Late-stage Chronic Kidney Disease Research Articles

Prevalence and comorbid for late-stage chronic kidney disease (CKD) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) due to urinary obstruction

Chronic Kidney Disease (CKD) is a condition of gradual or chronic decline in kidney function, which is quite severe and caused by various kidney diseases, including urinary obstruction. This disease is progressive and generally irreversible. CKD requires kidney replacement therapy, one of which is continuous ambulatory peritoneal dialysis (CAPD). To determine the prevalence and risk factors for End Stage Renal Disease (ESRD) in patients undergoing CAPD due to urinary obstruction. We performed a retrospective cohort with a cross-sectional study was conducted using secondary data from medical record data of ESRD patients with CAPD accompanied by urinary obstruction at Dr. Saiful Anwar General Hospital, Malang, Indonesia. The prevalence of CKD in patients with CAPD accompanied by urinary obstruction was 6,50% and dominated by males (57,8%) with an age range of 41-50 years (26%). The majority of comorbidities are severely high the Body Mass Index (BMI) (89,0%) and hypertension (80,8%). The location of obstruction is mostly unilateral (5,64%) with mild levels (4,06%). Urinary obstruction is a frequent clinical finding in CKD patients with CAPD. The most common risk factor in this study was hypertension. The prevalence and comorbidities among CAPD patients with Urinary obstruction (UO) are better understood because to this study. It is necessary to recognise its limitations, particularly the small sample size and single-centre design. Future studies should involve more centres and larger patient groups in order to provide a more thorough knowledge of the mechanisms behind the high survival rates among CAPD patients.

Carotid intima-media thickness, fibroblast growth factor 23, and mineral bone disorder in children with chronic kidney disease

BackgroundCarotid intima-media thickness (cIMT) is a measure of atherosclerotic vascular disease and a surrogate biomarker for cardiovascular risk in patients with chronic kidney disease (CKD). Mineral and bone disorders (MBD) are complications of CKD, contributing to vascular calcification and accelerated atherosclerosis. Increased fibroblast growth factor 23 (FGF23)—the earliest detectable serum abnormality associated with CKD-MBD—has been linked with cardiovascular disease in patients with CKD. This study aimed to identify factors and analyze the relationship associated with high cIMT, high FGF23, and poor MBD control in children with CKD.MethodsA cross-sectional study was conducted in Yogyakarta, Indonesia recruiting children with CKD. The correlations and factors between cIMT, FGF23, and MBD were explored.ResultsWe recruited 42 children aged 2–18 years old with CKD stages 2 to 5D. There were no significant correlations between cIMT and factors including advanced CKD, use of dialysis, body mass index, hypertension, anemia, MBD, FGF23 levels, and left ventricular mass index (LVMI). Patients with advanced CKD had poorly controlled anemia, hypertension, and higher LVMI. In multivariate analysis, CKD stages, hypertension stages, the presence of MBD, and LVMI were associated with FGF23 levels (p < 0.05).ConclusionsFGF23 levels increased with CKD progression, and MBD was more prevalent in advanced kidney disease. Elevated FGF23 is potentially associated with increased MBD prevalence in late-stage CKD. A larger study is needed to confirm the factors affecting cIMT in children with CKD.

Urinary cyclophilin A as an early marker of chronic kidney disease with underlying type 2 diabetes

Cyclophilin A (CypA) is a novel renal inflammation biomarker, with levels altered in various diseases, particularly in patients with diabetes mellitus (DM) and kidney damage. This study aimed to investigate the correlation between urinary cyclophilin A (uCypA) and chronic kidney disease (CKD) conditions with and without type 2 diabetes mellitus (T2DM) using an in-house enzyme-linked immunoassay (ELISA) method. A uCypA strip-test prototype was also developed. An indirect ELISA was performed to determine the uCypA levels. A 0.48 µg/mL uCypA cutoff differentiated healthy patients from those with early-stage CKD (stages I and II). The uCypA levels were significantly increased in patients with progression of renal deterioration, especially in the T2DM with late-stage CKD group, compared to the control group. Fasting blood sugar (FBS), estimated glomerular filtration rate (eGFR), albumin/creatinine ratio, and metformin use were associated with uCypA levels. Multinomial logistic regression analysis revealed an association between uCypA levels and T2DM diagnosed for over five years and early-stage CKD. This finding shows that uCypA could be used as a biomarker for distinguishing early-stage CKD as well as T2DM complications, which is beneficial for patients to be aware of their health status and change their behavior to slow kidney deterioration.

