Biocompatible dialysis membranes and acute renal failure: a study in post-operative acute tubular necrosis in cadaveric renal transplant recipients

Previous experimental and human data suggests a detrimental effect on the course of acute renal failure related to exposure of blood to artificial dialysis membranes of poor biocompatibility. We performed a 2.5-year prospective randomized trial to compare the clinical course of acute renal failure (post-operative ischemic acute tubular necrosis, ATN) in patients receiving a cadaveric renal transplant requiring supportive hemodialysis in the immediate post-transplant setting. Patients were randomized to either a cuprophane or polymethylmethacrylate (PMMA) conventional hollow fiber dialyzer. All patients received a standard immunosuppressive regimen which included induction therapy with either horse anti-thymocyte gamma globulin (ATGAM) or the murine anti-CD3 monoclonal antibody (OKT3). Of 53 patients randomized, 17 were excluded (2 for intervening biopsy-proven rejection prior to recovery from ATN, 10 for primary graft nonfunction and 5 for other reasons), leaving 36 evaluable cases of uncomplicated ATN, 18 in each group. There was no difference by age, race, gender, cause of ESRD, immunosuppressive regimen, cold or warm ischemia time, use of pre-transplant dialysis, percent oliguria or the incidence of intra-dialytic hypotension between the 2 groups. There was no difference in the mean time to recovery from ATN posttransplant (8.9 days in the cuprophane group vs 9.5 days in the PMMA group, p = NS) or in the average number of hemodialysis treatments required (3.6 in both groups, p = NS). There was also no difference in long term allograft outcome in terms of the nadir serum creatinine, the number of episodes of subsequent acute rejection or in the development of chronic rejection. An intent-to-treat analysis of all 53 originally randomized patients similarly yielded no significant differences. A subsequent, non-randomized study using a membrane of intermediate biocompatibility (Hemophan) also showed no difference in recovery time from ATN. Bioincompatible membranes do not seem to have a significant clinical impact on the course of recovery of this form of acute renal failure. The striking benefits of biocompatibility in the course of ARF seen in other human trials may relate more to the non-renal systemic toxic effects of bioincompatibility.     

Prevention of acute renal failure

Acute renal failure (ARF) induced by therapeutic agents that are nephrotoxic (e.g., gentamicin, cisplatin, amphotericin, and nonsteroidal anti-inflammatory drugs) or hypotension associated with anesthesia and surgery unfortunately occur with some regularity in small animal practice. Several clinical conditions have been identified that can increase the risk of hospital-acquired ARF in dogs. Recognition of these risk factors allows the clinician to assess the risk/benefit ratio for various drugs and/or procedures. Additionally, initiating protective measures and increasing the monitoring of renal function in those patients that require potentially harmful treatment may decrease the incidence of hospital-acquired ARF.     

Glyceraldehyde-3-phosphate dehydrogenase from Tetrahymena pyriformis: enzyme purification and characterization of a gapC gene with primitive eukaryotic features

The characteristics of acetate-free biofiltration (AFB) are now well documented in patients with chronic renal failure: hemodynamic tolerance, correction of acid-base imbalance, buffer-free dialysate (without acetate) and absence of backfiltration. This hemodialysis technique can be beneficial to patients with acute renal failure (ARF). In our intensive care unit, we prospectively studied 29 patients with isolated ARF or ARF associated with failure of other organs. All eligible patients were randomly assigned to undergo dialysis with bicarbonate hemodialysis (BH) or with (AFB). All used the same high flux biocompatible dialysis membranes. Effectiveness and hemodynamic tolerance of hemodialysis sessions and evolution of patients were analyzed. Correction of metabolic disorders, although better in the AFB group was not statistically different from that in the BH group. Re-equilibration of acid-base balance was also similar, with or without mechanical ventilation. Heparin consumption was significantly higher in the AFB group, with no effect on haemorrhagic complications. Analysis of hypo- and hypertensive episodes, defined as arterial pressure (AP) variations 20% greater than initial pressure, showed no difference in terms of number or degree of AP variation. However, weight loss and the rate of ultrafiltration led to a higher hypotensive risk in the BH group (p < 0.05). Finally, the clinical course and prognosis was similar in both groups. In summary, AFB may be considered as effective a hemodialysis technique as BH in patients with ARF. Weight loss was better tolerated in the AFB group and can be a favorable factor considering the deleterious effect of overhydration in patients admitted to an intensive care unit. This study invites a comparison of longer dialysis session of AFB therapy and continuous hemodiafiltration.     

