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Diabetic nephropathy is characterized by excessive deposition of extracellular matrix protein and disruption of the glomerular filtration barrier. Matrix metalloproteinases (MMPs) affect the breakdown and turnover of extracellular matrix protein, suggesting that altered expression of MMPs may contribute to diabetic nephropathy. Here we used an MMP-9 gene knockout mouse model, with in vitro experiments and clinical samples, to determine the possible role of MMP-9 in diabetic nephropathy. After 6 months of streptozotocin-induced diabetes, mice developed markedly increased albuminuria, glomerular and kidney hypertrophy, and thickening of the glomerular basement membrane. Gelatin zymographic analysis and western blotting showed that there was enhanced MMP-9 protein production and activity in the glomeruli. However, MMP-9 knockout in diabetic mice significantly attenuated these nephropathy changes. In cultured podocytes, various cytokines related to diabetic nephropathy including TGF-β1, TNF-α, and VEGF stimulated MMP-9 secretion. Overexpression of endogenous MMP-9 induced podocyte dedifferentiation. MMP-9 also interrupted podocyte cell integrity, promoted podocyte monolayer permeability to albumin, and extracellular matrix protein synthesis. In diabetic patients, the upregulation of urinary MMP-9 concentrations occurred earlier than the onset of microalbuminuria. Thus, MMP-9 seems to play a role in the development of diabetic nephropathy.Kidney International advance online publication, 26 March 2014; doi:10.1038/ki.2014.67.

A 23-year-old Asian man presented to our clinic with pitting edema of the lower limbs for 3 days and a small ulcer on his glans penis. He previously had unprotected sexual intercourse with different male partners and had previously used ketamine and ecstasy (3,4-methylenedioxy-N-methamphetamine). The patient had noticed a diffuse skin rash on his trunk, limbs, palms, and soles since several months ago, and secondary syphilis (RPR: >144 RU, TPHA: 2310 TU) was diagnosed 2 weeks prior to admission. A dose of benzathine penicillin was given upon admission, and fever developed the same evening. One week later, human immunodeficiency virus (HIV) infection was confirmed with western Blot analysis (his CD4-positive lymphocyte count was 500/cumm, viral load was 1230 copies/ml). A urinalysis result was positive for protein (3+) by dipstick. Biochemical examinations revealed hypoalbuminemia and massive proteinuria (blood urea nitrogen level, 15 mg/dl; creatinine level, 0.81 mg/dl; albumin level, 1.2 g/dl; urine protein-to-creatinine ratio, 13.8 g/g; and HbA1c level, 5.8%). Laboratory tests were negative for anti-nuclear antibodies, hepatitis B surface antigen, and anti-hepatitis C virus. Both kidneys were found to be enlarged on sonography. The renal biopsy findings are depicted in Figure 1.

Previous studies have shown that nonsteroidal anti-inflammatory drug (NSAID) use might be associated with a lower risk of developing cancer in the general population. Patients on dialysis have increased risk for cancer, but there are no studies to determine the relationship between NSAID use and cancer risk in these patients. To identify any association between NSAID use and cancer risk in patients with end-stage renal disease on dialysis, we used Taiwan's National Health Insurance database to conduct a nationwide population-based, propensity score–matched cohort study. All cancers between groups were compared by Cox proportional hazards models. Compared to nonuse of NSAIDs, the use of non-COX-2-selective inhibitors (hazard ratio 0.81, 95% confidence interval 0.67–0.97) or COX-2-selective inhibitors (0.78, 0.62–0.98) was associated with a lower risk of developing cancer. NSAID use reduced the risk of respiratory (0.39, 0.19–0.79), breast (0.41, 0.19–0.89), kidney (0.58, 0.38–0.88), digestive tract (0.64, 0.49–0.85), and bladder cancers (0.73, 0.55–0.96). NSAID use, however, significantly increased risk for upper gastrointestinal bleeding (odds ratio, 1.15, 1.07–1.23) but not adverse cardiac or cerebrovascular events. Thus, NSAID use was associated with a lower risk of developing cancer in chronic dialysis patients; however, they should still be used with caution due to the side effects of gastrointestinal bleeding.

Ho-Han Wu, Szu-Yuan Li and Wu-Chang Yang Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, Taipei, Taiwan and Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

A 64-year-old man presented with progressive painless right lower leg swelling for 5 years. The patient had a history of surgical resection of similar lesions over his right forearm and abdominal wall 5 and 8 years ago, respectively. He had bilateral recurrent renal stones over the past 5 years. The physical examination was normal except for a painless stone-hard right lower leg swelling (Figure 1). He had no skin lesions or lymphadenopathy. His blood tests revealed a total white blood cell count of 4700/mm3 (78% neutrophils), hemoglobin 10.4 g/dL, blood urea nitrogen 57 mg/dL, creatinine 4.68 mg/dL, calcium 14.6 mg/dL (normal 8.4–10.6), and normal C-reactive protein and creatine kinase level. Serum electrophoresis was normal. He had a serum intact parathyroid hormone of 9.36 pg/dL (