Features of preeclampsia in patients with chronic kidney disease

Aims: to study the characteristics of preeclampsia (PE) in women with chronic kidney disease (CKD) compared to PE in the general population.Method: a prospective observational study analyzed the course of PE in 24 women with a previously established diagnosis of CKD (Group 1) and 39 women in the general population (Group 2) without a complicating somatic history. In patients with CKD with a known pregestational creatinine level, the physiological response of the kidneys to pregnancy was assessed, defined as a decrease in serum creatinine by more than 10% in the first trimester. The angiogenic ratio (sFlt-1/PLGF) was studied in 13 patients with CKD.Results: the two groups did not differ in age or parity. In the first group, 16 patients had CKD stage 1-2, 5 had CKD 3A, and one patient each had CKD 3B, 4 and 5 (the later receiving hemodialysis). Nineteen (79%) of women with CKD had hypertension, proteinuria (PU), renal impairment or a combination of these factors before conception. Only 3 out of 16 patients had a physiological renal response. Early PE developed in 58.3% of patients with CKD compared to 35.3% in second group (p = 0.082). The duration of PE inversely correlated with the stage of CKD (r = -0.630; p = 0.001). As pregnancy progressed in patients with CKD, PU increased, reaching nephrotic level in 54% of women by the time of PE. HELLP syndrome or isolated hematological signs of TMA were noted in 8 patients in the general population group, and in 1 in the CKD group. The average sFlt-1/PLGF value in patients with early stages of CKD (n = 9) was 81.0±24.0, with late stages (n = 4) it was 14±8.Conclusion: the study identified the features of PE in CKD: early onset, increased PU reaching nephrotic level in half of the cases by the time PE is diagnosed, and the absence of a histological renal response to pregnancy in the 1st trimester. The lack of changes in the angiogenic coefficient in women with PE and late-stage CKD requires further study in a larger group of patients.

Clinical Outcomes of a Novel Multidisciplinary Care Program in Advanced Kidney Disease (PEAK)

IntroductionMulti-disciplinary care (MDC) for late-stage chronic kidney disease (CKD) has been associated with improved patient outcomes compared with traditional nephrology care, but the optimal MDC model is unknown. In 2015, we implemented a novel MDC model for patients with late-stage CKD informed by the Chronic Care Model conceptual framework, including an expanded MDC team, care plan meetings, clinical risk prediction, and a patient dashboard. MethodsWe conducted a single-center, retrospective cohort study of adults with late-stage CKD (estimated glomerular filtration rate [eGFR] < 30 mL/min per 1.73m2) enrolled from May 2015 to February 2020 in the Program for Education in Advanced Kidney disease (PEAK). Our primary composite outcome was an optimal transition to end-stage kidney disease (ESKD) defined as starting in-center hemodialysis (ICHD) as an outpatient with an arteriovenous fistula (AVF) or graft (AVG), or receiving home dialysis, or a pre-emptive kidney transplant. Secondary outcomes included home dialysis initiation, pre-emptive transplantation, vascular access at dialysis initiation, and location of ICHD initiation. We used logistic regression to examine trends in outcomes. Results were stratified by race, ethnicity, and insurance payor and compared with national and regional averages from the United States Renal Data System (USRDS) averaged from 2015 to 2019. ResultsAmong 489 patients in the PEAK program, 37 (8%) died prior to ESKD and 151 (31%) never progressed to ESKD. Of the 301 (62%) patients who progressed to ESKD, 175 (58%) achieved an optimal transition to ESKD, including 54 (18%) peritoneal dialysis, 16 (5%) home hemodialysis, and 36 (12%) preemptive transplant. Of the 195 (65%) patients starting ICHD, 51% started with an AVF or AVG and 52% started as an outpatient. The likelihood of starting home dialysis increased by 1.34 times per year from 2015 to 2020 (95% CI 1.05 – 1.71, p = 0.018) in multivariable adjusted results. Optimal transitions to ESKD and home dialysis rates were higher than national USRDS data (58% vs. 30%; 23% vs. 11%) across patient race, ethnicity, and payor. ConclusionsPatients enrolled in a novel comprehensive MDC model coupled with risk prediction and health information technology were nearly twice as likely to achieve an optimal transition to ESKD and start dialysis at home, compared with national averages.

Tolvaptan therapy for edema in patients with chronic kidney disease.