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.     

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.     

Regulation by serotonin of tooth-germ morphogenesis and gene expression in mouse mandibular explant cultures

Acute renal failure (ARF) is one of the major complications after cardiopulmonary bypass for open heart operations. The present study was undertaken to identify the risk factors for the development of ARF following cardiopulmonary bypass (CPB). Four hundred and forty-seven consecutive patients who underwent open heart procedures from July 1994 to June 1995 were analyzed retrospectively. Their mean age was 55.6 +/- 14.2 (SD) years (range, 18 to 80). Dialysis was instituted whenever a patient exhibited inadequate urine output (<0.5 mL/kg/hr) for 2 to 3 hours despite correction of hemodynamic status and diuretic therapy, especially if fluid overload, hyperkalemia, or metabolic acidosis were also present. Twenty variables were analyzed by univariate analysis; these included nine preoperative variables--age, sex, hypertension, atherosclerosis, diabetes mellitus, left ventricular end-diastolic dimension (LVEDD) >5 cm, preoperative congestive heart failure, renal insufficiency (serum creatinine > or =130 micromol/L on two occasions), and sepsis--10 intraoperative variables--duration of CPB, redo procedures, emergency surgery, use of intraaortic balloon pump (IABP) in operating room, use of gentamicin, use of ceftriaxone, use of sulbactam/ampicillin, requirement of deep hypothermic circulatory arrest, duration of low mean perfusion pressure (mean pressure <50 mmHg for more than 30 minutes), operation on multiple valves--and one postoperative variable--significant hypotension (systolic blood pressure less than 90 mmHg for more than 1 hour). Significant variables or the variables having a trend (p<0.1) to be associated with ARF were included in stepwise multiple logistic regression analyses. Three regression analyses were performed separately. The incidence of ARF requiring dialysis in the study period was 15.0%. Significant risk factors for whole group of patients (regression I) were preoperative renal insufficiency (p<0.0001), postoperative hypotension (p<0.0001), cardiopulmonary bypass time more than 140 min (p<0.005), preoperative congestive heart failure (p<0.01), and history of diabetes mellitus (p<0.01). The risk factors in the valve group of patients (regression II) were preoperative renal insufficiency (p<0.0001) and postoperative hypotension (p<0.05). Risk factors in the CABG patients (regression III) were postoperative hypotension (p=0.0001), CPB time more than 140 min (p<0.05), preoperative renal insufficiency (p<0.05), and age (p<0.05). The authors conclude that preoperative renal insufficiency and postoperative hypotension are the most important independent risk factors for ARF in postcardiac surgical patients. In addition, CPB time greater than 140 minutes and old age are also independent risk factors for ARF in CABG patients. CPB time more than 140 minutes, history of diabetes mellitus, and preoperative congestive heart failure are independent risk factors for development of ARF in our total group of patients. These findings may have important clinical implications in the prevention of ARF in postcardiac surgical patients.     

Applications and outcome of hemodialysis in cats: a review of 29 cases

Hemodialysis (HD) has been used in the management of renal failure in dogs, but its feasibility has not been reported for uremic cats. Therefore, we investigated the technical possibility, efficacy, and complications of intermittent HD in cats with severe uremia. A total of 160 HD treatments were performed on 29 cats with acute renal failure (ARF) (n = 15), chronic renal failure (CRF) (n = 6), or acute on CRF (n = 8) between November 1993 and June 1996. Hemodialysis treatments were performed with transcutaneous dialysis catheters using a bicarbonate-based delivery system, sodium modeling, and volumetric-controlled ultrafiltration. Presenting serum chemistries (mean +/- SD) for all cats were creatinine, 16.4 +/- 7.5 mg/dL; blood urea nitrogen (BUN), 229 +/- 87 mg/dL; phosphate, 15.4 +/- 5.4 mg/dL; potassium, 6.0 +/- 1.6 mEq/L; and HCO3-, 16.0 +/- 4.4 mEq/L. For intensive HD treatments, pre-HD versus post-HD creatinine changed from 10.3 +/- 4.4 to 1.6 +/- 0.9 mg/dL and BUN from 105 +/- 33 to 8 +/- 10 mg/dL. One or more adverse events occurred during 111 (69%) treatments. Dialysis-related events included hypotension, dialysis dysequilibrium, clotting, and bleeding. Nine of 15 (60%) cats with ARF and 1 cat with CRF recovered sufficiently to survive without ongoing need for HD. For the remaining cats, the proximate causes of death were dialysis related in 9 cats, uremia related in 6 cats, and iatrogenic or unknown in 4 cats. Hemodialysis is technically feasible and effectively controls the biochemical disturbances of uremic cats. It is especially valuable for the management of severe ARF, permitting recovery in a large number of cats refractory to conventional therapy. Technical complications and chronic debility, however, may limit its usefulness for cats with advanced CRF.     

