal insufficiency has been excluded and well before the occurrence of complications or uremic symptoms. Failure of other organs, rate of increase of urea and creatinine, anticipated catabolism, and urine output should be taken into account. Benefits of early dialysis have to be weighed against the effect of dialysis on residual renal function.

Limitations of conventional dialysis

The major disadvantage of intermittent dialysis is the frequent occurrence of hypotension, sometimes requiring premature discontinuation of the treatment. Dialysis hypotension can usually be attributed to preload reduction because rapid ultrafiltration exceeds fluid recruitment from the interstitium. In turn, the plasma refilling rate is adversely affected by rapid decreases of serum osmolality with intracellular fluid shifts. Acetate and bio-incompatible membranes also contribute to hypotension by induction of inappropriate vasodilatation. Reduction of myocardial contractility is mostly attributable to hypoxemia or acidosis. Convective solute removal (regardless of the ultrafiltration rate, small solute clearance, buffer, and membrane) appears to be hemodynamically better tolerated than diffusion. The mechanism underlying diffusion-related hypotension has not been elucidated. Possible explanations are increased diffusive removal of a small-molecular-weight substance (e.g. an...

Intraocular Pharmacokinetics Using Microdialysis

Breaching Endothelial Cells

Gunnarson et al. (22) first utilized in vivo dialysis technique to sample the vitreous chamber. Studies were carried out to measure endogenous amino acids in the preretinal vitreous space. The effects of high potassium and nipecotic acid, a potent gamma-aminobutyric acid (GABA) inhibitor, on amino acid concentrations were measured. A dialysis probe was implanted in the vitreous of the eye of albino rabbits (Fig. 1). The integrity of the blood-retinal barrier was demonstrated by measuring the concentrations of 3HOH and 14C mannitol in the vitreous effluent following intracarotid injections. 3HOH was detected in the vitreous within a few minutes, whereas 14C mannitol was mostly excluded. Among the amino acids, glutamine had a concentration similar to that in the plasma and cerebrospinal fluid (CSF). Vitreous concentration of all amino acids was lower than in plasma, the majority being below 50 of the plasma concentrations. The taurine level was approximately 70 that of plasma. A...

Microdialysis Probe Recovery

Microdialysis Probe

Recovery may be defined as the proportion of solute extracted from the medium surrounding the probe (55). Recovery is dependent on the following parameters dialysis membrane length, perfusion flow rate, diffusion rate of the solute through the compartment (the usual rate-limiting step in the process), and membrane properties (47). Recovery can also be time- and temperature-dependent. Typical recovery values observed in the literature range from a low of 10 up to 100 . By maximizing the dialysis membrane length, significant increases in recovery can be realized. Decreases in perfusion flow rate also increase the relative recovery (although they also decrease the available sample volume). The recovery of solute can be difficult to ascertain. Ideally, probe perfusate composition should closely match the environment of the medium in which it is placed. The probe also can create a microenvironment near the probe surface, which may be different than the medium more...

Acute Poststreptococcal Glomerulonephritis

Acute poststreptococcal glomerulonephritis (APSGN) is the most common postinfectious renal disease following group A streptococci (GAS) infection, and the first form of glomerular disease in which immunological mechanisms were suspected to play a role. In fact, its evolution is characterized by a serum sickness-like latent period followed by hypocomplementemia and nephritis (Nordstrand et al., 1999). Researchers originally believed that the pathogenic mechanism underlying APSGN was the renal deposition of CICs. This theory was consistent with the clinical picture the elevated serum levels of IgG and IgM in a high percentage of patients the pattern of CIC levels, which are high during the acute phase and usually return to normal within 6-9 months after the attack, but linger in patients with persisting hematuria and proteinuria (Lin, 1982) and the finding of extracellular streptococcal antigens typical of nephritogenic strains in the patients' CICs (Friedman et al., 1984). However,...

Nontraumatic Retinal Dialysis

Kathy Buckli

Nontraumatic retinal dialysis (Fig. 12.2) accounts for approximately 10 of all juvenile retinal detachment 17,43 . The male-to-female ratio is 3 2 43 and the majority of patients are hypermetropic or emmetropic 17,33,36 . In 97 of cases, the dialysis affects the inferotemporal quadrant but multiple dialyses occur in one-third and 37 may be bilateral 43 . Detachments associated with dialyses progress slowly, have a low incidence of PVR and characteristically present either as an incidental finding or when the macula becomes detached. They can be managed routinely with buckling techniques Fig. 12.2. Retinal detachment due to nontraumatic retinal dialysis Fig. 12.2. Retinal detachment due to nontraumatic retinal dialysis and the use of a small (typically 3-mm) circumferential sponge reduces the likelihood of postoperative motility problems. Although the anatomical success rate of surgery is high, visual recovery may remain poor if there has been chronic macular involvement. Examination...

Postinfectious nephritis streptococcal or other causes

Normal C3 occurs with viral upper respiratory infection. 3. Henoch-Schonlein nephritis. Systemic findings include rash, abdominal pain, and joint problems. 4. Chronic nephritis. Focal segmental, membranous, or membranoproliferative disease usually causes significant proteinuria. 5. Lupus nephritis. Low C3 other systems may be affected.

Pharmacokinetics in Patients with Impaired Renal Function Study Design Data Analysis and Impact on Dosing and Labeling

This guidance is intended for sponsors who, during the investigational phase of drug development, plan to conduct studies to assess the influence of renal impairment on the PK of an investigational drug. Topics covered in this guidance are deciding whether to conduct a study in patients with impaired renal function (when studies may be important, when studies may not be important) study design (basic full study design, reduced staged study design, population PK studies, effect of dialysis on PK, PD assessments) data analysis (parameter estimation, modeling the relationship between renal function and PK, development of dosing recommendations) and labeling (clinical pharmacology, precautions warnings, dosage and administration, overdosage).

Hemofiltration andor hemodialysis

This is usually unnecessary in patients with intact renal function. Patients with predictably transient hyperkalemia can usually be maintained at acceptable potassium levels by using a combination of glucose-insulin, sodium bicarbonate, and forced diuresis, possibly supplemented with b 2 agonists. In patients where these methods fail and in those with established acute or acute-on-chronic renal failure, hyperkalemia usually reflects a generalized metabolic disturbance and is an indication to start renal replacement therapy. In extremis, peritoneal dialysis has been used successfully in the management of hyperkalemic cardiac arrest pending institution of more conventional treatments.

Acute intrinsic renal failure

Or nephrotoxins (contrast, antibiotics, rhabdomyolysis), and most often by their combination ( Dinour and Brezis 1998). Acute intrinsic renal failure is synonymous with vasomotor nephropathy and acute tubular necrosis. Although acute intrinsic renal failure and the prerenal state represent two extremes of renal hypoperfusion, intrinsic failure implies renal parenchymal damage (tubular epithelium) that is not immediately reversible upon elimination of the precipitating factor and restoration of blood flow.

