Kidney Function Decline Research Articles

Lymphatic vessels in patients withcrescentic glomerulonephritis: association with renal pathology and prognosis.

Various immune cells, including T cells, B cells, macrophages, and neutrophilscontribute to the development of crescentic glomerulonephritis. Previous animal studies have suggested that lymphangiogenesis is involved in the migration of inflammatory cells and the activation of adaptive immunity. However, the extent of the association between lymphatic vessels and crescentic glomerulonephritis severity and prognosis remains unknown. In this study, we assessed lymphatic vessel density in 71 patients withcrescentic glomerulonephritis who underwent renal biopsies between June 2017 and June 2022. By immunohistochemistry and immunofluorescence, we identified increased lymphatic vessel density in thekidneys of patients with crescenticglomerulonephritiscompared to controls. Lymphatic vessels were categorized as total, periglomerular, and interstitial. Spearman's rank correlation analysis showed a positive correlation between total and periglomerular lymphatic vessel density and glomerular crescent proportion. High lymphatic vessel density (total and periglomerular) correlated with declining kidney function, increased proteinuria, and severe glomerular and interstitial pathology. Interstitial lymphatic vessel density had minimal relationship with renal lesions. After a median duration of 13 months of follow-up, higher total and periglomerular lymphatic vessel density was associated with poorer prognosis. Transcriptomic analysis revealed increased immune cell activation and migration in crescentic glomerulonephritis patients compared to healthy controls. Periglomerular lymphatic vessels might play a significant role in immune cell infiltration and renal injury. Elevated lymphatic vessel density in patients withcrescentic glomerulonephritis is associated with poor prognosisand may serve as a predictive factor for adverse outcomes in these patients.

Abstract P417: A Cumulative Score Approach to Evaluating the Impact of Five Modifiable Lifestyle Factors on Kidney Function

Background: Data from the Gubbio population study were used to investigate the impact of a cumulative score combining physical activity, intake of alcohol, sodium, potassium and protein on the decline of kidney function. Methods: The Gubbio Study is a longitudinal study on the population of Gubbio, a town in central Italy; it started in the year 1983, and addressed the resident population aged 5 +. Three exams were performed: Exam 1 (baseline) Exam 2 (6-year follow-up) and Exam 3 (20-year follow-up); this analysis is on the 3,039 adult individuals (Age 18+ at baseline) who participated in Exam 2 (1989-92) and Exam 3 (2001-07). Kidney function was estimated as glomerular filtration rate (eGFR) with the CKD-Epi equation (mL/min x 1.73 m 2 ). Habitual physical activity and alcohol intake were assessed by standard questionnaires. Dietary intake of protein, sodium and potassium were measured by urinary markers. Each factor received score 0 for the tertile associated with greater eGFR decline, score 1 for the tertile associated with intermediate decline and score 2 for the tertile associated with greater decline. A cumulative score (CS) was then calculated for each individual and used as main independent variable. Results: After correction to avoid low-n bias, the CS ranged from 1 (low risk for all factors) to 9 (high risk for all factors). The mean was 5+/-2, with skewness = 0.016. Multiple linear regression showed a relation with the annualized decline in eGFR (slope = - 0,027, 95% CI = - 0.039/ - 0.014, p < 0.001). Incidence of low eGFR was higher in the groups with higher CS, ranging from 2% in the group with CS = 1 to 12.9% in the group with CS = 9. Multivariate logistic regression analysis confirmed the correlation (p < 0.001). Conclusion: These data indicate a significant independent association between a score comprising five modifiable lifestyle factors and the long-term decline of kidney function, providing a tool for the quantification of its impact on the long-term incidence of low eGFR.

Abstract 55: Associations Between Cardiovascular Disease, Cognition, Kidney Function and Polyepigenetic Scores of Atherosclerosis in the Health and Retirement Study

