Stephen W. Zimmerman

Exercise capacity in hemodialysis, CAPD, and renal transplant patients

Eighteen hemodialysis, 12 chronic ambulatory peritoneal dialysis (CAPD), and 20 renal transplant patients performed maximal treadmill exercise tests. Heart rates and blood pressures were determined every minute and maximal oxygen consumption was measured directly. Exercise capacity as measured by VO2 max is low in dialysis patients and similar to sedentary normal individuals in renal transplant patients. Maximal heart rates were significantly lower in hemodialysis patients than transplant recipients. The lower exercise tolerance in end-stage renal disease indicates that most patients regardless of the treatment mode could benefit from attempts through exercise training to increase physical working capacity.

Randomized Controlled Trial of Prophylactic Rifampin for Peritoneal Dialysis-Related Infections

Staphylococcal infections are a major cause of catheter infections and peritonitis in peritoneal dialysis patients. Since catheter-related infections are associated with nasal carriage of Staphylococcus aureus in this population, we studied the effect of intermittent rifampin, an antibiotic known to decrease S aureus nasal carriage, on catheter-related infections and peritonitis. We randomly assigned 64 patients to receive either rifampin 300 mg twice daily for 5 days every 3 months or no treatment. The rifampin-treated patients had a significant delay in time to first catheter-related infection (P less than 0.015) and significantly fewer catheter-related infections overall (P less than 0.001). The catheter-related infection rate in rifampin-treated patients was .26 per patient-year versus .93 per patient-year in untreated patients. Multivariate analysis defined baseline colonization of nares or catheter exit-site and prior renal transplant as risk factors for catheter-related infections. There was no significant difference in peritonitis rates between groups, although the trend was for a delayed time to first episodes and fewer episodes in rifampin-treated patients. Adverse effects necessitated withdrawal of rifampin in four patients. We conclude that intermittent rifampin administration is effective in decreasing catheter-related infections in a peritoneal dialysis population.

Prospective trial of warfarin and dipyridamole in patients with membranoproliferative glomerulonephritis

A prospective trial of warfarin and dipyridamole was performed in patients with membranoproliferative glomerulonephritis. Eighteen completed either a control or treatment year, and 13 completed both a control and treatment year. To obviate the bias of excluding control patients who had renal failure after one year, both an unpaired and a paired analysis were performed. The unpaired analysis compared 10 patients followed for an initial control year with eight patients receiving treatment first. Renal function remained stable over the year in the treated group, but worsened in the control group. Slopes of regression lines for reciprocal serum creatinine values were significantly different between groups (p less than 0.025). Urine protein excretion also decreased in the treated group. Four of 10 control patients had a two-fold increase in serum creatinine levels, but no treatment patient did. In the paired crossover analysis, significant differences in renal function were detected between control and treatment years in six patients whose renal function significantly changed over one of the years. In every instance, there was better preservation of renal function in the treatment year. Urinary protein also decreased significantly over the treatment year compared with the control year. Bleeding was the most frequent complication. These data suggest that warfarin and dipyridamole have a beneficial effect on renal function in membranoproliferative glomerulonephritis.

Exercise Tolerance Changes Following Renal Transplantation

Maximal exercise capacity was measured in 20 nondiabetic patients with end-stage renal disease before and soon after successful renal transplantation. Maximal oxygen consumption increased significantly in all patients posttransplant. Increases in maximal heart rate and heart rates at 70% of maximal levels were also observed. The changes in maximal oxygen consumption were not significantly correlated with changes in hematocrit. The removal of uremia may result in improved functioning of one or more of the systems involved in oxygen transport and utilization that determine exercise capacity.

Exercise in End-Stage Renal Disease

Available studies indicate that exercise tolerance in renal patients is low. Although significant improvements in maximal oxygen consumption have been reported following exercise training in these patients, there may be physiologic limitations to the attainable levels of aerobic capacity due to the multisystemic nature of the disease. Long-term exercise training may result in other medical benefits. Compliance to regular exercise in hemodialysis patients remains a problem, however, exercise training during the dialysis treatment may prove beneficial in terms of compliance and supervision.

Goodpasture's syndrome with normal renal function

Two male patients with Goodpastures syndrome manifesting as severe pulmonary hemorrhage with minimal renal abnormalities are described. Both patients had microscopic hematuria with normal renal function, and one had transient proteinuria. Renal glomerular histology was normal and electron microscopic findings revealed no electron-dense deposits, but immunofluorescence of immunoglobulin G (IgG) was positive in a linear fashion along glomerular capillary basement membranes in both patients. Pulmonary hemorrhage was arrested following prednisone therapy, and both patients have normal pulmonary and renal function at five and 13 months of follow-up. The literature on patients with Goodpastures syndrome, pulmonary hemorrhage and normal renal function with minimal proteinuria is reviewed. It is suggested that a subset of patients with Goodpastures syndrome have pulmonary hemorrhage as their major manifestation. Since prednisone seems to have an apparent beneficial effect on pulmonary hemorrhage, and relatively good prognosis, this diagnosis should be considered in patients with idiopathic pulmonary hemorrhage.

