Prevent Chronic Kidney Disease Progression Research Articles

High prevalence of unrecognized chronic kidney disease in the Lolland-Falster Health Study: a population-based study in a rural provincial area of Denmark.

Chronic kidney disease (CKD) affects 10-15% globally and is a marked independent risk factor for cardiovascular disease. Prevalence estimations are essential for public health planning and implementation of CKD treatment strategies. This study aimed to estimate the prevalence and stages of CKD in the population-based Lolland-Falster Health Study, set in a rural provincial area with the lowest socioeconomic status in Denmark. Additionally, the study characterized participants with CKD, evaluated the overall disease recognition, including the awareness of CKD and compared it with other common conditions. Cross-sectional data were obtained from clinical examinations, biochemical analyses, and questionnaires. CKD was defined as albuminuria (urine albumin-creatinine ratio ≥30 mg/g), estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m², or by a diagnosis in the National Patient Register. Patient awareness was assessed by self-reported CKD, and overall disease recognition by either a registered hospital diagnosis or self-reported CKD. Among 16 097 adults (median age 58.6 years), CKD prevalence was 18.0% (n = 2903), with 70.1% identified by albuminuria, 28.4% by reduced eGFR, and 1.5% by a registered diagnosis alone. Of those with CKD, 98.8% had stages 1-3 (eGFR ≥30 ml/min/1.73 m²), and 1.2% had stages 4-5 (eGFR <30 ml/min/1.73 m²). Female sex, comorbidities, smoking, and low socioeconomic parameters were independently associated with CKD. Patient awareness of CKD was 4.4%, compared to >50% for hypertension and >80% for diabetes, and the overall CKD recognition (self-reported or registered diagnosis) was 7.1%. Thus, in this population-based study, CKD was highly prevalent but poorly recognized, indicating great potential for preventing CKD progression and related complications.

E -cigarettes and kidney health: current knowledge and future perspectives.

Chronic conventional cigarette smoking has been closely linked to incident chronic kidney disease (CKD) in the general population. It is associated with the acceleration of pre-existing CKD and failure of kidney allograft function. Cessation of conventional cigarette smoking is effective in reducing the increased risk of smoking induced kidney damage. This narrative review summarizes current knowledge and future study perspectives of the impact of e-cigarettes (e-cigs) use on kidney health. The past decade has seen a dramatic increase in the use of electronic nicotine delivering systems, also called e-cigs. Compared to conventional cigarette smoking, little is known concerning the effects of e-cigs use on kidney health. A few cross-sectional studies suggest an association between vaping and kidney damage (albuminuria, reduction in estimated glomerular filtration rate) in adolescents and young adults. Furthermore, limited animal experiments indicate that e-cigs constituents/aerosols may lead to structural and functional kidney damage. The renal health effects of e-cigs remain largely uncertain and make it difficult to draw definitive conclusions about e-cigs use and kidney health. The relatively new popularity of e-cigs, the wide variability in device design and e-liquid formulations, and the lack of standardized methods to measure daily or life-long e-cigs exposure make it challenging to conduct comprehensive long-term studies. Nephrologists should actively address smoking habits in their patients and urge cessation of conventional cigarette smoking as well as e-cigs use to prevent CKD progression and improve overall health.

Efficacy of oral AB070597 for the management of chronic kidney disease in cats: a prospective, randomised, controlled parallel-group study.

It has been reported that AB070597, which contains amino acids and peptides, may prevent the progression of chronic kidney disease (CKD) in cats. The aim of this study was to evaluate the effect of AB070597 on CKD in International Renal Interest Society (IRIS) stage 2 or 3 cats compared with a placebo. A prospective, randomised, controlled parallel-group study was conducted on 35 cats with CKD. The cats were randomly allocated to receive 300 mg of AB070597 or placebo for 180 days, and cats were re-examined every 30 days. Changes in the results were compared from baseline to endpoint in each group, and the efficacy of AB070597 in cats with CKD was assessed. A total of 35 cats met the inclusion criteria, of which 20 received AB070597 and 15 received a placebo. Blood urea nitrogen (BUN), creatinine (Cre) and phosphorus levels increased significantly in the placebo group at 180 days compared with those at baseline, 30 days and 60 days, whereas these values were not significantly changed in the AB070597 group during the study period. The IRIS stage was also stable in cats with AB070597 from the baseline to the end of the study, whereas the IRIS stage progressed from stage 2 to stage 3 in 26% of cats with placebo. Body weight did not change significantly in either group. The administration of AB070597 in cats with CKD may be effective in preventing CKD progression.