Introduction: Atherosclerosis, characterized by the accumulation of arterial fatty and fibrous materials, underlies various morbidities, particularly cardiovascular disease (CVD). Epigenetic processes, like DNA methylation (DNAm), may function as mediators or biomarkers of atherosclerosis. In this study, we estimated polyepigenetic scores, which are risk-profile scores calculated from the results of an external epigenome-wide association study, for coronary artery calcification (DNAm-CAC) and carotid plaque (DNAm-cPlaque). We assessed the hypothesis that these scores are associated CVD, cognitive function, and renal function. Methods: We utilized data from the Health and Retirement Study, a longitudinal survey of U.S. adults over age 50. DNAm was measured on a representative sample of respondents aged 56 years and older who consented to blood draws in 2016 (N=3,875). We defined CVD based on self-reported physician diagnoses, cognitive function/dementia status using the Langa-Weir classification, and kidney function using serum cystatin C. We used weighted linear regression for modeling associations with cognitive and kidney function, logistic regression for prevalent CVD, and Cox proportional hazards models for incident CVD and dementia over a four-year follow-up period. Results: In 2016, the sample had a mean age of 67.4 years (SD=8.5). Most participants were females (57%), with Whites/Caucasians comprising 75% and Blacks/African Americans 17% of the sample. Both DNAm-CAC and DNAm-cPlaque were higher in smokers, individuals with a history of stroke, and those of Black/African American ancestry, while participants with higher education and greater wealth had lower scores (p<0.05). In unadjusted models, DNAm-CAC was linked to higher CVD (Odds ratio: 1.16, 95% CI: 1.07-1.26, p = 3.7х10 -4 ), worse cognitive function (Beta: -0.50, 95%CI: -0.68 - -0.32, p=8.0х10 -9 for DNAm-CAC and -0.38, 95% CI: -0.56 - -0.20, p=1.1х10 -5 for DNAm-cPlaque), and declining kidney function (1.02 fold-increase, 95% CI: 1.01-1.03, p=0.004). Adjusting for comorbidities/lifestyle factors attenuated CVD and kidney function associations but not cognition (Beta = -0.30, 95% CI: -0.14 - -0.30 for DNAm-CAC; -0.23, 95% CI:-0.05- -0.23 for DNAm-cPlaque). DNAm-cPlaque was associated with dementia/cognitive impairment incidence (hazard ratio: 1.16, 95% CI: 1.01-1.32, p=0.03) after adjusting for comorbidities/lifestyle factors including APOE -E4 genotype. For both cognitive function and dementia/cognitive impairment incidence, adjusting for race/ethnicity, education, and wealth fully attenuated the associations. Conclusions: Our findings highlight the significance of polyepigenetic scores of atherosclerosis as potential biomarkers for associated morbidities in a representative U.S. sample and underscore the role of social factors as a pathway influencing these associations.

Abstract P161: Association Between Kidney Function and Pre-Heart Failure: Insights From the Echocardiographic Study of Latinos (Echo-SOL)

Background: Impaired kidney function is an independent risk factor for heart failure (HF), but its association with pre-HF is not as well studied. We assessed kidney function in relation to pre-HF in a diverse Hispanic/Latino population in the US. Methods: Echocardiographic data from visit (V) 1 and 2 of Echo-SOL were analyzed (unweighted n=1643). Prevalent pre-HF was defined as any abnormal echocardiographic parameter at V1: left ventricular (LV) systolic dysfunction (LVSD) [ejection fraction <50%, global longitudinal strain >15%]; LV diastolic dysfunction (LVDD) >grade 1; and LV remodeling (LVR) [LV mass index >115 g/m2 in men, >95 g/m2 in women, relative wall thickness >0.42]. Incident pre-HF was defined at V2 among those without pre-HF at V1 (unweighted n=588). Kidney function was assessed by cystatin C (per 10 mg/L), eGFR (MDRD-traditional and CKD-EPI, per 5 mL/min/1.73 m2), and urine albumin creatinine ratio (UACR, per 10 units). Survey logistic regression analyses were used to examine the association of kidney function measures with prevalent and incident pre-HF and its domains (LVSD, LVDD, LVR), unadjusted and adjusted for age and sex and accounting for the complex survey design. Results: At V1 (mean age 56 years, 55% female), 66.7% had prevalent pre-HF; at V2, 66.3% had incident pre-HF. UACR was significantly associated with prevalent pre-HF and LVR in all models (Table 1-2). Higher cystatin C was significantly associated with incident pre-HF, LVDD, and LVR in all models; whereas eGFR (CKD-EPI) showed a marginal inverse relation with prevalent and incident pre-HF, LVDD and LVR, but only remained associated with LVR in adjusted models (Table 1-2). Conclusion: Declining kidney function (higher UACR and cystatin C) is associated with prevalent and incident pre-HF, diastolic dysfunction, and cardiac remodeling. Lower eGFR is also associated with cardiac remodeling in this population. Screening for kidney function could help us identify pre-HF and start protective therapies earlier to most effectively prevent overt HF.

Dotinurad restores exacerbated kidney dysfunction in hyperuricemic patients with chronic kidney disease.