Causes Of Kidney Failure

According to the 1998 USRDS, the annual incidence of pediatric ESRD is 1,087, or 13 per million.1 Many causes of pediatric ESRD are unique (Table 13B.1). Alport's syndrome is the association of nephropathy, deafness, and cataracts. Infantile polycystic kidney disease (ARPKD) is autosomal recessive, occurs one in 10,000 to one in 40,000 live births, and involves both kidneys and liver. Adult or autosomal dominant polycystic kidney disease (AKPDK) occurs one in 250 live births, but only 10 present in the first two decades of life. Hemolytic uremic syndrome (HUS) is a disease of infancy characterized by microangiopathic hemolytic anemia, renal cortical necrosis, renal failure, and thrombocytopenia. IgA nephropa-thy (Berger's disease) presents as a respiratory illness, hematuria, and glomerular mesangial IgA deposits. Henoch Schonlein syndrome (HSP) is characterized by purpuric skin lesions, abdominal pain, arthralgia, and renal dysfunction. Cysti-nosis is a rare, autosomal recessive,...

Indications for Dialysis

Supportive dialysis for fluid removal to allow adequate nutritional support. VI. Problem Case Diagnosis. The previously healthy 2-year-old boy had visited a petting zoo 1 week before becoming ill. On admission, he was irritable with hepatosplenomegaly and petechiae. CBC was remarkable for hemoglobin of 8.2 g dL and platelet count of 50,000 mm3. Urinalysis was positive for blood and protein. E coli O157 H7 was isolated from the heme-positive stool. The child was diagnosed with HUS (acute renal failure, hemolytic anemia, and thrombocytopenia).

Principles of Dialysis

Dialysis involves the separation of two compartments containing differing concentrations of a solute in solution by a semi-permeable membrane. This membrane allows passage of solutes of sufficiently small size from one compartment to the other along a concentration gradient. Theoretically, the solute concentration in both compartments will establish equilibrium such that there is no net flux of solute the concentration of solute not bound to nonpermeable macromolecules then will be equal in both compartments. The solute diffusion rate, as described by Fick's law, is a function of membrane surface area, thickness, concentration gradient, compartment volume, and ligand diffusion coefficient (43). Pharmacodynamic effects of drugs are considered to be a function of the unbound concentration in plasma (45). For this reason, it is important to determine the unbound (i.e., therapeutically relevant) concentration of pharmacological agents. Dialysis techniques are well suited to make these...

Morphological Biomarkers Of Kidney Function

Figure 2 Parenchymal hypointensity on T2w images (A) Paroxysmal nocturnal hemoglobinuria. Axial T2w image obtained at 2 T shows that the SI of the renal cortex is decreased, whereas it remains normal in the medulla. (B) Acute ischemic nephropathy. Decrease of SI on a T2w image within the outer medulla on axial view. Pathologic examination of the outer medulla showed iron in the interstitium compatible with hemosiderin deposition. Abbreviations T2w, T2-weighted SI, signal intensity. Source Part (A) from Ref. 3. Figure 2 Parenchymal hypointensity on T2w images (A) Paroxysmal nocturnal hemoglobinuria. Axial T2w image obtained at 2 T shows that the SI of the renal cortex is decreased, whereas it remains normal in the medulla. (B) Acute ischemic nephropathy. Decrease of SI on a T2w image within the outer medulla on axial view. Pathologic examination of the outer medulla showed iron in the interstitium compatible with hemosiderin deposition. Abbreviations T2w, T2-weighted SI, signal...

Part B Kidney Transplantation

Transplantation is the optimal renal replacement therapy for infants and children with end-stage renal disease (ESRD). Compared to dialysis, a successful transplant at any age improves survival, allows for more normal growth and development, and provides an excellent quality of life. In large measure, these data are from living related (LR) recipients on cyclosporine (CsA) based immunosuppression. This chapter will review pediatric renal transplantation and the impact of these factors on outcome.


Microdialysis is used to introduce or withdraw a constant amount of a biologically active substance into or from the extracellular cerebro-spinal fluid in living animals. The microdialysis probe is designed to mimic a capillary system in which the substrate has to cross a semi-permeable membrane. The direction of flow depends primarily on concentration gradients. The gradient built up by the substance in question is not exclusively dependent on the differences in concentration between sample and extracellular fluid, but depends also on the velocity of flow inside the microdialysis chamber. For instance, when a physiological salt solution is dialyzed from inside the chamber, the solution equilibrates with the extracellular fluid, i.e. solutes diffuse from the cerebro-spinal fluid across the membrane into the probe. After a period of time, the chamber contains the substance (and other solutes) in an amount representative of that dissolved in the extracellular cerebral fluid. On the...

Renal failure

Renal failure occurs in approximately 10 per cent of patients, unless the cause is acetaminophen (paracetamol) poisoning when the incidence is very much higher, approaching 75 per cent in patients with grade IV encephalopathy. The mechanism in this circumstance is a direct nephrotoxic effect of acetaminophen. In patients without acetaminophen poisoning, many factors may contribute to the pathogenesis of renal failure. The usual form of renal failure is the hepatorenal syndrome, characterized by a progressive increase in plasma creatinine concentration, oliguria, low urine sodium concentration (usually 10 mmol l), and histologically normal kidneys. Acute tubular necrosis may also occur as a result of hypotension, hypovolemia, or severe sepsis. It may be difficult to differentiate between these two syndromes, and often a diagnosis of hepatorenal syndrome can only be made after correction of the predisposing causes for acute tubular necrosis. Management includes monitoring of volume...

Lupus Nephritis

Systemic lupus (SLE) is an autoimmune disease characterized by several autoantibodies directed against intracellular antigens. Kidney involvement is frequent and indeed constitutes one of the primary causes of morbidity and mortality. It is generally agreed that antibodies are the principal agents at work in lupus nephritis, forming immune deposits by different mechanisms, more than one of which may be involved. Their central role in causing renal damage has been convincingly demonstrated in a genetically manipulated autoimmune mouse strain. MRL lpr-lpr mice lacking Ig heavy chain Jh genes, and therefore lacking B cells and autoantibodies, do not develop glomerular, tubular, or interstitial damage, even in the presence of the lpr mutation (Shlomchik et al, 1994). While not excluding the contribution of T cells, soluble mediators, and B cell functions other than antibody formation (Chan et al., 1999 Tipping and Holdsworth, 2003), antibodies have been demonstrated to be a key factor in...


Diabetes-related nephropathy affects 40 of patients with type 1 disease and 10-20 of those with type 2 disease of 20 or more years duration. Microalbuminuria of 30 to 300 mg 24 hours heralds the onset of nephropathy. Microalbuminuria can be detected with annual urine screening for albumin creatinine ratio. Abnormal screening test results should be confirmed, and a 24-hour urine sample should be obtained for total microalbuminuria assay and evaluation for creatinine clearance. 2. The clinical progression of nephropathy can be slowed by (1) administering ACE inhibitors, such as lisinopril, enalapril or captopril (Capoten), (2) controlling blood pressure to 130185 mm Hg or lower, (3) promptly treating urinary tract infections, (4) smoking cessation, and (5) limiting protein intake to 0.6 g kg day.


