N-terminal pro-B-type natriuretic peptide, eGFR, and progression of kidney disease in chronic kidney disease patients without heart failure.

Background: Cardiorenal syndrome highlights the bidirectional relationship between kidney and heart dysfunction. N-terminal pro-B-type natriuretic peptide (NT-proBNP), which is the gold standard biomarker in heart failure (HF), may be an important biomarker for chronic kidney disease (CKD) progression. However, NT-proBNP is negatively related with estimated glomerular filtration rate (eGFR). In this study, we investigated the association of NT-proBNP, eGFR, and progression of kidney disease in CKD patients without HF. Methods: This multicentric retrospective cohort study recruited 23 860 CKD patients without HF, who had at least one NT-proBNP record from China Renal Data System database. Linear regression model evaluated the relationship between eGFR and NT-proBNP. Cox regression analysis assessed the association between NT-proBNP and CKD progression. Sensitivity analysis examined the robustness of the main findings. Results: This study involved 23 860 CKD patients without HF, distributed across different CKD stages: 10 526 in stages G1-2, 4665 in G3a, 3702 in G3b, 2704 in G4, and 2263 in G5. NT-proBNP was negatively correlated with eGFR, particularly in stages 4-5 CKD. A 15-unit decrease in eGFR was associated with increases in log (NT-proBNP) levels by 1.04-fold, 1.27-fold, 1.29-fold, 1.80-fold, and 3.50-fold for stages 1-2, 3a, 3b, 4, and 5, respectively. After excluding patients who developed CKD progression within 1 year, the Cox regression analysis revealed that the relationship between NT-proBNP and CKD progression was not significant in stages 4 and 5. However, for stages 1-3, each standard deviation increase in log (NT-proBNP) was associated with a 26%, 36%, and 28% higher risk of CKD progression, with P interaction ≤.001. The hazard ratios were 1.26 (95% confidence intervals (CI), 1.18 to 1.35), 1.36 (95% CI, 1.22 to 1.51), and 1.28 (95% CI, 1.14 to 1.43) for stages 1-2, stage 3a, and stage 3b, respectively. Conclusions: Despite its strong inverse association with eGFR, NT-proBNP was positively associated with the risk of progression of kidney disease in CKD patients with stages 1-3 without HF. Future studies should investigate the effectiveness of NT-proBNP as a predictive biomarker for the progression of kidney disease across diverse racial groups and healthcare settings.

Association between serum uric acid variability and mild eGFR decline in Chinese adults: a retrospective cohort study.

BACKGROUND: The present retrospective cohort study focused on evaluating the effects of fluctuations in serum uric acid (SUA) on a mildly reduced glomerular filtration rate (eGFR) in a population with a normal eGFR in Urumqi, China. METHODS: A total of 2,154 normal individuals with a normal eGFR were recruited from 2018 to 2021. This study included questionnaire surveys, physical measurements, and blood sampling. We deemed the mildly reduced eGFR to be 60-90 ml·min-1·(1.73 m2)-1. The relationship between changes in SUA levels and the eGFR was assessed. RESULTS: (1) During the 3-year follow-up period, 433 individuals (20.10%) presented mildly reduced eGFR. (2) After stratification by the degree to which uric acid changed into five groups, the group showing the greatest change in uric acid concentration had significantly lower eGFR values than the other four groups. As the uric acid concentration (ΔSUA) increased, the degree of mild eGFR reduction (ΔeGFR) also increased (P < 0.05). When classified into five groups by the degree of eGFR change (ΔeGFR), analysis of variance revealed no statistically significant differences between baseline SUA and follow-up SUA (P > 0.05). Pearson correlation analysis showed a negative correlation between ΔSUA and ΔeGFR (r = -0.211, P < 0.01). (3) Multifactorial logistic regression, in which the endpoint event was an eGFR decreasing to 60 to 90 ml·min-1·(1.73 m2)-1, revealed that the ΔSUA was a risk factor that independently predicted a reduced eGFR (OR = 1.347, P < 0.001). CONCLUSION: In people with a normal eGFR in Urumqi, a high SUA level is associated with a mild reduction in the eGFR.

Association of initial serum sodium change and clinical outcome in patients with diabetes receiving sodium-glucose cotransporter-2 inhibitor therapy: A multicentre database analysis in Taiwan.

