Chronic Kidney Disease Stage Research Articles

Modified yoga program for Chronic Kidney Disease (CKD) patients undergoing hemodialysis: Study protocol for a randomized controlled trial

Background and objectivesHemodialysis is a life-saving treatment for end-stage renal disease (ESRD). Dialysis patients have a variety of physical and psychological side effects that significantly lower their quality of life. Yoga demonstrated to significantly improve Chronic Kidney Disease (CKD) patients' physical and psychological symptoms. The current study evaluates the impact of Yoga on the renal, cardiac, and psychological health of hemodialysis-dependent individuals with CKD. Methods and analysisEighty ESRD patients with CKD stage-5 undergoing dialysis will be recruited for the study. 40 people in each group will be randomly assigned to the yoga and wait-list control groups. A modified sixty-minute yoga program will be given to the yoga group as an intervention in addition to the standard treatments (medication and hemodialysis). The wait-list control group's standard treatments will continue. Data will be collected at baseline, the end of the first month, the third month, and six months. The estimated Glomerular Filtration Rate (eGFR) is the primary variable. Secondary variables include renal function tests, hemoglobin, C-reactive protein, and subjective variables obtained through questionnaires (pain, depression, anxiety, fatigue, symptom score, sleep quality, and Quality of Life). Data will be analyzed with appropriate statistical tests after normality checks. The current study results could underscore the need for a patient-centered, holistic approach in hospital care that takes into account individual health dimensions. Ethics and disseminationThe study is approved by the Institutional Ethics Committee of S-VYASA Deemed to be University. Voluntary participation and a written consent form will be obtained prior to the inclusion of participants. The findings of the study will be disseminated through research articles and conferences. Trial registration numberCTRI/2021/11/038244 at Clinical Trial Registry of India.

Myosteatosis: an underrecognized risk factor for mortality in non-dialysis chronic kidney disease patients.

Low muscle mass quantity and quality (myosteatosis) can be evaluated by computed tomography (CT)by measuring skeletal muscle area and muscular attenuation, respectively, at the third lumbar vertebra. We aimed to define cut-off points of skeletal muscle area and muscular attenuation to predict mortality in non-dialysis chronic kidney disease (CKD)patients. We conducted a retrospective study including non-dialysis CKD patients over two years, who underwent an opportunistic computed tomography within a two year period, and for whom creatinine was measured within 90days of CT. Skeletal muscle area was normalized for stature to calculate the skeletal muscle index. Area under the receiver operating characteristic (AuROC) curve and Youden's index were used, to identify the cut-point, separatelyaccording to sex. One hundred sixty-seven patients (50.9% male, mean age of 68.3 ± 16.4years) were included, most with CKD stages 3 and 4. During a median follow-up of 4.9 (4.2) years, 39 (23.4%) patients died. Muscular attenuation showed a better ability to predict mortality (AuROC curve 0.739 [95% CI 0.623-0.855] in women and 0.744 in men [95% CI 0.618-0.869]) than skeletal muscle index (AuROC curve 0.491 [95% CI 0.332-0.651] in women and 0.711 [95% CI 0.571-0.850] in men). For muscular attenuation, the best cut-off values to predict mortality were 27.56 Hounsfield units in women and 24.58 Hounsfield units in men. For skeletal muscle index, the best cut-off values were 38.47 cm2/m2 in women and 47.81 cm2/m2 in men. In univariable Cox-regression both low muscle mass and myosteatosis were associated with increased mortality. In multivariable Cox-regression models only myosteatosismaintained a significant association with mortality (Hazard Ratio 2.651 (95% CI 1.232-5.703, p = 0.013)). We found sex-specific cut-off values for muscle parameters using CT analysis in non-dialysis CKD patients that were associated with mortality. In this population, myosteatosis may be more closely associated with mortality than muscle quantity.

Indoxyl Sulfate Inhibits Osteogenesis in Bone Marrow Mesenchymal Stem Cells through the AhR/Hes1 Pathway.

