Chronic Kidney Disease Status Research Articles

#1816 CA 125 as a surrogate marker for plasma volume in patients with cardiorenal syndrome

Abstract Background and Aims Assessing volume status in heart failure (HF) and end-stage chronic kidney disease (CKD) is challenging. Plasma volume expansion is an early step in the pathophysiology of decompensated HF and an independent risk factor for death and HF hospitalization, and should be addressed early. Evaluating plasma volume, especially its variation with diuretic therapy, can be a useful clinical tool for guiding decongestive therapy. There's a growing need for accurate and simple tools to guide clinician decisions on patient volume management. Cancer antigen 125 (CA125), a glycoprotein produced in mesothelial cells in the pericardium, pleura, or peritoneum, is primarily associated with ovarian and gynecological malignancies. Recent studies link CA125 to inflammation and congestion. In acute HF, elevated CA125 is associated with fluid overload indicators like increased central venous and pulmonary wedge pressure. Elevated CA125 in acute HF patients is linked to worse outcomes in death and hospital stay length. Evidence supports CA125-guided therapy in acute HF, but its role in managing chronic volume overload is still uncertain. We aim to assess the relationship between CA125 levels and estimated plasma volume (ePV). Method A retrospective unicentric observational study was conducted between June 2022, and April 17, 2023, at the Renocardiac clinic of a tertiary hospital. Clinical data were extracted from electronic patient records. CKD staging was determined following the Kidney Disease Improving Global Outcomes (KDIGO) classification. ePV was calculated using the Kaplan-Hakim formula. CA125 and ePV were assessed for the same patient in 2 different visits and their variation was calculated. The correlation between CA125 and ePV, as well as CA125 and ePV variation, was evaluated using Spearman's rank correlation coefficient for bivariate analysis, conducted with IBM SPSS®. Results This study comprised 65 patients, totaling 124 hospital visits. The patient demographic was 67.7% male, with a mean age of 76.4 (±12.47) years. In terms of CKD staging, 48.5% were classified as KDIGO 5, 40.6% as KDIGO 4, 9.4% as KDIGO 3, and 1.5% as KDIGO 2. HF etiology distribution included 59% ischemic, 9.8% hypertensive, 6.5% valvular, and 24.5% other causes. The mean ejection fraction was 37.35 (±12.36)% and 19% had preserved ejection fraction; 75% of them were treated with prognostic-modifying medication, including SGLT2 inhibitors. This proportion was lower (19%) in patients with reduced ejection fraction, receiving ACE/angiotensin ± neprilysin inhibitor + mineralocorticoid receptor inhibitor + beta-blocker + SGLT2 inhibitor. During the follow-up period, 13 hospitalizations, 1 major adverse cardiovascular event (MACE), and 5 deaths were recorded. The mean CA125 level was 193.98 (±154.55) U/mL, and patients had a mean ePV of 2.41 (±1.19) L. A significant positive correlation was found between CA125 levels and ePV (r = 0.355, p = 0.000). However, there was no significant correlation between the variation of CA125 and ePV levels between visits (p = 0.535). Conclusion This study focuses on a population with limited implementation of disease-modifying therapy due to advanced CKD, complicating the clinical management of volume status, kidney function, potassium levels, and long-term prognosis in both CKD and HF. CA125 shows potential clinical utility as a marker of congestion, aiding clinicians in assessing volume status by correlating with plasma volume. However, this study found no correlation between CA125 variation and changes in plasma volume. The outpatient nature of the studied population, typically euvolemic, may hinder assessing the relationship between CA125 and ePV changes. Future studies with larger sample sizes are essential to clarify this relationship and potentially identify volume-expanded patients early.

#305 Global health inequalities of CKD: a systematic review and meta-analysis examining prevalence and disparities in age, sex and socio-economic status

Abstract Background and Aims Chronic kidney disease (CKD) is a significant contributor to global morbidity and mortality. Age, sex and socio-economic status are considered to be influential in the development, progression and outcomes from CKD. This study investigated disparities in age, sex and socio-economic status in CKD and updated global prevalence estimates through systematic review and meta-analysis. Method Five databases (MEDLINE/PubMed, Embase, Cochrane CENTRAL Library, CINAHL, Web of Science) were searched from 2014 to 2022, with 14,871 articles screened, 119 papers included and data analysed on 29,159,948 participants. Studies were included if they described CKD prevalence in participants over the age of 18 and were carried out in the general population. CKD was defined on the basis of albuminuria/proteinuria and/or an estimated glomerular filtration rate of <60 ml/min/m2. Random effects meta-analyses using generalised linear mixed models were conducted to determine overall prevalence, prevalence of stages 3–5 and prevalence in males and females. Influences of age, sex and socio-economic status were assessed in subgroup analyses, and risk of bias assessment and meta-regressions were conducted to explore heterogeneity. Results Overall prevalence of CKD was 13.0% (11.3–14.8%) and 6.6% (5.6–7.8%) for stages 3–5. Prevalence was higher in studies where all participants were over the age of 60 (19.3% for stages 1–5. 15.0% for stages 3–5) and meta-regression demonstrated association of age, body mass index, diabetes and hypertension with prevalence of CKD stages 3–5. The prevalence of CKD stages 1–5 was similar in males and females (13.1% versus 13.2%) but prevalence of stages 3–5 was higher in females (6.4% versus 7.5%). Overall prevalence was 11.4%, 15.0% and 10.8% in low, middle and high-income countries respectively; for stages 3–5 prevalence was 4.0%, 6.7% and 6.8%, respectively. Risk of bias of included studies was generally moderate or high, with 8% at low risk of bias, 44% at moderate risk of bias and 48% at high risk of bias. Conclusion With nearly 30 million participants, this study is the largest systematic review on CKD prevalence to date, with prevalence demonstrated to be persistently high globally. It has highlighted that important disparities related to age, sex and socio-economic status may exist, and addressing these concerns should be a priority for policymakers. Future research should focus on targeted screening and treatment approaches, improving access to care and more effective data monitoring, particularly in low and middle income countries.

