Different Stages Of Chronic Kidney Disease Research Articles

Outcomes of leadless pacemaker in chronic kidney disease patients: real-world data from the i-LEAPER registry

Abstract Background Chronic kidney disease (CKD) represents a major risk factor for patients requiring transvenous pacemaker (TV-PM), resulting in a high rate of operative complications and PM-related infection rate (21.9% and 12.5%, respectively), with both complications parallels to severity of CKD. Moreover, TV leads represent an important concern for end-stage CKD patients, often needing vascular access patency for renal replacement therapy. In this setting leadless pacemakers (LPMs) represent an attractive alternative to TV-PM for their lower device-related infection rate and the absence of TV leads. To date, limited data on LPM safety and efficacy profile in CKD patients are available. Purpose to assess operative and long-term safety and efficacy of LPMs implantation in patients with different stages of CKD in the real-world setting. Methods Consecutive patients who underwent LPM implantation in 12 European centers joining the i-LEAPER registry were retrospectively enrolled. CKD stage was assessed according to CKD-EPI equation for eGFR. Patients with CKD stage G3a/b (N=245) and stage G4/G5 (N=67) were compared with patients with normal kidney function (NKF) (N=867). Primary safety endpoint was LPM-related major complications rate at implant and during follow-up (FU). Additionally, the rate of patients showing sub-optimal electrical performance (pacing threshold [PT] >1V@0.24ms) was compared between groups. Results 1179 patients were enrolled and followed for a median of 33 [IQR 24-47] months. When compared with the NKF group, patients with CKD stage G3a/b and stage G4/G5 showed a higher burden of cardiovascular comorbidities (Table 1). The choice of a LPM was mainly due to vascular concern in the CKD stage G4/G5 group, while a perceived highest infective risk was reported in CKD stage G3a/b group (Table 1). Major complication rate at implant and during FU did not differ between groups, regardless of renal impairment stage (Table 2). All-cause mortality incidence resulted higher in CKD stage G4/G5 group when compared with NKF group (17.9% vs 6.8%; HR 4.24; 95%CI 4.25-7.94, p<0.001) (Figure A). The rate of patients with PT>V1@0.24ms during FU did not differ between groups, not exceeding 13.8%, and therefore remaining consistent with historical data for LPM (Figure B). Conclusion In the real-world setting, LPM showed a remarkable safety and efficacy profile in CKD patients regardless of renal impairment stage that was comparable to NKF population. LPM should be considered as first choice in CKD patients requiring a PM.

#3012 Great impact of the results of PREMs and PROMs in all stages of chronic kidney disease. Analysis of 281 patients

Abstract Background and Aims In recent years, there has been a growing interest in the use and relevance of Patient-Reported Outcomes Measures (PROMs) and Patient-Reported Experience Measures (PREMs). The main objective of the study is to analyze scores in quality of life, anxiety, depression, and functional capacity using tests that assess PREMs and PROMs in patients at different stages of chronic kidney disease (CKD). Method Multicenter, cross-sectional, observational, non-interventional study with 281 patients (84 on hemodialysis, 48 on peritoneal dialysis, 50 with kidney transplant, 50 with advanced CKD, and 49 patients with CKD stages 1-2). Two professionals conducted interviews for data collection from all patients. Collected data: For PROMs: PFS (Piper Fatigue Scale), HADS (Hospital Anxiety and Depression Scale), FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue Scale), SF-36, VAS (Visual Analogue Scale). For PREMs - PACIC test (Patients' Assessment of Chronic Illness Care), in addition to other comorbidity indices and laboratory analyses. ANOVA statistical analysis was used for group comparison. Results Although patients showed significant differences in age and comorbidities, our analysis shows that the most PROMs do not discriminate between different stages of CKD. The PROMs that most discriminate between different stages of CKD are those related to the Piper Fatigue Scale test. PREMs, analyzed using the PACIC scale, do achieve said discrimination (Table 1). Conclusion The analysis of PROMs and PREMs show the significant impact that CKD has on health-related quality of life. Some PROMs can discriminate between different stages of CKD, but the most effective ones are PREMs, which are an indirect indicator of the quality of care received, contributing to patient involvement in decision-making and empowerment.