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.     

Loop diuretics in the management of acute renal failure: a prospective, double-blind, placebo-controlled, randomized study

BACKGROUND: Studies on the role of loop diuretics in patients with acute renal failure (ARF) are largely retrospective, anecdotal, and poorly controlled. We report the results of a prospective, randomized, placebo-controlled, double-blind study examining the effect of loop diuretics on renal recovery, dialysis, and death in patients with ARF. METHODS: Ninety-two patients with ARF were enrolled into the study. All received intravenous dopamine, 2 micrograms/kg body weight/min throughout, 20% mannitol, 100 ml every 6 h for the first 3 days, and, in a double-blind manner, either torasemide, frusemide, or placebo, 3 mg/kg body weight i.v. every 6 h for 21 days or until renal recovery or death. RESULTS: Renal recovery, the need for dialysis, and death were no different in the three groups. Patients given a loop diuretic had a significant rise in urine flow rate in the first 24 h compared to placebo (P = 0.02). Based on the urine flow rate during the first post-medication day patients were divided into two groups--oliguric (< 50 ml/h) and non-oliguric (> or = 50 ml/h). Non-oliguric patients had a significantly lower mortality than oliguric patients (43% vs 69%, P = 0.01). However, they were less ill (APACHE II score 17.2 vs 20.6, P = 0.008) and had less severe renal failure at entry (creatinine clearance 14 ml/min vs 4 ml/min, P < 0.0001). CONCLUSION: The use of loop diuretics in oliguric patients with ARF can result in a diuresis. There is no evidence that these drugs can alter outcome.     

Acute renal failure: controversies, clinical trials, and future directions

Acute renal failure (ARF) is an important clinical syndrome. Despite the frequent occurrence of ARF, nephrologists have not made major therapeutic inroads in the treatment or prevention of ARF. This article will speculate as to why it has been so difficult to gain a substantial foothold in the ongoing battle against ARF. First, some of the major controversies regarding the pathogenesis of ARF will be considered. Scientific debates regarding the mechanisms of ARF have greatly enriched the scientific literature, but may have slowed the development of clinically applicable therapies. Controversies regarding the treatment of ARF will then be discussed. Next, the fate of several recent clinical trials in ARF will be examined. Finally, the future directions that research in ARF may pursue will be contemplated.     

Acute renal failure syndromes in human immunodeficiency virus infection

Two major groups of renal complications in human immunodeficiency virus (HIV) disease are a spectrum of disorders that result in potentially reversible acute renal failure, primarily acute tubular necrosis (ATN), and HIV-associated nephropathy (HIVAN), predominantly focal and segmental glomerulosclerosis (FSGS), leading to end-stage renal disease (ESRD). Fluid-electrolyte and acid-base derangements frequently encountered in acquired immune deficiency syndrome (AIDS) are major risk factors for the development of acute renal failure (ARF). HIVAN is an unusual form of poorly responsive glomerular disease characterized by nephrotic syndrome, FSGS, and a rapid fulminant progression to ESRD. ARF syndromes encountered in HIV patients are diverse in nature; many are similar to that in non-HIV subjects, whereas some are more common and unique. In general, HIV disease patients with ARF are younger and much sicker. Although ATN secondary to ischemic and toxic injuries is the commonest ARF syndrome, urinary obstruction is a rare cause of severe renal failure. In many AIDS patients afflicted with complicated infections and multi-organ failure, ATN is a terminal event, whereas in others treated aggressively, ARF is associated with good prognosis. In our large comparative study of severe ARF, recovery of renal function and mortality were determined by patient's general hemodynamic status, and not by the presence or absence of HIV infection. The prognosis of hemolytic uremic and thrombotic thrombocytopenic purpura syndromes often observed in HIV patients is much worse than in non-HIV patients. The syndrome of crystalluria-induced ARF is common, and protease inhibitor induced disease is confined to HIV patients.     

