Early Chronic Kidney Disease Research Articles

Long‐term myocardial DNA methylation and metabolomic responses to exertional heat stroke in mice

Epidemiological studies indicate that exposure to exertional heat stroke (EHS) can increase the risk of all‐cause cardiovascular and systemic disease and promote early mortality. Using a preclinical mouse model of EHS, we previously characterized profound DNA methylation changes in immune cells at 30 d of recovery and severe cardiometabolic disturbances in the ventricular myocardium (VM) at 9‐14 d. These observations indicate that a single exposure to EHS can result in long‐term epigenetic and metabolic alterations. However, whether a long‐term epigenetic responses occur in the VM and or whether cardiometabolic perturbations persist is unknown.PURPOSETo determine if long‐term alterations to (1) DNA methylation and (2) the metabolome occur within the VM after 30 d of recovery from EHS and (3) whether epigenetic alterations predict imbalances within the metabolome.METHODSSixteen C57BL6 female mice underwent a standardized EHS protocol using a forced running wheel (environmental temp: 37.5°C, 40% humidity) or a matched exercise control trial (EXC) (22.5°C). The EHS mice achieved peak core temps of ~42.4°C, accompanied by transient loss of consciousness. Mice were sacrificed after 30 d of recovery; left ventricles were isolated and frozen in liquid nitrogen for DNA methylation sequencing and untargeted metabolomics.RESULTSFollowing 30 d of recovery from EHS, more than 6,000 differentially methylated cytosines (DMCs) were observed within promoter regions; 900 differentially methylated regions (DMRs) were also observed (i.e ≥ 5 differentially DMCs within 300 base pairs) at (Q < 0.05) compared to EXC. Pathway analysis of promoter DMRs indicated changes in genes that modulate basic cell functions, DNA binding, transcription, and metabolism. Cardiometabolic perturbations were found to largely resolve compared to observations at 9‐14 d. Some metabolic disturbances remained, e.g. reductions in α‐ketoglutarate and increases in several lipid intermediates. These remnant alterations are known to be common in early onset heart failure and chronic kidney disease. Repressive DMCs (P < 0.05) were observed within transcriptional regulatory regions of enzymes that regulate α‐ketoglutarate, e.g. isocitrate dehydrogenase 1 & 2 (IDH1 & IDH2), suggesting a potential link with metabolomic findings.CONCLUSIONSA single EHS episode results in a robust epigenetic response in VM when observed at 30 d of recovery, whereas all but a subset of metabolites within the VM had fully recovered. These long‐term molecular changes may induce altered or maladaptive physiological outcomes in response to future environmental or medical challenges.

Early Identification of CKD—A Scoping Review of the Global Populations

IntroductionDecisions on whether to screen for chronic kidney disease (CKD) or not remain contentious in nephrology. This study provides a global overview of early CKD identification efforts.MethodsGuidelines for scoping reviews were followed and studies were identified by searching MEDLINE, EMBASE, Cochrane Library, CINAHL, ISI Web of Science, and PsycINFO. Data extracted from included studies focused on the following 4 themes: study population, measurement methods, interventions used, and available policies.ResultsWe identified 290 CKD screening and detection programs from 83 countries. Overall sample size was 3.72 million (North East Asia: 1.19 million), detection of CKD was the aim in 97.6%, 63.1% used population-based screening methods, and only 12.4% were in rural populations. Reported CKD prevalence (stages 3–5) was higher in targeted- (14.8%) than population-based studies (8.0%). Number of persons needed to screen (NNS) to identify 1 case was also lower in targeted studies (7 vs. 13). Single measurements (80%) and the combination of estimation of glomerular filtration rate with a urine test (albuminuria/proteinuria) (71.4%) were frequently used to detect CKD. Only 2.8% of studies included an intervention such as pharmacotherapy in identified cases. Policies on early identification were available in 30.1% of countries included.ConclusionMethods for early CKD identification vary worldwide, often leading to wide variations in the reported prevalence. Efforts to standardize measurement methods for early detection focusing on high-risk populations and ensuring appropriate interventions are available to those identified with CKD will improve the value of programs and improve patient outcomes.