Pharmacokinetics of Intraperitoneal, Intravenous, and Subcutaneous Recombinant Human Erythropoietin in Patients on Continuous Ambulatory Peritoneal Dialysis

The pharmacokinetics of recombinant human erythropoietin (Epo) were compared after mean single 99.1 U/kg intraperitoneal (IP), intravenous (i.v.), and subcutaneous (SC) doses in eight noninfected patients on peritoneal dialysis in a randomized, three-way, cross-over fashion. Continuous ambulatory peritoneal dialysis was performed in all patients on the days of the study. The IP dose was instilled into an empty peritoneum; total dwell time was 10 hours (4 hours dry, 6 hours with 2 L of peritoneal dialysis fluid). Blood samples were collected for 96 hours following IP and SC Epo, and for 72 hours following i.v. Epo. For the IP dose, a 10-hour effluent dialysate sample was collected to determine Epo recovery. Enzyme immunoassay was used for Epo analysis. The mean apparent volume of distribution was 0.05 L/kg, equivalent to 4.5% of total body weight; the mean total body clearance was 0.08 mL/min/kg. All eight patients exhibited multiexponential decay in serum Epo concentrations following i.v. Epo. Absorption of IP Epo was significantly greater than previous reports, presumably due to its administration into a dry peritoneum. The maximum concentrations following the IP and SC doses were nearly identical, but amounted to only 5% of the maximum concentrations for the i.v. dose. Subcutaneous Epo took nearly twice as long as IP Epo to achieve peak serum concentrations (17.1 +/- 5.0 hours v 9.4 +/- 1.9 hours). Compared with the IP route, the SC dose achieved a higher area under the serum concentration time curve from time 0 to 96 hours (AUC0-96; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasmapheresis and Dipyridamole for Recurrent Focal Glomerular Sclerosis

A 38-year-old man had recurrence of nephrotic syndrome with focal glomerular sclerosis (FGS) in two consecutive cadaveric renal allografts. His first graft was lost to recurrent disease after 30 months. Because prior animal experiments performed when he had his first graft indicated a possible serum factor or factors capable of enhancing urine protein excretion, three plasmapheresis periods of 6-8 treatments each were performed 3, 23 and 34 months after recurrence of FGS in the second graft. Urine protein excretion was decreased transiently in the first treatment period when the allograft biopsy revealed only glomerular foot process effacement. The second and third plasmapheresis treatment periods were performed after typical lesions of FGS were present in the graft and moderate renal insufficiency occurred. Dipyridamole was also given at this time. There has been associated stabilization of renal function for over 31 months. Prior to this, renal function was significantly (p less than 0.001) decreasing with time. The reasons for stabilization of renal function in this man with recurrent FGS are not defined, but the results suggest the need to further evaluate plasmapheresis and the platelet inhibitor dipyridamole in native and recurrent FGS.

A multicenter study of noncompliance with continuous ambulatory peritoneal dialysis exchanges in US and Canadian patients

Recent evidence suggested that noncompliance (NC) with continuous ambulatory peritoneal dialysis (CAPD) exchanges may be more common in US than in Canadian dialysis centers. This issue was investigated using a questionnaire-based method in 656 CAPD patients at 14 centers in the United States and Canada. NC was defined as missing more than one exchange per week or more than two exchanges per month. Patients were ensured of the confidentiality of their individual results. Mean patient age was 56 +/- 16 years, 52% were women, and 39% had diabetes. The overall admitted rate of NC was 13%, with a rate of 18% in the United States and 7% in Canada (P < 0.001). NC was more common in younger patients (P < 0.0001), those without diabetes (P < 0.001), and employed patients (P < 0.05). It was also more common in black and Hispanic than in Asian and white patients (P < 0.001). NC was more common in patients prescribed more than four exchanges daily (P < 0.0001) but was not affected by dwell volume. On multiple regression analysis, the independent predictors of NC, in order of importance, were being prescribed more than four exchanges per day, black race, being employed, younger age, and not having diabetes. Being treated in a US unit did not quite achieve significance as a multivariate independent predictor. These findings suggest that NC is not uncommon in CAPD patients and is more frequent in US than in Canadian patients. However, country of residence is less powerful as a predictor of NC than a variety of other demographic and prescription factors.

Continuous Ambulatory Peritoneal Dialysis in Diabetes mellitus

14 insulin-dependent diabetic patients completed 122 patient months on continuous ambulatory peritoneal dialysis (CAPD), using only intraperitoneal insulin for glucose control. Survival was 70% at 1 y