The average patient on haemodialysis requires 3.5 h of dialysis three times per week to achieve adequate creatinine clearance. (81) Haemodialysis has enabled the survival of countless thousands of patients with chronic renal failure and provides a temporary management tool for patients on transplantation waiting lists. However, it is not a benign procedure, and has a number of potential neuropsychiatric complications. Patients on haemodialysis are at high risk for developing volume overload, pulmonary oedema, hyperkalaemia, hyperphosphataemia, and metabolic bone disease if compliance with restricted diet and fluid intake is not optimal. Patient adherence to these diet and fluid-intake protocols are used as a criterion for making decisions about appropriateness for transplantation. Psychiatric reasons for non-compliance should be addressed and are usually reversible, with the exception of personality disorders. These include mood disorders, phobias, panic disorder, substance-related...

Dialysis Fistulas

Dialysis fistulas are also prone to infection, particularly if they include implanted prosthetic material, while native vessel arteriovenous fistulas are relatively resistant to infection. Staphylococcus aureus accounts for 60-90 of access site infections, suggesting direct contamination from skin at the time of access. As with other graft infections, clinical findings can be extremely subtle and are completely absent in approximately one-third of cases. Nuclear imaging of a dialysis fistula can be difficult to perform and challenging to interpret. Frontal and profile views of the fistula are required, but it can be difficult to control for the degree of forearm pronation. Furthermore, some camera designs are cumbersome to position for areas close to the antecubital fossa. The large amount of blood contained within the fistula can often be seen as low-grade activity, especially on early images or when significant erythrocyte cross-labeling has occurred. Occasionally, normal bone...


As with obstructive renal failure, ultrasound is the first-line imaging modality ( LevineJ 994). It may detect a perirenal abscess as a complication of the pyonephrosis, which can be treated with a percutaneous drain inserted at the time of the nephrostomy. In very obese patients, retroperitoneal collection may be difficult to exclude with certainty on ultrasound and a CT scan may be indicated. If access to an abscess is then thought to be awkward, a catheter drain can be inserted under CT guidance.

Dialysis Initiation

Of the necessary dietary changes leading up to and extending to the initiation of elective dialysis (3). Dialysis guidelines from the National Kidney Foundation promote the early initiation of RRT for diabetic patients, due to an increased susceptibility to uraemic symptoms at lower serum creatinine levels than non-diabetic subjects (4). Early RRT for diabetic renal failure not only relieves the symptoms of nausea, anorexia and vomiting but also helps reduce overall mortality. However, despite these recommendations, dialysis is frequently delayed due to either personal resistance or inadequate dialysis resources. Some diabetic patients with already compromised renal function, will require the emergency initiation of dialysis during an intercurrent illness. However, this does not mean that all will require long-term RRT.


While survival on dialysis continues to improve, diabetic patients still do less well than non-diabetic patients (6). Results from the Italian Cooperative Peritoneal Study Group Registry show the 10-year patient survival for the 301 diabetic patients to be less than half that of the 1689 non-diabetic subjects (20.6 vs 55.6 ) (7). Higher mortality rates among diabetic patients receiving HD also occur (8), but with good glycaemic control these rates can be improved (9). Peritoneal dialysis is the preferred mode of treatment for diabetic patients with microvascular and macrovascular co-morbidities. Continuous ambulatory peritoneal dialysis allows for a slow ultrafiltration process that provides greater cardiovascular stability than HD. Blood pressure control is easier and residual renal function is preserved for longer. It also provides incidentally for an alternative route of insulin administration. Initial concerns that diabetic CAPD patients may have higher dialysis-associated...


Dialysis uses diffusion and hydrostatic pressure to drive solutes across a semipermeable membrane. Concentration gradients are created by flushing dialysate solution counter current to blood flow on the effluent side of the device. Alternating 2000 ml of 0.5 DIANEAL with 1000 ml of normal saline with 50 meq sodium bicarbonate added helps to maintain a normal pH (Fig. 16.2). 1. Moore RA, Laub GW. Hemofiltration, Dialysis and Blood Salvage Techniques During Cardiopulmonary Bypass. In Gravlee G, Davis R, Utley J, eds. Cardiopulmonary Bypass-Principals and Practice. Baltimore Williams and Wilkens, 1993 233-245.

The Future of Modified Fibers

The future of fiber technology for medical and specialty applications depends largely on the future needs of our civilization. It has been said that unmet needs drive the funding that sparks ideas . In this regard recent emphasis on United States homeland security has encouraged new biofiber research, resulting in the development of anti-bacterial fibers for producing clothing and filters to eliminate pathogens and enzyme-linked fibers to facilitate decontamination of nerve toxins from human skin 1 . Magnetic fibers may also have future security applications including fiber-based detectors for individual and material recognition. Interest in smart and interactive textiles is increasing with a projected average annual growth rate of 36 by 2009 2 . More specific markets including medical textiles and enzymes will grow even more rapidly. Among the medical textiles are interactive wound dressings, implantable grafts, smart hygienic materials, and dialysis tubing. Some of the medical and...

Neuroradiology And Ultrasound

MRA is most useful in the detection and evaluation of aneurysms that have no history of SAH or where there has been a significant delay in the diagnosis. Standard MR sequences are also performed at the time of the examination as aneurysms may be seen as low signal. Aneurysms as small as 2 mm can be shown but an accuracy of at least 80 is seen for aneurysms of 5 mm and larger. Aneurysms that present with mass effect and cranial nerve palsy can be very accurately demonstrated (or excluded) by MRI with MRA. The non-invasive nature of MRA makes it very attractive as a screening test for aneurysms. This may be desirable in certain high-risk groups such as polycystic kidney disease or familial aneurysm disease. The implications of aneurysm screening for an incidental aneurysm have to be carefully discussed with the patient. Recent evidence suggests a much lower risk of hemorrhage (0.05 year in small aneurysms) than have previous studies and also a higher morbidity mortality (up to 14 ) for...

Steroid Free Immunosuppression

We have avoided maintenance steroids at Northwestern Memorial Hospital in more than 500 kidney transplant recipients with two different antibody induction regimens since mid 1998. All recipients were treated with tacrolimus and either MMF or sirolimus. Each also received intravenous methylprednisolone daily for three days only (500 mg, 250 mg, 125 mg, stop). From mid 1998 until September 2001 the induction antibody basiliximab was given in the operating room and on the third post-transplant day. After September 2001, intraoperative antibody treatment consisted of a single 30 mg I.V. infusion of alemtuzumab. First year patient and graft survival in both groups are 99 and 97 respectively. Acute rejection episodes occurred in 9 percent of recipients in both groups. The main difference between the two induction antibodies in these prednisone free protocols is that the onset of first rejection episode was earlier with basiliximab (7.5 days) than with alemtuzumab (107 days). In general,...

