Metabolic encephalopathy as a complication of renal failure: mechanisms and mediators

Among patients with end-stage renal disease, nervous system dysfunction remains a major cause of disability. Patients with chronic renal failure who have not yet received dialysis may develop symptoms ranging from mild sensorial clouding to delirium and coma. Dialysis itself is associated with at least three distinct disorders of the CNS: dialysis disequilibrium syndrome; dialysis dementia; and progressive intellectual dysfunction. Peripheral neuropathy is also a major cause of disability in uremic subjects. It is believed that aluminum contributes to the pathogenesis of dialysis dementia. Biochemically, brain calcium is elevated in patients with renal failure, probably because of actions of parathyroid hormone on the brain. The diagnosis of dialysis disequilibrium syndrome, intellectual dysfunction, dialysis dementia, and uremic neuropathy can be made by the characteristic clinical pictures of these syndromes and the exclusion of other causes of nervous system dysfunction.     

Free phenols in chronic renal failure

Serum total free phenols are elevated in chronic renal failure, acute renal failure and hepatic coma. Being partly protein-bound, phenols behave during dialysis in a similar manner to considerably larger molecules which are not protein-bound. In view of their potential toxicity they should be considered as an alternative to 'middle molecules'. Patients on regular hemodialysis have retention of phenols if their post-dialysis serum creatinine is above 6-7 mg/dl. Patients on short time dialysis have high pre-dialysis neutral phenol levels. Such levels are sufficiently high to suggest a role in the genesis of neurological symptoms, anemia and bone disease. Certainly pre-dialysis free phenols reflect adequacy of dialysis.     

Treatment of acute renal failure

Acute renal failure is a life threatening illness whose mortality has remained high since the introduction of hemodialysis 25 years ago, despite advances in supportive care. Acute renal failure is an extremely morbid and costly disorder with a significant proportion of patients progressing to end-stage renal disease requiring dialysis. To the nephrologist, acute renal failure remains an extremely frustrating disease, because the pathophysiology is not well understood and the limited therapeutic options force the nephrologist to sit on the sidelines and wait for renal function to return. For example, dialysis remains the only FDA-approved treatment for acute renal failure, but dialysis may also cause renal injury that prolongs renal failure. The purpose of this perspective is to understand the results of the recent, largely negative, clinical trials in view of recent advances in the epidemiology of ARF. This review will also discuss diagnostic tools, strategies for improved design of clinical trials, and other therapeutic interventions that will be needed to properly treat acute renal failure in the 21st century.     

Astrocytic pathology in progressive supranuclear palsy: significance for neuropathological diagnosis

It has been shown that hepatitis C virus (HCV) infection is closely associated with mixed type cryoglobulinaemia. It is also known that HCV infection is rampant among chronic haemodialysis patients. We studied 531 renal failure patients on maintenance dialysis including 170 with positive HCV antibodies for cryoglobulinaemia, and its incidence was compared with controls which consisted of 242 chronic hepatitis C patients without renal failure and 183 healthy adults. Cryoglobulinaemia was present in 30.6% of dialysis patients with HCV infection, 10.8% of dialysis patients without HCV infection, 29.8% of patients with chronic hepatitis C without renal failure, and 0% of healthy adults. Among the 30 new renal failure patients who were started on dialysis within 6 months, four were positive for HCV antibodies, and one of them had cryoglobulinaemia; of the 26 HCV-negative patients, four (15%) were cryoglobulinaemic. The cryocrit values among dialysis patients were much lower than those of the control cases and other reports on non-dialysis cases. Patients with cryoglobulinaemia were generally younger compared with patients negative for this condition. There was no correlation between cryoglobulinaemia and past blood transfusion, underlying disease or length of dialysis. Cryoglobulinaemic patients seem to develop renal failure at relatively young ages and a considerable proportion of cryoglobulinaemic dialysis patients may have already had cryoglobulinaemia at the time of the start of haemodialysis. There was no indication that the presence of cryoglobulin in serum adversely affects the liver disease nor increases serum virus load in HCV-infected dialysis patients. Thus, it was concluded that although HCV infection has a certain role in the development of cryoglobulinaemia in dialysis patients, they develop cryoglobulinaemia less frequently and produce cryoglobulin to a lesser degree in the presence of HCV infection as compared with non-dialysis patients.     

