Treatment of BK Virus-Associated Nephropathy With Cidofovir in Renal Transplantation

BK virus-associated nephropathy (BKVN) has become recognized as an important cause of allograft dysfunction among transplant recipients. Despite reduction in immunosuppression, 30%-40% of recipients progress to allograft loss. Cidofovir is an antiviral agent that has been proposed for treatment of BKVN. We describe the clinical course, renal function, and blood viral measurement in 6 renal transplant recipients with BKVN who were treated with low doses of cidofovir. Administration of cidofovir was associated with clearance of BK virus DNA from blood and stabilization of renal function in 5 cases. These data suggest that cidofovir may be useful as adjuvant therapy for BKVN.     

Treatment With Cinacalcet of Secondary Hyperparathyroidism After Renal Transplantation

Background

The treatment of posttransplant secondary hyperparathyroidism (SHP) with vitamin D analogues is determined by their effectiveness to reverse hypercalcemia. Calcimimetics inhibit parathyroid hormone (PTH) secretion by modulating the calcium-sensing receptor in the parathyroid gland. Cinacalcet, a calcimimetic drug, has proven its effectiveness for the treatment of SHP among patients in phase V of chronic renal disease.

Patients and Methods

This retrospective analysis included 48 patients with SHP who were treated with cinacalcet. The initial dose of 30 mg/d could be increased to 180 mg, administering calcitriol also, depending on the serum calcium and PTH levels. The objectives were a PTH level between 75 and 125 pg/mL or a decrease >40%, and a serum calcium level below 10.5 mg/dL.

Results

The average PTH at baseline was 244 pg/mL, decreasing to 131 pg/mL at 1 year (P < .01). The average calcium at baseline was 10.1 mg/dL descending to 9.2 mg/dL at 1 year (P < .01). Among patients with hypercalcemia, the calcium decreased from 11 to 9.6 mg/dL at 1 year (P < .01). Seventy percent of patients without hypercalcemia reached the desired value of PTH, and 100% of those with hypercalcemia. Among patients with hypercalcemia, the desired calcium level was reached in 91% of cases. Ten patients developed hypocalcemia. In 3 cases we stopped the treatment with cinacalcet due to digestive intolerance.

Conclusions

Treatment with cinacalcet controlled hyperparathyroidism and hypercalcemia among patients with posttransplant SHP. It was a safe drug, with a low incidence of side effects.     

Induction With Basiliximab in Renal Transplantation

Introduction

The use of monoclonal antibodies in renal transplantation for induction therapy has been associated with a marked reduction in acute rejection rates with an impact on graft and patient survivals.

Objective

We sought to evaluate the efficacy of renal transplant induction protocols using Basiliximab based on the rates of acute rejection episodes (ARE) and delayed graft function (DGF) of infectious complications in the first 6 months posttransplant, as well as patient and graft survivals.

Methods

We retrospectively evaluated all renal transplants performed between 2000 and 2008 that were primary grafts from cadaveric heart-beating donors, into recipients with a panel reactive antibody titer <5% and who were treated with an immunosuppression scheme based on cyclosporine, mycophenolate mofetil/mycophenolic acid plus corticosteroids, with (group 1) or without basiliximab (group 2).

Results

We enrolled 52 recipients in group 1 (induction with basiliximab) and 189 in group 2 (without basiliximab). The baseline characteristics were similar among the groups, except for time on dialysis which was longer in group 1 and the number of HLA matches, which was lower in group 1. The ARE rate was lower among group 1 (7.8% vs 27.8%; P = .001); rates of DGF and infectious complications were similar. There was no significant difference in graft and patient survivals.

Conclusion

In this study, induction with basiliximab was associated with a reduced rate rate of ARE, despite a lower number of HLA matches and a longer previous time on dialysis. The use of this induction modality was not associated with a greater rate of infectious complications.     

Pulmonary Hypertension in Patients With End-Stage Renal Disease Undergoing Renal Transplantation

Introduction

Pulmonary hypertension (PHT) has been reported to occur in a considerable proportion of patients with end-stage renal disease (ESRD). It is a progressive condition of the pulmonary circulation that poses prognostic importance. In this study, we sought to investigate the prevalence and the predictors of PHT among ESRD patients undergoing renal transplantation.

