Kai-Chung Tse

Long-Term Study of Mycophenolate Mofetil as Continuous Induction and Maintenance Treatment for Diffuse Proliferative Lupus Nephritis

Mycophenolate mofetil (MMF) and the sequential use of cyclophosphamide followed by azathioprine (CTX-AZA) demonstrate similar short-term efficacy in the treatment of diffuse proliferative lupus nephritis (DPLN), but MMF is associated with less drug toxicity. Results from an extended long-term study, with median follow-up of 63 mo, that investigated the role of MMF as continuous induction-maintenance treatment for DPLN are presented. Thirty-three patients were randomized to receive MMF, and 31 were randomized to the CTX-AZA treatment arm, both in combination with prednisolone. More than 90% in each group responded favorably (complete or partial remission) to induction treatment. Serum creatinine in both groups remained stable and comparable over time. Creatinine clearance increased significantly in the MMF group, but the between-group difference was insignificant. Improvements in serology and proteinuria were comparable between the two groups. A total of 6.3% in the MMF group and 10.0% of CTX-AZA-treated patients showed doubling of baseline creatinine during follow-up (P = 0.667). Both the relapse-free survival and the hazard ratio for relapse were similar between MMF- and CTX-AZA-treated patients (11 and nine patients relapsed, respectively) and between those with MMF treatment for 12 or >/=24 mo. MMF treatment was associated with fewer infections and infections that required hospitalization (P = 0.013 and 0.014, respectively). Four patients in the CTX-AZA group but none in the MMF group reached the composite end point of end-stage renal failure or death (P = 0.062 by survival analysis). It is concluded that MMF and prednisolone constitute an effective continuous induction-maintenance treatment for DPLN in Chinese patients.

A long-term study on hyperlipidemia in stable renal transplant recipients

Abstract:  Objectives:  Hyperlipidemia is a common and important risk factor after renal transplantation, but there is little long‐term data on its incidence, pattern, and evolution in stable renal allograft recipients on low dose maintenance immunosuppression.

Potential Benefit of Plasma Exchange in Treatment of Severe Icteric Leptospirosis Complicated by Acute Renal Failure

ABSTRACT Leptospirosis is a common zoonosis seen worldwide, but it is rare in our locality (Hong Kong). Clinical manifestations of leptospirosis are variable and may range from subclinical infection to fever, jaundice, hemorrhagic tendency, and fulminant hepato-renal failure. Severe hyperbilirubinemia and acute renal failure have been associated with high mortality. We report our experience with a patient who developed severe Weils syndrome with marked conjugated hyperbilirubinemia and oliguric acute renal failure. These complications persisted despite treatment with penicillin and hemodiafiltration. Plasma exchange was instituted in view of the severe hyperbilirubinemia (970 μmol/liter). This was followed by prompt clinical improvement, with recovery of liver and renal function. The beneficial effects of plasma exchange could be attributed to amelioration of the toxic effects of hyperbilirubinemia on hepatocyte and renal tubular cell function. We conclude that plasma exchange should be considered as an adjunctive therapy for patients with severe icteric leptospirosis complicated by acute renal failure who have not shown rapid clinical response to conventional treatment.

Nephrotoxicity of immunosuppressive agents in renal transplantation

Abstract The outcome of solid organ transplantation has improved significantly in the past few decades with the advent of cyclosporine and other newer immunosuppressive agents including tacrolimus, mycophenolate mofetil, interleukin-2 receptor blockers, and rapamycin. A prominent consequence of the development in posttransplant immunosuppressive regimens is the reduced incidence of acute rejections, from 30% to 40% to approximately 15% or even lower (Gjertson, Clin Transpl 2000:467-80), although it still remains an important risk factor compromising long-term renal allograft survival. The acute and chronic nephrotoxicity of immunosuppressive agents, notably calcineurin inhibitors, have attracted increasing attention, and the reduction of these untoward effects has constituted an important theme of clinical research in transplantation. The current knowledge on the spectrum and mechanisms of nephrotoxicity pertinent to immunosuppressive agents used in renal transplantation is reviewed in this article and possible strategies for prevention or amelioration of the nephrotoxicity; the future directions for investigations are also discussed.

