Idiopathic retroperitoneal fibrosis: a role for mycophenolate mofetil.

PURPOSE: Idiopathic retroperitoneal fibrosis (IRPF) is an unusual progressive illness for which consistent therapeutic recommendations have not been devised. The present report describes a collaborative nephrology and urology approach to distinguish IRPF from secondary disease and then combine necessary acute surgical or radiological intervention with short-term corticosteroid and with mycophenolate mofetil (MM) to facilitate steroid tapering and long-term management. MATERIALS AND METHODS: 21 patients have been evaluated and followed over a 7-year period, 16 with characteristic IRPF and 5 with secondary retroperitoneal disease. IRPF patients initially received high-dose corticosteroid and MM. We report clinical follow-up along with imaging studies of the retroperitoneum and related organs, serologic markers for systemic disease, and nonspecific acute-phase reactants as indicators of ongoing disease activity. RESULTS: Among IRPF patients, uniform success in stabilizing clinical signs and symptoms, radiological disease in the retroperitoneum and associated organs, and inflammatory indicators have been observed. Corticosteroid therapy can be limited to 6 months or less and MM to approximately 2 years, all with substantial impact on the natural history of IRPF. CONCLUSIONS: This is not a randomized, controlled trial, and patients were often referred with prior complications and/or treatments, however, the systematic approach and consistent results support the utility of MM as a safe and effective choice for long-term stabilization in IRPF.

Renal replacement therapy for severe acute renal failure.

Acute renal failure (ARF) is a sentinel event that signals increased complexity and risk during the course of any general hospital admission. The initial diagnosis and specific treatment of the ARF already pose a daunting challenge, but the stakes are even higher when ARF is severe and renal replacement therapy (RRT) is needed. This paper addresses the onset and diagnosis of ARF only briefly and then turns to the specific choice and design of RRT modality that will optimize the ultimate outcome. Some guidelines are proposed since definitive standards for the treatment of severe ARF in critically ill patients are still evolving.

Estimating the impact of renal replacement therapy choice on outcome in severe acute renal failure.

BACKGROUND: Mortality in severe acute renal failure (ARF) requiring renal replacement therapy (RRT) approximates 50% and varies with clinical severity. Continuous RRT (CRRT) has theoretical advantages over intermittent hemodialysis (IHD) for critical patients, but a survival advantage with CRRT is yet to be clearly demonstrated. To date, no prospective controlled trial has sufficiently answered this question, and the present prospective outcome study attempts to compare survival with CRRT versus that with IHD. METHODS: Multivariable Cox-proportional hazards regression was used to analyze the impact of RRT modality choice (CRRT vs. IHD) on in-hospital and 100-day mortality among ARF patients receiving RRT during 2000 and 2001 at University of Michigan, using an "intent-to-treat" analysis adjusted for multiple comorbidity and severity factors. RESULTS: Overall in-hospital mortality before adjustment was 52%. Triage to CRRT (vs IHD) was associated with higher severity and unadjusted relative rate (RR) of in-hospital death (RR = 1.62, p = 0.001, n = 383). Adjustment for comorbidity and severity of illness reduced the RR of death for patients triaged to CRRT and suggested a possible survival advantage (RR = 0.81, p = 0.32). Analysis restricted to patients in intensive care for more than five days who received at least 48 hours of total RRT, showed the RR of in-hospital mortality with CRRT to be nearly 45% lower than IHD (RR = 0.56, n = 222), a difference in RR that indicates a strong trend for in-hospital mortality with borderline statistical significance (p = 0.069). Analysis of 100-day mortality also suggested a potential survival advantage for CRRT in all cohorts, particularly among patients in intensive care for more than five days who received at least 48 h of RRT (RR = 0.60, p = 0.062, n = 222). CONCLUSION: Applying the present methodology to outcomes at a single tertiary medical center, CRRT may appear to afford a survival advantage for patients with severe ARF treated in the ICU. Unless and until a prospective controlled trial is realized, the present data suggest potential survival advantages of CRRT and support broader application of CRRT among such critically ill patients.

