Chronic Kidney Disease In Adults Research Articles

MO539HEMATOLOGIC EFFICACY OF VADADUSTAT FOR ANEMIA IN PATIENTS WITH KIDNEY FAILURE ON DIALYSIS

Abstract Background and Aims Vadadustat is a small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase being developed for treatment of anemia associated with chronic kidney disease (CKD). The vadadustat phase 3 program includes four efficacy and cardiovascular safety outcome trials of vadadustat versus the erythropoiesis-stimulating agent (ESA) darbepoetin alfa. Here we describe detailed results on hematologic efficacy in two of the four phase 3, randomized, open-label, sponsor-blind trials (the INNO2VATE trials) in adult patients with dialysis-dependent (DD) CKD and anemia, where vadadustat met prespecified noninferiority criteria compared with darbepoetin alfa with respect to cardiovascular safety and correction/maintenance of hemoglobin (Hb) target concentrations. Method The mean screening Hb range for the incident DD-CKD trial (NCT02865850) was 8.0-11.0 g/dL; for the prevalent DD-CKD trial (NCT02892149), it was 8.0-11.0 g/dL in the United States (US) and 9.0-12.0 g/dL for non-US. Patients in the incident and prevalent DD-CKD trials had initiated dialysis within <16 weeks with limited or no prior ESA exposure and >12 weeks with established ESA treatment prior to screening, respectively. Vadadustat starting dose was 300 mg/day for all patients, whereas initial darbepoetin alfa dose depended on each patient’s prior dose or product label. Both vadadustat and darbepoetin alfa doses were titrated according to prespecified dosing algorithms to achieve target Hb concentrations (US: 10-11 g/dL; non-US: 10-12 g/dL) during the primary evaluation period (PEP; weeks 24-36) and the secondary evaluation period (SEP; weeks 40-52). Herein, we present topline results from PEP and SEP endpoints, as well as other, more detailed hematologic erythrocyte parameters. Results A total of 3923 patients (369 with incident DD-CKD and 3554 with prevalent DD-CKD) were randomized 1:1 to vadadustat or darbepoetin alfa. Vadadustat was noninferior to darbepoetin alfa in achieving target-range Hb concentrations (primary efficacy endpoint) among patients who were new to, or established on, dialysis. The respective proportions of patients (vadadustat vs. darbepoetin alfa) with an average Hb value within the geography-specific target range in the PEP and SEP were 43.6% versus 56.9% and 39.8% versus 41.0% in the incident trial and 49.2% versus 53.2% and 44.3% versus 50.9% in the prevalent dialysis trial. The proportion of patients who achieved an Hb increase >1.0 g/dL from baseline to week 52 was assessed only for the incident trial and was 84.0% (95% CI: 77.8%, 89.0%) for vadadustat versus 89.9% (95% CI: 84.7%, 93.8%) for darbepoetin alfa. Hematologic erythrocyte parameters at time points within the PEP and SEP are presented in Table 1. In the incident trial, reticulocyte count was slightly increased from baseline at 28 and 52 weeks for vadadustat, whereas for darbepoetin alfa, reticulocyte count was slightly decreased or unchanged in both trials. Erythrocyte mean corpuscular volume and erythrocyte mean corpuscular Hb showed increases by week 52 for both groups. Conclusion Vadadustat demonstrated similar profiles across erythrocyte parameters compared with darbepoetin alfa in the treatment of anemia associated with CKD in adults in both incident dialysis and prevalent dialysis settings.

Dietary Amino Acid Patterns Are Associated With Incidence of Chronic Kidney Disease

No findings are available regarding the association of the dietary amino acid (AA) intakes with the risk of chronic kidney disease (CKD) in adults. We aimed to assess the association between dietary AA patterns and incidence of CKD in adults. This study was conducted within the framework of Tehran Lipid and Glucose Study on 4,233 adults, who were free of CKD at baseline (2009-2011) and were followed for 3.1years (2011-2014). The principal component analysis was used based on 8 AA groups to characterize major AA patterns. Multivariable logistic regression models were used to estimate the risk of CKD across quartiles of dietary AA pattern scores. Three major AA patterns were extracted: (1) higher loads of branched-chain, alcoholic, and aromatic AAs; (2) higher loads of acidic AAs, proline, and lower load of alkaline AAs and small AAs; and (3) higher loads of sulfuric AAs and small AAs. The mean±standard deviation age of participants (45.9% male) was 39.4±11.7 at baseline and the incidence of CKD was 12.1% (513 cases) after 3.1 years of follow-up. The highest score of first dietary AA pattern tended to be associated with an increased risk of CKD (odds ratio=1.43, 95% confidence interval1.06-1.93); however, the second pattern was related to a decreased risk of CKD (odds ratio=0.71, 95% confidence interval: 0.52-0.97) in the multivariable model. These novel findings suggest that the dietary AA patterns may modify risk of CKD.