Tolvaptan is a vasopressin V2 receptor antagonist that is commonly prescribed to alleviate edema associated with renal diseases. However, the clinical benefits of tolvaptan in chronic kidney disease (CKD) remain unclear. This study aimed to evaluate the effectiveness of tolvaptan in managing edema caused by CKD. The efficacy and treatment regimen of tolvaptan were assessed in a cohort of 96 patients with renal edema and CKD. During the treatment, the patients' creatinine (CR), uric acid (UA), and estimated glomerular filtration rate (eGFR) were monitored as important indicators of kidney function. Coagulation-associated molecules including fibrinogen, D-dimer, and fibrin degradation products (FDPs) were measured. Electrolyte disorders and acute kidney injury were closely monitored. Tolvaptan was administered at a daily dose of 7.5 mg, and 30 mg of edoxaban was administered to manage deep vein thrombosis. During the course of tolvaptan therapy, the eGFR of the patients was not declined. Edema was eliminated in 82.18% of patients. Proteinuria was reduced in the patients (p<0.05). There were no significant changes in serum sodium levels throughout treatment, and no significant difference was observed in blood volume between the end of treatment and baseline levels. Importantly, acute kidney injury did not occur, and renal edema and deep vein thrombosis were successfully treated. As long as a rational treatment regimen is followed, tolvaptan is a safe and effective diuretic for treating edema in CKD, even in the late stages of CKD without reducing residual renal function in the patients.

#1848 Body composition and multimorbidity in patients with chronic kidney disease

Abstract Background and Aims Frailty and multimorbidity are increasingly prevalent, particularly in the chronic kidney disease (CKD) population, and they seem to be more pronounced and accelerated in people receiving haemodialysis. We aimed to study the relationship between body composition, frailty and multimorbidity in people with CKD and end stage renal disease (ESRD) on haemodialysis (HD). Method This was a single centre study, involving 42 patients with CKD stage 3 to 5 (pre-dialysis) and 29 patients receiving in-centre haemodialysis. InBody 770 was used to measure body composition using bioelectrical impedance analysis. Multimorbidity of participants were assessed using the simplified Cambridge multimorbidity score. Frailty assessment was performed using the Clinical Frailty Scale. Results Phase angle was lower in later stages of CKD—mean phase angle in CKD stage 3 was 5.28°, stage 4 was 4.44 and stage 5 was 4.13 (p = 0.008). Visceral adiposity correlated with multimorbidity scores but in a multivariate regression analysis (including albumin and visceral fat area) only whole body phase angle independently predicted multimorbidity in CKD stage 4-5 (adjusted R2 for the whole model = 0.47, p = 0.007). In haemodialysis patients, there was no correlation between multimorbidity and phase angle (r = −0.149, p = 0.441). However, there was a significant correlation between frailty score and whole body phase angle in this group (r = −0.559, p = 0.002). In a univariate analysis, age (R2 = 0.2, Beta = 0.045, p = 0.015), albumin (R2 = 0.217, Beta = −0.214, p = 0.009) and skeletal muscle mass (R2 = 0.282, Beta = −0.101, p = 0.003) predicted frailty score in haemodialysis patients. In multivariate regression analysis age, albumin level and skeletal muscle mass continued to independently predict frailty scores in HD patients (adjusted R2 for the whole model = 0.503). Conclusion Phase angle measurement refers to cell membrane integrity and fat-free mass, with higher values suggesting improved cell health. Using body composition measures, in particular phase angle, is a useful measure to predict multimorbidity and frailty in CKD patients. They are quick, accessible and easy to use tools that can be incorporated in clinical practice routinely. The relationship between visceral adiposity and multimorbidity merits further investigation. Preservation of skeletal muscle mass through nutritional and exercise interventions could be a clinical target to reduce frailty in this population.

#1171 Effect of methoxy polyethylene glycol-epoetin beta on delaying dialysis in anemic patients with Stage 4-5 chronic kidney disease