Early Identification and Management of Chronic Kidney Disease: A Narrative Review of the Crucial Role of Primary Care Practitioners.

Early-stage (stage1-3) chronic kidney disease (CKD) has an asymptomatic presentation such that most people with CKD are unaware of their disease status and remain undiagnosed. CKD is associated with multiple long-term conditions (MLTC), or multimorbidity, the most common of these being cardiovascular disease, hypertension, and type2 diabetes. Primary care practitioners (PCPs) are crucial in the early identification and management of patients with CKD. For individuals at high risk of CKD, measurements of estimated glomerular filtration rate, urine albumin-creatinine ratio, and blood pressure should be obtained regularly and recorded in a timely manner. The importance of lifestyle changes in the prevention and management of CKD should also be highlighted. A recent addition to the treatment of CKD in people with and without type2 diabetes has been the recommendation by clinical practice guidelines of a sodium-glucose co-transporter2 (SGLT2) inhibitor alongside a renin-angiotensin-aldosterone system inhibitor as foundational therapy. SGLT2 inhibitors prevent CKD progression and reduce fatal and non-fatal kidney and cardiovascular events, hospitalization for heart failure, and all-cause mortality, and they have a favorable safety and tolerability profile. However, uptake has been slow, particularly in people with CKD without type2 diabetes. A multifaceted approach is required to ensure that people with CKD receive optimal kidney protection. Measures to raise awareness of the importance of early identification and intervention include local/national campaigns via social media and practice-based education; clinical education programs; integration of clinical decision support tools into electronic health records; detection programs built around electronic health records; and good interdisciplinary communication. PCPs at the forefront of multidisciplinary care are best placed to implement the evidence-based clinical practice CKD guidelines for lifestyle modification and guideline-directed medical therapy.

Renal denervation benefits in chronic kidney disease: An updated review

Hypertension (HTN) may not be properly controlled despite the ideal blood pressure (BP)-lowering drugs and good patient compliance. These scenarios emphasize the need for innovative approaches to treat HTN cases that are difficult to manage pharmaceutically. Numerous recent studies have documented the effectiveness of renal denervation (RDN) therapy in reducing sympathetic nerve system (SNS) overactivity. Although this therapy is invasive and expensive, its appropriate use in specific cases is still being refined.SNS overactivity is documented in HTN, chronic kidney disease (CKD), and end-stage renal disease patients. Over the past decade, RDN therapy has been used in different countries to treat HTN, with a positive response in most cases. However, some hospitals have no resources or interventionists to perform these procedures. Nonetheless, there is an increased number of physicians expressing interest in using RDN in sustained HTN therapy and prevention of CKD progression. There are no consensus guidelines worldwide; however, some societies have developed guidelines for using RDN based on updated information covering the BP-lowering mechanism, efficacy, patient selection, post- and preprocedural assessment, and procedural safety. In this review, we aimed to evaluate the effectiveness of the RDN procedure for treating HTN and prevention of CKD development and progression.

Investigating Interleukin-6 Levels in Type 2 Diabetes Mellitus Patients With and Without Diabetic Nephropathy.

