Effects of chlorpromazine or diltiazem given intraperitoneally alone or in combination on peritoneal transport of solute and water.

Calcium channel blocker given intraperitoneally (i.p.) in rats was reported to increase urea D/P ratio without protein loss. Chlorpromazine (CP) given i.p. in humans was reported to increase ultrafiltration (UF) and urea clearance. We studied the effects of i.p. Diltiazem (DZ) (15 mg/kg) and i.p. chlorpromazine (0.25 mg/L dialysate)--given alone or in combination--on urea D/P ratio, dialysate protein (Dpro), glucose concentration (Dg), UF, and drainage volume (Vd). Six male Sprague-Dawley rats were studied. The rats underwent 21 consecutive 30-minute exchanges with 15 mL of 1.5% of Dianeal solution (Baxter Healthcare Inc., Deerfield, Illinois, U.S.A.). DZ or CP was added to the dialysis solution during exchanges 4-6 and 10-12. During exchange 16-18 both DZ and CP were added to the dialysis solution. Exchanges 1-3, 7-9, 13-15, and 19-21 were control exchanges performed with 1.5% Dianeal solution alone. The mean weight of the rats was 541.6 +/- 44 g. The animals' blood pressure remained stable during the study period. An increase in D/Purea ratio was observed with DZ, with CP, and with the two drugs in combination, without increase in dialysate protein loss. An increase in UF with a decrease in D/D0 was observed with DZ, with CP, and with the two drugs in combination, suggesting a mechanism other than osmotic gradient--such as increased blood flow or decreased surface tension.

Ganciclovir-associated hypercalcemia in a renal transplant patient.

We describe a renal transplant patient who developed hypercalcemia during treatment with ganciclovir for cytomegaloviral (CMV) infection. To our knowledge such an association has not previously been reported. Hypercalcemia was associated with low levels of serum parathormone (PTH) and an increase in 1,25 dihydroxy vitamin D concentrations. The mechanism(s) of ganciclovir-associated hypercalcemia remains unclear.

De novo membranous glomerulopathy in a renal transplant patient treated with FK 506. The first reported case.

We describe a case of de novo membranous glomerulopathy in the renal allograft of a diabetic patient, treated with the newer immunosuppressive agent FK 506. Twenty-two months later this patient developed nephrotic range proteinuria.

Lipid-lowering effects of fluvastatin in renal transplant patients. A clinical observation.

A Atherosclerosis-related cardiovascular disease remains an important cause of morbidity and mortality in renal transplant patients. We assessed the efficacy and safety of the newer synthetic HMG-CoA reductase inhibitor, fluvastatin, in 12 renal transplant patients who remained hypercholesterolemic, despite having been on the American Heart Association (AHA) Step I diet for 6 weeks. At 8 weeks, compared to the control phase, fluvastatin therapy, 20 mg/day, reduced the total cholesterol (TC) from 321 +/- 57 [+/-SD] to 301 +/- 123 mg/dl (p = 0.3); low-density lipoprotein cholesterol (LDL-C), from 209 +/- 56 to 176 +/- 81 mg/dl (p = 0.2); and the triglyceride (TG) levels from 343 +/- 119 to 277 +/- 117 mg/dl (p = 0.06); all these changes were statistically insignificant. However, the therapy significantly increased the high-density lipoprotein cholesterol (HDL-C) from 37 +/- 11 to 46 +/- 13 mg/dl (p = 0.006). During this short-term treatment period no adverse biochemical effects were noted with the therapy.

ATGAM associated coagulopathy in renal transplant patients: a report of two unusual cases.

Polyclonal antibodies, used for both induction and rejection therapy in renal transplant recipients, are associated with such side effects as chills and fever. We describe two patients who developed a coagulopathy during antithymocyte globulin (ATGAM) therapy, a previously unknown complication. The laboratory tests revealed prolonged prothrombin and partial thromboplastin times and thrombocytopenia. Discontinuation of ATGAM therapy resulted in correction of these abnormalities.