#2904 Chronic kidney disease staging in the very old: the role of cystatin C

Abstract Background and Aims Over the past decade, an unanswered question has emerged: which is the best equation for estimating glomerular filtration rate (eGFR) in older patients with chronic kidney disease (CKD)? Despite the lack of consensus, cystatin C appears to hold promise, as it is not influenced by factors often affected in the very elderly, such as muscle mass or protein intake, offsetting the limitations of creatinine-dependent formulas. This may have implications for correctly classifying patients across the different stages of CKD. The aim of this study is to analyze the concordance between different eGFR formulas and the Chronic Kidney Disease Epidemiology Collaboration formula combining the use of creatinine and cystatin C (CKD-EPIcr-cys), which is recommended by the European Renal Best Practice Group. Method A cross-sectional observational study was conducted with patients ≥85 years old with CKD admitted to an Acute Geriatric Unit due to acute illness over a period of four months. Variables included age, sex, previous Barthel Index (BI), dementia (defined by Reisberg's GDS≥4), frailty (FRAIL scale ≥3), polypharmacy (≥5 drugs), comorbidities (degree of CKD according to CKD-EPI, hypertension, diabetes mellitus, dyslipidemia, chronic heart failure (CHF), Charlson Comorbidity Index (CCI)), nutritional and laboratory parameters (Mini Nutritional Assessment-Short Form (MNA-SF), body mass index (BMI), serum cholesterol and albumin, glucose, glycated hemoglobin), and estimated glomerular filtration rate at admission by CKD-EPIcr-cys, CKD-EPIcys, CKD-EPI, MDRD and Cockcroft-Gault. The intra-class correlation coefficient (ICC) and the Kappa index were used to analyze concordance. Results A total of 407 patients were recruited, with a mean age of 90.7±4.1 years, 68.1% female. The previous BI was 59.1±32.3. Dementia was present in 28.3%. Frailty was noted in 66.6%, and polypharmacy in 90.9%. CKD stage: G3a (37.6%), G3b (44.2%), G4 (17.7%), G5 (0.5%). Comorbidities included hypertension (90.7%), CHF (68.3%), dyslipidemia (53.8%), and diabetes mellitus (37.8). The CCI was 2.9±1.8. MNA-SF score was 9.5±2.4 (18.4% malnutrition), and average BMI was 28±5.5 kg/m2 (29% obesity). The mean values for cholesterol, albumin, glucose, and glycated hemoglobin were 156.3±47.7 mg/dL, 35.5±4.6 g/L, 126.1±91.3 mg/dL, and 5.9±2%, respectively. The eGFR at admission according to CKD-EPIcr-cys was 31.9±12.2 mL/min/1.73 m2, while using CKD-EPI, CKD-EPIcys, MDRD, and Cockcroft-Gault were 37.5±14.5 mL/min/1.73 m2, 28.2±12.1 mL/min/1.73 m2, 42.8±16 mL/min/1.73 m2, and 30.4±11.7 mL/min/1.73 m2, respectively. The formulas showed high concordance with CKD-EPIcr-cys: CKD-EPI (ICC=0.90 [0.52 to 0.96; p < 0.001]), CKD-EPIcys (ICC=0.94 [0.79 to 0.97; p < 0.001]), MDRD (ICC=0.80 [-0.14 to 0.94; p < 0.001]), Cockcroft-Gault (ICC=0.86 [0.82 to 0.88; p < 0.001]). However, when comparing stratification into different stages of CKD, the concordance with the various formulas was lower: CKD-EPI (k=0.4; p < 0.001), CKD-EPIcys (k=0.59; p < 0.001), MDRD (k=0.12; p < 0.001), Cockcroft-Gault (k=0.4; p < 0.001). When referencing CKD-EPIcr-cys, it is notable that only 34.3% of patients were correctly classified using MDRD, followed by CKD-EPI (57.1%), Cockcroft-Gault (59.8%), and CKD-EPIcys (73%). Specifically, of the patients classified as stage G4 according to CKD-EPIcr-cys, there was a reclassification to stage G3b in 2.1% (CKD-EPIcys), 18.1% (Cockcroft-Gault), 33.3% (CKD-EPI), and 52.1% (MDRD). Conclusion

#1984 Extracellular vesicles drive loss of endothelial homeostasis in pediatric chronic kidney disease

Abstract Background and Aims Cardiovascular disease (CVD) is the main cause of mortality in chronic kidney disease (CKD). However, the pathogenesis of CVD in CKD remains incompletely understood. Extracellular vesicles (EVs) emerged as mediators of inter-organ cross-talk and endothelial EVs (EC-EVs) were previously associated with CVD. We hypothesized that CKD drives endothelial EV release in CKD and that these EC-EVs drive CVD in CKD. Method A cohort of 94 children (mean age 10.9 years) at different stages of CKD (patients with or without dialysis and after kidney transplantation (KTx)) and age-matched healthy donors was recruited, offering the unique opportunity to analyze cardiovascular effects of CKD and EV dynamics in absence of age-related comorbidities. Thorough characterization of plasma EVs by electron microscopy, nanoparticle tracking analysis (NTA), flow cytometry and miRNA sequencing was carried out. Functional properties of patient EVs and CKD-specific EV release mechanisms were tested in vitro. Results EC-EVs were elevated in hemodialysis (HD) patients (as measured by flow cytometry) while total EV counts showed higher concentrations in peritoneal dialysis patients (according to NTA). Longitudinal follow-ups revealed that EC-EVs decreased after receiving KTx. EV small RNA sequencing showed lower abundance of 30 microRNAs in EVs from CKD patients, most pronounced in HD patients compared to both healthy donors and KTx recipients. Downregulation of let-7d-5p, miR-19a-3p, miR-24-3p, miR-103a-3p and miR-142-3p was confirmed using RT-qPCR. Gene enrichment analyses predicted angiogenesis and smooth muscle cell (SMC) proliferation as targets of differentially regulated miRNAs in CKD. In vitro, angiogenesis of Human Umbilical Vein Endothelial Cells (HUVECs) was decreased upon treatment with CKD EVs as indicated by decreased vascular tube formation, endothelial migration and proliferation while SMC proliferation remained unchanged. To assess the putative role of uremic toxins for EV release in CKD, we focused on tryptophan metabolites and performed targeted plasma metabolomics that showed stage-dependent increases of uremic toxins of indole and kynurenine pathways in children with CKD, with highest levels in dialysis patients and almost normal levels after KTx. Uremic toxins indoxyl sulfate, formylkynurenine and xanthurenic acid correlated positively with EC-EVs in our cohort, but were not sufficient to trigger EV release from aortic endothelial cells alone. However, high shear stress together with indoxyl sulfate increased EV release from venous endothelial cells corresponding to higher endothelial EV concentrations in HD patients with arterio-venous fistulas (AVF) and recapitulated EV miRNA changes in vitro observed in CKD in vivo (lower abundance of let-7d-5p and miR-24-3p). Conclusion Endothelial EV release and decreased EV miRNAs associate with advanced CKD while increased endothelial shear stress and indoxyl sulfate form potential causative factors of altered EV phenotype. CKD EVs inhibit angiogenesis in vitro, potentially caused by dysregulated EV miRNAs that could form novel therapeutical targets to reduce CVD burden in CKD.

