Nafamostat Mesilate Attenuates Ischemia-Reperfusion-Induced Renal Injury.

BACKGROUND: It has been reported that nafamostat mesilate (NM) inhibits inflammatory injury via inhibition of complement activation in ischemic heart, liver, and intestine. However, it is unclear if NM also inhibits apoptosis in ischemia-reperfusion (IR)-injured kidney. We therefore investigated whether NM attenuates IR renal injury that involves inhibition of apoptosis. METHODS: HK-2 cells and male C57BL/6 mice were used for this study. C57Bl/6 mice were divided into 4 groups: sham, NM (2 mg/kg) + sham, IR injury (IR injury; reperfusion 27 minutes after clamping of both the renal artery and vein), and NM + IR injury. Kidneys were harvested 24 hours after IR injury, and functional and molecular parameters were evaluated. For in vitro studies, HK-2 cells were incubated for 6 hours with mineral paraffin oil to induce hypoxic injury, and then treated with various doses of NM to evaluate the antiapoptotic effects. RESULTS: Blood urea nitrogen, serum creatinine levels, and renal tissue injury scores in NM + IR-injured mice were significantly lower than those of control IR mice (all P < .01). NM significantly improved cell survival in hypoxic HK-2 cells (P < .01), significantly decreased renal Bax expression (P < .05), and increased renal Bcl-2 protein levels in IR kidneys and hypoxic HK-2 cells compared with those of the sham and control groups. The numbers of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling- and 8-oxo-2'-deoxyguanosine-positive cells were significantly lower in NM + IR-injured kidneys compared with those in control IR-injured mice (P < .05); NM treatment decreased the expression of inducible and endothelial nitric oxide synthase in IR-injured mice (P < .05). CONCLUSIONS: NM ameliorates IR renal injury via inhibition of apoptosis by, at least in part, lowering nitric oxide overproduction, reducing Bax, and increasing Bcl-2.

Spinning: an arising cause of rhabdomyolysis in young females.

BACKGROUND: 'Spinning' is an indoor cycling regimen. The number of case reports of spinning-induced rhabdomyolysis (SIR) has increased since 2004 in South Korea. AIM: The aim of this study is to evaluate the clinical characteristics of SIR and compare it with other causes of rhabdomyolysis. METHODS: Patients who were diagnosed with rhabdomyolysis from 1 September 2011 to 30 April 2015 were included. We analysed the incidence of rhabdomyolysis, biochemical parameters and forced hospitalisation, which was defined as the days from admission to creatinine phosphokinase < 2000 IU/L. RESULTS: Among 70 included patients, 13 (18.6%) patients were diagnosed with SIR. The mean age of the patients with SIR was 25.69 ± 5.0 years, and most were females under 35 years old (12, 92.3%). Interestingly, the mean duration of spinning exercise before admission was only 59.23 min. Moreover, the patients with SIR showed more severe progress than the all-patients-except-SIR (AESIR) group. The serum creatinine phosphokinase, aspartate transaminase and alanine transaminase levels of the patients with SIR were statistically significantly higher than the patients with AESIR. Additionally, the duration of forced hospitalisation was longer than that of the AESIR (P < 0.01). CONCLUSIONS: Spinning could be an important cause of rhabdomyolysis in young, unfit females, which is typically severe. A graded exercise programme is advised at the first session.

Pretreatment with the tumor nerosis factor-alpha blocker etanercept attenuated ischemia-reperfusion renal injury.

INTRODUCTION: Tumor necrosis factor (TNF)-alpha mediates inflammation and apoptosis in ischemia-reperfusion (IR) injury of the kidneys. Etanercept, a soluble TNF-alpha receptor, has shown anti-inflammatory and anti-apoptotic effects in several animal models of renal injury, including chronic insufficiency and unilateral ureteral obstruction. We evaluated the protective effect of etanercept against experimental renal IR injury. METHODS: Male Sprague-Dawley (SD) rats were divided into 4 groups: saline-treated sham rats, etanercept-treated sham rats, saline-treated IR rats, and etanercept-treated IR rats. Renal messenger RNA (mRNA) levels of TNF-alpha and monocyte chemotactic protein-1 (MCP-1) were measured by real-time polymerase chain reaction (PCR) at 24 hours after IR injury. The protein levels of renal Bcl-2 associated X (Bax), B-cell lymphoma 2 (Bcl), extracellular signal-regulated kinase (ERK), and caspase-3 activation were evaluated using Western blot analysis. The degree of apoptosis of renal tubular cells was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. RESULTS: At 24 hours after IR injury, the serum levels of blood urea nitrogen (BUN) and creatinine were significantly lower among etanercept-treated than saline-treated IR rats. Renal mRNA levels of TNF-alpha and MCP-1 in saline-treated IR rats were significantly higher than the levels in saline-treated sham rats, and TNF-alpha and MCP-1 mRNA levels in etanercept-treated IR rats were significantly lower than those in saline-treated IR rats. Etanercept pretreatment of IR-injured rats significantly increased EKR phosphorylation and reduced the renal Bcl-2/Bax ratio, the renal caspase-3 activation, and the number of TUNEL-positive apoptotic cells. CONCLUSION: Etanercept improved resistance to renal injury during IR by enhancing the activation of ERK and increasing the Bcl-2/Bax ratio.

Acute poststreptococcal glomerulonephritis superimposed on IgA nephropathy.

Superimposition of poststreptococcal glomerulonephritis (PSGN) on the course of IgA nephropathy (IgAN) is uncommon. A case of PSGN during IgA nephropathy is presented. A 30-year-old man who had alternating gross and microscopic hematuria for 7 months underwent a renal biopsy. The first renal biopsy revealed IgAN with mesangial deposits of IgA and C3. Two months later, the patient suffered generalized edema, proteinuria, hematuria, an increased ASO titer and a decreased C3 level. A second renal biopsy revealed diffuse endocapillary proliferative glomerulonephritis with epimembranous hump-like electron-dense deposits of C3, but the original mesangial IgA deposits had disappeared. A diagnosis of acute PSGN was indicated. Two months after the onset of acute nephritic syndrome, the patient remained asymptomatic, except for microscopic hematuria and proteinuria. Some cases with persistent proteinuria or hematuria after PSGN are probably related to preexisting IgAN.

Spontaneous bladder rupture in a chronic hemodialysis patient.

Spontaneous bladder rupture is very rare. A 67-year-old woman who was nearly anuric and had been on chronic hemodialysis therapy for diabetic end-stage renal disease for 6 years complained of severe low abdominal pain and fever for 2 days. Abdominal computerized tomography and retrograde cystography revealed the extraperitoneal leakage of contrast medium, confirming bladder perforation. Partial cystectomy around the perforation site and repair of the bladder rupture were performed. Microscopic examination of the excised bladder tissue revealed that the bladder mucosa was ulcerated. Severe suppurative inflammation was observed throughout the bladder wall. Antibiotic treatment was continued for 3 weeks postoperatively, and repeated retrograde cystography showed no evidence of contrast extravasation. She was discharged, with no other complications.