Abstract Background and Aims The optimal hemoglobin (Hb) target for treating anemia in pre-dialysis chronic kidney disease (CKD) remains controversial. This study investigates the efficacy and safety of methoxy polyethylene glycol-epoetin beta, in delaying the initiation of kidney replacement therapy (KRT), all-cause mortality, CKD progression, and quality of life in stage 4-5 CKD patients. It compares outcomes between patients targeting an Hb level of 10.5-11.5 g/dL versus 8.5-9.5 g/dL. Method This was a single-center, open-label, parallel-group randomized controlled trial. Patients with estimated glomerular filtration rates (eGFR) of 8-15 ml/min/1.73 m2, who had not yet started dialysis, were randomized into two groups based on different Hb targets (Group A: 10.5-11.5 g/dL, Group B: 8.5-9.5 g/dL). Methoxy polyethylene glycol-epoetin beta (MIRCERA®) was prescribed by a pre-specified protocol to achieve these Hb targets. Iron supplements were administered to maintain transferrin saturation &amp;gt;20% or serum ferritin &amp;gt;200 ng/ml. Primary outcomes included a composite of all-cause death and KRT initiation, with secondary outcomes encompassing eGFR slope, hospitalization incidence, blood transfusion necessity, and quality of life measured by the 36-Item Short Form Health Survey (SF-36). Results A total of 62 participants were randomized. The mean age was 64.0 years (SD ±16.0), with 51.6% being female. The mean estimated Glomerular Filtration Rate (eGFR) at enrollment was 12.1 ml/min/1.73 m2 (SD ±3.1). Group A had a significantly higher time-averaged Hemoglobin (Hb) level (10.5 g/dL, SD ±1.2) compared to 8.5 g/dL (SD ±0.9) in the control group (p &amp;lt; 0.001). There was no significant difference in the composite endpoint of all-cause death and Kidney Replacement Therapy (KRT) initiation between the two groups (Hazard Ratio [HR] 0.69; 95% Confidence Interval [CI] 0.32-1.50; p = 0.35, as shown in the Figure). The eGFR slope was similar in both groups (−2.54 vs. −2.53 ml/min/1.73 m2 per year, p = 0.9). Time-averaged ferritin, transferrin saturation, blood pressure, and dietary sodium/protein intake showed no significant differences. Participants in the lower Hb target group required more blood transfusions (11 vs 1 unit, Incidence Rate Ratio [IRR] = 0.075, 95% CI 0.002-0.517, p = 0.001). Rates of hospital admissions, and changes in SF-36 quality of life domains were comparable between the groups, as detailed in the Table. Conclusion The study indicates that using methoxy polyethylene glycol-epoetin beta to maintain a higher Hb target in anemic patients with stage 4-5 CKD does not significantly alter the rate of all-cause mortality, the initiation of KRT, and rate of eGFR decline compared to a lower Hb target. However, a higher Hb target may reduce the need for blood transfusions without adversely affecting the progression of CKD, hospitalization rates, or quality of life. These findings suggest that while higher Hb targets may not dramatically alter key clinical outcomes, they could offer benefits in reducing transfusion requirements, thus providing a more nuanced approach to managing anemia in late-stage CKD.

#1993 Analysis of the characteristics of IgA nephropathy patients using real-world data from five European countries

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally; it has a significant health burden and a highly variable disease course. As IgAN is a heterogeneous disease, it is important to appreciate the associated patient characteristics in order to understand disease progression and how best to implement individualised treatment regimens. To determine the patient characteristics associated with IgAN, a physician questionnaire and patient chart audit were conducted. Method From 21 December 2022 to 6 February 2023, physicians from five European countries (France, Germany, Spain, Italy and the UK) completed a questionnaire and patient chart review of their IgAN patients. Physicians were required to have ≥50 patients with stage 1–4 chronic kidney disease (CKD); at least four of these were required to be non-dialysis IgAN patients. Patients whose charts were included were required to be aged 12 years or older, non-dialysis IgAN patients and have an estimated glomerular filtration rate of ≥15 mL/min/1.72 m2. The charts included were required to be from patients who had seen a participating physician within the prior 6 months. Results 261 physicians answered the questionnaire and completed chart audits on 473 of their most recently seen patients. Patient charts audited were largely from male (71%) Caucasian (78%) patients from 31–49 years of age (38%). 22% of patients were referred to their current physician within the past year. Most patients (70%) were referred by a primary care physician and 9% by another nephrologist. Of those referred by a nephrologist, 32% were referred for specialised care. Participating physicians perceived that close to 30% of patients were referred to them late or extremely late, with contributing factors including lack of engagement from patients with annual follow-ups and patients remaining asymptomatic for a long time. At the most recent visit, 24.3% had CKD stage 1 or 2, 26.6% of patients had CKD stage 3a, 30.4% had stage 3b and 18.6% had stage 4 disease. Nephrologists characterised 53% of their CKD stage 4 patients as having severe IgAN. The symptoms reported with greatest frequency at the most recent visit included fatigue (59%), blood in the urine (41%) and increased weight gain (41%). In total, 71% of patients had proteinuria &amp;gt;0.5 g/day (8% had no values available) and 8% of patients had nephrotic syndrome (urine protein &amp;gt;3.5 g/day and low serum albumin). In total, 28% of patients had no co-morbid conditions. More than half (54%) of the patients whose charts were audited had comorbid hypertension. Other comorbidities included hyperlipidaemia (22%), obesity (17%), type 2 diabetes (15%) and peripheral oedema (7%). Counterintuitively, when asked about the overall health of their patients, physicians perceived the majority (98%) of patients to be in good or excellent overall health. Patients were prescribed five medications on average, with most (92%) taking an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, or both. The number of medications prescribed increased after the age of 50. Two-thirds (66%) of physicians felt that patients completely adhered to their treatment regimen. However, 54% of physicians reported some form of dissatisfaction with the response of their patients to their overall treatment regimen; though, levels of satisfaction varied between individual treatment options. Conclusion Despite high rates of proteinuria and patients often in late-stage CKD at referral, physicians perceived the majority of patients to be in good or excellent overall health, revealing a potential gap in physicians’ perceptions of patients’ health and their risk of progression to kidney failure. As a result, patients were often diagnosed or referred late and their perception of their own health may have led to a lack of engagement with physicians. These data indicate that there is an unmet need for early diagnosis and treatment of IgAN to ensure that patients receive appropriate care.