In this study, we aimed to clarify the beneficial effects of urate-lowering treatment with the novel agent dotinurad on renal function in patients with chronic kidney disease (CKD) and hyperuricemia (HUA). Thirty-five patients with CKD (mean age 65.4 ± 14.8years, 23 men) diagnosed with HUA were recruited. Changes in eGFR before and after dotinurad administration were assessed. Patients first underwent a 3-month observation period and then 3months treatment with dotinurad. During the observation period, mean eGFR (mL/min/1.73 m2) declined significantly. The baseline eGFR was 31.8 ± 16.4 and the serum urate level (sUA, mg/dL) was 8.1 ± 1.7. During the treatment period, eGFR recovered to 36.5 ± 17.5 and sUA decreased to 6.7 ± 1.0. The increase in eGFR after dotinurad administration was correlated with a decrease in sUA (R = 0.375, p = 0.0263). Dotinurad administration to patients with CKD and HUA appears to be beneficial in restoring kidney function. Dotinurad may represent a potential medication for the prevention of kidney function decline caused by HUA.

Gut microbiota in the association between obesity and kidney function decline: a metagenomics-based study in a rat model

Objectives Obesity can induce dysbiosis in the gut microbiota and is considered a separate risk factor for kidney function decline. Nonetheless, the precise function of intestinal microorganisms in facilitating the connection between obesity and kidney function decline remains uncertain. Hence, the objective of this study was to investigate the alterations in the gut microbiota composition that take place during obesity and their correlations with renal function utilizing a rat model. Methods For 20 weeks, 25 Sprague–Dawley rats were fed either a high-fat diet (HFD) or a normal-fat normal diet (ND). Physiological indices, peripheral plasma, kidney tissue, and colon contents were collected for comparison between groups. Metagenomic analysis of intestinal flora was performed. Results The HFD group demonstrated significantly increased levels of creatinine and urea nitrogen in the peripheral blood. Additionally, the HFD rats exhibited a significantly larger glomerular diameter compared to the ND group, accompanied by the presence of glomerulosclerosis, tubular vacuolar transformation, and other pathological changes in certain glomeruli. Metagenomics analysis revealed a notable rise in the prevalence of the Firmicutes phylum within the HFD group, primarily comprising the Rumenococcus genus. Functional analysis indicated that the gut microbiota in the HFD group primarily correlated with infectious diseases, signal transduction, and signaling molecules and interactions. Conclusions This study provides evidence that the consumption of a HFD induces modifications in the composition and functionality of the gut microbiome in rats, which may serve as a potential mechanism underlying the relationship between obesity and the progression of kidney function decline.

Preoperative Age and Its Impact on Long-Term Renal Functional Decline after Robotic-Assisted Partial Nephrectomy: Insights from a Tertiary Referral Center.

Background and Objectives: to investigate the impact of age on renal function deterioration after robotic-assisted partial nephrectomy (RAPN) focusing on a decline to moderate and severe forms of chronic kidney disease (CKD). Materials and Methods: This is a single center prospective analysis of patients who underwent RAPN. The outcomes include the development of de novo CKD-S 3a [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2)] and de novo CKD-S 3b (eGFR < 45 mL/min/1.73/m2). Multivariable analysis (MVA) via Cox regression identified predictors for CKD-S 3a/b. Kaplan -Meier Analyses (KMA) were fitted for survival assessment. Multivariable linear regression was utilized to identify the predictors of last-eGFR. Results: Overall, 258 patients were analyzed [low age (<50) n = 40 (15.5%); intermediate age (50-70) n = 164 (63.5%); high age (>70) n = 54 (20.9%)] with a median follow-up of 31 (IQR 20-42) months. MVA revealed an increasing RENAL score [Hazard Ratio (HR) 1.32, p = 0.009], age 50-70 (HR 6.21, p = 0.01), age ≥ 70 (HR 10.81, p = 0.001), increasing BMI (HR 1.11, p < 0.001) and preoperative CKD 2 (HR 2.43, p = 0.014) are independent risk factors associated with an increased risk of CKD-S 3a; conversely, post-surgical acute kidney injury was not (p = 0.83). MVA for CKD-S 3b revealed an increasing RENAL score (HR 1.51, p = 0.013) and age ≥ 70 (HR 2.73, p = 0.046) are associated with an increased risk of CKD-S 3b. Linear regression analysis revealed increasing age (Coeff. -0.76, p < 0.001), increasing tumor size (Coeff. -0.31, p = 0.03), and increasing BMI (Coeff. -0.64, p = 0.004) are associated with decreasing eGFR at last follow-up. We compare the survival distribution of our cohort stratified by age elderly patients experienced worsened CKD-S 3a/b disease-free survival (p < 0.001; p < 0.001, respectively). Conclusions: Age is independently associated with a greater risk of significant and ongoing decline in kidney function following RAPN. Recognizing the impact of aging on renal function post-surgery can guide better management practices. Further investigations are required.

