Rapid eGFR Decline Research Articles

Association of kidney function and albuminuria with frailty worsening and death in very old adults.

Studies analysing the association of albuminuria and prevalent frailty in community-dwelling very old adults are scarce and lack information on incident frailty. We investigated the association of kidney function decline and increase of albuminuria with frailty worsening or death in very old adults. Longitudinal analyses with biennial visits of the Berlin Initiative (cohort) Study and a frailty follow-up of 2.1years. 1,076 participants with a mean age of 84.3 (5.6) years of whom 54% were female. Partial proportional odds models were used to assess the association of estimated glomerular filtration rate (eGFR) decline and/or albuminuria (albumin creatinine ratio, ACR) with frailty worsening or death. At frailty baseline, 1,076 participants with an eGFR of 50 (13) ml/min/1.73m2, 48% being prefrail and 31% frail were included. After median 2.1years, 960 (90%) participants had valid information on frailty transition: 187 (17.5%) worsened and 111 (10.3%) died. In the multivariable model, the odds of frailty worsening for participants with albuminuria in combination with eGFR <60ml/min/1.73m2 were elevated [OR (95% CI): 2.47 (1.41-4.31)] compared to participants without albuminuria and eGFR ≥60ml/min/1.73m2 as there was a rapid eGFR decline of ≥3ml/min/1.73m2 per year [1.55 (1.04-2.33)] and albuminuria trajectories six years prior [1.53 (1.11-2.10)] to frailty baseline. The odds of death for each exposure were even higher. In older adults, advanced stages of CKD and albuminuria alone were associated with 2-fold odds of frailty worsening independent of death.

Rapid Decline of Estimated Glomerular Filtration Rate and its Effect on Mortality Risk of Patients with Hepatocellular Carcinoma

Background: In patients with Hepatocarcinoma (HCC), the association between the rapid decline of kidney function and clinical outcomes is still unknown, although kidney-liver crosstalk is comprehensively studied. Objectives: We aimed to investigate the prevalence and determinants of the rapid decline of kidney function and its potential prognostic role and influence on mortality in HCC patients treated by percutaneous injection therapy (PEIT). Methods: This prospective cohort included 114 HCC, with 64.9% males and a mean age of 65.17 years. The rapid decline of kidney function was defined according to kidney disease improving global outcome (KDIGO). The cancer of the liver Italian program (CLIP) score was calculated to predict survival. Multivariable logistic regression analysis for rapid estimated glomerular filtration rate (eGFR) decline was performed after evaluating individual covariates. Multivariable Cox regression models for rapid eGFR decline and mortality were analyzed. Results: During a median follow-up of 31 months, 43.85% of patients presented a rapid decline in eGFR. The baseline eGFR was significantly higher in the group with the rapid decline of kidney function: 86.08 ± 19.17 mL/min/1.73m2 vs. 75.53 ± 25.7 mL/min/1.73 m2 (P = 0.001). The CLIP score (hazard ratio [HR] = 2.55, 95% confidence interval [CI]: 1.70 - 3.84, P &lt; 0.001) was independently associated with rapid eGFR decline. In Cox regression, rapid eGFR decline was independently associated with mortality (HR = 3.49, 95%CI: 1.28 - 9.56, P = 0.015). Conclusions: Nearly half of the HCC patients presented a rapid eGFR decline. The HCC severity evaluated by the CLIP score was an independent predictor of the rapid decline of kidney function. The rapid decline in eGFR was associated with a higher mortality risk in HCC patients, independent of other known risk factors.

Significance of co-positivity for anti-dsDNA, -nucleosome, and -histone antibodies in patients with lupus nephritis