#1235 Comparative effect on bone remodeling and inflammation biomarkers of citrate dialysate and bicarbonate dialysate in HDF-OL patients

Abstract Background and Aims Hemodialysis (HD) treatment increases the inflammatory state of chronic kidney disease (CKD), which is associated with dysregulation of mineral bone metabolism. Reduced inflammation and increased bone formation have been described in Hemodiafiltration (HDF) compared with conventional HD. On the other hand, HD and OL-HDF using citrate-enriched dialysate are known to be safe and anti-inflammatory. However, the effects of post-dilution OL-HDF with citrate dialysate compared to bicarbonate dialysate on biomarkers of bone formation and resorption have not been studied. We aimed to compare the effect of bone remodeling markers and inflammation of different dialysates (citrate vs bicarbonate) in post dilution OL- HDF treatment. Method A total of 33 patients on conventional HD with bicarbonate citrate were included. At month 1, 18 patients, who did not require individualized adjustment of the dialysate composition such as potassium, were changed to HD with citrate dialysate and 15 patients remained with bicarbonate dialysate. By the second month, however, all patients were on OL-HDF with no change in buffer dialysate. Pre-dialysis blood samples were taken in both treatment groups at baseline (prior to the initiation of citrate dialysate in 18 patients), and at the first, second and fifth months after the introduction of citrate. Measurements of mineral homeostasis (calcium, phosphate, magnesium, parathyroid hormone, intact parathyroid hormone), inflammation (interleukin-6, β2-microglobulin, C-reactive protein) and bone remodeling markers (carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX), as a biomarker of bone resorption and procollagen type 1 N-terminal pro-peptide (P1NP), as a biomarker of bone formation) were performed. All samples were collected before a mid-week dialysis session. Mineral homeostasis measurements were also performed before and after HD at the first and second month of the switch to citrate dialysate. Normally distributed data were presented as mean (standard deviation, SD) and median (interquartile range). Intra-subjects comparisons were analyzed using paired sample t-test or Wilcoxon signed-rank test. Comparisons between groups were analyzed using Mann-Whitney U test. Statistical analyses were performed using the SPSS (version 15.0, Chicago, IL, USA). p-value < 0.05. Results Overall, 75.7% (n = 25) of the subjects were male, the median age was 69 years (SD: 12) and 39.3% suffered diabetes (n = 13). Patients on citrate and bicarbonate dialysates were comparable for age, sex, comorbidities, months on dialysis and anemia control. Baseline mineral, bone remodeling and inflammation markers before HD, were also comparable in both groups. Only patients on bicarbonate dialysate had higher β2-microglobulin levels at baseline. Changes in serum levels of mineral, bone remodeling and inflammatory biomarkers at 5 months compared to baseline for both groups are shown in Table 1. After 5 months of follow-up, a 22% trend-reduction (p = 0.08) in P1NP as bone formation biomarker was observed in patients on citrate dialysate compared to those on bicarbonate dialysate. In addition, the fold change observed in CTX as parameter of bone resorption was attenuated in the citrate dialysate group (11% vs 116% in the bicarbonate dialysate group, p < 0.001). β2-microglobulin levels decreased significantly in both groups at 5 months but It is explained by the known effect of OL-HDF treatment on the inflammatory state of dialysis patients. Conclusion In patients on OL-HDF treatment the use of the citrate as dialysate may provide a benefit in bone remodeling by reducing bone resorption and trend to balance the bone formation/resorption. However, our results are in line with previous studies, where caution should be adopted in patients with very high parathyroid hormone levels, as this may be enhanced by reduced mineral turnover.