Tangshen Formula alleviates inflammatory injury against aged diabetic kidney disease through modulating gut microbiota composition and related amino acid metabolism

Diabetic kidney disease (DKD) is leading causes and one of the fastest growing causes of chronic kidney disease worldwide, and leads to high morbidity and mortality. Emerging evidences have revealed gut microbiota dysbiosis and related metabolism dysfunction play a dominant role in DKD progression and treatment through modulating inflammation. Our previous studies showed that Tangshen Formula (TSF), a Chinese herbal prescription, exhibited anti-inflammatory effect on DKD, but underlying mechanism that involved gut microbiota and related metabolism in aged model remained obscure. Here, BTBR ob/ob mice were used to establish aged DKD model, and 16S rRNA sequence and untargeted metabolomic analyses were employed to investigate the correlation between colonic microbiota and serum metabolism. The aged ob/ob mice exhibited obvious glomerular and renal tubule injury and kidney function decline in kidney, while TSF treatment significantly attenuated these abnormalities. TSF also exhibited potent anti-inflammatory effect in aged ob/ob mice indicating by reduced proinflammatory factor IL-6 and TNF-α, MCP-1 and COX-2 in serum, kidney and intestine, which suggested the involvement of gut microbiota with TSF effect. The 16S rDNA sequencing of the colonic microbiome and untargeted serum metabolomics analysis revealed significant differences in gut microbiota structure and serum metabolomic profiles between WT and ob/ob mice. Notably, TSF treatment reshaped the structure of gut microbiota and corrected the disorder of metabolism especially tryptophan metabolism and arginine biosynthesis. TSF increased Anaeroplasma and Barnesiella genera and decreased Romboutsia, Akkermansia, and Collinsella genera, and further elevated tryptophan, 5-hydroxyindoleacetate, glutamic acid, aspartate and reduced 4-hydroxy-2-quinolinecarboxylic acid, indole-3-acetic acid, xanthurenic acid, glutamine. Further correlation analysis indicated that disturbed gut microbiota was linked to tryptophan metabolism and arginine biosynthesis to regulate inflammation in aged DKD. Our data revealed that TSF attenuated renal inflammation by modulating gut microbiota and related amino acid metabolism in aged DKD model, highlighting gut microbiota and related metabolism functioned as potential therapeutic target for DKD in elderly patients.

Association between blood pressure variability and risk of kidney function decline in hypertensive patients without chronic kidney disease: a post hoc analysis of Systolic Blood Pressure Intervention Trial study.

Blood pressure variability (BPV) is a risk factor for poor kidney function independent of blood pressure (BP) in chronic kidney disease (CKD). Little is known about the association between kidney function decline and BPV in hypertensive patients without CKD. A post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) was performed. BPV was measured as standard deviation (SD) and average real variability (ARV). Cox proportional hazard models were employed to explore the relationship between BPV and incident CKD and albuminuria. A total of 5700 patients were included, with a mean age of 66.4 years old. During a median of 3.29 years follow-up, 150 (2.6%) patients developed CKD and 222 (7.2%) patients developed albuminuria. Patients were divided into four groups according to the quartiles of BPV. Compared with SBPV Q1, the incidence of CKD was higher in SBPV Q2-Q4; hazard ratios and 95% confidence interval were 1.81 (1.07-3.04), 1.85 (1.10-3.12) and 1.90 (1.13-3.19), respectively. The association between incident CKD and albuminuria with DBPV was less significant than SBPV. Similar results were found when measuring BPV as ARV and SD. No interaction was detected in BP-lowering strategy and SBPV on incident CKD and albuminuria ( P > 0.05). This study found that BPV was a risk factor for incident CKD and albuminuria in patients without CKD, especially SBPV. Although intensive BP control increased the risk of CKD, the association between SBPV and kidney function decline did not differ between the two treatment groups. URL: https://clinicaltrials.gov/ , Unique identifier: NCT01206062.

Plasma levels and dietary intake of minerals in patients with type 2 diabetes and chronic kidney disease: A case-control study

