Toxic Nephropathies of the Tubulointerstitium: Core Curriculum 2024

Toxic nephropathies are a clinically common group of disorders characterized by toxin-induced renal injury that can affect the glomerulus, vasculature, or tubulointerstitium. Various endogenous (eg, myoglobin, hemoglobin, monoclonal light chains, and lysozymes) and exogenous toxins (eg, therapeutic drugs, herbal medications, heavy metals, radiocontrast, intoxicants, and environmental exposures) have been implicated. The kidney's primary role of metabolism and excretion of substances via glomerular filtration and tubular secretion increases its susceptibility to their adverse effects. The structure, dose, metabolic handling, and excretory pathway of the drug/toxin through the kidney determines its nephrotoxic risk. Patient characteristics that impact risk include genetic determinants of drug metabolism, transport and excretion, immune response genes, and comorbid conditions. Clinical manifestations depend on site and severity of renal injury. Toxin-induced tubulointerstitial injury often presents as a decline in renal function and/or solute transport defects and renal solute wasting. Injury is often reversible with limited toxin exposure; however, irreversible renal injury can occur with prolonged exposure. In this Core Curriculum, we will focus on discussing mechanisms of common toxin-induced tubulointerstitial renal injury and review their causes, clinical presentations, diagnosis, and management.