#366 Humanistic burden of immunoglobulin A nephropathy and focal segmental glomerulosclerosis on patients and care-partners (HONUS): results for Europe

Abstract Background and Aims Rare proteinuric kidney diseases are associated with clinical and economic burden, however, the humanistic burden associated with these conditions has not been directly evaluated. HONUS is a multi-national, cross-sectional survey study designed to evaluate the humanistic burden associated with two rare kidney diseases, immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS), from the patient and caregiver perspectives in the United States and Europe. The current analysis presents preliminary results from adults with IgAN or FSGS and their care-partners in Spain, Germany, France, or the United Kingdom. Method The study recruited adult patients (≥ 18 years old) with IgAN or FSGS and their adult care-partners. Participants completed an online survey including demographic and clinical characteristics, health-related quality of life (HRQoL) (i.e., Kidney Disease Quality of Life Instrument [KDQoL] including 12-Item Short Form Survey [SF-12]), anxiety and depression (i.e., Generalized Anxiety Disorder Assessment [GAD-7], Patient Health Questionnaire [PHQ-9]), and disease impact on work productivity (i.e., Work Productivity and Activity Impairment [WPAI]). Descriptive analyses were conducted. Results From Europe, 26 IgAN patients, 9 FSGS patients, and their care-partners (4 IgAN and 2 FSGS patients did not report having a care-partner) participated in the survey before November 2023. Mean age for IgAN and FSGS patients was 42.2 years and 51.4 years, with 61.5% and 44.4% being female, respectively. Over two-fifths of both IgAN (42.3%) and FSGS patients (44.4%) were in chronic kidney disease (CKD) stage 3, 4 or 5 (on dialysis), while over one-quarter had received a kidney transplant (IgAN: 26.9%; FSGS: 44.4%). Most patients had worse CKD status since diagnosis (IgAN: 61.5%; FSGS: 77.8%). Hypertension and anemia were the most common comorbidities in both groups. In terms of HRQoL, mean (SD) SF-12 physical and mental component scores (PCS, MCS) indicated IgAN patients were more impacted on the mental component (PCS: 47.3 [11.6], MCS: 43.2 [10.9]), with FSGS patients more impacted on the physical component (PCS: 40.6 [6.0], MCS: 43.8 [9.1]), reflecting generally worse HRQoL (lower scores) than previously published European general population scores (50.0 for PCS and MCS). Moderate to severe anxiety was reported by 30.8% of IgAN and 33.3% of FSGS patients, and moderate to severe depression by 30.8% of IgAN and 44.4% of FSGS patients. Among employed IgAN patients (69.2%), mean percent absenteeism (work time missed) was reported at 13.3%, presenteeism (impairment while working) at 17.7%, and overall work productivity loss at 17.7% due to IgAN-related reasons (only 3 FSGS patients [33.3%] were employed; outcomes not shown). Mean percent activity impairment was reported at 27.3% in IgAN and 43.3% in FSGS patients. Most paired care-partners were partners of patients (IgAN: 81.8%, FSGS: 71.4%), with a mean age of 46.6 years (IgAN) and 50.1 years (FSGS). Mean (SD) SF-12 PCS and MCS of IgAN care-partners were 53.3 (8.8) and 47.9 (10.8), respectively (FSGS: 47.0 [10.6], 49.4 [9.5]). Mild to moderate anxiety was reported in 31.8% (IgAN) and 42.9% (FSGS) of care-partners, with one IgAN care-partner (4.6%) reporting severe anxiety. Mild to moderate depression was reported in 27.3% (IgAN) and 71.4% (FSGS) of care-partners, with two IgAN care-partners (9.1%) reporting moderately severe or severe depression. Among employed IgAN care-partners (86.4%), mean percent absenteeism was reported at 14.2%, presenteeism at 9.3%, and overall work productivity loss at 9.9% due to IgAN-related reasons. Mean percent activity impairment was reported at 18.6% in IgAN and 17.1% in FSGS care-partners. Conclusion Patients with IgAN and FSGS in Europe experience impaired HRQoL compared to previously published European population estimates, as well as anxiety, depression, and impaired productivity. Care-partners of these patients also experience impaired HRQoL, in terms of mental components, and reduced overall productivity.

Frailty, but not cognitive impairment, improves mortality risk prediction among those with chronic kidney disease-a nationally representative study.

Though older adults with chronic kidney disease (CKD) have a greater mortality risk than those without CKD, traditional risk factors poorly predict mortality in this population. Therefore, we tested our hypothesis that two common geriatric risk factors, frailty and cognitive impairment, and their co-occurrence, might improve mortality risk prediction in CKD. Among participants aged ≥ 60years from National Health and Nutrition Examination Survey (2011-2014), we quantified associations between frailty (physical frailty phenotype) and global/domain-specific cognitive function (immediate-recall [CERAD-WL], delayed-recall [CERAD-DL], verbal fluency [AF], executive function/processing speed [DSST], and global [standardized-average of 4 domain-specific tests]) using linear regression, and tested whether associations differed by CKD using a Wald test. We then tested whether frailty, global cognitive impairment (1.5SD below the mean), or their combination improved prediction of mortality (Cox models, c-statistics) compared to base models (likelihood-ratios) among those with and without CKD. Among 3,211 participants, 1.4% were cognitively impaired, and 10.0% were frail; frailty and cognitive impairment co-occurrence was greater among those with CKD versus those without (1.2%vs.0.1%). Frailty was associated with worse global cognitive function (Cohen's d = -0.26SD,95%CI -0.36,-0.17), and worse cognitive function across all domains; these associations did not differ by CKD (pinteractions > 0.05). Mortality risk prediction improved only among those with CKD when accounting for frailty (p[likelihood ratio test] < 0.001) but not cognitive impairment. Frailty is associated with worse cognitive function regardless of CKD status. While CKD and frailty improved mortality prediction, cognitive impairment did not. Risk prediction tools should incorporate frailty to improve mortality prediction among those with CKD.