Background and aimDiabetic kidney disease (DKD) is the primary cause of chronic kidney disease (CKD) worldwide. Altered mineral levels leading to adverse outcomes are widely reported in diabetes but limited in DKD, in the Indian scenario, hence this study was taken up to address this issue. MethodsA hospital-based case-control study was taken up with 54 healthy controls (C) and 140 subjects with type 2 diabetes wherein 74 subjects with diabetes and CKD formed the DKD group, and 66 subjects with diabetes but no CKD formed the diabetic no-chronic kidney disease (DNCKD) group. High-resolution inductively coupled plasma mass spectrometry was used to evaluate the blood levels of minerals (calcium (Ca), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), and selenium (Se)), and a raw food-based food frequency questionnaire for dietary intakes. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (mL/min/1.73 m2) and albuminuria. Spearman’s rank correlation was used to evaluate the relationship between the categorical variables. ResultsThe median values of plasma Ca in the DKD group were significantly lower compared with the DNCKD and C groups (10.5 mg/dL vs. 11.0 mg/dL and 11.7 mg/dL, p<0.001). Furthermore, plasma Ca levels lowered with declining kidney function, as evidenced by the eGFR and albuminuria segregation. Dietary intake of minerals did not correlate with the corresponding plasma levels. However, in the DKD group, eGFR correlated positively with the plasma levels of Ca (r= 0.422, p=0.001), Cr (r= 0.351, p=0.008), Mn (r= 0.338, p=0.011), Fe (r= 0.403, p=0.002), Cu (r= 0.274, p=0.041) and negatively with Se (r= −0.486, p<0.001). ConclusionPlasma Ca levels are lower in the DKD group with a strong positive association with eGFR, indicating its role in predicting the onset and progression of kidney function decline.

Diet quality in relation to kidney function and its potential interaction with genetic risk of kidney disease among Dutch post-myocardial infarction patients

PurposeWe examined the relation between diet quality, its components and kidney function decline in post-myocardial infarction (MI) patients, and we explored differences by genetic risk of chronic kidney disease (CKD).MethodsWe analysed 2169 patients from the Alpha Omega Cohort (aged 60–80 years, 81% male). Dietary intake was assessed at baseline (2002–2006) using a validated food-frequency questionnaire and diet quality was defined using the Dutch Healthy Diet Cardiovascular Disease (DHD-CVD) index. We calculated 40-months change in estimated glomerular filtration rate (eGFR, mL/min per 1.73m2). We constructed a weighted genetic risk score (GRS) for CKD using 88 single nucleotide polymorphisms previously linked to CKD. Betas with 95%-confidence intervals (CIs) were obtained using multivariable linear regression models for the association between DHD-CVD index and its components and eGFR change, by GRS.ResultsThe average DHD-CVD index was 79 (SD 15) points and annual eGFR decline was 1.71 (SD 3.86) mL/min per 1.73 m2. The DHD-CVD index was not associated with annual eGFR change (per 1-SD increment in adherence score: -0.09 [95% CI -0.26,0.08]). Results for adherence to guidelines for red meat showed less annual eGFR decline (per 1-SD: 0.21 [0.04,0.38]), whereas more annual eGFR decline was found for legumes and dairy (per 1-SD: -0.20legumes [-0.37,-0.04] and − 0.18dairy [-0.34,-0.01]). Generally similar results were obtained in strata of GRS.ConclusionThe DHD-CVD index for overall adherence to Dutch dietary guidelines for CVD patients was not associated with kidney function decline after MI, irrespective of genetic CKD risk. The preferred dietary pattern for CKD prevention in CVD patients warrants further research.

Geriatric Nutritional Risk Index as a Possible Predictor of Decline in Kidney Function in Older People.

The Geriatric Nutritional Risk Index (GNRI) is associated with morbidity and mortality in older individuals. Our study explored the relationship between GNRI, decline in kidney function, and all-cause mortality in older individuals. This retrospective cohort study analyzed data from participants aged ≥60 years who underwent a general health checkup between 2002 and 2018. The primary exposure was the GNRI, divided into quartiles. The primary and secondary outcomes were a decline in kidney function assessed using the 5-year estimated glomerular filtration rate (eGFR) and all-cause mortality, respectively. The analysis included a total of 1,599 participants (median age, 63 years; interquartile range [IQR], 61-67; 54% males). The mean±standard deviation of GNRI was 114±7. Compared with the highest GNRI quartile, the lower GNRI quartiles were associated with steeper 5-year slopes in eGFR, with a fully adjusted beta coefficient and 95% confidence intervals (CIs) of -0.50 (-0.86, -0.14), -0.29 (-0.63, 0.05), and -0.19 (-0.53, 0.14) for the first, second, and third GNRI quartiles, respectively. The median follow-up duration was 7.4 years (IQR, 4.6-12.4). During this period, we identified 108 deaths (7.8 per 1,000 person-years). The first GNRI quartile was associated with all-cause mortality compared to the highest GNRI quartile (hazard ratio of 2.20; 95% CI 1.23, 3.95). Nutritional status, as evaluated using the GNRI, was associated with 5-year changes in kidney function and all-cause mortality in older individuals.

Increased cardiovascular risk in patients with chronic kidney disease.