Diabetic nephropathy (DN), a severe complication affecting 40% of diabetic individuals, is a leading cause of chronic kidney disease (CKD). It involves a progressive increase in urinary albumin and a decline in the glomerular filtration rate. Early detection and intervention are crucial to preventing CKD progression. The current marker, albuminuria, measured as the urine albumin-to-creatinine ratio (UACR), has limitations, highlighting the need for alternative biomarkers. Researchers have linked the proinflammatory cytokine interleukin-6 (IL-6) to the progression of DN, observing elevated levels in DN patients compared to those without DN. IL-6 also regulates glucose metabolism, promoting insulin effectiveness and secretion. Inflammation and glucose control are two things that IL-6 does. This makes it a promising biomarker and therapeutic target for DN and type 2 diabetes mellitus (T2DM). This study focuses on IL-6 levels in T2DM patients with and without DN. From September 2022 to June 2024, the Department of General Medicine, Dr. D. Y. Patil Medical College, Hospitaland Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to be University),Pune, conducted an observational cross-sectional comparative study on 80 T2DM patients, with 40 in group A (cases = T2DM patients with DN) and 40 in group B (controls = T2DM patients without DN). The study included patients with T2DM between the ages of 40 and 80. The study excludes conditions such as diabetic ketoacidosis, patients with end-stage renal disease, and conditions that increase IL-6, such as COVID-19. The study excluded autoimmune conditions with elevated IL-6, such as rheumatoid arthritis, systemic lupus erythematous, ankylosing spondylitis, psoriasis, and Crohn's disease. We obtained ethical approval and written consent from participants. In the current study, 61 patients (76.2%) were 60 years old or younger, while 19 patients (23.8%) were older than 60 years. Among the participants, 38 were females (47.5%) and 42 were males (52.5%). The case group, which consisted of 40 T2DM patients with DN, had a mean glycated hemoglobin (HbA1c) of 7.1700 ± 0.71044. In contrast, the control group, comprising 40 T2DM patients without DN, had a mean HbA1c of 6.8650 ± 0.57179. This difference was statistically significant, with a p value of 0.038. Additionally, the mean UACR in the case group was 134.34 ± 95.56, significantly higher than the control group's mean UACR of 22.32 ± 9.90. This difference was highly significant, with a p value of 0.001. Furthermore, the case group exhibited elevated mean IL-6 levels of 15.48 ± 4.27 compared to the control group's 7.02 ± 2.46, which is also highly significant, reflected by a p value of 0.001. As the concentration of IL-6 rises in diabetic patients with nephropathy, this study suggests that IL-6 may have an effect on the development of DN. This cytokine is necessary for both the initiation and progression of the condition. Using IL-6 as a supportive diagnostic test could help rule out other potential causes of DN in T2DM. Moreover, this marker does not require invasive procedures, and early measurement may help reduce mortality and morbidity.

Prevalence and characteristics of chronic kidney disease in people with type 2 diabetes mellitus in the Autonomous Community of Aragon

AimsThe main objective in this study was to determine the prevalence of Chronic Kidney Disease (CKD) in people with Type 2 Diabetes Mellitus (T2DM) in the Autonomous Community (AC) of Aragon (Spain) and to detect whether or not there is under-registration in the patient's history. As a secundary objetive, it was proposed to study the most relevant demographic and clinical characteristics of people with CKD. MethodsObservational and retrospective real world data study of the population over 18 years of age with a diagnosis of T2DM, between January 2017 and December 2021. A descriptive analysis of qualitative and quantitative variables, and a comparison using the parametric Student's t-test or the non-parametric Mann-Whitney U-test between both groups was performed. ResultsThe prevalence of T2DM was 8.07 % and that of CKD 31.4 %, with an under-reporting of 47 %. The main risk factor associated with CKD was arterial hypertension (p<0.001), followed by dyslipidemia (p<0.001). The main treatment used for diabetes control was metformin, both in patients with and without CKD (p<0.001). A total of 56.81 % of people with T2DM and CKD did not undergo annual monitoring of their renal function (glomerular filtration rate) or determination of albuminuria. ConclusionsThe prevalence of CKD increases in patients with T2DM (31.4 %), and in almost half of patients the diagnosis is not registered (47 %). This under-reporting delays the implementation of measures needed to prevent CKD progression.

Risk factors for chronic kidney disease progression over 20 years for primary prevention in Japanese individuals at a preventive medicine research center: Focus on the influence of plasma glucose levels.

Chronic kidney disease (CKD) is a very important issue globally because of the risk of its progressing to end-stage renal disease. We aimed to identify factors contributing to long-term estimated glomerular filtration rate (eGFR) decline to determine an early diagnosis and prevent CKD progression. From January 2003 to December 2006, 5,507 individuals underwent health checkups at our hospital's Preventive Medicine Research Center. We ultimately enrolled 2,175 individuals. The eGFR was ≥60 mL/min/1.73 m2 at the start of observation period, which was 20 years. The event onset time was the day that the eGFR became <30 mL/min during the 20-year period. Baseline risk factors - in particular, the effect of plasma glucose levels on the eGFR - were extracted and evaluated by using Fine and Gray analysis. During the 20-year observation, the hazard ratio (HR) of CKD progression was examined. A fasting plasma glucose (FPG) level ≥105 mg/dL was significantly associated with the risk of CKD progressing to an eGFR <30 mL/min. This trend was similar in the slope of eGFR. An FPG ≥105 mg/dL or an glycated hemoglobin level ≥6.5% was useful for intervening in CKD progression. Multivariate analysis showed that independent risk factors were an FPG level ≥105 mg/dL (HR 1.9; P < 0.001), age ≥60 years (HR 3.86; P < 0.001), obesity (HR 1.61; P < 0.01) and urinary protein (HR 1.55; P < 0.01). For early intervention against a reduction in the eGFR, detecting mild increases in FPG ≥105 mg/dL in patients with CKD with or without diabetes is useful.