Autosomal dominant tubulointerstitial kidney disease: more than just HNF1β.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) refers to a group of disorders with a bland urinary sediment, slowly progressive chronic kidney disease (CKD), and autosomal dominant inheritance. Due to advances in genetic diagnosis, ADTKD is becoming increasingly recognized as a cause of CKD in both children and adults. ADTKD-REN presents in childhood with mild hypotension, CKD, hyperkalemia, acidosis, and anemia. ADTKD-UMOD is associated with gout and CKD that may present in adolescence and slowly progresses to kidney failure. HNF1β mutations often present in childhood with anatomic abnormalities such as multicystic or dysplastic kidneys, as well asCKD and a number of other extra-kidney manifestations. ADTKD-MUC1 is less common in childhood, and progressive CKD is its sole clinical manifestation, usually beginning in the late teenage years. This review describes the pathophysiology, genetics, clinical characteristics, diagnosis, and treatment of the different forms of ADTKD, with an emphasis on diagnosis. We also present data on kidney function in children with ADTKD from the Wake Forest Rare Inherited Kidney Disease Registry.

Hypertriglyceridemic waist phenotype and risk of chronic kidney disease in community-dwelling adults aged 60\u2009years and older in Tianjin, China: a 7-year cohort study

BackgroundThe hypertriglyceridemic waist (HTGW) phenotype has been proposed to be related to the occurrence and progression of chronic kidney disease (CKD). The ageing trend of the Chinese population continues to intensify, and elderly individuals are at high risk of CKD. The purpose of this study was to investigate the cross-sectional and longitudinal associations between the HTGW phenotype and the risk of CKD by following community-dwelling adults aged 60 years and older in Tianjin, China, for 7 years.MethodsThis study was an observational cohort study conducted between 2013 and 2019. Of 2050 participants aged 60 years and older who underwent an annual health examination in 2013, 1605 individuals with complete data were enrolled in the cross-sectional analysis. Among them, 1271 individuals were observed until 2019. Detailed follow-up records were available for 816 participants, of whom 600 participants without CKD at baseline were eligible for inclusion in the retrospective analysis. The HTGW phenotype was defined as a waist circumference of 90 cm or more and triglyceride concentrations of 2.0 mmol/L or more in males or a waist circumference of 85 cm or more and triglyceride concentrations of 1.5 mmol/L or more in females. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 and/or proteinuria (urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g). Multivariable logistic regression analyses were performed to evaluate the relationship between the HTGW phenotype and CKD.ResultsIn 2013, the prevalence of CKD among older adults was 31.03%, and the prevalence of CKD in the HTGW phenotype group was 37.81%. Over a 7-year observation period, 195 individuals developed CKD, with an incidence rate of 32.50%. Statistically significant associations were observed between the HTGW phenotype and CKD in older adults in both cross-sectional surveys and retrospective analyses, with odds ratios and 95% confidence intervals of 1.38 (95% CI: 1.03–1.86, P = 0.033) and 2.27 (95% CI: 1.30–3.97, P = 0.004), respectively, after adjustment for confounders.ConclusionsIn this community-based cohort study, the HTGW phenotype was confirmed to be independently associated with an increased risk of prevalent and incident CKD in older adults aged 60 years and above in Tianjin, China.

POS-287 TREATMENT BURDEN AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH NON–DIALYSIS-DEPENDENT ANAEMIA OF CHRONIC KIDNEY DISEASE RECEIVING ERYTHROPOIESIS-STIMULATING AGENTS: A SYSTEMATIC LITERATURE REVIEW