Cardiovascular disease (CVD) is highly prevalent in patients suffering from chronic kidney disease (CKD). The risk of patients with CKD developing CVD is manifested already in the early stages of CKD development. The impact of declined kidney function on increased cardiovascular risk and the underlying mechanisms are complex and multifactorial. This review discusses the impact of (a) traditional cardiovascular risk factors such as smoking, dyslipidemia, diabetes, and hypertension as well as (b) CKD-specific pathophysiological and molecular mechanisms associated with an increased cardiovascular risk. The latter include uremic toxins, post-translational modifications and uremic lipids, innate immune cell activation and inflammation, oxidative stress, endothelial cell dysfunction, increased coagulation and altered platelet responses, vascular calcification, renin-angiotensin-aldosterone-system (RAAS) and sympathetic activation, as well as anemia. Unraveling the complex interplay of different risk factors, especially in the context of patient subcohorts, will help to find new therapeutic approaches in order to reduce the increased cardiovascular risk in this vulnerable patient cohort.

Deterioration of Kidney Function Is Affected by Central Arterial Stiffness in Late Life.

Cardiovascular diseases affect kidney function. The aim of this study was to investigate the possible associations between hemodynamic parameters and change in kidney function in individuals aged 75 years and older. Data on hemodynamics and blood and urine samples were collected at baseline and during one-year visits. Hemodynamics were split into two groups based on median values. Changes in the estimated glomerular filtration rate (eGFR) were investigated between low and high groups for each hemodynamic parameter using analysis of variance. Changes in the albumin-creatinine ratio (ACR) were examined as binary outcomes (large increase vs. stable) using logistic regression. The population consisted of 252 participants. Participants in the high central systolic blood pressure (cSBP) group had a greater decline in eGFR than participants in the low cSBP group (-6.3% vs. -2.7%, p = 0.006). Participants in the high aortic pulse wave velocity (aPWV) group had a greater decline in eGFR than those in the low aPWV group (-6.8% vs. -2.5%, p = 0.001). Other hemodynamic parameters were not associated with eGFR changes. Hemodynamics were not associated with changes in the ACR; aPWV and cSBP appear to be predictors for eGFR decline in older age; monitoring and treatment of elevated stiffness might be helpful in order to prevent kidney function decline.

COVID-19−Associated Acute Kidney Injury and Longitudinal Kidney Outcomes

COVID-19 infection is associated with a high incidence of acute kidney injury (AKI). Although rapid kidney function decline has been reported in the first few months after COVID-19-associated AKI (COVID-AKI), the longer-term association of COVID-AKI with kidney function remains unknown. To assess long-term kidney outcomes of patients who had COVID-19-associated AKI. This was a retrospective longitudinal multicenter cohort study conducted in a large hospital system using electronic health records data on adult hospitalized patients with AKI and COVID-19 or other illnesses. Included patients were hospitalized during the COVID-19 pandemic (March 2020-June 2022), were screened for SARS-CoV-2, had AKI, and survived to discharge, or had been hospitalized during the 5 years before the pandemic (October 2016-January 2020), had a positive influenza A or B test result, had AKI, and survived to discharge. Patients were followed up for a maximum of 2 years after hospital discharge. Data analyses were performed from December 2022 to November 2023. COVID-19 and influenza. The primary outcome was major adverse kidney events (MAKE), defined as a composite of mortality and worsened kidney function (estimated glomerular filtration rate [eGFR] decline by ≥25% from discharge eGFR or kidney failure requiring dialysis). Multivariable time-to-event analyses were performed to compare MAKE between individuals with COVID-AKI and those who had AKI associated with other illnesses hospitalized during the same period. For further comparison, this outcome was assessed for a historic cohort of patients with influenza-associated AKI. The study cohort included 9624 hospitalized patients (mean [SD] age, 69.0 [15.7] years; 4955 [51.5%] females) with AKI, including 987 patients with COVID-AKI, 276 with influenza-associated AKI, and 8361 with AKI associated with other illnesses (other-AKI). Compared with the other 2 groups, patients with COVID-19-associated AKI were slightly younger in age, had a higher baseline eGFR, worse baseline comorbidity scores, higher markers of illness severity, and longer hospital stay. Compared with the other-AKI group, the COVID-AKI group had lower MAKE (adjusted hazard ratio [aHR], 0.67; 95% CI, 0.59-0.75) due to lower all-cause mortality (aHR, 0.31; 95% CI, 0.24-0.39) and lower rates of worsened kidney function (aHR, 0.78; 95% CI, 0.69-0.88). The findings of this multicenter cohort study indicate that survivors of hospitalization with COVID-AKI experience lower rates of MAKE, long-term kidney function decline, and mortality compared with patients with AKI associated with other illnesses.