High concentration of symmetric dimethylarginine is associated with low platelet reactivity and increased bleeding risk in patients with acute coronary syndrome

BackgroundDual antiplatelet therapy (DAPT) prevents ischemic events in patients with acute coronary syndrome (ACS), but is associated with increased risk of bleeding events. Symmetric dimethylarginine (SDMA) is one of nitric oxide (NO)-related pathway metabolites and stands as a promising biomarker of early chronic kidney disease (CKD) and cardiovascular diseases (CVDs). ObjectivesOur study evaluated the role of SDMA in predicting bleeding events in patients after ACS treated with DAPT. MethodsWe compared plasma concentrations of NO-related pathway metabolites in patients with ACS (n = 291) and investigated the prognostic value of SDMA as a bleeding predictor during 1-year follow-up. We measured the metabolites concentration using ultra performance liquid chromatography. Platelet reactivity was determined using impedance aggregometry. ResultsPatients with the highest quartile (4th) of SDMA concentration had significantly lower platelet aggregation compared to those in the 1st-3rd quartiles of SDMA, based on ADP + PGE1-, AA-, and ADP-induced platelet reactivity tests (p = 0.0004, p = 0.002, p = 0.014, respectively). Patients with major or minor bleeding events had significantly higher concentrations of SDMA as compared to those without bleeding events or to those with minimal bleeding events (p = 0.019, p = 0.019, respectively). ConclusionHigher SDMA concentration is associated with lower platelet reactivity and is associated with major and minor bleeding events in patients with ACS on DAPT. Therefore, SDMA stands as a potential biomarker for individualization of duration and potency of antiplatelet therapies in the ACS population at high risk of bleeding complications.

One-third of patients with lupus nephritis classified as complete responders continue to accrue progressive renal damage despite resolution of proteinuria

ObjectiveTreatment response in lupus nephritis (LN) is defined based on proteinuria, yet protocol kidney biopsy studies have shown that patients with lupus can have active nephritis in the absence of...

State-of-the-art Medical Therapy Versus Roux-en-Y Gastric Bypass Alone for Treatment of Early Diabetic Kidney Disease

Type 2 diabetic kidney disease (DKD) is the most common global cause of kidney disease and failure. Obesity is a major risk factor for DKD due to its causal relationship with diabetes, hypertension, and other factors promoting kidney disease. We thereforeinvestigated whether metabolic surgery such as Roux-en-Y gastric bypass is more effective than state-of-the-art medical therapy(i.e., renin-angiotensin-aldosterone system, sodium-glucose co-transporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists) in treating DKD. In a post hoc analysis of the Microvascular Outcomes after Metabolic Surgery trial, we compared the likelihood of regression of microalbuminuria as the primary endpoint and other renal and metabolic secondary endpoints in a population of patients with obesity, type 2 diabetes, microalbuminuria, and early chronic kidney disease followed for 24months. Nine patients underwent Roux-en-Y gastric bypass, and 24 patients were on state-of-the-art medical therapy. The gastric bypass arm had a significantly higher rate of regression of microalbuminuria (P<.001), borderline significant reduction in mean urine albumin-to-creatinine ratio (P=.055), and much greater weight loss (P=.001). There were no statistically significantdifferences between arms in estimated glomerular filtration rate, risk of developing estimated glomerular filtration rate <60mL/min/1.73m2 over 5years, mean hemoglobin A1c, systolic blood pressure, low-density lipoprotein cholesterol, or the American Diabetes Association triple endpoint. We found that metabolic surgery offers more kidney protection than state-of-the-art triple therapy for DKD at 24months. Prospective studies in this area are necessary to better define the benefits and risks of medical versus surgical treatment of DKD.

Diabetic kidney disease and risk of incident stroke among adults with type 2 diabetes

