Explore the vast range of titles available.

To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality. Individual participant data meta-analysis. Cohorts from 40 countries with data collected between 1970 and 2017. Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607). GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m ) and all cause mortality. Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index. Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR.

Limited data are available regarding in-hospital outcomes of transcatheter aortic valve implantation (TAVI) in the octogenarian population with chronic kidney disease (CKD). We sought to study the cardiovascular outcomes of TAVI in CKD hospitalization with different stages at the national cohort registry. We used the National Inpatient Sample database to compare TAVI CKD low-grade (LG) (stage I to IIIa, b) versus TAVI CKD high-grade (HG) (stage IV to V) in octogenarians. Outcomes such as inpatient mortality, cardiogenic shock, new permanent pacemaker implantation, acute kidney injury), sudden cardiac arrest, mechanical circulatory support, major bleeding, transfusion, and resource utilization were compared between the 2 cohorts. A total of 74,766 octogenarian patients (TAVI CKD-HG n = 12,220; TAVI CKD-LG n = 62,545) were included in our study. On matched analysis, TAVI CKD-HG had higher odds of in-hospital mortality (adjusted odds ratio [aOR] 2.18, 95% confidence interval [CI] 1.0−2.5, p <0.0001), cardiogenic shock (aOR 1.22, 95% CI 1.07 to 1.39, p = 0.0019), permanent pacemaker implantation (aOR 1.14, 95% CI 1.06 to 1.23, p = 0.0006), acute kidney injury (aOR 1.19, 95% CI 1.13 to 1.27, p <0.0001), sudden cardiac arrest (aOR 1.32, 95% CI 1.09 to 1.61, p = 0.004), major bleeding (aOR 1.1, 95% CI 1.006 to 1.22, p <0.0368) and higher rates of blood transfusion (aOR 1.62, 95% CI 1.5 to 1.75, p <0.0001) when compared with the TAVI CKD-LG cohort. However, there was no statistically significant difference in the odds of cerebrovascular accident and mechanical circulatory support use between the 2 groups.

[alpha]-Klotho was first identified as an aging gene and was later shown to be a regulator of phosphate metabolism. Fibroblast growth factor 23 (FGF23) is the key regulator of phosphate metabolism. Serum levels of soluble [alpha]-Klotho in chronic kidney disease (CKD) patients have not previously been determined, especially in relation with FGF23 and creatinine levels. This study was designed to investigate whether serum soluble [alpha]-Klotho levels are modulated by renal function, age, and FGF23 level in CKD patients. This study is the first report on the utility of measuring soluble [alpha]-Klotho levels in human CKD. A total of 292 CKD patients were enrolled. Serum samples were collected, and FGF23 and soluble [alpha]-Klotho levels were measured using enzyme-linked immunosorbent assay kits. In addition, serum creatinine, hemoglobin, albumin, calcium, and phosphate levels were measured. Serum soluble [alpha]-Klotho levels were associated positively with estimated glomerular filtration rate (eGFR) (P < 0.0001) and inversely with serum creatinine level (P < 0.01). Interestingly, [alpha]-Klotho levels were significantly decreased in stage 2 CKD compared with stage 1 (P = 0.0001). Serum FGF23 levels were associated positively with serum creatinine and negatively with eGFR. FGF23 levels were significantly increased in stage 5 compared with stage 1 CKD. Soluble [alpha]-Klotho was associated inversely with log-transformed FGF23 level (P < 0.01). Our data indicate that soluble [alpha]-Klotho levels are significantly decreased in stage 2 CKD compared to stage 1, and not only in the advanced stages of the disease. Soluble [alpha]-Klotho may thus represent a new biomarker for the diagnosis of CKD, especially in the early stage.[PUBLICATION ABSTRACT]

