Latin Americans are underrepresented in the current equations used to estimate glomerular filtration rate (GFR), and the applicability of their predictions to this population may therefore be questionable. The objective of this study was to develop a new equation to estimate GFR based on data from Argentina. A cross-sectional study was conducted. We included 583 Argentinian adults in development sample (DS) and 78 in temporary validation sample (TVS). Urinary iothalamate clearance (reference method), and different predictive variables were used to develop candidate equations to estimate GFR. The performance was assessed through 10-fold cross-validation in DS, and by direct validation in TVS, using root mean squared error (RMSE), correlation (r), bias, P15, P30 and correct classification percentage (CC%) in CKD stages. The Argentinian equation (AE) chosen is based on a quasi-likelihood model which predicts GFR from creatinine, age, sex, single kidney, albumin and urea. Within the previous creatinine based equations (MDRD, MCQ, CKD-EPI and EKFC), the ones with the best performance were CKD-EPI 2009 and 2021. In the DS, AE showed lower RMSE, similar r, higher P15, median bias closer to zero and higher CC% compared to CKD-EPI 2009, and very slight differences in comparison to CKD-EPI 2021. In the TVS, AE presented lower RMSE, higher (or equal) r, P30 and CC%, and median bias closer to 0 compared to CKD-EPI in its two versions. In addition, it presented higher P15 than CKD-EPI 2009. In conclusion, AE presented a better performance to estimate GFR in Argentinian people and its use could have a positive impact on the clinical management of these patients.

The objective of this study was to detect the prevalence of incidental chronic kidney disease (CKD) in patients newly diagnosed with type 2 diabetes (T2D).

 This was a cross-sectional study conducted from July 2023 to November 2024, at Faiha Specialized Diabetes, Endocrine, and Metabolism Center and Al-Rafidain Specialized Center in Basrah, southern Iraq. A total of 202 newly diagnosed drug-naïve T2D patients were included. The baseline clinical and biochemical characteristics for the patients at inclusion. CKD was diagnosed by measuring the estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR).

The mean age of patients included in the study was 49.1±12 years. CKD was diagnosed in 68 (33.7%) patients based on GFR <60 mL/minute/1.73 m2 and/or UACR ≥ 30 mg/g. The CKD categories G1, 2, G3a, and 3b were prevalent in 71.3%, 24.2%, 3.0%, and 1.5%, respectively. For albuminuria, 31.2% had UACR 10-30 mg/g, 22.8% had UACR 30-300 mg/g, and 7.9% had UACR higher than 300 mg/g. A stepwise binary regression analysis showed that higher patients' age and HbA1c levels were the factors that were significantly associated with CKD.

incidental CKD is prevalent in one-third of the newly diagnosed T2D. Early screening for CKD is highly recommended as it will affect overall management.

Aims/Background The present study aimed to assess the capability of biomarkers, including inflammatory indicators, anaemic markers, lipid markers, and renal function indices, to differentiate between different stages of chronic kidney disease (CKD). Expected to provide a new strategy for monitoring the development of CKD and stratified treatment management, providing valuable insights for future biomarker studies to explore early detection of CKD. Methods The changes in inflammatory markers (interferon gamma [IFN-γ], interleukin [IL]-17A, IL-10, IL-6, IL-4, IL-2, IL-1 and white blood cells [WBC]), lipid markers (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], and triglyceride [TG]), indicators of kidney injury (serum creatinine [Scr] and blood urea nitrogen [BUN]) in 451 patients with different stages of CKD were examined. Furthermore, these markers were compared between 299 anemic patients and 53 non-anemic patients. Univariate and multivariate regression analyses were employed to analyze the association between these biomarkers and estimated glomerular filtration rate (eGFR). To identify risk factors associated with the development of CKD, we utilized principal component analysis to evaluate their utility as potential diagnostic and prognostic markers for the disease. Results Significant differences were found in IL-6, BUN, and hemoglobin (Hb) levels across CKD stages 2 to 5. Anaemic individuals had elevated levels of IL-6, Scr, and BUN compared to non-anaemic individuals. In addition, the multivariate linear regression analysis revealed that IL-1 (p = 0.022), IL-6 (p = 0.022), Hb (p < 0.001), and BUN (p < 0.001) were statistically significant predictors of eGFR. Furthermore, it was discovered that the blood levels of IL-6 (p = 0.012), BUN (p < 0.001), and Hb (p < 0.001) were risk factors associated with the stages of CKD. Conclusion Serum levels of IL-6, BUN and Hb have been associated with the progression of CKD. Using a combination of serum biomarkers is a potential strategy for tracking the development of CKD, facilitating stratified management and early intervention.

