Hyperuricemia and Acute Renal Failure in Renal Transplant Recipients Treated With High-Dose Mizoribine.

BACKGROUND: Hyperuricemia is a common adverse event frequently found in renal transplant recipients with mizoribine (MZ). Hyperuricemia itself will be a cause of renal dysfunction, and renal dysfunction also will be a cause of hyperuricemia simultaneously. This study investigates frequency of hyperuricemia and renal failure in renal transplant recipients treated with high-dose MZ. PATIENTS AND METHODS: From December 2007 to October 2015, there was a total of 32 living related renal transplant recipients treated with high-dose MZ. Of the 32 patients, 28 were treated with urate-lowering medications. RESULTS: One patient received allopurinol (AP) and 13 patients received benzbromarone (BB). For 6 of them, their urate-lowering medications were converted to febuxostat (FX) form AP or BB. In the remaining 14 patients, FX was administered from the beginning. In 2 cases of ABO-incompatible living related renal transplant recipients who were maintained with high-dose MZ and BB, severe hyperuricemia and acute renal failure occurred. One patient was a 48-year-old man, and his creatinine (Cr) level increased to 8.14 mg/dL and his serum uric acid (UA) was 24.6 mg/dL. Another patient was a 57-year-old man, and his Cr level increased to 3.59 mg/dL and his UA was 13.2 mg/dL. In both cases Cr and UA were improved, and no finding of acute rejection and drug toxicity was observed in graft biopsy specimens. BB was switched to FX and discontinuance or reduction of MZ was done. CONCLUSION: Combination of MZ and BB has the risk of acute renal dysfunction after renal transplantation. Latent renal dysfunction should be watched for in renal transplant recipients receiving high-dose MZ.

Improved graft survival in ABO-incompatible living donor kidney transplantation.

INTRODUCTION: We reviewed ABO-incompatible living donor kidney transplantations (LDKT) performed in our institute. PATIENTS: Fourteen ABO-incompatible LDKT were carried out in the first era (September 1990-August 1996) and 13 were in the second era (October 2001-July 2004). All patients were treated with sessions of plasmapheresis before transplantation to reduce antibody titers <1:8. In the second era, those with rebound increase of antibody titers >1:64 after repeated plasmapheresis were not subjected to transplantation. Posttransplantation immunosuppression consisted of cyclosporin, predonisone, azathioprine, gusperimus hydrochloride (DSG), and antilymphocyte globulin (ALG) in the first era, and tacrolimus, mycophenolate mofetil, predonisone, and DSG in the second era. Splenectomy was performed during the transplantation. Anticoagulant therapy was introduced in the second era. RESULTS: One-, 2-, and 5-year graft survival in the first era was 57%, 57%, and 50%, respectively, values that were significantly lower than those of ABO-compatible cases in the same period (n = 101), namely, 1-, 3-, and 5-year graft survival rates 93%, 83%, and 76%, respectively. The main reason for graft and patient losses was infectious complications. In the second era, no recipient suffered a severe infectious complication and 1- and 2-year graft survival rates were both 100%. Four patients in the first era and 1 in the second era experienced a graft rejection episode between 10 days and 14 months after transplantation, but they were successfully treated with steroid pulse therapy. CONCLUSION: Although patients with high blood group antibody titers remain problematic, ABO-incompatible LDKT is an increasingly viable option for patients whose only donor is blood group-incompatible.

Therapeutic drug monitoring of mycophenolic acid in renal transplant recipients.

Immunosuppressive regimens including mycophenolate mofetil (MMF, Cellcept) were used in a renal transplant transplant program since May 2000 including 67 patients in whom it was the primary drug. Acute rejection (AR) occurred in 9 cases (13%) with 1-year graft survival rate of 96.8%. Pharmacokinetic (PK) studies of mycophenolic acid (MPA) were performed in 46 recent patients (total, 127 times). There was no correlation between dose (mg/kg) and blood concentration (AUC0-9: r2= 0.27). AUC0-9 was well correlated with AUC0-4 (r2= 0.91), but not with a single timepoint concentration. MPA AUC0-9 level was significantly higher among the AR-negative group (n = 33; 34.2 +/- 16.8 ng.hr/mL) compared with AR-positive group (n = 3; 28.2 +/- 1.9 ng.hr/mL; P = .04085) over the 2 weeks after transplantation. MPA AUC0-9 level was higher among the adverse event (AE-positive) group (n = 15; 39.2 +/- 22.8 ng.hr/mL) compared with the negative group (n = 21; 30.1 +/- 8.0 ng.hr/mL; P = .08772) within 2 weeks after transplantation. These results suggest the necessity of measuring AUC for therapeutic drug monitoring (TDM) of MMF-containing immunosuppressive therapy. The possible target level of MPA AUC0-9 would be approximately 30 ng.hr/mL using the present immunosuppressive regimen.

Renovascular reconstruction of grafts with renal artery variations in living kidney transplantation.