Comparison of 3 vancomycin dosage regimens during hemodialysis with cellulose triacetate dialyzers: post-dialysis versus intradialytic administration.

AIMS: Traditionally, vancomycin is administered following dialysis to minimize drug loss when high-flux membranes are employed. Unfortunately, this approach is extremely inconvenient for patients and staff, requiring the patients to remain in the unit for at least 1 hour following dialysis. This study was designed to evaluate the feasibility of administering vancomycin during hemodialysis. Specifically, this study was designed to compare the pharmacokinetics of vancomycin when administered during the last 1-2 hours of dialysis (i.e. intra-dialytic administration) to that administered after completion of dialysis. MATERIALS AND METHODS: In a randomized, 3-way crossover trial, the pharmacokinetics of vancomycin were evaluated in 9 hemodialysis patients, comparing vancomycin 15 mg/kg following dialysis (Phase I), vancomycin 15 mg/kg during the last hour of hemodialysis (Phase II) or vancomycin 30 mg/kg during the last 2 hours of hemodialysis (Phase III). Vancomycin plasma concentrations were obtained over an 8-day period and subsequent comparisons between the treatment approaches were made with paired t-tests or ANOVA, as appropriate. Dialysate vancomycin concentrations determined on Day 1 and Day 3 of Phases II and III were used to calculate the fraction of vancomycin dose removed, and were compared to plasma data using paired t-tests. RESULTS: Vancomycin was significantly removed (33.4 to 39.5%) during a 3- to 4-hour high-flux dialysis session occurring on Day 3 after vancomycin administration. Mean serum concentrations immediately following intradialytic vancomycin administration of 15 mg/kg over the last hour of dialysis or 30 mg/kg over the last 2 hours of dialysis were initially high (77.7 and 95.5 mcg/ml respectively), but fell to 25.9 and 40.5 mcg/ml, respectively, by 4 hours post-dialysis. Predialysis concentrations on Days 3, 5 and 8 were similar for vancomycin 30 mg/kg administered over the last 2 hours of dialysis as compared with a 15 mg/kg dose given after dialysis. Vancomycin 15 mg/kg over the last hour of dialysis resulted in significantly lower subsequent predialysis concentrations than the other dosing schemes. CONCLUSIONS: Vancomycin administration of 30 mg/kg over the last 2 hours of dialysis achieves serum concentrations similar to conventional dosing of 15 mg/kg after dialysis and would allow dosing on a weekly basis.

Analysis of variable flow Doppler hemodialysis access flow measurements and comparison with ultrasound dilution.

The variable flow (VF) Doppler method determines access blood flow from the pump speed-induced change in Doppler signal between the arterial and venous needles. This study evaluated 35 patients in two analyses to assess VF Doppler measurement reproducibility (54 paired measurements) and compared VF Doppler and ultrasound dilution flow measurements (24 paired measurements). VF Doppler measurement variations were 4% for access flow less than 800 mL/min (n = 17), 6% for access flow of 801 to 1,600 mL/min (n = 22), and 11% for access flow greater than 1,600 mL/min (n = 15). The mean measurement coefficient of variation was 7% for VF Doppler compared with 5% for ultrasound dilution. Correlation coefficients (r) between VF Doppler and ultrasound dilution access flow measurements were 0.79 (n = 24; P < 0.0001), 0.84 for access flow less than 2,000 mL/min (n = 20; P < 0.0001), and 0.91 for access flow less than 1,600 mL/min (n = 18, P < 0.0001). VF Doppler measurements using indicated versus measured pump flow rates correlated highly (r = 0.99; P < 0.0001). VF Doppler therefore yields reproducible access volume flow measurements that correlate with ultrasound dilution measurements. The VF Doppler method is dependent on the pump-induced change in access Doppler signal and therefore is inherently most accurate and reproducible at lower access blood flow rates. This method appears capable of determining access flow rates in the clinically useful range.

