Kidney International

In chronic kidney disease (CKD), anemia and disordered iron homeostasis are prevalent and associated with significant adverse consequences. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) issued an anemia guideline for managing the diagnosis, evaluation, and treatment of anemia in CKD. Since then, new data have accrued from basic research, epidemiological studies, and randomized trials that warrant a re-examination of previous recommendations. Therefore, in 2019, KDIGO decided to convene two Controversies Conferences to review the latest evidence, explore new and ongoing controversies, assess change implications for the current KDIGO anemia guideline, and propose a research agenda...

The genome-wide association study (GWAS) is a powerful means to study genetic determinants of disease traits and generate insights into disease pathophysiology. To date, few GWAS of circulating metabolite levels have been performed in African Americans with chronic kidney disease. Hypothesizing that novel genetic-metabolite associations may be identified in a unique population of African Americans with a lower glomerular filtration rate (GFR), we conducted a GWAS of 652 serum metabolites in 619 participants (mean measured glomerular filtration rate 45 mL/min/1...

Chronic active T cell-mediated rejection (CA TCMR) is a newly described variant of kidney allograft rejection associated with long-term graft loss. Whether this form of rejection is related to under immunosuppression is debated and the benefit of immunosuppressive therapy in CA TCMR is unknown. Here we investigate the amenability of CA TCMR to treatment and examine the impact of clinical, histologic, and molecular parameters on outcomes. In a retrospective single institution review, we identified 48 cases of isolated CA TCMR, of which 44 were treated with pulse steroids and/or anti-thymocyte globulin...

Hypertension is a major cause of cardiovascular morbidity and mortality, despite the availability of antihypertensive drugs with different targets and mechanisms of action. Here, we provide evidence that pharmacological inhibition of TMEM16A (ANO1), a calcium-activated chloride channel expressed in vascular smooth muscle cells, blocks calcium-activated chloride currents and contraction in vascular smooth muscle in vitro and decreases blood pressure in spontaneously hypertensive rats. The acylaminocycloalkylthiophene TMinh-23 fully inhibited calcium-activated TMEM16A chloride current with nanomolar potency in Fischer rat thyroid cells expressing TMEM16A, and in primary cultures of rat vascular smooth muscle cells...

Various cellular insult and injury to renal epithelial cells stimulate repair mechanisms to adapt and restore the organ homeostasis. Renal tubular epithelial cells (RTECs) are endowed with regenerative capacity, which allows for a restoration of nephron function after acute kidney injury (AKI). However, recent evidence indicates that the repair is often incomplete, leading to maladaptive responses that promote the progression to CKD. The dysregulated cell cycle and proliferation is also a key feature of RTECs in polycystic kidney disease (PKD) and HIV-associated nephropathy (HIVAN)...

Inferring causality from observational studies can be challenging because of the perennial threat of biases from selection, measurement, and confounding. The gold standard study design in clinical research is the randomized controlled trial, since random allocation to treatment ensures that, on average, comparison groups are balanced with respect to both known and unknown prognostic factors. However, most clinically relevant exposure-outcome relationships are not amendable (logistically or ethically) to randomization...

Vadadustat is an investigational hypoxia-inducible factor prolyl hydroxylase inhibitor that increases endogenous erythropoietin production, and has been shown to decrease hepcidin levels, ameliorate iron restriction, and increase hemoglobin concentrations in anemic patients with chronic kidney disease (CKD). In studies of physiological responses to other erythropoietic stimuli, erythropoietin induced erythroblast secretion of erythroferrone (ERFE), which acts on the liver to suppress hepcidin production and mobilize iron for erythropoiesis...

Prolyl hydroxylase domain enzyme (PHD) inhibitors are effective in the treatment of chronic kidney disease (CKD)-associated anemia by stabilizing hypoxia inducible factor (HIF), thereby increasing erythropoietin and consequently erythropoiesis. However, concern for CKD progression needs to be addressed in clinical trials. Although pre-clinical studies showed an anti-inflammatory effect in kidney disease models, the effect of PHD inhibitors on kidney fibrosis was inconsistent probably because the effects of HIF are cell type and context dependent...