#2546 CKD-PC risk model for CKD progression: validation and association with outcomes in the FIDELITY population

Abstract Background and Aims The Chronic Kidney Disease Prognosis Consortium (CKD-PC) recently developed risk models to predict the 3-year risk of a ≥40% decrease in estimated glomerular filtration rate (eGFR) or to predict kidney failure in the general population. Unlike the kidney failure risk equation, the CKD-PC model is valid for all levels of eGFR (above and below 60 mL/min/1.73 m2) and includes chronic kidney disease (CKD) progression risk factors besides age, sex, eGFR and albuminuria; namely: systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, body mass index, glycated hemoglobin, insulin use, and oral diabetes medication use [1]. We evaluated whether the CKD-PC model, developed using electronic health record data, is valid for use in a contemporary clinical population using the FIDELITY pooled dataset from international randomized clinical trials of finerenone [2]. Additionally, to inform clinical practice, we evaluated the efficacy of finerenone using categories of 3-year CKD progression risk as predicted by the model. Method FIDELITY was an individual, patient-level, prespecified, pooled efficacy and safety analysis of the phase III FIDELIO-DKD and FIGARO-DKD trials of patients with CKD and type 2 diabetes (T2D), randomized 1:1 to finerenone or placebo. The 3-year CKD progression risk of these patients was predicted and the validity of the CKD-PC model was evaluated using area under the curve (AUC) score (with higher scores indicating better risk prediction), Brier score (lower scores indicating better prediction), and by calibration plots of observed versus predicted risk by deciles of 3-year CKD progression risk. To evaluate the efficacy of finerenone, 3-year risk was categorized in quartiles and the effect of finerenone versus placebo on a kidney composite outcome, defined as kidney failure, a sustained ≥40% decrease in eGFR from baseline over ≥4 weeks, or renal death, was assessed. Results The FIDELITY population comprised 13,026 individuals with a mean eGFR of 58 mL/min/1.73 m2 and urine albumin-to-creatinine ratio of 515 mg/g. The median follow-up was 3 years and there were 1849 total kidney outcome events. Of 12,968 patients analyzed, the median 3-year risk of kidney failure was 15% (Q1–Q3: 9–24%). Overall, the model demonstrated good discrimination to predict a ≥40% kidney composite outcome for patients with CKD and T2D in FIDELITY: AUC score 0.726 (95% confidence interval [CI] 0.712–0.739) and Brier score 0.100 (95% CI 0.097–0.103). The predicted 3-year risk was generally slightly higher than the observed risk (Fig. 1). Finerenone was effective in preventing CKD progression across the risk quartiles (p-interaction = 0.094) with a trend towards greater efficacy in the higher risk quartiles (3-year risk of CKD progression ≥10%) (Fig. 2). All risk groups showed benefit with finerenone compared to placebo regarding eGFR decline in the chronic phase. Conclusion The CKD-PC risk model for CKD progression performed well in a large global clinical trial population of patients with CKD and T2D. Finerenone was effective across the range of baseline risk of CKD progression.

Group2 innate lymphoid cells ameliorate renal fibrosis and dysfunction associated with adenine-induced CKD

Renal fibrosis is a common pathway of chronic kidney disease (CKD) progression involving primary kidney injury and kidney diseases. Group 2 innate lymphoid cells (ILC2s) mediate type 2 immune responses irrespective of antigen presentation and play a reno-protective role in kidney injury and disease. In the present study, we observed a decrease in kidney-resident ILC2s in CKD and found that enrichment of ILC2s in the kidney ameliorates renal fibrosis. In CKD kidney, ILC2s preferentially produced IL-13 over IL-5 in response to IL-33 stimulation, regardless of ST2L expression. Moreover, GATA3 expression was decreased in ILC2s, and T-bet+ ILC1s and RORγt+ ILC3s were increased in CKD kidney. Adoptive transfer of kidney ILC2s into adenine-induced CKD model mouse improved renal function and fibrosis. Renal fibroblasts cultured with IL33-activated kidney ILC2s suppressed myofibroblast trans-differentiation through Acta2 and Fn-1 regulation. These results suggest that kidney ILC2s prevent CKD progression via improvement of renal fibrosis. Our findings also suggest that ILC2s may contribute to the development of new therapeutic agents and strategies for tissue fibroses.

