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The majority of calcium filtered by the glomerulus is reabsorbed along the nephron. Most is reabsorbed from the proximal tubule (> 60%) via a paracellular pathway composed of the tight junction proteins claudins-2 and -12, a process driven by sodium and consequently water reabsorption. The thick ascending limb reabsorbs the next greatest amount of calcium (20-25%), also by a paracellular pathway composed of claudins-16 and -19. This pathway is regulated by the CaSR, whose activity increases the expression of claudin-14, a protein that blocks paracellular calcium reabsorption. The fine tuning of urinary calcium excretion occurs in the distal convoluted and connecting tubule by a transcellular pathway composed of the apical calcium channel TRPV5, the calcium shuttling protein calbindin-D28K and the basolateral proteins PMCA1b and the sodium calcium exchanger, NCX. Not surprisingly, mutations in a subset of these genes cause monogenic disorders with hypercalciuria as a part of the phenotype. More commonly, "idiopathic" hypercalciuria is encountered clinically with genetic variations in CLDN14, the CASR and TRPV5 associating with kidney stones and increased urinary calcium excretion. An understanding of the molecular pathways conferring kidney tubular calcium reabsorption is employed in this review to help explain how dietary and medical interventions for this disorder lower urinary calcium excretion.

Background Previous studies in piglets show a direct relationship between intestinal mass and arginine (Arg) synthesis. We aimed to study the effects of 75% intestinal resection on whole-body Arg synthesis. Methods Piglets were allocated to sham or jejunocolic (JC) surgery and to enteral nutrition (EN) at 20% [sham (n = 8), JC (n = 10)], or 40% [sham (n = 4), JC (n = 5)]. A gastric tube was placed for EN and a venous catheter for parenteral nutrition and blood sampling. On day 6, a primed bolus and constant infusion of Arg m + 2 label and proline m + 1 label was delivered. In addition, 40% EN piglets received a citrulline (Cit) m + 3 tracer. Blood sampling was undertaken and whole-body Arg synthesis was calculated. On day 7, intestinal length was measured, and samples were collected for gene expression (PCR quantification) and histopathology. Results On Day 7, sham piglets showed intestinal lengthening compared to JC (p = 0.02). Whole-body Arg synthesis was similar between groups (p = 0.50). Adjusting for absolute small intestinal length, JC piglets had greater Arg synthesis (p = 0.01). Expression of arginosuccinase was upregulated in the jejunum of JC compared to sham on 20% EN (p = 0.03). Conclusion This demonstrates for the first-time adaptive changes in intestinal Arg synthesis following intestinal resection. Impact The intestine makes a critical contribution to whole-body arginine synthesis, particularly in neonates, a human population at risk for short bowel syndrome. Therefore, we studied intestinal arginine synthesis in a neonatal piglet model of short bowel syndrome and demonstrated adaptive changes in the intestine that may preserve whole-body arginine synthesis, despite loss of intestinal mass. This research adds new information to our understanding of the effects a massive intestinal resection has on amino acid metabolism during neonatal development.

The SLC9 gene family encodes Na+/H+ exchangers (NHEs). These transmembrane proteins transport ions across lipid bilayers in a diverse array of species from prokaryotes to eukaryotes, including plants, fungi, and animals. They utilize the electrochemical gradient of one ion to transport another ion against its electrochemical gradient. Currently, 13 evolutionarily conserved NHE isoforms are known in mammals [22, 46, 128]. The SLC9 gene family (solute carrier classification of transporters: www.bioparadigms.org ) is divided into three subgroups [46]. The SLC9A subgroup encompasses plasmalemmal isoforms NHE1-5 (SLC9A1-5) and the predominantly intracellular isoforms NHE6-9 (SLC9A6-9). The SLC9B subgroup consists of two recently cloned isoforms, NHA1 and NHA2 (SLC9B1 and SLC9B2, respectively). The SLC9C subgroup consist of a sperm specific plasmalemmal NHE (SLC9C1) and a putative NHE, SLC9C2, for which there is currently no functional data [46]. NHEs participate in the regulation of cytosolic and organellar pH as well as cell volume. In the intestine and kidney, NHEs are critical for transepithelial movement of Na+ and HCO3 − and thus for whole body volume and acid–base homeostasis [46]. Mutations in the NHE6 or NHE9 genes cause neurological disease in humans and are currently the only NHEs directly linked to human disease. However, it is becoming increasingly apparent that members of this gene family contribute to the pathophysiology of multiple human diseases.

Background Practice variation is common for nephrotic syndrome (NS) treatment. Methods A cross-sectional, web-based survey on NS treatment was administered to 58 Canadian pediatric nephrologists with the aim to document existing practice variation and compare practice with the recommendations of the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for NS. Results Of the 58 nephrologists asked to participate in the survey, 40 (69 %) responded. Among these, 62 % prescribed initial daily glucocorticoid (GC) therapy for 6 weeks, 26 % for 4w eeks by 26 %, and 10 %p rescribed‘other’ .A lternateday GC was continued for 6 weeks by 63 % of respondents and for >6 and

Owing to restricted energy resources and the worldwide ambitions to reduce CO2 emissions, renewable energy sources, such as wind energy, are gaining economical interest and promise great growth potential. This is closely connected with the increase of plant unit sizes. The wall thickness of the tower construction is rising accordingly and leads to increasing costs for the joining technology. The rising number of weld passes for submerged arc welding (SAW) leads to rising process times and high filler material consumption. The employment of non-vacuum electron beam welding (NVEBW) can significantly reduce the number of passes, the welding time, and the filler consumption. A substantial aspect of the control of the welding process is the formation of solidification cracks. Formation mechanisms and preventions methods such as preheating, alloying, and full penetration welding will be presented and experimentally backed up. The subsequent application of the SAW and NVEBW processes will be compared to standard multi-pass SAW for an exemplary weld of 30 mm thick high-strength steel. An additional aim of current research is the overall reduction of the wall thickness of wind turbine towers applying high-strength steels. Here, it is of chief concern to preserve the advantages of the material.

Young children with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT) have traditionally experienced high rates of morbidity and mortality; however, detailed long-term follow-up data is limited. Using a population-based retrospective cohort with data from a national organ failure registry and administrative data from Canada’s universal health care system, we analysed the outcomes of 87 children starting RRT (before age 2 years) and followed them until death or date of last contact [median follow-up 4.7 years, interquartile range (IQR) 1.4–9.8). We assessed secular trends in survival and the influence of: (1) age at start of RRT and (2) etiology of ESRD with survival and time to transplantation. Patients were mostly male (69.0 %) with ESRD predominantly due to renal malformations (54.0 %). Peritoneal dialysis was the most common initial RRT (83.9 %). Fifty-seven (65.5 %) children received a renal transplant (median age at first transplant: 2.7 years, IQR 2.0–3.3). During 490 patient-years of follow-up, there were 23 (26.4 %) deaths, of which 22 occurred in patients who had not received a transplant. Mortality was greater for patients commencing dialysis between 1992 and 1999 and among the youngest children starting RRT (0–3 months). Children with ESRD secondary to renal malformations had better survival than those with ESRD due to other causes. Among the transplanted patients, all but one survived to the end of the observation period. Children who start RRT before 3 months of age have a high risk of mortality. Among our paediatric patient cohort, mortality rates were much lower among children who had received a renal transplant.