Outcomes In Chronic Kidney Disease Patients Research Articles

#1798 Infection-related outcomes in CKD patients with lupus nephritis: a nationwide cohort study

Abstract Background and Aims Although absolute risks of infection in patients with lupus nephritis (LN) are believed high, it is not known whether they differ from those of patients with other etiologies of moderate and advanced chronic kidney disease (CKD). The aim of this study was to compare infection outcomes between patients with LN-CKD and other forms of CKD. Method Using data from the Swedish Renal Registry (2006-2021), we compared infection-related outcomes between LN-patients with moderate and advanced, non-dialysis, CKD and patients with 1) diabetic kidney disease (DKD), 2) primary glomerular diseases (PGD, i.e. IgA nephropathy, focal segmental glomerulosclerosis, membranous nephropathy), and 3) autosomal dominant polycystic kidney disease (ADPKD). Cause-specific Cox proportional hazard models were used to estimate the adjusted hazard ratios of death due to infection, first all-cause infection-related hospitalization and first cause-specific infection-related hospitalization (sepsis, pulmonary, gastrointestinal, genitourinary, and other infections). Results We identified 317 patients with LN (61 years, 76% women, median eGFR 30 mL/min per 1.73 m²), 8877 patients with DKD (71 years, 33% women, eGFR 24 mL/min per 1.73 m²), 2296 patients with PGD (57 years, 30% women, eGFR 29 mL/min per 1.73 m²) and 1855 patients with ADPKD (59 years, 45% women, eGFR 26 mL/min per 1.73 m²). Over a median follow-up of 2.8 [1.2; 5.0] years, 667 (5%) deaths due to infection and 4034 (30%), infection-related (first-time) hospitalizations occurred, including 2127 (16%) pulmonary, 1507 (11%) genitourinary, 1130 (8%) gastrointestinal, 615 (5%) other infections, and 450 (3%) sepsis. In multivariable analyses, and when compared to DKD, patients with LN had a similar risk of death due to infection (adjusted HR 1.15 [95% CI: 0.62-2.11]) and sepsis (HR 1.24 [0.64-2.4]), but a higher risk of all infection-related hospitalization (HR 1.31 [1.04-1.65]), the latter being mainly driven by pulmonary, gastrointestinal, and other infections (Figure panel A). The risks of death due to infection (HR LN vs PGD 2.78 [1.62-4.77], HR LN vs ADPKD 2.34 [1.31-4.19]), of infection-related hospitalization (HR 1.87 [1.52-2.31], HR 1.43 [1.16-1.77]), and of cause-specific infection-related hospitalization were higher in LN than in PGD and ADKPD, respectively, except for the risk of sepsis which was similar between LN and ADPKD. The risk of genitourinary infection tended to be lower in LN than in ADPKD, although the 95% CI slightly overlapped (Figure panels B-C). Conclusion LN patients had higher risk of infection-related hospitalization than all other investigated CKD etiologies, and a higher risk of death due to infections than patients with PGD and ADPKD. Our findings highlight the need for improvements in infection prevention in patients with LN. Whether a more tailored immunosuppressive treatment approach could further improve outcomes in this high-risk population remains to be investigated.

#2099 Long term outcomes in chronic kidney disease patients with heart failure with preserved ejection fraction