Variable flow Doppler for hemodialysis access evaluation: theory and clinical feasibility.

Access thrombosis remains an enormous problem for patients on hemodialysis. Current evidence suggests that decreasing access blood flow rate is an important predictor of future access thrombosis and failure. This article describes a method for determining access volume flow and detecting access pathology. The Doppler ultrasound signal downstream from the arterial needle as a function of the variable hemodialysis blood pump flow rate, is used to determine access blood flow. By using this variable flow (VF) Doppler technique compared with duplex volume flow estimates measured in 18 accesses (16 patients with 12 polytetrafluorethylene [PTFE] grafts and 6 autogenous fistulas), the results showed a correlation of 0.83 (p < 0.0001) between these methods. In grafts with lower blood flow rates, aberrant flow patterns were observed, including stagnant or reversed flow during diastole while forward flow was maintained during systole. When reversed diastolic flow was severe, it was accompanied by access recirculation. In conclusion, we report the theory and clinical feasibility of determining access blood flow by using a VF Doppler technique. Measurements are made without the need to determine the access cross sectional area required for duplex volume flow calculations and without the need to reverse the lines required for various indicator dilution techniques. Important information is also obtained about aberrant flow patterns in patients at risk of access failure.

Comparing continuous hemofiltration with hemodialysis in patients with severe acute renal failure.

Continuous venovenous hemofiltration (CVVH) or CVVH with additional diffusive dialysis (CVVH-D) has theoretical advantages in treating severe acute renal failure (ARF), but no prospective clinical trials or restrospective comparison studies have clearly shown its superiority over intermittent hemodialysis (HD). To evaluate this question, all 349 adult patients with ARF receiving renal replacement therapy (RRT) at our medical center during 1995 and 1996 were analyzed using multivariate Cox proportional hazards methods. Initial univariate analysis showed the odds of death when receiving initial CVVH to be more than twice those when receiving initial HD (risk for death, 2.03; P < 0.01). Progressive exclusion of patients in whom the RRT modality might not be open to choice and the risk for death was very high (systolic blood pressure < 90 mm Hg; total bilirubin level > 15 mg/dL; or total RRT < 48 hours) for total RRT left 227 patients in whom the risk for death was 1.09 (95% confidence interval [CI], 0.67 to 1.80; P = 0.72) for initial CVVH, virtually equivalent to the risk for initial HD. Comorbid indicators significantly associated with death or failure to recover renal function included: older age; medical rather than surgical diagnosis; preexisting infection or trauma and liver disease as primary diagnoses; and abnormal bilirubin level or vital signs at initiation of RRT. These results show that the high crude mortality rate of patients undergoing CVVH was related to severity of illness and not the treatment choice itself. With the addition of more inclusive comorbidity data and a broader spectrum of interim outcomes, this type of analysis is a practical alternative to what would almost assuredly be a cumbersome and costly prospective, controlled trial comparing traditional HD with CVVH.

Preparation of ethanol-enriched, bicarbonate-based hemodialysates.

We describe a method to produce bicarbonate-based dialysates containing approximately 100 mg/dl ethanol by introducing the alcohol into one of the dialysate concentrate solutions geared for the production of bicarbonate-based dialysates.

The use of peritoneal dialysis in special situations.

This brief review outlines several situations in which peritoneal dialysis (PD) can be used to address clinical situations that are out of the ordinary for end-stage renal disease (ESRD). For example, PD methodology can be used not only to treat ESRD patients with difficult psychosocial problems that obviate other dialysis options, but also to control ascites accumulation in patients with liver failure, to treat congestive heart failure in azotemic patients with progressive cardiomyopathy, to administer systemic medication via the peritoneal cavity, and to provide additional clearance in demanding circumstances. In discussing these unusual applications for PD, we open the door to extending the indications for PD to a broader spectrum of clinical problems.

