#4440 prevalence of genes involved in hereditary kidney disease as a tool for the development of a gene panel

Abstract Background and Aims Genetic study is the fundamental tool for the diagnosis of Hereditary Kidney Diseases (HKD). The proliferation of its use has led to an increase in diagnostic complexity due to phenotypic overlap and genotypic heterogeneity. The aim of this study is to evaluate the prevalence of genes in our series of adult patients with suspected monogenic kidney disease in order to develop the basis for the elaboration of a gene panel that will make its usefulness in our routine clinical practice profitable. Method A retrospective descriptive observational study was performed with the collection of all genetic studies that were positive in the period between October 2014 and December 2020 in our center. With a description of the causative genes involved, as well as the clinical data of the proband patients who turned out to be carriers of these variants. Descriptive results of continuous variables are expressed as mean and standard deviation (SD) or median and interquartile range (IQR) according to their distribution. For categorical data, frequency and percentage are reported. Results The results of a total of 77 genetic studies on probands were collected, of whom 51% were women with a mean age at diagnosis of 46 years (SD ± 13.4) and 64.9% had a family history of kidney disease. Renal function measured by mean estimated glomerular filtration rate (eGFR) using the CKD-EPI (CKD Epidemiology Collaboration) was 90.1 ml/min/1,73 m2 (SD ± 29.64) with a mean proteinuria quantified in 24-hour urine of 627.9 mg (SD ±43.7) and 7.7% were on renal replacement therapy. (Table 1) 40.25% of probands were carriers of a mutation for Alport syndrome, in this group the most frequent gene was COL4A3 in 50% of cases. The second most frequent entity was autosomal dominant polycystic kidney disease (ADPKD) with 37% of the studies and among these the great majority were carriers of a variant in the PKD1 gene with 96.5%. The remaining diagnostic entities in order of frequency were Fabry disease, autosomal dominant tubulointerstitial nephropathy (ADTKD), congenital anomalies of the kidney and urinary tract (CAKUT), nephrotic syndrome, hereditary angiopathy with nephropathy, aneurysm and cramps syndrome (HANAC) and tuberous sclerosis (Figure 1). Conclusion Alport syndrome was the most frequently identified entity in patients with suspected monogenic renal disease in whom the genetic study was performed. Based on the results of our series, a proposal has been made for the genes to be included in a panel for hereditary renal diseases in our center. The development of these panels increases the efficiency and increases the cost-effectiveness of genetic studies in the diagnosis of these patients.