A study of hospitalized COVID-19 patients with AKI in a setting of multiracial developing country

BackgroundThe commonest indication for hospitalization in COVID-19 patients is hypoxemia or severe respiratory symptoms. However, COVID-19 disease may result in extrapulmonary complications including kidney-related pathology. The reported incidence of renal involvement related to COVID infection varies based on geographical location.ObjectiveThis study aimed to assess the incidence rate of AKI in hospitalized COVID-19 patients and identify risk factors and prognostic predictors.MethodIn this retrospective study, we recruited hospitalized COVID-19 patients from January 2021 until June 2021 at the University Malaya Medical Center. The inclusion criteria were hospitalized for ≥ 48 h with confirmed COVID-19 infection and at least 18 years old. Patient demographic and clinical data were collected from electronic medical records. The staging of AKI was based on criteria as per KDIGO guidelines.ResultsOne thousand five hundred twenty-nine COVID patients fulfilled the inclusion criteria with a male-to-female ratio of 759 (49.6%) to 770 (50.3%). The median age was 55 (IQR: 36–66). 500 patients (32.7%) had diabetes, 621 (40.6%) had hypertension, and 5.6% (n = 85) had pre-existing chronic kidney disease (CKD). The incidence rate of AKI was 21.1% (n = 323). The percentage of COVID patients in different AKI stages of 1,2 and 3 were 16.3%, 2.1%, and 2.7%, respectively. Fifteen hospitalized patients (0.98%) required renal replacement therapy. 58.8% (n = 190) of AKI group had complete recovery of kidney function.Demographic factors included age (p < 0.001), diabetes (p < 0.001), hypertension (p < 0.012), CKD (p < 0.001), and vaccination status (p = 0.042) were associated with an increased risk of developing AKI. We found that the AKI cohort had statistically significant lower platelet counts and higher ferritin levels than the non-AKI cohort. AKI is a risk predictor of prolonged hospitalization (p < 0.001) and higher mortality rates (P < 0.001).ConclusionAKI is a common clinical complication among hospitalized COVID-19 patients. The etiology of AKI is multifactorial and may have an adverse impact on patient morbidity and mortality.

The role of advanced practice nurses in improving healthcare outcomes for patients with chronic kidney disease: A scoping review protocol.

The number of patients with chronic kidney disease is increasing worldwide; previous studies have suggested that advanced practice nurses, including nurse practitioners and clinical nurse specialists, with expert practice skills can provide high-quality care and solve complex healthcare problems. In general, nurse practitioners are generalist nurses who work as autonomous clinicians with whole personal care. Clinical nurse specialists, in contrast, are nurses with advanced nursing knowledge and skills for individuals or specific populations. Their roles are independent and different; however, similarities exist in their role in potentially improving healthcare outcomes. Although two previous studies described the role of nephrology nurse practitioners, they were systematic reviews, and their outcomes were limited. To clarify the overall aspect of advanced practice nurses' role, it is necessary to extract the studies illustrating advanced practice nurses' practices for patients with chronic kidney disease. This study aims to map the literature describing the role of advanced practice nurses in improving healthcare outcomes for patients with chronic kidney disease. This scoping review will be conducted using the Joanna Briggs Institute methodology for scoping review. Online databases will be searched across MEDLINE (PubMed), CINAHL (EBSCOhost), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Web of Science. Only studies published in English will be included, and no date limit will be set. Chronic kidney disease, renal replacement therapy, and advanced practice nurses as keywords and related search terms will be used. Two independent reviewers will screen the title and abstract/full-text; in case of discrepancy, a third reviewer will make the final decision. The results will be extracted and presented following the review question concerning the study characteristics, patients' characteristics, condition of chronic kidney disease, and role of advanced practice nurses.

Comparison of mortality and amputation after lower extremity bypass versus peripheral vascular intervention in patients with chronic limb-threatening ischemia and comorbid chronic kidney disease