AIM: The study aimed to assess the impact of varying degrees of initial serum sodium change among patients with type 2 diabetes (T2D) starting sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy and their subsequent clinical outcome. METHODS: We used medical data from a multicentre health care provider in Taiwan and recruited 4400 patients with T2D with baseline normal serum sodium (135-145 mmol/L) and follow-up serum sodium measures available after 3 months of SGLT2i treatment from 1 June 2016 to 31 December 2021. RESULTS: After a median of 2.9 (2.4, 3.4) months of SGLT2i treatment, overall, there was a minimal change in serum sodium levels (from 139.6 ± 2.4 to 139.5 ± 3.7 mmol/L). Most patients (87.8%) maintained normal sodium levels, while 8.6% (n = 378) experienced hyponatraemia (<135 mmol/L) and 3.6% (n = 158) hypernatraemia (>145 mmol/L). Factors independently associated with hyponatraemia included cancer history, chronic lung disease, insulin use, higher glycated haemoglobin, impaired liver function, lower baseline sodium and greater initial decline in kidney function. Conversely, factors linked to hypernatraemia included older age, absence of cancer history, loop diuretic and non-steroidal anti-inflammatory drug use, higher baseline sodium and a lesser initial decline in kidney function. Over a median of 26.0 months of follow-up, hyponatraemia shortly after starting SGLT2i therapy was associated with significantly increased risks of major adverse cardiovascular events [hazard ratio (HR): 2.52; 95% confidence interval (CI): 1.83-3.48], heart failure for hospitalization (HR: 1.66; 95% CI: 1.16-2.37), major adverse renal events (HR: 2.27; 95% CI: 1.73-2.96) and all-cause death (HR: 2.98; 95% CI: 2.17-4.11) after adjusting for clinically relevant factors. Non-linear analysis indicated that a more pronounced initial decline in serum sodium levels correlated steeply with higher risks of these adverse events. CONCLUSION: While most patients with T2D maintain stable serum sodium homeostasis on SGLT2i therapy, a subset may experience dysnatraemic events with potential worse clinical consequences. Physicians should be vigilant about monitoring sodium levels and considering the associated risks when initiating SGLT2i therapy in patients with risk.

Comparative efficacy and choice of lipid-lowering drugs for cardiovascular and kidney outcomes in patients with chronic kidney disease: A systematic review and network meta-analysis.

BACKGROUND: The effect of exact classes of lipid-lowering drugs (LLDs) on preventing major adverse cardiovascular events (MACEs) and poor renal outcomes is not well characterized in the chronic kidney disease (CKD) population. METHODS: We performed a frequentist random-effects network meta-analysis of randomized controlled trials (RCTs) to evaluate the protective effect of the LLDs in non-dialysis CKD patients. The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched for relevant trials published before March 31, 2024. The primary outcome was the incidence of MACEs. The secondary outcomes comprised all-cause mortality, end-stage kidney disease, changes in estimated glomerular filtration rate (eGFR) and proteinuria, and safety. RESULTS: Forty-nine eligible RCTs with 77,826 participants with non-dialysis CKD were included. With moderate confidence in the evidence, rosuvastatin and atorvastatin showed statistically significantly more efficacy in reducing the risk of MACE, with a pooled risk ratio of 0.55 (95% CI 0.33-0.91) for rosuvastatin and 0.67 (0.49-0.90) for atorvastatin, respectively, compared with the control group. For the change in the eGFR, atorvastatin (mean difference [MD], 1.40; 95% CI, 0.61 to 2.18), rosuvastatin (MD, 1.73; 95% CI, 0.63 to 2.83), and statin plus ezetimibe (MD, 2.35; 95% CI, 0.44 to 4.26) showed statistically significant increases in the mean eGFR. CONCLUSION: In patients with non-dialysis CKD, there is sufficient evidence to show that rosuvastatin and atorvastatin were statistically significantly more effective and preferable in reducing the risk of MACE and increasing the mean eGFR compared with the control group.

Short term sodium glucose transport protein 2 inhibitors are associated with post contrast acute kidney injury in patients with diabetes.

Although sodium-glucose transport protein-2 (SGLT2) inhibitors (SGLT2i) do not increase the risk of acute kidney injury (AKI) in general, they may pose a risk in patients undergoing angiography. This prospective cohort study aimed to evaluate the safety and efficacy of SGLT2i for post-contrast AKI (PC-AKI) in patients with type 2 diabetes mellitus (T2DM). Following screening, 306 patients with T2DM selected to undergo coronary arterial angiography with or without percutaneous intervention were enrolled. Patients were divided into the SGLT2i exposure and non-exposure groups. The primary outcome was PC-AKI, defined as an increase in serum creatinine levels > 0.5 mg/dL (44.2 µmol/L), or 25% above the baseline, within 48-72 h after exposure to contrast medium. The incidence of PC-AKI in the overall T2DM population was 5.2% (16/306). Following 1:1 propensity score matching, the incidence of PC-AKI was significantly higher in the SGLT2i group than in the non-SGLT2i group (10.7% vs. 2.9%; P = 0.027), with an odds ratio of 4.5 (95% confidence interval: 1.0-20.2; P = 0.047). Furthermore, PC-AKI occurred at a higher rate among short-term users of SGLT2i than long-term users (20.5% vs. 3.4%, P = 0.018). Thus, our findings suggest an increased risk of PC-AKI associated with short-term SGLT2i therapy in patients with T2DM.