#2343 Fabry disease screening in patients with chronic kidney disease and dialysis at a single medical center in Taiwan

Abstract Background and Aims Chronic Kidney Disease (CKD) poses a significant global health challenge, with diverse contributing factors impacting its progression. Among these, Fabry Disease, a rare lysosomal storage disorder, has emerged as a potential complicating factor. Despite its relevance, the prevalence of Fabry Disease among CKD patients, particularly in Taiwan, remains insufficiently explored. Recognizing and understanding the occurrence of Fabry Disease in CKD populations are crucial for comprehensive patient care and may have implications for treatment strategies. Additionally, investigating the relationship between kidney function and Plasma α-Gal A activity is essential. α-Gal A, the enzyme deficient in Fabry Disease, may experience altered activity levels in the presence of compromised kidney function. Clarifying this connection is pivotal for gaining insights into the intricate interplay between Fabry Disease and CKD. This study aims to achieve three key objectives (1) Determine Fabry Disease Prevalence among CKD Patients in Taiwan.(2) Investigate the Impact of Kidney Function on Plasma α-Gal A Activity.(3) Characterize Gene Mutation Patterns and Demographic Data of Fabry Patients in CKD Population in Taiwan: Method Fabry Disease assessment involved a two-stage process, tailored to the patient's gender. Males underwent a dry blood test measuring α-galactosidase activity; samples below 15% of the adult average were deemed positive. Females were screened based on lyso-Gb3 levels in whole blood; a result exceeding 0.8 ng/ml was considered positive. Positive screenings prompted genomic DNA extraction, and the GLA gene's seven exons and intron 4 segment ([GRCh38/Hg38] chrX:101,399,610-101,399,874) were PCR-amplified. Sanger sequencing identified pathogenic variants. This gender-specific, multi-step approach ensures precision. Defined thresholds and advanced genomic techniques enhance diagnostic accuracy. The method provides a robust means of identifying Fabry Disease, supporting early intervention and personalized treatment. Results Study Recruitment: Initially, 2000 subjects enrolled, but 155 withdrew, yielding a final cohort of 1845 patients for analysis. Screening and Referral: Among 1602 subjects, 26 males (1.6%) were referred for DBS LysoGB3 check-up due to low serum α-Gal A activity. In a cohort of 243 females, 6 individuals (2.4%) underwent GLA genetic sequencing due to elevated lyso-GB3 levels. Clinical Presentation - Male Case: A male with acute stroke symptoms and CKD stage 3b (eGFR 34.5 mL/min/1.73 m²) showed significantly low DBS α-Gal A activity (0.48 μmol/hr) and elevated Plasma LysoGB3 (28.08 ng/ml).GLA genetic sequencing revealed a specific deletion (c.1072-1074delGAG, p. (Glu358 del)) in exon 7, leading to a Fabry disease diagnosis, classifying it as a specific type. The family pedigrees of this male patient are visually represented in Fig. 1, illustrating the genetic relationships within the family. Clinical Presentation - Female Case: A female on hemodialysis for four years, cause unknown, exhibited a DBS LysoGB3 level of 0.5 ng/ml. GLA genetic sequencing identified a nucleotide variation (c.640-801G>A) in intron 4, establishing a diagnosis of Fabry disease with the cardiac variant (301500). Fig. 2 demonstrates the relationship between serum DBS GLA activity and different stages of CKD. Our analysis reveals that in CKD stages 1, 2, 3 (3a and 3b), and 4, the serum GLA activity is significantly higher compared to stage 5. Conclusion The prevalence of Fabry Disease in our cohort was 0.1% (2 out of 1845 individuals), featuring one female with the cardiac variant and one male with the class type. Our investigation unveiled a significant rise in serum GLA activity in CKD stages 1–4 compared to stage 5, suggesting potential implications for early CKD detection. Moreover, serum α-Gal A activity displayed a notable correlation with age, BUN, and eGFR across CKD stages 1–5, questioning its status as a biomarker for advanced CKD and aging in CKD patients. This prompts consideration for a large-scale study to validate this hypothesis.

#331 Vascular and lipid profile interplays in pediatric CKD patients

Abstract Background and Aims Chronic kidney disease (CKD) is characterized by irreversible kidney damage and/or progressive loss of function. Children with CKD often have additional CVD risk factors, including hypertension and dyslipidemia. They may have myocardial abnormalities and early atherosclerosis evidence, such as coronary artery calcification, abnormal flow-mediated dilation, increased carotid intima-medial thickness (CIMT), and increased aortic stiffness. These abnormalities seem to be, in part, related to the degree of uremia. This study aimed at assessing the interrelationship between vascular status and lipid profile abnormalities in different stages of CKD in pediatric patients. Method This cross-sectional study was done on 99 patients: 33 with stage 5 CKD on regular hemodialysis & 33 pre-dialysis CKD stage 2-4 on conservative management & 33 age and sex matched controls. Anthropometric measures, blood pressure readings, and a lipid profile were done to all groups. Intima media thickness was measured using B-mode ultrasound doppler in both the common and internal carotid arteries (CCA, ICA). Which is a non-invasive way to measure the artery walls and track the early impacts of the atherosclerotic process. Results There was an obvious increase in blood pressure the percentiles in all CKD patients in relation to controls. The waist-to-hip ratio in CKD 2-4 patients was significantly higher than in CKD 5 patients, and both were higher than the controls, with means (±SD) of 1.01 (0.19), 0.88 (0.10), and 0.86 (0.05), respectively. Except for high-density lipoproteins (HDL), the lipid profile, including triglycerides, cholesterol, and low-density lipoproteins (LDL), were all significantly increased when comparing CKD 2-4 to CKD 5, and both higher than the controls: 170.45 (42.04), 166.00 (45.57), and 100.88 (26.19) for triglycerides (p 0.001). The right and left ICA and CCA showed a significant increase in the intimal thickness being higher in the CKD 5 group than the CKD 2-4 and both higher than the controls. On studying the correlation between the duration of CKD in years and other variables, we found a positive correlation with triglycerides (r = 0.409 & p = 0.001) and right CCA IMT (r = 0.271 & p = 0.028); however, the HDL (r = −0.326 & p = 0.007) revealed a negative correlation in all CKD patients. The HDL level showed an inverse correlation with right CCA and ICA. Conclusion Patients with CKD have an increased waist-to-hip ratio, dyslipidemia, and increased carotid IMT, which are factors that lead to the early development of atherosclerosis. Special care should be directed to CKD patients, especially those in stages 2-4, to control their lipid profile and postpone the development of atherosclerosis as much as possible.