Uremic toxins cause bone disorders in patients with chronic kidney disease (CKD). These disorders are characterized by low turnover osteodystrophy and impaired bone formation in the early stages of CKD. Evidence indicates that the aryl hydrocarbon receptor (AhR) mediates signals that suppress early osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). However, whether the AhR mediates the effects of indoxyl sulfate (IS), a uremic toxin, on BMSC osteogenesis remains unclear. We investigated whether IS affects osteogenesis through the AhR/Hes1 pathway. Expression levels of osteogenesis genes (Runx2, Bmp2, Alp, and Oc), AhR, and Hes1 were measured in mouse BMSCs (D1 cells). At concentrations of 2-50 μM, IS significantly reduced mineralization, particularly in the early stages of BMSC osteogenesis. Furthermore, IS significantly downregulated the expression of Runx2, Bmp2, Oc, and Alp. Notably, this downregulation could be prevented using an AhR antagonist and through Ahr knockdown. Mechanistically, IS induced the expression of Hes1 through AhR signaling, thereby suppressing the transcription of Runx2 and Bmp2. Our findings suggest that IS inhibits early osteogenesis of BMSCs through the AhR/Hes1 pathway, thus suppressing the transcription of Runx2 and Bmp2. Our findings may guide new therapeutic strategies against CKD-related bone disorders.

Deep learning radiomics based on ultrasound images for the assisted diagnosis of chronic kidney disease.

This study aimed to explore the value of ultrasound (US) images in chronic kidney disease (CKD) screening by constructing a CKD screening model based on grey-scale US images. According to the CKD diagnostic criteria, 1049 patients from Tongde Hospital of Zhejiang Province were retrospectively enrolled in the study. A total of 4365 renal US images were collected from these patients. Convolutional neural networks were used for feature extractions and a screening model was constructed by fusing ResNet34 and texture features to identify CKD and its stage. A comparative analysis was performed to compare the diagnosis results of the model with physicians. When diagnosing CKD or non-CKD, the receiver operating characteristic curve (AUC) of our model was 0.918 and that of the senior physician group was 0.869 (p < .05). For the diagnosis of CKD stage, the AUC of our model for CKD G1-G3 was 0.781, 0.880, and 0.905, respectively, while the AUC of the senior physician group for CKD G1-G3 was 0.506, 0.586, and 0.796, respectively; all differences were statistically significant (p < .05). The diagnostic efficiency of our model for CKD G4 and G5 reached the level of the senior physicians group. Specifically, the AUC of our model for CKD G4-G5 was 0.867 and 0.931, respectively, while the AUC of the senior physician group for CKD G4-G5 was 0.838 and 0.963, respectively (all p > .05). Our deep learning radiomics model is more effective than senior physicians in the diagnosis of early CKD.

Quality of life in children at different stages of chronic kidney disease in a developing country.

Children with chronic kidney disease (CKD) require comprehensive assessments, including medical and quality of life (QoL) evaluations. Few studies have been conducted in developing countries. This cross-sectional study included 2-18-year-old patients who were categorized into 4 groups: the CKD stage 2-3, stage 4-5, stage 5 with dialysis (D), and kidney transplantation (KT) groups. QoL was measured using the Pediatric Quality of Life Inventory™ (PedsQL™) version 4.0; relationships between different factors and QoL were determined using multivariable linear regression analysis. Eighty-seven patients (mean age: 13.3 (4.1) years) were included. The self-reported total scores were 77.5 (12.5), 78.9 (11.2), 77.4 (16.2), and 76.1 (10.9) in the stage 2-3, stage 4-5, stage 5D and KT groups, respectively. Parent-reported scores showed a weak-to-moderate correlation with self-reported scores (r = 0.12-0.42), with total scores of 71.8 (12.7), 69.5 (14.9), 63.4 (14.8), and 70.8 (18.1) in the stage 2-3, 4-5, 5D and KT groups, respectively. Multivariable linear regression revealed that the parent-reported score in the stage 5D group was 15.92 points lower than that in the stage 2-3 group (p = 0.02); the score in the low maternal education group was 10.13 points lower than that in the high maternal education group (p = 0.04). Parent-reported scores showed weak-to-moderate correlation with self-reported scores. Patients with CKD stage 5D and patients with low maternal education had lower QoL. Regular QoL assessment is recommended for patients with advanced CKD and those with socioeconomic vulnerabilities.

Hyperkalemia and risk of chronic kidney disease progression: A propensity score matched analysis.