The association of physical activity with kidney function risk among adults with long working hours.

Introduction: Long working hours are likely associated with the decreased of kidney function, while physical activity (PA) was linked to improvements in kidney function. However, whether PA can offset the negative impact of long working hours on kidney function was unclear, which is the focus of this study. Methods: A cross-sectional study was conducted. Three approaches were adopted to distinguish the association between long working hours and regular working hours. Moderate to vigorous physical activity (PA) was assessed by a structured questionnaire. eGFR and chronic kidney disease (CKD) or not were utilized to evaluate the kidney function. Linear and logistic regression analyses were conducted to assess the association between weekly working hours, PA, and kidney function. Results: A total of 18,431 adults were enrolled in this study, including 9981 males (54.2%) and 8450 females (45.8%). The average eGFR was (99.54 ± 17.55 mL/min/1.73 m2). The people worked more than 40 h/wk (98.89 ± 17.06 mL/min/1.73 m2) had lower eGFR compared to those worked less than 40 h/wk (99.93 ± 17.83 mL/min/1.73 m2) (p < 0.05). Individuals working longer hours exhibited lower eGFR (ß = -0.772, 95% CI: -1.241, -0.303, for > 40 h/wk compared to working ≤ 40 h/wk). Engagement in moderate to vigorous PA was associated with higher eGFR values (ß = 1.159, 95% CI: 0.699, 1.619) compared to low PA (< 150 minutes/wk), but this association did not reach statistical significance for the prevalence of CKD. Furthermore, PA was insufficient to reverse the decline of eGFR related to prolonged working hours. Discussion: Prolonged working hours were associated with a decline in eGFR, while PA was found to have a protective effect on kidney function. However, PA alone may not fully mitigate the negative impact of prolonged working hours on renal health. More robust measures to protect renal function should be implemented to mitigate the damage caused by prolonged working hours.

Outpatient Renal Function Screening Before Contrast-Enhanced CT Examinations.

Intravascular administration of iodinated contrast media can cause contrast-induced acute kidney injury, especially in patients with an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m². The American College of Radiology (ACR) and the European Society of Urogenital Radiology (ESUR) guidelines recommend renal function screening based on medical history, but their effectiveness has been under-evaluated. This retrospective study included 2,560 consecutive adult outpatients without eGFR measurements within 180 days before contrast-enhanced computed tomography (CT) at a single tertiary hospital from July through September 2023. On the day of CT, they underwent eGFR tests and 1.1% had an eGFR < 30 mL/min/1.73 m², preferentially with histories of gout and renal disease. According to the ACR and ESUR strategies, 16.9% and 38.8% of all study participants were positive, respectively, identifying 92.6% and 96.3% of patients with renal insufficiency. Both strategies demonstrated high negative predictive values. These results support selective renal function screening before contrast-enhanced examinations.

IPNA consensus definitions for clinical trial outcomes in steroid-resistant nephrotic syndrome.

Assessment of the true impact of therapeutic interventions is a challenge in the absence of universal, standardized definitions for clinical trial endpoints in children with kidney diseases. Steroid-resistant nephrotic syndrome (SRNS) is a difficult kidney disease to treat, with unremitting disease progressing to kidney failure. Currently, available therapies result in suboptimal cure rates. Clinical trials with innovative, targeted treatments will likely be conducted for this disease in the foreseeable future. An international consortium of the IPNA Best Practices and Standards Committee and the Pediatric Nephrology Expert Group of the conect4children (c4c) network developed through consensus, standardized, internationally acceptable definitions for trial outcomes for SRNS. The endpoint definitions were formulated for use with urine protein to creatinine ratios and estimated glomerular filtration rates. Definitions of complete remission, partial remission, non-remission of disease, reduction in proteinuria, kidney disease progression, kidney failure, and composite kidney outcome were refined using an iterative process until a consensus was achieved.

Finerenone's Impact on Major Adverse Cardiovascular Events in Chronic Kidney Disease and Type 2 Diabetes Mellitus: A Systematic Review.