Objective The aim of this study was to define the clinical, histopathologic, and prognostic features associated with simultaneous positivity for anti-dsDNA, -nucleosome, and -histone antibodies (3-pos) in Korean patients with biopsy-proven lupus nephritis (LN). Methods The 102 patients included in the study had undergone kidney biopsy prior to the start of induction treatment, were treated with immunosuppressives, and followed-up for >12 months. Results In total, 44 (43.1%) of the 102 LN patients were 3-pos. Patients with 3-pos had a higher SLEDAI-2K score (p = .002), lower lymphocyte count (p = .004), and higher rates of proteinuria > 3.5 g/24 h (p = .039) and positivity for urinary sediments (p = .005) at the time of renal biopsy than non-3-pos patients. 3-pos patients had a more proliferative form of LN (p = .045) in the renal histopathologic findings, and as co-positivity gradually increased from 0 to 3, the total activity score in the renal biopsy findings increased significantly (p = .033). In addition, 3-pos patients had a more rapid eGFR decline than non-3-pos patients after a follow-up of 83.2 months (p = .016). Conclusions Our findings suggest that 3-pos is related to severe LN and that 3-pos patients are more likely to experience a rapid decline of renal function than non-3-pos patients. KEY MESSAGE Patients with co-positivity for anti-dsDNA, -nucleosome, and -histone antibodies (3-pos) had higher disease activity and a worse renal histopathology than those without co-positivity. 3-pos patients had a more rapid decline of renal function than non-3-pos patients.

Association between rapid renal function deterioration and cancer mortality in the elderly: A retrospective cohort study.

Kidney function is associated with clinical outcomes in patients with cancer. This study aimed to assess the association between kidney function decline and cancer-related mortality among community-dwelling elderly individuals. This was a retrospective longitudinal cohort study. The 61,988 participants were from an elderly health examination database in Taipei City from 2005 to 2012. Multivariable logistic regression was used to assess the association between baseline covariates and rapidly deteriorating estimated glomerular filtration rate (eGFR). In addition, Cox proportional hazards model and the Fine-Gray model were used to quantify the effects of covariates on total cancer mortality and six specific cancer mortalities. During the follow-up period, 1482 participants died of cancer. Their baseline average eGFR was 73.8 ± 19.9 mL/min/1.73 m2 , and 18.3% had rapid renal function decline (≥5 mL/min/1.73 m2 per year). Rapid renal function decline was positively related to age, baseline eGFR, proteinuria, hypertension, waist circumferences, high log triglyceride levels, and diabetes mellitus (DM) history. In Cox proportional hazard models, participants with rapid eGFR decline had an increased risk of cancer mortality [hazard ratio (95% CI): 1.97 (1.73, 2.24); p < 0.001] compared to those without rapid eGFR decline. In the analysis of site-specific cancer mortality risk, rapid eGFR decline was associated with six site-specific cancer mortality, namely gastrointestinal tract, hepatobiliary, lung, prostate, urinary tract, and hematological malignancies. Elderly individuals with rapid kidney function decline had higher cancer mortality risks. Serial assessments of dynamic changes in eGFR might provide information relevant for cancer prognosis.

Clinicopathological Characteristics and Risk Factors for Rapid eGFR Decline in Chinese Patients with Biopsy-Proven Obesity-Related Glomerulopathy.

To investigate the clinicopathologic features and the related risk factors for rapid estimated glomerular filtration rate (eGFR) decline in Chinese obesity-related glomerulopathy (ORG) patients. A total of 63 ORG patients, who underwent a renal biopsy and received follow-up for at least 12 months, were recruited in our study. These patients were classified as rapid decliners and slow decliners based on the eGFR slope value (-5.0 mL/min/1.73 m2/year). Logistic regression analysis was used to determine the risk factors for rapid eGFR decline. Of the 63 ORG patients, 48 (76.2%) were male, the mean age was 38.7 ± 9.0 years, the median of urinary protein excretion was 1.62 g/24 h, 27.0% of them had nephrotic-range proteinuria, while hypoalbuminemia was observed in 7.9% of them. The incidence of obvious hypertriglyceridemia, hypertension, glucose dysmetabolism and hyperuricemia were 71.4%, 60.3%, 36.5% and 27.0%, respectively. 13 (20.6%) patients became rapid decliners during the median 45 months of follow-up. Their mean BMI was 31.8 ± 3.6 kg/m2, the median of baseline eGFR and urinary protein excretion were 71.8 (range of 30.5-118.2) mL/min/1.73 m2/year and 3.57 g/24 h, respectively. Multivariate logistic regression analysis showed that smoking (OR 9.205, 95% CI 1.704-49.740, P = 0.01), hyperuricemia (OR 5.541, 95% CI 1.079-28.460, P = 0.04) and nephrotic-range proteinuria (OR 6.128, 95% CI 1.311-28.637, P = 0.021) were the independent risk factors for rapid eGFR decline. Chinese ORG patients were more likely to have clinical characteristics with hypertriglyceridemia, hypertension and hyperuricemia, and mild to severe degrees of urinary protein excretion at diagnosis, while patients with nephrotic-range proteinuria lacked hypoalbuminemia and hypercholesterolemia. Smoking, hyperuricemia and nephrotic-range proteinuria were independent risk factors for rapid eGFR decline in ORG patients.