Background Chronic Kidney Disease (CKD) of uncertain origin (CKDu) has affected North Central Province (Anuradhapura and Polonnaruwa districts) of Sri Lanka. The cause is still unknown. The objective of this study was to describe the incidence, prevalence and trend of CKD/CKDu in North Central Province of Sri Lanka. Methods A cross sectional survey conducted in North Central Province with GPS mapping in CKDu highly affected areas. The diagnosis of CKD and staging were made according to the Kidney Disease: Improving Global Outcomes paper. Descriptive statistics used with chi-square test for evaluating dichotomous variables. Log rank test was used to compare survival rates. The population data was obtained from the 2011 Census. Results There were 30,566 CKD/CKDu patients in the North Central Province. Incidence of 0.10 in 2009, 0.39 in 2016 in Anuradhapura district, decreased slightly to 0.29 in 2017. Incidence of 0.09 in 2009, 0.46 in 2016 in Polonnaruwa district, decreased slightly to 0.41 in 2017. The point prevalence in high incidence areas ranged from 2.44–4.35. The 5 year survival rate was 71.2 (Anuradhapura 72.4 and Polonnaruwa 68.3, p  = 0.0212). More than 70, 40 and 33% of patients were over 50, 60 and 70 years of age respectively. A male preponderance was seen in all the divisional areas (ranging from 1.3:1 to 2.6:1) and in all the age groups. Farmers were the most affected (70.6% Anuradhapura district and 65.1% Polonnaruwa district). Majority in CKD stage I (4943, 69.6%). There were 1685 deaths (17.5% of total CKD/CKDu patients, 67.6% of total deaths in CKD/CKDu patients) occurring within the first 3 years of diagnosis. GPS mapping shows that there is a clustering of households with CKD/CKDu. Conclusions The incidence of CKD/CKDu increased up to 2016 with a slight decrease in 2017. The most vulnerable age group was 40 to 60 years. There is a male preponderance. Farmers at a higher risk. Majority were in CKD stage 1. More than two thirds of the deaths of CKD/CKDu patients occurred within three years of diagnosis with disparities in 5 year survival rate among the two districts. There is clustering of cases.

Chronic kidney disease (CKD) is a frequent diagnosis in cats attending primary care practice and the most frequent cause of death in cats aged over five years, yet there is limited published research for CKD in cats attending primary care practice. This study aimed to estimate the prevalence of CKD and investigate risk factors for diagnosis and survival of cats diagnosed with CKD in UK primary care practices. The study included cats attending VetCompass TM practices from January 1, 2012 to December 31, 2013. A nested case‐control and cohort study were undertaken. From 353,448 cats attending 244 clinics, the prevalence of CKD was estimated as 1.2 per cent (95 per cent CI 1.1 per cent to 1.3 per cent). Most cats with CKD had clinical signs at diagnosis (66.6 per cent). Few cats underwent investigations or monitoring of serum creatinine (32.6 per cent), urine protein:creatinine ratio (14.9 per cent) or blood pressure measurement (25.6 per cent). A proprietary renal diet was the most frequently prescribed management (63.8 per cent). Median survival time following diagnosis was 388 days (IQR 88–1042 days). This study provides generalisable evidence from the wider cat population to aid veterinarians in improved diagnosis and management of CKD that can benefit the health and welfare of cats with CKD in the UK.

Mitochondria are heterogeneous and highly dynamic organelles, playing critical roles in adenosine triphosphate (ATP) synthesis, metabolic modulation, reactive oxygen species (ROS) generation, and cell differentiation and death. Mitochondrial dysfunction has been recognized as a contributor in many diseases. The kidney is an organ enriched in mitochondria and with high energy demand in the human body. Recent studies have been focusing on how mitochondrial dysfunction contributes to the pathogenesis of different forms of kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD). AKI has been linked to an increased risk of developing CKD. AKI and CKD have a broad clinical syndrome and a substantial impact on morbidity and mortality, encompassing various etiologies and representing important challenges for global public health. Renal mitochondrial disorders are a common feature of diverse forms of AKI and CKD, which result from defects in mitochondrial structure, dynamics, and biogenesis as well as crosstalk of mitochondria with other organelles. Persistent dysregulation of mitochondrial homeostasis in AKI and CKD affects diverse cellular pathways, leading to an increase in renal microvascular loss, oxidative stress, apoptosis, and eventually renal failure. It is important to understand the cellular and molecular events that govern mitochondria functions and pathophysiology in AKI and CKD, which should facilitate the development of novel therapeutic strategies. This review provides an overview of the molecular insights of the mitochondria and the specific pathogenic mechanisms of mitochondrial dysfunction in the progression of AKI, CKD, and AKI to CKD transition. We also discuss the possible beneficial effects of mitochondrial-targeted therapeutic agents for the treatment of mitochondrial dysfunction-mediated AKI and CKD, which may translate into therapeutic options to ameliorate renal injury and delay the progression of these kidney diseases.

