Copeptin is associated with kidney length, renal function, and prevalence of simple cysts in a population-based study.

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts.

A pilot study identifying a set of microRNAs as precise diagnostic biomarkers of acute kidney injury

In the last decade, Acute Kidney Injury (AKI) diagnosis and therapy have not notably improved probably due to delay in the diagnosis, among other issues. Precocity and accuracy should be critical parameters in novel AKI biomarker discovery. microRNAs are key regulators of cell responses to many stimuli and they can be secreted to the extracellular environment. Therefore, they can be detected in body fluids and are emerging as novel disease biomarkers. We aimed to identify and validate serum miRNAs useful for AKI diagnosis and management. Using qRT-PCR arrays in serum samples, we determined miRNAs differentially expressed between AKI patients and healthy controls. Statistical and target prediction analysis allowed us to identify a panel of 10 serum miRNAs. This set was further validated, by qRT-PCR, in two independent cohorts of patients with relevant morbi-mortality related to AKI: Intensive Care Units (ICU) and Cardiac Surgery (CS). Statistical correlations with patient clinical parameter were performed. Our results demonstrated that the 10 selected miRNAs (miR-101-3p, miR-127-3p, miR-210-3p, miR-126-3p, miR-26b-5p, miR-29a-3p, miR-146a-5p, miR-27a-3p, miR-93-3p and miR-10a-5p) were diagnostic biomarkers of AKI in ICU patients, exhibiting areas under the curve close to 1 in ROC analysis. Outstandingly, serum miRNAs estimated before CS predicted AKI development later on, thus becoming biomarkers to predict AKI predisposition. Moreover, after surgery, the expression of the miRNAs was modulated days before serum creatinine increased, demonstrating early diagnostic value. In summary, we have identified a set of serum miRNAs as AKI biomarkers useful in clinical practice, since they demonstrate early detection and high diagnostic value and they recognize patients at risk.

Transition en transplantation rénale [Transition in kidney transplantation].

La transition en transplantation rénale constitue une étape importante dans la vie d'un jeune adolescent greffé. Durant cette période, les impératifs de la greffe se heurtent aux changements physiologiques et psychologiques de l'adolescence, avec un risque augmenté de non-observance thérapeutique et donc de perte du greffon. Il n'existe pas encore un modèle optimal de transition unanimement accepté, mais il a été démontré que la mise en place d'une équipe multidisciplinaire de professionnels pédiatres et adultes, ayant une formation dans la gestion des adolescents et jeunes adultes, est bénéfique. Cette équipe doit assurer une transition progressive des jeunes patients vers la clinique adulte selon un plan bien défini. Transition from pediatric to adult care in renal transplantation has emerged as a critical step in the life of a young kidney recipient. During this phase, young patients are faced with the physiological and psychological changes associated with adolescence that can lead to non-compliance and potentially graft loss. To date, there is not a unique accepted model of transition, however it has been proved that the presence of a multidisciplinary team including specialists in adolescent management and in the transition from pediatric to adult transplant care is beneficial during this at-risk phase. The goal of this team is to ensure a progressive transition of the patients according to a precise plan and time line.

Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure.

Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

Correction : Comparison of "Live High-Train Low" in Normobaric versus Hypobaric Hypoxia

[This corrects the article DOI: 10.1371/journal.pone.0114418.].

Serum 25-hydroxyvitamin D level and kidney function decline in a Swiss general adult population.