#1986 Incidence of renal anemia among patients with atrial fibrillation and chronic kidney disease stage IIIb-V

Abstract Background and Aims According to the QICKD study, the prevalence of anemia in stage IIIb-V chronic kidney disease (CKD) is 22%. The incidence of renal anemia ranges from 8.4% in patients with stage I CKD to 83.7% in patients with stage V CKD. In patients on program hemodialysis, anemia develops in 94.5% of cases. The problem is associated with an increased risk of unfavorable outcome of CKD, therefore, the study of aspects of anemia among patients receiving anticoagulant therapy with atrial fibrillation (AF) and CKD remains the most relevant today. The purpose of the study is to study the prevalence of renal anemia among patients with AF and CKD stages IIIb-V. Method 794 patients were admitted to the cardiology department with a diagnosis of AF and late stages of CKD—IIIb (glomerular filtration rate (GFR) 45–30 ml/min/1.73 m2), IV (GFR 29–15 ml/min/1.73 m2), V (GFR &amp;lt;15 ml/min/1.73 m2), for the first identified sustained decrease in glomerular filtration rate (FISD in GFR) of less than 45 ml/min/1.73 m2. The classification of renal anemia was carried out according to the recommendations of the World Health Organization. Results Renal anemia was diagnosed in 505 (63%) patients with AF and GFR less than 45 ml/min/1.73 m2. In total, among patients with CKD stage IIIb, anemia was detected in 207 (59%) patients, with CKD stage IV—in 110 (89%), with CKD stage V—in 43 (97%), with FISD in GFR—in 145 (51%). A mild degree of anemia (hemoglobin (Hb) in men 110-129 g/l, in women 110-119 g/l) was diagnosed in 39% of patients, with CKD stage IIIb in 85 (24%) patients, with CKD stage IV in 28 (22%) patients, with CKD stage V in 9 (20%) patients, with FISD in GFR in 75 (26%) patients. A moderate degree of anemia (Hb 81-109 g/l) was detected in 47.3% of cases, with CKD stage IIIb in 86 (25%) patients, with CKD stage IV in 60 (48%) patients, with CKD stage V in 29 (66%) patients, with FISD in GFR in 64 (23%) patients. Severe anemia (Hb 81-109 g/l) was detected in 47.3% of patients, with CKD stage IIIb in 36 (10%) patients, with CKD stage IV in 22 (19%) patients, with CKD stage V in 5 (11%) patients, with FISD in GFR in 6 (2%) patients. Conclusion Every fourth patient in the cardiology department with AF and GFR &amp;lt;45 ml/min/1.73 m2 was diagnosed with renal anemia, and its prevalence increases with a decrease in GFR. The above results indicate that a more careful selection of anticoagulant therapy is recommended for this patient population due to the high risk of progression of renal anemia in this cohort of patients.

#1982 Transcriptomic approach to predict drug targets in late-stage hypertensive nephropathy

Abstract Background and Aims Hypertensive nephropathy (HN) is a significant contributor to chronic kidney disease, yet the factors influencing the disease progression remains elusive. Notably, late-stage chronic kidney disease significantly impacts patient outcome. This project aims to unveil novel therapeutic targets for late-stage of HN using transcriptomic approach. Method A cohort of adult patients (n = 21; n = 9 females, mean age 57 years) with biopsy-confirmed HN were selected from the Norwegian Kidney Biopsy Registry (NKBR). Patients were classified as late-stage if eGFR≤45 ml/min/1.73 m2 at the time of biopsy. Patients were thereafter divided into “stable” (eGFR decline &amp;lt;3 ml/min/year) or “progressive” (eGFR decline ≥3 ml/min/year or start of renal replacement therapy) after a median follow-up of 9 years (5-15). TruSeq Exome sequencing was performed post-RNA extraction (miRNeasy FFPE kit, Qiagen) at Novogene, Cambridge, UK. R Studio (v4.2.0) and drug CTD repository in ShinyGO 0.80 facilitated data and drug interaction analysis. Results We focused on two distinct subgroups of HN patients: late stable (LS, n = 9) and late progressive (LP, n = 12). A total of n = 674 of differentially expressed genes (DEG, p-value &amp;lt; 0.05 and fold change (FC) ≥1.5) was identified in LS vs. LP. The subsequent drug interactive analysis of these DEGs unveiled 336 pathways with false discovery rate (FDR) &amp;lt; 0.05. Notably, the probenecid-related pathway demonstrated significant fold enrichment (FE=9, FDR = 1.5E-04), as depicted in Fig. 1. Particularly, key members of the SLC22 family, including SLC22A6 (FC=2.49, p-value = 0.002), SLC22A8 (FC=2.65, p-value = 0.004), SLC22A11 (FC=1.65, p-value = 0.036) and SLC22A12 (FC=1.97, p-value = 0.009) were prominently featured in this pathway. Besides their role as sole transporters, it is postulated that these proteins have central role in modulating local and systemic physiology, such as blood pressure, suggesting a potential significance of probenecid in the context of hypertensive nephropathy. Conclusion Transcriptomic profiling of kidney biopsies has strong potential to discover novel therapeutic targets, such as the probenecid-related pathway, in hypertensive nephropathy patients.

