Risk Of Chronic Kidney Disease Research Articles

Hemodynamic gain index and risk of chronic kidney disease: A prospective cohort study of middle-aged and older men.

The hemodynamic gain index (HGI), a novel non-invasive hemodynamic marker, represents a promising advancement in cardiovascular risk assessment. Cardiovascular disease and chronic kidney disease (CKD) are closely intertwined and share bidirectional relationships. We aimed to assess the association of HGI with CKD risk in a prospective study. Hemodynamic gain index was calculated using heart rate and systolic blood pressure (SBP) responses measured in 1765 men aged 42-61years with normal kidney function during exercise testing using the formula: [(Heart ratemax x SBPmax)-(Heart raterest x SBPrest)]/(Heart raterest x SBPrest). Multivariable adjusted hazard ratios (HRs) (95% confidence intervals, CIs) were estimated for CKD. Over a median follow-up duration of 25.9years, 175 CKD cases occurred. In analysis adjusted for established risk factors, a unit (bpm/mmHg) higher HGI was associated with a decreased risk of CKD (HR 0.78, 95% CI 0.65-0.95). Comparing extreme tertiles of HGI, the corresponding adjusted HR (95% CI) for CKD was 0.53 (0.33-0.85). Addition of HGI to a CKD risk prediction model containing established risk factors improved risk discrimination and reclassification (p-value for difference in -2 log likelihood = .011; net-reclassification-improvement = 59.37%, p = .018; integrated-discrimination-improvement = 0.0064, p = .008). Higher HGI is associated with a lower CKD risk and improves the prediction and classification of CKD beyond common established risk factors.

Prognostic Assessment of Histopathologic Lesions in Patients with Community-Acquired Acute Kidney Injury with Biopsy-Proven Acute Tubular Necrosis.

Community-acquired acute kidney injury (CA-AKI) was more likely to be comorbid with underlying kidney histopathological lesions in addition to acute tubular necrosis (ATN). Thus, we tried to clarify the histological determinants that could influence the prognosis and recovery of CA-AKI patients with biopsy-proven ATN. Adult patients with CA-AKI with biopsy-proven ATN who underwent renal biopsy at Shanghai Changzheng Hospital from January 1, 2010, to December 31, 2018, were included and followed up for 5 years. The impacts of histopathological lesions on short-term and long-term renal dysfunction were also analysed. Multivariate analysis revealed that ATNs, crescents, and decrease of arteriole lumens increased short-term dialysis requirements. The severity of ATN was closely associated with renal survival. According to the Kaplan-Meier analysis, the severity of ATN was significantly associated with short-term dialysis needs and long-term development of end-stage kidney disease (ESKD) during follow-up. Crescent and decrease of arteriole lumens are significantly associated with progression to ESKD and exert synergistic effects with ATN. For patients who did not progress to dialysis, tubular atrophic/interstitial fibrosis and endocapillary lesions were more relevant to partial recovery of renal function after CA-AKI at the three-month follow-up and increased the risk of chronic kidney disease (CKD) stage 3-5 at the five-year follow-up. According to our correlation analysis, endocapillary lesions and crescents were positively correlated with ATN. Histopathologic lesions, apart from tubular necrosis, contributed to the detrimental short-term and long-term renal prognosis of CA-AKI patients with ATN; concomitant histopathologic lesions exerted a combined impact on renal survival together with ATN in CA-AKI patients.

MAFLD criteria are better than MASLD criteria at predicting the risk of chronic kidney disease.

