[Collapsing Glomerulopathy Secondary to Anabolic Steroids for Bodybuilding: A Case Series].

The abuse of anabolic androgenic steroids (AAS) for competitive (and non-competitive) purposes for bodybuilding practice is increasingly common. The consequences of these substances on the various organs are only partially known. Cases of FSGS following the use of AAS have been reported in the literature, even with evolution to ESKD. We describe three cases of bodybuilding athletes who presented alterations in renal function indices after taking AAS for a long time. Three renal biopsies were performed with histological diagnosis of FSGS collapsing variant. We examine the lesions observed on histological examination. Two athletes had rapid progression of renal disease requiring replacement therapy. The third one continues conservative treatment for chronic renal failure. We discuss the risks related to the intake of doping substances and how bodybuilders are exposed to different causes of kidney damage: anabolic steroids, supplements, and a high-protein diet.

Glomerular Microangiopathy with Cellular Crescent-like Formation and Endotheliopathy Due to Ramucirumab Treatment for Metastatic Sigmoid Colon Cancer.

We encountered a 77-year-old Japanese man who presented with nephrotic-range proteinuria 20 days after receiving ramucirumab treatment for metastatic sigmoid colon cancer. A kidney biopsy showed two characteristic histological findings. The first finding was podocyte injury with cellular crescent-like formation, although focal segmental glomerulosclerosis (FSGS) (collapsing variant) according to the Columbia classification may have been a more appropriate name for this injury, as hypertrophy and hyperplasia of epithelial cells, presumably resulting from podocyte injury, were seen between Bowman's capsule and the glomerular basement membrane (GBM); these changes appeared to be due to the collapse of the GBM rather than to GBM destruction with fibrinoid necrosis. The second finding was endotheliopathy characterized by prominent mesangial interposition via enlargement of the mesangial matrix with mesangiolysis. Proteinuria and renal dysfunction subsided after discontinuation of ramucirumab. Bevacizumab has been reported to induce glomerular microangiopathy with endothelial damage and swelling six months after treatment, but in this case, ramucirumab may have induced focal segmental glomerulosclerosis (FSGS) collapsing variant and glomerular microangiopathy with endotheliopathy via mesangial damage within 1 month. We believe that the damage to the glomerular podocyte and endothelial cells via mesangial damage secondary to ramucirumab in our patient was a different type of glomerular microangiopathy than the endothelial cell damage with enlargement of the subendothelial space caused by bevacizumab.

Renal comorbidities in collapsing variant focal segmental glomerulosclerosis: more than a coincidence?

BACKGROUND: Collapsing focal segmental glomerulosclerosis (FSGS) has various underlying etiologies and often leads to renal failure. The impact of biopsy-proven renal comorbidities in promoting collapsing glomerulopathy (CG) has not been systematically evaluated in large comparative studies. Those data are reported here. METHODS: Biopsies with the initial diagnosis of CG in native (n = 321) or transplant kidneys (n = 30) were identified in the University of North Carolina nephropathology database (1 January 2011 to 1 January 2016). Two cohorts were defined: 'sole' CG without and 'accompanied' CG with significant morphologic renal comorbidities. Tip-variant FSGS (T-FSGS) and time-matched biopsies served as control cohorts for comparative analyses. RESULTS: CG was significantly more common in native (4.4%) and transplant biopsies (4.1%) compared with T-FSGS (0.7 and <0.1%, respectively, difference versus CG P < 0.01). 'Associated' disease was significantly more common in CG (native: 151/321; 47.0%, transplant: 21/30; 70%, P < 0.05) versus T-FSGS (native: 14/51; 27.5%, transplant: exceptional; all differences versus CG P < 0.05). In native biopsies with 'accompanied' CG but not in control groups, stenosing vasculopathies including thrombotic microangiopathies were significantly more prevalent (P < 0.01). In transplants, the high incidence of 'accompanied' CG was linked to de novo diseases, mainly rejection and vascular injury. In native kidneys, membranous glomerulopathies were prevalent in 'accompanied' T-FSGS (36%) and CG (14%) (difference versus time-matched controls P < 0.01 and P < 0.05, respectively); they were uncommon in transplants. CONCLUSIONS: CG but not T-FSGS shows a high rate of comorbidities, with prominent vasculopathies presumably driving 'ischemic' CG-specific glomerular injury and also the disease course. These findings facilitate future studies into therapy, prognosis and reversibility of 'accompanied' CG.

Focal segmental glomerulosclerosis and concurrent glomerular microangiopathy after long-term imatinib administration.

A 79-year-old Japanese man was admitted to our hospital because of proteinuria and kidney dysfunction. He was diagnosed with chronic myeloid leukemia 13 years before and was treated with imatinib. Deep molecular response was achieved but he developed 1+ proteinuria in the first year, which gradually worsened thereafter. Imatinib was discontinued 12 years later but proteinuria and kidney dysfunction were progressive. Percutaneous kidney biopsy revealed mild mesangial hyper-cellularity and matrix increase, swelling of endothelial cells, and partial double contours of glomerular tufts. Subendothelial edema in the interlobular artery was also noted. Immunofluorescence was not remarkable. Electron microscopy revealed endothelial injury with severe sub-endothelial edema. Since imatinib had already been discontinued, conservative therapy with maximal dose of azilsartan was administered. A second biopsy was performed 1 year later because of further deterioration of kidney function, which revealed markedly increased global glomerulosclerosis and severe interstitial fibrosis and tubular atrophy. Segmental glomerulosclerosis with podocyte hyperplasia was also observed. Electron microscopy revealed glomerulosclerotic changes and partially attenuated endothelial injury. Two and a half years later, proteinuria reduced, progression of kidney dysfunction slowed, and he was independent on dialysis therapy. Molecular response of chronic myeloid leukemia was also maintained. The clinical course suggested that endothelial and podocyte injuries were induced by imatinib, and that the nephrotoxic effects lasted for a few years after discontinuation.

[FSGS collapsing variant during anabolic steroid abuse: Case Report].

Anabolic Androgenic Steroids (AAS) is an hormone family whose use has considerably increased among body-builders during the last decades. The AAS abuse, especially associated with other drugs or nutritional supplements and protein loads, may cause a variety of pathologies to several organs with a mechanism related to dosage, timing and substance. The kidney is the main metabolizer of these drugs and it can be acutely or chronically damaged with ESKD. The literature reports some cases of Focal Segmental Glomerulosclerosis (FSGS) in body-builders who abused of AAS. However, the link is not well understood and limited to some case-studies. In this paper, we report the case of a young body-builder who developed a FSGS collapsing variant with ESKD after prolonged abuse of AAS and a strongly hyperproteic diet and other dietary supplements. The patient underwent a genetic test because of the rapid and irreversibile onset of ESKD. The test showed a gene mutation of ACTN4, predisposing and causal of some genetic forms of FSGS. It was a very complex case, caused by several factors. The mutant protein of ACTN4 gene makes most vulnerable the cytoskeleton of the podocytes to external disturbances. That would explain why in those patients where the mutation has occurred, only those patients subject to "unfavorable environmental conditions", like the abuse of AAS, can develop a disease.