Longitudinal progression trajectory of estimated glomerular filtration rate in children with chronic kidney disease: results from the KNOW-Ped CKD (KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease).

The natural course of chronic kidney disease (CKD) progression in children varies according to their underlying conditions. This study aims to identify different patterns of subsequent decline in kidney function and investigate factors associated with different patterns of estimated glomerular filtration rate (eGFR) trajectories. We analyzed data from the KNOW-Ped CKD (KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease), which is a longitudinal, prospective cohort study. A latent class linear mixed model was applied to identify the trajectory groups. In a total of 287 patients, the median baseline eGFR (mL/min/1.73 m2) was 63.3, and the median age was 11.5 years. The eGFR decline rate was -1.54 during a 6.0-year follow-up. The eGFR trajectory over time was classified into four groups. Classes 1 (n = 103) and 2 (n = 11) had a slightly reduced eGFR at enrollment with a stable trend (ΔeGFR, 0.2/year) and a rapid decline eGFR over time (ΔeGFR, -10.5/year), respectively. Class 3 had a normal eGFR (n = 16), and class 4 had a moderately reduced eGFR (n = 157); both these chasses showed a linear decline in eGFR over time (ΔeGFR, -4.1 and -2.4/year). In comparison with classes 1 and 2, after adjusting for age, causes of primary renal disease, and baseline eGFR, nephrotic-range proteinuria was associated with a rapid decline in eGFR (odds ratio, 8.13). We identified four clinically relevant subgroups of kidney function trajectories in children with CKD. Most children showed a linear decline in eGFR; however, there are different patterns of eGFR trajectories.

PPARα/δ dual agonist H11 alleviates diabetic kidney injury by improving the metabolic disorders of tubular epithelial cells

Diabetic kidney disease (DKD) is responsible for nearly half of all end-stage kidney disease and kidney failure is a major driver of mortality among patients with diabetes. To date, few safe and effective drugs are available to reverse the decline of kidney function. Kidney tubules producing energy by fatty acid metabolism are pivotal in development and deterioration of DKD. Peroxisome proliferator-activated receptors (PPARs), comprising PPARα, PPARδ and PPARγ play a senior role in the pathogenesis of DKD for their functions in glycemic control and lipid metabolism; whereas systemic activation of PPARγ causes serious side-effects in clinical settings. Compound H11 was a potent PPARα and PPARδ (PPARα/δ) dual agonist with potent and well-balanced PPARα/δ agonistic activity and a high selectivity over PPARγ. In this study, the potential therapeutic effects of compound H11 were determined in a db/db mouse model of diabetes. Expressions of PPARα and PPARδ in nuclei of tubules were markedly reduced in diabetes. Transcriptional changes of tubular cells showed that H11 was an effective PPARα/δ dual agonist taking effects both in vivo and in vitro. Systemic administration of H11 showed glucose tolerance and lipid metabolic benefits in db/db mice. Moreover, H11 treatment exerted protective effects on diabetic kidney injury. In addition to fatty acid metabolism, H11 also regulated diabetes-induced metabolic alternations of branch chain amino acid degradation and glycolysis. The present study demonstrated a crucial role of H11 in regulation of energy homeostasis and metabolism in glucose-treated tubular cells. Overall, compound H11 holds therapeutic promise for DKD.

Molecular Docking Based Predictive Study of Bougainvillea Glabra against Mtorc1 Protein for the Treatment of Diabetic Nephropathy: Network Pharmacology

Background: The decline in kidney function experienced by people with type 1 and type 2 diabetes who are chronically ill is known as diabetic nephropathy (DN) or diabetic kidney disease. The condition is known to progress in a number of stages and is related to blood pressure and glycemic management. Nevertheless, despite strict blood sugar management, the prevalence of chronic kidney disease (CKD) in diabetic patients has not decreased over the past 20 years, which has led to the discovery of new risk factors for the illness's development. The medical characteristics of the Paper Flower, Bougainvillea spectabilis, include anti-inflammatory, anti-hepatotoxic, anti-inflammtory, anti-hyperlipidemic, antibacterial, antioxidant, and antiulcer capabilities. Alkaloids, flavonoids, glycosides, phenolics, phytobannins, quinones, saponins, tannins, and terpenoids are examples of phytoconstituents that have been claimed to have medicinal characteristics. Method: In the current study, a molecular docking technique was used to try and identify mTORC1protein inhibitors. A grid-based docking strategy was used to determine the binding using the Auto Dock software. Merck Molecular Force Field was used to build the 2D structures of compounds, convert them to 3D, and then energetically reduce them up to arms gradient of 0.01. (MMFF). Result: The molecular docking of Ferulic acid &amp; Gallic acid with mTORC1 protein showed binding energy (Kcal/mol) -5.37 &amp; -4.56 respectively. Conclusion: Theoretically, all the ligand molecules have shown encouraging docking score. The docking result of ferulic acid revealed that their docking scores was -5.37 kcal mol–1, and it can be predicted as good inhibitor of mTORC1 protein and thereby prevents dysregulation of intracellular protein synthesis and the metabolic balance along with decreasing oxidative stress on the kidney.