Hypocholesterolemia is not associated with neurotoxicity in renal transplant patients.

Cyclosporine-associated neurotoxicity has been reported in recipients of solid organ and bone marrow transplantation. Neurotoxicity during cyclosporine therapy has been suggested to be associated with low levels of serum total cholesterol (TC). We report seven hypocholesterolemic (TC < 150 mg/dl) renal transplant recipients who remained asymptomatic during cyclosporine therapy. Three of these patients were hypocholesterolemic at the time of transplantation and received intravenous cyclosporine as induction therapy. The other four patients became hypocholesterolemic > or = 9 months after renal-transplantation. None of these patients developed neurologic signs or symptoms during cyclosporine therapy. Our short and long-term observations in renal transplant recipients suggest that perhaps factors other than low cholesterol levels may be responsible for cyclosporine-associated neurotoxicity.

Goodpasture's syndrome superimposed on membranous nephropathy. A case report.

We describe a patient with idiopathic membranous glomerulopathy who developed acute deterioration in renal function; this was associated with hemoptysis, severe hypertension, and anti-glomerular basement membrane (anti-GBM) antibody in the serum. Despite aggressive therapy with plasmapheresis, cyclophosphamide and prednisone, the patient progressed to end-stage renal failure and is on maintenance hemodialysis.

Does cholestyramine interfere with cyclosporine absorption? A prospective study in renal transplant patients.

Increased cardiovascular deaths have been reported in long-term survivors after renal transplantation. In the primary and secondary coronary prevention trials, reduction of elevated cholesterol has been demonstrated to decrease the incidence of cardiovascular events. The authors previously reported that only 33% of renal transplant patients achieved the National Cholesterol Education Program Expert Panel target values of total and low density lipoprotein cholesterol with niacin > or = 2 g/day or lovastatin 40 mg/day. Indeed, combination therapy with the bile acid sequestrant, cholestyramine appears to be a logical choice. Hence, the pharmacokinetics of cyclosporine were studies before (baseline, on day 1) and after starting cholestyramine 4 g/day, given as a single dose at noon (study repeated on day 4) in six nondiabetic renal transplant patients. Included were 1 woman and 5 men; their mean age (+/- SEM) was 45 +/- 6 years, and they were all > 1 year post transplantation. These patients were receiving cyclosporine, azathioprine, and prednisone based maintenance immunosuppression. Compared to day 1 (baseline period), the peak (644 +/- 142 ng/ml versus 625 +/- 168 ng/ml; ns) and trough (196 +/- 17 ng/ml versus 214 +/- 32 ng/ml; ns) cyclosporine levels and the time to peak (2 hr versus 2 hr) were not significantly different on day 4 (post cholestyramine period) of the study. Furthermore, the area under the curve (3721 +/- 586 ng/hour/ml versus 4143 +/- 778 ng/hour/ml; ns) was not significantly different. Our data suggest that cholestyramine 4 g, given once a day at noon, did not interfere with the absorption of oral cyclosporine. Hence, combination therapy with cholestyramine appears to be a reasonable choice in renal transplant patients with resistant hypercholesterolemia.

Effects of nicotinic acid and lovastatin in renal transplant patients: a prospective, randomized, open-labeled crossover trial.