Contrastinduced Nephrotoxicity

A number of risk factors for the development of CIN have been described, particularly pre-existing renal insufficiency (21-26). Patients whose renal failure is the result of diabetic nephropathy are at even greater risk, and when renal failure occurs, it is more likely to be irreversible (27). However, the presence of diabetes mellitus alone (in the absence of renal failure) is probably not a risk factor for contrast-induced renal failure (28-30). Other risk factors that have been implicated include American Heart Association class IV congestive heart failure, hyperuricemia, dehydration, concurrent use of such nephrotoxic drugs as aminoglycoside antibiotics and nonsteroidal anti-inflammatory agents, advanced age, and administration of large doses of contrast media for one or multiple contrast-enhanced studies performed within a short period of time (14,19,31,32). Multiple myeloma has long been considered a risk factor but may not be important if the patient is hydrated (14,33). The...

Radiographic and Other Studies

Treat non-AG metabolic acidosis by replacing volume losses. Use isotonic fluid with low Cl- content. Specific treatments exist for most causes of AG metabolic acidosis. These may include insulin for diabetic ketoacidosis dialysis for renal failure fluids, inotropes, pressors, and antibiotics for septic shock. Use of HCO3 for lactic acidosis is controversial if warranted, HCO3 therapy can be guided by the following formula

Obesity as a Chronic Disease

The DCCT was conducted over 10 years at multiple centers in America and Canada. Four times a day participants' blood glucose levels were checked and insulin was given. Participants followed a healthy diet and regular exercise and had monthly contact with the healthcare system. The results were remarkable. Compared to the standard of diabetic care at the time of this study, the intervention greatly reduced patients' relative risk of developing micro-vascular complications. Nephropathy was reduced by 50 , neuropathy by 60 , and retinopathy by 76 8 .

Adverse effects of ACE inhibitors

Angiotensin II receptor blockers (ARBs) decrease BP by inhibiting the coupling of AII to the angiotensin receptor. ARBs are as effective as other major classes of antihypertensives at reducing BP. In contrast to ACE inhibitors, ARBs have not been shown to slow the progression to renal failure in patients with diabetes. ARBs do not cause cough or angioedema, but they may cause hyperkalemia.

Macronutrient Composition Of The Diet

A combination of carbohydrate and cis-monounsaturated fatty acids should provide 60-70 total daily energy intake. Total fat intake should be restricted to 35 total energy. Ci's-monounsaturated fatty acids should provide between 10 and 20 total energy. Saturated and trans-fatty acids should provide under 10 total energy. Polyunsaturated fatty acids should not exceed 10 total energy. Protein intake should range between 10 and 20 total energy. Protein intake should not go below 0.6 g kg normal body weight day but should be at the lower end of the range (0.8 g kg body weight day) in cases of nephropathy or where abnormal microalbuminuria has been identified.

The presence of coma without focal signs or meningism

These patients are likely to have a metabolic or anoxic cause for the coma one of the commonest causes remains that of drug overdose and it is appropriate to withdraw blood to send to the toxicology laboratories from patients presenting in this way. In general there will be a clue from the circumstances in which the patient was discovered and from the previous history. Reliance is placed upon the assessment of metabolic and toxic metabolites in the blood and evidence should be sought for hepatic failure, renal failure, hyperglycaemia, hypoglycaemia, and disturbances of electrolytes or acidosis. Most commonly available drugs can now be assayed within the blood and serum enzymes should also be estimated. Problems inevitably arise when patients who are conscious have been consuming alcohol and an assessment of the relevant importance of this in causing the unconsciousness may be difficult. Again the problem may be helped by the expedient of measuring the blood alcohol level.

Preface to the First Edition

Includes chapters on BALT and pulmonary diseases, mucosal immunity in asthma, respiratory infections, and inhalant allergy (Chapters 43-46). Section G presents information on the oral cavity, upper airway, and mucosal regions in the head and neck (Chapters 47-50), as well as ocular immunity, tonsils and adenoids, and middle ear. Sections H and I are devoted to mammary glands and genitourinary tract, respectively. These sections consist of chapters on milk, immunological effects of breast feeding (Chapters 51 and 52), IgA nephropathy, immunology of female and male reproductive tracts, endocrine regulation of genital immunity, mucosal immunopathophysiol-ogy of HIV infection, and genital infections relative to maternal and infant disease (Chapters 53-58).

Herbicides and Rodenticides

The bipyridyl herbicides paraquat and diquat are broad-spectrum herbicides. As little as 10 mL of paraquat concentrate is lethal in adults. Paraquat damages the lungs and may result in the appearance of a respiratory distress syndrome appearing 1 or 2 weeks after poisoning. In contrast, diquat causes minimal lung damage because it does not selectively accumulate in the lung. Acute renal failure, liver toxicity, and gastrointestinal damage are sequelae to diquat poisoning.

Prescribing of Antidiabetic Drugs for Type 2 Diabetes

Other regimens may be equally effective or even more so. However, comparative studies are sparse. With very prevalent diseases such as type 2 diabetes, pharmacoeconomics become extremely important. Thus, both the economy of society at large and the economy of the individual patient must be taken into account when choosing drug therapy. Safety issues remain important since treatment will often be continued for many years or even life-long, during which time complications, for example, nephropathy or cardiovascular disease, that may alter the safety profile of certain drugs may develop.

Vectorborne Rickettsial Diseases Typhus and spotted fever

The disease is an acute febrile illness, with sudden onset of headache and chills followed by a fever that persists for 2-3 weeks, and a characteristic rash appearing on the trunk and extremities on about the 4th day of the disease. Delirium, shock and renal failure may occur in severe cases, and despite the use of antibiotics, the case-fatality rate has remained at about 5 . The disease occurs widely throughout South, Central and North America, where it is transmitted by several genera of ixodid ticks (Derma-centor, Ixodes, Rhipicephalus and Amblyomma) depending upon the locality. The ticks serve both as reservoirs and vectors of spotted fever group rickettsiae. The infection is maintained in the tick during all stages of the developmental cycle, and most tissues are infected, including the salivary glands. Humans coming into contact with ticks become infected during the feeding process.

Immunosuppression And Infection

Ease caused by a variety of fungi from the order Muco-rales in the class Zygomycetes. These organisms are widespread molds that we are exposed to regularly in daily life, but disease is rare because of their low virulence and because of host defenses. The people most susceptible are the debilitated, injured, and diabetic (especially ketoacidotic, poorly controlled diabetics), and those who are immunocompromised, most commonly by corticosteroids. Renal dialysis patients have also been commonly affected possibly because of the previous widespread use of deferoxamine in these patients to treat aluminum or iron overload.39 Iron overload of itself may be a risk factor also,40 with some evidence that the acidosis found in diabetics alters iron metabolism and enhances the ability of the Mucor organisms to grow in tissues.41 AIDS patients do not appear to have an increased susceptibility to mucormycosis. This is probably because of the vital role of polymorphonuclear neutrophils (PMNs) in the...