Hyperkalemia is a known complication of chronic kidney disease (CKD); however, it is not known whether hyperkalemia directly contributes to CKD progression and the risk of death. Clarifying the extent to which hyperkalemia is associated with CKD progression and mortality can inform clinical practice and guide future research. The objective of this study was to quantify the risks of CKD progression and mortality associated with hyperkalemia in patients with stages 3b/4 CKD. This was a real-world, exact and propensity score-matched, observational cohort study using data (January 2016-December 2021) from Optum's deidentified Market Clarity Data, a large US integrated insurance claims/electronic medical record database. The study included matched adult patients with stages 3b/4 CKD with and without hyperkalemia, not regularly treated with an intestinal potassium (K+) binder. Measured outcomes were CKD progression and all-cause mortality. CKD progression was defined as diagnosis of CKD stage 4 (if stage 3b at index), CKD stage 5 or kidney failure, or receipt of dialysis or kidney transplantation. After matching, there were 6,619 patients in each of the hyperkalemia and non-hyperkalemia cohorts, with a mean (standard deviation) follow-up time of 2.12 (1.42) years. Use of any renin-angiotensin-aldosterone system inhibitors (RAASi) during baseline was common (75.9%) and most patients had CKD stage 3b (71.2%). Patients with hyperkalemia had a 1.60-fold (95% confidence interval [CI] 1.50, 1.71) higher risk of CKD progression and a 1.09-fold (1.02, 1.16) higher risk of all-cause mortality relative to patients without hyperkalemia. Relative risks of CKD progression associated with hyperkalemia were similar within the subset of patients receiving RAASi and across CKD stages, and when alternative definitions of CKD progression were used. Patients with CKD stages 3b/4 and hyperkalemia experienced significantly higher risks of CKD progression and all-cause mortality than propensity score-matched patients without hyperkalemia.

Генетически-фенотипический профиль детей с атипичным гемолитико-уремическим синдромом

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening disease caused by dysregulation of the alternative complement pathway as a result of mutations in complement genes or the formation of antibodies (AB) to some of the complement factors. Identification of the gene mutations incidence and the corresponding phenotypic features in pediatric patients with aHUS in Russia is aimed at improving the diagnosis and prognosis of the disease as well as treatment tactics planning for patient management. The purpose of this research was to determine the patterns of progression, prognosis and outcomes of aHUS in children depending on their genetic profile. Materials and methods used: the Article represents data from a retro- and prospective analyses of the characteristics of the course of aHUS in 172 children depending on their genetic profile performed in Jan. 2012-Feb. 2022. The sporadic form of aHUS was diagnosed after exclusion of the other forms of thrombotic microangiopathy (TMA), the familial form (in cases with the familial records), the acquired (CFH-Ab HUS) in cases with AB increase to factor H. AutoAb against factor H was determined by enzyme-linked immunosorbent assay (ELISA-VIDITEST anti-complement factor H). The search for mutations (n=167) was carried out using Next-generation Sequencing (NGS) and Sanger sequencing methods. Results: the sporadic form of aHUS was diagnosed in 96.9% of cases, familial in 3.1% and CFH-Ab HUS in 23.8%. The genetic nature of aHUS was confirmed in 53.4% of cases. Pathogenic mutations were detected in 8.6% of cases, probably pathogenic in 42.8% and those with unclear clinical significance in 46.8%. The complement genes mutations were detected in 88.5% of cases and mutations of genes not related to the complement system (ADAMTS13, DGKE, INF2) in 11.5%. The most frequently identified mutations were in the CFH (17.1%), C3 (12.9%) and CD46 (12.9%) genes and less frequently in CFI (7.1%), THBD (5.7%), CFHR5 (5.7%) and CFB (1.4%). In children with CFH-Ab HUS, the CFHR1/CFHR3 deletion was detected in 87.8% of cases, including in 19.4% in combination with mutations of unknown clinical significance. Multiple organ failure syndrome had developed in 77.8% of cases in children with pathogenic/probably pathogenic mutations, in 85.3% in patients with mutations of unknown clinical significance, in 91.8% in patients without mutations and in 83.3% in patients with CFHR1/CFHR3 deletion. Chronic kidney disease (CKD) stages 3 to 5 in sporadic/familial aHUS, regardless of genetic profile, had counted for 14.5% and 16.7% in CFH-Ab HUS. Lethal outcome occurred in 4.3% of cases in the presence of mutations, in 4.9% in the absence of mutations and in 2.8% in cases of CFHR1/CFHR3 deletion. Relapses of aHUS prior to the Eculizumab treatment had developed more often in the presence of CFHR1/CFHR3 mutations and deletion in comparison with children without mutations (31.4% v. 13.1%, p=0.0313 and 44.4% v. 13.1%, p= 0.004). Relapse of aHUS after discontinuation of the Eculizumab therapy had developed in 16.4% of cases. Risk factors for the relapse of aHUS were as follows: patient’s age above 12 months old at the time of the development of aHUS, severe arterial hypertension in the acute period, the use of Eculizumab at the fourth week after the onset of the disease and/or later, recurrent course of aHUS and the presence of CKD prior to the start of the Eculizumab therapy. Conclusion: The genetic profile of patients does not determine the severity and outcome of aHUS though it does affect the relapse rate. The prognosis and survival of patients with aHUS are determined by the severity of the acute period and the timeliness of the complement blocking therapy management.

