The Renal Tubulointerstitium.

Abstract

2016 by the National Kidney Foundation, Inc. All rights reserved. 1548-5595/$36.00 http://dx.doi.org/10.1053/j.ackd.2016.11.015 T renal tubulointerstitium is an often underappreciated compartment of the kidney but of great importance in acute kidney disease and CKD. As early as the 1970s, Bohle and colleagues recognized that kidney function did not correlate well with the severity of glomerular disease but rather with the relative interstitial volume. We now know that the microenvironment encompassing the tubulointerstitium is composed of tubular epithelial cells, interstitial cells, peritubular capillary endothelium, pericytes, and extracellular matrix, which have complex structural and functional relationships. Profibrotic and inflammatory factors influencing this compartment are a major determinant of kidney disease progression. There is a crucial role of direct toxic, ischemic, and inflammatory injury to the renal tubules and interstitium in acute, progressive, and chronic kidney failure. Additionally, while glomerular damage, including glomerulosclerosis, associates with proteinuria and an active urinary sediment, the downstream effects on the tubulointerstitium are thought to result in the reduction of glomerular filtration rate. When acute changes to the tubulointerstitium are not reversible, fibrosis ensues with chronic kidney failure progressing toward ESRD. This issue of Advances in Chronic Kidney Disease is focused on acute and chronic tubulointerstitial kidney diseases as a reflection of the need to address maintaining kidney function in patients with any form of kidney injury. This is an increasingly important area in light of the apparent increasing incidence of acute interstitial nephritis particularly among the elderly, the prevalence of CKD which is estimated to affect 7%-10% of adults in the United States, and the relative rise in cases of more severe kidney impairment particularly in those aged 4564 years despite a leveling off in the incidence of CKD overall. The issue begins with an overview by Perazella of the clinical presentation and evaluation of the patient with tubulointerstitial disease. The use and limitations of laboratory studies, imaging, and kidney biopsy in the challenging diagnosis of interstitial nephritis are discussed. This is followed by articles on medications inducing interstitial nephritis. Medications have been used to treat illnesses for many millennia. Herbal and mineral medications were detailed in the Ebers Papyrus, a medical document discovered in Thebes dating from 1550 BC, which likely contains known information about previous medication usage copied from earlier texts. There has been an explosion of therapeutics since the late 19th century, with the discovery of medicines that can relieve pain, provide anesthesia, fight infections, and lessen or cure disease. The discovery of penicillin by Fleming in 1928, and the wide use of antibiotics during the latter part of World War II, ushered in an era of widespread drug use for everyday ailments and common diseases. However, medications are not without their complications. In 1899, Louis Lewin published Die Nebenwirkungen der Arzneimittel, a treatise on the unwanted effects of drug treatments. Subsequently, Leopold Meyler published a

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