Chronic kidney disease (CKD) impacts about 10% of adults globally and substantially elevates the risk of major adverse cardiovascular events (MACE), such as heart attacks, strokes, cardiovascular-related deaths, and hospital admissions due to heart failure. The interplay between CKD and cardiovascular disease (CVD) leads to poor health outcomes. Nevertheless, there is a scarcity of systematic reviews focusing on the effectiveness of finerenone, a new non-steroidal mineralocorticoid receptor antagonist (MRA), in lowering these risks. In this systematic review, we aim to evaluate the impact of finerenone on reducing MACE in individuals with CKD and type 2 diabetes mellitus (T2DM). CKD pathophysiology involves hyperglycemia, hypertension, and dyslipidemia, leading to glomerular hyperfiltration, inflammation, and fibrosis. Traditional treatments, including angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i), often fall short in preventing cardiovascular events. Steroidal MRAs like spironolactone and eplerenone, while effective in reducing proteinuria, are limited by hyperkalemia risks. Finerenone offers a more selective mechanism, reducing sodium retention, inflammation, and fibrosis, with a lower risk of hyperkalemia. We searched five electronic databases comprehensively, identifying studies consistently demonstrating that finerenone significantly reduces MACE and improves renal outcomes by reducing albuminuria and slowing the fall in estimated glomerular filtration rate (eGFR). However, limitations include study heterogeneity, short follow-up periods, and potential publication bias. In conclusion, finerenone shows promise as a therapeutic option for CKD and T2DM, reducing MACE and improving renal outcomes. Further research is needed to understand its long-term benefits and safety across diverse populations.

Prevalence, risk factors and effect of curative parathyroidectomy on nephrocalcinosis in Asian-Indian patients with symptomatic primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is characterized by inappropriate secretion of parathyroid hormone, causing hypercalcemia and hypercalciuria, leading to renal stone diseases and nephrocalcinosis. The frequency, risk factors, and curative effect on nephrocalcinosis in post-parathyroidectomy have not been identified yet. Therefore, the present study evaluated the clinico-biochemical, radiological parameters and curative effect on nephrocalcinosis. A total of 583 PHPT patients were analysed in four groups viz. Group 1 (PHPT with nephrocalcinosis-98; 16.8%); Group 2 (PHPT with nephrolithiasis-227; 38.9%); Group 3 (PHPT with both nephrolithiasis and nephrocalcinosis-59; 10.1%); and Group 4 (PHPT without renal diseases-199, 34.1%). In the sub-group analysis, younger age (p ≤ 0.05), male gender (p ≤ 0.05), and hematuria (p ≤ 0.005) were significant in Group 1 vs. Group 4. Dysuria and low eGFR were significant in Group 1 vs. Group 2 (p ≤ 0.0005; p ≤ 0.05) and Group 1 vs. Group 4 (p ≤ 0.0005; p ≤ 0.0005). Polyuria (p ≤ 0.05; p ≤ 0.05, p ≤ 0.005), and gravluria (p ≤ 0.05; p ≤ 0.0005, p ≤ 0.005) were frequent in Group 1 vs. other groups. A significant difference was observed in S.Ca and, 24-hrs U.Ca in Group 1 vs. Group 2 {(12.2 (10.8-13.4) vs. 11.2 (10.7-12.4), p ≤ 0.05; 301 (189.5-465) vs. 180 (92.5-323.1), p ≤ 0.05} and Group 1 vs. Group 4 {(12.2 (10.8-13.4) vs. 11.4 (10.7-12.5), p ≤ 0.05 ; 301 (189.5-465) vs. 213 (110-360), p ≤ 0.0005}. Multivariate logistic regression showed gravluria [aOR = 9.2, p = 0.0001], S.Ca (aOR = 1.30, p = 0.003) and, 24-hrs U.Ca (aOR = 1.02, p = 0.042) to be independent predictors of nephrocalcinosis. Pre and post-operative assessment revealed decreased S. Ca levels [(11.9 ± 1.9) vs. (10.5 ± 1.0) mg/dL; p = 0.04] and complete radiological resolution (10.4%) in PHPT with nephrocalcinosis. Therefore, serum calcium, 24-hrs Urinary calcium, and gravluria were independent predictors of nephrocalcinosis with 10.4% showing complete radiological resolution post-operatively.