Protein Intake and Mortality in Older Adults With Chronic Kidney Disease

Avoiding high protein intake in older adults with chronic kidney disease (CKD) may reduce the risk of kidney function decline, but whether it can be suboptimal for survival is not well known. To estimate the associations of total, animal, and plant protein intake with all-cause mortality in older adults with mild or moderate CKD and compare the results to those of older persons without CKD. Data from 3 cohorts (Study on Cardiovascular Health, Nutrition and Frailty in Older Adults in Spain 1 and 2 and the Swedish National Study on Aging and Care in Kungsholmen [in Sweden]) composed of community-dwelling adults 60 years or older were used. Participants were recruited between March 2001 and June 2017 and followed up for mortality from December 2021 to January 2024. Those with no information on diet or mortality, with CKD stages 4 or 5, or undergoing kidney replacement therapy and kidney transplant recipients were excluded. Data were originally analyzed from June 2023 to February 2024 and reanalyzed in May 2024. Cumulative protein intake, estimated via validated dietary histories and food frequency questionnaires. The study outcome was 10-year all-cause mortality, ascertained with national death registers. Chronic kidney disease was ascertained according to estimated glomerular filtration rates, urine albumin excretion, and diagnoses from medical records. The study sample consisted of 8543 participants and 14 399 observations. Of the 4789 observations with CKD stages 1 to 3, 2726 (56.9%) corresponded to female sex, and mean (SD) age was 78.0 (7.2) years. During the follow-up period, 1468 deaths were recorded. Higher total protein intake was associated with lower mortality among participants with CKD; adjusted hazard ratio (HR) for 1.00 vs 0.80 g/kg/d was 0.88 (95% CI, 0.79-0.98); for 1.20 vs 0.80 g/kg/d, 0.79 (95% CI, 0.66-0.95); and for 1.40 vs 0.80 g/kg/d, 0.73 (95% CI, 0.57-0.92). Associations with mortality were comparable for plant and animal protein (HRs, 0.80 [95% CI, 0.65-0.98] and 0.88 [95% CI, 0.81-0.95] per 0.20-g/kg/d increment, respectively) and for total protein intake in participants younger than 75 years vs 75 years or older (HRs, 0.94 [95% CI, 0.85-1.04] and 0.91 [95% CI, 0.85-0.98] per 0.20-g/kg/d increment in total protein intake, respectively). However, the hazards were lower among participants without CKD than in those with CKD (HRs, 0.85 [95% CI, 0.79-0.92] and 0.92 [95% CI, 0.86-0.98] per 0.20-g/kg/d increment, respectively; P = .02 for interaction). In this multicohort study of older adults, higher intake of total, animal, and plant protein was associated with lower mortality in participants with CKD. Associations were stronger in those without CKD, suggesting that the benefits of proteins may outweigh the downsides in older adults with mild or moderate CKD.

