The autopsy study of Buettner et al provides very interesting data on kidney changes in illicit drug abusers who underwent forensic autopsy following drug-related death. This cross-sectional autopsy study provides relevant and somewhat surprising information on kidney changes in a relatively young European white population of chronic illicit drug users. Review of the literature can be misleading and confusing because most kidney biopsy studies describing changes in drug abusers represent a selected population who underwent kidney biopsy for indication of acute or chronic kidney injury. From this autopsy study, we learn that in spite of young age (median age of death was 39 years), significant kidney parenchymal injury is present in a substantial proportion of drug abusers. As expected, chronic cocaine use was associated with ischemic/hypertensive/obliterative vascular changes. A surprising finding was the very high percentage of renal parenchymal calcifications (58.1% of kidneys contained some degree of visible calcium deposition). The calcium deposits were primarily in the tubular basement membrane close to the renal papilla. Obviously, based on the autopsy findings and the limited clinical history, authors could not determine the cause of calcifications; they propose an imbalance in the electrolyte metabolism in drug abusers. Because they did not see capillary sclerosis/calcification in the renal medulla/papilla or in the pelvic soft tissue, and because obvious papillary necrosis was absent, they do not believe that the calcifications are related to analgesic nephropathy. However, the definition of analgesic nephropathy is different among pathologists and clinicians/radiologists, and the diagnosis relies mainly on clinical history and imaging studies instead of kidney biopsies. According to imaging studies, medullary calcifications associated with reduced kidney size and uneven renal contours have a high specificity for analgesic nephropathy (see De Broe & Elseviers). The diagnosis of analgesic nephropathy cannot be made on kidney biopsy because the findings are nonspecific. Calcifications in the renal medulla can occur for a variety of reasons, and it is likely that such calcifications are not sampled in kidney biopsies. An adequate kidney biopsy usually does not contain deep renal medulla, and pathologists are focusing on changes in the renal cortex. After the study of Buettner et al, pathologists should take a closer look at the deep renal medulla if present in the biopsy specimen. It is possible that, at least to some degree, combined illicit drug abuse and analgesic use is responsible for these widespread calcifications in the renal medulla. The frequent medullary calcifications in kidneys of illicit drug abuser is a significant and unexpected finding, and warrants further detailed studies to clarify the pathogenesis.
No specific pathologic lesions were associated with hepatitis C infection, or heroin or other IV drug abuse in this autopsy series. This is not unexpected considering that the study included 129 unselected consecutive autopsy cases. Literature on the association of hepatitis C virus infection and a membranoproliferative pattern of glomerulonephritis (or cryoglobulinemic glomerulonephritis) or the association of IV drug abuse with focal segmental glomerular sclerosis is based on a selected patient population with clinically evident renal/glomerular disease. It would be very interesting to see a similar autopsy study in African or African American patients to see if race is a predisposing factor to the different kidney lesions commonly associated with illicit drug abuse.
Tibor Nadasdy, MD
eAJKD Contributor and AJKD Kidney Biopsy Teaching Case Advisory Board member