Low protein intake (LPI) has been suggested as a treatment for chronic kidney disease (CKD). However, protein intake is essential for bone health.

We studied the database of the National Health and Nutrition Examination Survey, 2005-2010. Basic variables, metabolic diseases, and bone density of different femoral areas were stratified into four subgroups according to different protein intake (DPI) (that is, <0.8, 0.8-1.0, 1.0-1.2, and >1.2 g/kg/day).

Significant differences were found among all lumbar area bone mineral density (BMD) and T-scores (p < 0.0001). There was an apparent trend between a decreasing BMD in the CKD groups with increasing DPI in all single lumbar spines (L1, L2, L3, and L4) and all L spines (L1-L4). Compared with DPI (0.8-1.0 g/day/kg), higher risks of osteoporosis were noticed in the subgroup of >1.2 g/day/kg over L2 (relative risk (RR)=1.326, 95% confidence interval (CI)=1.062-1.656), subgroup >1.2 g/day/kg over L3 (RR = 1.31, 95%CI = 1.057-1.622), subgroup <0.8 g/day/kg over L4 (RR = 1.276, 95%CI = 1.015-1.605), subgroup <0.8 g/day/kg over all L spines (RR = 11.275, 95%CI = 1.051-1.548), and subgroup >1.2 g/day/kg over all L spines (RR = 0.333, 95%CI = 1.098-1.618). However, a higher risk of osteoporosis was observed only in the non-CKD group. There was an apparent trend of higher DPI coexisting with lower BMD and T scores in patients with CKD. For osteoporosis (reference:0.8-1.0 g/day/kg), lower (<0.8 g/day/kg) or higher DPI (>1.2 g/day/kg) was associated with higher risks in the non-CKD group, but not in the CKD group.

In the CKD group, LPI for renal protection was safe without threatening L spine bone density and without causing a higher risk of osteoporosis.

Chronic limb-threatening ischemia (CLTI) significantly increases the risk of major adverse limb events (MALE) and major adverse cardiac events (MACE) after lower extremity revascularization (LER). This study aims to identify novel biomarkers that help to further reduce the risk of postoperative cardiovascular complications. In this prospective, nonrandomized, observational study, baseline serum levels of sirtuin 1 (SIRT1) were assessed in 147 diabetic patients scheduled for LER due to CLTI, and participants were followed for the occurrence of MALE and MACE over 12 months. Fifty-three patients experienced MALE, and 33 experienced MACE within the follow-up period. Lower baseline SIRT1 levels were significantly associated with an increased risk of MALE and MACE, independent of other risk factors. The ROC curve analysis identified a SIRT1 cutoff of 3.79 ng/mL for predicting the risk of MALE. Moreover, incorporating SIRT1 into predictive models significantly enhanced the accuracy of predicting adverse outcomes. Results suggest serum SIRT1 is a potential independent marker for predicting MALE and MACE in diabetic patients with CLTI undergoing LER. Further research is needed to clarify the mechanistic pathways in which SIRT1 may influence cardiovascular outcomes, and the role of this novel biomarker in the management of PAD and CLTI among patients with diabetes.

Renal insufficiency and/or chronic kidney disease are common comorbidities in patients with lung cancer, potentially affecting their prognosis. The aim of the present study was to assess the existing evidence on the association between renal insufficiency (RI)/chronic kidney disease (CKD) and the overall survival (OS) and disease-free survival (DFS) of patients with lung cancer (LC). Comprehensive electronic searches in the PubMed, Embase and Scopus databases were performed for observational cohort and case-control studies and randomized controlled trials that investigated the association between RI/CKD and the OS and/or DFS of patients with LC. Random-effect models were used, and the combined effect sizes were reported as either standardized mean differences or relative risks, along with 95% confidence intervals (CI). A total of 10 studies were included. The duration of follow-up in the included studies ranged from 12 months to 5 years. Compared with patients with normal renal function, patients with LC with RI/CKD had worse OS rates [hazard ratio (HR), 1.38; 95% CI, 1.16-1.63] but similar DFS rates (HR, 1.12; 95% CI, 0.75-1.67) at follow-up. Subgroup analysis demonstrated a significant association between poor OS and RI/CKD in patients with stage I/II LC [HR, 1.76; 95% CI, 1.30-2.37] but not in patients with stage III/IV LC [HR, 1.18; 95% CI, 0.91, 1.54]. Furthermore, irrespective of the treatment modality i.e., surgery [HR, 1.78; 95% CI, 1.40-2.27] or medical management [HR, 1.37; 95% CI, 1.25-1.50], RI/CKD was notably associated with a poor OS at follow-up. The findings of the present study underscore the adverse impact of RI/CKD on the long-term survival of patients with LC.