Association of arteriovenous fistulae with precapillary pulmonary hypertension – A single center retrospective analysis of invasive hemodynamic parameters

BackgroundPulmonary hypertension (pH) is a well-known complication among patients with chronic kidney disease (CKD). Arteriovenous fistulae (AVF) have been associated with pH mainly by increasing cardiac output. However, the burden of precapillary pH in individuals with CKD and an AVF is unclear. ObjectivesTo better and more fully understand the mechanism and development of precapillary pH in patients with AVF, as well as the consequences of precapillary pH in these patients. MethodsThis was a large retrospective study of patients with CKD stage 4 or 5 who underwent right heart catheterization (RHC) from 2018 to 2023. The data were stratified according to the presence of AVF. To determine if AVF was independently associated with precapillary pH, we used a multivariable logistic regression analysis adjusting for demographics and potential comorbidities associated with precapillary pH, including diagnosis of chronic lung disease, obstructive sleep apnea, connective tissue disease, history of venous thromboembolism, chronic anemia, and heart failure. ResultsOf 651 patients with CKD4 or CKD5, 145 (22 %) had AVF and 506 (78 %) did not have AVF. Within the AVF group, the median age was 64 years (IQR 54–71), and they were predominantly males (61 %, n = 88) and African American (77 %, n = 111). A total of 31 % (n = 45) had evidence of precapillary pH, 30 % (n = 43) of combined pH, and 14 % (n = 20) of isolated postcapillary pH. Compared to the non-AVF group, precapillary pH was more likely in the AVF group (31% vs 17 %, p < 0.0001). On multivariable analysis, AVF was independently associated with precapillary pH (OR 2.47, CI 1.56–3.89; p < 0.0001). The median time from dialysis initiation to RHC date (and precapillary pH diagnosis) was 6 years (IQR 3–8). ConclusionBased on RHC findings, almost one-third of patients with CKD and AVF had precapillary pH. The presence of AVF was independently associated with precapillary pH.

Clinical and pathological significance of Orai1 channel expression in human diabetic nephropathy.

Targeted therapies for diabetic nephropathy (DN) are lacking, partly due to their irreversible nature. The role of Orai1, a store-operated Ca2+ channel, in DN remains debated, with conflicting evidence on its effect on proteinuria in animal models. We aimed to elucidate the functional relevance of Orai1 expression for clinicopathological parameters in patients with DN. In this study, we included 93 patients diagnosed with DN between 2009 and 2019. Immunohistochemical staining for Orai1 was performed on paraffin-embedded kidney sections. The significance of Orai1 expression in human DN was assessed by examining its correlation with DN's pathological and clinical parameters using Pearson's correlation coefficient and univariate logistic regression. Orai1 was significantly overexpressed in DN patients compared to control. A strong correlation was observed between increased Orai1 expression and higher Renal Pathology Society DN classification, enhanced interstitial fibrosis and tubular atrophy scores. Positive correlations with serum creatinine levels and prognosis of chronic kidney disease (CKD) by glomerular filtration rate (GFR) and albuminuria category were noted but the estimated GFR was inversely related to Orai1 expression. Orai1's association with advanced CKD stages persisted even after adjusting for confounding variables in multivariate logistic regression analysis. Orai1 expression is closely associated with histological and clinical severities of DN, suggesting its potential as a predictive biomarker for disease progression and prognosis. These findings provide new perspectives on therapeutic interventions targeting Orai1 in DN.

Bilirubin not just a routine parameter plays an important role in chronic kidney disease

Background: Chronic kidney disease (CKD) is a major health burden in India as well as throughout the world. Imbalance between antioxidant defense and oxidative stress plays a major role in this multifactorial disorder. Recent studies have shown that serum total bilirubin plays an important role in the progression of CKD. Aims and Objectives: The aim of the study is to estimate serum total bilirubin, estimated glomerular filtration rate (eGFR), urea, creatinine and to find out whether there is correlation between serum total bilirubin, eGFR, and different stages of CKD. Materials and Methods: The study is conducted in the department of biochemistry after getting ethical clearance. Two hundred and sixty-nine samples of controls and cases of CKD collected. Serum total bilirubin, urea, and creatinine were calculated in autoanalyzer using standard protocol. eGFR is calculated using a standard formula. Results: There is a significant positive correlation (spearman’s correlation r=0.196, P=0.001) between serum total bilirubin and eGFR value. There is also a significant negative correlation (r=−0.239, P&lt;0.0001) between serum total bilirubin and stages of CKD. Median value of serum urea is also high in cases compared to control. Conclusion: The serum bilirubin may be an important biomarker in the pathogenesis of CKD.