Abstract Background and Aims Heart failure (HF) is frequent in chronic kidney disease (CKD) and leads to high morbidity and mortality in this patient category. The aim of our study is to assess the clinical and biological profile, and outcomes in CKD patients with preserved left ventricular ejection fraction (LVEF). Method We prospectively enrolled CKD patients (pts) in pre-dialysis, stratified in two groups by the presence of heart failure symptoms: pts with NYHA class 1-2 (asymptomatic HF) versus pts with NYHA class 3-4 (symptomatic HF). Demographics, clinical history, co-morbidities, physical exam, ambulatory blood pressure monitoring, extensive blood chemistry, systemic inflammation and mineral bone disease parameters were recorded. Cardiac structure and systolic and diastolic function were assessed by echocardiography. Carotid Doppler ultrasound assessed intima media thickness (IMT). Al patients were followed until death of loss from records; patients with less than 6 months of surveillance were excluded. Primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular mortality, a composite cardiac endpoint composite cardiac endpoint comprising coronary heart disease, heart failure hospitalization and new-onset arrhythmia, and reaching the end stage of renal disease (ESRD). Results We included 76 CKD patients (2 pts CKD stage 1, 9 pts CKD stage 2, 19 pts CKD stage 3a, 28 pts CKD stage 3b, 18 pts CKD stage 4) with LVEF ≥ 50%. Mean age 64.7 ± 11.4 years (yrs), men = 56 (73.7%). Mean follow up period was 86 ± 46.4 months (range 6-156 months). Patients with symptomatic HF (54 pts, 71.1%) were older (68 ± 9 vs 56 ± 12 yrs), hypertensive (98.1% vs 86.4%, p < 0.05), more frequent coronary artery disease (66.7% vs 27.3%, p < 0.05), had worse baseline biological profile: lower eGFR (36.9 ± 12.9 vs 55.5 ± 22.7 ml/min/1.73 m2, p < 0.05), lower serum albumin (4.1 ± 0.5 vs 4.4 ± 0.4 g/dl, p < 0.05), as well as higher levels of osteoprotegerin and fetuin A (p < 0.05). Also, symptomatic HF pts had more severe endothelial disease (higher IMT 0.81 ± 0.14 vs 0.63 ± 0.11 mm, p < 0.05), more severe subclinical LV dysfunction revealed by less negative global longitudinal strain GLS (−16.7 ± 2.66 vs −19.2 ± 2.95, p < 0.05) and higher ratio of mitral velocity to early diastolic velocity of the mitral annulus E/E` (12.64 ± 3.63 vs 9.68 ± 2.73, p < 0.05), as well as higher LV mass index (121.5 ± 31 vs 104.9 ± 22.7 g/m2, p < 0.05) and higher left atrial volume index LAVI (42.8 ± 16.8 vs 31.8 ± 11.3 ml/m2, p < 0.05) All-cause mortality was 17.1% (13 events), while cardiovascular mortality was 6.6% (5 events). All deaths were recorded in the symptomatic HF group. Also, a higher percent of pts from symptomatic HF group reached the composite cardiac endpoint (44.4% vs 22.7%) and ESRD (33.3% vs 18.2%) compared to asymptomatic HF group. Kaplan-Meier survival analysis showed significantly higher all-cause mortality (log rang = 0.008) and lower ESRD-free survival (log rank= 0.045) in symptomatic HF group. All-cause mortality was significantly correlated with NYHA class (p < 0.0001), etiology of CKD (p = 0.038), eGFR (p < 0.0001), proteinuria (p = 0.001), intact PTH (p = 0.008), osteocalcin (p = 0.012), osteopontin (p = 0.029), FGF23 (p = 0.044), IL6 (p = 0.037), GLS (p = 0.023), E/E` (p = 0.009). Cardiovascular mortality was significantly correlated with NYHA class (p = 0.019), etiology of CKD (p = 0.008), eGFR (p = 0.011), proteinuria (p = 0.001), intact PTH (p = 0.008), osteocalcin (p = 0.011), osteopontin (p = 0.006), FGF23 (p = 0.006). Cox regression analysis identified NYHA class (p = 0.004), FGF23 (p = 0.009) and IL6 (p = 0.025) as predictors for all-cause mortality, while E/E` (p = 0.032) and intact PTH (p-0.042) were predictors for cardiovascular mortality. Conclusion In our study, CKD pts with symptomatic HF carry a significant burden of morbidity and mortality, even in the case of preserved LV ejection fraction. This emphasizes the need for more comprehensive regular assessments of subclinical cardiac dysfunction in CKD pts. This approach might support targeted interventions, better symptom control, and improved long term outcomes.

#1804 Long-term outcomes of CKD patients with lupus nephritis: a nationwide cohort study

Abstract Background and Aims Health trajectories of patients with lupus nephritis (LN) are poorly understood in the setting of moderate and advanced chronic kidney disease (CKD). Furthermore, data on comparison of outcomes of LN to other forms of CKD are scarce. Therefore, the aim of this study was to compare long-term outcomes between LN and CKD from other etiologies. Method Using data from the Swedish Renal Registry (2006-2021), we compared clinical outcomes between patients with moderate and advanced CKD related to LN (LN-CKD), and patients with CKD due to primary glomerular diseases (PGD-CKD, i.e. IgA nephropathy, focal segmental glomerulosclerosis, membranous nephropathy), and due to other common CKD etiologies with high cardiovascular risk (Other-CKD, mostly diabetes and nephrosclerosis). Cox proportional hazard models were used to estimate the adjusted hazard ratios of mortality, major cardiovascular events (MACE), heart failure (HF), kidney replacement therapy (KRT) and acute kidney injury (AKI). Models were adjusted for age, sex, comorbidities, clinical and biological data including kidney function, medications and healthcare utilization. Results At baseline, patients with LN-CKD (N = 317, 61 years, 76% women, median eGFR 30 mL/min per 1.73 m²) and PGD-CKD (N = 2296, 57 years, 30% women, eGFR 29 mL/min per 1.73 m²), were younger and had lower prevalence of cardiovascular disease than patients with Other-CKD (N = 34778, 75 years, 36% women, eGFR 25 mL/min per 1.73 m²). Over a median follow-up of 6.2 [3.3; 9.8] years, 19029 deaths (51%), 15768 (42%) MACE and 8390 (22%) KRT events occurred. The unadjusted 5-year absolute risks of death and MACE were high both in patients with LN-CKD (27% and 25%) and Other-CKD (50% and 44%), but lower in those with PGD-CKD (16% and 14%), whereas the 5-year absolute KRT risk was higher in patients with PGD-CKD (PGD-CKD: 37%, LN-CKD: 23%, Other-CKD: 23%). In multivariable analyses and as compared to PGD-CKD, patients with LN-CKD had a higher risk of death (adjusted HR: 1.63 [95% CI: 1.32-2.02]), MACE (1.65 [1.31-2.08]), HF (1.68 [1.31-2.14]) and AKI (1.45 [1.02-2.05]) and showed a lower risk of KRT (HR: 0.81 [0.64-1.02]), although the 95% CI slightly overlapped (Figure, panel A). In contrast, the risks of adverse events were similar between patients with LN-CKD and those with Other-CKD (Figure, panel B). Conclusion While LN-CKD had a lower risk of KRT than PGD-CKD, they exhibited a higher risk of death, MACE, KRT, HF and AKI, reaching the risk magnitude of patients with high cardiovascular burden (Other-CKD). Our findings may inform decisions for care planning in patients with advanced CKD and LN.