Acetohexamide hypoglycemia: treatment by peritoneal dialysis

Acetohexamide hypoglycemia in a patient with renal failure has been successfully treated by peritoneal dialysis. Peritoneal dialysis was done in such a patient, and specimens of serum were collected to measure levels of acetohexamide and its main active metabolite, hydroxyhexamide. During dialysis, hypoglycemia was corrected. After 17 1/2 hours of dialysis, serum acetohexamide level was essentially unchanged. Serum hydroxyhexamide level had decreased at a slower rate than the rate of decrease previously measured in a uremic patient not on dialysis. Although peritoneal dialysis may correct the hypoglycemia, the data suggest that acetohexamide and hydroxyhexamide are not dialyzable. Due to these problems this drug should not be used in patients with chronic renal failure. The drug of choice to control hyperglycemia in patients with renal insufficiency is insulin. If for any reason insulin cannot be used, tolbutamide is the oral hypoglycemic agent of choice.     

Dialysis in the treatment of renal failure in patients with liver disease

The value and effects of treating renal failure by dialysis are analyzed in a series of 84 patients with various types of liver disease. Although none of the 25 patients with cirrhosis survived, six of 50 with fulminant hepatic failure recovered completely as did seven of nine patients with renal failure secondary to extrahepatic biliary tract obstruction or with liver and renal damage following episodes of severe hypotension. Dialysis was required for seven weeks before diuresis occurred in one patient in the latter group. Both peritoneal and hemodialysis satisfactorily controlled plasma urea and creatinine levels, except in patients with fulminant hepatic failure in whom this was only achieved by hemodialysis. Complications of dialysis were most common in patients with cirrhosis and fulminant hepatic failure and included hypotension, gastrointestinal bleeding, and intraperitoneal sepsis. Overall, the results show that dialysis is only worth attempting in those patients in whom recovery of the underlying liver lesion is possible, and even then treatment for prolonged periods may be necessary.     

Acute venous hemodialysis using the unipuncture apparatus

Hemodialysis is a well recognized treatment modality for the support of patients with acute renal failure. In such patients, rapid access to the circulation for hemodialysis is important. For those patients with self-limited acute renal failure in whom recovery is expected, a rapid means of gaining temporary access to the circulation would be particularly desirable. The Seldinger technic for femoral vein catheterization and the use of the unipuncture dialysis apparatus have been combined to meet this requirement. The efficiency of unipuncture dialysis through a single femoral catheter compares favorably with the efficiency of dialysis by the standard two catheter technic.     

Thyroid dysfunction in uremia: evidence for thyroid and hypophyseal abnormalities

Disturbances in thyroid function and a high prevalence of goiter develop in patients on chronic hemodialysis. This study shows that in patients on dialysis, mean serum thyroxine and triiodothyronine levels are lower than normal. Patients with chronic renal failure not on dialysis, have mean serum thyroxine levels similar to normal subjects and low mean serum triiodothyronine levels. However, both serum thyroxine and triiodothyronine concentrations decrease as the renal failure worsens. In addition, both groups of patients with renal failure have a decreased serum thyroxine response to oxogenous thyrotrophin and a diminished serum thyrotrophin response to thyrotrophin-releasing hormone. These data suggest the presence of an intrathyroidal and an hypophyseal defect in uremic patients. Although serum iodide concentrations are elevated, there is no correlation between the level of serum iodide and the degree of renal failure. Therefore, we have no direct evidence that iodide excess is responsible for the abnormalities observed.     

