Clinical phenotype of familial hypertensive nephropathy

Familial kidney disease is common in Cyprus. Patients with a glomerular phenotype are most likely to have an autosomal dominant variant in collagen type IV alpha 3 chain ( COL4A3 ) or collagen type IV alpha 4 chain ( COL4A4 ) genes but pathogenic variants are not found in the majority of families. We compare the clinical phenotype between two groups of 10 Turkish Cypriot families who lack a pathogenic variant of COL4A3 or COL4A4 but have either the COL4A4 variant p.G545A or p.G999E. Both groups had identical clinical phenotypes with microscopic haematuria detected at least once in 76% of affected family members; urine protein was less than 1 g/day until glomerular filtration rate (GFR) was <30 ml/min. End-stage kidney disease (ESKD) occurred in 24.1% of those over 50 at a median age of 62.8 (36-86) years. Although the genetic cause of renal injury in this large group is still unknown, these families present with a clinical phenotype best characterised as familial hypertensive nephropathy. We propose that this condition accounts for the great excess of renal failure in the Eastern Mediterranean in those over 65 years of age.