Anaemia of chronic kidney disease (CKD) is associated with morbidity, poor health-related quality of life (HRQoL) and increased mortality. Standard of care includes erythropoiesis-stimulating agents (ESAs), but they are not widely used in non–dialysis-dependent (NDD) patients, due to safety concerns. A broader assessment of patient-centric outcomes is needed. We performed a systematic literature review of treatments for anaemia of CKD in NDD patients. We report the treatment burden, including safety, and HRQoL in patients with NDD anaemia of CKD from ESA trials. We searched electronic databases and other sources to identify randomised controlled trials (phase 2+) for ESAs in the treatment of anaemia of CKD in adults. The search was not limited to outcomes or countries. Other criteria were English publications between database inception and 23 January 2020 (search date). We conducted risk of bias and descriptive assessments of study and patient characteristics, treatment burden and HRQoL. Overall, 4,024 abstracts were screened, and 325 publications were reviewed; 38 ESA NDD-CKD trials of 12,594 randomised patients with anaemia were included. Although 27 trials (71%) had a risk of bias based on quality appraisal, these were included in the descriptive analysis. Overall, 6/38 (16%) trials were phase 3, 24 (63%) were open-label, and 9 (24%) were double-blind. ESAs, such as darbepoetin alfa (DPO) and epoetin alfa, were investigated and often compared with an active comparator, such as other ESAs or iron. Four trials compared high/low haemoglobin (Hb) targets in both ESA treatment arms. Rescue therapy included iron use (45%; 17 trials) and RBC transfusion (3%; 1 trial). Across trials, the mean age was 46.0–84.4 years; baseline Hb range was 8.2–12.2 g/dL. Treatment burden (e.g. discontinuations and adverse events) was evaluated in the safety populations (n=13,082); the burden of treatment administration was not observed. Hypertension was reported frequently as an adverse event across treatment arms (up to 37% of patients) in 18 trials. Treatment discontinuation was reported in 27 trials; common reasons included adverse events, dialysis, treatment failure or other illnesses. The most commonly used HRQoL instruments were Short Form-36 (SF-36; 9 trials), EQ-5D (2 trials), Linear Analogue Self-Assessment (2 trials) and the KDQoL Questionnaire (2 trials). SF-36 scores were statistically significant for ESA vs. placebo as early as 8 weeks (1 trial) and through 1 year (1 trial), though domain-specific results were inconsistent across trials. HRQoL outcomes, such as changes in physical functioning and fatigue scores, were reported in 14 trials; 2 trials evaluated exercise capacity. HRQoL was generally maintained or showed clinically relevant improvements across instruments, particularly for patients receiving ESAs vs. other comparators. Hypertension, as an adverse event was common across treatment arms. Patient-reported treatment burden and HRQoL outcomes were not measured consistently. Questionnaire use was low; SF-36 was mostly frequently used, which is not specific to kidney disease/anemia of CKD. More consideration and consistency of patient-centric outcomes, including complementary evidence from observational studies, may help better understand the holistic impact of ESA treatment on clinical management.

POS-288 THE BURDEN OF HEART FAILURE IN PATIENTS WITH NON–DIALYSIS-DEPENDENT ANAEMIA OF CHRONIC KIDNEY DISEASE RECEIVING ERYTHROPOIESIS-STIMULATING AGENTS: A SYSTEMATIC LITERATURE REVIEW

Anaemia of chronic kidney disease (CKD) is associated with significant morbidity and increased mortality, particularly cardiovascular complications such as heart failure (HF). We performed a systematic literature review of the treatment options for anaemia of CKD in non-dialysis-dependent (NDD) patients. This abstract reports HF-related outcomes from clinical trials in patients with NDD anaemia of CKD. We identified randomised controlled trials (RCTs; phase 2+) for erythropoiesis-stimulating agents (ESAs) for the treatment of anaemia of CKD in adults, from electronic databases (Embase®, MEDLINE®, Cochrane library), grey literature and other sources. Outcomes were not used in the search to avoid excluding eligible trials. Other criteria were, English publications between database inception and 23 January 2020 (search date). Risk of bias was assessed using a quality appraisal checklist. Descriptive statistics assessed study and patient characteristics and HF-related outcomes in ESA trials. A total of 4,024 abstracts were screened and 325 full-text publications reviewed; 38 ESA RCTs that randomised 12,594 patients with NDD-CKD and anaemia met the inclusion criteria. Mean age range was 46.0–84.4 years; median study duration was 50.5 weeks. Most trials (24; 63%) were open-label; 9 (24%) were double-blind. Twenty-seven trials were determined to have a risk of bias but remained in the descriptive assessment. Comparative trials most often investigated darbepoetin alfa or its biosimilar (DPO; 12 trials), epoetin alfa (EPO A) or its biosimilar and recombinant human erythropoietin (16 trials) and continuous erythropoietin receptor activator (3 trials). HF-related outcomes were reported in 19 trials, including as the primary endpoint in 7 trials. HF occurrence as an adverse event (AE; 15 trials), change in left ventricular mass index (LVMI; 7 trials), and hospitalisation related to HF (1 trial) were reported. Heterogeneity in outcome definitions and reporting was observed. One trial comparing a low haemoglobin (Hb) target (9.0–11.0 g/dL) with low dose ESA vs. a high Hb target (11.0–13.0 g/dL) with DPO reported significant LVMI reduction from baseline in the high Hb group (−7.8 g/m2; 95% CI: −12.1 to −3.6 g/m2; P<0.001). Another study reported a significantly reduced LVMI (P=0.02) with EPO A (−5.7±14.2 g/m2) and DPO (−5.6±15.8 g/m2) vs. controls (no ESA); however, no difference in LVMI decrease was observed between treatment arms. One study included hospitalisation for congestive HF without renal replacement therapy as a component of the composite primary endpoint. Of the 222 composite events, 101 (45.5%) hospitalisations for congestive HF were reported in the high and low Hb EPO A treatment arms combined. The proportions of patients from the safety populations (n=13,082) with a congestive HF AE ranged from 0% to 9.0% across trials and treatment arms. Findings of this review suggested a potentially high occurrence of HF-related outcomes, such as LVMI reduction and hospitalisations. We observed substantial heterogeneity in the reporting and results of HF-related outcomes in ESA RCTs. Information from observational studies may also be needed to fully characterise the burden of HF in patients with NDD-CKD and anaemia on ESA treatment.