A prospective study of ward referrals for renal disease at a Jamaican and a United Kingdom hospital

Seventy ward referrals for renal disease were prospectively studied at each of two tertiary hospitals: University Hospital of the West Indies (UHWI), Kingston, Jamaica and Nottingham City Hospital (NCH), England. At UHWI, the referral population was significantly younger, 89% being less than 60 years of age compared to 40% at NCH (p < 0.05). The leading cause of acute renal failure (ARF) at UHWI was systemic lupus erythematosus (SLE) followed by acute tubular necrosis (ATN). The leading causes of ARF at NCH were ATN and obstructive uropathy. Primary renal disease and diabetes mellitus were the major causes of end-stage renal disease (ESRD) at both centres, followed by SLE and hypertension at UHWI and renovascular disease and chronic pyelonephritis at NCH. Nephrotic syndrome occurred more frequently at UHWI than at NCH but the numbers were small (p < 0.05). Mortality rates were similar among patients with ARF and nephrotic syndrome at both centres, but were higher for patients with chronic renal failure (CRF) at UHWI than at NCH (p < 0.05). Continuous ambulatory peritoneal dialysis (CAPD) was a frequent mode of renal replacement therapy at NCH (76% v 19% on haemodialysis). At UHWI, CAPD was not available and 45% of patients with ESRD were not offered maintenance dialysis because of inadequate facilities. The major difference in management and outcome between the two centres occurred in cases with CRF, suggesting that survival in patients with CRF in Jamaica could be improved if this therapeutic modality was available.     

Renal insufficiency after intravenous immune globulin therapy: a report of two cases and an analysis of the literature

Over the past decade, intravenous immune globulin therapy (IVIG) has gained widespread use for a variety of clinical disorders. IVIG treatment is associated with a number of complications, including acute renal failure (ARF). Although the cause of IVIG-associated ARF is unknown, it may be related to the stabilizing agent used in the IVIG preparation. The development and resolution of ARF is typically rapid, but is some cases recovery may be delayed and require renal replacement therapy. In such patients, recurrence of ARF may be avoided by selection of a preparation with a different stabilizing agent. Two cases of IVIG-induced ARF are described, and all reported cases are analyzed to assess the probable mechanism of renal injury.     

Endothelial cell dysfunction in patients with impaired renal function

In order to investigate endothelial cell dysfunction in patients with impaired renal function, we measured circulating endothelin (ET-1) and thrombomodulin (Tm) concentrations used as markers for endothelial cell injury in patients with renal failure. 1) ET-1 and Tm were significantly higher in patients with renal failure and pre-dialysis patients than in normal subjects. Tm in CRF patients was significantly greater than that in ARF patients. In contrast, ET-1 was significantly greater in ARF than in CRF. 2) A positive correlation was found between serum creatinine concentration (Cr) and Tm in pre-dialysis patients. However, no correlation was found between Cr and ET-1. 3) A positive correlation was found between Tm and the duration of dialysis in HD patients, but not in CAPD patients. 4) With the improvement of renal function after regular HD treatment, a substantial reduction was found in ARF patients in both Tm and ET-1, but not in CRF patients. The present study suggests the presence of endothelial cell dysfunction in patients with impaired renal function. The progression of endothelial cell damage may differ between patients on HD and those on CAPD. In addition, it is suggested that endothelial cell dysfunction reverses in ARF patients with improved renal function.     

Renal failure following gentamicin in combination with clindamycin

Acute renal failure (ARF) occurred concomitantly with the administration of gentamicin in combination with clindamycin in three patients in whom no other known predisposing cause of ARF could be demonstrated. The evidence for combined nephrotoxicity consisted of the temporal relationship between administration of the antibiotics and the development of ARF, and the prompt improvement in renal function upon cessation of therapy. Complete or partial recovery of renal function occured in all patients. Renal function should be carefully monitored in patients receiving this antibiotic combination.     