Association between Depressive Symptom Trajectory and Chronic Kidney Disease Progression: Findings from the Chronic Renal Insufficiency Cohort Study.

While depression is highly prevalent among individuals with chronic kidney disease (CKD), little is known about the course of depressive symptoms over time. We characterized trajectories of depressive symptoms and CKD progression and evaluated the association between depressive symptoms trajectory and CKD progression. 2361 individuals with mild-to-moderate CKD enrolled in the Chronic Renal Insufficiency Cohort Study. The Beck Depression Inventory (BDI) was used to assess depressive symptoms at baseline and biennially. Higher BDI scores indicate worse depressive symptoms. Estimated glomerular filtration rate (eGFR) was calculated using the 2021 CKD-EPI equation. Group-based trajectory models were used to determine trajectories of BDI score and eGFR change over time. Multinomial logistic regression was used to examine factors associated with BDI trajectories and to evaluate the association of BDI trajectories with eGFR change. Over 8 years of follow-up, three patterns of depressive symptoms were identified: persistently low BDI score (57.7%), persistently moderate BDI score (33.1%), and persistently high BDI score (9.2%). Three eGFR trajectory groups were identified: non-linear, rapid eGFR decline (21.5%); linear, expected eGFR decline (54.8%); and stable eGFR (23.7%). Predictors of persistently moderate and high BDI trajectories included low educational attainment, smoking, and poor quality of life. Compared to those with a persistently low BDI score, the odds for non-linear, rapid eGFR decline were higher for those with persistently moderate BDI scores (OR, 1.45; 95% CI, 1.04-2.03) and persistently high BDI scores (OR, 1.90; 95% CI, 1.02-3.56). No association between moderate BDI score and linear, expected eGFR decline was observed. Depressive symptoms remained largely stable among individuals with mild-to-moderate CKD, and persistently moderate and high BDI scores were associated with non-linear, rapid eGFR decline. Future work is needed to better understand the interplay between depression and CKD progression.

The Effect of Metabolic Syndrome and Its Individual Components on Renal Function: A Meta-Analysis

Observational studies have reported inconsistent findings in the relationship between metabolic syndrome (MetS), its components, and loss of renal function, mainly including eGFR decline, new-onset CKD, and ESRD. This meta-analysis was performed to investigate their potential associations. PubMed and EMBASE were systematically searched from their inception to 21 July 2022. Observational cohort studies in English assessing the risk of renal dysfunction in individuals with MetS were identified. Risk estimates and their 95% confidence intervals (CIs) were extracted and pooled using the random-effects approach. A total of 32 studies with 413,621 participants were included in the meta-analysis. MetS contributed to higher risks of renal dysfunction (RR = 1.50, 95% CI = 1.39-1.61) and, specifically, rapid decline in eGFR (RR 1.31, 95% CI 1.13-1.51), new-onset CKD (RR 1.47, 95% CI 1.37-1.58), as well as ESRD (RR 1.55, 95% CI 1.08-2.22). Moreover, all individual components of MetS were significantly associated with renal dysfunction, while elevated BP conveyed the highest risk (RR = 1.37, 95% CI = 1.29-1.46), impaired fasting glucose with the lowest and diabetic-dependent risk (RR = 1.20, 95% CI = 1.09-1.33). Individuals with MetS and its components are at higher risk of renal dysfunction.

A Retrospective Cohort Study That Examined the Impact of Cannabis Consumption on Long-Term Kidney Outcomes.