Other bedside technologies

It is inexpensive, easy to perform and reproducible 42 . Bioelectrical impedance has been validated against both underwater weighing and isotope dilution, two bench research gold standards used for determining body composition 43 . One drawback of BIA is its assumption of a normal body water status being approximately 72 -74 . Therefore, in clinical cases of body edema or body dehydration, BIA may be inaccurate 44 . A study in patients with renal failure found BIA to be inaccurate secondary to an abnormal volume status 45 . In contrast, BIA was found to be accurate in determining muscle mass in a group of patients with cystic fibrosis when compared to isotope dilution methods 46 .

Absorption Metabolism Excretion

Hepatic O-dealkylation and glucuronide formation appear to be major pathways of biotransformation. Only about 10 of orally administered prazosin is excreted in the urine. Plasma levels of prazosin are increased in patients with renal failure the nature of this interaction is unknown.

Cadaver And Living Kidney Donation

The annual number of patients that receive a kidney transplant are determined by the number of cadaveric kidneys available and the number of living kidney donors. Cadaver kidney transplants make up the majority, numbering 8,493 in 2002. The bulk of the increase in kidney transplants over the past several years is due to greater numbers of living donors. There were 6,235 living donor kidney transplants in 2002. Numerous strides have been made to increase the total number of cadaver kidneys available by public education programs encouraging organ donation. There is also a new classification of expanded criteria organ donors, and more liberal consideration of controlled and uncontrolled non-heart-beating donors. In addition, many programs are expanding their living kidney donor experience by including distantly related donors such as spouses, cousins, aunts, uncles, close friends, and even emotionally unrelated donors. This has resulted in an increase in the proportion of all kidney...

Absorption Metabolism and Excretion

Labetalol is almost completely absorbed from the gastrointestinal tract. However, it is subject to considerable first-pass metabolism, which occurs in both the gastrointestinal tract and the liver, so that only about 25 of an administered dose reaches the systemic circulation. While traces of unchanged labetalol are recovered in the urine, most of the drug is metabolized to inactive glucuronide conjugates. The plasma half-life of labetalol is 6 to 8 hours, and the elimination kinetics are essentially unchanged in patients with impaired renal failure.

Transplant Nephrectomy

Transplant nephrectomy is the surgical removal of a kidney transplant. The indications for transplant nephrectomy include irreversible technical complications that result in acute failure of the transplant, hyperacute rejection, and chronic loss of renal allograft function associated with local or systemic signs of symptoms. Transplant nephrectomy may be required within days of the transplant or even years after a transplant has failed.

With Type 1 Diabetes Mellitus

At the turn of the century a patient diagnosed with Type 1 diabetes mellitus had average life expectancy of only two years. The development of insulin as a therapeutic agent revolutionized the treatment of diabetes mellitus by changing it from a rapidly fatal disease into a chronic illness. Unfortunately this increased longevity brought to the fore serious secondary complications including nephropathy, neuropathy, retinopathy and macro- and microvascular complications in survivors 10 to 20 years after disease onset. The annual national direct and indirect costs of Type 1 and 2 diabetes in 2002 - including hospital and physician care, laboratory tests, pharmaceutical products, and patient workdays lost because of disability and premature death - exceeded 130 billion.1

Noncardiac causes of bradyarrhythmias

Frequent non-cardiac causes seen in the intensive care unit include severe electrolyte disturbances. These can be reflected in the ECG, as can the response to therapy. Hyperkalemia is common and can be fatal. It is often due to severe renal failure and can also result from potassium salts of penicillin, digitalis toxicity, or acidosis. The action potential across the cell membrane depends upon the concentration of ions across the membrane. Hyperkalemia shortens the action potential duration and slows conduction. Severe hyperkalemia can have negative inotropic effects and can increase the threshold for capture of artificial pacemakers. Hyperkalemia can lead to non-conducted atrial beats, asystole, ventricular tachycardia, ventricular fibrillation, and conduction disturbances including both type I and type II second-degree atrioventricular block, accelerated idioventricular ventricular rhythm, and ventricular escape rhythms. ECG changes progress from a flattened PR interval to peaked T...

Pseudomalignant hypertension

Elderly patients with diabetes or renal failure and diffuse vascular disease can occasionally develop a condition called 'pseudomalignant hypertension' ( Messerii.,. 1985). As a result of advanced atherosclerosis, their blood vessels become relatively non-compressible. This makes it very difficult, and sometimes impossible, to measure an accurate cuff blood pressure and can result in artefactually elevated blood pressure measurements. There are numerous case reports of such patients receiving unnecessarily aggressive antihypertensive agents in efforts to control their artefactual hypertension, which even result in shock or cardiac arrest of the patient. In such cases, intra-arterial catheter monitoring shows the true pressure to be much lower than that measured by sphygmomanometry. These patients can

Immunological Aspects Of Pancreas Transplantation

The outcome of pancreas transplantation with respect to graft survival rates and rejection rates is most dependent upon the choice of immunotherapeutic agents employed. There is consensus that the risk of pancreas allograft rejection is much greater than that observed with kidney transplantation. The precise reasons are not well defined but likely involve greater immunogenicity of the pancreati-coduodenal graft. Recurrent autoimmune reactions are extremely rare. The majority of pancreas transplant programs are using induction therapy combined with microemulsion cyclosporine or tacrolimus, plus mycophenolate mofetil or sirolimus, and prednisone. This combination has significantly improved graft survival rates. The incidence of acute rejection has been reduced by more than half. The avoidance of induction therapy with this maintenance immunosuppression protocol is also associated with excellent patient graft survival rates but with a higher rate of acute rejection. There are steroid...

General Considerations For The Analysis Of mRNA 3 Processing in Vitro

Originally developed by Dignam et al. (1985) for the analysis of RNA polymerase II transcription initiation. Subsequent modifications of the Dignam protocol, developed in the Keller lab (Ruegsegger et al., 1996), have yielded superior extracts active for pre-mRNA 3' processing. The Keller nuclear extract may be used directly for 3' processing assays or may be dialyzed into an appropriate buffer prior to use. Dialysis, however, consistently results in a loss of processing activity on the order of approximately twofold. The protocols presented below address the use of both dialyzed and undialyzed nuclear extracts. The extracts are quick frozen in liquid N 2 and stored at 80 C. Freeze-thawing does not appear to have a large impact on processing activity, but in principle, it should be avoided whenever possible.

Techniques of surgical treatment

As surgical treatment centers on debridement of necrotic tissue, simple peritoneal dialysis cannot be considered adequate as its effects are restricted to the abdominal cavity and do not address the necrotizing process in the retroperitoneal space. Controlled trials have shown no reduction in overall mortality of severe acute pancreatitis.