Chronic Kidney Disease Risk of Isolated Systolic or Diastolic Hypertension in Young Adults: A Nationwide Sample Based-Cohort Study.

BackgroundHypertension among young adults is common. However, the effect of isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), or systolic and diastolic hypertension (SDH) among young adults on chronic kidney disease (CKD) development is unknown.Methods and ResultsFrom a nationwide health screening database, we included 3 030 884 participants aged 20 to 39 years who were not taking antihypertensives at baseline examination in 2009 to 2010. Participants were categorized as having normal blood pressure (BP), elevated BP, stage 1 IDH, stage 1 ISH, stage 1 SDH, stage 2 IDH, stage 2 ISH, and stage 2 SDH. The primary outcome was incident CKD. A total of 5853 (0.19%) CKD events occurred. With normal BP as the reference, multivariable‐adjusted hazard ratios (HRs) (95% CIs) for CKD were 1.14 (95% CI, 1.04–1.26), elevated BP; 1.19 (95% CI, 1.10–1.28), stage 1 IDH; 1.24 (95% CI, 1.08–1.42), stage 1 ISH; 1.39 (95% CI, 1.28–1.51), stage 1 SDH; 1.88 (95% CI, 1.63–2.16), stage 2 IDH; 1.84 (95% CI, 1.54–2.19), stage 2 ISH; 2.70 (95% CI, 2.44–2.98), stage 2 SDH. The HRs for CKD were attenuated in the patients who were antihypertensive and began medication within 1 year of medical checkup than in those without antihypertensives.ConclusionsAmong Korean young adults, those with elevated BP, stage 1 IDH, stage 1 ISH, stage 1 SDH, stage 2 IDH, stage 2 ISH, and stage 2 SDH were associated with a higher CKD risk than those with normal BP. The CKD risk in ISH and IDH groups was similar but lower than that in the SDH group. Antihypertensives attenuated the risk of CKD in young adults with hypertension.

Obesity, Abdominal Obesity and Chronic Kidney Disease in Young Adults: A Nationwide Population-Based Cohort Study.

Obesity has become a pandemic. It is one of the strongest risk-factors of new-onset chronic kidney disease (CKD). However, the effects of obesity and abdominal obesity on the risk of developing CKD in young adults has not been elucidated. From a nationwide health screening database, we included 3,030,884 young adults aged 20–39 years without CKD during a baseline examination in 2009–2010, who could follow up during 2013–2016. Patients were stratified into five levels based on their baseline body mass index (BMI) and six levels based on their waist circumference (WC; 5-cm increments). The primary outcome was the development of CKD. During the follow up, until 2016, 5853 (0.19%) participants developed CKD. Both BMI and WC showed a U-shaped relationship with CKD risk, identifying the cut-off values as a BMI of 21 and WC of 72 cm in young adults. The obesity group (odd ratio [OR] = 1.320, 95% confidence interval [CI]: 1.247–1.397) and abdominal obesity group (male WC ≥ 90, female WC ≥ 85) (OR = 1.208, 95%CI: 1.332–1.290) showed a higher CKD risk than the non-obesity or non-abdominal obesity groups after adjusting for covariates. In the CKD risk by obesity composite, the obesity displayed by the abdominal obesity group showed the highest CKD risk (OR = 1.502, 95%CI: 1.190–1.895), especially in those under 30 years old. During subgroup analysis, the diabetes mellitus (DM) group with obesity or abdominal obesity paradoxically showed a lower CKD risk compared with the non-obesity or non-abdominal obesity group. Obesity and abdominal obesity are associated with increased risk of developing CKD in young adults but a decreased risk in young adults with diabetes.

Association between metabolic syndrome and incident chronic kidney disease among Chinese: A nation-wide cohort study and updated meta-analysis.