Serious renal disease in Egypt

We studied serious renal disease in Egypt by registering all 155 patients coming to the nephrology service at the University of Cairo during a period of 62 days in 1993. The patients presented with severe uremic symptoms. Admission creatinine and urea levels were high, 804 mumol/l and 64 mmol/l. Fifteen percent of the patients died; 115 underwent dialysis. Sixty patients presented with chronic renal failure; 53 with acute renal failure, but 24 of these were later found to have end-stage renal failure. Of 29 patients with true acute renal failure, 11 (38%) had pre-renal failure and 7 (24%) post-renal failure. Twenty-one patients were followed up after transplantation and chronic dialysis, another 17 had nephrotic syndrome, 3 hypertension, and one had asymptomatic urinary abnormalities. The most common specific etiology for chronic end-stage renal failure was diabetes mellitus type II in the older patients; second most common was Schistosoma in the younger ones. Most diabetic patients came from the city. All but one Schistosoma patient came from rural Egypt. In the 22 patients who underwent renal biopsy the most common diagnosis was mesangio capillary glomerulonephritis. The prevalence of acute renal failure, particularly iatrogenic-toxic, is increasing.     

The pathogenesis and consequences of AGE formation in uraemia and its treatment

Advanced glycation endproducts (AGEs) accumulate in uraemia as a consequence of diminished clearance of low molecular weight forms which retain their reactivity and may subsequently combine with circulating and tissue macromolecules. Successful renal transplantation is the only form of renal replacement therapy which effectively clears these circulating AGEs; both haemodialysis and peritoneal dialysis are comparatively ineffective although high-flux haemodialysis confers some benefits. De novo AGE formation may be accelerated in uraemia due to carbonyl and oxidative stress leading to further accumulation. The consequences for the patient with chronic renal failure may be acceleration of vascular disease, renal failure progression and dialysis-related amyloidosis. Accelerated peritoneal AGE formation as a consequence of treatment with peritoneal dialysis fluids may be detrimental to peritoneal membrane function but does not appear to contribute to systemic elevation of AGEs.     

Acute renal failure following copper sulphate intoxication

Eleven out of a series of twenty-nine patients (37-9%) with acute copper sulphate poisoning developed acute renal failure. Intravascular haemolysis appeared to be the chief factor responsible for renal lesions in these patients. Histological lesions observed in the kidney varied from those of mild shock to well established acute tubular necrosis. In one case, granulomatous lesions were seen in response to tubulorrhexis. Renal failure was the chief indication for dialysis in ten patients, whereas one patient was dialysed primarily for removal of copper. Notwithstanding the adequate control of uraemia by dialysis, only six of the eleven patients recovered. Septicaemia was responsible for death in three, hepatic failure in one and methaemoglobinaemia in another. It is postulated that release of copper from haemolysed red cells during acute haemolytic episodes may initiate, or contribute to, the development of renal damage.     

The protective effect of Clostridium novyi type B alpha-toxoid against challenge with spores in guinea pigs

Acute renal failure continues to be a difficult clinical problem despite developments in dialysis and critical care. Diagnosis of the etiology frequently determines treatment. Urinalysis remains an essential diagnostic tool in the approach to acute renal failure, particularly with the current emphasis on cost-containment and evidence-based medicine. This review focuses on some of the characteristic features in the urinalysis found in different forms of acute renal failure, current developments into the molecular basis for these urinary abnormalities, and new markers on the horizon.     

Polymorphism in the microsatellite located in the promoters of the Tnfa and Tnfb genes of different mouse strains

BACKGROUND: Hyperparathyroidism is common in patients with renal disease. These patients may require operation for this disease if it cannot be controlled by medical therapy. Because these patients continue to have renal failure, the risk of recurrence and reoperation is high. METHODS: Sixty-nine patients with renal failure underwent operation for hyperparathyroidism. These patients were followed up on dialysis or after transplantation. RESULTS: Sixty-nine patients, aged 2 to 71 years old, with end-stage renal disease required parathyroidectomy for hyperparathyroidism 6.2 +/- 4.2 (standard deviation) years after beginning dialysis. Thirty-six patients had undergone renal transplantation (creatinine = 1.6 +/- 0.4 mg/dL). All patients had elevated parathyroid hormone (PTH) levels. Sixty-eight patients had hyperplasia; 1 patient had adenoma. Six patients required reoperation for recurrent hyperparathyroidism 30 to 123 months after their initial parathyroidectomy. CONCLUSION: Patients with end-stage renal disease are prone to abnormalities of calcium metabolism. They frequently develop parathyroid hyperplasia. Recurrence can occur following operation because of continuing renal failure.     