ObjectiveComorbid chronic kidney disease (CKD) is associated with worse outcomes for patients with chronic limb-threatening ischemia (CLTI). However, comparative effectiveness data are limited for lower extremity bypass (LEB) vs peripheral vascular intervention (PVI) in patients with CLTI and CKD. We aimed to evaluate (1) 30-day all-cause mortality and amputation and (2) 5-year all-cause mortality and amputation for LEB vs PVI in patients with comorbid CKD. MethodsIndividuals who underwent LEB and PVI were queried from the Vascular Quality Initiative with Medicare claims-linked outcomes data. Propensity scores were calculated using 13 variables, and a 1:1 matching method was used. The mortality risk at 30 days and 5 years in LEB vs PVI by CKD was assessed using Kaplan-Meier and Cox proportional hazards models, with interaction terms added for CKD. For amputation, cumulative incidence functions and Fine-Gray models were used to account for the competing risk of death, with interaction terms for CKD added. ResultsOf 4084 patients (2042 per group), the mean age was 71.0 ± 10.8 years, and 69.0% were male. Irrespective of CKD status, 30-day mortality (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.63-1.42, P = .78) was similar for LEB vs PVI, but LEB was associated with a lower risk of 30-day amputation (sub-HR [sHR]: 0.66, 95% CI: 0.44-0.97, P = .04). CKD status, however, did not modify these results. Similarly, LEB vs PVI was associated with a lower risk of 5-year mortality (HR: 0.79, 95% CI: 0.71-0.88, P < .001) but no difference in 5-year amputation (sHR: 1.03, 95% CI: 0.89-1.20, P = .67). CKD status did not modify these results. ConclusionsRegardless of CKD status, patients had a lower risk of 5-year all-cause mortality and 30-day amputation with LEB vs PVI. Results may help inform preference-sensitive treatment decisions on LEB vs PVI for patients with CLTI and CKD, who may commonly be deemed too high risk for surgery.

Acute Kidney Injury and Electrolyte Imbalances Caused by Dapagliflozin Short-Term Use.

Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), has shown demonstrated benefits for renal and cardiovascular outcomes in large clinical trials. However, short-term concerns regarding its impact on renal function and electrolyte balance exist. This study aimed to evaluate the short-term effects of dapagliflozin on renal function and electrolyte balance in patients newly prescribed the medication. A retrospective analysis of 246 patients who initiated dapagliflozin therapy was conducted. Serum creatinine, sodium, and potassium levels were measured at baseline (before dapagliflozin) and 5-8 days after initiation (endpoint). A Wilcoxon signed-rank test, Pearson's chi-square test, and Fischer's exact test were used for the data analysis. Glycemia and sodium levels were significantly higher at the baseline compared to the endpoint (p < 0.001). Conversely, creatinine and potassium levels were significantly higher at the endpoint than at the baseline (p < 0.001). The prevalence of hyponatremia and hyperkalemia were increased at the endpoint (17.5% vs. 10.2% and 16.7% vs. 8.9%, respectively). Although not statistically significant, a trend towards increased hyponatremia with the co-administration of furosemide was observed (p = 0.089). No significant association was found between potassium-sparing medications (p > 0.05) and hyperkalemia, except for angiotensin receptor blockers (p = 0.017). The combination of dapagliflozin and furosemide significantly increased the risk of acute kidney injury (AKI) at the endpoint (p = 0.006). Age, gender, and chronic kidney disease status did not significantly influence the occurrence of AKI, hyponatremia, or hyperkalemia (p > 0.05). These findings emphasize the importance of the close monitoring of renal function and electrolyte balance, particularly in the early stages of dapagliflozin therapy, especially in patients receiving diuretics or renin-angiotensin-aldosterone system inhibitors.

Systemic reserve dysfunction and contrast-associated acute kidney injury following percutaneous coronary intervention.

Developing contrast-associated acute kidney injury (CA-AKI) following percutaneous coronary intervention (PCI) is closely related to patient-related risk factors as well as contrast administration. The diagnostic and prognostic roles of neutrophil gelatinase-associated lipocalin (NGAL) in CA-AKI following PCI are not well established. Consecutive patients undergoing PCI were enrolled prospectively. CA-AKI was defined as an increase in the serum creatinine level ≥0.3 mg/dL within 48 hours or ≥1.5 times the baseline within 7 days after PCI. Serum NGAL concentrations were determined immediately before and 6 hours after PCI. The participants were classified into four NGAL groups according to the pre- and post-PCI NGAL values at 75th percentile. CA-AKI occurred in 38 (6.4%) of 590 patients. With chronic kidney disease status (hazard ratio [HR] 1.63, 95% confidence interval [CI]: 1.06-2.52), NGAL groups defined by the combination of pre- and 6 h post-PCI values were independently associated with the occurrence of CA-AKI (HR 1.69, 95% CI: 1.16-2.45). All-cause mortality for 29-month follow-ups was different among NGAL groups (log-rank p<0.001). Pre-PCI NGAL levels significantly correlated with baseline cardiac, inflammatory, and renal markers. Although post-PCI NGAL levels increased in patients with larger contrast administration, contrast media made a relatively limited contribution to the development of CA-AKI. In patients undergoing PCI, the combination of pre- and post-PCI NGAL values may be a useful adjunct to current risk-stratification of CA-AKI and long-term mortality. CA-AKI is likely caused by systemic reserve deficiency rather than contrast administration itself.