We prospectively examined the relationship between metabolic syndrome (MetS) and incident chronic kidney disease (CKD) among middle-aged and elderly Chinese, and conducted a systematic review and meta-analysis of all cohort studies on this topic. Our research data were derived from the China Health and Retirement Longitudinal Study. Participants (n=5752, age ≥45 years) without CKD (defined as estimated glomerular filtration rate <60ml/min/1.73m2 ) at baseline were followed up for 4 years. We applied logistic regressions to examine the association of MetS with incident CKD. In addition, we pooled our effect estimates and those from previous cohort studies in the meta-analysis. In a 4-years follow-up, 61 (4.27%) developed CKD in participants with MetS versus 102 (2.36%) in participants without MetS. After adjustment for potential confounders, odds ratio for incident CKD was 1.82 [95% confidence interval (95% CI): 1.19-2.78] comparing participants with MetS with those without MetS. There was a linear positive association between the number of MetS components and incident CKD (p for trend <0.001). In the updated meta-analysis of 25 studies among 350,655 participants with 29,368 incident cases of CKD, the pooled relative risk of developing CKD in participants with MetS was 1.34 (95% CI: 1.28-1.39), compared with those without MetS. Individuals with MetS had higher risk of incident CKD in middle-aged and elderly Chinese adults, which was supported by a comprehensive review of cohort studies from multiple populations. It may be advisable to routinely monitor renal functions among individuals with MetS.

Chronic kidney disease: Definition, updated epidemiology, staging, and mechanisms of increased cardiovascular risk.

Chronic kidney disease: Definition, updated epidemiology, staging, and mechanisms of increased cardiovascular risk.

Obesity as a predictive factor for chronic kidney disease in adults: systematic review and meta-analysis.

Chronic kidney disease (CKD) is one of the main chronic diseases affecting the world population due to its high prevalence and increasing morbidity. Similarly, obesity gained the interest of the scientific community as it directly or indirectly increases mortality from cardiovascular causes, and its prevalence characterizes a pandemic. The objective of this study was to investigate obesity measured by body mass index as a predictor for end-stage renal disease in the general adult population. A systematic review and meta-analysis was carried out by searching 10 databases for prospective or retrospective cohort studies, with no restrictions on the language of publication, including adults with obesity without previous renal disease and who evolved to CKD (diagnosed by estimated glomerular filtration rate below 60 mL&mac_middot;min-1&mac_middot;(1.73 m2)-1 over the follow-up period. The R software and Meta package were used for data analysis. After removing duplicates, 5431 studies were submitted to the steps of the systematic review, and 21 articles were included in the data analysis. In total, 3,504,303 patients, 521,216 with obesity, and an average follow-up time of 9.86 years were included. The relative risk of obese people for developing CKD in the random effects model was 1.81 (95%CI: 1.52-2.16). The evidence found in this meta-analysis confirmed that obese people are at higher risk of developing CKD that the non-obese population (1.81 times higher), with obesity being a priority risk factor in preventive actions.

Diabetes drug to treat chronic kidney disease in adults has licence extension granted

Diabetes drug to treat chronic kidney disease in adults has licence extension granted

Epidemiological Clinical Profile of Chronic Kidney Disease in Adults under 50 at the University Hospital of Brazzaville

Introduction: Chronic Kidney Disease (CKD) is a major global public health problem. In Congo, we have very few studies on it. Patients and Methods: We carried out an analytical cross-sectional study with retrospective data collection including patients aged 18 to 49 years, hospitalized for CKD in the nephrology department of University Hospital of Brazzaville, during the period from January 1, 2016 to August 31, 2020. The variables considered were socio-demographic, clinical, paraclinical, therapeutic and evolutionary. The statistical test used was Pearson’s chi-square test. Results: CKD in those under 50 represented 21.1% of admissions and 35.6% of CKD. The mean age was 35.9 ± 8.4 years. There was a male predominance with a sex ratio of 1.27. Hypertension was the most common comorbidity (49.2%), followed by HIV (13.6%) and diabetes mellitus (13.2%). Stage 5 CKD was most prevalent (82.7%). Indeterminate kidney disease was in the order of 55.9%. The low socioeconomic level (74.9% of cases) hampered the achievement of dialysis in 66.3% of patients for whom this treatment was indicated. Failure to perform dialysis significantly influenced the occurrence of death (p-value = 0.005). Conclusion: CKD is common among people under 50 and more affects males with a high mortality rate due to lack of access to dialysis. The main causes are hypertension and HIV.

Initial and Recurrent Hyperkalemia Events in Patients With CKD in Older Adults: A Population-Based Cohort Study.

