Glomerular Pathology in Dent Disease and Its Association with Kidney Function

Area of Science:

• Nephrology
• Genetics
• Pathology

Background:

• Dent disease is a rare X-linked disorder typically presenting as a renal tubular disease with low molecular weight proteinuria.
• Recent observations suggest glomerulosclerosis may also occur in Dent disease patients.
• This study aimed to characterize renal histopathology in Dent disease and its correlation with kidney function.

Purpose of the Study:

• To investigate the histopathologic features of Dent disease in renal biopsies.
• To assess the association between these features and kidney function, including estimated glomerular filtration rate (eGFR).
• To determine if glomerular pathology contributes to disease progression.

Main Methods:

• Analysis of renal biopsy reports and slides from 30 male patients diagnosed with Dent disease, collected between 1995 and 2014.
• Histopathological findings were systematically evaluated, including glomerulosclerosis, foot process effacement, interstitial fibrosis, and inflammation.
• Correlation of histopathologic findings with clinical data such as eGFR and 24-hour urine protein levels.

Main Results:

• Focal global glomerulosclerosis was observed in 83% of patients, with an average glomerular involvement of 16%.
• Mild segmental foot process effacement was present in 57% of evaluated biopsies.
• Higher degrees of glomerulosclerosis, foot process effacement, and interstitial inflammation were linked to lower eGFR and faster decline in kidney function.

Conclusions:

• Glomerular pathology, particularly podocyte involvement, may play a significant role in the progression of Dent disease.
• Dent disease should be considered in males presenting with unexplained proteinuria and characteristic findings of focal global glomerulosclerosis and segmental foot process effacement on renal biopsy.