INTRODUCTION: The shortage of grafts in living kidney transplantation has forced the use of marginal grafts with arterial disease or grafts with multiple renal arteries (MRA). We reviewed the outcomes of transplants using allografts with MRA procured by open donor nephrectomy and report two cases requiring vascular reconstruction. PATIENTS AND METHODS: We reviewed 31 cases where renovascular reconstruction of an MRA graft was performed. A ex vivo pantaloon (side-to-side) anastomosis to create a common channel was performed in 24 cases including two cases of renal artery aneurysms in the grafts, where vascular reconstruction was performed in the same fashion after resection of the aneurysm. In four cases, an accessory artery was anastomosed sequentially after revasculization of the main artery. In three cases of grafts with multiple renal arteries, multiple anastomoses were done in situ after various ex vivo renovascular reconstructions. RESULTS: Twenty one MRA grafts including grafts with a renal aneurysm are functioning well for a mean follow-up 135 months. The graft survival rate was 71.0% at 5 years after transplantation and 67.7% at 10 years. The donors whose grafts had a renal aneurysm were also well and normotensive with normal renal function at present. Ten grafts failed mainly due to chronic allograft nephropathy. CONCLUSION: MRA grafts procured by open nephrectomy, including those with renal artery aneurysms, were engrafted successfully by applying appropriate renovascular surgery. The use of those grafts was safe for both the recipient and the donor.

Twenty-five-year survival of living related kidney transplants: thirty-five years' experience.

AIM: Although better graft survival in patients treated with CsA has been obtained, chronic rejection continues to be a common complication in renal transplantation. In this study, we examined the graft survivals and complications among renal transplant patients followed for more than 25 years. METHODS: Between April 1970 and April 1979, 110 consecutive renal transplantations from living donors were performed in 110 patients. There were 83 men and 27 women of mean age of 27 +/- 7.0 years. A combination of azathioprine (AZ) and prednisolone (PSL) was used for the initial immunosuppressive therapy in all patients. RESULTS: Over 25 years postoperatively, 41 patients died with or without a functioning graft due to complications including infections and malignancies. Therefore, the 25-year patient survival was 62.5% and 34 patients returned to hemodialysis, yielding an actual 25-year graft survival of 36/110 (32.1%). The longest surviving graft is 30 years and 2 months. The main causes of death were infectious disease and malignancy; 73% of graft loss was due to chronic rejection. Mean serum creatinine of the patient with functioning grafts over 25 years is 1.2 mg/dL; 75% of patients displayed a value under 1.5 mg/dL. The mean dosage of Az was 52.3 mg/d and PSL was 5.6 mg/d.

Recurrence of focal glomerulosclerosis in post-renal transplant recipients: report of two cases.

INTRODUCTION: Focal segmental glomerulosclerosis (FGS) has a tendency to recur frequently after kidney transplantation. To evaluate the incidence and outcome of recurrence of FGS, we report 2 cases of recurrence. PATIENTS: Among 12 patients with renal failure caused by biopsy-proved FGS who received kidney allografts from living related donors, 2 experienced recurrent FGS. CASE REPORTS: Case 1 was a 28-year-old man who received a renal transplant from his mother. The recurrence of FGS happened just after the scheduled reduction in immunosuppressants at 36 months after the transplantation. He developed subsequently end-stage renal failure (ESRD) 50 months after transplantation. Case 2 was a 22-year-old man who received a renal transplant from this ABO disparate mother. A few days after renal transplantation, he displayed a severe nephrotic syndrome due to recurrent FGS, reaching ESRD at 23 months. To treat recurrent FGS, plasma exchange was partially effective, reducing the proteinuria but not stopping the progression of disease. DISCUSSION: Two recipients with severe proteinuria were diagnosed as having recurrent FGS. The incidence of recurrent FGS was 16.7% with 5-year and 10-year graft survival rates among recipients with ESRD caused by FGS of 79.6% and 68.2%, respectively. The incidence and graft survival rates were better than those expected based upon previous reports. Once the recurrence occurred, it was difficult to halt the progression of disease. Effective prevention of FGS and careful observations with maintained of immunosuppression are necessary in these patients.

An autopsy case of bacterial septic shock 12 years following ABO-incompatible renal transplantation.

We report the case of an ABO-incompatible kidney transplant recipient who died suddenly following a good transplant course of 12 years. For 10 years after transplantation, the graft function had been stable (s-Cr: 1.0-1.5 mg/dL), although chronic hepatitis C had developed, with elevation of transaminase. In the 11th year, he was admitted into the hospital with low-grade fever and general fatigue. Jaundice and anaemia progressed, and he died 2 months after admission. The autopsy diagnosis was: (1) post-renal transplantation state, (2) phlegmonous enterocolitis with septic infarction, (3) cellulitis and necrotic myositis, and (4) sepsis. The transplanted kidney graft showed well-preserved glomeruli and tubules, corresponding to chronic allograft nephropathy (CAN) grade Iota (ci1, ct1, cv1), according to the Banff classification. The pathological changes observed in this long-surviving ABO-incompatible kidney graft were similar to those of an ABO-compatible graft, although its degree was milder.