Associations between inflammatory and angiogenic proteomic biomarkers, and cardiovascular events and mortality in relation to kidney function

ABSTRACT Background The links between chronic kidney disease (CKD) and the high burden of cardiovascular disease remain unclear. We aimed to explore the association between selected inflammatory and angiogenic biomarkers, kidney function and long-term outcome in patients with an acute coronary syndrome (ACS) and to test the hypothesis that CKD status modifies this association. Methods A total of 1293 ACS patients hospitalized between 2008 and 2015 were followed until 31 December 2017. Plasma was collected on days 1–3 after admission. A total of 13 biomarkers were a priori identified and analysed with two proteomic methods, proximity extension assay or multiple reaction monitoring mass spectrometry. Boxplots and multiple linear regression models were used to study associations between biomarkers and kidney function and adjusted standardized Cox regression with an interaction term for CKD was used to assess whether CKD modified the association between biomarkers and major adverse cardiovascular events and death (MACE+). Results The concentrations of nine biomarkers—endothelial cell-specific molecule-1 (ESM-1), fibroblast growth factor 23 (FGF-23), fractalkine (CX3CL1), interleukin-1 receptor antagonist (IL-1RA), interleukin-18 (IL-18), monocyte chemotactic protein-1 (MCP-1), placenta growth factor (PlGF), transmembrane immunoglobulin 1 (TIM-1) and vascular endothelial growth factor A (VEGFA)—were inversely associated with kidney function. ESM-1, FGF-23 and TIM-1 showed associations with MACE+. Only FGF23 remained independently associated after adjustment for the other biomarkers (hazard ratio per standard deviation increase 1.34; 95% Bonferroni corrected confidence interval 1.19–1.50). None of the biomarkers showed an interaction with CKD. Conclusions The concentrations of 9 of the 13 prespecified inflammatory and angiogenic proteomic biomarkers increased when kidney function declined. Only FGF-23 demonstrated an independent association with MACE+, and this association was not modified by CKD status. These findings further support FGF-23 as an independent prognostic marker in ACS patients with and without CKD.

Switching from Conventional Fibrates to Pemafibrate Has Beneficial Effects on the Renal Function of Diabetic Subjects with Chronic Kidney Disease.

Fibrates have renal toxicity limiting their use in subjects with chronic kidney disease (CKD). However, pemafibrate has fewer toxic effects on renal function. In the present analysis, we evaluated the effects of pemafibrate on the renal function of diabetic subjects with or without CKD in a real-world clinical setting. We performed a sub-analysis of data collected during a multi-center, prospective, observational study of the effects of pemafibrate on lipid metabolism in subjects with type 2 diabetes mellitus complicated by hypertriglyceridemia (the PARM-T2D study). The participants were allocated to add pemafibrate to their existing regimen (ADD-ON), switch from their existing fibrate to pemafibrate (SWITCH), or continue conventional therapy (CTRL). The changes in estimated glomerular filtration rate (eGFR) over 52 weeks were compared among these groups as well as among subgroups created according to CKD status. Data for 520 participants (ADD-ON, n=166; SWITCH, n=96; CTRL, n=258) were analyzed. Of them, 56.7% had CKD. The eGFR increased only in the SWITCH group, and this trend was also present in the CKD subgroup (P<0.001). On the other hand, eGFR was not affected by switching in participants with severe renal dysfunction (G3b or G4) and/or macroalbuminuria. Multivariate analysis showed that being older and a switch from fenofibrate were associated with elevation in eGFR (both P<0.05). A switch to pemafibrate may be associated with an elevation in eGFR, but to a lesser extent in patients with poor renal function.

Iron Deficiency and Incident Heart Failure in Older Community-Dwelling Individuals.

Among persons with prevalent heart failure (HF), iron deficiency has been linked to HF admissions, and intravenous iron replacement improves HF outcomes. Recent studies in persons with chronic kidney disease (CKD) demonstrate that iron deficiency is associated with incident HF. This study aimed to determine the relationship of iron status with incident HF in community-dwelling older adults irrespective of their kidney function. In this case-cohort study, 1,006 Cardiovascular Health Study participants (785 from the random sub-cohort [including 193 HF cases] and 221 additional HF cases [N=414 total HF cases]) aged ≥ 65years without HF (41% with CKD), we used weighted Cox models to evaluate associations of iron status with incident HF. Participants were categorized based on quartiles of transferrin saturation and ferritin as "iron replete" (27.3%), "functional iron deficiency" (7.7%), "iron deficiency" (11.8%), "mixed iron deficiency" (5.6%), "high iron" (9.3%) and "non-classified" (38.1%), consistent with prior studies. Compared to older persons who were iron replete, those with iron deficiency were at higher risk of incident HF (HR 1.47; 1.02-2.11) in models adjusting for demographics, HF risk factors, and estimated glomerular filtration rate. Other iron categories did not associate with incident HF. The relationship of iron deficiency with incident HF did not differ by CKD status (interaction P value 0.2). Among community-dwelling elders, iron deficiency is independently associated with incident HF, an association that was similar irrespective of CKD status. Our findings support conduct of clinical trials of iron replacement for prevention of HF in older adults with iron deficiency.

