Bahar Bastani

The effects of lipid-lowering agents on acute renal allograft rejection

Background. Preliminary results from clinical trials suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors may help prevent acute renal allograft rejection. However, the mechanism for this putative effect of 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors, and whether it is independent of lipid-lowering per SE are unknown. Methods. Immediately after renal transplantation we randomly allocated (proportioned 2:1:2) patients to: 1) simvastatin (10 mg/day, n=53), 2) simvastatin placebo plus gemfibrozil (dose adjusted for renal function, n=36), and 3) simvastatin placebo (n=52). Results. Simvastatin, but not gemfibrozil, reduced total and low density lipoprotein cholesterol during the first 90 days posttransplant. There were no major adverse effects of therapy. However, there were no effects of treatment on acute rejection. Indeed, survival free of acute rejection at 90 days was 72% in the simvastatin group, 72% in the gemfibrozil group, and 77% in the placebo control group (P =0.771). A post hoc power analysis suggested that there was only a 7.5% chance that a true effect of simvastatin on acute rejection (versus placebo) was not detected, and a 2.5% chance that an effect of gemfibrozil on acute rejection (versus placebo) was not detected in this study. Conclusion. Lipid-lowering agents may not reduce the incidence of acute renal allograft rejection. However, additional studies are needed to confirm this observation. In the mean time, many if not most renal transplant recipients should be treated with HMG-CoA reductase inhibitors starting early posttransplant to prevent cardiovascular disease complications. The results of this study suggest that starting lipid-lowering therapy immediately after renal transplantation is both safe and effective in lowering total and low density lipoprotein cholesterol.

A randomized controlled trial of oral versus intravenous iron in chronic kidney disease

Background: It is unknown whether intravenous iron or oral iron repletion alone can correct anemia associated with chronic kidney disease (CKD). We conducted a randomized multicenter controlled trial in adult anemic, iron-deficient non-dialysis CKD (ND-CKD) patients (≧stage 3) not receiving erythropoiesis-stimulating agents (ESAs). Methods: The participants were randomized to receive either a sodium ferric gluconate complex (intravenous iron) 250 mg i.v. weekly × 4 or ferrous sulfate (oral iron) 325 mg t.i.d. × 42 days. Hemoglobin (Hgb), ferritin and transferrin saturation (TSAT) were measured serially, and the Kidney Disease Quality of Life (KDQoL) questionnaire was administered on days 1 and 43. The primary outcome variable was change from baseline (CFB) to endpoint in Hgb values. Results: Seventy-five patients were analyzed (intravenous iron n = 36, oral iron n = 39). CFB in Hgb was similar in the two groups (intravenous iron 0.4 g/dl vs. oral iron 0.2 g/dl, p = n.s.). However, the increase in Hgb was only significant with intravenous iron (p < 0.01). In comparison to oral iron, intravenous iron achieved greater improvements in ferritin (232.0 ± 160.8 vs. 55.9 ± 236.2 ng/ml, p < 0.001) and TSAT (8.3 ± 7.5 vs. 2.9 ± 8.8%, p = 0.007). Intravenous iron caused greater improvements in KDQoL scores than oral iron (p < 0.05). The most common side effect reported with intravenous iron was hypotension, while constipation was more common with oral iron. Conclusions: Oral and intravenous iron similarly increase Hgb in anemic iron-depleted ND-CKD patients not receiving ESAs. Although in comparison to oral iron, intravenous iron may result in a more rapid repletion of iron stores and greater improvement in quality of life, it exposes the patients to a greater risk of adverse effects and increases inconvenience and cost.

The natural history of renal function following orthotopic heart transplant

Abstract:  Background:  The outcome of solid organ transplantation has dramatically improved after the introduction of the calcineurin inhibitor cyclosporine. With the increasing longevity of heart transplant recipients, the long‐term effects of cyclosporine on renal function have become more evident. The natural history of kidney function following orthotopic heart transplant is not well defined and long‐term follow up studies are scant.