Epidemiological studies document strong associations between acute or chronic kidney injury and kidney tumors. However, whether these associations are linked by causation, and in which direction, is unclear. Accumulating data from basic and clinical research now shed light on this issue and prompt us to propose a new pathophysiological concept with immanent implications in the management of patients with kidney disease and patients with kidney tumors. As a central paradigm, this review proposes the mechanisms of kidney damage and repair that are active during acute kidney injury but also during persistent injuries in chronic kidney disease as triggers of DNA damage promoting the expansion of (pre-)malignant cell clones...

APOL1 kidney risk variants (RVs) were identified in 2010 as major drivers of glomerular, tubulointerstitial and renal microvascular disease in individuals with sub-Saharan African ancestry. In December 2020, the "APOL1 at Ten" conference summarized the first decade of progress and discussed controversies and uncertainties that remain to be addressed. Topics included trypanosome infection and its role in the evolution of APOL1 kidney RVs, clinical phenotypes in APOL1-associated nephropathy, relationships between APOL1 RVs and background haplotypes on cell injury and molecular mechanisms initiating disease, the role of clinical APOL1 genotyping, and development of novel therapies for kidney disease...

Co-stimulation is a prerequisite for pathogenic activity in T cell-mediated diseases and has been demonstrated to achieve tolerance in organ-specific autoimmunity as a therapeutic target. Here, we evaluated the involvement of the tumor necrosis factor family members CD30 and OX40 in immune-complex mediated kidney disease. In vitro stimulation and proliferation studies were performed with CD4+ cells from wild type and CD30/OX40 double knock-out (CD30OX40-/- ) mice. In vivo studies were performed by induction of nephrotoxic serum nephritis in wild type, CD30OX40- /- , CD30-/- , OX40-/- , reconstituted Rag1-/- and C57Bl/6J mice treated with αCD30L αOX40L antibodies...

The role of paclitaxel-coated balloons has been established in the coronary and peripheral arterial circulations with recent interest in the use of paclitaxel-coated balloons to improve patency rates following angioplasty of arteriovenous fistulas. To assess the efficacy of paclitaxel-coated angioplasty balloons to prolong the survival time of target lesion primary patency in arteriovenous fistulas, we designed an investigator-led multi-center randomized controlled trial with follow up time variable for a minimum of one year...

The hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function constitutes a serious complication of hepatic decompensation. Coexistence of liver/kidney damage, mentioned in the dropsy literature, was highlighted by Richard Bright in 1827 and confirmed in 1840 by his contemporary nephrology pioneer Pierre Rayer. Cholemic nephrosis was described in 1861 by Friedrich Frerichs, and the renal tubular lesions of HRS by Austin Flint in 1863. The term 'acute hepato-nephritis' was introduced in 1916 by Paul Merklen and its chronic form designated HRS by Marcel Dérot in 1930s...

No abstract text is available yet for this article.

Heavy chain/light chain (HLC) antibodies target conformational epitopes at the junctions of the heavy chain and light chain constant regions (CH1 and CL) of serum IgGκ, IgGλ, IgAκ, IgAλ, IgMκ, and IgMλ to provide quantitation of intact HLC pairs. Here, we developed an HLC tissue immunofluorescence protocol to test if it can complement conventional immunofluorescence in the diagnosis of monoclonal gammopathy-associated kidney diseases. HLC immunofluorescence was performed on archived frozen tissue of 104 kidney biopsies...

No abstract text is available yet for this article.

Patients with end stage kidney disease receiving in-center hemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. Following infection, patients receiving ICHD frequently develop circulating antibodies to SARS-CoV-2, even with asymptomatic infection. Here, we investigated the durability and functionality of the immune responses to SARS-CoV-2 infection in patients receiving ICHD. Three hundred and fifty-six such patients were longitudinally screened for SARS-CoV-2 antibodies and underwent routine PCR-testing for symptomatic and asymptomatic infection...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Kidney fibrosis is characterized by the development of myofibroblasts originating from resident kidney and immigrating cells. Myofibroblast formation and extracellular matrix production during kidney damage are triggered by various cytokines. Among these, transforming growth factor β1 (TGFβ1) is considered a central trigger for kidney fibrosis. We found a highly upregulated expression of TGFβ1 and TGFβ receptor 2 (TGFβ-R2) mRNAs in kidney interstitial cells in experimental fibrosis. Here, we investigated the contribution of TGFβ1 signaling in resident kidney interstitial cells to organ fibrosis using the models of adenine induced nephropathy and unilateral ureter occlusion in mice...