Molecular evidence suggests that levels of vitamin D are associated with kidney function loss. Still, population-based studies are limited and few have considered the potential confounding effect of baseline kidney function. This study evaluated the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline, and incidence of CKD and albuminuria. Baseline (2003-2006) and 5.5-year follow-up data from a Swiss adult general population were used to evaluate the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline (annual loss >3 ml/min per 1.73 m(2)), and incidence of CKD and albuminuria. Serum 25-hydroxyvitamin D was measured at baseline using liquid chromatography-tandem mass spectrometry. eGFR and albuminuria were collected at baseline and follow-up. Multivariate linear and logistic regression models were used considering potential confounding factors. Among the 4280 people included in the analysis, the mean±SD annual eGFR change was -0.57±1.78 ml/min per 1.73 m(2), and 287 (6.7%) participants presented rapid eGFR decline. Before adjustment for baseline eGFR, baseline 25-hydroxyvitamin D level was associated with both mean annual eGFR change and risk of rapid eGFR decline, independently of baseline albuminuria. Once adjusted for baseline eGFR, associations were no longer significant. For every 10 ng/ml higher baseline 25-hydroxyvitamin D, the adjusted mean annual eGFR change was -0.005 ml/min per 1.73 m(2) (95% confidence interval, -0.063 to 0.053; P=0.87) and the risk of rapid eGFR decline was null (odds ratio, 0.93; 95% confidence interval, 0.79 to 1.08; P=0.33). Baseline 25-hydroxyvitamin D level was not associated with incidence of CKD or albuminuria. The association of 25-hydroxyvitamin D with eGFR decline is confounded by baseline eGFR. Sufficient 25-hydroxyvitamin D levels do not seem to protect from eGFR decline independently from baseline eGFR.

The use of beta-blockers is associated with the occurrence of acute kidney injury in severe alcoholic hepatitis.

BACKGROUND & AIMS: The beneficial effect of nonselective beta-blockers (NSBB) has recently been questioned in patients with end-stage cirrhosis. We analysed the impact of NSBB on outcomes in severe alcoholic hepatitis (AH). METHODS: This study was based on a prospective database of patients with severe, biopsy-proven AH. Patients admitted from July, 2006 to July, 2014 were retrospectively studied. Patients were divided into two groups (with and without NSBB) and assessed for the occurrence of Acute Kidney Injury (AKI) and transplant-free mortality during a 168-day follow-up period. RESULTS: One hundred thirty-nine patients were included, the mean Maddrey score was 71 ± 34 and 86 patients (61.9%) developed AKI. Forty-eight patients (34.5%) received NSBB. The overall 168-day transplant-free mortality was 50.5% (95%CI, 41.3-60.0%). The overall 168-day cumulative incidence of AKI was 61.9% (95%CI, 53.2-69.4%). When compared, patients with NSBB had a lower heart rate (65 ± 13 vs 92 ± 12, P < 0.0001) and a lower mean arterial pressure (MAP, 78 ± 3 vs 87 ± 5, P < 0.0001). Patients with NSBB had comparable MELD scores, Maddrey scores, and medical histories. The 168-day transplant-free mortality was 56.8% (95%CI, 41.3-69.7%) in patients with NSBB and 46.7% (95%CI, 35.0-57.6%) without NSBB (P = 0.25). The 168-day cumulative incidence of AKI was 89.6% (95%CI, 74.9-95.9%) with NSBB compared to 50.4% (95%CI: 39.0-60.7) for no NSBB (P = 0.0001). The independent factors predicting AKI were a higher MELD score and the presence of NSBB. CONCLUSIONS: The use of NSBB in patients with severe AH is independently associated with a higher cumulative incidence of AKI.

Prooxidant/Antioxidant Balance in Hypoxia: A Cross-Over Study on Normobaric vs. Hypobaric "Live High-Train Low".

"Live High-Train Low" (LHTL) training can alter oxidative status of athletes. This study compared prooxidant/antioxidant balance responses following two LHTL protocols of the same duration and at the same living altitude of 2250 m in either normobaric (NH) or hypobaric (HH) hypoxia. Twenty-four well-trained triathletes underwent the following two 18-day LHTL protocols in a cross-over and randomized manner: Living altitude (PIO2 = 111.9 ± 0.6 vs. 111.6 ± 0.6 mmHg in NH and HH, respectively); training "natural" altitude (~1000-1100 m) and training loads were precisely matched between both LHTL protocols. Plasma levels of oxidative stress [advanced oxidation protein products (AOPP) and nitrotyrosine] and antioxidant markers [ferric-reducing antioxidant power (FRAP), superoxide dismutase (SOD) and catalase], NO metabolism end-products (NOx) and uric acid (UA) were determined before (Pre) and after (Post) the LHTL. Cumulative hypoxic exposure was lower during the NH (229 ± 6 hrs.) compared to the HH (310 ± 4 hrs.; P<0.01) protocol. Following the LHTL, the concentration of AOPP decreased (-27%; P<0.01) and nitrotyrosine increased (+67%; P<0.05) in HH only. FRAP was decreased (-27%; P<0.05) after the NH while was SOD and UA were only increased following the HH (SOD: +54%; P<0.01 and UA: +15%; P<0.01). Catalase activity was increased in the NH only (+20%; P<0.05). These data suggest that 18-days of LHTL performed in either NH or HH differentially affect oxidative status of athletes. Higher oxidative stress levels following the HH LHTL might be explained by the higher overall hypoxic dose and different physiological responses between the NH and HH.