Empagliflozin and other SGLT2 inhibitors in patients with heart failure and preserved ejection fraction: a systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) is a highly prevalent disease, among the primary factors contributing to morbidity and death. One of its types is heart failure with preserved ejection fraction (HFpEF) comprising 40%-50% of newly diagnosed HF cases. Despite the high prevalence of HFpEF, there is still a lack of knowledge regarding the best drugs and treatment approaches to be used. However, the sodium-glucose co-transporter 2 (SGLT2) inhibitors could be a promising treatment. OBJECTIVES: To examine SGLT2 inhibitors' effect on hospitalization, cardiovascular death, and estimated glomerular filtration rate (eGFR) in HFpEF patients. SEARCH METHODS: We conducted searches for randomized controlled trials (RCTs) in PubMed, Embase, Scopus, and Web of Science up to July 2024. SELECTION CRITERIA: We chose RCTs that examined the effects of SGLT2 inhibitors and placebo in individuals with higher than 40% ejection fraction (HFpEF). DATA COLLECTION AND ANALYSIS: The methodology for the systematic review and meta-analysis was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. MAIN RESULTS: We included 8 studies with 16,509 participants. Drugs examined in our paper included empagliflozin, dapagliflozin, sotogliflozin, and ertugliflozin. Various outcomes were analyzed in different papers. However, different SGLT2 inhibitors lead to a decreased risk of cardiovascular hospitalization and kidney injury. Our meta-analysis showed a decreased risk of cardiovascular hospitalization but not death due to cardiovascular causes or other causes. These results were regardless of baseline status of eGFR, systolic blood pressure, atrial fibrillation or flutter, diabetes mellitus, sex, body mass index, and nt-proBNP. The included studies were of moderate to high quality. CONCLUSION: For individuals with HFpEF, SGLT2 inhibitors have been proven to be a safe and effective medication. However, more studies are needed for longer durations, reporting adverse events, effects on exercise tolerance, and other secondary outcomes.

Associations between inflammatory markers and carotid plaques in CKD: mediating effects of eGFR-a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) is a significant public health concern associated with a high prevalence of carotid plaques, which are indicators of atherosclerosis and predictors of adverse cardiovascular outcomes. Inflammation is a hallmark of CKD, contributing to both renal dysfunction and cardiovascular complications. This study aims to investigate the association between inflammatory markers-systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), aggregate inflammatory status index (AISI), monocyte to high-density lipoprotein cholesterol ratio (MHR), neutrophil to high-density lipoprotein cholesterol ratio (NHR), neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR)-and carotid plaques in CKD patients, and to explore the potential mediating role of estimated glomerular filtration rate (eGFR) in this relationship. METHODS: A cross-sectional analysis was conducted on patients admitted to the Division of Nephrology between January 2023 and June 2023. The primary endpoint was the presence of carotid plaques assessed using ultrasound imaging. Multivariable logistic regression models were used to examine the associations between inflammatory markers and carotid plaques, and trend tests were performed to evaluate the trending association of carotid plaques risk and inflammatory markers in tertiles. Restricted cubic spline (RCS) analysis was used to assess potential non-linear relationships, and subgroup analyses were conducted to examine consistency across different strata. Mediation analysis was performed to explore the role of eGFR. RESULTS: Of the 609 participants, 387 were included in the final analysis after applying exclusion criteria. Elevated levels of LnSIRI (OR = 1.87, 95% CI = 1.25-2.80), LnSII (OR = 1.67, 95% CI = 1.09-2.56), LnAISI (OR = 1.70, 95% CI = 1.22-2.37), LnMHR (OR = 1.94, 95% CI = 1.15-3.26), LnNHR (OR = 1.82, 95% CI = 1.10-3.02), and LnMLR (OR = 2.26, 95% CI = 1.18-4.34) were significantly associated with the presence of carotid plaques. There were significant trends for increasing tertiles of SIRI, AISI, MHR and NHR. RCS analysis showed no significant non-linear associations. Subgroup analyses indicated similar associations across most strata. eGFR partially mediated these relationships, with proportions mediated ranging from 14.7 to 17.5%. CONCLUSIONS: Inflammatory markers are significantly associated with carotid plaques in CKD patients, with eGFR playing a partial mediating role. These findings highlighted the importance of managing inflammation and maintaining renal function to mitigate the risk of atherosclerosis in CKD patients. TRIAL REGISTRATION: Not applicable.

Efficacy of atorvastatin on renal function in patients with contrast-induced nephropathy after percutaneous coronary intervention.

BACKGROUND: At present, the clinical methods for preventing and treating contrast-induced nephropathy (CIN) are limited, and statins can play a better role during this process. So, we aimed to assess the atorvastatin on renal function in nephropathy patients after percutaneous coronary intervention (PCI). METHODS: In this work, 100 elderly patients with coronary heart disease (CHD) were selected into an experimental group (Exp group, 50 cases, 40 mg/d po atorvastatin) and a control group (Ctrl group, 50 cases, 10 mg/d po atorvastatin). The renal function indicators, blood routine indicators, and the incidence of adverse reactions (ARs) were compared between patients in Exp and Ctrl groups. RESULTS: After surgery, the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cystatin C (CysC), high-sensitivity C-reactive protein (hs-CRP), and interleukin (IL6) in patients in the Exp group were much lower, and the levels of estimated glomerular filtration rate (eGFR) and superoxide dismutase (SOD) were higher (all P < 0.05). Meanwhile, the incidences of ARs during hospitalization between patients in the Exp and Ctrl groups were all 8%, showing no observable difference (P > 0.05). Compared with conventional doses of atorvastatin, high-dose atorvastatin can effectively prevent renal function damage in patients with CIN, decrease the inflammation and oxidative stress in patients, and will not increase the risk of ARs during hospitalization. CONCLUSION: Taken together, high-dose atorvastatin can be applied in treating patients with CHD after PCI due to its excellent efficacy and high safety.