Patients and methods

We retrospectively evaluated the records, clinical and demographic data as well as laboratory results of 500 adult patients who underwent renal transplantation at our institution. A comprehensive Doppler echocardiographic examination was performed in all patients as part of the preoperative assessment. Systolic pulmonary artery pressure (SPAP) was calculated using Bernoulli equation; a value of >30 mm Hg was accepted as PHT.

Results

The mean age of the study population was 31.6 ± 10.2 years. The mean duration of dialysis was 40 months; 432 patients (86.4%) were on hemodialysis (HD) and 68 (13.6%) on peritoneal dialysis (PD). PHT was detected in 85 (17%) patients with a mean SPAP of 46.7 ± 8.7 mm Hg (range = 35-75 mm Hg). The mean age, sex, and laboratory variables were similar between patients with versus without PHT (P > .05 for all). The mean duration of dialysis therapy was longer in the PHT group than those subjects with normal SPAP (50.8 vs 38.5 months; P = .008). Concerning the type of dialysis, the ratio of patients having PHT was higher in the HD compared with the PD group (18.8% vs 5.9%; P = .008). The prevalence of chronic obstructive pulmonary artery disease, asthma, smoking, hypertension, and diabetes mellitus did not differ between patients with versus without PHT (P > .05 for all).

Conclusion

The findings of this study revealed that PHT was a common clinical condition among patients with ESRD evaluated for renal transplantation. The time on renal replacement therapy particularly HD as the treatment was associated with greater prevalences. Since it may be of prognostic importance in patients undergoing renal transplantation, a careful preoperative assessment including a comprehensive Doppler echocardiographic examination is needed to identify PHT.     

Results of Renal Transplantation in Patients With Schistosoma Infection

Purpose

We evaluated the results of renal transplantation in patients infected with Schistosoma haematobium, as well as the risks of urological complications and post-transplant reinfection.

Materials and Methods

The outcome of 20 kidney transplants was retrospectively studied. Based on our experience and review of the literature, our clinical practice to prevent urological complications consisted of antischistosomal chemotherapy given at the pre-transplant evaluation, with endovesical ureteroneocystostomy preferred in case of bladder calcifications. A Foley catheter was maintained for 10 days. A transurethral bladder neck incision was performed before removal of the Foley catheter when bladder neck sclerosis was present.

Results

The 1 and 2-year patient survival rate was 93%, and 1 and 2-year graft survival rates were 88 and 81%, respectively, which were not different from those of a cohort of 167 patients without schistosomal infection. Surgical complications included 2 postoperative hemorrhages, 2 urinary leaks and 1 nonschistosomal related ureteral stricture. Post-transplant schistosomal infection never occurred when antischistosomal chemotherapy was given at the pre-transplant evaluation.

Conclusions

Patients with schistosomal infection are suitable recipients for kidney transplantation, although they are at risk for urological complications. Unlike other infectious diseases, such as tuberculosis, the risk of recurrence due to reactivation of chronically hosted pathogens seems to be low or absent in patients who received antischistosomal chemotherapy at the pre-transplant evaluation. Long-term urological followup is recommended, including urethrocystoscopy, because of the theoretically increased risk for bladder malignancy.     