#511 Inadequate diagnostic investigations and low treatment rates in CKD anemia: an inertia that can only change with long-term follow-up

Abstract Background and Aims Anemia is observed from the early stages in the course of chronic kidney disease (CKD), and as the stage progresses, the severity of anemia and its impact on quality of life increase. Early diagnosis of anemia in chronic kidney disease, assessments related to its etiology, and treatment are therefore crucial. There is no comprehensive and long-term study in Turkey addressing the diagnostic and therapeutic management of anemia seen in the course of chronic kidney disease. The aim of this study is to investigate the frequency of anemia in different stages of CKD in patients diagnosed with Stage 3 and more advanced stages, to evaluate the effectiveness of diagnostic approaches, and management of iron parameters and anemia, and to investigate the effect of anemia on patient survival. We aim to present “real-life” data from this study to guide clinical practice and correct errors or deficiencies in anemia management. Method This study is a single-center, observational-descriptive retrospective study. 1321 outpatients with Stage 3A and advanced CKD and anemia who admitted to Hacettepe University Faculty of Medicine Nephrology Clinic between 2014 and 2018 were included in the study. Data for demographics, CKD etiologies and stages, anemia severities, comorbid diseases were collected from electronic health system (Table 1). Diagnostic investigations for anemia evaluation and therapeutic interventions such as administration of iron, folic acid, vitamin B12, erythropoiesis stimulating agents (ESA) were assessed. The long-term yield of diagnostic and therapeutic approaches and their effects on survival were also evaluated. The study investigated whether the severity of anemia and improvement in anemia had an effect on survival. Results Ferritin is the most commonly performed test for the etiology of anemia (76.4%). Request rates for tests such as B12, folic acid, transferrin saturation and reticulocyte are below 20%. More than half of the patients with anemia (59.4%) have not received any form of anemia treatment. Even among those whose ferritin test was checked and the value was <100 µg/dL, only 41.4% were given iron treatment. As the clinical follow-up period of the patients increased, it was observed that anemia treatment was applied better and target values were reached more frequently (p < 0.001). More than one third of the patients (34.8%) died during follow-up. The overall survival in patients whose anemia improved was 79.8%, and it was 62.8% in patients whose anemia did not improve the overall survival was (p = 0.002) (Fig. 1). When examining the relationship between survival status and anemia severity for the non-dialysis-dependent CKD Stage 3-5 group, there was a statistically significant survival difference between the Hb group of 10-11.9 g/dL to Hb group of <10 g/dL (p = 0.004). Conclusion This study has shown that diagnostic tests for etiology of anemia were insufficiently ordered. It was also found that a significant majority of anemic patients who underwent etiological evaluation were not even adequately treated. Long-term follow up improved anemia treatment, and patients with improved anemia had better survival. In conclusion, we recommend an optimal evaluation of CKD patients with anemia and initiating treatment as early as possible.

#2477 Longitudinal serum bicarbonate and mortality risk in older patients with advanced chronic kidney disease: analyses from the EQUAL cohort

Abstract Background and Aims Serum bicarbonate (SBC) disorders have been consistently linked to mortality in chronic kidney disease (CKD) patients. Low SBC levels have been extensively associated with increased mortality in CKD patients, possibly due to the detrimental effects of acidosis on various organs and systems. Likewise, several studies have identified high levels of SBC as a risk factor for mortality in the CKD population. To date, most studies have focused on the association between SBC levels and patient survival during the pre-kidney replacement therapy (KRT) period or the period after KRT initiation, considered separately. None have explored this association across the continuum of CKD (e.g., from pre-KRT to post-KRT start), which is relevant since metabolic acidosis is expected to be managed through dialysis in the KRT population, and thus its clinical outcomes might change after KRT initiation. To provide new insights on this topic, we aimed to explore the relationship between SBC and mortality in advanced CKD during three distinct treatment periods: during the pre-KRT period, during the transition phase surrounding the start of KRT (transition-CKD), and during KRT. Method Using the European QUALity Study on treatment in advanced CKD (EQUAL) cohort, which includes patients aged ≥65 years and eGFR ≤20 ml/min per 1.73 m2 from six European countries, we explored the association between longitudinal SBC and all-cause mortality in three separate CKD populations: pre-KRT, transition-CKD and in the KRT populations, using multivariable time-dependent Cox regression models. The cumulative time-averaged, the cumulative exposure of SBC, and the slope of the SBC trajectory during the pre-KRT phase were calculated and evaluated for association with all-cause mortality in the transition-CKD population. Subgroup analysis were used to evaluate the effect modification by pre-specified variables on the relationship between SBC and mortality. Results We included 1485 patients with a median follow-up of 2.9 (IQR 2.7) years, during which 529 (35.6%) patients died. A U-shaped relationship between SBC levels and all-cause mortality was observed in the pre-KRT population (p = 0.03; Fig.). Low cumulative exposure, defined as the area under the SBC trajectory before KRT initiation, was associated with increased mortality risk after transitioning to KRT (p = 0.01). Similarly, in the KRT population, low SBC levels showed a trend towards increased mortality risk (p = 0.13). We observed effect modification on the relationship between SBC and mortality by subjective global assessment category (p-value for interaction = 0.02) and KRT initiation (p-value for interaction = 0.02). Conclusion Our study has provided important insights into the relationship between SBC and mortality in advanced CKD patients. A U-shaped relationship describes the association between SBC and mortality in the advanced CKD pre-KRT population, whereas in patients that initiate KRT only low SBC levels are associated with an increased mortality risk. Our findings suggest that the relationship between SBC and mortality varies across different stages of CKD and that this relationship is modified by KRT initiation. From this point of view, it would be appropriate to consider a personalized management of acid-base balance disorders based on a comprehensive evaluation of the clinical status of the patient.

