Kidney International

Accumulating evidence indicates that asymptomatic hyperuricemia is involved in the development of hypertension and chronic kidney disease. A two-hit model has been proposed to explain the role of urate in hypertension. The first hit entails activation of the renin-angiotensin system and inhibition of nitric oxide synthesis, which promote endothelial dysfunction, proliferation of vascular smooth-muscle cells and sodium reabsorption, leading to a moderate but consistent increase in systemic blood pressure. The second hit involves the immune system...

No abstract text is available yet for this article.

Trials in children with chronic kidney disease (CKD) do not consistently report outcomes that are critically important to patients and caregivers. This can diminish the relevance and reliability of evidence for decision-making, limiting the implementation of results into practice and policy. As part of the Standardized Outcomes in Nephrology - Children and Adolescents (SONG-Kids) initiative, we convened two consensus workshops in San Diego, United States (7 patients, 24 caregivers, 43 health professionals; and Melbourne, Australia (7 patients, 23 caregivers, 49 health professionals)...

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Most epidemiological studies on chronic kidney disease (CKD) are based solely on estimated glomerular filtration rates (eGFR). Few studies have included proteinuria, while the chronicity criterion is usually omitted. To explore this, we examined the prevalence of CKD stages 1-5 in Iceland based on multiple markers of kidney damage. All serum creatinine values, urine protein measurements and diagnostic codes for kidney diseases and comorbid conditions for people aged 18 years and older were obtained from electronic medical records of all healthcare institutions in Iceland in 2008-2016...

In recent years, a substantial body of experimental and clinical work has been devoted to C3 glomerulopathy and immunoglobulin-mediated membranoproliferative glomerulonephritis. Despite the rapid accumulation of data, several uncertainties regarding these two rare forms of nephropathies persist. They concern their pathophysiology, classification, clinical course, relevance of biomarkers and of pathology findings and assessment of the efficacy of available therapies. The present review discusses the impact of these uncertainties on the clinical management of patients...

When multiple living donor candidates come forward to donate a kidney to the same recipient, some living donor programs evaluate one candidate at a time to avoid unnecessary evaluations. Evaluating multiple candidates concurrently rather than sequentially may be cost-effective from a societal perspective if it reduces the time recipients spend on dialysis. We used a simple decision tree to estimate the cost-effectiveness of evaluating two to four candidates simultaneously rather than sequentially as potential kidney donors for the same intended recipient...

Polycystin-1 (PC1) and -2 (PC2), products of the PKD1 and PKD2 genes, are mutated in autosomal dominant polycystic kidney disease (ADPKD). They localize to the primary cilia; however, their ciliary function is in dispute. Loss of either the primary cilia or PC1or PC2 causes cyst formation. However, loss of both cilia and PC1 or PC2 inhibits cyst growth via an unknown pathway. To help define a pathway, we studied cilium length in human and mouse kidneys. We found cilia are elongated in kidneys from patients with ADPKD and from both Pkd1 and Pkd2 knockout mice...

Podocyte maintenance and stress resistance are exquisitely based on high basal rates of autophagy making these cells a unique model to unravel mechanisms of autophagy regulation. Polyamines have key cellular functions such as proliferation, nucleic acid biosynthesis and autophagy. Here we test whether endogenous spermidine signaling is a driver of basal and dynamic autophagy in podocytes by using genetic and pharmacologic approaches to interfere with different steps of polyamine metabolism. Translational studies revealed altered spermidine signaling in focal segmental glomerulosclerosis in vivo and in vitro...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Membranous glomerulopathy (MGN) is characterized by global subepithelial immune deposits that stain most intensely by immunofluorescence for IgG. Here we describe the clinical and pathologic findings in a cohort of patients with MGN in which, by definition, only segmental immune deposits are present. This rare variant, termed segmental MGN (sMGN), is poorly characterized. We retrospectively identified all patients with sMGN diagnosed at Columbia University from January 2010 to October 2018, excluding those with systemic lupus erythematosus...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

To investigate the cause of salt sensitivity in a normotensive animal model, we treated rats with a low-dose of the nitric oxide synthase inhibitor, L-NAME, that does not elevate blood pressure per se or induce kidney fibrosis. A high salt diet increased the circulating blood volume both in L-NAME-treated and nontreated animals for the first 24 hours. Thereafter, the blood volume increase persisted only in the L-NAME-treated rats. Blood pressure was higher in the L-NAME-treated group from the start of high salt diet exposure...

Glomerular podocytes undergo structural and functional changes with advanced age, that; increase susceptibility of aging kidneys to worse outcomes following superimposed glomerular; diseases. To delineate transcriptional changes in podocytes in aged mice, RNA-seq was performed on isolated populations of reporter-labeled (tdTomato) podocytes from multiple young (two to three months) and advanced aged mice (22 to 24 months, equivalent to 70 plus year old humans). Of the 2,494 differentially expressed genes, 1,219 were higher and 1,275 were lower in aged podocytes...

Systemic lupus erythematosus is a systemic and chronic autoimmune disease characterized by loss of tolerance towards nuclear antigens with autoreactive CD4+ T cells implicated in disease pathogenesis. However, very little is known about their receptor specificity since the detection of human autoantigen specific CD4+ T cells has been extremely challenging. Here we present an analysis of CD4+ T cells reactive to nuclear antigens using two complementary methods: T cell libraries and antigen-reactive T cell enrichment...

Sodium magnetic resonance imaging (MRI) is a powerful, non-invasive technique to assess the sodium distribution within the kidney. Here we undertook pre-clinical and clinical studies to quantify the corticomedullary sodium gradient in healthy individuals and in a porcine model of diuresis. The results demonstrated that sodium MRI could detect spatial differences in sodium biodistribution across the kidney. The sodium gradient of the kidney changed significantly after diuresis in the pig model and was independent of blood electrolyte measurements...

No abstract text is available yet for this article.

Anemia is a frequent complication of chronic kidney disease (CKD), related in part to the disruption of iron metabolism. Iron therapy is very common in children with CKD and excess iron has been shown to induce bone loss in non-CKD settings, but the impact of iron on bone health in CKD remains poorly understood. Here, we evaluated the effect of oral and parenteral iron therapy on bone transcriptome, bone histology and morphometry in two mouse models of; juvenile CKD (adenine-induced and 5/6-nephrectomy). Both modalities of iron therapy effectively improved anemia in the mice with CKD, and lowered bone Fgf23 expression...