BackgroundData on the relations between kidney function abnormalities and stroke in type 2 diabetes are limited. We evaluated the associations of kidney function abnormalities and chronic kidney disease (CKD) stages with incident stroke in a large sample of adults with type 2 diabetes.MethodsParticipants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study without history of stroke at baseline were included. Urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were assessed at baseline. CKD categories were defined according to the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) for stroke in relation to measures of kidney function and CKD categories.ResultsA total of 9170 participants (mean age 62.8 [SD: 6.6] years, 38.2% women, 62.9% white) were included. Over a median follow-up of 4.9 years (interquartile range: 4.0–5.7), 156 participants developed a stroke (incidence rate 3.6/1000 person-years [95% CI 3.0–4.2]). After adjusting for relevant confounders, higher UACR and lower eGFR were each associated with increased risk of stroke. Compared to UACR < 30 mg/g, moderate albuminuria and severe albuminuria were associated with increasing hazards for stroke (HR 1.61 [95% CI 1.12–2.32] and 2.29 [95% CI 1.39–3.80], respectively). Compared to eGFR of ≥ 60 mL/min/1.73 m2, decreased eGFR (eGFR < 60 mL/min/1.73 m2) was associated with higher risk of stroke (HR 1.50, 95% CI 0.98–2.29). Compared to no CKD, worsening CKD stage was associated with an increasing risk of stroke (HRs of 1.76 [95% CI 1.10–2.83] for CKD G1, 1.77 [95% CI 1.13–2.75] for CKD G2, and 2.03 [95% CI 1.27–3.24] for CKD G3).ConclusionsIn a large sample of adults with type 2 diabetes, increasing albuminuria and worsening stages of early CKD were independently associated with higher risk of incident stroke.Trial registrationClinicalTrials.gov. Identifier: NCT00000620.

Associations between dietary patterns and stages of chronic kidney disease

BackgroundStudies have revealed that patients with chronic kidney disease (CKD) have dietary patterns different from those of the general population. However, no studies have compared the dietary patterns of between patients with early-stages (stages 1–3a) and late-stages (stages 3b–5) of CKD. Our objective was to investigate the associations between dietary patterns in early and late-stage CKD.MethodsWe analyzed 4480 participants with CKD at various stages based on the data recorded between 2007 and 2016 from the database of the American National Health and Nutrition Examination Survey.ResultsIn total, 3683 and 797 participants had early and late-stage CKD, respectively. Through principal components analysis, the dietary intake dimension was reduced from 63 variables to 3 dietary patterns. We adopted logistic regression for analysis. The three dietary patterns are as follows: (1) saturated fatty acids and mono-unsaturated fatty acids (MUFA); (2) vitamins and minerals; and (3) cholesterols and polyunsaturated fatty acids (PUFA). These 3 patterns explained > 50% of dietary nutrient intake. Results indicated that among participants with dietary patterns 2 (vitamins and minerals) and 3 (cholesterols and PUFA), those with low intakes were more likely to have late-stage CKD. The odds ratios for patterns 2 and 3 were 1.74 (95% CI: 1.21–2.50) and 1.66 (95% CI: 1.13–2.43), respectively.ConclusionsThis study revealed that intakes of vitamins and minerals and cholesterols and PUFA were associated with the stages of CKD.

A Lifestyle Intervention to Delay Early Chronic Kidney Disease in African Americans With Diabetic Kidney Disease: Pre-Post Pilot Study.

BackgroundBehavioral factors, such as lifestyle, have been shown to explain approximately 24% of the excess risk of chronic kidney disease (CKD) among African Americans. However, there are limited intervention studies culturally tailored to African Americans with type 2 diabetes mellitus and CKD.ObjectiveThe main objective of this study was to examine the feasibility and preliminary efficacy of a culturally tailored lifestyle intervention among African Americans with type 2 diabetes mellitus and CKD.MethodsA pre-post design was used to test the feasibility of a lifestyle intervention in 30 African American adults recruited from the Medical University of South Carolina between January 2017 and February 2017. A research nurse delivered the manualized study intervention weekly for 6 weeks. Clinical outcomes (hemoglobin A1c, blood pressure, and estimated glomerular filtration rate [eGFR]) were measured at baseline and postintervention. Disease knowledge, self-care, and behavior outcomes were also measured using validated structured questionnaires at baseline and postintervention. Descriptive statistics and effect sizes were calculated to determine clinically important changes from baseline.ResultsSignificant pre-post mean differences and decreases were observed for hemoglobin A1c (mean 0.75%, 95% CI 0.16-1.34; P=.01), total cholesterol (mean 16.38 mg/dL, 95% CI 5.82-26.94; P=.004), low-density lipoprotein (mean 13.73 mg/dL, 95% CI 3.91-23.54; P=.008), and eGFR (mean 6.73 mL/min/1.73m2, 95% CI 0.97-12.48; P=.02). Significant pre-post mean differences and increases were observed for CKD self-efficacy (mean −11.15, 95% CI −21.55 to −0.75; P=.03), CKD knowledge (mean −2.62, 95% CI −3.98 to −1.25; P<.001), exercise behavior (mean −1.21, 95% CI −1.96 to −0.46; P=.003), and blood sugar testing (mean −2.15, 95% CI −3.47 to −0.83; P=.003).ConclusionsThis study provides preliminary data for a large-scale appropriately powered randomized controlled trial to examine a culturally tailored lifestyle intervention in African Americans with type 2 diabetes mellitus and CKD in order to improve clinical, knowledge, self-care, and behavior outcomes in this population.