Correlation between Urinary Angiotensinogen (AGT) and Albuminuria in Chronic Kidney Disease (CKD)

Chronic kidney disease (CKD) is a global health concern associated with significant morbidity and mortality. Albuminuria, a hallmark of kidney damage, is a strong predictor of CKD progression and adverse outcomes. Recent research has focused on understanding the correlation between urinary angiotensinogen (AGT) levels, a component of the renin-angiotensin system (RAS), and albuminuria in CKD patients. This review article synthesizes evidence from various studies exploring this correlation and elucidates its mechanistic insights and clinical implications. Clinical studies consistently demonstrate a positive correlation between urinary AGT levels and albuminuria in CKD patients. Elevated urinary AGT levels are associated with increased albuminuria, independent of traditional risk factors, suggesting a potential role for AGT in the pathogenesis of kidney damage and proteinuria in CKD. Mechanistic insights suggest that increased intrarenal RAS activity may lead to enhanced AGT production and secretion, contributing to glomerular hypertension, inflammation, and fibrosis, ultimately promoting albuminuria and CKD progression. The clinical implications of this correlation are profound. Elevated urinary AGT levels may serve as a non-invasive biomarker for assessing intrarenal RAS activity and predicting CKD progression and adverse outcomes. Furthermore, interventions targeting the RAS pathway, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), may help reduce urinary AGT levels and mitigate albuminuria, offering promising therapeutic opportunities for improving patient outcomes in CKD. In conclusion, the correlation between urinary AGT and albuminuria in CKD represents a complex interplay between renal physiology, RAS activation, and kidney damage. By elucidating this correlation, we gain valuable insights into the pathogenesis of CKD and identify urinary AGT as a potential biomarker and therapeutic target for personalized CKD management. Further research is warranted to validate these findings, explore the clinical utility of urinary AGT measurement, and develop targeted interventions aimed at mitigating albuminuria and slowing CKD progression. Through continued investigation, we can strive to improve outcomes and quality of life for patients living with CKD.

The role of hypoxia in chronic kidney disease: a nuanced perspective.

This review critically examines the role of hypoxia in chronic kidney disease (CKD). While traditionally viewed as detrimental, recent insights suggest a more nuanced understanding of hypoxia's role during renal disease. Emerging evidence challenges the traditional view that hypoxia is universally harmful in CKD context. We review here the recent evidence about hypoxia and HIF activation in CKD. We also discuss the effect of hypoxia on the renal tissue, and the relative inhibition of different HIF isoforms. Recent advancements in therapies, such as HIF prolyl hydroxylase inhibitors (HIF-PHIs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors seem to target the HIF pathway. These drugs impact anemia associated with CKDbut also renoprotection, hinting at a more complex interplay between hypoxia, HIF activation, and renal health. A certain level of hypoxia and specific HIF pathway activation, especially HIF-α, can be beneficial in CKD progression. Therapeutic strategies targeting HIF stabilization, such as with HIF-PHIs and SGLT2 inhibitors, offer promising avenues for enhancing renal protection. Future investigations should aim at better understanding the precise effects on HIF pathway and optimize their clinical application to improve outcomes for CKD patients.

Periodontitis and risk of mortality in patients with chronic kidney disease: A systematic review with meta-analysis.