Fatty liver disease is a multisystem disease. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a more accurate indicator of chronic kidney disease (CKD) than nonalcoholic fatty liver disease (NAFLD). However, the relationship between recently defined metabolic dysfunction-associated steatotic liver disease (MASLD) and CKD is currently unclear. The objective of this cross-sectional study was to investigate the prevalence of CKD and albuminuria among individuals diagnosed with either MAFLD or MASLD. This study involved 5,492 participants who provided biochemical marker and liver ultrasound data from the U.S. National Health and Nutrition Examination Survey (2017-2020). Multiple logistic regression analyses were conducted to assess the independent associations of nonoverlapping MAFLD and MASLD with the presence of CKD or albuminuria (urinary albumin-to-creatinine ratio ≥ 3 mg/mmol). MAFLD and MASLD were identified in 47% and 44.5% of the participants, respectively. Individuals with MAFLD had a greater prevalence of CKD (29.60% vs. 26.56%, P < 0.05) and albuminuria (29.60% vs. 26.56%, P < 0.05) than did those with MASLD. Importantly, after adjusting for factors such as sex, age, ethnicity, and alcohol use, it was demonstrated that individuals in the MAFLD-only group had a 4.73-fold greater likelihood of having prevalent CKD than those in the MASLD-only group (P < 0.03). The MAFLD criteria better identify patients with CKD than do the MASLD criteria. Therefore, it is suggested that the MASLD criteria be reconsidered, as currently, the justification for changing from MAFLD to MASLD criteria may not be appropriate.

Different cardiovascular risks associated with elevated creatinine-based eGFR and cystatin C-based eGFR

To compare the association of elevated estimated glomerular filtration rate (eGFR) based on creatinine (eGFRcr) and cystatin C (eGFRcys) with the risk of cardiovascular diseases (CVD) and chronic kidney diseases (CKD). 372,060 participants free of CVD and CKD in the UK Biobank were included. Participants were categorized into low, normal and high eGFR groups according to the age- and sex-specific 5th and 95th percentiles of eGFR. The primary outcome was incident CVD, defined as a combination of ischemic heart disease, stroke, heart failure, and atrial fibrillation. Thresholds for high eGFR varied with age and sex, ranging from 96.5 to 116.0 mL/min/1.73 m2 and 100.3 to 120.1 mL/min/1.73 m2 for eGFRcr and eGFRcys, respectively. During a median follow-up of 12.4 years, 39,855 (10.7%) participants developed CVD. Compared with normal eGFR levels, high eGFRcr levels were associated with a higher risk of CVD (HR, 1.19; 95% CI: 1.14–1.25), while high eGFRcys levels were associated with a lower risk of CVD (HR, 0.90; 95% CI: 0.85–0.95). Compared to normal eGFR levels, both high eGFRcr and high eGFRcys levels were related to a lower risk of CKD. Elevated eGFRcr levels were associated with a higher risk of CVD, and elevated eGFRcys levels were associated with a lower risk of CVD.

Comparative mathematical modeling of causal association between metal exposure and development of chronic kidney disease

BackgroundPrevious studies have identified several genetic and environmental risk factors for chronic kidney disease (CKD). However, little is known about the relationship between serum metals and CKD risk.MethodsWe investigated associations between serum metals levels and CKD risk among 100 medical examiners and 443 CKD patients in the medical center of the First Hospital Affiliated to China Medical University. Serum metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). We analyzed factors influencing CKD, including abnormalities in Creatine and Cystatin C, using univariate and multiple analysis such as Lasso and Logistic regression. Metal levels among CKD patients at different stages were also explored. The study utilized machine learning and Bayesian Kernel Machine Regression (BKMR) to assess associations and predict CKD risk based on serum metals. A chained mediation model was applied to investigate how interventions with different heavy metals influence renal function indicators (creatinine and cystatin C) and their impact on diagnosing and treating renal impairment.ResultsSerum potassium (K), sodium (Na), and calcium (Ca) showed positive trends with CKD, while selenium (Se) and molybdenum (Mo) showed negative trends. Metal mixtures had a significant negative effect on CKD when concentrations were all from 30th to 45th percentiles compared to the median, but the opposite was observed for the 55th to 60th percentiles. For example, a change in serum K concentration from the 25th to the 75th percentile was associated with a significant increase in CKD risk of 5.15(1.77,8.53), 13.62(8.91,18.33) and 31.81(14.03,49.58) when other metals were fixed at the 25th, 50th and 75th percentiles, respectively.ConclusionsCumulative metal exposures, especially double-exposure to serum K and Se may impact CKD risk. Machine learning methods validated the external relevance of the metal factors. Our study highlights the importance of employing diverse methodologies to evaluate health effects of metal mixtures.

Utility of the ACD-GENE-CLI Score in Asian Patients with Critical Limb Ischemia Undergoing Endovascular Interventions.