Association of Tumor Necrosis Factor-Alpha (TNF-α) rs1800629 Polymorphism in Chronic Kidney Disease.

Background Chronic kidney disease (CKD) is characterized by progressive loss of kidney function. Tumor necrosis factor-alpha (TNF-α) is a cytokine implicated in inflammatory processes, including those affecting the kidneys. Although this association is not yet comprehensible, a tie-up between renal disease and markers of inflammation - interleukin-6 (IL-6), preceded by TNF-α - is eminent. However, a pause in research is evident concerning the TNF-α gene with kidney disease in the inhabitants of India. So, this study investigates the association between TNF-α rs1800629 polymorphism and CKD. Methodology A prospective case-control study was conducted in Andhra Pradesh for over three years. A total of 579 patients participated in the study. These were divided into premature, late-stage CKD, and control groups. The amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR)was used, and biochemical investigations and genotyping were carried out for the study participants. Hardy-Weinberg expected frequencies (HWE) with chi-square test was used for detecting allele and genotype frequencies. The association between TNF-α (-308 G/A, rs1800629) and CKD was assessed using odds ratios (ORs) with 95% confidence intervals (CIs). Results We found a higher prevalence of CKD among males (n= 301, 52%) compared to females (n= 278, 48%).Both male and female participants diagnosed with CKD exhibited significantly elevated blood urea and serum creatinine levels compared to the control group, indicating impaired kidney function.Furthermore, these markers were generally higher in the late-stage CKD group compared to the early-stage group, suggesting a progressive decline in kidney function as the disease worsens. The homozygous genotype GG was more prevalent in late-stage CKD patients compared to both early-stage CKD patients and controls. Further, the heterozygous genotype GA was more frequent in the early-stage CKD group compared to the late-stage group.The homozygous genotype AA also showed a higher prevalence in the early-stage CKD group compared to the late-stage group. The G/G genotype and the G allele (rs1800629) were significantly associated with susceptibility to CKD (P<0.005). Conclusions Our study reported the TNF-α rs1800629 polymorphism and CKD risk in a South Indian population. G/G genotype and the G allele (rs1800629) were significantly associated with the risk of CKD. However, further research with larger sample sizes is warranted to confirm these observations and elucidate the underlying mechanisms by which TNF-α might influence CKD risk.

Development of a Conceptual Model of Physical Functioning Limitations Experienced by Patients with Late-Stage Chronic Kidney Disease: A Qualitative Interview Study

Development of a Conceptual Model of Physical Functioning Limitations Experienced by Patients with Late-Stage Chronic Kidney Disease: A Qualitative Interview Study

Urinary angiotensin-converting enzyme 2 and its activity in cats with chronic kidney disease.

Angiotensin-converting enzyme 2 (ACE2) played an important role in the renin-angiotensin-aldosterone system (RAAS) and it was proved to be renoprotective in renal disease. Urinary angiotensin-converting enzyme 2 (uACE2) has been shown to reflect renal injury in human and experimental studies, but its role in feline kidney disease remains unknown. Our objectives involve comparing uACE2 concentrations and activities in cats across CKD stages with healthy controls, investigating the relationship between uACE2 concentrations, activities, and clinicopathological data in feline CKD patients, and assessing the predictive abilities of both for CKD progression. A retrospective, case-control study. The concentration and activity of uACE2 were measured by commercial ELISA and fluorometric assay kits, respectively. The concentration was adjusted to give uACE2 concentration-to-creatinine ratios (UACCRs). In total, 67 cats consisting of 24 control and 43 chronic kidney disease (CKD), including 24 early-stage CKD and 19 late-stage CKD, were enrolled in this study. UACCR values were significantly higher in both early-stage (2.100 [1.142-4.242] x 10-6) and late-stage feline CKD (4.343 [2.992-5.0.71] x 10-6) compared to healthy controls (0.894 [0.610-1.076] x 10-6; p < 0.001), and there was also significant difference between-early stage group and late-stage group (p = 0.026). Urinary ACE2 activity (UAA) was significantly lower in CKD cats (1.338 [0.644-2.755] x pmol/min/ml) compared to the healthy cats (7.989 [3.711-15.903] x pmol/min/ml; p < 0.001). UACCR demonstrated an independent, positive correlation with BUN (p < 0.001), and UAA exhibited an independent, negative correlation with plasma creatinine (p < 0.001). Both UACCR and UAA did not yield significant results in predicting CKD progression based on the ROC curve analysis. uACE2 concentration and activity exhibit varying changes as renal function declines, particularly in advanced CKD cats.

