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Genetic testing in patients with suspected hereditary kidney disease may not reveal the genetic cause for the disorder as potentially pathogenic variants can reside in genes that are not yet known to be involved in kidney disease. To help identify these genes, we have developed KidneyNetwork, that utilizes tissue-specific expression to predict kidney-specific gene functions.KidneyNetwork is a novel method that we used to enrich a kidney RNA-sequencing co-expression network of 878 samples with a multi-tissue network of 31,499 samples. It then uses expression patterns to predict which genes have a kidney-related function and which (disease) phenotypes might result from variants in these genes, based on established gene-phenotype associations. We applied KidneyNetwork to prioritize rare variants in exome sequencing data from 13 kidney disease patients without a genetic diagnosis.KidneyNetwork can accurately predict kidney-specific gene functions and (kidney disease) phenotypes for disease-associated genes. Applying it to exome sequencing data of kidney disease patients allowed us to highlight a convincing candidate gene for kidney and liver cysts: ALG6.We present KidneyNetwork, a kidney-specific co-expression network that accurately predicts which genes have kidney-specific functions and can result in kidney disease. We show the added value of KidneyNetwork by applying it to kidney disease patients without a molecular diagnosis and consequently, we propose ALG6 as candidate gene in one of these patients. We designed an easy-to-use online interface that allows clinicians and researchers to use gene expression and co-regulation data and gene-phenotype connections to accelerate advances in hereditary kidney disease diagnosis and research.

A 57-year-old female patient with a history of tophaceous gout based on chronic renal insufficiency caused by systemic lupus erythematosus nephritis developed bursitis of the right lateral malleolus. This was taken for gout and was treated with colchicine and an increased dose of her maintenance therapy of oral glucocorticoids. Since this had no effect, a local diagnostic puncture was performed. Aspiration yielded pus from which Staphylococcus aureus was cultured; upon polarisation microscopy many uric acid crystals were seen. The diagnosis was gout and coincident bacterial infection. Therapy consisted of incision of the bursa and antibiotic therapy. Local recovery was uneventful. In patients suspected of an acute gout attack who have an increased risk of bacterial infection, e.g. elderly and patients with severe comorbidity or immunodeficiency, a local diagnostic aspiration is the only adequate investigation. Only if (coincident) bacterial infection has been ruled out, patients with contraindications for non-steroidal anti-inflammatory drug therapy and colchicine may safely be treated for a gout attack with oral glucocorticoids.