Nephropathy in Illicit Drug Abusers: A Postmortem Analysis

Maike Buettner, MD; Stefan W. Toennes, PhD; Stefan Buettner, MD; Markus Bickel, MD; Regina Allwinn, MD; Helmut Geiger, MD; Hansjuergen Bratzke, MD; Kerstin Amann, MD; Oliver Jung, MD

Disclosures

Am J Kidney Dis. 2014;63(6):945-953. 

In This Article

Abstract and Introduction

Abstract

Background. Illicit drug abuse is an independent risk factor for chronic kidney disease, but the pathogenic consequences of long-term exposure to illicit drugs and contaminants under unsterile conditions remains unclear.

Study Design. Case series.

Setting & Participants. All deceased persons (n = 129) who underwent forensic autopsy because of suspected connection with illicit drug abuse between January 1, 2009, and April 30, 2011, in Frankfurt/Main, Germany.

Predictor. Clinical characteristics and patterns of drug abuse.

Outcomes. Histopathologic alterations of the kidney.

Measurements. Hematoxylin and eosin, periodic acid–Schiff, Sirius, and Congo Red stainings and immunoglobulin A immunohistochemistry of all cases; additional histochemical stainings or immunohistochemistry and electron microscopy in selected cases.

Results. Individuals were mostly white (99.2%), were male (82.2%), and had intravenous drug use (IVDU) (81.4%). Median age at death was 39 years and duration of drug abuse was 17 years. The majority (79.1%) took various drugs in parallel as assessed by toxicologic analysis. Despite a young age, the deceased had a high burden of comorbid conditions, especially cardiovascular disease, liver cirrhosis, and infections. Evaluation of the kidneys demonstrated a broad spectrum of pathologic alterations predominated by arteriosclerotic and ischemic damage, mild interstitial inflammation, calcification of renal parenchyma, and interstitial fibrosis and tubular atrophy, with hypertensive-ischemic nephropathy as the most common cause of nephropathy. Interstitial inflammation (OR, 16.59; 95% CI, 3.91–70.39) and renal calcification (OR, 2.43; 95% CI, 1.03–5.75) were associated with severe IVDU, whereas hypertensive and ischemic damage were associated with cocaine abuse (OR, 6.00; 95% CI, 1.27–28.44). Neither specific glomerular damage indicative for heroin- and hepatitis C virus–related disease nor signs of analgesic nephropathy were found.

Limitations. White population, lack of a comparable control group, incomplete clinical data, and absence of routine immunohistochemistry and electron microscopy.

Conclusions. Illicit drug abuse is associated with a broad but unspecific spectrum of pathologic alterations of the kidneys. Cocaine abuse has a deleterious role in this setting by promoting hypertensive and ischemic damage.

Introduction

Illicit drug abuse is associated with an extensive number of psychiatric and somatic diseases, including chronic kidney disease (CKD).[1–7] Since the 1970s, kidney disease has been linked to intravenous drug use (IVDU), mainly in the setting of heroin-associated nephropathy, characterized by nephrotic syndrome with rapid progression and focal segmental sclerosis on kidney biopsy.[1,8] Since the early 1990s, as human immunodeficiency virus (HIV)-associated nephropathy became more common, heroin-associated nephropathy almost disappeared.[9,10] However, serologic testing was not available for HIV and hepatitis C virus (HCV) until the mid-1980s and early 1990s, respectively, which made it impossible to separate the contributions of IVDU, HIV, and HCV to kidney disease. Subsequently, contemporary reports have related CKD in persons with IVDU more to common concomitant chronic HIV, hepatitis B virus (HBV), and HCV infection in this population.[6,9,11–14]

In addition, an association between cocaine abuse and chronic kidney failure has been demonstrated, although confirmation by kidney biopsy was not attained in most studies.[1–3,15]

Moreover, renal AA amyloidosis as a complication of chronic and/or recurrent inflammatory disease in persons with IVDU has been described consistently since the 1970s,[16,17] and recent studies have reported an increased prevalence of renal AA amyloidosis among individuals having IVDU.[5,18,19]

To date, few data are available about the burden of CKD in persons with IVDU and results have been contradictory because medical management of this population is challenging. Patients frequently do not appear for follow-up and ask for medical advice only when they are acutely sick. Kidney biopsy is performed infrequently and the diagnosis of underlying kidney disease often is established only clinically. Hence, insight obtained is derived from small case series and kidney biopsy studies with only a small number of individuals included.[5,12,13,17,20] The small sample size and patient selection may explain the discordant results presented by different studies. Moreover, larger autopsy studies that have been conducted mainly predated the surveillance of HCV and HIV.[1,16,20] Thus, it is unclear whether the drugs themselves or other aspects of drug abuse put users at risk for kidney disease.

We conducted a postmortem analysis in illicit drug abusers, unselected for pre-existing kidney disease, to examine the impact of illicit drug abuse on kidney integrity and evaluate the associations between clinical characteristics, as well as patterns of drug abuse, and renal pathologic alterations.

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