Critical limb ischemia (CLI) is an emerging public health threat and lacks a reliable score for predicting the outcomes. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD-GENE) risk score helps identify patients with coronary artery disease who have cytochrome P450 2C19 (CYP2C19) polymorphism-related drug resistance and are at risk for cardiovascular adverse events. However, its application to CLI remains unknown. In this study, we aim to validate a modified ACD-GENE-CLI score to improve the prediction of major adverse limb events (MALEs) in patients with CLI receiving clopidogrel. Patients with CLI receiving clopidogrel post-endovascular intervention were enrolled prospectively in two medical centers. Amputation and revascularization as MALEs were regarded as the outcomes. A total of 473 patients were recruited, with a mean follow-up duration of 25 months. Except for obesity, old age, diabetes, chronic kidney disease (CKD), and CYP2C19 polymorphisms were significantly associated with MALEs. Using bootstrap regression analysis, we established a modified risk score (ACD-GENE-CLI) that included old age (≥ 65 years), diabetes, CKD, and CYP2C19 polymorphisms. At a cutoff value of 8, the ACD-GENE-CLI score was superior to the CYP2C19 deficiency only, and the conventional ABCD-GENE score in predicting MALEs (area under the curve: 0.69 vs. 0.59 vs. 0.67, p=0.01). The diagnostic ability of the ACD-GENE-CLI score was consistent in the external validation. Also, Kaplan-Meier curves showed that in CYP2C19 deficiency, the ABCD-GENE and ACD-GENE-CLI scores could all differentiate patients with CLI who are free from MALEs. The modified ACD-GENE-CLI score could differentiate patients with CLI receiving clopidogrel who are at risk of MALEs. Further studies are required to generalize the utility of the score.

Early Identification of Sepsis-Induced Acute Kidney Injury by Using Monocyte Distribution Width, Red-Blood-Cell Distribution, and Neutrophil-to-Lymphocyte Ratio

Sepsis-induced acute kidney injury (AKI) is a common complication in patients with severe illness and leads to increased risks of mortality and chronic kidney disease. We investigated the association between monocyte distribution width (MDW), red-blood-cell volume distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), sepsis-related organ-failure assessment (SOFA) score, mean arterial pressure (MAP), and other risk factors and sepsis-induced AKI in patients presenting to the emergency department (ED). This retrospective study, spanning 1 January 2020, to 30 November 2020, was conducted at a university-affiliated teaching hospital. Patients meeting the Sepsis-2 consensus criteria upon presentation to our ED were categorized into sepsis-induced AKI and non-AKI groups. Clinical parameters (i.e., initial SOFA score and MAP) and laboratory markers (i.e., MDW, RDW, and NLR) were measured upon ED admission. A logistic regression model was developed, with sepsis-induced AKI as the dependent variable and laboratory parameters as independent variables. Three multivariable logistic regression models were constructed. In Model 1, MDW, initial SOFA score, and MAP exhibited significant associations with sepsis-induced AKI (area under the curve [AUC]: 0.728, 95% confidence interval [CI]: 0.668–0.789). In Model 2, RDW, initial SOFA score, and MAP were significantly correlated with sepsis-induced AKI (AUC: 0.712, 95% CI: 0.651–0.774). In Model 3, NLR, initial SOFA score, and MAP were significantly correlated with sepsis-induced AKI (AUC: 0.719, 95% CI: 0.658–0.780). Our novel models, integrating MDW, RDW, and NLR with initial SOFA score and MAP, can assist with the identification of sepsis-induced AKI among patients with sepsis presenting to the ED.

Long-term functional outcomes in patients undergoing radical nephrectomy for renal cell carcinoma and tumor thrombus.