Successful Renal Transplantation in Children With Posterior Urethral Valves

PurposeThe treatment of children with posterior urethral valve (PUV) and end-stage renal disease can be challenging. Some series have had poor outcomes after renal transplantation with an increased risk of graft dysfunction and urinary tract infections. We present our experience with a pediatric population and compare it to all the other pediatric renal transplants done at our institution.Materials and MethodsWe identified 10 patients with PUV who underwent a total of 13 renal transplants between 1990 and 2000. The comparison group included 120 transplants done in 95 patients during the same period. Cumulative allograft survival and function were recorded.ResultsOverall patient survival in the PUV group was 100%. Mean age at transplant in the PUV group was 10.0 years and mean followup was 3.9 years. Six patients underwent high proximal urinary tract diversion, while the remainder had primary transurethral valve ablation. Three patients had bladder augmentation before transplantation. Cumulative allograft survival in the PUV group at 1 and 5 years was 85% and 64%, respectively. Of the 10 patients 9 currently have functioning living related donor transplants. One patient lost 3 cadaveric donor transplants to chronic rejection. No patients lost grafts due to infection or bladder dysfunction. Mean serum creatinine of the functioning grafts was 1.1 mg/dl.ConclusionsRenal transplantation can be performed safely and effectively in patients with PUV, including those who have undergone previous proximal urinary tract diversion. Preoperative bladder management and continued monitoring of bladder and kidney function postoperatively are paramount in the preservation of allograft function.     

Alemtuzumab Pre-Conditioning With Tacrolimus Monotherapy in Pediatric Renal Transplantation

We employed antibody pre-conditioning with alemtuzumab and posttransplant immunosuppression with low-dose tacrolimus monotherapy in 26 consecutive pediatric kidney transplant recipients between January 2004 and December 2005. Mean recipient age was 10.7 +/- 5.8 years, 7.7% were undergoing retransplantation, and 3.8% were sensitized, with a PRA >20%. Mean donor age was 32.8 +/- 9.2 years. Living donors were utilized in 65% of the transplants. Mean cold ischemia time was 27.6 +/- 6.4 h. The mean number of HLA mismatches was 3.3 +/- 1.3. Mean follow-up was 25 +/- 8 months. One and 2 year patient survival was 100% and 96%. One and 2 year graft survival was 96% and 88%. Mean serum creatinine was 1.1 +/- 0.6 mg/dL, and calculated creatinine clearance was 82.3 +/- 29.4 mL/min/1.73 m(2). The incidence of pre-weaning acute rejection was 11.5%; the incidence of delayed graft function was 7.7%. Eighteen (69%) of the children were tapered to spaced tacrolimus monotherapy, 10.5 +/- 2.2 months after transplantation. The incidence of CMV, PTLD and BK virus was 0%; the incidence of posttransplant diabetes was 7.7%. Although more follow-up is clearly needed, antibody pre-conditioning with alemtuzumab and tacrolimus monotherapy may be a safe and effective regimen in pediatric renal transplantation.     

Combination Treatment With Plasmapheresis and Rituximab for Recurrent Focal Segmental Glomerulosclerosis After Renal Transplantation

Therapy for recurrent focal segmental glomerulosclerosis (FSGS) in the renal allograft is largely based on case reports. The use of plasmapheresis alone (based on its effectiveness in children) appears less effective in adults, reaching a response rate of <40%. Recently, rituximab, an anti‐CD20 monoclonal chimeric antibody, showed promising results as rescue therapy in plasmapheresis‐resistant recurrent FSGS. However, following rituximab administration, response is variable, often slow and consequently overlooked. We report a series of four cases of recurrent FSGS following renal transplantation successfully treated with a combination of plasmapheresis and rituximab. Complete remission of proteinuria occurred in two and partial remission in the other two patients whereas renal function improved or remained stable. During treatment and the follow‐up period (18–60 months) no severe infectious complications were observed. Our data suggest that the combination of plasmapheresis and rituximab is an acceptable treatment in patients with post‐transplantation recurrent FSGS.     

儿童肾移植的临床特点(附22例报告)

目的:探讨儿童肾脏移植的手术、围手术期处理及免疫移植剂应用的特点.方法:对我院22例儿童尿毒症患者行肾移植术,尸体肾移植21例,活体亲属供肾的肾移植1例.供肾动脉与受者的髂总动脉吻合8例,供肾动脉与受者的髂外动脉吻合3例,供肾动脉与受者的髂内动脉吻合11例.免疫抑制剂方案:7例为CsA加Aza加Pred;9例为CsA加MMF加Pred;6例为FK506加MMF加Pred.结果:1、3、5年人/肾存活率分别为 96.6%/ 94.8%, 88.2%/ 81.8%, 82.5%/ 76.3%;急性排斥反应、急性肾小管坏死发生率各为 18.1%;术后免疫抑制剂每千克体重剂量较成人显著高.结论:良好的组织配型、成功的手术和正确的围手术期处理,对患者相当重要;加强随访,提高患儿的依从性.     

