Study Cohort and Clinical Characteristics According to Premortem Medical Records
A total of 139 deceased persons were referred for forensic autopsy because death was suspected to be in the context of illicit drug abuse. Ten deceased were excluded; 6 had no history of drug abuse but died because of intoxication with analgesics or narcotics prescribed in the setting of advanced chronic illness, for example, malignancy, mostly with suicidal intention, and in 4, histologic evaluation of the kidney was not possible because the corpse was in an advanced stage of decomposition when it was found. Thus, 129 deceased individuals were included in this study.
A summary of characteristics of the study cohort according to premortal medical records is shown in Table 1 . All the deceased, except for 1 of African descent, were white (99.2%) and mostly men (82.2%). Median age at time of death was 39 (IQR, 32–46) years and documented duration of drug abuse was 17 (IQR, 10–24) years. The majority were known to have had IVDU (81.4%). Diagnosis of various types of chronic diseases had been established in <10% of individuals during their lifetimes, with the exception of chronic HCV infection (41.9%) and hypertension (24.0%). Seven individuals (5.4%) had been given a diagnosis of CKD, none biopsy proven because the deceased had not been preselected for kidney disease in this study.
In external examination, 64.3% had injection sites, which might be attributable to IVDU but also to medical treatment, whereas 29.5% had injection tracks as markers for severe and long-time IVDU ( Table 2 ). Deceased drug abusers were found to have a high burden of morbidities on autopsy, including cardiovascular disease (left ventricular hypertrophy, 62.0%, and coronary heart disease, 21.7%), liver cirrhosis (20.9%), and acute infections (30.2%). HCV antibody testing was positive in the majority of deceased (66.7%), whereas HBV surface antigen and HIV antibodies were detected in only individual cases.
Toxicologic Results of Drug Intake and Causes of Death
Toxicologic analysis of blood for determination of acute drug intake prior to death and hair for determination of drug abuse behavior in the weeks prior to death demonstrated a broad spectrum of substances abused ( Table 3 ). Among illicit drugs, opioid and cocaine intake were most frequent. Additionally, alcohol consumption was verified in the majority of cases (60.7%). Most patients had consumed different types of drugs in parallel because 2 or more different drugs were found in 102 cases (79.1%).
Drug intoxication was the predominant cause of death according to the final medico-legal report (78.3%), with opioids being the predominant drug in 70.5% (Table S1, available as online supplementary material). Other causes of death were attributable mainly to cardiovascular disease (5.5%), pneumonia (6.2%), and trauma (6.2%).
Pathologic Alterations of the Kidneys
A detailed histologic analysis of renal parenchyma collected during the autopsy was performed for all 129 deceased individuals. Frequencies of morphologic changes are summarized in Table 4 . The diagnosis of hypertensive-ischemic nephropathy was made in cases with morphologic changes indicative of hypertensive injury, including atherosclerosis (at least moderate), and when arterial hypertension was diagnosed during life time (12 cases), left ventricular hypertrophy was present (2 cases) or atheromatosis/atherosclerosis was documented (2 cases). Histologic changes were considered sufficient for the diagnosis of relevant hypertensive-ischemic damage when at least one of the following 3 characteristics was found: >10% obliterated glomeruli, >10% interstitial fibrosis and tubular atrophy, and severe arteriosclerosis. In conclusion, in 16 cases, presumptive hypertensive-ischemic nephropathy was diagnosed (Figure 1A), with signs of subacute thrombotic microangiopathy in one case. Mesangioproliferative IgA glomerulonephritis was seen in 6 cases, of which in 5, IgA immunohistochemistry (Figure 1B) was clearly positive; in the sixth case, IgA staining was very faintly positive and focal osmiophilic deposits were found in the mesangia by electron microscopy. In 2 HIV-positive persons, AA amyloidosis was diagnosed (Figure 1C and D). In one case, chronic interstitial inflammation suspected to be chronic interstitial nephritis was observed. In all other cases, the interstitial inflammation was too mild to justify the diagnosis of interstitial nephritis. In 12 patients, segmental sclerosis, segmental scarring, or a segmentally accentuated hypercellularity/matrix increase restricted to single glomeruli was observed. In one case reminiscent of genuine focal segmental glomerulosclerosis (FSGS), electron microscopy was performed, but despite autolysis, the findings did not justify the diagnosis of a primary podocytopathy. None of the kidneys showed membranoproliferative glomerulonephritis (MPGN). The case classified as subacute thrombotic microangiopathy was the only case with a picture reminiscent of MPGN with mesangial increase of matrix and thickened, questionably double-contoured basement membranes. However, C3c and IgG immunohistochemistry yielded negative results and electron microscopy showed no characteristics of MPGN, but rather of thrombotic microangiopathy.
(A) Periodic acid–Schiff stain (original magnification, ×100) of a kidney with hypertensive-ischemic damage with global glomerulosclerosis, signs of glomerular ischemia, tubular atrophy, and arteriosclerosis. (B) Immunoglobulin A (IgA) immunohistochemistry (original magnification, ×400) of a kidney with distinct granular IgA deposits in the mesangia. Deposits are clearly seen despite signs of autolysis. (C) Congo Red stain (original magnification, ×200) of a kidney with AA amyloidosis. The inlay shows birefringence in polarization microscopy in a corresponding area of the section. (D) Amyloid A immunohistochemistry (original magnification, ×200) of the amyloidosis depicted in C. In the inlay, fibrillary deposits with a periodicity typical of amyloid are seen in electron microscopy (original magnification, ×31,500). (E) Conspicuous calcification in the papilla of a renal specimen accentuated along the tubular basement membranes in von Kossa stain (original magnification, ×50). No prominent capillary sclerosis in the renal medulla or the suburothelial soft tissue is found. (F) Hematoxylin and eosin stain (original magnification, ×200) of papillary calcifications with prominent circular deposits at the tubular basement membranes. All pictures were taken on a Zeiss Axio Imager A1.
Conspicuous calcifications of the renal parenchyma were seen in numerous cases (58.1%). In 15 cases, calcium deposits along the tubular basement membranes were observed in renal papillae (Figure 1E and F). No capillary sclerosis of medulla/papillae or pelvic soft tissue and no papillary necroses were observed as signs of analgesic nephropathy.
Clinical Characteristics and Patterns of Drug Abuse With or Without Renal Pathologic Alterations
The deceased were grouped according to the presence or absence of different histologic pathologic states as indicated in Table 4 and compared for clinical characteristics and modalities of drug abuse, including severity of drug use according to toxicologic measurements.[22,23]
Patients with and without different parameters of kidney pathology were comparable for most clinical parameters (data not shown). Parameters associated significantly with different types of renal pathology in univariable analysis included age, duration of drug abuse, and IVDU, as well as positive testing for HCV antibodies and cocaine ( Table 5 ). When using stepwise multivariable logistic regression, the presence of injection tracks was associated positively with >10% obliterated glomeruli, >10% interstitial fibrosis and tubular atrophy, interstitial inflammation, and calcification of renal parenchyma, whereas a positive test result for cocaine was associated with signs of glomerular ischemia, arteriosclerosis greater than 2, and diagnosis of hypertensive-ischemic nephropathy only. In addition, interstitial inflammation was associated with longer duration of IVDU, and diagnosis of hypertensive-ischemic nephropathy was associated with longer duration of drug abuse (all P < 0.05).
Am J Kidney Dis. 2014;63(6):945-953. © 2014 The National Kidney Foundation
The National Kidney Foundation
Published by Elsevier