Up to 15% of patients with locally advanced renal cell carcinoma (RCC) harbors tumor thrombus (TT). In those cases, radical nephrectomy (RN) and thrombectomy represents the standard of care. We assessed the impact of TT on long-term functional and oncological outcomes in a large contemporary cohort. Within a prospective maintained database, 1207 patients undergoing RN for non-metastatic RCC between 2000 and 2021 at a single tertiary centre were identified. Of these, 172 (14%) harbored TT. Multivariable logistic regression analyses evaluated the impact of TT on the risk of postoperative acute kidney injury (AKI). Multivariable Poisson regression analyses estimated the risk of long-term chronic kidney disease (CKD). Kaplan Meier plots estimated disease-free survival and cancer specific survival. Multivariable Cox regression models assessed the main predictors of clinical progression (CP) and cancer specific mortality (CSM). Patients with TT showed lower BMI (24 vs. 26kg/m2) and preoperative Hb (11 vs. 14g/mL; all-p < 0.05). Clinical tumor size was higher in patients with TT (9.6 vs. 6.5cm; p < 0.001). After adjusting for potential confounders, the presence of TT was significantly associated with a higher risk of postoperative AKI (OR 2.03, 95% CI 1.49-3.6; p < 0.001) and long-term CKD (OR: 1.32, 95% CI 1.10-1.58; p < 0.01). Notably, patients with TT showed worse long-term oncological outcomes and TT was a predictor for CP (2.02, CI 95% 1.49-2.73, p < 0.001) and CSM (HR 1.61, CI 95% 1.04-2.49, p < 0.03). The presence of TT in RCC patients represents a key risk factor for worse perioperative, as well as long-term renal function. Specifically, patients with TT harbor a significant and early estimated glomerular filtration rate (eGFR) decrease. However, despite TT patients show a greater eGFR decline after surgery, they retain acceptable renal function, which remains stable over time.

The association between circadian syndrome and chronic kidney disease in an aging population: a 4-year follow-up study

IntroductionCircadian syndrome (CircS) is proposed as a novel risk cluster based on reduced sleep duration, abdominal obesity, depression, hypertension, dyslipidemia and hyperglycemia. However, the association between CircS and chronic kidney disease (CKD) remains unclear. To investigate the cross-sectional and longitudinal association between CircS and CKD, this study was performed.MethodsA national prospective cohort (China Health and Retirement Longitudinal Study, CHARLS) was used in this study. To define CKD, the estimated glomerular filtration rate (eGFR) was calculated based on the 2012 CKD-EPI creatinine-cystatin C equation. Participants with eGFR &amp;lt;60 mL.min-1/1.73/m2 were diagnosed with CKD. Multivariate binary logistic regression was used to assess the cross-sectional association between CircS and CKD. Subgroup and interactive analyses were performed to determine the interactive effects of covariates. In the sensitivity analysis, the obese population was excluded and another method for calculating the eGFR was used to verify the robustness of previous findings. In addition, participants without CKD at baseline were followed up for four years to investigate the longitudinal relationship between CircS and CKD.ResultsA total of 6355 participants were included in this study. In the full model, CircS was positively associated with CKD (OR = 1.28, 95% CI = 1.04-1.59, P &amp;lt; 0.05). As per one increase of CircS components, there was a 1.11-fold (95% CI = 1.04-1.18, P &amp;lt; 0.05) risk of prevalent CKD in the full model. A significant interactive effect of hyperuricemia in the CircS-CKD association (P for interaction &amp;lt; 0.01) was observed. Sensitivity analyses excluding the obese population and using the 2009 CKD-EPI creatinine equation to diagnose CKD supported the positive correlation between CircS and CKD. In the 2011-2015 follow-up cohort, the CircS group had a 2.18-fold risk of incident CKD (95% CI = 1.33-3.58, P &amp;lt; 0.01) in the full model. The OR was 1.29 (95% CI = 1.10-1.51, P &amp;lt; 0.001) with per one increase of CircS components.ConclusionCircS is a risk factor for CKD and may serve as a predictor of CKD for early identification and intervention.

Combined effects of blood pressure and glucose status on the risk of chronic kidney disease.