In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered. The inflammatory, cardio-vascular and fibrogenic systems were those most frequently affected and they are one by one major actors in the high morbidity and mortality of CKD but also the mechanisms that have most frequently been studied. A scoring system was built with the intention to classify the reviewed compounds according to the experimental evidence of their toxicity (number of systems affected) and overall experimental and clinical evidence. Among the highest globally scoring solutes were 3 small water-soluble compounds [asymmetric dimethylarginine (ADMA); trimethylamine-N-oxide (TMAO); uric acid], 6 protein bound compounds or groups of protein bound compounds [advanced glycation end products (AGEs); p-cresyl sulfate; indoxyl sulfate; indole acetic acid; the kynurenines; phenyl acetic acid;] and 3 middle molecules [β2-microglobulin; ghrelin; parathyroid hormone). In general, more experimental data were provided for the protein bound molecules but for almost half of them clinical evidence was missing in spite of robust experimental data. The picture emanating is one of a complex disorder, where multiple factors contribute to a multisystem complication profile, so that it seems of not much use to pursue a decrease of concentration of a single compound.

Among patients with type 2 diabetes and stage 4 chronic kidney disease, bardoxolone methyl, as compared with placebo, did not reduce the risk of end-stage renal disease or cardiovascular death. Cardiovascular events in the bardoxolone group prompted trial termination. Type 2 diabetes mellitus is the most important cause of progressive chronic kidney disease in the developed and developing worlds. Various therapeutic approaches to slow progression, including restriction of dietary protein, glycemic control, and control of hypertension, have yielded mixed results. 1 – 3 Several randomized clinical trials have shown that inhibitors of the renin–angiotensin–aldosterone system significantly reduce the risk of progression, 4 – 6 although the residual risk remains high. 7 None of the new agents tested during the past decade have proved effective in late-stage clinical trials. 8 – 12 Oxidative stress and impaired antioxidant capacity intensify with the progression of chronic kidney disease. 13 In . . .

The burden of chronic kidney disease (CKD) and other comorbidities, such as hypertension and diabetes, which increase the risk of developing CKD, is on the rise in the Middle East and Africa. The Middle East and Africa CKD (MEA-CKD) steering committee, comprising eminent healthcare specialists from the Middle East and Africa, was formed to identify and propose steps to address the gaps in the management of CKD in these regions. The current article lists the MEA-CKD steering committee meeting outcomes and evaluates the available evidence supporting the role of novel therapeutic options for patients with CKD. The need of the hour is to address the gaps in awareness and screening, early diagnosis, along with referral and management of patients at risk. Measures to bring about appropriate changes in healthcare policies to ensure access to all benefit-proven protective therapies, including novel ones, at community levels are also vital for reducing the overall burden of CKD on the healthcare system as well as governing bodies, especially in developing countries of the Middle East and Africa.

Acute kidney injury (AKI) is an increasing health burden with high morbidity and mortality rates worldwide. AKI is a risk factor for chronic kidney disease (CKD) development and progression to end stage renal disease (ESRD). Rapid action is required to find treatment options for AKI, plus to anticipate the development of CKD and other complications. Therefore, it is essential to understand the pathophysiology of AKI to CKD transition. Over the last several years, research has revealed maladaptive repair to be an interplay of cell death, endothelial dysfunction, tubular epithelial cell senescence, inflammatory processes and more—terminating in fibrosis. Various pathological mechanisms have been discovered and reveal targets for potential interventions. Furthermore, there have been clinical efforts measures for AKI prevention and progression including the development of novel biomarkers and prediction models. In this review, we provide an overview of pathophysiological mechanisms involved in kidney fibrosis. Furthermore, we discuss research gaps and promising therapeutic approaches for AKI to CKD progression.