Lipid abnormalities are seen frequently in renal transplant patients. Cardiovascular disease is an important cause of morbidity and mortality in these patients. We assessed the efficacy and safety of the lipid-lowering drugs, nicotinic acid (short acting) and lovastatin, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Twelve renal transplant patients who had persistent hyperlipidemia despite 6 weeks of dietary treatment participated in this prospective, randomized, open-labeled crossover trial. At 16 weeks, when compared with control values, nicotinic acid (> or = 1.5 g twice a day) significantly reduced the total cholesterol (from 312 +/- 18 [+/- SEM] mg/dL to 229 +/- 19 mg/dL; P = 0.03) and the low-density lipoprotein cholesterol (from 218 +/- 15 mg/dL to 142 +/- 13 mg/dL; P = 0.03) and significantly increased the high-density lipoprotein cholesterol (from 44 +/- 3 mg/dL to 58 +/- 5 mg/dL; P = 0.03). The triglyceride level was reduced from 255 +/- 40 mg/dL to 150 +/- 23 mg/dL (P = 0.09). At 16 weeks, lovastatin therapy (40 mg/d) significantly reduced the total cholesterol (from 285 +/- 13 mg/dL to 233 +/- 10 mg/dL; P = 0.005) and the low-density lipoprotein cholesterol (from 201 +/- 11 mg/dL to 147 +/- 7 mg/dL; P = 0.001). There were no significant changes in the triglyceride and high-density lipoprotein cholesterol levels. Although flushing developed in 67% of patients treated with nicotinic acid, this was not a reason for any of the study dropouts. During this short-term study period no adverse biochemical effects were noted with either of the drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

De novo membranous glomerulopathy in renal allografts with unusual histology.

We describe two cases of de novo membranous glomerulopathy in the renal allograft, with unusual histologic findings. In one patient the allograft nephrectomy specimen showed numerous foam cells in the intima of hyperplastic arteries along with prominent features of chronic rejection. In the other patient, prominent IgM deposits were seen in the glomerular mesangium without chronic rejection.

De novo malignancy after renal transplantation.

We reviewed the incidence of de novo malignancy in renal transplant recipients who received their grafts between 1979 and 1989, and had at least two years of graft function. Multiple attempts were made to contact 236 patients who were then surviving, or, in whom the medical history could be validated prior to death. There were 94 successful contacts, among whom 19 patients (20.12%) had developed 30 malignant lesions. There were 24 instances of skin and 6 of non-skin malignancy. Squamous cell carcinoma of the skin was the most common new malignancy observed.

Long term effects of ACE inhibitors on the erythrocytosis in renal transplant recipients.

Erythrocytosis is infrequently seen in renal transplant recipients. Both theophylline and angiotensin converting enzyme (ACE) inhibitors have been reported to decrease the elevated hematocrit (Hct) and hemoglobin (Hgb) levels. We studied the efficacy of the ACE inhibitors ramipril (n = 6) and enalapril (n = 1) in seven stable renal transplant recipients. Although the ACE inhibitors significantly reduced the elevated Hct and Hgb levels during the short and long term (Hct 53 +/- 1 vs 48.8 +/- 0.7%; Hgb 17.8 +/- 0.4 vs 16.7 +/- 0.3 vs 16.7 +/- 0.3 gm/dl, at 1 year), the clinical significance of these reductions remains unknown. During therapy there were no significant changes in the blood pressure, serum creatinine and potassium levels and the medications were well tolerated.

Lithium carbonate decreases ultrafiltration rates in an experimental model of PD.

Animal studies have shown increased fluid absorption from the peritoneal cavity following intraperitoneal (ip) vasopressin. Lithium is known to antagonize vasopressin effects on fluid absorption in kidney distal nephrons. The aim of the present study was to see whether lithium-containing exchanges increase the ultrafiltration rates (UF) during peritoneal dialysis (PD) in rats. PD was carried out in 6 Sprague-Dawley rats with 1.5% dextrose-containing PD solution using 15-ml volumes. Each exchange (ex) took 1 min for inflow, 4 mins for outflow and 25 mins for dwell. All rats underwent 9 consecutive half-hourly exs. During exs 4-6 lithium carbonate 2.5 mM was added to the PD solution. During lithium-containing exs significant increases in the glucose absorption rates (3.9 +/- 7.8 vs 37.5 +/- 8.1 mg/ex; p = 0.025) were associated with significant reductions in the UF (3.03 +/- 0.25 vs 1.78 +/- 0.12 ml/ex; p = 0.005). In conclusion, the isolated increase in glucose absorption without increases in the dialysate protein concentration with ip lithium, may suggest either a selective increase in size of the pores with a mean dimater near that of the glucose molecule or enhanced lymphatic absorption. ip lithium did not increase the UF in a rat model of PD.