#2034 CKD-MBD management: results from a national survey on bone turnover biomarkers practice and therapeutic strategies among Italian nephrologists

Abstract Background and Aims Advanced stages of chronic kidney disease (CKD) are constantly characterized by a mineral and bone disorders (MBD) syndrome concerning a complex systemic condition that includes laboratory abnormalities of bone and mineral metabolism involving calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; abnormalities in bone turnover, mineralization, volume, or strength; extra-skeletal calcifications, such as vascular or other soft tissue. CKD-MBD syndrome determines relevant consequences in terms of fragility fractures, cardiovascular events and higher mortality. The nephrologist's awareness of CKD-MBD diagnostic and management tools and therapeutic strategies is key to improving CKD patients’ prognosis and outcomes. Method A new national survey (composed of 17 online questions) was conducted among Italian nephrologists to investigate the reference laboratory availability of bone turnover markers (BTMs), the clinical attitude on secondary hyperparathyroidism (sHPT) management, and the CKD-MBD therapeutic approach in different stages of CKD and dialysis patients. Results 89 Italian nephrologists participated in the survey. The reference laboratories largely fulfill the biomarkers request of ionized calcium (97.7%), phosphorus (100%), PTH (100%), alkaline phosphatase (ALP) (100%), magnesium (100%), 25-OH and 1,25-OH vitamin D levels (92.1%; 53.9%); while most of the hospital laboratories do not regularly support the availability of specific BTMs, both for diagnosis and monitoring the bone resorption and formation (Fig. 1)—such as bone ALP (75.3%), calcifediol (37.1%), calcitriol (40.5%), fibroblast growth factor-23 (FGF-23) (intact 9% and c-terminal 4.5%), vitamin K (33.7%), Klotho (6.75%, soluble 4.5%), osteocalcin (38.2%), matrix gla protein (10.1%), tartrate-resistant acid phosphatase 5b (TRAP-5b) (6.75%), cross-linked collagen type I peptide (CTX) (32.6%) and procollagen type 1 n-terminal propeptide (P1NP) (10.1%). The nephrologist's attitude to start management and treatment of sHPT is revealed to be mainly led by KDOQI (n = 42, 47%) and KDIGO (n = 39, 44%) guidelines considering their PTH cut-off values; in 53.9% of clinicians the measure of PTH levels is then performed every 3 months according to KDOQI guidelines. In relation to the definition of high turnover metabolic bone disease by BTMs, this metabolic pattern is identified in > 50% and 30-40% of patients with CKD 4-5D by 31.5% and 21.4% of nephrologists, respectively. 65% of clinicians currently considered ALP of equal importance as alterations of PTH as a predictor of fracture events. Other biomarkers, such as FGF-23, P1NP or TRAP-5b, emerge to not be still used in regular clinical practice. In patients diagnosed with CKD-MBD and skeletal fragility, 76.4% of nephrologists consider the AIFA (Italian Medicines Agency) note 79 to support osteoporosis treatment. The therapeutic strategies of CKD-MBD include the administration of vitamin D (e.g. cholecalciferol 27-37.1%, calcifediol 9-12.4%, calcitriol 42.7-55.1%) and its analogues (e.g. paricalcitol 23.6-52.8%) and the use of antiresorptive agents (e.g. alendronate 3.4%-23.6%, denosumab 22.5%-30.3%) with variable frequencies among different advanced CKD stages and for those patients on peritoneal or hemodialysis (Fig. 2). Conclusion Results present a suboptimal use of BTMs and a current heterogeneous therapeutic management of CKD-MBD syndrome and renal osteodystrophy in Italian clinical practice. The survey represents a starting point of work to further implement awareness of diagnostic and therapeutic issues of CKD-MBD.

Prevalence of dysmagnesemia among CKD patients in North India

Prevalence of dysmagnesemia among CKD patients in North India

Financial Toxicity in Renal Patients (FINTORE) Study: A Cross-Sectional Italian Study on Financial Burden in Kidney Disease-A Project Protocol.

Financial toxicity (FT) refers to the negative impact of health-care costs on clinical conditions. In general, social determinants of health, especially poverty, socioenvironmental stressors, and psychological factors, are increasingly recognized as important determinants of non-communicable diseases, such as chronic kidney disease (CKD), and their consequences. We aim to investigate the prevalence of FT in patients at different stages of CKD treated in our universal health-care system and from pediatric nephrology, hemodialysis, peritoneal dialysis and renal transplantation clinics. FT will be assessed with the Patient-Reported Outcome for Fighting Financial Toxicity (PROFFIT) score, which was first developed by Italian oncologists. Our local ethics committee has approved the study. Our population sample will answer the sixteen questions of the PROFFIT questionnaire, seven of which are related to the outcome and nine the determinants of FT. Data will be analyzed in the pediatric and adult populations and by group stratification. We are confident that this study will raise awareness among health-care professionals of the high risk of adverse health outcomes in patients who have both kidney disease and high levels of FT. Strategies to reduce FT should be implemented to improve the standard of care for people with kidney disease and lead to truly patient-centered care.

A real-world exploration into clinical outcomes of direct oral anticoagulant therapy in people with chronic kidney disease: a large hospital-based study.

