Genetic Diseases Associated with Tubulointerstitial Nephritis

Genetic forms of tubulointerstitial kidney disease may be more prevalent than presently recognized. Early diagnosis can help prevent inappropriate use of immunosuppressive therapy, help focus on extrarenal manifestations, and facilitate earlier planning for kidney transplantation. Autosomal dominant tubulointerstitial kidney disease (ADTKD) and an autosomal recessive tubulointerstitial kidney disease known as nephronophthisis (NPHP) have both unique and overlapping features. Both typically have a bland urinary sediment, small-to-normal sized kidneys, and chronic inflammation and fibrosis with progressive chronic kidney disease. Family history can suggest the diagnosis but should not be required for consideration, particularly when extrarenal manifestations such as gout or others discussed below are also present. Genetics-based diagnosis has facilitated streamlined nomenclature. ADTKD has now replaced prior terms of medullary cystic disease, familial hyperuricemic nephropathy, and glomerulocytic kidney disease. Below we discuss clinical description, epidemiology, pathogenesis, diagnosis, therapies, and need for ongoing research in ADTKD and NPHP.