Quality of life and cognitive assessment in healthy older Asian people with early and moderate chronic kidney disease: The NAHSIT 2013-2016 and validation study.

Taiwan has the highest prevalence of chronic kidney disease (CKD). Impaired cognition and quality of life are significant phenomena in the late stages of CKD. We sought to obtain an overview and the attributable effect of impaired glomerular filtration on multiple domains in cognition and dimensions of quality of life for community-based healthy older adults in Taiwan. The study was derived from the Nutrition and Health Survey in Taiwan (NAHSIT) 2013-2016, a nationwide cross-sectional study conducted to sample healthy, community-based older adults aged ≥65 years in Taiwan. Participants were categorized into four CKD groups: CKD stage 1, stage 2, stages 3a and 3b, and stages 4-5. The Mini-Mental State Examination (MMSE) and the QoL questionnaire derived from the 12-item Short Form Health Survey (SF-12) were measured. Generalized linear mixed models (GLMMs) and principal component regressions were employed for the analysis and validation, respectively. Participants with moderate CKD (stages 3a and 3b) showed deficits in global MMSE, domain orientation to time, calculation, complex commands, and role-physical and vitality in QoL questionnaires. In GLMMs, impaired eGFR per 30 mL/min/1.73 m² was associated with lower global MMSE scores (β = -0.807, standard error [SE] = 0.235, P = 0.0007), domain orientation to time (β = -0.155, SE = 0.047, P = 0.0011), calculation (β = -0.338, SE = 0.109, P = 0.0020), complex commands (β = -0.156, SE = 0.079, P = 0.0494), and role-physical (β = -2.219, SE = 0.779, P = 0.0046) dimensions of QoL. Elderly Han Chinese adults with moderately impaired renal filtration could manifest cognitive deficits in orientation to time, calculation, and impaired quality of life in physical role functioning.

Low Turnover Renal Osteodystrophy With Abnormal Bone Quality and Vascular Calcification in Patients With Mild-to-Moderate CKD

IntroductionLimited information is available on renal osteodystrophy (ROD) and vascular calcification (VC) during early chronic kidney disease (CKD). This study was designed to evaluate ROD and VC in 32 patients with CKD stages II to IV.MethodsPatients underwent dual-energy X-ray absorptiometry (DXA) for assessment of bone mineral density (BMD) and trabecular bone score (TBS), thoracic computed tomography for VC scoring using the Agatston method, and anterior iliac crest bone biopsy for mineralized bone histology, histomorphometry, and Fourier transform infrared spectroscopy (FTIR). Classical and novel bone markers were determined in the blood.ResultsMean estimated glomerular filtration rate (eGFR) was 44 ± 16 ml/min per 1.73 m2. Of the patients, 84% had low bone turnover. In Whites, eGFR correlated negatively with the turnover parameter activation frequency (Ac.f) (r −0.48, P = 0.019) and with parameters of bone formation. Most patients had VC (>80%) which correlated positively with levels of phosphorus, c-terminal fibroblast growth factor-23, and activin. Aortic calcifications (ACs) correlated negatively with bone formation rate (BFR) and Ac.f (rho −0.62, −0.61, P < 0.001). TBS correlated negatively with coronary calcification (rho −0.42, P = 0.019) and AC (rho −0.57, P = 0.001). These relationships remained after adjustment of age. The mineral-to-matrix ratio, an FTIR metric reflecting bone quality, was negatively related to Ac.f and positively related to AC.ConclusionLow bone turnover and VC are predominant in early stages of CKD. This is the first study demonstrating mineral abnormalities indicating reduced bone quality in these stages of CKD.

