EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: Autosomal dominant polycystic kidney disease is a common cause of end-stage renal disease and a common indication for renal transplant. This study was undertaken to evaluate the demographics, outcomes, and complications of renal transplant in patients with autosomal dominant polycystic kidney disease compared with other nephropathies.

Materials and Methods: In a retrospective case-control design, we reviewed the records of 7 patients with autosomal dominant polycystic kidney disease from a total of 701 renal transplant patients over a 30-year period (1986-2016). For each patient, a matched control was selected based on sex, age, year of transplant, and type of kidney donor. We excluded patients who underwent kidney transplant abroad and those with a follow-up period of less than 2 years.

Results: The number of patients with autosomal dominant polycystic kidney disease requiring transplant at our center was estimated at 0.23 per year, and the condition represented 1.57% of initial nephropathy causes. The mean patient age at transplant was 50.8 ± 8.05 years. There were 5 male and 2 female patients in the case group, with a male-to-female ratio of 2.5. The source of the graft was predominantly a living related donor (5/7). Four patients had extrarenal manifestations, the most common of which were liver cysts (3 patients). Rejection occurred in a single study patient (14.2%) and in 4 control patients (57.1%; P = .51). Two patients did not develop any complications. Complications noted after transplant included infection (3/7 cases vs 2/7 controls; P = .67) and cerebrovascular accidents (2/7 cases vs 0/7 controls).

Conclusions: Further studies with longer follow-up and greater numbers of patients are needed to compare more precisely the complications and results of transplant between patients with autosomal dominant polycystic kidney disease and other kidney transplant recipients.

Key words : Comparative study, Kidney diseases, Prognosis

Autosomal dominant polycystic kidney disease (ADPKD) affects both sexes equally and occurs in all ethnicities. It accounts for 5% to 10% of patients with end-stage renal disease (ESRD), making it the fourth leading global cause of kidney failure.1 Approximately 50% of patients with ADPKD will develop ESRD in their fourth to sixth decade of life. The entity has strikingly high phenotypic variability.¹ The rate of disease progression is quite variable, and the expected increase in total kidney volume ranges from 1% to 10% per year.² For patients with ADPKD who reach ESRD, kidney transplant is the preferred type of renal replacement therapy.³ We aim to evaluate the demographics, outcomes, and complications of renal transplant in patients with ADPKD compared with other nephropathies.

Materials and Methods

We conducted a single-center retrospective review of consecutive patients with ADPKD undergoing transplant between 1986 and 2016. The following clinical variables were evaluated: patient sex, age, ethnicity, type of dialysis, duration of dialysis before transplant, comorbidities, type of donor, number of human leukocyte antigen incompatibilities, cold ischemia time, induction therapy, type of immunosuppression, and timing of native nephrectomy, if performed (eg, before, simultaneously, or after transplant). We also evaluated delayed graft function, graft failure, and death. Delayed graft function was defined as a dialysis requirement within the first 7 days after transplant. Patient- and graft survival were the primary outcomes. The other outcomes included baseline creatinine level and glomerular filtration rate using the Modification of Diet in Renal Disease formula at 1 month, 1 year, 3 years, and at last follow-up. Complications such as graft dysfunction and surgical, infectious, cardiovascular, metabolic, and neoplastic issues were noted. The types of graft rejection were confirmed by biopsy, and the mortality associated with these causes was evaluated.

All information was collected from the medical records and added to a StatView database (SAS Institute, Cary, NC, USA). In a retrospective case-control design, patients with ADPKD were matched with a control based on sex, age, year of transplant, and type of kidney donor. We excluded patients who underwent kidney transplant abroad and those with a follow-up of less than 2 years. The quantitative variables were described as means or medians with their respective standard deviations or percentiles in StatView, according to the data distribution identified using the Shapiro-Wilks test. Analysis of variance was used to compare the quantitative variables and the outcomes in the variables that reached normality. The chi-square test, with a level of significance of .05, was used for qualitative variables. All of the protocols conformed to the ethical guidelines of the 1975 Helsinki Declaration.

Of 701 renal transplants performed over a 30-year period at our center, there were 7 patients with ADPKD. The number of patients with ADPKD requiring transplant was estimated at 0.23 per year, and ADPKD represented 1.57% of initial nephropathy. The mean patient age at transplant in the ADPKD group was 50.8 ± 8.05 years. There were 5 male and 2 female patients, with a male-to-female ratio of 2.5. Four patients had extrarenal manifestations of ADPKD, the most common of which were liver cysts (3 patients). No intracranial aneurysms were observed in our series. The source of the graft was predominantly a living related donor (5/7). The demographic and clinical characteristics of the 7 ADPKD patients and the 7 control patients are listed in Table 1.