Effects of dietary therapy on post renal transplant hyperlipidemia. A prospective study.

Hyperlipidemia often occurs after renal transplantation and may contribute to increased cardiovascular morbidity. The National cholesterol education program guidelines (NCEP) recommend dietary modification as the initial therapeutic intervention. We evaluated the effects of the AHA Step I and Step II diets on the serum total cholesterol (TC) and the triglyceride (TG) levels in nondiabetic renal transplant patients. Both the AHA Step I (TC 296 +/- 7 vs 294 +/- 9 mg/dL, p = ns) and Step II diets (TC 282 +/- 8 vs 292 +/- 16 mg/dL, p = ns) failed to significantly lower the serum total cholesterol and the triglycerides levels. During this dietary intervention, the patients' body weight and serum creatinine level remained stable. Our data suggest that neither the AHA Step 1 nor the Step II diet are effective in significantly lowering elevated serum lipids in nondiabetic renal transplant recipients.

Hyperlipidemia in continuous ambulatory peritoneal dialysis patients.

Hyperlipidemia is frequently seen in continuous ambulatory peritoneal dialysis patients. The cause of abnormal lipid profile in these patients is multifactorial. In both short and long term studies, abnormal levels of total cholesterol, triglycerides, and, HDL cholesterol were observed. In short term studies, both lovastatin and gemfibrozil were shown to favorably alter the lipid profile.

Lipid-lowering effects of lovastatin in CAPD patients.

Increased incidence of cardiovascular morbidity and mortality has been observed in continuous ambulatory peritoneal dialysis (CAPD) patients. Hyperlipemia is an important etiologic factor in the pathogenesis of coronary artery disease. Lovastatin has been shown to effectively lower both the serum total cholesterol and triglyceride levels, the most common abnormalities in these patients. In a retrospective study we assessed the lipid-lowering effects of lovastatin (20 mg/day) in 8 CAPD patients whose serum cholesterol and/or triglycerides remained greater than 240 mg/dL, despite a low cholesterol diet. At 6 months of lovastatin therapy, moderate reductions in total cholesterol and triglyceride levels were observed in 2 patients. Although 20 mg/day of lovastatin were well tolerated, the treatment was not universally effective in lowering the serum cholesterol and triglyceride levels.

Cost effectiveness and accuracy of renal scans in the management of patients undergoing renal transplantation.

Following renal allograft transplantation, renal scans are frequently performed to evaluate anatomical and functional causes for allograft dysfunction. In our retrospective study of 20 patients, renal scans were found to be more expensive compared to renal biopsies $68,688 vs $7,421, and, in only one patient was aggressive anti-rejection therapy instituted based solely on the renal scan results. The 95% confidence interval for the proportion of correct diagnosis by renal scan was 0.16 to 0.62.

Systemic mastocytosis associated with membranous nephropathy and peripheral neuropathy.

A report of the occurrence of membranous nephropathy and peripheral neuropathy in a patient with systemic mastocytosis is presented. Previous reviews of patients with systemic mastocytosis have not noted this association. During cyclical therapy with prednisone and chlorambucil in this case, nephrotic-range proteinuria remitted. Peripheral neuropathy resolved 10 months after discontinuation of therapy. Pathophysiological mechanisms resulting in this clinical presentation may be immunologically mediated.

Coxsackie virus-induced acute pancreatitis in a long-term dialysis patient.

This report describes a patient on continuous ambulatory peritoneal dialysis (CAPD) who developed acute pancreatitis with pseudocyst formation and cloudy dialysate with pleocytosis in the absence of bacterial or fungal organisms. To our knowledge, pancreatitis, in the absence of hypertriglyceridemia in a CAPD patient, has not been previously reported. There was a significant increase in Coxsackie B1 and B6 viral titers by complement fixation test, suggesting Coxsackie virus-induced pancreatitis.