The efficacy of rehabilitation for elderly chronic kidney disease patients: a retrospective, single-center study.

As the geriatric population is growing rapidly, so is the prevalence of chronic kidney disease (CKD). Suitable rehabilitation programs are needed to decrease disability and improve functionality to maintain independence in activities of daily life. To assess the impact of CKD on the efficacy of rehabilitation in the geriatric population. Retrospective single-center cohort study, demographic and clinical data of 190 elderly, non-dialysis dependent CKD patients, who underwent rehabilitation, during 2016-2020 were analyzed. Early CKD patients had longer duration of rehabilitation as compared with advanced CKD (32.6 ± 19.5 vs. 25.1 ± 17.6days, p = 0.011) and tended to be more independent at discharge (37.2% vs. 27.9%, respectively; p < 0.001). Duration of rehabilitation, Mini-Mental State Examination (MMSE), Functional Independence Measurement (FIM) admission and estimated GFR were important predictors of FIM at discharge. Age was negatively correlated with admission FIM, eGFR, MMSE, and discharge FIM. The odds ratio for mortality among patients with advanced as compared to early CKD was 2.197 (CI 95% 1.159-4.166, p = 0.015). Existing rehabilitation programs raise questions of suitability for the consistently aging population, play an indispensable part in the goal of achieving functional independence in the elderly and should promote further investigation of the efficacy of rehabilitation for CKD patients. Advanced CKD was associated with lower FIM at admission and discharge, shorter duration of rehabilitation and more dependence at discharge, as compared to patients with early CKD. Implementing a multidisciplinary team, focused on the specific needs of geriatric CKD patients, with clear, objective parameters and goals may lead to better rehabilitative outcomes, with decreased public and private costs of ongoing care.

Adding creatinine to routine pregnancy tests: a decision tree for calculating the cost of identifying patients with CKD in pregnancy.

Even in its early stages, chronic kidney disease (CKD) is associated with adverse pregnancy outcomes. The current guidelines for pregnancy management suggest identifying risk factors for adverse outcomes but do not mention kidney diseases. Since CKD is often asymptomatic, pregnancy offers a valuable opportunity for diagnosis. The present analysis attempts to quantify the cost of adding serum creatinine to prenatal screening and monitoring tests. The decision tree we built takes several screening scenarios (before, during and after pregnancy) into consideration, following the hypothesis that while 1:750 pregnant women are affected by stage 4-5 CKD and 1:375 by stage 3B, only 50% of CKD cases are known. Prevalence of abortions/miscarriages was calculated at 30%; compliance with tests was hypothesized at 50% pre- and post-pregnancy and 90% during pregnancy (30% for miscarriages); the cost of serum creatinine (production cost) was set at 0.20 euros. A downloadable calculator, which makes it possible to adapt these figures to other settings, is available. The cost per detected CKD case ranged from 111 euros (one test during pregnancy, diagnostic yield 64.8%) to 281.90 euros (one test per trimester, plus one post-pregnancy or miscarriage, diagnostic yield 87.7%). The best policy is identified as one test pre-, one during and one post-pregnancy (191.80 euros, diagnostic yield 89.4%). This study suggests the feasibility of early CKD diagnosis in pregnancy by adding serum creatinine to routinely performed prenatal tests and offers cost estimates for further discussion.

Hyperparathyroidism and Associated Factors in Chronic Kidney Disease

Background: The normal axis of calcium, phosphorus, vitamin D, and intact parathyroid hormone (iPTH) come under stress when chronic kidney disease (CKD) progresses beyond stage 3(GFR&lt;30 ml/kg/1.732). This results in increased secretion of iPTH which is known as secondary hyperparathyroidism. This exacerbates further if simultaneous deficiency of nutritional vitamin D (Cholecalciferol) is also found. Secondary hyperparathyroidism results in vascular calcification and increases cardiac mortality. Early intervention in form of dietary modification (low phosphorus, low potassium), correcting vitamin D deficiency along with the addition of active vitamin D (calcitriol) would help in alleviating patients’ suffering and saving costs as well.&#x0D; Material and method: This study was conducted from Jan 2017 to Jan 2018 at The Indus Hospital, Karachi with the age group ≥14 years of either gender who were suffering from chronic kidney disease (CKD). Patients on dialysis, chronic liver disease, and vitamin D supplementation were excluded. Their history, demographic, BMI, Calcium, Phosphorus, Alkaline Phosphatase, 25-Hyydorxyvitamin D, albumin, and intact parathyroid hormone (iPTH) were all noted.&#x0D; Results: 265 patients were enrolled for final analysis in this data with a male to female ratio of 1:1.03 (146/121). Hyperparathyroidism (iPTH&gt; 68 pg/ml) was seen in 190 (71.2%) patients. Mean values of all quantitative variables were not statistically significant when compared hyper parathyroid with normal parathyroid. Hyperparathyroidism was found significant in late CKD in comparison to early CKD (P-value &lt;.001), While vitamin D deficiency was significantly associated with hyperparathyroidism in early CKD but not in late CKD.&#x0D; Conclusion: Hyperparathyroidism is significantly present in CKD which is contributed by CKD progression and vitamin D deficiency.