Four of the 7 patients with ADPKD underwent nephrectomy. Two patients underwent pretransplant native nephrectomy, with 1 of these being unilateral. Simultaneous unilateral nephrectomy was performed in 1 patient. All pretransplant and simultaneous nephrectomies were performed using an open technique. One patient underwent posttransplant native nephrectomy. The cyclosporine-mycophenolate-prednisolone immunosuppression protocol was used in 5 of 7 patients, with tacrolimus-mycophenolate-prednisolone used in the other 2 patients. The median glomerular filtration rate after 3 years of follow-up was 96 ± 18 mL/min. The common complications noted after transplant included infection (3/7 cases vs 2/7 controls; P = .67) and cerebrovascular accident (2/7 cases vs 0 controls). New-onset diabetes occurred in 3 cases and 2 controls (P = .62). Rejection occurred in 1 case (14.2%) and in 4 controls (57.1%). Two patients did not develop any complications. Transplant rejection was confirmed by biopsy, and there was no significant difference in the number of rejections according to the cause of ESRD (P = .51). During follow-up, 2 patients died: 1 from cardiovascular disease and 1 from infection.

Our single-center study aimed to evaluate the patient and graft survival rates in a kidney transplant population, comparing ADPKD with other nephropathies that cause ESRD. We did not observe a significant difference in patient or graft survival between the 2 groups; this agrees with the results of previous studies.^4,5A number of renal and nonrenal complications have been reported in kidney transplant recipients with ADPKD. Cerebrovascular events only marginally affect morbidity and mortality, whereas cardiac morbidity and mortality are not increased. No complications are found to occur more frequently in ADPKD patients.

Liver cysts are the most frequent extrarenal abnormality in ADPKD. Conservative surgery can be offered to patients with large cysts when somatostatin analogue therapy is not available.⁶ In our series, liver cysts were present in 3 patients; these were stable in size and there have been no complications thus far. In the literature, the prevalence of asymptomatic intracranial aneurysm in patients with ADPKD is approximately 8%,which is 2 to 3 times higher than in the general population.⁷ In our series, cerebral magnetic resonance imaging was performed in 4 patients; none showed signs of a cerebral aneurysm. In our patients, diabetes was not significantly associated with ADPKD compared with other nephropathies. However, a previous meta-analysis demonstrated a significant association between ADPKD and new-onset diabetes after transplant8; most of the included studies evaluated this association within 1 year of surgery. The risk of diabetes requiring insulin is not significant.5 Although the underlying mechanisms linking diabetes and ADPKD are not yet known,^9,10 it has been proposed that insulin-resistant genes are cotransmitted with PKD1 and PKD2 mutations and may interfere with insulin secretion and hepatic gluconeogenesis.¹¹

Native nephrectomy can be performed before, during, or after transplant. In the 1970s, bilateral nephrectomy was consistently performed before transplant in patients with ADPKD to prevent the infections related to posttransplant cyst, hematuria, and hypertension.¹² However, this procedure had high mortality and morbidity; therefore, today it is performed primarily electively.¹³ In our series, 2 patients with ADPKD underwent pretransplant native nephrectomy. Simultaneous unilateral nephrectomy was performed in 1 patient and posttransplant native nephrectomy in 1 patient. No postoperative complications were noted. Fuller and associates¹⁴ compared the results of pretransplant, concomitant, and posttransplant native nephrectomy in patients with polycystic kidney disease, showing that concomitant native nephrectomy may be performed safely and graft function in the early period is not adversely affected. Some studies suggest that simultaneous nephrectomy and kidney transplant is preferable to pretransplant nephrectomy in asymptomatic patients with ADPKD, and nephrectomy should be requested only if massive kidney size prevents graft placement.^15,16 We should note that no patients in our control group underwent nephrectomy. The indications for native nephrectomy in non-ADPKD patients include uncontrolled hypertension, Goodpasture syndrome, recurrent or chronic pyelonephritis, structural urinary tract abnormalities, urolithiasis, and massive proteinuria.¹⁷ As in the literature, our study showed a slightly better patient outcome during short- and long-term follow-up in the ADPKD population than in the control group; however, this was not statistically significant.

Similar studies have shown a good outcome for patients with ADPKD, but their patients did not do better than those in our series. Further studies with longer follow-up and greater numbers of ADPKD patients are needed to compare the complications and results of transplant between ADPKD and other causes of ESRD.

Volume: 15 Issue: 1 February 2017 - Supplement - 1

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