Limited data have addressed frailty's role in cardiorenal risk among older adult patients with chronic kidney disease (CKD). We investigated whether frailty could predict major renal and cardiovascular events, healthcare utilization, and mortality in these patients.

We conducted a prospective cohort enrolling patients aged ≥75 years with a stable estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. The frailty phenotype consists of shrinking, low activity, exhaustion, weakness, and slowness, scored 0 to 5. The primary composite renal outcome was a ≥25% decrease in eGFR concurrent with CKD stage progression or dialysis initiation. Secondary outcomes included major adverse cardiovascular events (MACE), emergency room (ER) visits, all-cause mortality, and hospitalization. Using multivariate Cox models with/without competing risk analyses, we explored frailty's impact on these outcomes.

Among 203 older CKD patients (mean age: 81.6 ± 5.0 years, female: 40.9%, diabetes: 33.0%, body mass index: 24.9 ± 3.7 kg/m2), 67.9% were frail. Over 3.47 years, 38.9% faced composite renal outcomes; 13.3%, MACE; 15.3%, mortality; and more than half utilized healthcare. Every one-point frailty elevated renal outcome risk by 28.0% (HR: 1.28, 95% confidence interval [CI]: 1.03-1.59) and significantly increased secondary outcomes (MACE [HR: 1.43, 95% CI: 0.99-2.08], hospitalization [HR: 1.24, 95% CI: 1.06-1.46], unexpected ER visit [HR: 1.20, 95% CI: 1.03-1.39], and mortality [HR: 1.51, 95% CI: 1.06-2.16]). Results were consistent across subgroups and competing risk analysis.

In CKD patients aged ≥75 years, frailty was associated with progressive kidney disease, increased mortality, and healthcare utilization.

Despite early diagnosis and medical interventions, patients with methylmalonic acidemia (MMA) suffer from multi-organ damage and recurrent metabolic decompensations.

We conducted the largest retrospective multi-center cohort study so far, involving five transplant centers (NCCHD, KUH, KUHP, ATAK, and EMC), and identified all MMA patients (n = 38) undergoing LDLT in the past two decades. Our primary outcome was patient survival, and secondary outcomes included death-censored graft survival and posttransplant complications.

The overall 10-year patient survival and death-censored graft survival rates were 92% and 97%, respectively. Patients who underwent LDLT within 2 years of MMA onset showed significantly higher 10-year patient survival compared to those with an interval more than 2 years (100% vs. 81%, p = 0.038), although the death-censored graft survival were not statistically different (100% vs. 93%, p = 0.22). Over the long-term follow-up, 14 patients (37%) experienced intellectual disability, while two patients developed neurological complications, three patients experienced renal dysfunction, and one patient had biliary anastomotic stricture. The MMA level significantly decreased from 2218.5 mmol/L preoperative to 307.5 mmol/L postoperative (p = 0.038).

LDLT achieves favorable long-term patient and graft survival outcomes for MMA patients. While not resulting in complete cure, our findings support the consideration of early LDLT within 2 years of disease onset. This approach holds the potential to mitigate recurrent metabolic decompensations, and preserve the long-term renal function.

Identifying the biomarkers associated with new-onset glomerular filtration rate (GFR) decrease in an initially healthy population could offer a better understanding of kidney function decline and help improving patient management.

Here we described the proteomic and transcriptomic footprints associated with new-onset kidney function decline in an initially healthy and well-characterized population with a 20-year follow-up. This study was based on 1087 individuals from the familial longitudinal Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) cohort who attended both visit 1 (from 1993 to 1995) and visit 4 (from 2011 to 2016). New-onset kidney function decline was approached both in quantitative (GFR slope for each individual) and qualitative (defined as a decrease in GFR of >15 ml/min/1.7 m2) ways. We analysed associations of 445 proteins measured both at visit 1 and visit 4 using Olink Proseek® panels and 119 765 genes expressions measured at visit 4 with GFR decline. Associations were assessed using multivariable models. The Bonferroni correction was applied.

We found several proteins (including PLC, placental growth factor (PGF), members of the tumour necrosis factor receptor superfamily), genes (including CCL18, SESN3), and a newly discovered miRNA-mRNA pair (MIR1205-DNAJC6) to be independently associated with new-onset kidney function decline. Complex network analysis highlighted both extracellular matrix and cardiovascular remodelling (since visit 1) as well as inflammation (at visit 4) as key features of early GFR decrease.