Background: Cannabis consumption for recreational and medical use is increasing worldwide. However, the long-term effects on kidney health and disease are largely unknown. Materials and Methods: Post hoc analysis of cannabis use as a risk factor for kidney disease was performed using data from the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study that enrolled hospitalized adults with and without acute kidney injury from four U.S. centers during 2009-2015. Associations between self-reported cannabis consumption and the categorical and continuous outcomes were determined using multivariable Cox regression and linear mixed models, respectively. Results: Over a mean follow-up of 4.5±1.8 years, 94 participants without chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m2) who consumed cannabis had similar rates of annual eGFR decline versus 889 nonconsumers (mean difference=-0.02 mL/min/1.73 m2/year, p=0.9) and incident CKD (≥25% reduction in eGFR compared with the 3-month post-hospitalization measured eGFR and achieving CKD stage 3 or higher) (adjusted hazard ratio [aHR]=1.2; 95% confidence interval [CI]=0.7-2.0). Nineteen participants with CKD (eGFR <60 mL/min/1.73 m2) who consumed cannabis had more rapid eGFR decline versus 597 nonconsumers (mean difference=-1.3 mL/min/1.73 m2/year; p=0.02) that was not independently associated with an increased risk of CKD progression (≥50% reduction in eGFR compared with the 3-month post-hospitalization eGFR, reaching CKD stage 5, or receiving kidney replacement therapy) (aHR=1.6; 95% CI=0.7-3.5). Cannabis consumption was not associated with the rate of change in urine albumin to creatinine ratio (UACR) over time among those with (p=0.7) or without CKD (p=0.4). Conclusions: Cannabis consumption did not adversely affect the kidney function of participants without CKD but was associated with a faster annual eGFR decline among participants with CKD. Cannabis consumption was not associated with changes in UACR over time, incident CKD, or progressive CKD regardless of baseline kidney function. Additional research is needed to investigate the kidney endocannabinoid system and the impact of cannabis use on kidney disease outcomes.

Sex differences in risk factors for end-stage kidney disease and death in type 2 diabetes: A retrospective cohort study.

This study investigated the sex differences in the risk of end-stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes. This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models. During a median follow-up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34; 95% CI 1.02-1.75; p=.034) and death (HR 1.64; 95% CI 1.24-2.16; p=.001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo- and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mg/g. No differences were detected in the association of sex and death across baseline patient subgroups. In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD.

Lower range of serum uric acid level increases risk of rapid decline of kidney function in young and middle-aged adults: the Yuport Medical Checkup Center Study

BackgroundThe effect of low serum uric acid (sUA) levels on kidney function is unclear. This study aimed to clarify the relationship between low sUA levels and the rapid decline in kidney function.MethodsWe examined the relationship between sUA levels and kidney function decline in health check-up examinees. A total of 10,547 participants were enrolled using data from the Yuport Medical Checkup Center Study between 1998 and 2002 for baseline and data from 2002 to 2006 as the follow-up period in Japan. According to sUA level (mg/dL), we classified the participants into the following six groups: (1) 2.0–2.9 (n = 247), (2) 3.0–3.9 (n = 1457), (3) 4.0–4.9 (n = 2883), (4) 5.0–5.9 (n = 2899), (5) 6.0–6.9 (n = 2010), and (6) 7.0–7.9 (n = 1,051). The relationship between sUA level and rapid decline in estimated glomerular filtration rate (ΔeGFR ≥ 3 mL/min/1.73 m2/year) was examined using a logistic regression model.ResultsDuring study period (5.4 ± 1.6 years), the incidence of rapid eGFR decline for the respective sUA groups (2.0–2.9, 3.0–3.9, 4.0–4.9, 5.0–5.9, 6.0–6.9, 7.0–7.9) were as follows: 4.5%, 4.0%, 2.4%, 3.3%, 3.1%, 3.4%. The crude and adjusted odds ratios (OR) for rapid eGFR decline were significantly higher in the 2.0–2.9 (OR:1.93 and 1.86) and 3.0–3.9 (OR:1.72 and 1.73) groups than in the 4.0–4.9 groups (reference). Stratified analysis of age differences revealed that the detrimental effect of low sUA was not evident in older adults (age ≥ 65 years).ConclusionA lower normal sUA level is related to an increased risk for a rapid decline in kidney function.

Anemia is a risk factor for rapid eGFR decline in type 2 diabetes.

To investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes. This was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 ml/min per 1.73 m2 per year was defined as rapid eGFR decline. The prevalence of DKD and clinical characteristics were compared between anemia and non-anemia patients. Correlation analysis was conducted between anemia and clinical parameters. Comparison of clinical features were carried out between rapid eGFR decline and slow eGFR decline groups. The risk factors for rapid DKD progression were analyzed using logistic regression analysis. The prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine β2-MG, urine NAG/Cr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAG/Cr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline. Anemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.

Association between sleep duration and quality with rapid kidney function decline and development of chronic kidney diseases in adults with normal kidney function: The China health and retirement longitudinal study.

Research have shown that sleep is associated with renal function. However, the potential effects of sleep duration or quality on kidney function in middle-aged and older Chinese adults with normal kidney function has rarely been studied. Our study aimed to investigate the association of sleep and kidney function in middle-aged and older Chinese adults. Four thousand and eighty six participants with an eGFR ≥60 ml/min/1.73 m2 at baseline were enrolled between 2011 and 2015 from the China Health and Retirement Longitudinal Study. Survey questionnaire data were collected from conducted interviews in the 2011. The eGFR was estimated from serum creatinine and/or cystatin C using the Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI). The primary outcome was defined as rapid kidney function decline. Secondary outcome was defined as rapid kidney function decline with clinical eGFR of <60 ml/min/1.73 m2 at the exit visit. The associations between sleep duration, sleep quality and renal function decline or chronic kidney disease (CKD) were assessed based with logistic regression model. Our results showed that 244 (6.0%) participants developed rapid decline in kidney function, while 102 (2.5%) developed CKD. In addition, participants who had 3-7 days of poor sleep quality per week had higher risks of CKD development (OR 1.86, 95% CI 1.24-2.80). However, compared with those who had 6-8 h of night-time sleep, no significantly higher risks of rapid decline in kidney function was found among those who had <6 h or >8 h of night time sleep after adjustments for demographic, clinical, or psychosocial covariates. Furthermore, daytime nap did not present significant risk in both rapid eGFR decline or CKD development. In conclusion, sleep quality was significantly associated with the development of CKD in middle-aged and older Chinese adults with normal kidney function.

Causal Effects of Specific Gut Microbiota on Chronic Kidney Diseases and Renal Function-A Two-Sample Mendelian Randomization Study.

Targeting the gut microbiota may become a new therapeutic to prevent and delay the progression of chronic kidney disease (CKD). Nonetheless, the causal relationship between specific intestinal flora and CKD is still unclear. To identify genetically predicted microbiota, we used summary data from genome-wide association studies on gut microbiota in 18340 participants from 24 cohorts. Furthermore, we genetically predicted the causal relationship between 211 gut microbiotas and six phenotypes (outcomes) (CKD, estimated glomerular filtration rate (eGFR), urine albumin to creatinine ratio (UACR), dialysis, rapid progress to CKD, and rapid decline of eGFR). Four Mendelian randomization (MR) methods, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode were used to investigate the casual relationship between gut microbiotas and various outcomes. The result of IVW was deemed as the primary result. Then, Cochrane's Q test, MR-Egger, and MR-PRESSO Global test were used to detect heterogeneity and pleiotropy. The leave-one method was used for testing the stability of MR results and Bonferroni-corrected was used to test the strength of the causal relationship between exposure and outcome. Through the MR analysis of 211 microbiotas and six clinical phenotypes, a total of 36 intestinal microflora were found to be associated with various outcomes. Among them, Class Bacteroidia (=-0.005, 95% CI: -0.001 to -0.008, p = 0.002) has a strong causality with lower eGFR after the Bonferroni-corrected test, whereas phylum Actinobacteria (OR = 1.0009, 95%CI: 1.0003-1.0015, p = 0.0024) has a strong causal relationship with dialysis. The Cochrane's Q test reveals that there is no significant heterogeneity between various single nucleotide polymorphisms. In addition, no significant level of pleiotropy was found according to MR-Egger and MR-PRESSO Global tests. Through the two-sample MR analysis, we identified the specific intestinal flora that has a causal relationship with the incidence and progression of CKD at the level of gene prediction, which may provide helpful biomarkers for early disease diagnosis and potential therapeutic targets for CKD.

Predialysis trajectories of estimated GFR and concurrent trends of Chronic Kidney Disease-relevant biomarkers.

