The Pathology of Tubulointerstitial Kidney Disease: A Clinicopathologic Approach to Narrowing the Differential Diagnosis

Tubulointerstitial kidney disease can be recognized histologically as tubulointerstitial injury that is out of proportion to glomerular or vascular pathology. While recognizable as a histologic entity, determining a more precise underlying etiology for tubulointerstitial disease can be a diagnostic challenge. This review presents a clinicopathologic approach intended to help nephrologists and pathologists narrow the clinical differential diagnosis of tubulointerstitial disease. Inflammatory tubulointerstitial disease can often be subcategorized based on the presence of specific types of inflammatory infiltrates, such as eosinophils, neutrophils or granulomas. Recognition of these inflammatory phenotypes raises and lowers some entities in the differential diagnosis. Broadly speaking, underlying causes of inflammatory tubulointerstitial disease include drug reaction, infection, and autoimmune diseases. The most common causes of acute noninflammatory tubulointerstitial disease are ischemic and toxic tubular injuries. Much of the time there is substantial overlap in the morphology of ischemic and toxic tubular injury, but there are distinctive findings in noninflammatory tubulointerstitial disease, including casts and crystals, that may allow for a more specific histologic diagnosis that maps to a narrower clinical differential diagnosis. Ultimately, understanding the root cause of tubulointerstitial disease requires careful integration of clinical history with histopathologic findings.