Avilagates4560

Autosomal dominant tubulo-interstitial kidney disease due to

mutations (ADTKD-

) is a rare condition associated with high variability in the age of end-stage kidney disease (ESKD). The minor allele of rs4293393, located in the promoter of the

gene, is present in 19% of the population and downregulates uromodulin production by approximately 50% and might affect the age of ESKD. The goal of this study was to better understand the genetic and clinical characteristics of ADTKD-

and to perform a Mendelian randomization study to determine if the minor allele of rs4293393 was associated with better kidney survival.

An international group of collaborators collected clinical and genetic data on 722 affected individuals from 249 families with 125 mutations, including 28 new mutations. The median age of ESKD was 47 years. Men were at a much higher risk of progression to ESKD (hazard ratio 1.78,

< 0.001).

The allele frequency of the minor rs4293393 allele was only 11.6% versus the 19% expected (

< 0.01), resulting in Hardy-Weinberg disequilibrium and precluding a Mendelian randomization experiment. An

score reflecting the severity of the trafficking defect of uromodulin mutants was found to be a promising predictor of the age of ESKD.

We report the clinical characteristics associated with 125

mutations. Male gender and a new

score predict age of ESKD.

We report the clinical characteristics associated with 125 UMOD mutations. Male gender and a new in vitro score predict age of ESKD.

In the Mayo Imaging Classification (MIC) for autosomal dominant polycystic kidney disease(ADPKD), the height-adjusted total kidney volume (HtTKV) growth rate is estimated for classification. Estimated HtTKV slope, termed as eHTKV-α, is calculated by the equation [HtTKV at age t]= K(1+α/100)

, where K= 150 and A= 0 are used in MIC. If eHTKV-α is nearly stable during a standard-of-care period, the change in eHTKV-α from baseline can be used for estimation of the treatment effect on the HtTKV slope.

The constancy of eHTKV-α (A= 0 and K= 150) was evaluated using 453 placebo-assigned subjects in the Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 34 trial. A and K were sought out respectively by a converged pattern of regression lines of log10(HtTKV) plotted against age for subgroups divided according to MIC, and by change in eHTKV-α from baseline. A total of 239 standard-of-care patients from the Kyorin University Cohort (KUC) served as validation. Changes in eHTKV-α from baseline were evaluated in 809 tolvaptan-treated subjects in TEMPO 34.

In placebo-assigned subjects, eHTKV-α (A= 0 and K= 150) changed significantly from baseline at the third year. As regression lines of placebo-assigned subgroups converged around age 0, A was set as 0, which was confirmed by KUC. K= 130 was selected because of minimal change in eHTKV-α from baseline. The KUC validated the constancy of eHTKV-α (A= 0 and K= 130) but not that of eHTKV-α (A=0 and K=150). In tolvaptan-treated subjects, eHTKV-α remained significantly lower than baseline for 3years.

eHTKV-α (A= 0 and K= 130) was nearly stable from baseline through follow-up in standard-of-care adults. Treatment effects on the HtTKV slope can be estimated by changes in eHTKV-α from baseline.

eHTKV-α (A = 0 and K = 130) was nearly stable from baseline through follow-up in standard-of-care adults. Treatment effects on the HtTKV slope can be estimated by changes in eHTKV-α from baseline.

Antibody-mediated rejection (ABMR) impacts kidney allograft outcome. The diagnosis is made based on findings from invasive kidney transplant biopsy specimens. The aim of this study was to identify a noninvasive urinary protein biomarker for ABMR after kidney transplantation.

We performed a multicenter case-control study to identify a urinary biomarker for ABMR (training cohort,

= 249) and an independent, prospective multicenter cohort study for validation (

= 391). We used concomitant biopsies to classify the samples according to the Banff classification. After untargeted protein identification and quantification, we used a support vector machine to train the model in the training cohort. The primary endpoint was the diagnostic accuracy of the urinary biomarker for ABMR in the validation cohort.

We identified a set of 10 urinary proteins that accurately discriminated patients with (

= 60) and without (

= 189) ABMR in the training cohort with an area under the curve (AUC) of 0.98 (95% confidence interval [CI], 0.96-1.00). The diagnostic accuracy was maintained in the validation cohort (AUC, 0.88; 95% CI, 0.8-0.93) for discriminating the presence (

= 43) from the absence (

= 348) of ABMR. JTE 013 cost The negative predictive value of the 10-protein marker set for exclusion of ABMR was 0.99, and the positive predictive value was 0.33. The diagnostic accuracy was independent of the reason for performing the biopsy, time after transplantation, and better than the accuracy of gross proteinuria (AUC, 0.76).

We identified and validated a urinary protein biomarker set that can be used to exclude ABMR.

We identified and validated a urinary protein biomarker set that can be used to exclude ABMR.

Calciprotein particles (CPPs) are potentially modifiable mediators of phosphate toxicity in patients with kidney disease. We compared the effects of calcium carbonate (CC) and the non-calcium-based phosphate binder sevelamer on CPP levels in patients undergoing hemodialysis (HD). We hypothesized that treatment with sevelamer would achieve greater reductions in amorphous calcium phosphate-containing CPP (CPP-1) and hydroxyapatite-containing CPP (CPP-2) owing to reduced calcium loading and anti-inflammatory pleiotropic effects.

We conducted an open-label, randomized controlled trial (RCT) in which 31 stable prevalent HD patients were allocated to receive either sevelamer hydrochloride (SH), sevelamer carbonate (SC), or CC for 24 weeks. Dual primary endpoints were the between groups differences in serum CPP-1 and CPP-2 levels at 24 weeks in SH+ SC-treated versus CC-treated patients. Effects on aortic pulse wave velocity (aPWV), inflammatory cytokines (interleukin-6 and -8), and effects across individual treatment arms were also assessed.