Prognostic impact of switching to the 2021 chronic kidney disease epidemiology collaboration creatinine-based equation in Caucasian patients with type 2 diabetes: the Renal Insufficiency and Cardiovascular events (RIACE) Italian Multicenter Study.

BACKGROUND: A Chronic Kidney Disease (CKD) Epidemiology Collaboration (EPI) formula not including a Black race coefficient has been recently developed and is now recommended in the US. The new (2021) equation was shown to yield higher estimated glomerular filtration rate (eGFR) values than the old (2009) one in a non-Black general population sample, thus reclassifying a significant number of individuals to a better eGFR category. However, reclassified individuals were previously shown to have a lower risk of progression to end-stage kidney disease, but higher adjusted risks for all-cause death and morbidity and mortality from cardiovascular disease than those not reclassified. This study evaluated the prognostic impact of switching from the 2009 to the 2021 CKD-EPI equation in non-Black individuals with type 2 diabetes. METHODS: The Renal Insufficiency And Cardiovascular Events (RIACE) was a prospective cohort study enrolling 15,773 Caucasian patients in 19 Italian centers in 2006-2008. Cardiometabolic risk profile, treatments, complications, and comorbidities were assessed at baseline and eGFR was calculated with the two equations. Vital status was retrieved on 31 October 2015 for 15,656 participants (99.3%). RESULTS: With the 2021 equation, the eGFR value increased in all patients, except for 293 individuals with a 2009 eGFR ≥ 105 ml·min- 1·1.73 m- 2. The median difference was 4.10 ml·min- 1·1.73 m- 2 and was higher in males, older individuals and those in the G2 category. Reclassification decreased the percentage of patients with reduced eGFR from 17.28 to 13.96% and with any CKD from 36.23 to 34.03%. Reclassified individuals had better cardiometabolic risk profile and lower prevalence of complications and use of medications than non-reclassified individuals. Risk of death versus the 2009 G1 category was lower for reclassified than non-reclassified participants in all eGFR categories and, particularly, in each 2009 eGFR category, though difference was significant only in the G4-G5 category. The Receiver Operator Characteristic curves were statistically, but not clinically different with the two equations. CONCLUSION: Changing from the 2009 to the 2021 CKD-EPI equation results in higher eGFR and lower CKD prevalence, with a lower risk of death in reclassified patients with an eGFR < 30 ml·min- 1·1.73 m- 2, but virtually no impact on mortality prediction. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.

Role of baseline soluble tumor necrosis factor receptor 2 as a biomarker in primary podocytopathy: Implications for renal impairment and disease progression.

BACKGROUND: Podocytopathies, including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and collapsing glomerulopathy (CG), are kidney diseases that damage glomerular podocytes, leading to heavy proteinuria and nephrotic syndrome (NS). Inflammation plays a critical role in the progression of chronic kidney disease (CKD), with recent studies linking inflammatory biomarkers to declining kidney function. Tumor necrosis factor-alpha (TNF-α), an essential inflammatory cytokine, interacts with its circulating receptors, TNFR1 and TNFR2. The TNF-α pathway has been implicated in the pathogenesis of FSGS and MCD. Increased circulating TNFR2 levels have been associated with worsening renal function in podocytopathies, suggesting that the TNF-α inflammatory pathway significantly contributes to disease progression. METHODS: We conducted a study involving 53 patients with biopsy-proven MCD or FSGS and 53 healthy, age- and gender-matched controls. All patients were followed for 18 months. We analyzed serum and urine TNFR2 levels and gene expression at baseline and after three months. To assess the ability of TNFR2 to predict persistent decline in estimated glomerular filtration rate (eGFR < 30 mL/min/1.73m2), remission, and relapse, we employed Cox regression analysis. Additionally, we evaluated its prognostic utility for predicting progression to stage 4 CKD using ROC curve analysis. RESULTS: Serum and urine TNFR2 levels were significantly elevated in patients compared to controls. Serum TNFR2 was a significant predictor in univariate Cox regression analysis for persistent eGFR decline (HR 1.017, 95% CI: 1.003 to 1.032, p = 0.018), remission (HR 0.995, 95% CI: 0.992 to 0.999, p = 0.006), and relapse (HR 1.005, 95% CI: 1.001 to 1.010, p = 0.029). The ROC curve analysis demonstrated that serum TNFR2 levels had a strong prognostic ability for predicting progression to stage 4 CKD, with an AUC of 0.848 (95% CI: 0.737-0.960), sensitivity of 81%, and specificity of 71%. CONCLUSION: This study underscores the critical role of circulating TNFR2 in kidney injury among patients with primary podocytopathy. Elevated TNFR2 levels are significant predictors of persistent eGFR decline and disease relapse, highlighting their potential as biomarkers for disease progression and prognosis.