Intracranial Pressure Management

Several osmotic diuretic agents have been used to treat elevated ICP, including sucrose, albumin, urea and mannitol. Mannitol appears to be excluded from the CSF to a greater extent than other osmotic agents. Mannitol is a simple unbranched hydrocarbon with a half-life of approximately 0.25-1.7 hours. Its excretion is primarily renal, so its half-life may be extended in cases of impaired renal function. The recommended dose for mannitol is 0.25-2 g kg intravenously every 4 hours, with a peak decrease in ICP approximately 15 minutes after administration. Use of a loop diuretic 15 minutes after the administration of mannitol has been shown to potentiate its effect. Like all osmotic diuretics, mannitol works primarily by shifting water from the brain parenchyma to the intravascular space, thereby decreasing the volume of the intracranial contents and reducing ICP. Additionally, mannitol reduces intracranial elas-tance. Mannitol may also affect the reactivity of

Stability Of The Aspnat Complex

The large size and the multimeric nature of Asp-NAT called for an investigation on the stability characteristics of this complex. CHAPS and NaCl were used in increasing concentrations in the treatment medium to perturb the Asp-NAT complex. Enriched Asp-NAT preparations from a DEAE column were used in these studies in view of its higher enzyme activity. The results in Figure 6 show that CHAPS has a biphasic effect on Asp-NAT stability (Fig. 6A) as revealed by pre-treatment (0-4 oC, 1h). Asp-NAT activity decreased to 40 of the control at 12 mM CHAPS and 10 of the control at 20 mM CHAPS. Removal of excess CHAPS by dialysis had no restoring effect on the enzyme activity after pre-treatment at 12 mM CHAPS. Although NaCl decreased Asp-NAT activity at concentrations greater than 0.15 M, removal of excess NaCl by dialysis reversed the effect up to 1 M NaCl (Fig. 6B). Figure 6. Asp-NAT activity in the presence of varying concentrations of CHAPS (A) and NaCl (B). Relative activity ( ) with...

Diagnosis and Clinical Presentation

Differential diagnoses include all other causes of acidosis. It should be emphasised that many acute medical conditions induce stress ketosis and may be associated with acidosis. DKA is a metabolic aci-dosis characterised by a high anion gap and varying degrees of respiratory compensation. It is therefore crucial to obtain measures of ketone body concentrations and arterial gas analysis. If there is a major discrepancy between the extent of the ketonaemia and the acidemia, then lactate measurements are warranted. Starvation ketosis and alcoholic ketoaci-dosis can usually be identified by clinical history. Other conditions causing metabolic acidosis include lactic acidosis and intoxication with sali-cylate, methanol, ethylene glycol (antifreeze) and paraldehyde. The clinical picture may be blurred whenever the acidosis is aggravated by renal failure or respiratory failure. In addition DKA may imitate other diseases. High levels of potassium may cause ECG changes suggestive of...

Toxicity of protein excess

Therefore, along the course of providing nutritional support to patients, a comprehensive evaluation of the clinical parameters to assess tolerance, weaning and ventilator parameters, organ function, visceral proteins, volume status, glucose tolerance, and other biochemical markers such as blood urea nitrogen (BUN), ammonia and urinary urea nitrogen, or even indirect calorimetry measurements are necessary to adjust feeding regimens to adequate levels. For patients with a tendency toward or early signs of impaired renal function, the responses to protein intake should be more closely monitored.

Brain or Btype natriuretic peptide BNP

Cardiomyocytes produce and secrete cardiac natriuretic peptides. Plasma levels rise in a variety of conditions but high levels are predominantly associated with heart failure, and increase in relation to severity. A sensitivity of 90-100 is claimed, whereas specificity is approximately 70-80 . Numerous commercial assays for B-type natriuretic peptide (BNP) or proBNP are now available, each with their own diagnostic range. They are useful as a screening tool for patients presenting with dyspnoea, for prognostication, and for titration of therapy. Levels rise in the elderly, in renal failure, and in pulmonary diseases causing right ventricular overload (e.g. pulmonary embolus).

Dietary protein and amino acids

Major concerns about using higher-protein diets, particularly those rich in animal products, are an increased risk of renal failure and the association of cholesterol and, especially, saturated fatty acids with cardiovascular disease. There is little evidence for adverse effects of high-protein diets on renal function in individuals without established renal disease,134 although it is obvious that caution should be exerted in the case of susceptible groups. Likewise, it appears that moderately high protein diets are not harmful to cardiovascular health and may indeed be beneficial.135-137 In any case, although recent evidence supports potential benefits, rigorous longer-term studies are needed to investigate the safety and effects of high-protein diets on weight loss and weight maintenance.

Chapter References

Brady, H.R., Brenner, B.M., and Lieberthal, W. (1996). Acute renal failure. In The kidney (5th edn) (ed. B.M. Brenner), pp. 1200-52. W.B. Saunders, Philadelphia, PA. Espinel, C.H. (1976). The FENa test use in the differential diagnosis of acute renal failure. Journal of the American Medical Association, 236, 579-81. Levinsky, N.G., Alexander, E.A., and Venkatachalam, M.A. (1981). Acute renal failure. In The kidney (ed. B.M. Brenner and F.C. Rector Jr), pp. 1181-1236. W.B. Saunders, Philadelphia, PA. Schrier, R.W. and Conger, J.D. (1980). Acute renal failure pathogenesis, diagnosis, and management. In Renal and electrolyte disorders (ed. R.W. Schrier), pp. 375-407. Little, Brown, Boston, MA.

Vascular and hypoxic effects

The initial phase of ischemic acute intrinsic renal failure is characterized by a reduction of more than 50 per cent in renal blood flow, a disproportionate lowering of glomerular filtration rate, and a loss of renal autoregulation. Despite receiving a greater blood flow per unit weight of tissue than most other vital organs, the kidney is highly vulnerable to oxygen deprivation owing to the countercurrent urinary concentrating system. The most vulnerable nephron segments are the straight portion of the proximal tubule (S3 segment) and the medullary thick ascending loop of Henle because of their hypoxic milieu and high rates of oxygen consumption (active solute transport and reabsorption), while the inner medulla exhibits less metabolic demands ( Brezisand Rosen 1995).

Treatment with renal replacement therapy

In the majority of patients with severe ARF, residual renal function is so limited that renal replacement therapy becomes necessary to avoid complications and provide optimal levels of physiological support. Renal replacement therapy is now available in the form of continuous hemofiltration, intermittent hemodialysis, or peritoneal dialysis. All these therapies have advantages and disadvantages. However, the use of peritoneal dialysis for the dialytic treatment of severe ARF in the ICU in developed countries is now uncommon. This is because standard peritoneal dialysis is associated with limited urea clearances, a high risk of peritonitis ( 15 per cent), and limited ability to maintain volume control.

