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The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis Jingyuan Xie et al. # Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1

The Oxford Classification of IgA nephropathy (IgAN) includes the following four histologic components: mesangial (M) and endocapillary (E) hypercellularity, segmental sclerosis (S) and interstitial fibrosis/tubular atrophy (T). These combine to form the MEST score and are independently associated with renal outcome. Current prediction and risk stratification in IgAN requires clinical data over 2 years of follow-up. Using modern prediction tools, we examined whether combining MEST with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than current best methods that use 2 years of follow-up data. We used a cohort of 901 adults with IgAN from the Oxford derivation and North American validation studies and the VALIGA study followed for a median of 5.6 years to analyze the primary outcome (50% decrease in eGFR or ESRD) using Cox regression models. Covariates of clinical data at biopsy (eGFR, proteinuria, MAP) with or without MEST, and then 2-year clinical data alone (2-year average of proteinuria/MAP, eGFR at biopsy) were considered. There was significant improvement in prediction by adding MEST to clinical data at biopsy. The combination predicted the outcome as well as the 2-year clinical data alone, with comparable calibration curves. This effect did not change in subgroups treated or not with RAS blockade or immunosuppression. Thus, combining the MEST score with cross-sectional clinical data at biopsy provides earlier risk prediction in IgAN than our current best methods.

Abstract. This study analyzes the effects of fluid resuscitation in the crush victims of the Bingol earthquake, which occurred in May 2003 in southeastern Turkey. Questionnaires asking about demographic, clinical, laboratory, and therapeutic features of 16 crush victims were filled in retrospectively. Mean duration under the rubble was 10.3 Ϯ 7 h, and all patients had severe rhabdomyolysis. Fourteen patients were receiving isotonic saline at admission, which was followed by mannitolalkaline fluid resuscitation. All but two patients were polyuric. Admission serum creatinine level was lower than and higher than 1.5 mg/dl in 11 and 5 patients, respectively. Marked elevations were noted in muscle enzymes in all patients. During the clinical course, hypokalemia was observed in nine patients, all of whom needed energetic potassium chloride replacement. Four (25%) of 16 victims required hemodialysis. Duration between rescue and initiation of fluids was significantly longer in the dialyzed victims as compared with nondialyzed ones (9.3 Ϯ 1.7 versus 3.7 Ϯ 3.3 h, P Ͻ 0.03). Sixteen fasciotomies were performed in 11 patients (68%), nine of which were complicated by wound infections. All patients survived and were discharged from the hospital with good renal function. Early and vigorous fluid resuscitation followed by mannitol-alkaline diuresis prevents acute renal failure in crush victims, resulting in a more favorable outcome.

Background and objectives: Low serum testosterone levels in hemodialysis (HD) patients have recently been associated with cardiovascular risk factors and increased mortality. To confirm this observation, we investigated the predictive role of serum total testosterone levels on mortality in a large group of male HD patients from Turkey.Design, settings, participants, & measurements: A total of 420 prevalent male HD patients were sampled in March 2005 and followed up for all-cause mortality. Serum total testosterone levels were measured by ELISA at baseline and studied in relation to mortality and cardiovascular risk profile.Results: Mean testosterone level was 8.69 ؎ 4.10 (0.17 to 27.40) nmol/L. A large proportion of patients (66%) had testosterone deficiency (<10 nmol/L). In univariate analysis, serum testosterone levels were positively correlated with creatinine and inversely correlated with age, body mass index, and lipid parameters. During an average follow-up of 32 months, 104 (24.8%) patients died. The overall survival rate was significantly lower in patients within the low testosterone tertile (<6.8 nmol/L) compared with those within the high tertile (>10.1 nmol/L; 64 versus 81%; P ‫؍‬ 0.004). A 1-nmol/L increase in serum testosterone level was associated with a 7% decrease in overall mortality (hazard ratio 0.93; 95% confidence interval 0.89 to 0.98; P ‫؍‬ 0.01); however, this association was dependent on age and other risk factors in adjusted Cox regression analyses.Conclusions: Testosterone deficiency is common in male HD patients. Although testosterone levels, per se, predicted mortality in this population, this association was largely dependent on age.

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