Development of a time-resolved immunochromatographic test strip for rapid and quantitative determination of retinol-binding protein 4 in urine.

Urine retinol-binding protein 4 (RBP4) has recently been reported as a novel earlier biomarker of chronic kidney disease (CKD) which is a global public health problem with high morbidity and mortality. Accurate and rapid detection of urine RBP4 is essential for early monitor of impaired kidney function and prevention of CKD progression. In the present study, we developed a time-resolved fluorescence immunochromatographic test strip (TRFIS) for the quantitative and rapid detection of urine RBP4. This TRFIS possessed excellent linearity ranging from 0.024 to 12.50 ng/mL for the detection of urine RBP4, and displayed a good linearity (Y = 239,581 × X + 617,238, R2 = 0.9902), with the lowest visual detection limit of 0.049 ng/mL. This TRFIS allows for quantitative detection of urine RBP4 within 15min and shows high specificity. The intra-batch coefficient of variation (CV) and the inter-batch CV were both < 8%, respectively. Additionally, this TRFIS was applied to detect RBP4 in the urine samples from healthy donors and patients with CKD, and the results of TRFIS could efficiently discern the patients with CKD from the healthy donors. Thedeveloped TRFIS has the characteristics of high sensitivity, high accuracy, and a wide linear range, and is suitable for rapid and quantitative determination of urine RBP4.

Abstract P418: Pre-Stroke Use of Loop Diuretics in Elderly Patients Aggravates Renal Function at the Onset of Acute Stroke: A Propensity Score-Matched, Retrospective Cohort Study

Introduction: Renal function is often impaired in elderly patients experiencing acute stroke (AS) due to pre-existing chronic kidney disease (CKD), which can progress to severe renal dysfunction (SRD). SRD can limit pharmacological treatments, such as anticoagulants, antiplatelets, diabetes medicines, or antihypertensives during the AS phase. Therefore, preventing CKD progression to SRD and minimizing the use of renal-impairing agents before SRD development is crucial. Loop diuretics, commonly prescribed for heart failure, have been reported to exacerbate renal function. Sex-based differences in renal function due to gonadal hormones exist. However, the impact of loop diuretics on the risk of SRD before AS in both sexes remains unclear. Hypothesis: The pre-stroke use of loop diuretics in elderly patients aggravates renal function at the onset of AS in both sexes. Methods: We conducted a propensity score-matched, retrospective cohort study involving patients admitted within 24 hours of AS onset between January 2013 and March 2019 with available pre-stroke medication information. We defined SRD as a calculated creatinine clearance (Ccr) of &lt;30 ml/min. We analyzed logistic regression using variables for pre-stroke loop diuretics initiation, calculated propensity scores for pre-stroke loop diuretics usage, and implemented a one-to-one propensity score matching (PSM) by sex. We compared the incidence of SRD between loop diuretics users and non-users within each sex group. Results: Among 4294 patients with AS, 3472 met the inclusion criteria. Among these, 129 male and 143 female loop diuretic users were matched with non-users using the one-to-one PSM. After the PSM, median ages were 80 years in males and 86 years in females, respectively. The SRD incidence was 38.0% (49/129) versus 16.8% (21/129) in males (p&lt;0.0001) and 50.4% (78/143) versus 23.1% (48/143) in females (p&lt;0.0001), comparing users to non-users. Conclusions: The pre-stroke use of loop diuretics in elderly patients may increase the risk of SRD at the onset of AS in both sexes. Therefore, cautious utilization of loop diuretics in elderly patients is recommended to prevent SRD before AS. A possible option is to switch loop diuretics to other medications, which have been shown to have better renal protective effects. Further prospective studies are needed to validate our findings and establish the appropriate usage of loop diuretics in elderly patients before AS.

Population characteristics and diagnosis rate of chronic kidney disease by eGFR and proteinuria in Japanese clinical practice: an observational database study