Who does best on CAPD? A study to identify self-care determinants

Individuals with end-stage renal failure (ESRF) may be offered two main types of renal replacement therapy--haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). At present approximately 50% of individuals within the United Kingdom who require dialysis are maintained on CAPD whilst the remainder receive haemodialysis (1).     

Renal failure after snake bite

Three cases of acute renal failure after snake bite are presented. All required dialysis and the recovery phase was prolonged in each case. Investigations show that microangiopathic haemolytic anaemia was associated with the acute renal failure.     

Pharmacokinetics of cefamandole in patients undergoing hemodialysis and peritoneal dialysis

The pharmacokinetics of cefamandole nafate, a new parenteral cephalosporin derivative, were evaluated in 11 patients with chronic renal failure (creatinine clearance less than 5 ml/min), including five patients during hemodialysis, four patients during routine peritoneal dialysis, and two patients during the interdialytic period. Peak serum levels of cefamandole were comparable to those observed in patients with normal renal function. Clearance of the drug during the interdialytic period and during hemodialysis and peritoneal dialysis was minimal, with a resultant significant prolongation of serum half-life. The nondialyzability of cefamandole is in contrast with reported studies of cephalothin, where significant reduction of the serum half-life was achieved during hemodialysis but not peritoneal dialysis. The concentration of cefamandole in the peritoneal dialysate after parenteral administration was observed to be bactericidal for many gram-negative pathogens and, with the exception of Streptococcus faecalis, most gram-positive organisms found in bacterial peritonitis in patients with severe renal failure. The present data suggest that if stable bactericidal serum levels of cefamandole are to be maintained during hemodialysis and peritoneal dialysis, a parenteral loading dose must be administered followed by one-half the loading dose every half-life.     

Perioperative renal dysfunction and cardiovascular anesthesia: concerns and controversies

In patients with renal disease undergoing cardiovascular surgery, perioperative management continues to be a challenge. Traditional answers have turned into new questions with the introduction of new agents and the redesign of old techniques. For ARF prevention, early recognition of pending deleterious compensatory changes is critical. Theoretically, therapeutic intervention designed to prevent ischemic renal failure should be designed to preserve the balance between RBF and oxygen delivery on one hand and oxygen demand on the other. Maintenance of adequate cardiac output distribution to the kidney is determined by the relative ratio of renal artery vascular resistance to systemic vascular resistance. Indeed, it should not be surprising to learn that norepinephrine (despite its vasoconstricting effect) has been reported to have no deleterious renal effects in patients with low systemic vascular resistance. Until recently, strategies for the treatment of ARF have been directed to supportive care with dialysis (to allow tubular regeneration). Various therapeutic maneuvers have been introduced in an attempt to accelerate the recovery of glomerular filtration, including dialysis, nutritional regimens, and new pharmacologic agents. A recent small prospective trial of low-dose dopamine in the prophylaxis of ARF in patients undergoing abdominal aortic aneurysm repair showed no benefit in those patients receiving dopamine. Conversely, the effects of intravenous atrial natriuretic peptide in the treatment of patients with ARF appear to offer benefit in patients with oliguria. Among 121 patients with oliguric renal failure, 63% of those who received a 24-hour infusion of atrial natriuretic peptide required dialysis within 2 weeks compared with 87% who did not. Whether this effect will be borne out in the future remains to be determined. The administration of epidermal growth factor after induction of ischemic ARF in rats has been shown to enhance tubular regeneration and accelerate recovery of kidney function. Human growth factor administration has been shown to increase GFR 130% greater than baseline in patients with chronic renal failure, but no data for clinical ARF have been reported. In addition, there have been significant improvements in dialysis technology in the treatment of ARF. Modern dialysis uses bicarbonate as a buffer as opposed to acetate, which reduces cardiovascular instability, and has more precise regulation of volume removal. Dialysate profiles and temperatures improve hemodynamics and reduce intradialytic hypotension. Techniques of hemodialysis without anticoagulation have reduced bleeding complications. Finally, dialysis membranes activate neutrophils and complement less with the biocompatible membranes used today that reduce recovery time and dialysis treatment. Evidence indicates that activation of complement and neutrophils by older dialysis membranes caused a greater incidence of hypotension, adding to ischemic renal injury. It remains to be determined whether early and frequent dialysis with biocompatible membranes, as well as other therapeutic interventions, will increase the survival of patients with perioperative ARF.     