Exit-site and catheter care: review of important issues.

This brief review addresses the impact that several important aspects of catheter technology and exit-site care have on catheter-related infections and catheter longevity. The discussion includes exit-site microbiology, catheter configuration, exit-site care, and catheter salvage, following which a summary of recommendations is presented.

Simultaneous catheter removal and replacement in peritoneal dialysis infections: update and current recommendations.

Problematic peritoneal dialysis infection is a major cause of catheter loss and interruption of peritoneal dialysis (PD) therapy. In selected instances, problematic infection can be successfully treated by removing and replacing the catheter while continuing with PD. Accumulated experience has helped to define the circumstances under which a removal/replacement procedure is likely to be safe and under which complications are likely to arise. It appears that simultaneous removal and replacement can be expected to succeed when problematic infection is associated with tunnel infection, with recurring peritonitis repetitively culturing the same organism but clearing between episodes, and with gram-positive organisms. Success is less likely in the presence of ongoing inflammation, of active infection, of gram-negative or fungal organisms, or of any evidence of intra-abdominal adhesions. We review the literature on which these criteria are based and conclude with updated recommendations.

Peer resource consulting: redesigning a new future.

The current case describes a young woman with diabetes mellitus who developed end-stage renal disease (ESRD) and many other devastating complications related to her primary illness. Her experience illustrates many ways in which complicated illness can interrupt life's plans, dashing any dreams that she or her family might have for the future. Yet her story also illustrates the important role that a trained Peer Resource Consultant (PRC) can play in helping to better understand chronic illness, face and grieve losses, and even design new plans and create new dreams for the future. The discussion that follows includes several perspectives that offer poignant insight into the difficult situations characterized by the young diabetic with ESRD.

Central venous catheters for maintenance hemodialysis: a cautionary approach.

There is an increasing trend toward the use of indwelling central venous catheters (CVC) for maintenance hemodialysis. Although such devices are necessary in some problematic cases, the general use of CVC is worrisome. Not only may CVC prejudice the ultimate success of future permanent vascular access, but CVC also may be associated with reduced dialysis delivery and with several important complications. This review summarizes recent developments in catheter design, placement techniques, maintenance of the indwelling catheter, and complications of CVC use. Based on cumulated experience, a judicious position is taken that recognizes the place of CVC among the various access options but that favors permanent vascular access whenever feasible.

Racial group differences in plasma concentrations of antioxidant vitamins and carotenoids in hemodialysis patients.

Approximately 50% of the mortality in hemodialysis patients is due to cardiovascular disease. Antioxidant vitamins and carotenoids may be protective because oxidation of low-density lipoproteins appears to be a necessary prerequisite for the development of atherogenesis, and hemodialysis itself may stimulate the generation of oxygen reactive species. African Americans comprise a substantial proportion of dialysis patients because they have higher rates of hypertension, glomerulonephritis, and diabetic end-stage renal disease than do whites. The purpose of this cross-sectional study was to determine the plasma concentrations of antioxidant vitamins and carotenoids in hemodialysis patients and to investigate whether differences in these concentrations in the major racial or ethnic groups exist. Plasma concentrations of alpha- and gamma-tocopherol, carotenoids, and retinol were measured with HPLC and plasma vitamin C was measured with a spectrophotometric method in 109 white and African American hemodialysis patients. Dietary intakes of selected micronutrients were also compared by using data from a food-frequency questionnaire. Overall, plasma vitamin C and alpha-tocopherol concentrations were comparable but plasma carotenoid concentrations were lower than those reported for other populations. African American patients had significantly higher mean plasma concentrations of retinol (P < 0.04), lutein (P < 0.02), and total carotenoids minus lycopene (P < 0.04); whites had significantly higher mean plasma concentrations of alpha-tocopherol (P < 0.02), independent of age and plasma lipid concentrations. Diabetes comorbidity had an independent negative association with plasma beta-carotene concentration but was not associated with other measures.