Effect of ferric citrate hydrate on fibroblast growth factor 23 and platelets in non-dialysis-dependent chronic kidney disease and non-chronic kidney disease patients with iron deficiency anemia.

Iron deficiency anemia (IDA) increases levels of C-terminal fibroblast growth factor 23 (cFGF23) and platelet count (PLT), each of which is associated with cardiovascular events. Therefore, we hypothesized that iron replacement with ferric citrate hydrate (FC) would decrease cFGF23 levels and PLT in patients with IDA. In a randomized, open-label, multicenter, 24-week clinical trial, patients with non-dialysis-dependent chronic kidney disease (CKD) and non-CKD complicated by IDA (8.0 ≤ hemoglobin < 11.0g/dL; and serum ferritin < 50ng/mL [CKD]; < 12ng/mL [non-CKD]) were randomized 1:1 to FC-low (500mg:approximately 120 mg elemental iron/day) or FC-high (1000mg: approximately 240mg elemental iron/day). If sufficient iron replacement had been achieved after week 8, further treatment was discontinued. Seventy-three patients were allocated to FC-low (CKD n = 21, non-CKD n = 15) and FC-high (CKD n = 21, non-CKD n = 16). Regardless of CKD status, FC increased serum ferritin and transferrin saturation, did not change intact FGF23 or serum phosphorus, but decreased cFGF23. In FC-low group, median changes in cFGF23 from baseline to week 8 were -58.00 RU/mL in CKD and -725.00 RU/mL in non-CKD; in FC-high group, the median changes were -66.00RU/mL in CKD and -649.50 RU/mL in non-CKD. By week 8, FC treatment normalized PLT in all patients with high PLT at baseline (>35.2 × 104/µL; FC-low: 1 CKD, 8 non-CKD; FC-high: 3 CKD, 8 non-CKD). Regardless of CKD status, iron replacement with FC decreased elevated cFGF23 levels and normalized elevated PLT in patients with IDA. jRCT2080223943.

Global health inequalities of chronic kidney disease: a meta-analysis.

Chronic kidney disease (CKD) is a significant contributor to global morbidity and mortality. This study investigated disparities in age, sex and socio-economic status in CKD and updated global prevalence estimates through systematic review and meta-analysis. Five databases were searched from 2014 to 2022, with 14871 articles screened, 119 papers included and data analysed on 29159948 participants. Random effects meta-analyses were conducted to determine overall prevalence, prevalence of stages 3-5 and prevalence in males/females. Influences of age, sex and socio-economic status were assessed in subgroup analyses, and risk of bias assessment and meta-regressions were conducted to explore heterogeneity. Overall prevalence of CKD was 13.0% (11.3-14.8%) and 6.6% (5.6-7.8%) for stages 3-5. Prevalence was higher in studies of older populations (19.3% for stages 1-5, 15.0% for stages 3-5) and meta-regression demonstrated association of age, body mass index, diabetes and hypertension with prevalence of stages 3-5. The prevalence of CKD stages 1-5 was similar in males and females (13.1% versus 13.2%) but prevalence of stages 3-5 was higher in females (6.4% versus 7.5%). Overall prevalence was 11.4%, 15.0% and 10.8% in low, middle and high-income countries respectively; for stages 3-5 prevalence was 4.0%, 6.7% and 6.8%, respectively. Included studies were at moderate-high risk of bias in the majority of cases (92%), and heterogeneity was high. This study provides a comprehensive assessment of CKD prevalence, highlighting important disparities related to age, sex and socio-economic status. Future research should focus on targeted screening and treatment approaches, improving access to care and more effective data monitoring, particularly in low or middle income countries.

Association of serum magnesium with metabolic syndrome and the role of chronic kidney disease: A population-based cohort study with Mendelian randomization.

To assess the association of serum magnesium with prevalent and incident metabolic syndrome (MetS) and its individual components in the general population and to examine any effect modification by chronic kidney disease (CKD) status. We analysed longitudinal data from the population-based KORA F4/FF4 study, including 2996 participants (387 with CKD) for cross-sectional analysis and 1446 participants (88 with CKD) for longitudinal analysis. Associations with MetS, as well as single components of MetS, were assessed by adjusted regression models. Nonlinearity was tested by restricted cubic splines and analyses were stratified by CKD. Causality was evaluated by two-sample Mendelian randomization (MR). Serum magnesium (1 SD) was inversely associated with prevalent MetS (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.83, 0.98). The association was more pronounced in individuals with CKD (OR 0.75, 95% CI 0.59, 0.94). Among MetS components, serum magnesium was negatively associated with elevated fasting glucose (OR 0.78, 95% CI 0.71, 0.88) and, again, this association was more pronounced in individuals with CKD (OR 0.67, 95% CI 0.53, 0.84). Serum magnesium was not associated with incident MetS or its components. Restricted cubic spline analysis revealed a significant nonlinear inverse relationship of serum magnesium with MetS and elevated fasting glucose. MR analysis suggested an inverse causal effect of serum magnesium on MetS (OR 0.91, 95% CI 0.85, 0.97). Serum magnesium is associated with prevalent, but not incident MetS, and this effect is stronger in individuals with CKD. MR analysis implies a potential, albeit weak, causal role of magnesium in MetS.