Untargeted metabolomic profiling of serum from client-owned cats with early and late-stage chronic kidney disease

Evaluation of the metabolome could discover novel biomarkers of disease. To date, characterization of the serum metabolome of client-owned cats with chronic kidney disease (CKD), which shares numerous pathophysiological similarities to human CKD, has not been reported. CKD is a leading cause of feline morbidity and mortality, which can be lessened with early detection and appropriate treatment. Consequently, there is an urgent need for early-CKD biomarkers. The goal of this cross-sectional, prospective study was to characterize the global, non-targeted serum metabolome of cats with early versus late-stage CKD compared to healthy cats. Analysis revealed distinct separation of the serum metabolome between healthy cats, early-stage and late-stage CKD. Differentially abundant lipid and amino acid metabolites were the primary contributors to these differences and included metabolites central to the metabolism of fatty acids, essential amino acids and uremic toxins. Correlation of multiple lipid and amino acid metabolites with clinical metadata important to CKD monitoring and patient treatment (e.g. creatinine, muscle condition score) further illustrates the relevance of exploring these metabolite classes further for their capacity to serve as biomarkers of early CKD detection in both feline and human populations.

Retinoic acid receptor α activity in proximal tubules prevents kidney injury and fibrosis

Chronic kidney disease (CKD) is characterized by a gradual loss of kidney function and affects ~13.4% of the global population. Progressive tubulointerstitial fibrosis, driven in part by proximal tubule (PT) damage, is a hallmark of late stages of CKD and contributes to the development of kidney failure, for which there are limited treatment options. Normal kidney development requires signaling by vitamin A (retinol), which is metabolized to retinoic acid (RA), an endogenous agonist for the RA receptors (RARα, β, γ). RARα levels are decreased in a mouse model of diabetic nephropathy and restored with RA administration; additionally, RA treatment reduced fibrosis. We developed a mouse model in which a spatiotemporal (tamoxifen-inducible) deletion of RARα in kidney PT cells of adult mice causes mitochondrial dysfunction, massive PT injury, and apoptosis without the use of additional nephrotoxic substances. Long-term effects (3 to 4.5 mo) of RARα deletion include increased PT secretion of transforming growth factor β1, inflammation, interstitial fibrosis, and decreased kidney function, all of which are major features of human CKD. Therefore, RARα's actions in PTs are crucial for PT homeostasis, and loss of RARα causes injury and a key CKD phenotype.

Prognostic value of left ventricular structure and strain in chronic kidney disease patients by cardiovascular magnetic resonance imaging: a retrospective study.

Individuals suffering from chronic kidney disease (CKD) frequently face a heightened likelihood of experiencing cardiovascular complications, including heart failure and cardiac mortality. Cardiovascular magnetic resonance feature tracking (CMR-FT) is utilized to assess the micro-contraction function of the myocardium. The objective of this research is to explore the relationship between the left ventricular anatomy, myocardial strain, and the clinical outcomes in patients with CKD. A total of 77 patients with late-stage CKD were enrolled in this retrospective study. They underwent cardiac magnetic resonance imaging and were followed up, with no history of significant cardiac diseases. The patients were divided into two groups: those with a left ventricular global longitudinal strain (LVGLS) ≥ -15.2% (n=49) and those with LVGLS < -15.2% (n=28). The clinical endpoints were defined as hospitalization for heart failure or all-cause mortality. Over an average observation period of 22 ±9 months, 11 (14%) patients passed away and 30 (39%) were admitted to the hospital for heart failure, with eight encountering both incidents. Those with LVGLS ≥ -15.2% had markedly lower rates of event-free survival concerning heart failure admissions and overall mortality than their counterparts (log-rank P=0.014). Cox multivariable analysis indicated that reduced LVGLS consistently predicted a higher likelihood of combined outcomes of heart failure admissions and total mortality (HR: 3.40, 95% CI [1.35-8.56], P=0.009), even when factoring in age, diabetes, left atrial diameter, and left ventricular mass index (LVMI). However, the LVMI showed no significant correlation with the risk of heart failure admissions or overall mortality. Compared to patients with LVGLS < -15.2%, CKD patients with LVGLS ≥ -15.2% have an increased risk of heart failure hospitalization and all-cause mortality. The prognostic role of LVMI in assessing CKD patients among the Asian population requires further investigation.