Chronic kidney disease (CKD) guidelines recommend early identification and intervention to delay the progression of CKD. The Kidney Disease: Improving Global Outcomes (KDIGO) heatmap is widely used for risk evaluation in CKD management; however, real-world evidence on clinical characteristics based on the KDIGO heatmap remains limited worldwide including Japan. In order to understand the management of CKD including its diagnostic rates in a Japanese clinical setting on the basis of KDIGO heatmap, we utilized a medical record database that contains estimated glomerular filtration rate (eGFR) and urine protein data. Adult individuals (≥ 18 years) with two eGFR results of < 90 mL/min/1.73 m2, 90–360 days apart, were included. Approximately half of patients (452,996/788,059) had proteinuria test results and 6.9% (54,073) had quantitative results. CKD diagnosis rate in patients without proteinuria data was 5.9%, with a lower rate (2.9%) in stage G2; the corresponding rates with quantitative test results were 43.5% and 31.3%, respectively. The most frequent comorbidities were hypertension, diabetes, and cardiovascular disease, and their prevalence increased as the eGFR and proteinuria stages progressed. This study revealed a low rate of proteinuria assessment, especially using quantitative methods, and diagnosis in individuals with suspected CKD. With emerging treatment options to prevent CKD progression and complication onset, there is a need for early evaluation and diagnosis of CKD.

Biomedical Evaluation of Early Chronic Kidney Disease in the Air Force: Building a Predictive Model from the Taiwan Military Health Service.

Chronic kidney disease (CKD) is one of the most common diseases worldwide. The increasing prevalence and incidence of CKD have contributed to the critical problem of high medical costs. Due to stressful environments, aircrew members may have a high risk of renal dysfunction. A better strategy to prevent CKD progression in Air Force personnel would be to diagnosis CKD at an early stage. Since few studies have been conducted in Taiwan to examine the long-term trends in early CKD in Air Force aircrew members, this study is highly important. We investigated the prevalence of CKD and established a predictive model of disease variation among aircrew members. In this retrospective study, we included all subjects who had received physical examinations at a military hospital from 2004 to 2010 and who could be tracked for four years. The Abbreviated Modification of Diet in Renal Disease Formula (aMDRD) was used to estimate the glomerular filtration rate (GFR) and was combined with the National Kidney Foundation/ Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) to identify CKD patients. A total of 212 aircrew members were assessed. The results showed that the prevalence of CKD was 3.8%, 9.4%, 9.0%, and 9.4% in each of the four years. According to the logistic regression analysis, abnormal urobilinogen levels, ketones, and white blood cell (WBC) counts in urine and a positive urine occult blood test increased the risk of CKD. A positive urine occult blood test can be used to predict the future risk of CKD. Moreover, the generalized estimating equation (GEE) model showed that a greater risk of CKD with increased examination time, age and seniority had a negative effect. In conclusion, abnormal urobilinogen levels, ketones, and urine WBC counts in urine as well as a positive urine occult blood test might serve as independent predictors for CKD. In the future, we can focus not only on annual physical examinations but also on simple and accurate examinations, such as urine occult blood testing, to determine the risk of CKD and prevent its progression in our aircrew members.

The effect of oral supplementation of Paricalcitol on C-reactive protein levels in chronic kidney disease patients: GRADE-assessed systematic review and dose-response meta-analysis of data from randomized controlled trials

BackgroundPrevious studies investigating the effect of oral supplementation of paricalcitol on reactive protein levels in chronic kidney disease (CKD) patients reported inconsistent findings. In this systematic review and meta-analysis, we have analyzed and interpreted the results obtained from previous randomized clinical trials on the effect of paricalcitol on C-reactive protein in CKD patients in the literature.MethodsMEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched until January 2023 and related articles were obtained through a careful screening process allowing extraction of required data from selected articles. The effect size was calculated using a random effect model and weighted mean differences (WMD) and 95% confidence intervals (CI). Heterogeneity among studies was evaluated using Cochran’s Q test and I2.ResultsAmongst the 182 articles obtained from the initial search, 4 studies (6 arms) were finally included in the meta-analysis. Pooled analysis shows that C-reactive protein levels significantly decrease after oral supplementation with paricalcitol (WMD: -2.55 mg/L, 95% CI (-4.99 to -0.11; P = 0.04). The studies used in this meta-analysis showed significant heterogeneity (I2 = 66.3% and P = 0.01).ConclusionOral paricalcitol supplementation in CKD patients can significantly reduce C-reactive protein levels, which may prevent CKD progression.