This study aimed to assess the combined effects of blood pressure (BP) and glucose status on chronic kidney disease (CKD) incidence in young and middle-aged adults. We examined data from 1,297,341 Japanese individuals aged <60 years (60.1% men; mean age 41.4 ± 9.3 years) with no history of CKD at baseline. The interval-censored Cox proportional hazards model with covariates was used. During a median follow-up period of 2.1 years, new onset CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2 and/or proteinuria) occurred in 80,187 participants. In participants without antihypertensive treatment (AHT), the adjusted hazard ratios (95% confidence interval) per 1-standard deviation, that is, 15 mmHg increase in systolic BP for CKD incidence, were 1.08 (1.07-1.09), 1.12 (1.10-1.13), and 1.15 (1.12-1.18) in normoglycemia, borderline glycemia, and diabetes groups, respectively. These ratios were significantly higher in the borderline glycemia and diabetes groups compared with those in the normoglycemia group (interaction p < 0.0001). The interaction between BP and borderline glycemia was evident when the outcome definition was restricted to proteinuria. In participants under AHT, systolic BP was most strongly associated with CKD risk in the diabetes group, although no significant interaction was observed. High BP and high glucose status may synergistically increase the incidence of CKD. Strict BP management may play an important role in the early prevention of CKD in individuals with worse glucose status within the young and middle-aged population. This large-scale longitudinal cohort study showed high BP and diabetes synergistically increased the risk of CKD in individuals without AHT. Strict BP management may play an important role in the early prevention of CKD in individuals with worse glucose status within the young and middle-aged population.

Causal relationship between basal metabolic rate and kidney function: a bidirectional two-sample mendelian randomization study

BackgroundThe relationship between basal metabolic rate (BMR) and Chronic kidney disease (CKD) remains unclear and controversial. In this study, we investigated the causal role of BMR in renal injury, and inversely, whether altered renal function causes changes in BMR.MethodsIn this two-sample mendelian randomization (MR) study, Genetic data were accessed from published genome-wide association studies (GWAS) for BMR ((n = 454,874) and indices of renal function, i.e. estimated glomerular filtration rate (eGFR) based on creatinine (n =1, 004, 040), CKD (n=480, 698), and blood urea nitrogen (BUN) (n =852, 678) in European. The inverse variance weighted (IVW) random-effects MR method serves as the main analysis, accompanied by several sensitivity MR analyses. We also performed a reverse MR to explore the causal effects of the above indices of renal function on the BMR.ResultsWe found that genetically predicted BMR was negatively related to eGFR, (β= −0.032, P = 4.95*10-12). Similar results were obtained using the MR-Egger (β= −0.040, P = 0.002), weighted median (β= −0.04, P= 5.35×10-11) and weighted mode method (β= −0.05, P=9.92×10-7). Higher BMR had a causal effect on an increased risk of CKD (OR =1.36, 95% CI = 1.11-1.66, P =0.003). In reverse MR, lower eGFR was related to higher BMR (β= −0.64, P = 2.32×10-6, IVW analysis). Bidirectional MR supports no causal association was observed between BMR and BUN. Sensitivity analyses confirmed these findings, indicating the robustness of the results.ConclusionGenetically predicted high BMR is associated with impaired kidney function. Conversely, genetically predicted decreased eGFR is associated with higher BMR.

Plasma Proteins associated with Chronic Histopathologic Lesions on Kidney Biopsy.

The severity of chronic histopathologic lesions on kidney biopsy is independently associated with higher risk of progressive chronic kidney disease (CKD). Because kidney biopsies are invasive, identification of blood markers that report on underlying kidney histopathology has the potential to enhance CKD care. We examined the association between 6592 plasma protein levels measured by aptamers and the severity of interstitial fibrosis and tubular atrophy (IFTA), glomerulosclerosis, arteriolar sclerosis, and arterial sclerosis among 434 participants of the Boston Kidney Biopsy Cohort. For proteins significantly associated with at least one histologic lesion, we assessed renal arteriovenous protein gradients among 21 individuals who had undergone invasive catheterization and assessed the expression of the cognate gene among 47 individuals with single cell RNA sequencing data in the Kidney Precision Medicine Project. In models adjusted for estimated glomerular filtration rate (eGFR), proteinuria, and demographic factors, we identified 35 proteins associated with one or more chronic histologic lesions, including 20 specific for IFTA, 8 specific for glomerulosclerosis, and 1 specific for arteriolar sclerosis. In general, higher levels of these proteins were associated with more severe histologic score and lower eGFR. Exceptions included testican-2 and NELL1, which were associated with less glomerulosclerosis and IFTA, respectively, and higher eGFR; notably, both of these proteins demonstrated significantly higher levels from artery to renal vein, demonstrating net kidney release. In the Kidney Precision Medicine Project, 13 of the 35 protein hits had cognate gene expression enriched in one or more cell types in the kidney, including podocyte expression of select glomerulosclerosis markers (including testican-2) and tubular expression of several IFTA markers (including NELL1). Proteomic analysis identified circulating proteins associated with chronic histopathologic lesions, some of which have concordant site-specific expression within the kidney.