Choosing a loading dose

For a given drug, an average of four to five half-lives are required to reach therapeutic plasma concentrations. Loading doses are used routinely to provide rapid induction and achieve adequate therapeutic plasma concentrations in a short time, assuming that this is clinically feasible. The loading dose in patients with renal failure is usually no different from that in patients with normal renal function ( Bennettefal 1994). half-life of a drug does not explain solely the drug excretion process in contrast, it is a by-product of drug distribution and clearance (metabolism and excretion). In patients with renal failure, the half-life and the time to reach steady state are usually prolonged. If doses remain unchanged, the steady state plasma concentration in a patient with renal failure state will be higher than that in a patient with normal renal function. A loading dose is usually given, if feasible, to reduce the time required to achieve a therapeutic plasma concentration. Reduction...

Choosing a maintenance dose

Most drugs are given at regular intervals to maintain therapeutic plasma concentrations ( Bennett eia 1994). In the patient with renal failure, maintenance doses Table 1 Required dose intervals and maintenance doses for common intensive care drugs in renal failure Table 1 Required dose intervals and maintenance doses for common intensive care drugs in renal failure

Metabolic abnormalities

Kaliuresis is impaired in chronic renal failure with normal plasma levels maintained by an adaptive increase in secretion by the remaining nephrons and by increased colonic excretion under the influence of aldosterone. Potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, and non-steroidal anti-inflammatory drugs can precipitate hyperkalemia, and the composition of fluid replacement and feeding should be considered with care. Phosphate retention with reciprocal hypocalcemia and reduced dihydroxylation of 25-hydroxyvitamin D are triggers for the development of secondary hyperparathyroidism. Parathyroid hormone stimulates osteoclastic activity and liberates calcium from the bones in an effort to normalize serum calcium levels, and over time a minority of patients will develop hypercalcemia due to autonomous or tertiary hyperparathyroidism. The adverse neuromuscular effects of hypocalcemia are offset by the acidosis of renal failure which increases the ionized component...

Hyperosmolar Hyperglycaemia

Hyperosmolar hyperglycaemia (HH) is generally the fulminant result of poorly treated type 2 diabetes or delayed diagnosis of previously unknown type 2 diabetes. HH is less frequent than DKA, but mortality is higher and remains close to 15 in many centres 1,20 . As implied hyperosmolality is the primary clinical problem and there will be hyperglycaemia of 35-40 mmol L and an effective serum osmolality of 320 mOsm kg (Table 1). HH most often occurs in frail patients in combination with other potentially fatal conditions. Strict differentiation between DKA and HH can be difficult, because some degree of ketosis may be present in HH and because, for example, lactic acidosis, respiratory and renal failure may also be present. In practise this dilemma is mainly ornamental, since diagnostic and therapeutic efforts follow the same principles.

Pharmacokinetics and metabolism

The principal route of metabolism is by reduction and subsequent hepatic elimination. The significance of liver dysfunction in altering anthracycline kinetics has been controversial. Dose reductions are, however, recommended for patients with abnormal liver biochemistry tests as they are at risk of increased toxicity. Dose reductions are not usually required for patients with impaired renal function.

Medical Devices And Categories

In general, a medical device is defined as follows a medical device is an implant and equipment to be used either to achieve disease diagnosis, medical treatment, or disease prevention for human and animals, or to influence the physical structure and function of human and animals. Medical devices for humans may also be classified based on whether and how long the device is in contact with tissue or cells and on the degree of disjunction induced by the device when in a disabling situation. The term covers various categories, such as scissors and tweezers, with small risk to human function, to central venous catheters, artificial dialysis (human kidney), and pacemakers, with high risk to human function.

Clostridia Perfringens Epsilon Toxin

C. perfringens epsilon toxin is a potential biothreat agent no reported cases of human disease have occurred. The toxin is produced by C. perfringens as a 311-amino-acid protoxin which is cleaved into a 14-amino-acid peptide which is a potent necrotizing toxin. The toxin causes a rapidly fatal toxemia in herbivores when their gastrointestinal tracts are colonized by C. perfringens, leading to in situ toxin production.143 The toxin causes pulmonary edema, renal failure, and cardiovascular collapse. The lethal dose for rodents is 100ng kg, and it has been estimated that a lethal human dose would be 7 micrograms parenterally.144 Due to the toxin's potency and lethality, it has been classified as a Category B agent. It is thought that biothreat use would be via the aerosol inhalational route, leading to pulmonary edema followed by renal failure and cardiovascular collapse.

Clinical use of COP measurement

It is difficult not to support the use of colloid fluids in hypo-oncotic patients. In patients with renal failure the repeated use of colloid fluid may lead to a hyperoncotic state. This is associated with tissue dehydration and failure of glomerular filtration (thus prolonging the renal failure). Measurement of a high COP in patients who have been treated with artificial colloids should direct the use of crystalloid fluids. It is important to note that excessive diuresis may also lead to a hyper-oncotic state for which crystalloid replacement may be necessary.

To isolate DNA in the size range of 150200 kb

Transfer the pooled aqueous phases to a dialysis bag. Close the top of the bag with a dialysis tubing clip, allowing room in the bag for the sample volume to increase 1.5-2-fold during dialysis. b. Dialyze the solution at 4 C against 4 liters of dialysis buffer 6-1. Change the buffer three times at intervals of 6 hours. Because of the high viscosity of the DNA solution, dialysis generally takes 24 hours to complete. To isolate DNA that has an average size of 100-150 kb

Patients presenting with neuromuscular transmission defects after admission to the ICU

A second mechanism is a defect in neuromuscular transmission which occurs when neuromuscular blocking agents such as vecuronium or pancuronium bromide are given in the presence of renal failure. The action of these drugs is prolonged beyond hours to a number of days after they have been discontinued. Nerve stimulation studies show a typical postsynaptic defect. There is a decrement of the compound muscle action potential at slow rates of stimulation. The prognosis for recovery of muscle strength is quite good, although an accompanying critical illness (polyneuropathy) is often present and may further prolong recovery.

Opioid Modulation of Mesocorticolimbic Neurotransmission

Acute systemic administration of KOR agonists decreases DA levels in the NAc and dorsal striatum (75,76). In vitro studies assessing the modulation of electrically evoked 3H DA by opioid receptor activation revealed that in the NAc, olfactory tubercle, and PFC, DA release can be inhibited by activation of KOR (77,78). Evidence that the acute systemic administration of selective KOR agonists decreases dialysis levels of DA in the NAc and dorsal striatum has also been obtained (75). In vivo microdialysis studies in the rat have also shown that the intra-NAc infusion of the selective KOR agonist U-69593 decreases basal DA overflow in the NAc, whereas the selective blockade of KOR in this region significantly increases basal DA overflow (22). Infusion of KOR ligands into the VTA fails to modify basal DA overflow in the NAc, indicating the existence of a tonically active KOR system in the NAc that regulates basal DA tone in the NAc. In view of the localization of KOR on DA terminals, these...