FGF21 and autophagy coordinately counteract kidney disease progression during aging and obesity

ABSTRACT Chronic kidney disease (CKD) has reached epidemic proportions worldwide, partly due to the increasing population of elderly and obesity. Macroautophagy/autophagy counteracts CKD progression, whereas autophagy is stagnated owing to lysosomal overburden during aging and obesity, which promotes CKD progression. Therefore, for preventing CKD progression during aging and obesity, it is important to elucidate the compensation mechanisms of autophagy stagnation. We recently showed that FGF21 (fibroblast growth factor 21), which is a prolongevity and metabolic hormone, is induced by autophagy deficiency in kidney proximal tubular epithelial cells (PTECs); however, its pathophysiological role remains uncertain. Here, we investigated the interplay between FGF21 and autophagy and the direct contribution of endogenous FGF21 in the kidney during aging and obesity using PTEC-specific fgf21- and/or atg5-deficient mice at 24 months (aged) or under high-fat diet (obese) conditions. PTEC-specific FGF21 deficiency in young mice increased autophagic flux due to increased demand of autophagy, whereas fgf21-deficient aged or obese mice exacerbated autophagy stagnation due to severer lysosomal overburden caused by aberrant autophagy. FGF21 was robustly induced by autophagy deficiency, and aged or obese PTEC-specific fgf21- and atg5-double deficient mice deteriorated renal histology compared with atg5-deficient mice. Mitochondrial function was severely disturbed concomitant with exacerbated oxidative stress and downregulated TFAM (transcription factor A, mitochondrial) in double-deficient mice. These results indicate that FGF21 is robustly induced by autophagy disturbance and protects against CKD progression during aging and obesity by alleviating autophagy stagnation and maintaining mitochondrial homeostasis, which will pave the way to a novel treatment for CKD.

Dapagliflozin versus empagliflozin in patients with chronic kidney disease.

Background and Aim: Dapagliflozin and empagliflozin have demonstrated favorable clinical outcomes among patients with chronic kidney disease (CKD). However, their comparative monetary value for improving outcomes in CKD patients is unestablished. We examined the cost-per-outcome implications of utilizing dapagliflozin as compared to empagliflozin for prevention of renal and cardiovascular events in CKD patients. Methods: For calculation of preventable events we divided the allocated budget by the cost needed to treat (CNT) for preventing a single renal or cardiovascular event. CNT was derived by multiplying the annualized number needed to treat (aNNT) by the annual therapy cost. The aNNTs were determined based on data from the DAPA-CKD and EMPEROR-KIDNEY trials. The budget limit was defined based on the threshold recommended by the United States' Institute for Clinical and Economic Review. Results: The aNNT was 42 both dapagliflozin (95% confidence interval [CI]: 34-59) and empagliflozin (CI: 33-66). The CNT estimates for the prevention of one primary event for dapagliflozin and empagliflozin were comparable at $201,911 (CI: $163,452-$283,636) and $209,664 (CI: $164,736-$329,472), respectively. However, diabetic patients had a higher CNT with dapagliflozin ($201,911 [CI: $153,837-$346,133]) than empagliflozin ($134,784 [CI: $109,824-$214,656]), whereas non-diabetic patients had lower CNT for dapagliflozin ($197,103 [CI: $149,029-$346,133]) than empagliflozin ($394,368 [CI: $219,648-$7,093,632]). The CNT for preventing CKD progression was higher for dapagliflozin ($427,858 [CI: $307,673-$855,717]) than empagliflozin ($224,640 [CI: $169,728-$344,448]). For preventing cardiovascular death (CVD), the CNT was lower for dapagliflozin ($1,634,515 [CI: $740,339-∞]) than empagliflozin ($2,990,208 [CI: $1,193,088-∞]). Conclusion: Among patients with CKD, empagliflozin provides a better monetary value for preventing the composite renal and cardiovascular events in diabetic patients while dapagliflozin has a better value for non-diabetic patients. Dapagliflozin provides a better monetary value for the prevention of CVD, whereas empagliflozin has a better value for the prevention of CKD progression.

The prevalence of chronic kidney disease among type 2 diabetes mellitus patients in central South Africa.

Type 2 diabetes mellitus (T2DM) is a leading cause of chronic kidney disease (CKD). The prevalence of CKD among T2DM patients in Africa is 22.0%. The cut-off age for dialysing diabetic patients in the resource-limited state sector in South Africa is 50 years. Type 2 diabetes mellitus patients who develop CKD are likely to be excluded from chronic dialysis and rely on control of risk factors, including blood pressure and blood glucose levels, to prevent CKD progression. We aimed to determine the prevalence of CKD among T2DM patients attending the diabetes clinic at Pelonomi Academic Hospital, Bloemfontein. In this retrospective cross-sectional study, medical records of patients (January 2016 and December 2018) were reviewed to collect demographic and clinical information. In total, 244 records were reviewed. Sixty-one (25.0%, 95% confidence interval [CI]: 20% - 30.8%) T2DM patients had CKD. The rate of CKD was slightly higher in males (n= 24/81; 29.6%) compared with females (n= 37/163; 22.7%). Most patients with CKD (n= 58; 95.1%) were 50 years of age. Only 17.8% of patients achieved a glycosylated haemoglobin (HbA1c) of 7.0%. Blood pressure was controlled in 14.3% of hypertensive patients. Renin-angiotensin-aldosterone system inhibitors were used by 78.6% of patients. A high prevalence of clinically significant CKD among T2DM patients with poor prospects of chronic dialysis in a resource-limited setting was observed. The risk factors for CKD development and progression should be adequately managed in T2DM patients.Contribution:This study emphasises the need for further research and innovation to improve outcomes of T2DM patients with CKD in resource-constrained settings.

