Chronic Kidney Disease of Unknown Origin, a Tubulointerstitial Disease.

Chronic kidney disease of undetermined cause is characterized by distinctive histopathological features predominantly affecting the tubulointerstitial compartment of the kidney. Kidney biopsies from affected individuals consistently demonstrate interstitial fibrosis and tubular atrophy as the hallmark findings, observed in over 80-90% of cases, with severity correlating closely with decreased glomerular filtration rate. Interstitial inflammation is generally mild or absent in early disease stages but may increase in advanced fibrosis, with T lymphocytes and macrophages predominating. Tubulitis and acute tubular injury are rare and usually restricted to patients presenting acutely. Electron microscopy reveals ultrastructural tubular changes such as cell detachment, basement membrane thickening, and collagen fibril deposition, though these are nonspecific. Glomerular abnormalities are typically secondary, including glomerulosclerosis in less than 50% of glomeruli, glomerulomegaly, and periglomerular fibrosis, reflecting compensatory hypertrophy or reduced nephron number. Immune complex deposition is minimal or absent. Vascular changes are generally not prominent. Despite the diagnostic value of kidney biopsy in chronic kidney disease of undetermined cause, clinical use is limited by socioeconomic factors, procedural risks, and lack of targeted therapies. Standardized biopsy protocols and reporting are essential for improving diagnosis, prognosis, and understanding disease mechanisms to guide future research and treatment strategies.