Background:The risk of hyperkalemia is elevated in chronic kidney disease (CKD); however, the initial and recurrent risk among older individuals is less clear.Objectives:We set out to examine the initial and 1-year recurrent risk of hyperkalemia by level of kidney function (estimated glomerular filtration rate, eGFR) in older adults (≥66 years old).Design:Population-based, retrospective cohort studySettings:Ontario, CanadaParticipants:905 167 individuals (≥66 years old) from 2008 to 2015.Measurements:Serum potassium valuesMethods:Individuals were stratified by eGFR (≥90, 60-89, 30-59, 15-29 mL/min/1.73 m2) and examined for the risk of incident hyperkalemia (K ≥ 5.5 mEq/L) using adjusted Cox proportional hazards models. The 1-year risk of recurrent hyperkalemia was examined using multivariable Andersen-Gill models.Results:Among a population of 905 167 individuals (15% eGFR ≥ 90, 58% eGFR 60-89, 25% eGFR 30-59, 3% eGFR 15-29) with a potassium measurement, there were a total of 18 979 (2.1%) individuals with hyperkalemia identified. The event rate (per 1000 person-years) and adjusted hazard ratio (HR) of hyperkalemia was inversely associated with eGFR (mL/min; eGFR >90 mL/min: 8.8, referent, 60-89 mL/min: 11.8 HR 1.41; eGFR 30-59: 39.8, HR 4.37; eGFR 15-29: 133.6, 13.65) and with an increasing urine albumin-to-creatinine ratio (ACR, mg/mmol; ACR< 3: 14, referent, ACR 3-30: 35.1, HR 1.98; ACR >30: 93.7, 4.71). The 1-year event rate and adjusted risk of recurrent hyperkalemia was similarly inversely associated with eGFR (eGFR ≥ 90: 10.1, referent, eGFR 60-89: 14.4, HR 1.47; eGFR 30-59: 54.8, HR 4.90; eGFR 15-29: 208.0, HR 12.98). Among individuals with a baseline eGFR of 30 to 59 and 15 to 29, 0.9 and 3.8% had greater than 2 hyperkalemia events. The relative risk of initial and recurrent hyperkalemia was marginally higher with RAAS blockade. Roughly 1 in 4 individuals with hyperkalemia required hospitalization the day of or within 30 days after their hyperkalemia event.Limitations:Limited to individuals aged 66 years and above.Conclusions:Patients with low eGFR are at a high risk of initial and recurrent hyperkalemia.Trial registration: N/A

Augmented transcripts of kidney injury markers and renin angiotensin system in urine samples of overweight young adults

Obesity has been firmly established as a major risk factor for common disease states including hypertension, type 2 diabetes mellitus, and chronic kidney disease. Increased body mass index (BMI) contributes to the activation of both the systemic and intra-tubular renin angiotensin systems (RAS), which are in turn associated with increased blood pressure (BP) and kidney damage. In this cross-sectional study, 43 subjects of normal or increased body weight were examined in order to determine the correlation of BMI or body fat mass (BFM) with blood pressure, fasting blood glucose (FBG), and urinary kidney injury markers such as interleukin-18 (IL-18), connective tissue growth factor (CTGF), neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 (KIM-1). Our results showed that: (1) subjects with increased body weight showed significantly higher BP, BFM, total body water and metabolic age; (2) BMI was positively correlated to both systolic (R2 = 0.1384, P = 0.01) and diastolic BP (R2 = 0.2437, P = 0.0008); (3) BFM was positively correlated to DBP (R2 = 0.1232, P = 0.02) and partially correlated to urine protein (R2 = 0.047, P = 0.12) and FBG (R2 = 0.07, P = 0.06); (4) overweight young adults had higher urinary mRNA levels of renin, angiotensinogen, IL-18 and CTGF. These suggest that BMI directly affects BP, kidney injury markers, and the activation of the intra-tubular RAS even in normotensive young adults. Given that BMI measurements and urine analyses are non-invasive, our findings may pave the way to developing a new and simple method of screening for the risk of chronic kidney disease in adults.

High-Fat Diet Induced Hedgehog Signaling Modifications during Chronic Kidney Damage.

Excessive consumption of dietary fats leads to the deposition of unnecessary metabolites and multiple organ damage. Lipids, important key regulators of Hedgehog signaling, are involved in triggering fibrotic chronic kidney disease. The present study encompasses the assessment of renal morphofunctional modifications and alteration of lipid metabolism influencing the changes in gene expression of hedgehog signaling pathway genes. Fifteen male Rattus norvegicus of 200 ± 25 grams weight were equally divided into three groups: control (standard rat chow), D-1 (unsaturated high-fat diet) and D-2 (saturated high-fat diet). Animals were provided with respective diets and were followed for 16 weeks. Both HFD-fed groups did not show overall body weight gain as compared to the control. While significant downregulation of hedgehog pathway genes was found in fatty diet groups. In comparison with the control group, Shh, Gli1, Gli2, and Gli3 were downregulated after the consumption of both unsaturated and saturated fatty diets. Ihh and Smo exhibit a similar downregulation in the D-1 group, but an upregulation was detected in the D-2 group. D-2 group also had an increased serum urea concentration as compared to the control (P = 0.0023). Furthermore, renal histopathology revealed tubular necrosis, glomerular edema, glomerular shrinkage, and hypocellularity. Collagen deposition in both HFD groups marks the extent of fibrosis summary figure. Extravagant intake of dietary fats impaired normal kidney functioning and morphofunctionally anomalous kidney triggers on Hh signaling in adult rats. These anomalies can be linked to an escalated risk of chronic kidney disease in adults strongly recommending the reduced uptake of fatty diets to prevent impaired metabolism and renal lipotoxicity.