Iron biology.

Iron is a fundamental element for biological life, starting from bacteria till humans. Iron is essential for cell function and survival, energy production and metabolism, whereas increased levels cause oxidative stress. It is also a constituent of haemoglobin and thus it is necessary for oxygen transportation through the body. Given these multiple functions, the regulation of iron metabolism is complex and tight coupled with oxygen homeostasis at tissue and cellular levels, thanks to the interaction with the hypoxia inducible factor (HIF) system. In patients with chronic kidney disease (CKD), iron deficiency significantly contributes to anaemia development. This frequently overlaps with chronic inflammation, causing iron- restricted erythropoiesis. To add further complexity, metabolic hyperferritinemia may, on one side, increase the risk for CKD and, on the other, overlaps with functional iron deficiency. Excessive intracellular iron in certain cell types during CKD can also mediate cellular death (called ferroptosis), and contribute to the pathogenesis of kidney damage, atherosclerosis and vascular calcifications. This review is aimed at broadening the perspective of iron metabolism in the setting of CKD not just as a contributor to anaemia in CKD patients, but also as an important player with an impact on cell metabolism, renal fibrosis, and the cardiovascular system.

Apparent Mineralocorticoid Excess in Israel: A Case Series and Literature Review.

Apparent mineralocorticoid excess (AME) syndrome is an ultra-rare autosomal-recessive tubulopathy, caused by mutations in HSD11B2, leading to excessive activation of the kidney mineralocorticoid receptor, and characterized by early-onset low-renin hypertension, hypokalemia, and risk of chronic kidney disease (CKD). To date, most reports included few patients, and none described patients from Israel. We aimed to describe AME patients from Israel and to review the relevant literature. Retrospective cohort study. Clinical, laboratory, and molecular data from patients' records were collected. Five patients presented at early childhood with normal estimated glomerular filtration rate (eGFR), while two patients presented during late childhood with CKD. Molecular analysis revealed two novel homozygous mutations in HSD11B2. All patients presented with severe hypertension and hypokalemia. While all patients developed nephrocalcinosis, only one showed hypercalciuria. All individuals were managed with potassium supplements, mineralocorticoid receptor antagonists, and various antihypertensive medications. One patient survived cardiac arrest secondary to severe hyperkalemia. At last follow-up, those five patients who presented early exhibited normal eGFR and near-normal blood pressure, but two have hypertension complications. The two patients who presented with CKD progressed to end-stage kidney disease (ESKD) necessitating dialysis and kidney transplantation. In this 11-year follow-up report of two Israeli families with AME, patients who presented early maintained long-term normal kidney function, while those who presented late progressed to ESKD. Nevertheless, despite early diagnosis and management, AME is commonly associated with serious complications of the disease or its treatment.

Risk of chronic kidney disease in 260 patients with lupus nephritis-analysis of a nationwide multicentre cohort with up to 35 years of follow-up.

To compare proliferative (PLN) and membranous (MLN) lupus nephritis (LN) regarding clinical and laboratory presentation and long-term outcomes; To investigate predictors of progression to chronic kidney disease (CKD). Multicentre observational study, with retrospective analysis of a prospective cohort, using data from the Rheumatic Diseases Portuguese Registry-Reuma.pt. Patients with biopsy-proven PLN, MLN and mixed LN were included. Cox regression survival analysis was used to investigate predictors of CKD. 260 patients were included. Median follow-up was 8 years (IQR 11; minimum 1, maximum 35 years). MLN patients presented with significantly lower serum creatinine (0.70 (IQR 0.20; minimum 0.50, maximum 1.30) mg/dl vs 0.80 (IQR 0.31; minimum 0.26, maximum 2.60) in PLN, p= 0.003). Proteinuria levels did not differ between groups (p= 0.641). Levels of complement were reduced in PLN but nearly normal in MLN patients, and there were fewer patients with positive anti-dsDNA antibodies in the MLN group (p< 0.001). One year after the beginning of treatment, 62% of the patients achieved EULAR/ERA-EDTA complete response, with further 5% achieving partial response. Patients with lower proteinuria at diagnosis were more likely to achieve a complete renal response at one year, however, proteinuria at diagnosis or at one year did not predict long term CKD. Estimated glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 at one year was the strongest predictor of progression to CKD (HR 23 [95% CI 8-62], p< 0.001). Other possible predictors included the use of azathioprine for induction of remission, older age at diagnosis and male sex. Proteinuria levels did not predict LN histologic class in our cohort. eGFR cutoff of 75 mL/min/1.73 m2 after one year of treatment was strongly predictive of progression to CKD.