Smoking Increases Mortality Risk Among African Americans With Chronic Kidney Disease

BackgroundSmoking and chronic kidney disease (CKD) have a disproportionately high prevalence among African American (AA) adults, but their impact on mortality among AA adults is not well known. MethodsGiven the lack of evidence in published literature on specific factors affecting the relationship between CKD and mortality among AA adults, we examined the influence of smoking on mortality among AA adults with CKD. National Health and Nutrition Examination Survey (NHANES, 1999-2010) data were analyzed with study participants prospectively followed up for mortality analysis through December 31, 2019, using National Death Index (NDI) death certificate records. ResultsA total of 6,108 AA adults were included in the study sample, with more than two-fifths (44.9%) being smokers and 6.3% having CKD. AA individuals with CKD had 2.22 (95% CI = 1.38-3.57) times the risk of cardiovascular mortality, but when stratified by smoking, AA individuals with CKD who were current smokers had 3.21 times the risk of cardiovascular mortality. Similarly, in AA with CKD, the risk of all-cause mortality was 3.53 (95% CI = 1.31-9.47), but when stratified by smoking status, AA individuals with CKD who were current smokers had 5.54 times the risk of all-cause mortality. ConclusionsSmoking and CKD are highly prevalent in AA individuals and frequently cooccur, leading to higher rates of mortality. Smoking cessation interventions should be a priority in collaborative care models and interdisciplinary care teams for AA with CKD and current smoker status.

Association between prevalence and severity of chronic kidney disease and employment status: a nationwide study in Korea.

The prevalence of chronic kidney disease (CKD) is increasing globally, and understanding the association between CKD and employment status is crucial. This cross-sectional study aimed to investigate the association of CKD with employment and occupation type among patients with CKD. We analyzed data from 36,732 Korean adults aged ≥ 30 years, who participated in the Korean National Health and Nutrition Examination Survey between 2014 and 2021. CKD was detected based on the estimated glomerular filtration rate, and the employment status of the participants was classified into distinct categories: full-time permanent employment, unemployment, self-employment, and precarious employment. We analyzed the data using multiple logistic regression. We observed a significant association between CKD and a higher likelihood of unemployment compared to that in individuals without CKD (odds ratio, 1.70; 95% confidence interval, 1.47-1.96). This association was more prominent in patients with severe CKD. In the multivariable logistic analysis, patients with CKD had a higher likelihood for precarious employment (odds ratio, 1.29; 95% confidence interval, 0.92-1.88), self-employment (odds ratio, 1.3; 95% confidence interval, 0.90-1.88), and unemployment (odds ratio, 2.10; 95% confidence interval, 1.51-2.92) compared to individuals without CKD. Our study demonstrated that CKD is associated with a higher likelihood of unemployment and engagement in precarious employment. These findings highlight the challenges faced by patients with CKD in obtaining stable employment and emphasize the need for interventions to improve the employment outcomes of individuals with CKD.

Health literacy and self-care among patients with chronic kidney disease in a primary care setting.

The study objective was to determine the levels of self-care and health literacy (HL) and their associations among patients with chronic kidney disease (CKD). This was a cross-sectional, questionnaire-based study conducted in a public primary care setting in Singapore. A total of 289 participants aged 21-80 years with hypertension were recruited. Self-care profiles were measured using the Hypertension Self-Care Profile (HTN-SCP; range 0-240, domain range 0-80). Health literacy was measured using the Short-Form Health Literacy Scale (HLS-SF12; range 0-50, limited literacy ≤33). The mean self-care score was 182.7 (standard deviation [SD] 23.2). The median HL score was 34.7 (interquartile range [IQR] 31.9-40.3), and 31.1% of participants had limited HL. Self-care was not associated with age, CKD status, household income and education, but was associated with gender and HL score. In the final regression model, lower HL scores (adjusted β = 1.03, 95% confidence interval [CI] 0.7 to 1.36, P < 0.001) and male gender (adjusted β = -5.29, 95% CI -10.56 to -0.03, P = 0.049) were associated with lower self-care scores. The HL scores were associated with self-care domains of self-efficacy (HL: β = 0.30, 95% CI 0.17 to 0.42, P < 0.001), motivation (HL: β = 0.40, 95% CI 0.26 to 0.53, P < 0.001) and behaviour (HL: β = 0.38, 95% CI 0.26 to 0.50, P < 0.001). Thirty-one percent of the participants had limited HL. Self-care was not associated with age, race, CKD status, household income or education. Male gender and limited HL were associated with lower self-care. Self-care was associated with self-efficacy, motivation and behaviour. Future research could focus on more targeted approaches to improve self-care and HL among patients with CKD.

Cinacalcet in secondary hyperparathyroidism: evaluation of nutritional status, lipid and inflammatory in chronic kidney disease.

Cinacalcet in secondary hyperparathyroidism: evaluation of nutritional status, lipid and inflammatory in chronic kidney disease.