Associations between multi-metal joint exposure and decreased estimated glomerular filtration rate (eGFR) in solar greenhouse workers: A study of a unique farmer group.

BACKGROUND: Solar greenhouse workers, a unique farmer group, have been reported to have a higher risk of chronic kidney disease (CKD) compared to the general population, possible due to exposure to multiple metals. OBJECTIVE: This study aimed to investigate the associations between exposure to multiple metals and the estimated glomerular filtration rate (eGFR). METHODS: A cross-sectional study was conducted in the Northwest China. Urine samples were tested for concentration of 14 metals, including chromium, manganese, iron et al. Blood creatinine was measured to calculate eGFR, which was to evaluate the kidney function. Linear model and the Bayesian Kernel Machine Regression (BKMR) models were used to evaluate the associations between metals exposure and eGFR. RESULT: The study included 281 solar greenhouse workers, with 128 (45.6%) males and 153 (54.4%) females. The highest median concentrations of metals were zinc (418.55 µg/L), strontium (368.77 µg/L), and iron (55.73 µg/L), respectively. The linear model analysis showed that urinary levels of copper and zinc were negatively associated with eGFR [ß = -0.021, 95% CI (-0.048, -0.007); ß = -0.018, 95% CI (-0.068, -0.005)] considering a false discovery rate. BKMR results indicated a significant overall negative effect of 14 metals exposure on the eGFR when all metal levels were above the 50th percentile compared to the median value. CONCLUSIONS: The decrease in eGFR among solar greenhouse workers was related to mixed metal exposure. Reducing exposure to the metals of copper, zinc, and lead could effectively protects kidney function. Further prospective studies are needed to resolve concerns about reverse causality.

Evaluating a multicomponent intervention for managing kidney outcomes among patients with moderate or advanced chronic kidney disease (CKD): protocol for the Strategies for Kidney Outcomes Prevention and Evaluation (SKOPE) randomized controlled trial.

BACKGROUND: Chronic kidney disease (CKD) poses a global health challenge with high morbidity and mortality rates. Early detection and prompt intervention are critical in preventing progression to end-stage kidney disease (ESKD) and cardiovascular complications. Effective CKD management requires comprehensive care packages that integrate both pharmacological and non-pharmacological interventions within collaborative, team-based models, aiming to enhance patient outcomes and overall quality of life. The goal of the Strategies for Kidney Outcomes Prevention and Evaluation (SKOPE) study is to establish effective multicomponent intervention (MCI) strategies for evaluating and preventing kidney outcomes in patients with moderate to advanced CKD within primary care settings in Singapore. METHODS: This study is a 3-year randomized controlled trial among 896 participants aged between 40 and 80 years with moderate or advanced CKD in five government-subsidized polyclinics in Singapore. The components of the MCI are (1) nurses/service coordinators trained as health coaches for motivational conversation and CKD-specific lifestyle counseling on diet and exercise, using a hybrid follow-up approach of in-person, telephone, and secure video meetings; (2) training physicians in algorithm-based standardized management of CKD; (3) subsidy on SGLT2i medications for CKD; and (4) regular CKD case review meetings. The primary outcome is the estimated glomerular filtration rate (eGFR) total slope from randomization to final follow-up at 36 months. DISCUSSION: If shown to be effective, cost-effective, and acceptable, SKOPE should be considered for scaling country-wide and in similar regional healthcare systems. TRIAL REGISTRATION: ClinicalTrials.gov NCT05295368. Registered on March 25, 2022.

Impact of Mayo Adhesive Probability score and BMI on renal functional decline after robotic assisted partial nephrectomy.

