Abstract Background and Aims Inherited kidney disease (IKD) is one of the leading causes of end-stage of kidney disease. Genetic diagnosis plays an important role in the counseling and management of kidney transplant patients or those on the waiting list, as it makes it possible to identify the cause of CKD, help in the selection of living donors, carry out genetic counseling and find out the prognosis around the graft survival and the risk of recurrence of the primary disease. The objective of the following study is to analyze the prevalence of IKD in our kidney transplant population and those on the waiting list, the phenotypic characteristics, genetic findings, and the diagnostic reclassification performed after the genetic study. Method This retrospective study has incluyed all genetic test (by next-generation sequencing (NGS) until 529 genes associated with kidney disease) performance between January 2018 and January 2023 in kidney transplant patients or on the waiting list for kidney transplant at Doctor Peset Hospital, using a multidisciplinary team approach. The patients were considered for genomic evaluation if they met one of the inclusion criteria: CKD of unknown etiology, family history of CKD, glomerular disease or chronic tubulo–interstitial disease with no recognized cause, suspicion of aHUS, CKD and other extrarenal syndromic signs or with renal malformations or nephrocalcinosis. Demographic data, family burden and screening, CKD phenotype, urinary anormalities, hypertension, diabetes, results of genetic test, were analyzed. Results We performed genetic testing in 76 patients (43,4% women; 88% Caucasian). Median age at time of kidney failure was 37 years (range: 17–77), 62% of patients had a positive family history of CKD and 29% presented extrarenal manifestations. The majority were male patients (56.6%) and Caucasian patients (88.2%). Most patients presented with an original clinical diagnosis glomerular disease 52,6% (FSGS lesion on biopsy (8/27) and non-diagnostic histology (10/27)), followed by ciliopathy (13%), aHUS (10.5%), and chronic kidney disease of unknown cause (6.6%), tubulointerstitial nephritis (6.6%), and with congenital anomalies (6.6%). In 46 patients had a genetic diagnosis defined as finding a pathogenic or likely pathogenic gene variant that explained the patient's kidney disease. With majority being COL4 variants (26.3%), followed by autosomal dominant polycystic kidney disease (ADPKD) (10.5%), podocytopathy and autosomal dominant tubulointerstitial kidney diseases. There were confirmed within a clinical diagnostic in 28% (above all ADPKD) and resulted in reclassification of the clinical diagnosis in 33% (above all COL4-related nephropathy) and there are more frequently a negative result if clinical diagnosis was unknown etiology, congenital anomalies o aHUS until 60%. With this data, 78% of the patients could have avoided a biopsy and 50% a immunossuppresive treatment with the diagnosis by genetic test. A genetic cause was identified by family screening in 16 families comprising 19 patients. A genetic diagnosis were more likely to have a family history of kidney disease (47,4% versus 14,5%, P < 0.001). There was otherwise no statistically significant difference in any other clinical characteristic (age at onset of kidney disease, age at kidney failure, race, hypertension, diabetes, hematuria, renal cyst or stone). Conclusion Our study demonstrates the clinical utility of genetic study in kidney transplants with unknown etiology or glomerulonephritis or chronic tubule-interstitial disease with no recognized cause or with positive family history of kidney disease, getting a genetic diagnosis until 60%, with a reclassification of the clinical diagnosis in a one-third. A genetic diagnosis is necessary to evaluate to kidney transplant recipients, to identify the etiology of CKD, to perform a genetic counseling and to improve patient management and prognosis.
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Open Access
Sep 29, 2023
Carlotta Bertolina + 7