Studies examining the link between periodontitis and survival outcomes have yielded conflicting results in patients with chronic kidney disease (CKD). This systematic review with meta-analysis aims to assess the association between periodontitis and cardiovascular or all-cause mortality in CKD patients. A thorough search was conducted on the PubMed, Web of Science, and Embase databases for studies investigating the association between periodontitis and survival outcomes in CKD patients. Two authors independently scanned the titles or abstracts and then identified the eligible full-text article based on the PECOS criteria: Participants (CKD patients), Exposure (periodontitis), Comparison (mild/no periodontitis), Outcomes (cardiovascular or all-cause mortality), and Study design (retrospective or prospective cohort). Six cohort studies, including 7731 patients, were identified. The included studies had low-to-moderate risk of bias. The mean/median follow-up duration ranged from 18.1 months to 8.67 years. The all-cause mortality rate was 44.8% for patients with periodontitis and 28.0% for controls. Meta-analysis showed that periodontitis, defined through clinical attachment loss (CAL), was significantly associated with an increased risk of all-cause (adjusted hazard ratio [HR] 1.24; 95% confidence intervals [CI] 0.89-1.72; I2 = 80.9%) and cardiovascular mortality (HR 1.57; 95% CI 1.08-2.27; I2 = 34.0%). Additionally, a significant association between periodontitis and the risk of cardiovascular or all-cause mortality was observed in studies with a predominance of females, follow-up duration ≥5 years, all stages of CKD, and low risk of bias subgroups. Periodontitis is significantly associated with an increased risk of all-cause and cardiovascular mortality in CKD patients within low risk of bias subgroup or based on defining periodontitis through CAL. Registration number: PROSPERO CRD42018512391.

Effects of uric acid-lowering therapy (ULT) on renal outcomes in CKD patients with asymptomatic hyperuricemia: a systematic review and meta-analysis

BackgroundIt is well known that asymptomatic hyperuricemia and gout play an important role in patients with chronic kidney disease (CKD). However, the effect of uric acid-lowering therapy (ULT) on the prognosis of CKD patients with asymptomatic hyperuricemia remains controversial. Therefore, we aim to investigate the influence of ULT on renal outcomes in these patients.MethodsComprehensive searches were conducted in PubMed, EMBASE, China National Knowledge Internet (CNKI), and the Cochrane Library, up until January 2024. We included randomized controlled trials (RCTs) that evaluated the effects of ULT on renal outcomes in CKD patients with asymptomatic hyperuricemia.ResultsA total of 17 studies were included in the meta-analysis. Compared with placebo or no treatment, ULT preserved the loss of estimated glomerular filtrating rate (eGFR) (Weighted mean difference [WMD] and its 95% confidence intercal(CI): 2.07 [0.15,3.98] mL/min/1.73m2) at long-term subgroup. At the same time, short-term subgroup also proved the preserved loss of eGFR (WMD 5.74[2.09, 9.39] mL/min/1.73m2). Compared with placebo or no treatment, ULT also reduced the increase in serum creatinine (Scr) at short-term (WMD -44.48[-84.03,-4.92]μmol/L) subgroup and long-term (WMD -46.13[-65.64,-26.62]μmol/L) subgroup. ULT was associated with lower incidence of the events of doubling of Scr without dialysis (relative risk (RR) 0.32 [0.21, 0.49], p < 0.001). However, no difference was found for lower incidence of acute kidney injury (AKI) (p = 0.943).ConclusionsAccording to our study, ULT is beneficial for slowing CKD progression both in short to long-term follow-ups. Additionally, in patients younger than 60 years old, the protective effect of ULT on renal outcome is more pronounced. However, it showed no significant difference in the incidence of AKI. These findings underscore the importance of considering ULT in clinical strategies for CKD patients with asymptomatic hyperuricemia.

Factors influencing the occurrence of hyperuricemia and poor cardiac and renal outcomes in chronic kidney disease.

The aim of our study was to analyze the factors influencing the occurrence of hyperuricemia and poor cardiac and renal outcomes in chronic kidney disease (CKD). One hundred and sixteen patients with CKD admitted to our hospital from January 2022 to September 2022 were picked as the subjects. Fasting venous blood of these subjects was collected to value the serum uric acid (SUA) levels on an automatic biochemical analyzer. Patients were then grouped as the CKD-only group (n=80) and hyperuricemia group (n=36), according to the SUA results, or the good prognosis group (n=88) and poor prognosis group (n=28), according to the presence of cardiovascular diseases. The changes in laboratory indexes and clinical data were analyzed and compared. Multivariate logistic regression analysis was used to analyze the risk factors for combined hyperuricemia and the risk factors for poor cardiac and renal outcomes in patients with CKD. The correlation between SUA level and cardiac and renal indexes was analyzed by Pearson analysis. Patients in the CKD hyperuricemia group had markedly higher content of systolic blood pressure (SBP), diastolic blood pressure (DBP), B-type natriuretic peptide (BNP), urinary retinol-binding protein (RBP), urinary N-acetyl-β-D glucosidase (NAG), much higher proportion of heart failure episodes history, and much lower content of total cholesterol (TC), albumin (Alb), hemoglobin (Hb), urinary α1-microglobulin (α1-MG), and glomerular filtration rate (eGFR) than the CKD-only group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for combined hyperuricemia in CKD patients (p < 0.05). Besides, eGFR, albumin, and hemoglobin were independent protective factors for combined hyperuricemia in CKD patients (p < 0.05). Compared with the good prognosis group, the content of BNP, SBP, DBP, urinary RBP, urinary NAG, and SUA was much higher, the proportion of heart failure episodes history was obviously higher, and the levels of Alb, Hb, TC, eGFR, and urinary α1-MG were sharply lower in the poor prognosis group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for poor cardiac and renal outcomes (p < 0.05), and eGFR was an independent protective factor for poor cardiac and renal outcomes in patients with CKD (p < 0.05). The SUA level in CKD patients was positively correlated with BNP and SBP (r=0.463, 0.215, p < 0.05), but negatively correlated with eGFR (r=0.463, 0.215, p < 0.05). The serum SUA level was elevated with the aggravation of the CKD stage. High serum SUA level is a risk factor for the development of hyperuricemia and poor cardio-renal outcomes in CKD patients, suggesting that early monitoring of changes in SUA levels may help assess the risk of cardio-renal outcomes in CKD patients.