Comparison of Atorvastatin and Simvastatin in the Long-term Treatment of Hyperlipidemia After Kidney Transplantation

Background Hyperlipidemia is a common complication after kidney transplantation. However, there is little long-term data on the efficacy and tolerability of statin therapy in kidney transplant recipients. Methods We performed a prospective 3-year study to investigate the effects of atorvastatin treatment in 15 hypercholesterolemic stable renal allograft recipients on maintenance immunosuppression with corticosteroid and cyclosporine. Results were compared with data from 15 historical controls matched for baseline hyperlipidemia and renal allograft function who had been treated with simvastatin. Results Patients in the two treatment groups showed similar baseline characteristics. The average dosages of atorvastatin and simvastatin were 9.25 ? 2.82 mg and 8.38 ? 1.86 mg, respectively. Atorvastatin treatment reduced total cholesterol (TC) by 31.1%, 27.7%, 25.9% and 28.9%, and low-density lipoprotein (LDL) by 43.4%, 37.4%, 36.8% and 41.6%, after 3, 12, 24 and 36 months of treatment, respectively. A significant reduction in triglycerides (TG) was noted after 3 and 9 months, but was not sustained. High-density lipoprotein levels were unaltered. Reductions in TC and LDL after simvastatin treatment appeared less pronounced, although the differences did not reach statistical significance. At last follow-up, 90.9% of atorvastatin-treated patients achieved target LDL of less than 3.4 mmol/L, compared with 78.6% of the simvastatin group. No patients developed adverse reactions including abnormalities in liver enzyme or creatine kinase levels. Acute rejection was not observed, although one patient on simvastatin developed chronic allograft nephropathy. Conclusion Atorvastatin and simvastatin demonstrated sustained efficacy in reducing the levels of TC and LDL in stable renal allograft recipients. While atorvastatin may be more potent than simvastatin in the treatment of hypercholesterolemia, its TG-lowering effect was not sustained with long-term treatment. The difference in the therapeutic efficacy between the two drugs might have been due to dose rather than to the drugs themselves.

Sirolimus in Kidney Transplantation: A Pilot Study in Chinese Patients

We conducted a pilot open-label study on the use of sirolimus in 10 Chinese patients undergoing kidney transplantation who received triple prophylactic immunosuppression comprising prednisolone, cyclosporine and sirolimus. Sirolimus was given as a 6 mg loading dose followed by 2 mg/day maintenance. All patients achieved target sirolimus trough serum concentrations exceeding 5 ng/mL. Median duration of follow-up was 22 months after transplantation. One patient developed Type Ia acute cellular rejection at 6 months, which responded to pulse steroid therapy. Graft survival was 100% at 12 months and serum creatinine was 131 ± 36 μmol/L at 1 year. Low-density lipoprotein cholesterol and triglyceride levels were significantly increased after 2 months. Eight patients received atorvastatin, which was subsequently discontinued successfully in three patients. Infection was noted in two patients; one died of pneumocystis pneumonia 10 months after transplantation and the other had septicemia from urinary tract infection complicating graft vesicoureteric reflux. Two patients developed lymphocele in the early postoperative period, which resolved spontaneously in one patient and was treated successfully with ethanol sclerotherapy in the other. No patients developed thrombocytopenia or arthralgia. We conclude that sirolimus, when used together with prednisolone and cyclosporine, is well tolerated and effective in Chinese renal allograft recipients, and that hyperlipidemia early after transplantation is the most common adverse effect.

Acute renal tubular necrosis due to grass carp ingestion in a myeloma patient after allogeneic stem cell transplantation.

Acute renal tubular necrosis due to grass carp ingestion in a myeloma patient after allogeneic stem cell transplantation

A Misplaced Temporary Hemodialysis Catheter

Panel A A 50-year-old female with end stage renal failure due to focal segmental glomerulosclerosis on regular hemodialysis was found to have acute thrombosis of her right forearm arteriovenous fistula. A double lumen catheter was inserted at the bedside through a single puncture in the right internal jugular vein for temporary hemodialysis. During insertion of the catheter, the patient noted a vague discomfort over the shoulder with mild resistance on passage of the guide wire. The procedure was otherwise uneventful and no resistance was noted on aspiration of blood or flushing of the catheter ports. Postprocedural chest radiograph (CXR), however, showed malposition of the catheter tip in the right axillary vein (Panel A), and it was therefore urgently removed. Malposition is a known complication of temporary hemodialysis catheter insertion, which occurs in approximately 1% to 14% of catheter placements. Common sites are in the axillary vein or right atrium [1–3]. Although the value of routine postprocedural CXR has been questioned [2], it remains important for the detection of complications such as malposition of catheter tips, especially for insertion attempts that are not considered to be entirely smooth by the attending doctor [3].