Key words : Autosomal recessive tubulointerstitial nephropathy, Renal transplant, Transplant prognosis

Introduction
Nephronophthisis, an autosomal recessive tubulointerstitial nephropathy, is the most common genetic cause of kidney failure, accounting for 10% to 20% of cases in childhood.1 Nephronophthisis is genetically heterogeneous; so far, mutations in 25 pathogenic genes, which encode components of the primary cilium, have been identified. These genes and their protein products are linked within an interaction network into macromolecular complexes (called nephrocystin modules) as follows: NPHP 1-4-8 (the NPHP complex), NPHP 5-6, NPHP 2-3-9-ANKS6, and MKS.2-4

According to the clinical presentation, 3 different forms have been described: infantile, juvenile, and adolescent nephronophthisis. In juvenile nephronophthisis, which is the most common genetic cause of kidney failure among pediatric patients, the first symptoms begin at about 6 years of age and kidney failure develops at an average age of 13 years. Treatment of patients with nephronophthisis is symptomatic by support therapy, and kidney transplant is a good choice of treatment when kidney failure has developed. The use of living related donor transplants is more common (at approximately 67%) in these patients.1,5 Nephronophthisis has excellent posttransplant outcomes, and graft survival has been reported to be better than in patients with other diagnoses.1,5 Disease recurrence has never been reported after transplant.1,2,5-7 There are few reports of outcomes after kidney transplant of juvenile nephronophthisis. In this study, we reviewed and reported the outcomes of kidney transplant recipients who had a primary diagnosis of juvenile nephronophthisis and who had follow-up in our center.

Materials and Methods
Medical records of 180 pediatric kidney transplant recipients (aged 0-18 years), who had undergone kidney transplant and who received follow-up in our center between January 2011 and June 2021, were examined retrospectively. Seventeen patients with a primary diagnosis of juvenile nephronophthisis were analyzed. Demographic data of patients, donor type, rejection rate, glomerular filtration rate (GFR) at 1 and 5 years posttransplant, and graft loss were recorded. Posttransplant immunosuppression included corticosteroids, a calcineurin inhibitor (tacrolimus, cyclosporin) or sirolimus, and mycophenolate mofetil as induction therapy.

We compared patients whose primary kidney disease was juvenile nephronophthisis versus patients who had the other etiologies of kidney failure in terms of transplant age, donor type, immunosuppressive treatment, acute rejection, graft loss rate, and GFR at 1 and 5 years posttransplant.

Statistical analyses
Statistical analysis was performed with SPSS for Windows version 22.0 (IBM). Categorical variables are shown as frequencies (percentage) and numerical data as means ± SD (for normally distributed data) or medians and IQR (for nonnormally distributed data). Differences were analyzed using chi-square and Fisher exact tests. We used t tests for normally distributed data and Mann-Whitney U tests for nonnormally distributed data. Significance was determined as P < .05.

Results
Patient group with nephronophthisis
There were 17 patients (9.4%) with juvenile nephronoph-thisis as kidney failure etiology. The mean age of patients at transplant was 12.6 ± 4.3 years, and mean follow-up after transplant was 79.5 ± 41.9 months. Five patients (29.4%) received kidney transplants from deceased donors, and 12 patients (70.6%) received kidney transplants from living related donors. Preemptive kidney transplant was performed in 4 patients (23.5%). Thirteen patients (76.4%) received tacrolimus, 3 (17.6%) received cyclosporine, and 1 (5.8%) received sirolimus as induction posttransplantation immunosuppression. Acute rejection developed in 3 patients (17.6%), and graft loss developed in 1 patient (5.8%) in the follow-up period. The mean GFR after kidney transplant at 1 year was 96.7 ± 23.2 mL/min/1.73 m2; at 5 years, mean GFR was 84.7 ± 31.1 mL/min/1.73 m² (Table 1).

Comparison of patients with and without nephronophthisis as primary disease
The acute rejection rate was found to be statistically significantly higher in the group without nephronophthisis compared with those with nephronophthisis (34% vs 17.6%, respectively, P < .05) (Table 2). The groups with and without nephronophthisis were similar in terms of transplant age (12.6 ± 4.3 vs 13.8 ± 6.7 years, respectively; P > .05) and follow-up time (79.5 ± 41.9 vs 59.1 ± 38.8 months, respectively; P > .05). Donor type, immunosuppressive treatment, and GFR at 1 year (96.7 ± 23.2 vs 97.6 ± 28.4 mL/min/1.73 m2; P > .05) and 5 years (84.7 ± 31.1 vs 86.7 ± 21.7 mL/min/1.73 m2; P > .05) were also similar between groups (Table 2).

Discussion
In patients with juvenile nephronophthisis, the most common genetic cause of chronic kidney disease in childhood, kidney failure develops at a mean age of about 13 years. Kidney transplant is the best treatment of choice when kidney failure has established.^2,5-7 As reported previously, there are excellent posttransplant outcomes in patients with nephronophthisis, and disease recurrence has never been reported after kidney transplant.⁵ However, it is important to know clearly the posttransplant outcomes. Therefore, we investigated outcomes in kidney transplant recipients with a primary diagnosis of juvenile nephronophthisis who were followed in our center. We evaluated these patients by comparing them with other kidney transplant recipients with other primary diagnoses.

The rate of nephronophthisis was 9.4% among all kidney transplant recipients in our center; in another center in Turkey, this rate has been reported as 10.5%.¹ The use of living related donor kidney transplants is associated with better outcomes and graft survival than the use of deceased donors, especially when performed preemptively.⁸ Living related donor kidney transplant has been shown to be more common, at approximately 67% in patients with nephronophthisis.^1,5 Similarly, in our center, the rate of living related donor kidney transplant was 70.6% in patients with nephronophthisis, with preemptive kidney transplant performed in 4 patients.

An understanding of genetic diseases is important in living related donor kidney transplant patients when evaluating potential living donor candidates. Donor candidates who have been found to have a genetic kidney disease, especially one that can progress to kidney failure, should not donate. However, genetic diseases with an autosomal recessive mode of inheritance, such as nephronophthisis, are not usually contraindications for living kidney donation.⁹

Patients with nephronophthisis have excellent post-transplant outcomes with a previously reported 5-year GFR of 83.2 mL/min/1.73 m².¹ Similarly, the 5-year GFR among our kidney transplant recipients with nephronophthisis was 84.7 mL/min/1.73 m², with no difference versus patients with other primary diagnoses. According to the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), graft survival in patients with nephronophthisis was significantly better than survival shown in patients with other primary diagnoses.⁵ Although there was no difference in the 5-year GFR in patients with nephronophthisis versus patients with other primary diagnoses, we can say that kidney transplant recipients with juvenile nephronophthisis preserve graft function for longer periods according to the 5-year GFR finding of 84.7 mL/min/1.73 m². Moreover, disease recurrence did not develop in the follow-up period after transplant in our center, similar to that shown in previous reports. The posttransplant prognosis is good among kidney transplant recipients with juvenile nephronophthisis.^1,5

There was a statistically significant difference in term of acute rejection that we observed in 3 patients (17.6%) with nephronophthisis versus 34% in patients with other primary diagnoses. According to the NAPRTCS report, the acute rejection rate in kidney transplant recipients who have nephronophthisis was similar to that shown in patients with other primary diagnoses.⁵

We observed that kidney graft function was preserved for a long period. Thus, we suggest that posttransplant prognosis is good among kidney transplant recipients with juvenile nephronophthisis, the most common genetic cause of kidney failure in childhood.

References:

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