The glomerular filtration rate (GFR) decline varies in patients with advanced chronic kidney disease (CKD), and the concurrent changes in CKD-related biomarkers are unclear. This study aimed to examine the changes in CKD-related biomarkers along with the kidney function decline in various GFR trajectory groups. This study was a longitudinal cohort study originated from the pre-end-stage renal disease (pre-ESRD) care program in a single tertiary center between 2006 and 2019. We adopted a group-based trajectory model to categorize CKD patients into three trajectories according to estimated glomerular filtration rate (eGFR) changes. A repeated-measures linear mixed model was used to estimate the concurrent biomarker trends in a 2-year period before dialysis and to examine the differences among trajectory groups. A total of 15 biomarkers were analyzed, including urine protein, serum uric acid, albumin, lipid, electrolytes, and hematologic markers. Using longitudinal data from 2 years before dialysis initiation, 1758 CKD patients were included. We identified three distinct eGFR trajectories: persistently low eGFR levels, progressive loss of eGFR, and accelerated loss of eGFR. Eight of the 15 biomarkers showed distinct patterns among the trajectory groups. Compared with the group with persistently low eGFR values, the other two groups were associated with a more rapid increase in the blood urea nitrogen (BUN) level and urine protein-creatinine ratio (UPCR), especially in the year before dialysis initiation, and a more rapid decline in hemoglobin and platelet counts. A rapid eGFR decline was associated with lower levels of albumin and potassium, and higher levels of mean corpuscular hemoglobin concentration (MCHC) and white blood cell (WBC). The albumin level in the group with an accelerated loss of eGFR was below the normal range. Using longitudinal data, we delineated the changes in CKD biomarkers with disease progression. The results provide information to clinicians and clues to elucidate the mechanism of CKD progression.

Tumor necrosis factor-alpha mediates the negative association between telomere length and kidney dysfunction.

Aim/hypothesis: The relationship between peripheral blood leukocyte telomere length (LTL) and kidney dysfunction, especially in people with hypertension, remains unclear. No clinical study has explored the role of inflammation and oxidative stress in the relationship between LTL and kidney dysfunction. Therefore, we examined the relationship between baseline LTL and albuminuria progression and/or rapid renal function decline in Chinese patients with or without hypertension and investigated whether inflammation and oxidative stress played a mediating role in this relationship. Methods: We conducted a prospective study including 262 patients in a 7-year follow-up period from 2014 to 2021. Data on LTL, inflammation, oxidative markers, renal function, and urine protein levels were assessed. Kidney dysfunction was defined as either albuminuria progression, rapid decline in renal function, or the composite endpoint (albuminuria progression and rapid decline in renal function). Logistic regression and simple mediation models were used for the analysis. Results: In this cohort (mean age, 54.3±9.7 years; follow-up period, 5.9±1.1 years), 42(16.0%), 21(8.0%), and 59(22.5%) patients developed albuminuria progression, rapid eGFR decline, and the composite endpoint of kidney dysfunction, respectively. Logistic regression analysis showed that each standard deviation decrease of baseline LTL and the lower quartile (Q) of baseline LTL were significantly correlated with an increased risk of rapid decline in renal function (OR=1.83 [95% CI 1.07, 3.27] per 1SD, P=0.03; OR=7.57 [95% CI 1.25, 145.88] for Q1 vs. Q4, P for trend=0.031); and the composite endpoint of kidney dysfunction (OR=1.37 [95% CI 0.97, 1.96] per 1SD, borderline positive P=0.072; OR=2.96[95% CI 1.15, 8.2] for Q1 vs. Q4, P for trend=0.036). The mediating analysis showed that tumor necrosis factor (TNF)-a partly mediated the relationship between LTL and rapid decline in renal function (direct effect: β=0.046 95%CI [0.006, 0.090],P=0.02; indirect effect: β=0.013 95%CI [0.003, 0.020]), and the mediating proportion was 22.4%.In subgroup analyses, LTL was inversely associated with rapid decline in renal function or the composite endpoint of kidney dysfunction only in patients with hypertension (OR=49.07[3.72,211.12] vs.1.32[0.69,2.58] per 1SD, P for interaction=0.045;OR=3.10 [1.48, 7.52] vs.1.08[0.92,1.63] per 1SD, P for interaction=0.036). Conclusion: Baseline LTL could independently predict kidney dysfunction at follow-up, especially in participants with hypertension. TNF-a partially mediated the negative association between LTL and kidney dysfunction.