Caring for a rehabilitation patient with chronic renal failure and end-stage renal disease

Patients with chronic renal failure and end-stage renal disease frequently suffer medical setbacks that necessitate a course of rehabilitation. Planning care for these patients requires special consideration if they are to attain a level of function close to what they enjoyed prior to the event that required them to be hospitalized. In this article, the author describes chronic renal failure, end-stage renal disease, types of dialysis and types of access, assessment upon admission to rehabilitation, and nursing care for patients with chronic renal failure and end-stage renal disease in a rehabilitation facility. This information can help nurses learn about what to look for and what questions to ask, common medications and laboratory values, dietary management, and the creation of a successful rehabilitation experience.     

Guidelines for nonspecific bronchial provocation tests

This study evaluated the effects of a predialysis patient education programme on functioning and well-being in 28 uraemic patients. The programme consisted of four group sessions with the following themes: renal disease and dietary restriction, active renal replacement therapy, physical exercise, and the impact of chronic renal failure on economy, family and social life. Three to 9 months after having started dialysis the patients were evaluated regarding symptoms, perceived health (Health Index), functional (SIP) and emotional (STAI) status. Twenty-eight patients already on dialysis treatment informed according to conventional routines constituted the comparison group. There were no significant differences between the groups regarding age, sex, educational or social background, duration of kidney disease, choice of dialysis treatment, cause of renal disease and laboratory tests except for s-urea. The patients who participated in the education programme scored significantly better mood, less mobility problems (HI), less functional disabilities (SIP) and lower levels of anxiety (STAI) compared to the comparison group. There were no significant differences between the two groups regarding symptoms and overall health. The differences between the groups prevailed during the first 6 months on dialysis treatment, after which the differences disappeared. In the comparison group age correlated significantly to anxiety and overall SIP, which was not the case in the experimental group. In conclusion, the experimental group that participated in a predialysis patient education programme, showed better functional and emotional well-being than the non-educated comparison group. The positive effects of participating in an education programme prevailed during the first 6 months of dialysis treatment. Moreover, the younger patients seemed especially to benefit from participation in a predialysis patient education programme. It is suggested that patient education should be ongoing for patients with end-stage renal failure initiated during the predialysis stage and continued after maintenance dialysis has been established.     

The advanced glycation endproduct pentosidine and monocyte activation in uremia

RATIONALE: Advanced glycation endproducts (AGEs) contribute to the pathogenesis of vascular complications in diabetes, aging and end-stage renal disease (ESRD). Immune abnormalities in patients with chronic renal failure and those treated by dialysis contribute to high rates of morbidity and mortality. We therefore sought a relationship between a circulating marker of immune dysfunction and plasma levels of the AGE pentosidine. METHOD: We studied non-diabetic patients with mild to advanced renal failure (n = 60), and with ESRD treated by hemodialysis (HD) (n = 44) and peritoneal dialysis (PD) (n = 19). The plasma protein content of the well characterized AGE, pentosidine was measured using HPLC. In the same samples the monocyte activation product neopterin was measured by RIA. RESULTS: Plasma levels of pentosidine and neopterin increased in parallel with the progression of renal failure. Pentosidine and neopterin were highly correlated in all patients even after adjustment for Ccr. This correlation was also present in patients with ESRD. CONCLUSION: These data suggest that the AGE pentosidine is associated with monocyte activation in renal failure, an interaction which may contribute to accelerated rates of complication and death by as yet unknown mechanisms.