Treatment for patients with autosomal dominant polycystic kidney disease in the chronic kidney disease without kidney replacement therapy in real-world clinical practice: a descriptive retrospective cohort study.

In real-world clinical practice, treatments selected for patients with autosomal dominant polycystic kidney disease (ADPKD) in the chronic kidney disease (CKD) without kidney replacement therapy (KRT) have not been reported. This study investigated the oral treatments used in these patients and the changes in their use in recent years. Additionally, we studied the factors affecting tolvaptan dose reduction or discontinuation. This retrospective cohort study was conducted using the medical records of 160 hospitals in Japan. Patients with ADPKD or polycystic kidney disease registered on the database between January 2014 and December 2020 were selected. Changes in prescription proportions over time were assessed using the Cochran-Armitage test. We focused on patients prescribed with >15 mg of tolvaptan daily to identify the factors related to its dose reduction or discontinuation and used Multivariate Cox regression analysis to evaluate them. Tolvaptan use in patients with ADPKD in the CKD without KRT stage has increased. As of 2020, 25% of patients were treated with tolvaptan. Overall, 3639 patients with ADPKD were enrolled in the database, of whom 156 were treated with tolvaptan. Of these, 64 patients (41%) reduced or discontinued tolvaptan during the observation period. The presence of an estimated glomerular filtration rate <60 mL/min/1.73 m2 at the beginning of the treatment was associated with a higher risk of tolvaptan dose reduction or discontinuation. The proportion of patients with ADPKD treated with high-dose tolvaptan is increasing. However, patients with late-stage CKD tended to reduce or discontinue tolvaptan.

The influence of chronic renal insufficiency on multi-therapeutic modalities for breast cancer: a single-center experience.

Due to the presence of other comorbidities and multi-therapeutic modalities in breast cancer, renally cleared chemotherapeutic regimens may cause nephrotoxicity. The aim of this retrospective study is to compare the chemotherapy types and outcomes in breast cancer patients with or without chronic renal disease. We retrospectively enrolled 62 female patients with breast cancer and underlying late stages (stage 3b, 4, and 5) of chronic kidney disease (CKD) treated from 2000 to 2017. They were propensity score-matched 1:1 with patients in our database with breast cancer and normal renal function (totaln = 124). The main subtype of breast cancer was luminal A and relatively few patients with renal impairment received chemotherapy and anti-Her-2 treatment. The breast cancer patients with late-stage CKD had a slightly higher recurrent rate, especially at the locally advanced stage. The 5-year overall survival was 90.1 and 71.2% for patients without and with late-stage CKD, but the breast cancer-related mortality rate was 88.9 and 24.1%, respectively. In multivariate analyses, dose-reduced chemotherapy was an independent negative predictor of 5-year recurrence-free survival and late-stage CKD was associated with lower 5-year overall survivalrate. Breast cancer patients with late-stage CKD may receive insufficient therapeutic modalities. Although the recurrence-free survival rate did not differ significantly by the status of CKD, patients with breast cancer and late-stage CKD had shorter overall survival time but a lower breast cancer-related mortality rate, indicated that the mortality was related to underlying disease.

Review of the applicability of the DASH diet for patients with chronic kidney disease and chronic liver disease

Hypertension is a significant risk factor for cardiovascular diseases, and the DASH diet effectively lowers blood pressure. However, individuals with Chronic Kidney Disease (CKD) and Chronic Liver Disease (CLD) need adaptations in potassium and sodium/water intake to adhere to the DASH diet. This literature review examines the applicability of the DASH diet for patients with CKD and CLD by analyzing findings from a comprehensive search of relevant academic databases. The review explores various sources, including clinical studies, research articles, and expert recommendations, to assess the effectiveness and suitability of the DASH diet in managing the dietary needs of individuals with CKD and CLD. The review reveals that the DASH diet, with its emphasis on reduced sodium intake and increased consumption of fruits, vegetables, whole grains, and lean proteins, shows promising results in managing blood pressure and improving overall cardiovascular health in individuals with early stage CKD and CLD. Furthermore, the review concludes that individuals with advanced CKD and CLD should exercise caution when considering the DASH diet, as modifications are necessary to accommodate their specific conditions. For patients with advanced CKD, careful management of potassium intake is essential to prevent hyperkalemia; while individuals with late-stage CLD should monitor both sodium and water intake to avoid dilutional hyponatremia. Additionally, the review also emphasized the importance of individualized dietary modifications and consultations with healthcare professionals for optimizing the benefits of the DASH diet, especially for those patients with later stages of CKD and CLD.