Enoxaparin-associated severe retroperitoneal bleeding and abdominal compartment syndrome: a report of two cases

Abstract.Objective: To describe a complication of low-molecular-weight heparin (enoxaparin) in the setting of critically ill patients. Design: Case report. Setting: The medical and surgical intensive care units of a tertiary care university teaching hospital. Patients: Two adult patients receiving enoxaparin developed retroperitoneal hematoma and abdominal compartment syndrome. Both patients became anuric and required high-dose intravenous fluids and vasopressors to maintain blood pressure. Intervention: Discontinuation of enoxaparin, followed by exploratory laparotomy and evacuation of the hematoma. Measurements and results: Immediate clinical improvement following evacuation of hematoma. Conclusions: High-risk patients receiving low-molecular-weight heparin should be identified and closely monitored to prevent serious bleeding complications.

Percutaneous renal biopsy in the 1990s: Safety, value, and implications for early hospital discharge

To determine the parameters associated with significant bleeding and to examine the value of performing a renal biopsy, we studied 83 consecutive patients, including 24 renal allograft recipients, who had undergone percutaneous renal biopsy. The patients were stratified into four groups according to the percentage of decline in their hematocrit (Hct) at 24 hours postbiopsy, as follows: 10% or greater (n = 21; 25%) and less than 10% decline (n = 62; 75%). The latter group was further subgrouped into 5% to 10% (n = 22) and less than 5% decline (n = 40). There was a significant decline in Hct postbiopsy, with a linear correlation between the decrease in Hct at 6 and 24 hours (R2 = 0.47; P < 0.0001), suggesting that the former was a predictor of the latter. There was a linear correlation between the number of passes and number of cores obtained for the first four passes, but an inverse correlation when five passes or greater were required. Interestingly, there was no correlation between bleeding (>10% decline in Hct) and the number of passes or cores obtained. Gross hematuria and blood transfusion requirement were each encountered in three patients (3.6%). Importantly, the prebiopsy clinical diagnosis was altered in 18 of 59 native kidney biopsies (33%) and 10 of 24 transplant biopsies (41%). We conclude that percutaneous renal biopsy using an automated spring-loaded gun device coupled with ultrasound guidance is a safe technique and provides essential clinical information. Importantly, patients with a stable Hct at 6 hours were at low risk for bleeding at 24 hours while hospitalized. It remains to be determined if these findings could be extrapolated to early discharge from hospital.

Intraperitoneal Sodium Thiosulfate for the Treatment of Calciphylaxis

Calcific uremic arteriolopathy (or calciphylaxis) is a severe complication of renal failure characterized by subcutaneous calcification of the small arteries and tissue necrosis. We describe the case of a woman receiving continuous cycling peritoneal dialysis with calciphylaxis involving upper and lower extremities. After intolerance of intravenous sodium thiosulfate and limited intravenous access options, we administered sodium thiosulfate intraperitoneally and quantitated the amount of extra calcium removed. Intraperitoneal administration of sodium thiosulfate was well tolerated and led to removal of extra calcium with peritoneal dialysis.

Secondary Hyperparathyroidism, and not β2-Microglobulin Amyloid, as a Cause of Spontaneous Tendon Rupture in Patients on Chronic Hemodialysis

Spontaneous bilateral rupture of the extensor mechanisms of the knees, without significant history of trauma, has been reported rarely, generally in association with chronic metabolic disorders, such as chronic renal failure and secondary hyperparathyroidism. We report spontaneous tendon rupture in two patients on chronic hemodialysis for 4 and 11 years, with documented severe secondary hyperparathyroidism. One patient had spontaneous bilateral rupture of his quadriceps and partial avulsion of the left triceps tendons. The other patient had spontaneous rupture of his right quadriceps tendon. Both patients had markedly elevated serum intact parathyroid hormone and moderately elevated serum beta 2-microglobulin levels. Pathologic examination revealed diffuse immunohistochemical staining for beta 2-microglobulin but negative Congo-red staining of the ruptured tendon specimens. These cases and the previous reports in the literature suggest that secondary hyperparathyroidism may play a role in the pathogenesis of this clinical entity.

