Tubulointerstitial Kidney Disease Panel

Tubulointerstitial kidney disease (TKD) encompasses a group of disorders characterized by inflammation and damage to the renal tubules and surrounding interstitial tissue, leading to progressive kidney dysfunction. Renal biopsy may reveal interstitial fibrosis and/or tubular atrophy; however, these findings are often non-specific and a biopsy is not always necessary for diagnosis. Adult-onset TKDs are most commonly inherited in an autosomal dominant manner, whereas childhood-onset TKDs typically follow an autosomal recessive pattern.

Pathogenic variants in UMOD and MUC1, which cause Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD), account for the majority of adult-onset cases. Other genes associated with overlapping clinical features include HNF1B, DNAJB11, REN, and SEC61A1. These disorders are autosomal dominant, and a family history of chronic kidney disease affecting multiple generations is common. 

In contrast, childhood-onset TKDs are predominantly autosomal recessive. The most frequent form, nephronophthisis, in 80% of cases results from a recurrent 290 kb homozygous deletion at chromosome 2q13 that encompasses NPHP1 gene.

One mitochondrial gene is also included on this panel, MT-TF, which has been associated with tubulointerstitial kidney disease in multiple individuals in the literature.