Withdrawal from dialysis: a review with an emphasis on the black experience.

Withdrawal from dialysis has been shown to be a common occurrence in treated end-stage renal disease. Interestingly, there have been several reports documenting that blacks withdraw from dialysis one half to one third the rate of whites. There has been little research into the reasons for this marked discrepancy. This article reviews the existing literature on the different rates of withdrawal in blacks compared with whites. It then draws on a broad range of literature, including sociology, psychiatry, and anthropology, to propose possible reasons for the differences. From this review, it would seem that both medical and cultural factors play important roles in the decisions about withdrawal, but that cultural beliefs and attitudes are more important. More research is needed in both the medical and cultural aspects of rates of withdrawal to help explain the observed differences in blacks compared with whites.

Redefining the incidence of clinically detectable atheroembolism.

BACKGROUND AND OBJECTIVES: Atheroembolism, caused by peripheral embolization of small cholesterol crystals that fracture off of ruptured atherosclerotic plaques in the major vessels, leads to multifocal ischemic lesions and progressive tissue loss. The end result is often ischemic injury in the skin, kidney, brain, myocardium, and intestine, but any organ distal to the culprit lesion may be affected. The precise incidence of this serious clinical syndrome has been difficult to ascertain from the available literature, but it appears to be much more common than has been assumed. The objective of the present study is to clarify the incidence of atheroembolism among inpatients in an acute hospital setting. PATIENTS AND METHODS: We surveyed inpatient nephrology consultations during a 7-month period from January through July 1994. From a pool of 402 consultation charts, 99 were identified with two or more substantive risk factors for atheroembolism. The records of 85 of these patients were available for careful review. More than 300 additional patients were found to have ICD-9 discharge codes for other vascular conditions, but we were unable to confirm that any of these were in fact cases of atheroembolism, since there is no specific ICD-9 discharge code for this entity. In the 85 cases reviewed, a diagnosis of atheroembolism was made only if the patient had identifiable substantive risk factors, suggestive physical findings, and supporting laboratory results. RESULTS: Eleven of the 85 surveyed records documented strong evidence supporting a "probable" diagnosis of atheroembolism. Tissue was examined in 4 of these 11, resulting in definitive histologic confirmation in 3. Another 5 of the 85 surveyed records were "suggestive" of atheroembolism. Altogether, atheroembolism was a likely diagnosis in a total of 16 cases during this 7-month period, or 1 case in every 2 weeks. These cases comprised 19% of nephrology consultations in which 2 or more risk factors were present, or 4% or all nephrology consultations. The patients' records confirmed the serious implications of clinically detectable atheroembolism. Several patients underwent lower extremity amputation, nearly half required acute or chronic dialysis, and more than half died within several months of diagnosis CONCLUSIONS: The present study suggests that at least 4% of all inpatient nephrology consultations, representing approximately 5% to 10% of the acute renal failure encountered, involve clinically significant atheroembolism. Patients with atheroembolism appear at a rate of at least 1 case every 2 weeks. They often have identifiable substantive risk factors at initial consultation, and probably represent only the most severe cases of atheroembolism. In view of the serious implications of this basically untreatable syndrome, heightened awareness and preventive maneuvers in the population at risk are essential.

Long-term intraperitoneal deferoxamine for hemochromatosis.

Intraperitoneal deferoxamine is a well established treatment for aluminum accumulation syndrome in patients with end-stage renal disease receiving peritoneal dialysis, but the use of intraperitoneal deferoxamine has not been described outside of the setting of chronic renal failure. We present here a case of secondary hemochromatosis, complicated by cirrhosis and cardiomyopathy, in which a chronic peritoneal dialysis catheter was used both to treat ascites and to deliver parenteral deferoxamine for iron overload. Daily urinary iron excretion was similar to that achieved when using standard routes of deferoxamine administration. Over a 2-year period, reversal of both the biochemical indicators and the clinical manifestations of iron overload was accomplished.