A Research on Clinical Pharmacists' Assessment of Drug-Related Problems in Patients with Chronic Kidney Disease

The study focused on chronic kidney disease (CKD), emphasizing the need for early screening and treatment to prevent its progression. Conducted on 65 CKD patients, this prospective observational research aimed to analyze prescription patterns and identify drug-related issues (DRIs). Using the Pharmaceutical Care Network Europe categorization V 5.01, the study evaluated prescriptions and categorized DRPs. The participant group comprised 65 individuals, predominantly male (69.03%), with an average age of 44. The two primary comorbidities were diabetes mellitus (29.78%) and hypertension (34.97%). Notably, the average prescription count was 10, suggesting polypharmacy. Antibiotics emerged as the most commonly prescribed medication (13.98%). The study found medication interactions to be the most frequent DRP (48.54%), followed by drug choice problems (18.43%), dosage issues (8.36%), drug usage complications (10.46%), adverse reactions (1.24%), and other issues (11.28%). Lack of knowledge (42.16%) and the drug use process (30.81%) were identified as the leading causes of DRPs. The research underscores the critical role of continuous identification and management of DRPs by healthcare professionals to enhance patient health and quality of life, potentially leading to better clinical outcomes for CKD patients.

Transcatheter left atrial appendage occlusion in patients with chronic kidney disease: a systematic review and meta-analysis.

Chronic kidney disease (CKD) is a risk factor for embolic stroke, and many nonvalvular atrial fibrillation (NVAF) patients have concomitant CKD. Anticoagulation therapy can be challenging in CKD due to increased bleeding risk, and left atrial appendage occlusion (LAAO) may be a promising alternative. This systematic review aimed to consolidate current evidence on the safety and effectiveness of transcatheter LAAO in patients with CKD and end-stage renal disease (ESRD). Medline, Cochrane, and Embase databases were searched from inception to September 2, 2022. We conducted a meta-analysis if an outcome was evaluated in at least two similar studies. We included 15 studies with 77,780 total patients. Of the 15 studies, 11 had a cohort design (five prospective and six retrospective), and four were case series. Patients with CKD were older and had a higher prevalence of comorbidities than non-CKD patients. The two groups did not differ in procedural failure rate, vascular complications, or pericardial tamponade. CKD patients exhibited higher odds of in-hospital acute kidney injury (AKI) and bleeding, longer-term bleeding, and mortality than those without CKD. The risk of in-hospital and longer-term cardioembolic events was similar between CKD and non-CKD populations (odds ratio = 1.01 [95% CI 0.70-1.15] and 1.05 [95% CI 0.55-2.00], respectively). Patients with ESRD had higher odds of in-hospital mortality and cardioembolic events than non-ESRD patients, with no differences in risk of pericardial tamponade. Based on observational studies, LAAO may be an effective option to prevent cardioembolic events in CKD. However, CKD patients may have higher odds of AKI and in-hospital and long-term bleeding and mortality. The adverse clinical outcomes observed in CKD patients may be attributed to this population's high burden of comorbidities, especially among those with ERSD, rather than the LAAO procedure itself. To ensure maximum clinical benefit, careful patient selection, management, and surveillance involving multidisciplinary teams are essential for CKD patients undergoing LAAO. Transcatheter Left Atrial Appendage Occlusion (laao) Can Prevent Cardioembolic Events In Chronic Kidney Disease (ckd) Patients. However, Ckd Patients, Particularly Those With End-stage Renal Disease/dialysis (esrd), May Face Increased Odds Of Acute Kidney Injury, In-hospital And Long-term Bleeding, And Mortality. Notably, These Adverse Outcomes In Ckd Patients May Be Linked To Their High Comorbidity Burden, Particularly In Those With Esrd, Rather Than The Laao Procedure Itself. Careful Patient Selection, Management, And Surveillance Involving Multidisciplinary Teams Are Essential For Ckd Patients Undergoing Laao To Ensure Maximum Clinical Benefit Transcatheter left atrial appendage occlusion (LAAO) can prevent cardioembolic events in chronic kidney disease (CKD) patients. However, CKD patients, particularly those with end-stage renal disease/dialysis (ESRD), may face increased odds of acute kidney injury, in-hospital and long-term bleeding, and mortality. Notably, these adverse outcomes in CKD patients may be linked to their high comorbidity burden, particularly in those with ESRD, rather than the LAAO procedure itself. Careful patient selection, management, and surveillance involving multidisciplinary teams are essential for CKD patients undergoing LAAO to ensure maximum clinical benefit.