There is limited evidence to support definite clinical outcomes of direct oral anticoagulant (DOAC) therapy in chronic kidney disease (CKD). By identifying the important variables associated with clinical outcomes following DOAC administration in patients in different stages of CKD, this study aims to assess this evidence gap. An anonymised dataset comprising 97,413 patients receiving DOAC therapy in a tertiary health setting was systematically extracted from the multidimensional electronic health records and prepared for analysis. Machine learning classifiers were applied to the prepared dataset to select the important features which informed covariate selection in multivariate logistic regression analysis. For both CKD and non-CKD DOAC users, features such as length of stay, treatment days, and age were ranked highest for relevance to adverse outcomes like death and stroke. Patients with Stage 3a CKD had significantly higher odds of ischaemic stroke (OR 2.45, 95% Cl: 2.10-2.86; p = 0.001) and lower odds of all-cause mortality (OR 0.87, 95% Cl: 0.79-0.95; p = 0.001) on apixaban therapy. In patients with CKD (Stage 5) receiving apixaban, the odds of death were significantly lowered (OR 0.28, 95% Cl: 0.14-0.58; p = 0.001), while the effect on ischaemic stroke was insignificant. A positive effect of DOAC therapy was observed in advanced CKD. Key factors influencing clinical outcomes following DOAC administration in patients in different stages of CKD were identified. These are crucial for designing more advanced studies to explore safer and more effective DOAC therapy for the population.

Adverse pregnancy outcomes in pregnant women with chronic kidney disease: A systematic review and meta-analysis.

Chronic kidney disease (CKD) is associated with an increased risk of adverse pregnancy outcomes, but the risk at different stages of CKD (defined by estimated glomerular filtration rate, eGFR) compared with women without CKD has not been quantified in large cohorts. To quantify the association between CKD and adverse pregnancy outcomes according to CKD definition, CKD stage and presence or absence of diabetes. A systematic search of EMBASE and MEDLINE from inception to 5 January 2023. English-language randomised controlled trials as well as cohort and case-control studies investigating adverse pregnancy outcomes in pregnant women with CKD. Two reviewers conducted independent data extractions. A random-effects model was used to estimate risk. We included 19 studies with 3 251 902 women. Defining CKD using eGFR or serum creatinine produced results with greater effect size but wider confidence intervals. Compared with CKD stages 1-2, women with CKD stages 3-5 have a greater risk, but also greater imprecision in the risk estimate, of the following outcomes: pre-eclampsia (OR 55.18, 95% CI 2.63-1157.68, vs OR 24.74, 95% CI 1.75-348.70), preterm birth (OR 20.24, 95% CI 2.85-143.75, vs OR 8.18, 95% CI 1.54-43.46) and neonatal intensive care unit admission (OR 19.32, 95% CI 3.07-121.68, vs OR 9.77, 95% CI 2.49-38.39). Women with diabetic kidney disease, compared with women without diabetic kidney disease, have higher risks of maternal mortality, small-for-gestational-age neonates, pre-eclampsia and gestational hypertension. There is heterogeneity in the definition of CKD in pregnancy. Future studies should consider ways to standardise its definition and measurement in pregnancy.

ASSESSMENT OF COMPLETE BLOOD COUNT AND LIVER ENZYMES IN CHRONIC KIDNEY DISEASE PATIENT

Chronic renal failure (CRF) poses a significant global health challenge, with chronic kidney disease (CKD) characterised by kidney damage or a glomerular filtration rate (GFR) persistently below 60 ml/min for over three months. This observational study, conducted in Faisalabad from January to July 2023, aimed to evaluate haematological variables and liver enzymes across different stages of CKD. Using non-probability purposive sampling, 144 CKD patient files and 48 healthy control files were collected, excluding specific conditions. CKD staging was determined using the Modification of Diet in Renal Disease (MDRD) algorithm, categorizing patients into mild (Group A), moderate (Group B), severe (Group C) CKD, and controls (Group D). Data analysis was performed using SPSS v23. Mean ± SD values were presented for each parameter across the four groups. Haemoglobin levels (Hb g/dl) exhibited a decreasing trend in CKD patients compared to the control group, with values of 13.7 ± 1.50 in controls, 11.7 ± 0.64 in Group 1, 9.7 ± 0.57 in Group 2, and 6.7 ± 1.5 in Group 3. Red blood cell count (RBCs per million/mm3) also decreased progressively in CKD patients compared to controls, with values of 5.48 ± 0.59, 4.62 ± 0.15, 3.57 ± 0.28, and 2.81 ± 0.23 in the respective groups. Conversely, white blood cell counts (WBC thousand/mm3) increased with CKD progression, showing values of 8406 ± 1383 in controls, 10674 ± 1006 in Group 1, 12028 ± 643.5 in Group 2, and 13564 ± 741.29 in Group 3. Similarly, platelet counts (lakh/ul) exhibited a decreasing trend in CKD patients compared to controls, with values of 324708 ± 112970, 235458 ± 63853, 144979 ± 6935.8, and 126333 ± 4768.3, respectively. Analysis of liver enzymes revealed a progressive decrease in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as CKD advanced. AST levels (U/L) decreased from 29.104 ± 3.130 in controls to 7.5825 ± 1.543 in Group 3, while ALT levels (U/L) decreased from 48.145 ± 4.9679 in controls to 12.270 ± 3.3500 in Group 3. Our findings demonstrate that haemoglobin, red blood cell count, platelet count, and liver enzyme levels (AST and ALT) decrease as CKD progresses while white blood cell count increases. These insights into haematological and hepatic biomarkers underscore the dynamic nature of CKD pathology and may inform clinical management strategies.