Anion ChanneLs Osmoiyre Transport and pH ReGULAtion

Activation of Cl_ channels leads to cellular loss of KCl and osmotically obliged water and thus to cell shrinkage. Some anion channels further allow exit of organic osmolytes such as taurine (Lang et al., 1998b,e Moran et al., 2000), an effect contributing to cell shrinkage (Lang As organic osmolytes stabilize cellular proteins (Lang et al., 1998a), their loss could destabilize proteins. Inhibition ofinositol uptake has indeed been shown to induce renal failure, presumably because of apoptotic death of renal tubular cells (Kitamura et al., 1998).

Chemistry and Mechanism of Action

They produce analgesia, antipyresis, and antiinflamma-tory effects. However, they are more potent than aspirin, with a decreased incidence of side effects such as gastric irritation. Ketoprofen inhibits lipoxygenase and COX, thus decreasing the production of both leukotrienes and prostaglandins. It also decreases lysosomal release of enzymes in inflammatory diseases. The principal differences among these drugs lie in the time to onset and duration of action. Naproxen has a long half-life, whereas fenoprofen and ketoprofen have short half-lives. All of the drugs are extensively metabolized in the liver and require adequate kidney function for clearance of the metabolites. The drugs vary in plasma protein binding, but clearly all are bound to a relatively high degree and can interfere with the binding of other drugs that compete for plasma protein binding (as described for aspirin). The one exception is ketoprofen, which although highly bound to plasma proteins, does not appear to alter...

Treatment of hyperosmolar states

The therapeutic goal in hypernatremia is reduction of plasma osmolality towards normal by the administration of an excess of free water. Removal of solute is necessary only after inadvertant administration of NaCl it is not usually a part of therapy and is accomplished by dialysis or diuretic administration. When free-water administration is planned, the major therapeutic questions are the type of fluid to be given and its rate of administration. Most agree that patients with hypernatremic dehydration should be treated with fluid which provides free water in excess of electrolytes. Fluid therapy is usually calculated to be administered over about 48 h

Review Of Congestive Heart Failure

Congestive heart failure may be defined as nonefficient pumping of the heart. This inefficiency in pumping the heart leads to an increase in the size of the heart and an increase in the heart rate. This increase in heart size and heart rate result because of the heart's attempt to compensate for the poor efficiency in pumping blood to other parts of the body. Consequently, the kidneys improperly function. Improperly functioning kidneys result in edema of the extremities due to improper excretion (removal) of sodium and waste products in the urine. If a patient's congestive heart failure becomes acute, he may have pulmonary edema due to poor kidney function.

Glucoseinsulin infusions

Insulin promotes potassium entry into cells by mechanisms separate from glucose entry glucose is also required to prevent hypoglycemia. There is no general agreement on the dose to be used. Commonly used prescriptions include 15 units of soluble insulin in 50 ml of 50 per cent glucose given centrally over 20 to 30 min, and 15 to 20 units of insulin in 500 ml of 10 or 20 per cent glucose over 30 to 60 min. All methods will reduce plasma potassium by approximately 1 mmol l over a period of 30 to 60 min and will usually maintain potassium at the lower level for 3 to 6 h, after which the treatment may be repeated. This may be sufficient to maintain plasma potassium levels at acceptable levels, but is usually inadequate in hypercatabolic patients and those with established renal failure in such cases it will buy time for definitive treatment.

Diabetic ketoacidosis

In diabetic ketoacidosis, hyperkalemia may develop as a result of metabolic acidosis, insulin deficiency, and reduced renal excretion. Hyperkalemia usually accompanies a large whole-body potassium deficit. It is unusual for extreme methods of potassium control to be needed, and potassium levels will usually return to normal with replacement of the volume and insulin deficits. Very occasionally it is necessary to give calcium chloride or gluconate for myocardial protection, and a period of hemofiltration or dialysis may be required in patients with coexistent oliguric renal failure. In most patients it is necessary to start potassium replacement as plasma potassium levels fall into the upper part of the normal range thereafter plasma potassium levels should be checked frequently (every 1-2 h).

Goodpastures Syndrome

The role of T cells in the induction of anti-GBM disease is less clear. Initially, the therapeutic effects of cyclosporin A on anti-GBM antibody production and proteinuria in BN rats with EAG suggested that T cell help is required (Reynolds etal., 1991). Such a role has then been demonstrated in bursectomized chicks that, upon immunization with heterologous GBM, developed nephritis in the absence of autoantibodies. Oral tolerization of Wistar Kyoto rats (Reynolds and Pusey, 2001) and mice (Kalluri et al., 1997) leads to a significant reduction in circulating IgG2a but not IgG1, suggesting a downregulation of the Th1 response. Moreover, in rats that have been orally tolerized there is a dose-dependent reduction in the proliferative response of the splenic T cells to GBM antigens in vitro. Its in vivo counterpart probably is a significant reduction in the severity of the disease. In addition to indirect effects, a direct role of T cells in the induction of glomerular injury has also...

Other Nephritogenic Autoantibodies

Among the non-anti-DNA autoantibodies involved in kidney damage, those directed to a-enolase have recently been shown to be associated with nephritis. They are detectable in 27 of SLE patients (70 of them have active nephritis) (Pratesi et al., 2000), in 30 of mixed cryoglobulinemia patients with renal involvement (Sabbatini et al., 1997), in 40 of ANCA-positive vasculitis patients (Moodie et al, 1993), in 69 of patients with the primary form of the membranous nephritis, and in 58 of patients with secondary membranous nephritis (Wakui et al., 1999). Taken together, these data suggest that antibodies specific for a-enolase may play a role in nephritis. Plasminogen receptors are a heterogeneous group of proteins with carboxy-terminal lysines, characterized by a low affinity for plasminogen, a high density, and a ubiquitous distribution on different cell types. Plasminogen activation to plasmin takes place on fibrin surfaces or on cell membranes, where plasmin has increased fibrinolytic...

Alkali administration

Isolated alkali ingestion or administration only causes persistent metabolic alkalosis when the absorption is massive and prolonged. Much more commonly, metabolic alkalosis occurs after alkali administration in patients who present or develop oliguric renal failure. Typical situations in critically ill patients are abundant transfusions of citrated blood for hemorrhagic shock, or sodium bicarbonate therapy for metabolic acidosis due to circulatory arrest. Considerable alkalosis may develop when the excess lactate is metabolized and bicarbonate cannot be eliminated. In patients with renal failure, metabolic alkalosis can also result from the administration of lactate in the hemofiltration replacement fluid.

Digitalis And The Related Glycosides

Digitalis and related glycosides have very narrow therapeutic indices (the treatment dose is very close to the toxic dose) and many drug-drug interactions. The dose must also be adjusted in renal failure, which is common in CHF patients. For these reasons digitalis is reserved for acute symptomatic heart failure or in those patients with CHF and atrial fibrillation.

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