Vitamin K Supplementation in Chronic Kidney Disease Patients: Where is the Evidence?

Vascular calcification (VC) is highly prevalent in Chronic Kidney Disease (CKD) patients, progresses gradually with deterioration of kidney function and is a strong, independent predictor of cardiovascular (CV) mortality. Matrix Gla Protein (MGP), the most potent inhibitor of VC, requires vitamin K as a co-factor to become biologically active. Accumulating epidemiological data have associated vitamin K depletion with VC progression and CV outcomes. CKD patients are characterized by poor vitamin K status and at the same time, pronounced CV calcification. In early and advanced CKD, including end-stage kidney disease, exogenous supplementation of vitamin K (especially with menaquinone 7, its most bioavailable form) might decrease the inactive form of MGP (dephosphorylated, uncarboxylated MGP) and probably retard the progression or even reverse VC. Here, we focus and discuss the interventional human studies of vitamin K supplementation in CKD patients and suggest future directions in this area of interest.

Blood Plasma Metabolites in Diabetes-Associated Chronic Kidney Disease: A Focus on Lipid Profiles and Cardiovascular Risk.

BackgroundWe investigated a cross-sectional metabolomic analysis of plasma and urine of patients with early and late stage diabetes associated chronic kidney disease (CKD), inclusive of stages 1–5 CKD, to identify potential metabolomic profiles between the two groups.MethodsThis cross-sectional study recruited 119 adults. Metabolomic biomarkers were quantified in 119 non-fasted plasma and 57 urine samples using a high-throughput proton Nuclear Magnetic Resonance platform. Analyses were conducted using R with the ggforestplot package. Linear regression models were minimally adjusted for age, sex, and body mass index and p-values were adjusted for multiple comparisons using the Benjamini-Hockberg method with a false discovery rate of 0.05.ResultsApolipoprotein A1 concentration (ApoA1) was reduced (adj. p = 0.04) and apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoA1) was increased (adj. p = 0.04) in late CKD compared with early CKD. Low-density lipoprotein triglyceride (LDL-TG) had an increased concentration (adj. p = 0.01), while concentrations of high-density lipoprotein cholesterol (HDL-C) were reduced (adj. p = 0.04) in late CKD compared to early stages of disease.ConclusionOur results highlight the presence of abnormal lipid metabolism namely significant reduction in the protective ApoA1 and significant increase in atherogenic ApoB/ApoA1 ratio. The study also demonstrates significantly elevated levels of triglyceride-rich lipoproteins such as LDL-TG. We illustrate the significant reduction in protective HDL-C in individuals with diabetic CKD. It explores a detailed plasma lipid profile that significantly differentiates between the late and early CKD groups as well as each CKD stage. The study of complex metabolite profiles may provide additional data required to enable more specific cardiovascular risk stratification.

Renal biomarkers in cats: A review of the current status in chronic kidney disease.

Serum creatinine concentration, the classical biomarker of chronic kidney disease (CKD) in cats, has important limitations that decrease its value as a biomarker of early CKD. Recently, serum symmetric dimethylarginine concentration was introduced as a novel glomerular filtration rate biomarker for the early detection of CKD in cats. However, data on its specificity are still limited. The limitations of conventional biomarkers and the desire for early therapeutic intervention in cats with CKD to improve outcomes have prompted the discovery and validation of novel renal biomarkers to detect glomerular or tubular dysfunction. Changes in the serum or urinary concentrations of these biomarkers may indicate early kidney damage or predict the progression of kidney before changes in conventional biomarkers are detectable. This review summarizes current knowledge on renal biomarkers in CKD in cats, a field that has progressed substantially over the last 5 years.

Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis.

Inflammation and fibrosis play an important pathophysiological role in chronic kidney disease (CKD), with pro-inflammatory mediators and leukocytes promoting organ damage with subsequent fibrosis. Since chemokines are the main regulators of leukocyte chemotaxis and tissue inflammation, we performed systemic chemokine profiling in early CKD in mice. This revealed (C-C motif) ligands 6 and 9 (CCL6 and CCL9) as the most upregulated chemokines, with significantly higher levels of both chemokines in blood (CCL6: 3–4 fold; CCL9: 3–5 fold) as well as kidney as confirmed by Enzyme-linked Immunosorbent Assay (ELISA) in two additional CKD models. Chemokine treatment in a mouse model of early adenine-induced CKD almost completely abolished the CKD-induced infiltration of macrophages and myeloid cells in the kidney without impact on circulating leukocyte numbers. The other way around, especially CCL9-blockade aggravated monocyte and macrophage accumulation in kidney during CKD development, without impact on the ratio of M1-to-M2 macrophages. In parallel, CCL9-blockade raised serum creatinine and urea levels as readouts of kidney dysfunction. It also exacerbated CKD-induced expression of collagen (3.2-fold) and the pro-inflammatory chemokines CCL2 (1.8-fold) and CCL3 (2.1-fold) in kidney. Altogether, this study reveals for the first time that chemokines CCL6 and CCL9 are upregulated early in experimental CKD, with CCL9-blockade during CKD initiation enhancing kidney inflammation and fibrosis.

FGF23-Klotho Axis and Fractures in Patients Without and With Early CKD: A Case-Cohort Analysis of CARTaGENE.

Whether fibroblast growth factor-23 (FGF23) and α-Klotho are associated with fractures, especially in chronic kidney disease (CKD), remains controversial. We evaluated how FGF23, α-Klotho, and traditional mineral parameters predict fractures in individuals with and without early CKD. We conducted a stratified case-cohort analysis using CARTaGENE, a population-based survey from Quebec, Canada. Individuals aged 40 to 69 years were selected according to outcome and CKD status (non-CKD: eGFR > 60 mL/min/1.73 m2; CKD stage 3: eGFR 30-60 mL/min/1.73 m2]). Baseline levels of c-terminal FGF23 (cFGF23), α-Klotho, parathyroid hormone (PTH), phosphate, and calcium were analyzed for associations with osteoporotic fracture incidence from recruitment (2009-2010) through March 2016. Adjusted Cox models were used, and predictors were treated linearly or flexibly using splines. A total of 312 patients (159 non-CKD; 153 CKD) were included; 98 had ≥ 1 fracture at any site during a median follow up of 70 months. Compared with non-CKD, CKD patients had increased levels of cFGF23 but similar levels of α-Klotho. cFGF23 was linearly associated with increased fracture incidence (adjusted HR = 1.81 [1.71, 1.93] per doubling for all participants). The association of α-Klotho with fracture followed a U-curve (overall P = 0.019) but was attenuated by adjustment for potential mediators (bone mineral density, phosphate, PTH). PTH and phosphate also had U-shaped associations with fracture. Associations were mostly similar between non-CKD and CKD. Adjustment for cFGF23 strongly attenuated the association between CKD status and fractures. cFGF23 is associated linearly with fracture incidence while α-Klotho, PTH, and phosphate levels have a U-shaped association.

Commentary on the 2020 update of the KDOQI clinical practice guideline for nutrition in chronic kidney disease.

Commentary on the 2020 update of the KDOQI clinical practice guideline for nutrition in chronic kidney disease.

POS-313 Screening for CKD in a rural population in the Himalayan foothills of India

In India, given its huge population and rapid rise in chronic kidney disease (CKD) risk factors such as diabetes and hypertension, the rising incidence of CKD is likely to pose major problems for both healthcare and economy in future years. Unfortunately, there is paucity of information on CKD screening programs in rural India. The main objective of this pilot study was to test the effectiveness of a targeted screening program for early stages CKD in Manali, Himachal Pradesh (HP).