A Brief Review of Diagnostic Techniques and Clinical Management in Chronic Kidney Disease.

Given its increasing incidence and detrimental effects on life expectancy and quality of life, chronic kidney disease (CKD) is a significant worldwide health concern. This review article provides a complete summary of current information on the diagnosis and management of CKD, focusing on recent advances and innovative approaches. The article discusses the most current findings on CKD risk assessment, emphasizing the need for early diagnosis utilizing better biomarkers and predictive models. A rigorous examination of diagnostic tools such as albumin-to-creatinine ratio (ACR) in urine and glomerular filtration rate (GFR) highlights their importance in determining CKD phases and etiologies. In terms of therapy, the study explores evidence-based techniques to reduce the development of CKD, such as enhanced blood pressure control, glycemic management in diabetic patients, dietary changes, and renin-angiotensin-aldosterone system (RAAS) blocking. Novel therapeutic approaches, including antifibrotic and precision medicine, are evaluated regarding their potential to revolutionize CKD treatment. The study also underlines the need for multidisciplinary therapy and patient education to achieve the best possible CKD patient outcomes. It also highlights the financial and social effects of CKD, highlighting the importance of early treatment to lower medical expenses and enhance the patient's standard of living. Finally, this review article provides a comprehensive update on CKD diagnosis and treatment, highlighting present successes alongside future potential. It is a valuable resource for healthcare professionals, academics, and policymakers who want to improve CKD treatment methods and patient outcomes.

Statin therapy for patients with diabetic nephropathy: balance between safety and efficacy of statin treatment for patients with impaired kidney function.

The International Diabetes Federation estimates that by 2035, there will be 592 million people with diabetes worldwide, substantially increasing from the 382 million patients with diabetes recorded in 2013. Diabetes-related nephropathy is a leading cause of end-stage renal disease. Recently, the therapeutic use of statins in patients with chronic kidney disease (CKD) was explored in a series of meta-analyses, which revealed their potential for decreasing mortality and cardiovascular complications in this population, although not in patients undergoing hemodialysis. The current study reviews the current state of knowledge on statin therapy regarding its safety and efficacy concerning renal outcomes in diabetic patients with CKD. The evidence shows that statins may offer a beneficial renoprotective effect in inhibiting the progression of renal function decline. This effect is time-dependent and particularly strong in patients with type 2 diabetes and nephropathy. In addition, whether certain statin types are more beneficial than others in slowing renal function loss and reducing proteinuria remains unclear. Prior research has not examined the impact of high-intensity statin therapy on CKD patient outcomes.

How obesity and metabolic syndrome affect cardiovascular events, progression to kidney failure and all-cause mortality in chronic kidney disease.

Obesity and metabolic syndrome (MetS) are prevalent among chronic kidney disease (CKD) patients. However, it is unclear whether obesity without MetS is associated with a higher risk of adverse clinical outcomes in CKD patients. We searched the National Health Insurance Service database of Korea for patients who underwent national health screenings in 2009-11 and identified 59 725 CKD patients. Obesity was defined as a body mass index ≥25kg/m2. MetS was defined as the presence of three or more metabolic risks. The cumulative event rate of cardiovascular (CV) events, progression to end-stage kidney disease (ESKD) and all-cause mortality was the lowest among obese patients without MetS (all P<.001). In multivariable analysis, obese (versus non-obese) patients without MetS were not at increased risks of CV events [adjusted hazard ratio (HR) 1.02 (95% confidence interval 0.94-1.11)] or progression to ESKD [0.92 (0.77-1.09)]. Their risk of all-cause mortality was significantly decreased [0.82 (0.75-0.90)]. These findings were consistently observed in overweight, obese and morbidly obese patients without MetS. Moreover, despite a linear increase in HR for each additional metabolic abnormality in both obese and non-obese patients, the slope of HR increase for CV events was significantly slower in obese patients (P for interaction=.038). Obesity without MetS did not increase the risk of CV complications or progression to ESKD. The healthy effect of obesity on all-cause mortality risk and its weakening effect on the association between metabolic hazards and CV risk should be considered in CKD patients.

The effect of exercise on vascular health in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials.

