Development of Focal Segmental Glomerulosclerosis after Anabolic Steroid Abuse

Abstract

Anabolic steroid abuse adversely affects the endocrine system, blood lipids, and the liver, but renal injury has not been described. We identified an association of focal segmental glomerulosclerosis (FSGS) and proteinuria in a cohort of 10 bodybuilders (six white and four Hispanic; mean body mass index 34.7) after long-term abuse of anabolic steroids. The clinical presentation included proteinuria (mean 10.1 g/d; range 1.3 to 26.3 g/d) and renal insufficiency (mean serum creatinine 3.0 mg/dl; range 1.3 to 7.8 mg/dl); three (30%) patients presented with nephrotic syndrome. Renal biopsy revealed FSGS in nine patients, four of whom also had glomerulomegaly, and glomerulomegaly alone in one patient. Three biopsies revealed collapsing lesions of FSGS, four had perihilar lesions, and seven showed Ն40% tubular atrophy and interstitial fibrosis. Among eight patients with mean follow-up of 2.2 yr, one progressed to ESRD, the other seven received renin-angiotensin system blockade, and one also received corticosteroids. All seven patients discontinued anabolic steroids, leading to weight loss, stabilization or improvement in serum creatinine, and a reduction in proteinuria. One patient resumed anabolic steroid abuse and suffered relapse of proteinuria and renal insufficiency. We hypothesize that secondary FSGS results from a combination of postadaptive glomerular changes driven by increased lean body mass and potential direct nephrotoxic effects of anabolic steroids. Because of the expected rise in serum creatinine as a result of increased muscle mass in bodybuilders, this complication is likely underrecognized. INDEX CASEThe index case (patient 1) is a 30-yr-old white male professional bodybuilder who had no significant medical history and presented to a local hospital with lower extremity edema. The patient was on no prescription medications, but as part of his bodybuilding regimen, he regularly consumed a highprotein diet (Ͼ550 g/d) and dietary supplements including 10 g/d creatine monohydrate, 1000 mg/d branched-chain amino acids, 10 g/d glutamine, and multivitamins. For more than a decade, he regularly used anabolic androgenic steroids (AASs), including injectable testosterone, methyl-1-testosterone (taken orally), growth hormone, and insulin to augment his bodybuilding. At the time of biopsy, his steroid regimen consisted of growth hormone 4 IU 5 d/wk and testosterone 500 mg intramuscularly twice weekly. In addition, he took 75 mg of ephedrine and 600 mg of caffeine before each workout session.Physical examination revealed a height of 71 inches (180 cm), a weight of 295 pounds (134 kg extremely muscular, highly toned physique (Figure 1). BP was 145/80 mmHg, and there was 2ϩ bilateral lower extremity edema. The patient was found to have a serum creatinine of 2.7 mg/dl, blood urea nitrogen of 24 mg/dl, serum albumin of 1.9 g/dl, total serum protein of 5.7 g/dl, serum cholesterol of 212 mg/dl, hematocrit of 45%, and white blood cell count of 10.3 ϫ 10 9 /L with a normal differential and platelet count of 254 ϫ...

Nephrotoxic Effects of Common and Emerging Drugs of Abuse

“…Four of the 10 patients had perihilar lesions of FSGS, a finding classically seen in hyperfiltration-induced forms of FSGS, but three patients showed collapsing lesions, which are uncommon in the setting of postadaptive forms of FSGS. Electron microscopy showed a mean of 69% podocyte foot process effacement, and five of eight patients had .50% effacement, which is also uncommon in postadaptive FSGS (8,15,16). Figure 1 provides examples of the nephropathologic findings seen in the setting of AAS abuse.…”

“…Almost universally, AAS users ingest numerous "nutraceuticals" and dietary supplements, none of which are regulated by the US Food and Drug Administration. Bodybuilders report high protein consumption, sometimes in excess of 500 g/d, and the renal effects of this high metabolic burden are unknown (8). Nonandrogenic anabolic hormones, such as human growth hormone (9) and insulin (10), are used with moderate frequency by AAS users to further augment muscle gain.…”

“…Renal effects of AAS abuse in humans are primarily described in case reports (12)(13)(14) and a single small series (8). The series featured 10 long-term AAS abusers who presented with variable elevations in serum creatinine (mean, 3.0 mg/dl) and substantial proteinuria (mean, 10.1 g/d; range, 1.3-26.3 g/d).…”

“…Additional treatment aimed at reducing hyperfiltration injury, such as renin-angiotensin system blockade along with lifestyle modification (including a reduction of strenuous exercise and weight loss), has been reported to help reduce proteinuria and stabilize renal function (8). No evidence supports the use of immunosuppressive therapies, including corticosteroids.…”

Treatment with IFN-α, -β, or -γ Is Associated with Collapsing Focal Segmental Glomerulosclerosis

“…Collapsing FSGS also may follow treatment with pamidronate (23), with 15 cases reported in the medical literature (23,24). In contrast, FSGS NOS has been reported to result from treatment with lithium (25), sirolimus (26), and more recently anabolic steroids (27). Although rare cases of collapsing FSGS also have been reported after treatment with IFN-␣ (28 -30), this therapeutic agent is more commonly associated with minimalchange disease (MCD) (31)(32)(33)(34)(35)(36)(37)(38) and FSGS NOS (39 -47).…”