Reduction in Size of Renal Angiomyolipoma After Treatment With Everolimus in Lung Transplantation Due to Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM) is a rare disease characterized by abnormal proliferation of immature smooth muscle cells and cystic lung destruction, which determines the prognosis of the disease. The kidney angiomyolipomas are usually very common in this disease and are usually asymptomatic unless complications arise. In the absence of a curative treatment, recent publications show promising results in molecular therapy to prevent functional decline and to control the size of the angiomyolipomas. These therapies include mTOR complex inhibitors, especially sirolimus.We report a case of a patient diagnosed with LAM who underwent lung transplantation with reduction of renal angiomyolipoma size after treatment with the mTOR inhibitor everolimus.     

Association of IL-17F Gene Polymorphisms With Renal Transplantation Outcome

Objective

Although interleukin 17 (IL-17) has some roles in renal transplantation, the influence of IL-17 gene single-nucleotide polymorphisms (SNPs) on renal transplantation has not been studied.

Methods

The associations of 5 IL-17F gene SNPs (–1507G/A, 6329G/A, 7384A/G, 7470G/A, and 7489A/G) with renal transplantation outcome were analyzed. Polymerase chain reaction with sequence-specific primers (for –1507G/A and 6329G/A) and direct sequencing (for 7384A/G, 7470G/A, and 7489A/G) were performed on 282 renal transplantation recipients and 210 healthy controls.

Results

IL-17F SNPs were not associated with acute rejection. Recipients with G allele on 7489A/G showed lower graft survival than recipients without G allele (P = .04). In multivariate analysis, G allele on 7489A/G was an independent risk factor for graft failure (odds ratio = 2.77, P = .03).

Conclusion

IL-17F gene SNP 7489A/G was associated with renal graft failure. Further studies are needed in larger number of patients.     

Three-Month Experience With Tacrolimus Once-Daily Regimen in Stable Renal Allografts

Introduction

MR-4, the new oral formulation of tacrolimus that allows once-daily dosing, may improve patient compliance. The purpose of this study was to evaluate the safety and efficacy parameters among a group of stable renal allografts after conversion to MR-4.

Methods

We enrolled 82 stable kidney recipients, who had received their grafts 43.9 ± 38.3 months prior. They were of mean age 56 ± 12 years and included 70.7% men. Sixty-six patients were converted on a milligram-for-milligram basis from their total daily dose; the remaining patients were converted at the physician's discretion. Three patients were excluded: 1 because of the development of abdominal pain, and 2 because of dosing errors. Tacrolimus trough levels and renal function tests were evaluated at entry and on days 7, 30, and 90.

Results

Only 5 (7.6%) converted patients required a later dose adjustment. In the group of 61 patients who did not require this adjustment, the mean tacrolimus trough levels decreased during the first week (6.8 ± 1.7 to 5.8 ± 2.0; P < .000). Thirty-eight patients completed 3 months of follow-up. Their tacrolimus trough levels, serum creatinine levels, and proteinuria remained stable. The number of capsules per patient needed after the conversion to MR-4 was lower (3.9 ± 1.6 versus 2.9 ± 1.0; P < .000). There were no cases of acute rejection episodes.

Conclusion

Based on a milligram-for-milligram conversion, only 7.6% of our patients required a dose adjustment. With this conversion, an initial decrease in tacrolimus trough levels was documented at day 7, which remained stable to the end of the study. The patients needed a lower number of capsules. These results supported the safety of MR-4.     