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease. This increased risk cannot be fully explained by traditional risk factors such as hypertension. Endothelial dysfunction and arterial stiffness have been suggested as factors that explain some of the increased risk and are independently associated with important cardiovascular outcomes in patients with CKD. Studies in other disease populations have shown the positive effects of exercise on vascular dysfunction. The aim of this review was to determine whether exercise training interventions improve measures of vascular function and morphology in patients across the spectrum of CKD and which exercise training interventions are most efficacious. A systematic search of Medline, Embase, and the Cochrane Central Register identified 25 randomized controlled trials. Only randomized control trials using an exercise intervention with a nonexercising control group and at least one measure of vascular function or morphology were included. Participants were patients with nondialysis CKD or transplant patients or those requiring dialysis therapy. A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A meta-analysis was completed for pulse wave velocity, augmentation index, and measures of endothelium-dependent vasodilation. Data from 25 studies with 872 participants showed that exercise training reduced pulse wave velocity and augmentation index but had no effect on endothelium-dependent vasodilation. Subgroup analyses suggested that exercise interventions of at least moderate intensity were more likely to be effective. Limitations included the absence of observational studies or other interventions aimed at increasing habitual physical activity. Further studies are warranted to investigate which are the most effective exercise interventions.NEW & NOTEWORTHY A thorough systematic review and meta-analysis of the effects of exercise training on measures of vascular function in patients with chronic kidney disease, including arterial stiffness and endothelial function, were conducted. Subgroup analyses investigated how differences in exercise training, according to frequency, intensity, type, and timing, have an impact on the efficacy of the intervention.

The safety and efficacy of direct oral anticoagulants among chronic kidney disease patients on dialysis with non-valvular atrial fibrillation: a meta-analysis.

Individuals with chronic kidney disease (CKD) on dialysis are at an increased risk of stroke and embolic events especially in the presence of atrial fibrillation (AF). Vitamin K antagonists (VKA), including warfarin, have been used for decades for anticoagulation among CKD patients on dialysis with AF but recent evidence has shown increased bleeding. Direct oral anticoagulants (DOAC) have been emerging as an alternative to VKA which, based on several observational cohort studies, are at least as efficacious and safe as VKA. This meta-analysis looked into the safety and efficacy of DOACs compared to VKA among CKD patients on dialysis with non-valvular AF. This study used a random-effects meta-analysis using RevMan 5.4. PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov were searched from their dates of inception to June 2023. The risk of bias was assessed using Cochrane RoB2 and the certainty of evidence was assessed using GRADE. This meta-analysis showed that DOACs when compared to VKA have no significant difference in terms of risk for major bleeding (RR = 0.81, 95% CI 0.46-1.43), ischemic stroke (RR = 0.5, 95% CI 0.19-1.35), and cardiovascular death (RR = 1.34, 95% CI 0.69-2.60). This meta-analysis adds to the growing body of evidence supporting that the use of DOACs has similar efficacy and safety outcomes in CKD patients on dialysis with non-valvular AF patients compared to VKA. The findings need to be replicated in larger and more adequately powered clinical trials in order to ascertain its level of evidence.

Venous bicarbonate and CKD progression: a longitudinal analysis by the group-based trajectory model.

Metabolic acidosis accelerates chronic kidney disease (CKD) progression towards kidney failure in animal models. Clinical trials testing the effect of bicarbonate on kidney outcomes are underpowered and/or of suboptimal quality. On the other hand, observational studies testing the same hypothesis are generally based on bicarbonate measured at a single time point. We studied the longitudinal relationship between repeated venous bicarbonate levels and a predefined composite renal outcome (a ≥30% estimated glomerular filtration rate reduction, dialysis or transplantation) by using group-based trajectory model (GBTM) analysis. The GBTM analysis was used to classify patients based on individual bicarbonate levels over time. The relationship between trajectory groups and renal outcomes was investigated using crude and adjusted Cox regression models. A total of 528 patients with stage 2-5 CKD were included in the analysis. The GBTM analysis identified four distinct trajectories of bicarbonate levels: low, moderate, moderate-high and high. During the follow-up period, 126 patients experienced the combined renal endpoint. The hazard rate of renal events decreased dose-dependently from the lowest to the highest bicarbonate trajectory. After adjusting for potential confounders, there was a 63% risk reduction for the composite renal endpoint for patients in the high trajectory category compared with those in the low trajectory category. The study found that higher bicarbonate trajectories were associated with a lower risk of adverse renal outcomes in CKD patients. These results suggest that strategies to maintain higher bicarbonate levels may benefit patients with CKD. However, further high-quality randomised trials are needed to confirm these findings and recommend bicarbonate supplementation as a strategy to delay CKD progression.

Measured sodium excretion is associated with cardiovascular outcomes in non-dialysis CKD patients: results from the KNOW-CKD study.

