Search

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and fourth leading cause for renal replacement therapy worldwide. Disease progression is tightly linked to genotype, however, factors like genetic modifiers and environmental factors are responsible for a high phenotypic variability within- as well as between families. Individual’s risk of progression to kidney failure is assessed using prediction- or risk-assessment tools such as the predicting renal outcomes in ADPKD score (PROPKD score) and the Mayo Imaging Classification (MIC). The PROPKD score encompasses genetic and phenotypic parameters, while the MIC relies on renal imaging, height, and age of patients. Both methods categorize patients into low-risk, intermediate-risk, and high-risk for progression to kidney failure. In this retrospective, cross-sectional study, we calculated the risk of progression to kidney failure in our population and analyzed the agreement between the methods in three separate models with alternating stratification of MIC risk categories. We found a mismatch for risk assessment between the respective risk categories, indicating that the PROPKD score and MIC should not be used interchangeably. Preferably, the MIC should be used as a base for risk assessment and may be enhanced by genotypic and phenotypic information.

We describe the case of a 44-year-old male patient with a longstanding history of microhematuria and mildly impaired kidney function (CKD G2A1). The family history disclosed three females who also had microhematuria. Genetic testing by whole exome sequencing revealed two novel variants in COL4A4 (NM_000092.5: c.1181G>T, NP_000083.3: p.Gly394Val, heterozygous, likely pathogenic; Alport syndrome, OMIM# 141200, 203780) and GLA (NM_000169.3: c.460A>G, NP_000160.1: p.Ile154Val, hemizygous, variant of uncertain significance; Fabry disease, OMIM# 301500), respectively. Extensive phenotyping revealed no biochemical or clinical evidence for the presence of Fabry disease. Thus, the GLA c.460A>G, p.Ile154Val, is to be classified as a benign variant, whereas the COL4A4 c.1181G>T, p.Gly394Val confirms the diagnosis of autosomal dominant Alport syndrome in this patient.