Renal Function Is Preserved after Hematopoietic Stem Cell Transplantation for Sickle Cell Disease

Chronic kidney disease (CKD) is a common complication and a significant contributor to morbidity and mortality for patients with sickle cell disease (SCD). Hematopoietic stem cell transplantation (HSCT) is a curative strategy for SCD and potentially life-saving therapy. Though HSCT can reverse the SCD phenotype, acute and chronic kidney dysfunction may be an unintended consequence. The incidence of acute kidney injury (AKI) and the effect of different HSCT regimens on progression or amelioration of CKD in adults with SCD have not previously been reported. This cohort study analyzes prospectively collected data from 106 patients transplanted for SCD at the National Institutes of Health (NIH) Clinical Center, including HLA-matched sibling (N=71) and haploidentical HSCT (N=26) where nonmyeloablative conditioning was given, as well as gene therapy (N=9), where a myeloablative regimen was employed. Patients' renal function was assessed at baseline and annually thereafter for up to 3-years. We sought to define 1) the prevalence of CKD before and after HSCT 2) the incidence of CKD after HSCT 3) estimated glomerular filtration rate (eGFR) trends after HSCT 4) urine albumin to creatinine ratio (UACR) change after HSCT and 5) the incidence of AKI within 100 days of HSCT. We defined and staged AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria (stage 1: 1.5-1.9 times baseline serum creatinine increase or ≥0.3 mg/dl increase; stage 2: 2-2.9 times baseline; stage 3: 3 times baseline, increase in creatinine to ≥4.0 mg/dl, or initiation of renal replacement therapy). The baseline prevalence of CKD was 6% when defined conservatively (eGFR &amp;lt;60 ml/min/1.73m2); this prevalence did not change significantly post-HSCT. When using a more comprehensive definition of CKD (urine albumin to creatinine ratio (UACR) ≥30 mg/g OR eGFR &amp;lt;60 ml/min/1.73m2), 48% had CKD at baseline, 62% at 1 year, 55% at 2 years, and 55% at 3 years (with p=0.02, 0.26, 0.54 for longitudinal model comparing post-HCST prevalence to baseline). The incidence of CKD any time after HSCT was 1% and 11% according to each of these CKD definitions, respectively. 25% of participants had follow-up of ≤2 years, median follow-up was 3 years. The median eGFR remained within the normal range throughout the follow-up period but declined annually: the baseline median eGFR was 139.7 ml/min/1.73m2 and declined by 7.6, 11.6, and 20.9 ml/min/1.73m2 each year post-HSCT (p&amp;lt;0.0001). In an adjusted regression analysis, there was no association of gender, engraftment status, transplant regimen, or conditioning agent- specifically use of pentostatin, total body irradiation, or post-transplant cyclophosphamide- with worsening eGFR (p&amp;gt;0.05 for each variable). This eGFR trend represents an improvement in renal function toward the normal range: there was a statistically significant decrease in hyperfiltration (eGFR ≥150 ml/min/1.73m2), which was present in 34% patients at baseline but steadily declined to 12% by 3 years post-HSCT (p = 0.0006 for adjusted longitudinal model). There was a corresponding increase in patients with normal eGFR (60-149 ml/min/1.73m2) from 60% at baseline to 80% at 3 years post-HSCT. UACR showed an increase in the year following transplant that subsequently dissipated. Median UACR at baseline was 24.3 mg/g with annual follow-up median values of 62.2, 38.9 and 36.2 mg/g (p-values of 0.007, 0.41, and 0.69 for comparison to baseline from regression model of log transformed UACR). In our cohort, 58% of patients experienced AKI in the first 100 days post-HSCT; which is consistent with previous data. 77% of those were mild, stage 1; 13% were moderate, stage 2; and 10% were severe, stage 3 AKI. This study demonstrates that HSCT in patients with SCD is not associated with a significant increase in CKD incidence or prevalence at 2 and 3 years post-HSCT. While there is a substantial decline in eGFR from baseline to each annual follow-up, the proportion of patients whose eGFR was in the normal range increased and the prevalence of hyperfiltration decreased. The stability of UACR after an initial increase at the 1-year time point further suggests that even more mild renal damage may stabilize after transplant. Finally, AKI occurred in over half of the patients in our cohort, though the preponderance developed mild AKI. Disclosures Diamantidis: United Health Group: Membership on an entity's Board of Directors or advisory committees.