"Live High-Train Low and High" Hypoxic Training Improves Team-Sport Performance.

PURPOSE: This study aims to investigate physical performance and hematological changes in 32 elite male team-sport players after 14 d of "live high-train low" (LHTL) training in normobaric hypoxia (≥14 h·d at 2800-3000 m) combined with repeated-sprint training (six sessions of four sets of 5 × 5-s sprints with 25 s of passive recovery) either in normobaric hypoxia at 3000 m (LHTL + RSH, namely, LHTLH; n = 11) or in normoxia (LHTL + RSN, namely, LHTL; n = 12) compared with controlled "live low-train low" (LLTL; n = 9) training. METHODS: Before (Pre), immediately after (Post-1), and 3 wk after (Post-2) the intervention, hemoglobin mass (Hbmass) was measured in duplicate [optimized carbon monoxide (CO) rebreathing method], and vertical jump, repeated-sprint (8 × 20 m-20 s recovery), and Yo-Yo Intermittent Recovery level 2 (YYIR2) performances were tested. RESULTS: Both hypoxic groups similarly increased their Hbmass at Post-1 and Post-2 in reference to Pre (LHTLH: +4.0%, P < 0.001 and +2.7%, P < 0.01; LHTL: +3.0% and +3.0%, both P < 0.001), whereas no change occurred in LLTL. Compared with Pre, YYIR2 performance increased by ∼21% at Post-1 (P < 0.01) and by ∼45% at Post-2 (P < 0.001), with no difference between the two intervention groups (vs no change in LLTL). From Pre to Post-1, cumulated sprint time decreased in LHTLH (-3.6%, P < 0.001) and LHTL (-1.9%, P < 0.01), but not in LLTL (-0.7%), and remained significantly reduced at Post-2 (-3.5%, P < 0.001) in LHTLH only. Vertical jump performance did not change. CONCLUSIONS: "Live high-train low and high" hypoxic training interspersed with repeated sprints in hypoxia for 14 d (in season) increases the Hbmass, YYIR2 performance, and repeated-sprint ability of elite field team-sport players, with benefits lasting for at least 3 wk postintervention.

Microtubule Associated Protein 1b (MAP1B) Is a Marker of the Microtubular Cytoskeleton in Podocytes but Is Not Essential for the Function of the Kidney Filtration Barrier in Mice.

Podocytes are essential for the function of the kidney glomerular filter. A highly differentiated cytoskeleton is requisite for their integrity. Although much knowledge has been gained on the organization of cortical actin networks in podocyte's foot processes, less is known about the molecular organization of the microtubular cytoskeleton in primary processes and the cell body. To gain an insight into the organization of the microtubular cytoskeleton of the podocyte, we systematically analyzed the expression of microtubule associated proteins (Maps), a family of microtubules interacting proteins with known functions as regulator, scaffold and guidance proteins. We identified microtubule associated protein 1b (MAP1B) to be specifically enriched in podocytes in human and rodent kidney. Using immunogold labeling in electron microscopy, we were able to demonstrate an enrichment of MAP1B in primary processes. A similar association of MAP1B with the microtubule cytoskeleton was detected in cultured podocytes. Subcellular distribution of MAP1B HC and LC1 was analyzed using a double fluorescent reporter MAP1B fusion protein. Subsequently we analyzed mice constitutively depleted of MAP1B. Interestingly, MAP1B KO was not associated with any functional or structural alterations pointing towards a redundancy of MAP proteins in podocytes. In summary, we established MAP1B as a specific marker protein of the podocyte microtubular cytoskeleton.