Serum Creatinine Levels Across Different Stages of Chronic Kidney Disease and its Impact on Periodontal Health

Serum Creatinine Levels Across Different Stages of Chronic Kidney Disease and its Impact on Periodontal Health

Pathogenesis of Sarcopenia in Chronic Kidney Disease-The Role of Inflammation, Metabolic Dysregulation, Gut Dysbiosis, and microRNA.

Chronic kidney disease (CKD) is a progressive disorder associated with a decline in kidney function. Consequently, patients with advanced stages of CKD require renal replacement therapies, such as dialysis and kidney transplantation. Various conditions lead to the development of CKD, including diabetes mellitus, hypertension, and glomerulonephritis, among others. The disease is associated with metabolic and hormonal dysregulation, including uraemia and hyperparathyroidism, as well as with low-grade systemic inflammation. Altered homeostasis increases the risk of developing severe comorbidities, such as cardiovascular diseases or sarcopenia, which increase mortality. Sarcopenia is defined as a progressive decline in muscle mass and function. However, the precise mechanisms that link CKD and the development of sarcopenia are poorly understood. Knowledge about these linking mechanisms might lead to the introduction of precise treatment strategies that could prevent muscle wasting. This review discusses inflammatory mediators, metabolic and hormonal dysregulation, gut microbiota dysbiosis, and non-coding RNA alterations that could link CKD and sarcopenia.

Clinical effectiveness of oral antiviral agents for treating non-hospitalized COVID-19 patients with chronic kidney disease

ABSTRACT Objectives This study examined the effectiveness of nirmatrelvir plus ritonavir (NMV-r) and molnupiravir (MOV) in treating COVID-19 among chronic kidney disease (CKD) patients. Methods This retrospective cohort study, using the TriNetX research network, identified stage 3–5 CKD and end-stage kidney disease (ESKD) patients with non-hospitalized COVID-19 between 1 January 2022, and 31 May 2023. Propensity score matching (PSM) was used to compare patients on NMV-r or MOV (antiviral group) against those not receiving these treatments (control group). The primary composite outcome was the cumulative hazard ratio (HR) for all-cause hospitalization or death within the 30-day follow-up. Results After PSM, two balanced cohorts of 6,275 patients each were established. The antiviral group exhibited a lower incidence of all-cause hospitalization or mortality (5.93% vs. 9.53%; HR: 0.626; 95% CI: 0.550–0.713) than controls. Additionally, antiviral recipients were associated with a lower risk of all-cause hospitalization (HR: 0.679; 95% CI: 0.594–0.777) and mortality (HR: 0.338; 95% CI: 0.227–0.504). The beneficial effects of antiviral agents were consistent across sex, age, vaccination status, antiviral type, and CKD stage. Conclusion Oral antiviral agents could be associated with lower rates of all-cause hospitalization or death among non-hospitalized COVID-19 patients with CKD.

Urinary D-amino acid profiles in cats with chronic kidney disease.

Chronic kidney disease (CKD) is highly prevalent in domestic cats. This study aimed to compare urinary D-amino acid levels between control and CKD-afflicted cats as a novel noninvasive method for assessing CKD. Cats were divided into control and CKD stage II groups in accordance with the International Renal Interest Society guidelines. The urinary DL-amino acid levels of the cats were analyzed using chiral tandem liquid chromatography-tandem mass spectrometry, and their medical records were investigated. The CKD group had considerably lower urinary D-amino acid concentrations and enantiomeric ratios than the control group. The total urinary D-amino acid contents significantly correlated with blood parameters (creatinine and urea nitrogen). These findings may contribute towards the detection of CKD stage II in domestic cats.

Over Three Decades of Growth Hormone Treatment in Children With Chronic Kidney Disease-Associated Growth Failure Before and After Kidney Transplantation.