Manganese induces podocyte injury through regulating MTDH/ALKBH5/NLRP10 axis: Combined analysis at epidemiology and molecular biology levels

Manganese (Mn) is an essential micronutrient required for various biological processes but excess exposure to Mn can cause neurotoxicity. However, there are few reports regarding the toxicity effect of Mn on the kidney as well as the underlying molecule mechanism. Herein, in vivo experiments were adopted to assess the toxicity effects associated with Mn, and found that chronic Mn treatment induced the injury of glomerular podocytes but not renal tubule in rats. Genome-wide CRISPR/Cas9 knockout screen was then employed to explore the biotargets of the toxic effect of Mn on podocytes. Through functional analyses of the enriched candidate genes, NLRP10 was found to be significantly up-regulated and mediated Mn-induced podocyte apoptosis. Further mechanism investigation revealed that NLRP10 expression was regulated by demethylase AlkB homolog 5 (ALKBH5) in an m6A-dependent fashion upon Mn treatment. Moreover, Mn could directly bind to Metadherin (MTDH) and promoted its combination with ALKBH5 to promote NLRP10 expression and cell apoptosis. Finally, logistic regressions, restricted cubic spline regressions and uniform cubic B-spline were used to investigate the association between Mn exposure and the risk of chronic kidney disease (CKD). A U-shaped nonlinear relationship between CKD risk and plasma Mn level, and a positive linear relationship between CKD risk and urinary Mn levels was found in our case-control study. To sum up, our findings illustrated that m6A-dependent NLRP10 regulation is indispensable for podocyte apoptosis and nephrotoxicity induced by Mn, providing fresh insight into understanding the health risk of Mn and a novel target for preventing renal injury in Mn-intoxicated patients.

VALIDATION OF A RISK PREDICTION EQUATION FOR INCIDENT CHRONIC KIDNEY DISEASE IN A HYPERTENSIVE NON-DIABETES COHORT IN SINGAPORE PRIMARY CARE PATIENTS.

Background Accurate identification of individuals at risk of developing chronic kidney disease (CKD) may improve clinical care. Nelson et al developed prediction equations to estimate the risk of incident eGFR of less than 60 ml/min/1.73m2 in diabetic and non-diabetes patients using data from 34 multinational cohorts. We aim to validate the non-diabetes equation in our local multi-ethnic cohort and develop further prediction models. Methods Demographics, clinical and laboratory data of hypertensive non-diabetes patients with baseline eGFR ≥60ml/min/1.73m2 on follow up with primary care clinics between 2010 to 2015 were collected. Follow up was 5 years from entry to study. We validated Nelson's equation and developed our own model which we subsequently validated. The developmental cohort included patients between 2010 to 2014 while the validation cohort included patients in 2015. Variables included age, sex, eGFR, history of cardiovascular disease, ever smoker, body mass index, albuminuria, cholesterol and treatment. Primary outcome was incident eGFR<60/min/1.73m2 within five years. Model performance was evaluated by C-statistics and calibration was assessed. Results In the developmental cohort of 27,800 patients, 2823 (10.2%) developed the outcome during a mean follow-up of 4.4years while 638(12.8%) patients developed the outcome in the validation cohort of 4,994 patients. Applicability of the Nelson's equation was limited by missing albuminuria, absence of black race and exclusion of non-hypertensive patients in our cohort. Nonetheless, the modified Nelson's model demonstrated C-statistic of 0.85 (95%CI:0.84-0.86). The C-statistic of our bespoke model was 0.85 (0.85-0.86) and 0.87 (0.85-0.88) for the developmental cohort and validation cohort respectively. Calibration was suboptimal as the predicted risk exceeded the observed risk. Conclusions The modified Nelson's equation and our locally derived novel model demonstrated high discrimination. Both models may potentially be used in predicting risk of CKD in hypertensive patients who are managed in primary care, allowing for early interventions in high-risk population.