Purpose: The purpose of this study is to investigate the impact of Mayo Adhesive Probability (MAP) score and body mass index (BMI) on renal function decline after robotic assisted partial nephrectomy (RAPN). Methods: We queried our prospective database for patients who underwent RAPN between January 2018 and December 2023. Outcomes were development of de novo CKD-S3 (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m2). Multivariable analysis (MVA) via Cox regression identified predictors for CKD-S3. Kaplan-Meier Analyses was fitted for survival assessment. Finally, multivariable linear regression was utilized to identify predictors of delta eGFR at last follow-up (preoperative eGFR-last eGFR). Results: Two-hundred fifty-eight patients were analysed (obese n = 49 [19%]; MAP score 0-2 = 135 [52.33%]; MAP score 3-5 = 123 [47.6%]) with a median follow-up of 33 (IQR 20-42) months. MVA revealed, high MAP score (HR 2.29, p = 0.019), increasing RENAL score (HR 1.26, p = 0.009), increasing age (HR 1.04, p = 0.003), obesity (HR 2.38, p = 0.006) and diabetes mellitus (HR 2.38, p = 0.005) as associated with increased risk of development of CKD-S3, while trifecta achievement was not (p = 0.63). Comparing low MAP score versus high MAP score 4-year CKD-S3 free survival was 87.8% versus 56.1% (p < 0.001). Multivariable linear regression showed that high MAP score (coefficient 6.64, p = 0.001) and BMI (coefficient 0.51, p = 0.011) were significantly associated with increased delta eGFR at last follow up. Conclusions: MAP score and increasing BMI are predictor for long term renal functional detrimental. These insights may call consideration for closer follow-up or greater medical scrutiny prior surgery in obese patients and with elevated MAP score. Further investigations are requisite.

Primary and "Pre-Primary" Aldosteronism in Resistant Hypertension: A Practical, Pragmatic, and Prudent Approach in Resource-Limited Milieu.

Introduction Primary aldosteronism (PA), once considered rare, is now recognized as the most common cause of secondary hypertension, accounting for almost a quarter of resistant hypertension (RH) cases. Despite this, PA remains underdiagnosed, with an extremely low percentage of RH patients undergoing screening. Methods In a specialty diabetes-endocrinology clinic, the aldosterone:renin ratio (ARR) was assessed in 115 consecutive RH patients (ages 21-93 years; 47% male; 87% with type 2 diabetes). Fasting blood samples were drawn in a standing position after 30 minutes of walking. Adrenal imaging (CT/MRI) was performed for those with an ARR >20. Results ARR values ranged from 0.4 to 227 (ARR <10 (35%); 11-20 (19%), 21-40 (25%), and >40 (21%)), with corresponding stepwise decreasing plasma renin activity (PRA) (P= 1E-6) and increasing serum aldosterone (SA) (P= 8E-7). Increasing ARR tended to be associated with an increase in serum creatinine (R= 0.23; P= 0.03) and a decrease in estimated glomerular filtration rate (eGFR) (R= -0.24; P= 0.02) and an increase in urine albumin: creatinine ratio. The ARR> 40 group displayed the highest serum creatinine, lowest eGFR, higher urine albumin: creatinine ratio, highest serum sodium, lowest serum potassium, and highest (44%) abnormal adrenal imaging (bilateral hyperplasia diffuse/nodular; solitary adenoma), reflecting a later stage of the pathological spectrum. PA treatment with mineralocorticoid receptor antagonists (MRAs) had a salutary effect. Conclusions Our observations further reinforce that PA is not a binary condition, but exists as a spectrum disorder responsive to MRAs, even in patients with mildly elevated or normal aldosterone levels. Early disease detection/recognition ("renin-independent aldosterone production") can be facilitated by marking "pre-primary" aldosteronism (ARR 11-20), followed by monitoring progression (periodic rescreening) and optimizing treatment, with hopeful mitigation of end-organ damage in RH.

Causal associations between kidney function and aortic valve stenosis: a bidirectional Mendelian randomization analysis.

BACKGROUND: Aortic valve stenosis (AVS) is currently the most common heart valve disease. The results of observational studies on the incidence of AVS in the renal dysfunction population are contradictory due to the short follow-up period and different diagnostic criteria, etc. This study aimed to explore the causal relationship between kidney function and AVS using Mendelian randomization (MR) analysis. METHODS: We acquired summary statistics of estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) from the CKDGen Consortium and a study on AVS from the FinnGen biobank. Univariate and multivariable MR analyses were conducted to evaluate the causal associations. The MR-Egger intercept and MR-PRESSO Global test were applied to assess the pleiotropic effects. The heterogeneity of MR results was tested by Cochran's Q statistic. Moreover, the Bonferroni and FDR corrections were performed for multiple tests. RESULTS: Genetically predicted decreased eGFR may be associated with a raised risk of AVS (OR = 0.045, p = 1.317e-04 by IVW; OR = 0.002, p = 0.004 by MR-Egger, OR = 0.091, p = 0.057 by WM). The causal association still established after multiple comparisons. Quality control analyses indicated the absence of heterogeneity and pleiotropy in our MR research. In addition, the causality of eGFR and AVS remained significant in multivariable MR analysis after adjusting BMI, hypertension, T2DM, LDL-C, and smoking. CONCLUSION: Our MR study discovered that reduced eGFR may be a causative risk factor for AVS. In addition, the evidence did not support a significant causal association of AVS on kidney function.