Initiation of sodium-glucose cotransporter-2 inhibitors at lower HbA1c threshold attenuates eGFR decline in type 2 diabetes patients with and without cardiorenal disease: A propensity-matched cohort study

AimTo examine the association of initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) at lower glycemic threshold with decline in estimated-glomerular filtration rate (eGFR). MethodsWe analyzed a prospective cohort of Chinese patients with type 2 diabetes from Hong Kong. Patients initiating SGLT2i at HbA1c < 7.5 % (lower-HbA1c) versus ≥ 7.5 % (higher-HbA1c) were matched using 1:1 propensity score. We compared annual eGFR changes in the lower-HbA1c and higher-HbA1c groups using linear mixed-effect models. Binary logistic regression was used to explore associations of SGLT2i initiation at lower HbA1c with odds of rapid eGFR decline (>4% per year). ResultsAmong 3384 patients with a median follow-up of 1.9 years, the mean age was 60.2 ± 11.5 years and 62.1 % were male. The lower-HbA1c and higher-HbA1c groups had baseline HbA1c (%) of 6.9 ± 0.5 and 9.0 ± 1.3 respectively, with similar pre-index annual eGFR decline. The lower-HbA1c group had a slower post-index annual eGFR decline than the higher-HbA1c group (-0.99 versus −1.63 mL/min/1.73 m2, p < 0.001). Overall, the lower-HbA1c group had lower odds of rapid eGFR decline (OR = 0.15, 95 % CI: 0.07–0.29). Greater renoprotection from SGLT2i initiation at lower-HbA1c was observed in those with baseline eGFR < 60 mL/min/1.73 m2, albuminuria and/or treatment with renin-angiotensin-system inhibitors or insulin. ConclusionsIn this real-world study, SGLT2i initiation at HbA1c < 7.5 % was associated with slower eGFR decline especially in high risk patients, supporting the potential renal benefits of SGLT2i initiation at lower glycemic thresholds.

A study on thyroid, lipid profile and eGFR, protein-creatinine ratio, on assessing risk factor for renal failure

Aim: To assess the risk factors for renal dysfunction in a heterogeneous population. To determine the age and sex wise distribution of eGFR and Urinary spot Protein- Creatinine ratio (UPCR) in a heterogeneous population. To estimate the lipid profile and thyroid profile and assess their role as risk factor in renal dysfunction. Introduction: Chronic Kidney Disease (CKD), is a major health problem in India. As per the Kidney Diseases Improving Global Outcomes (KDIGO) 2012, CKD is defined1 as abnormalities of kidney structure or function present for more than three months. Thyroid hormones were also found to influence GFR, tubular secretion and absorption.16,17One study has shown that normal to high levels of Thyroid Stimulating Hormone (TSH) and normal to low levels of free triiodothyronine (FT3) were associated with increased risk of CKD in euthyroid subjects.18 It is also said that high level of serum free thyroxine (FT4) was associated with increased risk of CKD rather than TSH and FT3.There was also associated rapid decline in eGFR.19Many studies have found that hypothyroidism is associated with dyslipidemia and renal dysfunction.

Identifying Genetic Variants and Metabolites Associated with Rapid Estimated Glomerular Filtration Rate Decline in Korea Based on Genome-Metabolomic Integrative Analysis.

Identifying the predisposing factors to chronic or end-stage kidney disease is essential to preventing or slowing kidney function decline. Therefore, here, we investigated the genetic variants related to a rapid decline in the estimated glomerular filtration rate (eGFR) (i.e., a loss of >5 mL/min/1.73 m2 per year) and verified the relationships between variant-related diseases and metabolic pathway signaling in patients with chronic kidney disease. We conducted a genome-wide association study that included participants with diabetes, hypertension, and rapid eGFR decline from two Korean data sources (N = 115 and 69 for the discovery and the validation cohorts, respectively). We identified a novel susceptibility locus: 4q32.3 (rs10009742 in the MARCHF1 gene, beta = −3.540, P = 4.11 × 10−8). Fine-mapping revealed 19 credible, causal single-nucleotide polymorphisms, including rs10009742. The pimelylcarnitine and octadecenoyl carnitine serum concentrations were associated with rs10009742 (beta = 0.030, P = 7.10 × 10−5, false discovery rate (FDR) = 0.01; beta = 0.167, P = 8.11 × 10−4, FDR = 0.08). Our results suggest that MARCHF1 is associated with a rapid eGFR decline in patients with hypertension and diabetes. Furthermore, MARCHF1 affects the pimelylcarnitine metabolite concentration, which may mediate chronic kidney disease progression by inducing oxidative stress in the endoplasmic reticulum.