Adiponectin-to-leptin ratio and incident chronic kidney disease: Sex and body composition-dependent association.

The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition. In this prospective community-based cohort, participants with normal kidney function were analysed (N=5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of <60mL/min/m2 or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia. The participants' mean age was 57.2±8.3years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8-3.2] and 0.5 [0.3-0.9] μg/ng, P<0.001). During a median follow-up of 9.8 [9.5-10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33-0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80-0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI<23.0kg/m2 and those with sarcopenia. However, no significant association was observed between men with a BMI≥23.0kg/m2 and those without sarcopenia. A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI<23.0kg/m2 and sarcopenia.

Association between dyslipidemia and the risk of incident chronic kidney disease affected by genetic susceptibility: Polygenic risk score analysis.

The effect of dyslipidemia on kidney disease outcomes has been inconclusive, and it requires further clarification. Therefore, we aimed to investigate the effects of genetic factors on the association between dyslipidemia and the risk of chronic kidney disease (CKD) using polygenic risk score (PRS). We analyzed data from 373,523 participants from the UK Biobank aged 40-69 years with no history of CKD. Baseline data included plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride, as well as genome-wide genotype data for PRS. Our primary outcome, incident CKD, was defined as a composite of estimated glomerular filtration rate < 60 ml/min/1.73 m2 and CKD diagnosis according to International Classification of Disease-10 codes. The effects of the association between lipid levels and PRS on incident CKD were assessed using the Cox proportional hazards model. To investigate the effect of this association, we introduced multiplicative interaction terms into a multivariate analysis model and performed subgroup analysis stratified by PRS tertiles. In total, 4,424 participants developed CKD. In the multivariable analysis, PRS was significantly predictive of the risk of incident CKD as both a continuous variable and a categorized variable. In addition, lower total cholesterol, LDL-C, HDL-C, and higher triglyceride levels were significantly associated with the risk of incident CKD. There were interactions between triglycerides and intermediate and high PRS, and the interactions were inversely associated with the risk of incident CKD. This study showed that PRS presented significant predictive power for incident CKD and individuals in the low-PRS group had a higher risk of triglyceride-related incident CKD.

Ambient Air Pollution and Chronic kidney disease risk in Deltan communities: A Policy Brief, 2023

Chronic kidney disease (CKD) is a persistent, devastating, yet neglected, non-communicable disease in developing and emerging countries. National, regional, and international agencies’ communications and reports on non-communicable diseases intentionally or non-intentionally do not feature CKD. The traditional risk factors for CKD, such as hypertension and diabetes, which have received relatively ample attention, do not sufficiently explain the high burden of CKD in these countries. Ambient air pollution is an emerging significant environmental risk factor for CKD; however, epidemiological data and evidence are lacking for susceptible populations in developing countries. The Niger Delta region of Nigeria is a petrochemical hub known for environmental degradation, including air pollution, and thus, serves as a good case study for investigating the association between air pollution and CKD. This brief is based on the results of a mixed-methods study conducted in four communities situated near an oil and gas refinery in Warri, Nigeria. Air pollutant concentrations measured in partnership with citizen scientists showed that all except one air pollutant (ozone) exceeded the WHO acceptable limits in all four communities. The overall prevalence of CKD was high (12.3%) but even higher (18%) in a socially deprived semi-urban community closest to the oil refinery. Hypertension, diabetes, other behavioral risk factors, and exposures associated with CKD were prevalent among the inhabitants of the four communities. However, public environmental health information and education are lacking. A multifaceted approach is required to mitigate air pollution and the associated health risks in the state. Public inclusion is strongly recommended for the planning and implementation of future interventions. Kidney disease prevention and treatment should be emphasized in health policies and insurance schemes.