Reversible acute renal failure associated with hypothyroidism: Report of four cases with a brief review of literature

SUMMARY:   We present four adult cases of acute renal failure associated with hypothyroidism. All patients presented with symptoms suggestive of moderate to severe hypothyroidism, such as cold intolerance, constipation, muscle weakness, and lower extremity oedema. Initial serum creatinine levels ranged between 115 and 203 µmol/L (1.3 and 2.3 mg/dL), with creatinine clearances (CrCl) ranging between 0.58 and 0.97 mL/s (34.5 and 58 mL/min). After 6–12 weeks of treatment with levothyroxin, serum creatinine levels decreased to the range of 80 and 124 µmol/L (0.9 and 1.4 mg/dL) and CrCl increased to 0.74–1.64 mL/s (44–98 mL/min). One patient had proteinuria of 800 mg/day, which decreased to the normal range (<200 mg/day) after levothyroxin treatment. One patient developed acute gouty arthritis before normalization of thyroid‐stimulating hormone (TSH), which was successfully managed with prednisone therapy. All of our patients had increased creatine kinase (CK), ranging between 1000 and 2360 U/L (normal range, 22–165 U/L), which normalized after 6 weeks of levothyroxin treatment.

Cellular distribution of isoforms of protein kinase C (PKC) in pancreatic acini.

As in a previous study (Biochim, Biophys. Acta 1224 (1994) 127-138), we used quantitative immunoblot analysis and found that rat pancreatic acini possess four different isoforms of PKC-alpha, delta, epsilon and zeta. The phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) caused translocation of each isoform from the cytosol to the membrane fraction. CCK-8 increased diacylglycerol (DAG) and caused translocation of PKC-sigma and PKC-epsilon but not that of PKC-alpha or PKC-zeta. L-364,718, a CCK receptor antagonist, prevented as well as reversed the effects of CCK-8 on DAG and on translocation of PKC-sigma and PKC-epsilon. To explore the possibility that different isoforms of PKC might have different distributions in rat pancreas, we used immunocytochemistry to determine the cellular distribution of different isoforms of PKC in intact pancreas as well as pancreatic acini. In intact pancreas, PKC-alpha and PKC-sigma were detected in islet cells but not in duct or acinar cells. PKC-epsilon was detected in the apical region of acinar cells and PKC-zeta was detected over the luminal surfaces of acinar cells and the ductules that extend from the acinus. Neither PKC-epsilon nor PKC-zeta was detected in islets. In pancreatic acini PKC-alpha and PKC-sigma were detected in islets or fragments of islets that contaminated the preparation but were not detected in acinar cells. PKC-epsilon was detected in the apical region of acinar cells and adding 1 microM TPA or 1 microM CCK-8 accentuated the immunostaining but did not alter its cellular distribution. L-364,718 reversed the changes in immunostaining caused by CCK-8. PKC-zeta was detected over the luminal surface of the acinar cells. TPA, but not CCK-8 or CCK-8 followed by L-364,718, increased the number of acini that showed staining of the luminal surfaces of acinar cells. Thus, the present results demonstrate that different isoforms of PKC are distributed differently in rat pancreas and that the different patterns of distribution can explain, at least in part, the different responses to CCK-8.

Granulocyte-macrophage colony-stimulating factor as an adjuvant to hepatitis B vaccination in maintenance hemodialysis patients.

Patients on maintenance hemodialysis (HD) have poor seroconversion rate after hepatitis B vaccination. The present study was designed to test the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant to hepatitis B vaccination for improving seroconversion rate in maintenance HD patients. Twelve chronic HD patients were randomly assigned to receive either hepatitis B vaccination alone or hepatitis B vaccination 24 h after 1 dose of GM-CSF for primary immunization. A group of 16 chronic HD patients who had not seroconverted after a standard two-dose hepatitis B vaccination were randomly assigned either to a booster dose of hepatitis B vaccine alone or a booster dose given 24 h after one dose of GM-CSF. In the primary immunization group only 2 of 6 patients (33%) who had received vaccination alone, versus 5 of 6 patients (83%) who had received hepatitis B vaccine after one dose of GM-CSF, developed seroprotective antibody titers. Moreover, seroprotective antibody titers (IU/ml) were significantly higher in the latter group (275 ± 286.5 vs. 14 ± 22, p < 0.05). In patients who had not seroconverted with prior hepatitis B vaccination, GM-CSF adjuvant therapy significantly increased the seroconversion rate versus booster dose alone (87.5 vs. 25%, respectively, p < 0.02), with significantly higher seroprotective antibody titers (84 ± 80 vs. 19 ± 33 IU/ml, respectively, p < 0.05). These findings suggest that administration of one dose of GM-CSF, as adjuvant therapy, prior to primary or booster dose hepatitis B vaccination may significantly increase seroconversion rate and seroprotective antibody titers in chronic HD patients.