Glycated Haemoglobin A1c Variability Score Elicits Kidney Function Decline in Chinese People Living with Type 2 Diabetes.

Our aim was to investigate the association of glycated haemoglobin A1c (HbA1c) variability score (HVS) with estimated glomerular filtration rate (eGFR) slope in Chinese adults living with type 2 diabetes. This cohort study included adults with type 2 diabetes attending outpatient clinics between 2011 and 2019 from a large electronic medical record-based database of diabetes in China (WECODe). We estimated the individual-level visit-to-visit HbA1c variability using HVS, a proportion of changes in HbA1c of ≥0.5% (5.5 mmol/mol). We estimated the odds of people experiencing a rapid eGFR annual decline using a logistic regression and differences across HVS categories in the mean eGFR slope using a mixed-effect model. The analysis involved 2397 individuals and a median follow-up of 4.7 years. Compared with people with HVS ≤ 20%, those with HVS of 60% to 80% had 11% higher odds of experiencing rapid eGFR annual decline, with an extra eGFR decline of 0.93 mL/min/1.73 m2 per year on average; those with HVS &gt; 80% showed 26% higher odds of experiencing a rapid eGFR annual decline, with an extra decline of 1.83 mL/min/1.73 m2 per year on average. Chinese adults with type 2 diabetes and HVS &gt; 60% could experience a more rapid eGFR decline.

Estimated glomerular filtration rate trajectories in south Asians: Findings from the cardiometabolic risk reduction in south Asia study.

Few longitudinal data characterize kidney function decline among South Asians, one of the world's largest population groups. We aimed to identify estimated glomerular filtration rate (eGFR) trajectories in a population-based cohort from India and assess predictors of rapid kidney function decline. We used 6-year longitudinal data from participants of a population-representative study from Delhi and Chennai, India who had at least two serum creatinine measures and baseline CKD-EPI eGFR> 60 ml/min/1.73m2 (n=7779). We used latent class trajectory modeling to identify patterns of kidney function trajectory (CKD-EPI eGFR) over time. In models accounting for age, sex, education, and city, we tested the association between 15 hypothesized risk factors and rapid kidney function decline. Baseline mean eGFR was 108 (SD 16); median eGFR was 110 [IQR: 99-119] ml/min/1.73m2. Latent class trajectory modeling and functional characterization identified three distinct patterns of eGFR: class-1 (no decline; 58%) annual eGFR change 0.2 [0.1, 0.3]; class-2 (slow decline; 40%) annual eGFR change -0.2 [-0.4, -0.1], and class-3 (rapid decline; 2%) annual eGFR change -2.7 [-3.4, -2.0] ml/min/1.73m2. Albuminuria (>30 mg/g) was associated with rapid eGFR decline (OR for class-3 vs class-1: 5.1 [95% CI: 3.2; 7.9]; class-3 vs. class-2: 4.3 [95% CI:2.7; 6.6]). Other risk factors including self-reported diabetes, cardiovascular disease, peripheral arterial disease, and metabolic biomarkers such as HbA1c and systolic blood pressure were associated with rapid eGFR decline phenotype but potential 'non-traditional' risk factors such as manual labor or household water sources were not. Although mean and median eGFRs in our population-based cohort were higher than those reported in European cohorts, we found that a sizeable number of adults residing in urban India are experiencing rapid kidney function decline. Early and aggressive risk modification among persons with albuminuria could improve kidney health among South Asians. The CARRS study has been funded with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, under Contract No. HHSN2682009900026C and P01HL154996. Dr. Anand was supported by NIDDK K23DK101826 and R01DK127138.