Effects of Dietary Protein Restriction on Nutritional Status of Hemodialysis Patients

Haemodialysis is one of the three renal replacement therapies in which waste products and excess fluid are removed from blood when kidneys stop functioning properly. Protein catabolism is increased as patients lose some protein during haemodialysis treatment. Sufficient protein intake is of great significance, yet prevalence of inadequate protein consumption persists due to various reasons, resulting protein-energy malnutrition (PEM). The studies regarding low protein intake among haemodialysis patients is lower compared to studies conducted on non-dialysis chronic kidney disease (CKD) patients. The purpose of this study was to investigate the prevalence of protein restriction practices and its effect in nutritional status of haemodialysis patients. The study was descriptive exploratory analysis among 150 haemodialysis patients at one of the largest dialysis center of Kathmandu district using anthropometric, biochemical, clinical and dietary (ABCD) assessments. Among 150 haemodialysis patients, majority (63.3%) were male. 71.3% were undergoing haemodialysis for more than 1 to 5 years and 82.7% doing twice a week in- center haemodialysis. According to serum albumin report, 66.7% were identified as PEM. Body mass index (BMI) result also classified 3.3% as underweight. It was concluded that the effect of protein restriction resulted as malnourished among certain patients. The underlying causes for consuming low protein diets were associated with dislike to protein-rich foods, financial constraints, lack of awareness, and other factors. Establishing regular consultations with dieticians and closely monitoring dietary patterns appeared as crucial approaches for enhancing the nutritional status of these patients. It is essential to acknowledge that protein requirements vary based on different stages of CKD and the presence of concurrent health conditions. Consistent follow-up by a multidisciplinary team, utilizing a range of nutrition assessment methods specified for haemodialysis patients is vital step.

Uric acid level in Chronic Kidney Disease patients and its association with other established CKD risk factors

Introduction: Chronic Kidney Disease (CKD) is a rising global health concern with increased cardiovascular risks. Hyperuricemia, linked to CKD and related conditions, warrants investigation. Objectives: This study examines the uric acid in different stages of CKD and the association between uric acid levels and established CKD risk factors. Methodology: A hospital-based prospective cross-sectional study was conducted at Birat Medical College Teaching Hospital from 10 June 2023 to 30 August 2023. We enrolled 90 patients with non-dialytic chronic kidney disease (CKD) by complete enumeration sampling method. Ethical approval was obtained from the institutional review committee of the college. Written informed consent was obtained from each participant. Data was collected by means of a self developed questionnaire. Blood samples were obtained for estimation of serum creatinine and uric acid level and recorded in Microsoft excel sheet and analyzed by using SPSS software version 23. Results: Hyperuricemia was seen in 33(36.7%) ranging from 3.5-12 mg/dl with an average uric acid level of 6.38 mg/dl and a standard deviation of 1.43 mg/dl of total 90 patients. The mean serum uric acid level was highest in stage 2 CKD which includes 6.88±2.10 ranging from 4.3-12 mg/dl. CKD patients with a history of alcohol intake had increased risk of hyperuricemia and it was statistically significant (p value 0.005). Different stages of CKD (p value: 0.70), age groups, (p value 0.17), gender(P value 0.082), diabetes(p value 0.954), hypertension(p value 0.364), other CVDs(p value 0.649)and anemia(p value 0.0602)had no statistical significant association with hyperuricemia. Conclusion: In conclusion, hyperuricemia prevalence was observed in CKD patients, with the highest levels in stage 2 CKD. Notably, alcohol intake significantly correlated with hyperuricemia, while other studied factors did not show significant associations.

Left ventricular hypertrophy (LVH) in different stages of chronic kidney disease (CKD) patients and its correlation with anaemia

Background : Chronic kidney disease (CKD) is a public health problem that increases the risk of cardiovascular morbidity and mortality. Heart failure with preserved ejection fraction characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction is a common cardiovascular complication of CKD. Anaemia is present in both dialysis & non dialysis CKD patients. Anaemia causes left ventricular hypertrophy (LVH) which in turn leads to increases morbidity and mortality in CKD, even before progression of chronic kidney disease (CKD) to end stage renal disease (ESRD). Our study is aimed at to evaluate the prevalence of left ventricular hypertrophy (LVH) and its correlation with anaemia in hospitalized CKD patients. Materials and Methods : A cross-sectional study was done on 50 patients of different stages of CKD admitted in the chittagong medical college hospital (CMCH). All the clinical data were reviewed and recorded. Data was analyzed by SPSS-18 and p value <0.05 was considered statistically significant. Results : Majority of study population 64% was male, 36% was female. Most of the male patient (40%) of the study population were having abnormal left ventricular mass index (>130 gm/m2). More patients with severe left ventricular hypertrophy were found in stage 5 of CKD in female and male which was 8 and 23 respectively. Regarding correlation of Hb% with LVMI there was a significant negative correlation was found (r= -0.420, p = 0.003) between them means if Hb% decreases LVMI level increases. It was also found in male and female patients separately ( for male r = -0.778, p = 0.001 and for female r = -0.746, p = 0.001). Conclusion : Anemia is widely prevalent in our CKD patients. Severity of anemia is correlated to left ventricular hypertrophy in these patients. Hence correction of anemia early in these group of patients can halt or prevent cardiovascular morbidity and mortality. J Bangladesh Coll Phys Surg 2024; 42: 25-30

Implications of Untreated Hypertension on Chronic Kidney Disease: A Literature Review

The untreated progression of hypertension holds significant implications for the development and progression of chronic kidney disease (CKD). Therefore, necessitating the implementation of strategic hypertension management measures to mitigate its impact on CKD. This review highlights the necessity of precise diagnostic methodologies that employ oscillometric equipment and advocates for pharmacological interventions, the incorporation of combination therapies such as the "Polypill" to effectively control hypertension, and lifestyle adjustments. The pivotal role of the renin-angiotensin-aldosterone system (RAAS) in hypertension is acknowledged, noting the importance of stringent blood pressure regulation and the utilization of RAAS-blocking agents to attenuate its association with CKD. A comprehensive analysis is provided on the effects of various classes of antihypertensive medications on renal function, encompassing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and nonsteroidal mineralocorticoid receptor antagonists. Additionally, both non-invasive and invasive therapeutic modalities for managing resistant hypertension in CKD patients are examined, alongside discussions on prognostic indicators and outcomes across different stages of CKD. Lifestyle modifications such as sodium restriction, weight management, and moderation of alcohol intake are assessed for their influence on CKD prognosis. The review also extensively delves into the impact of ethnicity on the prevalence and outcomes of hypertension-induced CKD, highlighting disparities and distinctive trends among diverse ethnic cohorts including Indian, African American, Middle Eastern, Chinese, Pacific Islander, Native American, and Hispanic populations. Additionally, this study addresses the intricate relationship between cardiovascular abnormalities and CKD, the significance of gastrointestinal disorders, and the importance of multidisciplinary approaches in CKD management. Furthermore, insights are provided into the significance of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for identifying renal injury and CKD progression, alongside factors influencing adverse prognosis and life expectancy in CKD patients. This study accentuates the importance of tailored treatment assessments and interventions to address varied patterns and obstacles within ethnic groups, with the aim of optimizing CKD management strategies and reducing health disparitie

Speckle-Tracking: Incremental Role in Diastolic Assessment of Pediatric Patients with Chronic Kidney Disease.