Effect of sodium bicarbonate on cardiovascular outcome and mortality in patients with advanced chronic kidney disease.

Background: Metabolic acidosis is a common complication in patients with chronic kidney disease (CKD). Oral sodium bicarbonate is often used to treat metabolic acidosis and prevent CKD progression. However, there is limited information about the effect of sodium bicarbonate on major adverse cardiovascular events (MACE) and mortality in patients with pre-dialysis advanced CKD. Method: 25599 patients with CKD stage V between January 1, 2001 and December 31, 2019 were identified from the Chang Gung Research Database (CGRD), a multi-institutional electronic medical record database in Taiwan. The exposure was defined as receiving sodium bicarbonate or not. Baseline characteristics were balanced using propensity score weighting between two groups. Primary outcomes were dialysis initiation, all-cause mortality, and major adverse cardiovascular events (MACE) (myocardial infarction, heart failure, stroke). The risks of dialysis, MACE, and mortality were compared between two groups using Cox proportional hazards models. In addition, we performed analyzes using Fine and Gray sub-distribution hazard models that considered death as a competing risk. Result: Among 25599 patients with CKD stage V, 5084 patients (19.9%) were sodium bicarbonate users while 20515 (80.1%) were sodium bicarbonate non-users. The groups had similar risk of dialysis initiation (hazard ratio (HR): 0.98, 95% confidence interval (CI): 0.95-1.02, p < 0.379). However, taking sodium bicarbonate was associated with a significantly lower risks of MACE (HR: 0.95, 95% CI 0.92-0.98, p < 0.001) and hospitalizations for acute pulmonary edema (HR: 0.92, 95% CI 0.88-0.96, p < 0.001) compared with non-users. The mortality risks were significantly lower in sodium bicarbonate users compared with sodium bicarbonate non-users (HR: 0.75, 95% CI 0.74-0.77, p < 0.001). Conclusion: This cohort study revealed that in real world practice, use of sodium bicarbonate was associated with similar risk of dialysis compared with non-users among patients with advanced CKD stage V. Nonetheless, use of sodium bicarbonate was associated with significantly lower rate of MACE and mortality. Findings reinforce the benefits of sodium bicarbonate therapy in the expanding CKD population. Further prospective studies are needed to confirm these findings.

Lifestyle Modifications and Nutritional and Therapeutic Interventions in Delaying the Progression of Chronic Kidney Disease: A Review.

Chronic kidney disease (CKD) is a debilitating progressive illness that affects more than 10% of the world's population. In this literature review, we discussed the roles of nutritional interventions, lifestyle modifications, hypertension (HTN)and diabetes mellitus (DM) control, and medications in delaying the progression of CKD. Walking, weight loss, low-protein diet (LPD), adherence to the alternate Mediterranean (aMed) diet, and Alternative Healthy Eating Index (AHEI)-2010slow the progression of CKD. However, smoking and binge alcohol drinking increase the risk of CKD progression. In addition, hyperglycemia, altered lipid metabolism, low-grade inflammation, over-activation of the renin-angiotensin-aldosterone system (RAAS), and overhydration (OH) increase diabetic CKD progression. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend blood pressure (BP) control of <140/90 mmHg in patients without albuminuria and <130/80 mmHg in patients with albuminuria to prevent CKD progression. Medical therapies aim to target epigenetic alterations, fibrosis, and inflammation. Currently, RAAS blockade, sodium-glucose cotransporter-2 (SGLT2) inhibitors, pentoxifylline, and finerenone are approved for managing CKD. In addition, according to the completed Study of Diabetic Nephropathy with Atrasentan (SONAR), atrasentan, an endothelin receptor antagonist (ERA), decreased the risk of renal events in diabetic CKD patients. However, ongoing trials are studying the role of other agents in slowing the progression of CKD.