Leukocytes, cell adhesion molecules and ischemic acute renal failure

Ischemic acute renal failure (ARF) is a common clinical syndrome, associated with high morbidity and mortality, for which there is no specific therapy. Polymorphonuclear neutrophils (PMN) recruited during reperfusion have been implicated as mediators of renal parenchymal injury in ischemic ARF. Leukocyte adhesion molecules appear to facilitate PMN recruitment in this setting. Complementary studies using monoclonal antibodies, antisense oligonucleotides and gene "knock-out" indicate that blockade of CD11/CD18 integrins and intercellular adhesion molecule-1 (ICAM-1) attenuates ARF in some experimental models of renal ischemia. These exciting observations may herald the development of novel anti-adhesion strategies for use in human disease.     

Acute renal failure--etiologic and therapeutic considerations. A five-year experience at a single institution

In the present study we highlight the epidemiology, etiologic spectrum, and evaluation of ARF in adults. We then expand on the pathophysiologic mechanisms of renal failure and discuss the rationale for current therapeutic strategies in ARF patients. A total of 79 patients (45 male, female 34), aged 18-75 years (median age 51.2 +/- 17.7 years) with acute renal failure were studied in 5 years (January 1990 through October 1995). Emergency hemodialysis sessions following an acute anuric episode were instituted in 39 cases (49.3% of all patients). The median number of hemodialysis procedures per patient treated at our institution was 3.2 +/- 1.9. The total number of acute interstitial nephritis-associated ARF was 40. In 30 of them (75%) the acute renal insult included a combination of several therapeutic antimicrobial agents, in 2 cases (5%) ARF followed the administration of nonsteroidal anti-inflammatory drugs, in 1 (2.5%) it resulted from a combined therapeutic regimen and in the remaining 5 (12.5%) from the application of a single drug. Acute interstitial nephritis developed in 2 patients following a viral infection. In the hemodialysis-treated ARF group 12 patients (29.77%) had interstitial nephritis and 2 patients (5.13%) presented with renal impairment for an unspecified period of time preceding the development of overt ARF. In a subset of this group of patients, ARF occurred in 7 patients (17.95%) following an urologic intervention, in 8 patients (20.51%) as a consequence of thermal or mechanical trauma or intoxication and in 3 cases (7.69%) it resulted from fever of unknown origin. Three patients with postoperative peritonitis and 4 other (10.26%) with postoperative complications were encountered in our series. No cases of septic abortion-related or obstetric-related ARF were recorded. 92.3% of all hemodialysis-treated patients seen at our Institution had received a combination of antibiotics and only 2 patients had been pre-treated with a single antimicrobial agent. Our results underscore the strong tendency towards diversity in the etiologic spectrum of clinical entities causing ARF and the increase in the number of acute interstitial nephritis. These factors highlight the importance of precise dosing and administration of drugs, especially antibiotics, as well as the duration of antibiotic treatment.     

Livedo reticularis, acral necroses and renal failure. Cholesterol crystal embolisms

In a 67 year old patient with multiple cardiovascular risk factors a livedo reticularis, ischemic acral lesions as well as deterioration of renal function five weeks after cardiac catheterism and aorto-coronary bypass surgery led to suspicion of cholesterol embolism. Fundoscopy revealed cholesterol crystals in retinal vascular branches thus delivering important diagnostic information. Atheromatous lesions of the entire aorta and the ilio-femoral arteries were possible sources for embolism. The outcome was favorable. The lesions of the toes regressed and renal failure did not progress to dialysis. The diagnostic steps taken, the clinical picture of cholesterol embolism, the use of imaging and therapeutic options are discussed.     

Renal failure after open heart surgery

One hundred fifty of 490 patients undergoing open heart surgery had renal failure attributable to cardiopulmonary bypass. In 69, serum creatinine concentrations did not exceed 2 mg/dl and returned to normal by the fourth postoperative day. In 60 patients, serum creatinine attained levels between 2 and 5 mg/dl, oliguria did not develop, and recovery of renal function occurred within 4 to 37 days. Serum creatinine increased to levels exceeding 5 mg/dl in 21 patients, 11 of whom were oliguric. Despite dialysis, 14 of these patients died from cardiac causes or sepsis. Prolonged cardiopulmonary bypass time, hypotension, oliguria, low output syndrome, and hemoglobinemia during open heart surgery correlated with the development of renal failure postoperatively. Although severe renal failure was an uncommon complication after open heart surgery, its occurrence carried a grave prognosis.