Cardiovascular complications are the leading cause of mortality in pediatric patients with chronic kidney disease (CKD). Echocardiographic assessment of diastolic function in CKD has been limited to spectral and tissue Doppler imaging, known to be less reliable techniques in pediatrics. Two-dimensional Speckle tracking echocardiography (2DST) derived left atrial (LA) strain has recently been confirmed as a robust measure of diastolic function. To investigate LA strain role in diastolic assessment of children at different stages of CKD. From February 2019 to July 2022, 55 CKD patients without cardiovascular symptoms and 55 controls were evaluated by standard and 2DST echocardiograms. The level of significance was set at 5% (p<0.05). Patients and controls had similar age [9.78 (0.89 - 17.54) vs. 10.72 (1.03 -18,44) years; p = 0.41] and gender (36M:19F vs. 34M:21F; p=0.84). There were 25 non-dialysis patients and 30 dialysis patients. Left ventricular ejection fraction was ≥ 55% in all of them. Comparing CKD and controls, LA reservoir strain was lower (48.22±10.62% vs. 58.52±10.70%) and LA stiffness index was higher [0.14 (0.08-0.48)%-1 vs. 0.11 (0.06-0.23) %-1]; p<0.0001. LV hypertrophy was associated with lower LA reservoir strain (42.05±8.74% vs. 52.99±9.52%), higher LA stiffness [0.23(0.11 - 0.48)%-1 vs. 0.13 (0.08-0.23) %-1 and filling indexes (2.39±0.63 cm/s x %-1 vs. 1.74±0.47 cm/s x %-1; p<0.0001. Uncontrolled hypertension was associated with lower LA reservoir strain (41.9±10.6% vs. 50.6±9.7; p=0.005). LA strain proved to be a feasible tool in the assessment of pediatric CKD patients and was associated with known cardiovascular risk factors.

Chronic kidney disease in patients with long-term type 1 diabetes mellitus

BACKGROUND: Patients with type 1 diabetes mellitus (T1D) have an earlier age of onset and a longer course of the disease, already by middle age they have the development of microand macrovascular diabetic complications that reduce the quality and duration of life.AIM: To evaluate the prevalence of chronic kidney disease (CKD) and other late complications of T1D depending on renal dysfunction in the population of patients with T1D with disease duration of 20 and more years, who underwent examination and treatment in Endocrinology Research Centre.MATERIALS AND METHODS: A one-stage single-center epidemiological non-randomised study was conducted using the database of Endocrinology Research Centre with the study of 500 patients’medical histories with long-term T1D (20 years and mores), without kidney damage and with CKD at different stages (CKD C1–C5, C5D, after transplantation), examined and treated from 2011 to 2023.RESULTS: Normal renal function was observed in 10.8% of patients (n=54). Terminal stage of CKD was reached in 28.0% (n=140), of which 12.4% were on renal replacement therapy with program hemodialysis (RRT-HD), and 12.0% after isolated kidney transplantation or combined kidney and pancreas transplantation, the rest were at different stages of CKD. Normoalbuminuria was observed in 15.4% (n=77) among 500 patients. The prevalence of late complications of DM among the examined patients was high and increasing with the progression of renal dysfunction: diabetic retinopathy was diagnosed in 96% of patients, distal symmetrical polyneuropathy — in 97% of patients, various forms of autonomic neuropathy — in more than half of patients. About 60% of patients had diagnosed arterial atherosclerosis in the legs, about one third — atherosclerosis of brachiocephalic arteries, 23% — confirmed coronary heart disease, and suffered cardiovascular events (myocardial infarction, acute cerebral circulation disorder) — 19% of patients, about half of whom had CKD of different severity. Factors for increased risk of cardiovascular disease: estimated glomerular filtration rate (eGFR)&lt;60 mL/min/1.73m2, OR=7.1; 95% CI 3.6–8.4; p&lt;0.001), eGFR &lt;30 mL/min/1.73m2 OR=8.7; 95% CI 2.8–8.4; p&lt;0.001), eGFR &lt;15 mL/min/1.73m2 OR=14; 95% CI 6.3–31.3; p&lt;0.001); albuminuria &gt; 30 mg/g OR=2.4; 95% CI 1.6–3.6; p&lt;0.001), dialysis OR=14.1; 95% CI 6.2–32.1; p&lt;0.001), kidney transplant OR=11.7; 95% CI 5.4–24.9; p&lt;0.001). Manifestation of T1D between 1996–2002 reduced the risk of developing CKD by 10.75; 95% CI 4.37; 27.03) vs manifestation of T1D earlier. Age of T1D debut 6–17 years increased the risk of reaching terminal CKD vs age of debut &gt;18 years: OR=2.4; 95% CI 1.22; 5.022; p=0.012).CONCLUSION: Despite a significant reduction in the risk of developing CKD in individuals with T1D debut between 1996 and 2002, renal dysfunction is a frequent complication in patients with a long disease course, combining with other late complications and contributing to a high risk of terminal stage of CKD and cardiovascular events. Early age of T1D debut increases the risk of terminal CKD.