A mandatory practice in type 2 diabetes mellitus to maintain quality of life

Nepalese owing to modern lifestyle and processed food are racially at an elevated risk of acquiring central obesity-related insulin resistance (IR) and thus Type 2 diabetes mellitus (T2DM) and Diabetic Kidney Disease (DKD). Low birth weight in utero and later becoming obese risks the development of T2DM. In a total of eighty-four newly diagnosed treatment-naive Nepalese T2DMs, incidence of IR, percentage beta-cell function (%BCF) and percentage insulin sensitivity (%IS) were determined using Homeostatic Model Assessment 2 (HOMA2-IR). Association of HOMA2-IR with albuminuria, kidney function, hs-CRP, fatty liver, fatty pancreas, several anthropometric and biochemical parameters were analyzed. Among the eighty-four T2DMs, fifty-four agreeing regular follow-ups were prescribed a low-carbohydrate diet (&amp;#60;130gm/day). At 6 months, their glycemic controls were monitored. From 84 newly diagnosed T2DMs, 56 (66.7%) were insulin resistant and 28(33.3%) insulin-sensitive on HOMA2-IR. There was a significant association of HOMA2-IR with albuminuria and declining kidney function (p=0.006 and 0.034 respectively) and most of them were at reversible stages. Waist circumference (WC), waist-hip ratio (WHR), lipid profile ratios, fatty liver and fatty pancreas were elucidated as potential markers for IR. The IS group (ISG) had significantly inadequate %BCF (p=0.001) but high %IS (p&amp;#60;0.001) has healthier WHR (p=0.001) and lipid profile ratios which are opposite to IR group (IRG). 13 ISG had raised hs-CRP and 15 normal and 21 IRG had normal hs-CRP and 35 raised. At 6 months, the IRG achieved significantly better postprandial glycemic goals (p=0.04) and significant improvement in WC and WHR (p=0.008 and 0.03 respectively) with a low-carbohydrate diet as compared to ISG. Severe insulin resistance and IR-associated DKD, fatty liver and fatty pancreas are highly prevalent from the time of diagnosis of T2DM in the Nepalese population. Thus inspecting for IR and its consequences mandatorily at diagnosis and applying precision therapies like adjustments in the quality and quantity of staple food carbohydrates significantly improves IR-related parameters and glycemia.

HYDROchlorothiazide versus placebo to PROTECT polycystic kidney disease patients and improve their quality of life: study protocol and rationale for the HYDRO-PROTECT randomized controlled trial

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) leads to progressive renal cyst formation and loss of kidney function in most patients. Vasopressin 2 receptor antagonists (V2RA) like tolvaptan are currently the only available renoprotective agents for rapidly progressive ADPKD. However, aquaretic side effects substantially limit their tolerability and therapeutic potential. In a preliminary clinical study, the addition of hydrochlorothiazide (HCT) to tolvaptan decreased 24-h urinary volume and appeared to increase renoprotective efficacy. The HYDRO-PROTECT study will investigate the long-term effect of co-treatment with HCT on tolvaptan efficacy (rate of kidney function decline) and tolerability (aquaresis and quality of life) in patients with ADPKD.MethodsThe HYDRO-PROTECT study is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized clinical trial. The study is powered to enroll 300 rapidly progressive patients with ADPKD aged ≥ 18 years, with an eGFR of > 25 mL/min/1.73 m2, and on stable treatment with the highest tolerated dose of tolvaptan in routine clinical care. Patients will be randomly assigned (1:1) to daily oral HCT 25 mg or matching placebo treatment for 156 weeks, in addition to standard care.OutcomesThe primary study outcome is the rate of kidney function decline (expressed as eGFR slope, in mL/min/1.73 m2 per year) in HCT versus placebo-treated patients, calculated by linear mixed model analysis using all available creatinine values from week 12 until the end of treatment. Secondary outcomes include changes in quality-of-life questionnaire scores (TIPS, ADPKD-UIS, EQ-5D-5L, SF-12) and changes in 24-h urine volume.ConclusionThe HYDRO-PROTECT study will demonstrate whether co-treatment with HCT can improve the renoprotective efficacy and tolerability of tolvaptan in patients with ADPKD.