Growth retardation and short final height is a common complication of chronic kidney disease (CKD) beginning in childhood, with profound deleterious effects on quality of life, mental health, and social achievement. Despite optimal treatments of causative factors for growth retardation in children with CKD, more than 50% of patients reach end-stage renal failure with a height >2 SD below the mean, and most do not demonstrate "catch-up" growth after receiving a kidney transplant. Four decades ago, recombinant human growth hormone (rhGH) treatment was introduced after studies showed increased growth velocity and improved height SDS in uremic subjects. Since then, an abundance of published data showed significant improvements in health-related quality of life, and most studies revealed no significant adverse effects. Clinical practice guidelines recommended rhGH treatment in CKD Stages 3-5D and after transplantation. Despite these guidelines, this therapy remained underutilized. Most commonly cited barriers to the implementation of rhGH treatment were the need for daily injections, financial challenges, physicians' unfamiliarity with guidelines, and fear of adverse events. rhGH has been shown to improve growth and final height in short children with CKD, with minimal adverse effects. Despite data of its successful use generated over 3 decades, this treatment is underutilized. More judicious utilization of the treatment should emphasize educating patients, their care givers, and members of the multidisciplinary treating team. Additional studies are needed to assess the longer-term rhGH treatment in larger cohorts of patients, leading to additional supportive data and clearer recommendations.

Progression of Coronary Artery Calcification and Risk of Clinical Events in CKD: The Chronic Renal Insufficiency Cohort Study

Coronary artery calcification (CAC) progresses rapidly in people with chronic kidney disease (CKD) compared with the general population. We studied the association between CAC progression and higher risks of atherosclerotic cardiovascular disease (CVD), congestive heart failure, and all-cause mortality among adults with CKD. Prospective cohort study. & Participants: 1,310 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had at least one CAC scan with no prior history of CVD and with observed or imputed data on changes in CAC over time. Observed or imputed CAC progression, categorized as incident CAC among participants with zero CAC on the baseline scan, or progressive CAC when the baseline scan demonstrated CAC and there was an increase in CAC ≥50 Agatston units per year. Atherosclerotic CVD (myocardial infarction or stroke), congestive heart failure, and all-cause mortality. Cause-specific Cox proportional hazards regression, stratified by presence of CAC at baseline. A total of 545 participants without and 765 with prevalent CAC at baseline were included. During a mean 3.3 years between CAC assessments, 177 (32.5%) participants without baseline CAC developed incident CAC while 270 participants (35.3%) with baseline CAC developed a ≥50 Agatston units per year increase in CAC. After multivariable adjustment, incident CAC was associated with 2.42-fold higher rate of atherosclerotic CVD (95% confidence interval [CI]: 1.23-4.79) and 1.82-fold higher rate of all-cause mortality (95% CI: 1.03-3.22). Progressive CAC (≥50 units per year) was not associated with atherosclerotic CVD (hazard ratio [HR]: 1.42; 95% CI: 0.85-2.35) but was associated with a 1.73-fold higher rate of all-cause mortality (95% CI: 1.31-2.28). Progressive CAC was not associated with incident heart failure. Residual confounding and limited statistical power for some outcomes. Among adults with CKD stages 2-4, CAC progression over a mean 3.3 years was associated with higher risk of atherosclerotic CVD and all-cause mortality. The associations were strongest among participants without CAC at baseline.

IMPACT CKD: Holistic Disease Model Projecting 10-Year Population Burdens

IntroductionThe significant burden of chronic kidney disease (CKD) is not recognized as a global public health priority, although policies aimed at delaying progression to later stages are required. Hence, there is need for a holistic disease model to inform decision-making that accounts for the multi-dimensional impact of CKD, and the interrelated factors that modulate progression. MethodsIMPACT CKD is a microsimulation model that simulates CKD progression and incorporates the effect of clinical events and comorbidities. CKD status is assigned using estimated glomerular filtration rate (eGFR) and albuminuria levels, and CKD progression is predicted by an annual eGFR decline rate. The model projects clinical, healthcare resource use, economic, patient, societal, and environmental burdens from 2022-2032. During development, face, technical, and external validity were evaluated, with calibration conducted to population data. Further, cross-validation was conducted against two published models. The United Kingdom (UK) was selected as the case study for validation. ResultsA 7.7% increase in the CKD population by 2032 was predicted, with increasing numbers of patients with CKD stage 3-5 (21.7%), dialysis (75.3%), and transplantation (58.7%). The rise of renal replacement therapy patients results in an increase of 75% across freshwater use, fossil fuel depletion, and CO2 emissions over the next decade, and an estimated cost of £1.95 billion in 2032. Projections reflect validated findings from other models. ConclusionThe IMPACT CKD model is a robust simulation that delivers validated forecasts of the holistic CKD burden, which can support evaluation of diverse health policies and treatment strategies.