Chronic kidney disease in adults aged 18 years and older in Chile: findings from the cross-sectional Chilean National Health Surveys 2009-2010 and 2016-2017.

ObjectivesThis study estimates the prevalence of chronic kidney disease (CKD) among Chilean adults and examines its associations with sociodemographic characteristics, health behaviours and comorbidities.DesignAnalysis of cross-sectional data from the two most recent large nationally representative Chilean Health Surveys (Encuesta Nacional de Salud, ENS) 2009–2010 and 2016–2017.ParticipantsAdults aged 18+ years with serum creatine data (ENS 2009–2010: n=4583; ENS 2016–2017: n=5084).Primary and secondary outcome measuresReduced kidney function (CKD stages 3a–5) based on the estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m2) was the primary outcome measure. Using the urine albumin-to-creatinine ratio (ACR ≥30 mg/g), increased albuminuria was ascertained among adults aged 40+ years with diabetes and/or hypertension. Both outcomes were analysed using logistic regression with results summarised using OR. CKD prevalence (stages 1–5) among adults aged 40+ years was estimated including participants with an eGFR of >60 mL/min/1.73 m2 but with increased albuminuria (stages 1–2).ResultsOverall, 3.2% (95% CI: 2.4% to 3.8%) of adults aged 18+ in ENS 2016–2017 had reduced kidney function. After full adjustment, participants with hypertension (OR: 2.37; 95% CI: 1.19 to 4.74) and those with diabetes (OR: 1.66; 95% CI: 1.03 to 2.66) had significantly higher odds of reduced kidney function. In ENS 2016–2017, 15.5% (13.5% to 17.8%) of adults aged 40+ years with diabetes and/or hypertension had increased albuminuria. Being obese versus normal-weight (OR: 1.66; 95% CI: 1.08 to 2.54) and having both diabetes and hypertension versus having diabetes alone (OR: 2.30; 95% CI: 1.34 to 3.95) were significantly associated with higher odds of increased albuminuria in fully-adjusted analyses. At least 15.4% of adults aged 40+ years in ENS 2016–2017 had CKD (stages 1–5), including the 9.6% of adults at CKD stages 1–2.ConclusionsPrevention strategies and Chilean guidelines should consider the high percentage of adults aged 40 years and older at CKD stages 1–2.

Prevalence of chronic kidney disease in adults in England: comparison of nationally representative cross-sectional surveys from 2003 to 2016

ObjectivesTo identify recent trends in chronic kidney disease (CKD) prevalence in England and explore their association with changes in sociodemographic, behavioural and clinical factors.DesignPooled cross-sectional analysis.SettingHealth Survey for England 2003,...

Associations of accelerometer-measured physical activity and sedentary time with chronic kidney disease: The Framingham Heart Study.

BackgroundFew studies examined the individual and conjoint associations of accelerometer-measured physical activity (PA) and sedentary times with the prevalence of chronic kidney disease (CKD) among older adults.MethodsWe evaluated 1,268 Framingham Offspring Study participants (mean age 69.2 years, 53.8% women) between 2011 and 2014. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.732 and/or urine albumin-to-creatinine ratio (UACR) ≥25/35 μg/mg (men/women). We used multivariable logistic regression models to relate time spent being sedentary and active with the odds of CKD. We then performed compositional data analysis to estimate the change in the eGFR and UACR when a fixed proportion of time in one activity behavior (among the following: moderate to vigorous physical activity [MVPA], light intensity physical activity [LIPA], and sedentary) is reallocated to another activity behavior.ResultsOverall, 258 participants had prevalent CKD (20.4%; 120 women). Higher total PA ([MVPA+LIPA], adjusted-odds ratio [OR] per 30 minutes/day increase, 0.86; 95% CI, 0.78–0.96) and higher LIPA (OR per 30 minutes/day increase, 0.87; 95% CI, 0.76–0.99) were associated with lower odds of CKD. Additionally, higher sedentary time (OR per 30 minutes/day increase, 1.16; 95% CI, 1.04–1.29) was associated with higher odds of CKD. Reallocating 5% of the time from LIPA to sedentary was associated with the largest predicted difference in eGFR (-1.06 ml/min/1.73m2). Reallocating 1% of time spent in MVPA to sedentary status predicted the largest difference in UACR (14.37 μg/mg).ConclusionThe findings suggest that increasing LIPA and maintaining MVPA at the expense of sedentary time may be associated with a lower risk of CKD in community-based older adults.