SUN-205 Inherited Renal Disease at the Royal Melbourne Hospital – Prevalence, Impact and Benefit of a Specialist Renal Genetics Clinic

Abstract

Approximately 10% of the Australian population is affected by Chronic Kidney disease (CKD), with a large proportion caused by lifestyle factors including Type 2 Diabetes, Obesity and hypertension. Monogenic or inherited renal diseases are an under-recognised cause of CKD, causing between 10-25% of diagnoses. Polycystic Kidney Disease (PCKD) and Alport syndrome are the most frequently diagnosed. Assessment of the true prevalence and impact of monogenic renal disease has been limited by variability in both phenotype and disease penetration and reduced access to available genetic testing. More recently the proliferation of newly recognized genes has identified many more inherited diseases. We aimed to establish a renal genetics clinic to determine the prevalence and impact of monogenic renal diseases. This would offer genetic counseling and testing to proband individuals of high risk families. The advent of new genomic technologies including Whole Exome Sequencing (WES) and Whole Genome Sequencing has facilitated identification of other monogenic diseases and patterns of inheritance. WES is reported to identify the causative gene in 25-30% patients. Medical histories of all patients who had attended the Department of Nephrology at the Royal Melbourne Hospital Nephrology prior to November 2018 were reviewed. Those with possible monogenic conditions were invited to attend the Renal Genetics clinic for further investigation. Diagnostic data was available on 10500 living patients. 1012 patients were identified with possible monogenic disease including Autosomal dominant PCKD (437pt), Alport Syndrome (113pt), Fabry Disease (105pt), Primary FSGS (95pt), Autosomal Dominant Tubulo-interstitial Disease/Nephronophthisis (57pt), Tuberous Sclerosis (30pt), Tubulopathies (30pt), and Nephrogenic Diabetes Insipidus (13pt). To date, 82 patients have attended the Renal Genetics clinic of these 60 patients have affected family members. The remaining 22 had no affected relatives including 9 with atypical haemolytic uraemic syndrome and 5 with FSGS. 57 patients assessed have been offered WES with targeted analysis to potentially determine the gene(s) responsible for their inherited disease. WES analysis was available under the Melbourne Genomics Health Alliance funded by the Victorian Government and its 10 Alliance members. The other 25 patients included 6 with suspected PCKD who were excluded from WES but offered genetic counselling, 5 with possible complement defects were offered panel specific tests, 4 relatives for consequent cascade testing and 10 patients who were referred for single gene testing consistent with their phenotype. Approximately 9.6% of patients from our total cohort have a presumed inherited renal disease. Identifying these patients facilitates familial cascade testing, better resource planning, and possibly better treatment options including clinical trials for new therapies. A cost benefit analysis of genetic testing, against current standard diagnostic measures of each renal disease will follow.