Benefits of dapagliflozin in chronic kidney disease for US commercial payers: A cost-offset analysis.

One in 7 adults have chronic kidney disease (CKD), which is associated with high morbidity and mortality and substantial health care costs, especially in more advanced disease. Our data from a US commercial payer show rising per-member-per-year costs for renal and cardiac complications associated with CKD. To predict the clinical and economic impact of treatment with or without dapagliflozin from the perspective of a US commercial payer using a cost-offset model (COM). The COM used real-world cost and member count data from a US employer-sponsored commercial payer and results of the double-blind, randomized, phase 3 Dapagliflozin and Prevention of Adverse Outcomes in CKD clinical trial (NCT03036150) to predict the incidence of clinical events, including a greater than or equal to 50% decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease, and hospitalization for heart failure, and their associated costs over a 3-year period. The COM compared a hypothetical scenario of the experience with or without dapagliflozin in members with CKD stages 2-4, aged younger than 65 years. In the simulated populations of 130 members, the COM projected 9 events of a greater than or equal to 50% decline in estimated glomerular filtration rate for the experience with dapagliflozin vs 15 events for the experience without dapagliflozin (6 fewer events; number needed to treat [NNT] = 20, amounting to estimated cumulative cost offsets of $0.57 million [M] over a 3-year period). The COM projected similar results for end-stage kidney disease (8 events with dapagliflozin vs 14 events without dapagliflozin; NNT = 24, amounting to $1.92 M in cumulative cost offsets) and for hospitalization for heart failure (13 events with dapagliflozin vs 33 events without dapagliflozin; NNT = 7, amounting to $0.79 M in cumulative cost offsets). These projections translated to total mean, cumulative cost offsets of $3.89 M for all clinical events evaluated over the 3-year period (36.6% reduction with dapagliflozin vs without dapagliflozin), and net mean, cumulative cost offsets of $2.58 M over the 3-year period (24.2% reduction with dapagliflozin vs without dapagliflozin) after factoring in a discounted wholesale acquisition cost for dapagliflozin expenditure ($1.31 M over 3 years). Thus, the net mean, cumulative cost offsets were $19,843 per member over 3 years, representing a 197% return on investment for dapagliflozin expenditure. Results of our COM suggest that dapagliflozin can reduce clinical events and their associated costs over a 3-year period when compared with a scenario without dapagliflozin. Cost offsets increased with each year, indicating that US commercial payers can substantially reduce costs associated with CKD morbidity and mortality.

Kidney failure amongst Irish Travellers.

The occurrence of Kidney Failure with Replacement Therapy (KFRT) amongst Irish Travellers has not been well described. This study aims to determine the burden of KFRT amongst the Irish Traveller population and identify determinants of health amongst this cohort which may differ from the general population in Ireland. This retrospective cohort study included self-identifying Irish Travellers with KFRT registered in the National Kidney Disease Clinical Patient Management System between 1995 and 2022. KFRT was defined as Chronic Kidney Disease stage 5 (CKD G5) treated by dialysis or CKD G1-G5 after transplantation. The primary outcome measure was the prevalence of KFRT in Irish Travellers. Secondary exploratory outcomes included age at diagnosis, family history, biopsy diagnosis, kidney replacement therapy (KRT) modality, time to initiation of KRT, primary vascular access used, and time to receive a kidney transplant. Four of six Irish hospital groups participated in the study. A total of 38 patients were identified as Irish Travellers with KFRT, with a crude prevalence rate of KFRT of 0.12% (CI 0.084-0.161, 95%) or 11.9 per 10,000 Irish Travellers. The mean age for diagnosis of kidney disease was 43 (SD, 20.8) and at commencement of KRT was 45 (SD, 20.9) years. A biopsy-proven diagnosis was provided in 24%. Twenty-two per cent was diagnosed with polycystic kidney disease or congenital anomalies of the kidney and urinary tract. The predominant modality for KRT was haemodialysis (89%), with central venous catheters being the most common initial vascular access (79%). Kidney transplants occurred in 45% of those studied, with a mean waiting time of 1.96 (SD, 1.6) years. The Irish Traveller community have similar prevalence of KFRT when compared to the national prevalence, with a short time interval from diagnosis to commencement of KRT. They are less likely to avail of home therapies but have comparable wait times to the national waiting time to receive a kidney transplant.