Hamptonkorsgaard8548

Acute kidney injury (AKI) remains a significant clinical problem through its diverse etiologies, the challenges of robust measurements of injury and recovery, and its progression to chronic kidney disease (CKD). Bridging the gap in our knowledge of this disorder requires bringing together not only the technical resources for research but also the investigators currently endeavoring to expand our knowledge and those who might bring novel ideas and expertise to this important challenge. The University of Alabama at Birmingham-University of California-San Diego O'Brien Center for Acute Kidney Injury Research brings together technical expertise and programmatic and educational efforts to advance our knowledge in these diverse issues and the required infrastructure to develop areas of novel exploration. Since its inception in 2008, this O'Brien Center has grown its impact by providing state-of-the-art resources in clinical and preclinical modeling of AKI, a bioanalytical core that facilitates measurement of critical biomarkers, including serum creatinine via LC-MS/MS among others, and a biostatistical resource that assists from design to analysis. Through these core resources and with additional educational efforts, our center has grown its investigator base to include >200 members from 51 institutions. Importantly, this center has translated its pilot and catalyst funding program with a $37 return per dollar invested. Over 500 publications have resulted from the support provided with a relative citation ratio of 2.18 ± 0.12 (iCite). Through its efforts, this disease-centric O'Brien Center is providing the infrastructure and focus to help the development of the next generation of researchers in the basic and clinical science of AKI. This center creates the promise of the application at the bedside of the advances in AKI made by current and future investigators.Ammonia generated within the kidney is partitioned into a urinary fraction (the key buffer for net acid excretion) and an aliquot delivered to the systemic circulation. The physiology of this partitioning has yet to be examined in a kidney model, and that was undertaken in this work. This involves explicit representation of the cortical labyrinth, so that cortical interstitial solute concentrations are computed rather than assigned. A detailed representation of cortical vasculature has been avoided by making the assumption that solute concentrations within the interstitium and peritubular capillaries are likely to be identical and that there is little to no modification of venous composition as blood flows to the renal vein. The model medullary ray has also been revised to include a segment of proximal straight tubule, which supplies ammonia to this region. The principal finding of this work is that cortical labyrinth interstitial ammonia concentration is likely to be several fold higher than systemic arteria gap in our understanding of how ammonia generated within the cortex is channeled efficiently into the final urine.High-incidence regions of leptospirosis caused by Leptospira spp. coincide with chronic kidney disease. This study investigated whether asymptomatic leptospirosis is an emerging culprit that predisposes to progressive chronic kidney disease when superimposed on secondary nephrotoxic injury. Kidney histology/function and whole transcriptomic profiles were evaluated for Leptospira-infected C57/BL6 mice with adenine-induced kidney injury. The extent of tubulointerstitial kidney lesions and expression of inflammation/fibrosis genes in infected mice with low-dose (0.1%) adenine, particularly in high-dose (0.2%) adenine-fed superimposed on Leptospira-infected mice, were significantly increased compared with mice following infection or adenine diet alone, and the findings are consistent with renal transcriptome analysis. Pathway enrichment findings showed that integrin-β- and fibronectin-encoding genes had distinct expression within the integrin-linked kinase-signaling pathway, which were upregulated in 0.2% adeninesive chronic kidney disease.NEW & NOTEWORTHY Leptospira-infected mice followed by secondary nephrotoxic injury exacerbated immune/inflammatory responses and renal fibrosis. Comparison with the murine model revealed candidates involved in the progression of renal fibrosis in chronic kidney disease (CKD). Comparative transcriptome study suggests that secondary nephrotoxic injury in Leptospira-infected mice recapitulates the gene expression signatures found in CKD patients. This study indicates that secondary nephrotoxic injury may exacerbate CKD in chronic Leptospira infection implicating in the progression of CKD of unknown etiology.The hormone aldosterone is essential for maintaining K+ and Na+ balance and controlling blood pressure. Aldosterone has different effects if it is secreted due to hypovolemia or hyperkalemia. The kidney distal convoluted tubule (DCT) is believed to play a central role in mediating the differential responses to aldosterone. To determine the alterations in the DCT that may be responsible for these effects, male mice with green fluorescent protein expression specifically in the DCT were maintained on diets containing low NaCl (hypovolemic state) or high potassium citrate (hyperkalemic state) for 4 days, and DCT cells were isolated using fluorescence-activated cell sorting. This pure population of DCT cells was subjected to analysis by liquid chromatography-coupled tandem mass spectrometry. Over 3,000 proteins were identified in the DCT, creating the first proteome of the mouse DCT. Of the identified proteins, 210 proteins were altered in abundance following a low-NaCl diet and 625 proteins following the high-K+ ulated.Previous studies reported that the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT) was a risk factor in cardiovascular disease. Peripheral artery disease (PAD) is an important risk factor for cardiovascular death. DEG-35 cost However, only a few studies investigated the correlations between the AST/ALT ratio and PAD. We analyzed data from 10 900 patients with hypertension from the Chinese Hypertension Registry Study; 350 patients had PAD (prevalence 3.2%). After adjusting for potential confounders, the AST/ALT ratio was independently and positively associated with risk of PAD (OR 1.31, 95% CI, 1.13-1.59), and a significant increased risk of PAD for the third AST/ALT ratio tertile (T3) compared with the first tertile (T1; OR 1.49, 95% CI, 1.09-2.04, P trend = .005) was found. Moreover, when we combined T1 and T2 into one group and used it as a reference group, the risk of PAD increased with the increase in AST/ALT; the risk ratio was 1.52 (95% CI, 1.20-1.95). A higher AST/ALT ratio (≥1.65) was associated with PAD risk in Chinese adults with hypertension.