Early Outcomes in Renal Transplantation With Routine Intraoperative Duplex Ultrasound

BackgroundWhile intra-operative duplex ultrasound scanning can be readily performed in renal transplantation, the value of this intervention in routine practice is not established.MethodsThree hundred thirty-one consecutive single renal transplants in adult recipients underwent intraoperative scanning at implantation. Early graft losses were compared with those recorded in the ANZDATA Registry.ResultsNine overt vascular abnormalities were corrected prior to scanning. Four further suspected venous outflow restrictions were confirmed by ultrasound and revised. Another 11 major vascular revisions were performed following intraoperative ultrasound consisting of 7 otherwise unsuspected inflow abnormalities, all corrected, and 4 anastomoses redone to reposition the graft. Thirty-two (9.7%) grafts were repositioned under ultrasound guidance to improve cortical perfusion but without vascular revision. One graft with hyperacute rejection was explanted 4 days postimplantation and one graft with primary nonfunction remained well perfused. Two patients died within 90 days, both with functioning grafts. Twenty-three grafts were re-explored within 7 days, including 9 solely for graft hypoperfusion. There were no postoperative arterial thromboses and, at re-exploration, no arterial anastomoses required revision. There were no postoperative venous thromboses, although one venous anastomosis was revised. No grafts were lost within 90 days for surgical or technical reasons compared with 76 (1.0%) of 7603 contemporaneous grafts in the ANZDATA Registry (P = .077 Fisher's exact test, P = .069 χ² test).ConclusionsThe routine use of intraoperative ultrasound appears to be of benefit by identifying otherwise unrecognized vascular abnormalities, leading to a reduction in early graft losses because of surgical factors.     

Ten Year Experience With Renal Transplantation in Juvenile Onset Diabetics

Between 1968 and 1978, 305 juvenile onset diabetic patients with uremia and 462 nondiabetic uremic patients of similar age received primary renal allografts at the University of Minnesota. Two hundred eight of the diabetic patients are alive and 190 have functioning renal grafts three months to ten years after transplantation. Cumulative patient survival rates at two years for diabetic recipients of kidneys from HLA identical siblings, other related and cadaver donors are 90, 73 and 68%, respectively, the corresponding graft functional survival rates are 90, 67 and 55%. For nondiabetic patients receiving kidneys from the same donor categories the corresponding patient survival rates are 97, 86 and 75%, while the graft functional survival rates are 94, 77 and 64%. The differences in patient and graft survival between diabetic and nondiabetic recipients are statistically significant only for the patients receiving grafts from HLA-nonidentical related donors. For all recipients under the age of 30, there are no statistically significant differences in patient and graft survival. Regardless of the age of the patient or the source of the kidney, the survival of diabetic patients treated with transplantation at our institution is better than the use of chronic hemodialysis, alone. Technical complications do not occur more frequently in diabetic transplant recipients. Cardiovascular disease is responsible for most of the late deaths in these diabetic patients. Amputations of digits or extremities have been required in 15% of the diabetic patients. On the positive side, the vision of 88% of these recipients remained stable or had improved visual acuity, and 82% of the diabetic patients were actively rehabilitated after transplantation. Kidney transplantation is the treatment of choice for end-stage renal failure in diabetic patients, just as it is for most uremic patients.     

Association Of Marital Status With Access To Renal Transplantation

In this report we evaluated the association of marital status with access to renal transplantation. We analyzed data from the USRDS. In patients with ESRD aged ≥27 (mean age of first marriage in the US), we analyzed the association of marital status with two outcomes: (1) likelihood of being placed on the waiting list for renal transplantation or first transplant, (2) likelihood of receiving kidney transplant in patients already listed. We analyzed marital status as a categorical variable: (1) not married (including never been married and widowed); (2) divorced or separated; and (3) currently married. Subgroups based on age, race, sex, donor type and diabetic status were also analyzed. After adjustments for the included independent variables and compared to individuals never married or widowed, those who were divorced/separated (HR 1.55, p < 0.001) and currently married (HR 1.54, p < 0.001) had a higher likelihood of being placed on the transplant waiting list. Once listed, married individuals had higher chances of getting transplanted as well (HR 1.28, p = 0.033). This trend was consistent in most of the subgroups studied. We demonstrated that being married is associated with better access to renal transplantation compared to those who were never married/widowed.