There are insufficient studies on the effect of dietary salt intake on cardiovascular (CV) outcomes in chronic kidney disease (CKD) patients, and there is no consensus on the sodium (Na) intake level that increases the risk of CV disease in CKD patients. Therefore, we investigated the association between dietary salt intake and CV outcomes in CKD patients. In the Korean cohort study for Outcome in patients with CKD (KNOW-CKD), 1,937 patients were eligible for the study, and their dietary Na intake was estimated using measured 24h urinary Na excretion. The primary outcome was a composite of CV events and/or all-cause death. The secondary outcome was a major adverse cardiac event (MACE). Among 1,937 subjects, there were 205 (10.5%) events for the composite outcome and 110 (5.6%) events for MACE. Compared to the reference group (urinary Na excretion< 2.0g/day), the group with the highest measured 24h urinary Na excretion (urinary Na excretion ≥ 8.0g/day) was associated with increased risk of both the composite outcome (hazard ratio 3.29 [95% confidence interval 1.00-10.81]; P = 0.049) and MACE (hazard ratio 6.28 [95% confidence interval 1.45-27.20]; P = 0.013) in a cause-specific hazard model. Subgroup analysis also showed a pronounced association between dietary salt intake and the composite outcome in subgroups of patients with abdominal obesity, female, lower estimated glomerular filtration rate (< 60 ml/min per 1.73m2), no overt proteinuria, or a lower urinary potassium-to-creatinine ratio (< 46 mmol/g). A high-salt diet is associated with CV outcomes in non-dialysis CKD patients.

Dapagliflozin versus empagliflozin in patients with chronic kidney disease.

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

Dapagliflozin in patients with chronic kidney disease: a systematic review and meta-analysis on randomized, double-blind, placebo-controlled multicenter trials

Introduction: Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce the mortality rate, hospitalization, and cardiac morbidity in diabetic patients. However, their safety in chronic kidney disease (CKD) individuals is still debatable. Objectives: The present study aims to evaluate the effect of dapagliflozin on primary composite outcomes and mortality rate in CKD patients using a systematic review and meta-analysis approach. Materials and Methods: In this meta-analysis, Cochrane, Web of Science, Scopus, and PubMed databases, along with the Google Scholar search engine, were queried until March 2023. Data were analyzed by STATA software version 14 at a significance level of P&lt;0.05. Results: A total of nine randomized clinical trials (RCTs) articles were reviewed, with a sample size of 16720 in the dapagliflozin group and 13 476 in the placebo group. Dapagliflozin use (10 mg/d) compared to placebo improved primary composite outcomes in CKD patients by 39% (OR=0.61, 95% CI: 0.57, 0.65) while reducing the mortality rate by 31% (OR=0.69, 95% CI: 0.63, 0.76). In an analysis by treatment length, no statistically significant change was noted in early composite outcomes (OR=0.70, 95% CI: 0.48, 1.01) and mortality rate (OR=0.75, 95% CI: 0.39, 1.45) between patients who were on dapagliflozin for less than two years and the placebo group. However, patients receiving dapagliflozin for two years and above had significantly improved primary composite outcomes (OR=0.60, 95% CI: 0.55, 0.66) and mortality rate (OR=0.69, 95% CI: 0.61, 0.79) compared to the placebo group. Conclusion: Dapagliflozin use, compared to placebo, improved the early composite outcomes and mortality rate in CKD patients. Prescribing a daily dose of 10 mg for a treatment duration of over two years seems safe in these patients. Registration: This study has been compiled based on the PRISMA checklist, and its protocol was registered on the PROSPERO website (ID: CRD42023422186).

Fibroblast growth factor 23 but not copeptin is independently associated with kidney failure and mortality in patients with chronic kidney disease.

Copeptin and intact fibroblast growth factor 23 (iFGF23) increase early during chronic kidney disease (CKD) and may be predictive of unfavourable outcomes. The aim of this study was to evaluate their respective associations with renal and vital outcomes in CKD patients. We included CKD patients from the NephroTest cohort with concomitant measurements of plasma copeptin and iFGF23 concentrations and isotopic glomerular filtration rate measurement (mGFR). The primary endpoint was a composite outcome including kidney failure (KF) (dialysis initiation, pre-emptive transplantation or a 57% decrease of mGFR, corresponding to doubling of serum creatinine) or death before KF. Hazard ratios (HRs) of the primary endpoint associated with log-transformed copeptin and iFGF23 concentrations were estimated by Cox models. The slope of mGFR over time was analysed using a linear mixed model. A total of 329 CKD patients (243 men, mean age 60.3±14.6years) were included. Among them, 301 with an mGFR >15ml/min/1.73m2 were included in survival and mGFR slope analyses. During a median follow-up of 4.61years (quartile 1-quartile 3: 3.72-6.07), 61 KFs and 32 deaths occurred. Baseline iFGF23 concentrations were associated with the composite outcome after multiple adjustments {HR 2.72 [95% confidence interval (CI) 1.85-3.99]}, whereas copeptin concentrations were not [HR 1.01 (95% CI 0.74-1.39)]. Neither copeptin nor iFGF23 were associated with mGFR slope over time. Our study shows for the first time in population of CKD patients an independent association between iFGF23 and unfavourable renal and vital outcomes and shows no such association regarding copeptin, encouraging the integration of iFGF23 measurement into the follow-up of CKD.