These findings lay the foundation to further assess whether the proteins and genes herein identified may represent potential biomarkers or therapeutic targets to prevent renal function impairment.

In an era marked by a global demographic shift towards an aging society, there is a heightened prevalence of chronic kidney disease (CKD) among older adults. The burden of CKD spans from kidney-related complications to impacting psychological well-being, giving rise to depressive symptoms and caregiver burnout. This article delves into CKD prevention strategies within the context of aging, contributing to the discourse by exploring its multifaceted aspects. The prevention of CKD in the older adults necessitates a comprehensive approach. Primary prevention is centered on the modification of risk factors, acknowledging the intricate interplay of various comorbidities. Secondary prevention focuses on early CKD identification. Tertiary prevention aims to address factors contributing to CKD progression and complications, emphasizing the importance of timely interventions. This comprehensive strategy aims to enhance the quality of life for individuals affected by CKD, decelerating the deterioration of functional status. By addressing CKD at multiple levels, this approach seeks to effectively and compassionately care for the aging population.

To investigate the influence of glomerular filtration rate in renal disease decline and its association with diabetic retinopathy (DR) and age-related macular degeneration (ARMD) in patients in South India.

A population-based cross-sectional study was conducted including participants with DR and ARMD recruited from urban and rural populations. The data collection included medical history, anthropometric measurements, and ophthalmic work-up. The estimated glomerular filtration rate (eGFR) was calculated using the equation of chronic kidney disease-epidemiology collaboration (CKD-EPI). The grading of AMD was done by a single experienced (more than 5 years) vitreoretinal surgeon as per the International ARM Epidemiological Study Group and it was staged based on grading in the worsened eye.

A decline in eGFR was observed as the severity of DR increased ( P < 0.001). Baseline characteristics such as age ( P < 0.001), duration of diabetes ( P < 0.001), gender ( P < 0.001), creatinine ( P < 0.001), albumin to creatinine ratio (ACR; P < 0.001), albuminuria ( P = 0.023), blood urea ( P < 0.001), and high-density lipoprotein (HDL; P = 0.003) were found to be statistically significant. The risk for developing DR with CKD was found to be 5 times higher in male patients compared to female patients. Age and high blood urea level, diastolic blood pressure, mild and moderate DR were the risk factors associated with CKD. A decline in eGFR was observed as the severity of ARMD increased ( P < 0.001). The risk factors associated with CKD were age, gender, smoking, alcohol consumed, presence of hypertension, duration of diabetes, systolic and diastolic blood pressure, history of diabetes, body mass index (BMI), serum triglycerides, and serum HDL cholesterol.

Reduced eGFR values were associated with an increase in the severity of DR and ARMD.

Estimation of glomerular filtration rate using equations based on creatinine is widely used to manage chronic kidney disease. In the UK, the Chronic Kidney Disease Epidemiology Collaboration creatinine equation is recommended. Other published equations using cystatin C, an alternative marker of kidney function, have not gained widespread clinical acceptance. Given higher cost of cystatin C, its clinical utility should be validated before widespread introduction into the NHS.

Primary objectives were to: (1) compare accuracy of glomerular filtration rate equations at baseline and longitudinally in people with stage 3 chronic kidney disease, and test whether accuracy is affected by ethnicity, diabetes, albuminuria and other characteristics; (2) establish the reference change value for significant glomerular filtration rate changes; (3) model disease progression; and (4) explore comparative cost-effectiveness of kidney disease monitoring strategies.

A longitudinal, prospective study was designed to: (1) assess accuracy of glomerular filtration rate equations at baseline (n = 1167) and their ability to detect change over 3 years (n = 875); (2) model disease progression predictors in 278 individuals who received additional measurements; (3) quantify glomerular filtration rate variability components (n = 20); and (4) develop a measurement model analysis to compare different monitoring strategy costs (n = 875).

Primary, secondary and tertiary care.

Adults (≥ 18 years) with stage 3 chronic kidney disease.

Estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations.

Measured glomerular filtration rate was the reference against which estimating equations were compared with accuracy being expressed as P30 (percentage of values within 30% of reference) and progression (variously defined) studied as sensitivity/specificity. A regression model of disease progression was developed and differences for risk factors estimated. Biological variation components were measured and the reference change value calculated. Comparative costs of monitoring with different estimating equations modelled over 10 years were calculated.

Accuracy (P30) of all equations was ≥ 89.5%: the combined creatinine-cystatin equation (94.9%) was superior (p < 0.001) to other equations. Within each equation, no differences in P30 were seen across categories of age, gender, diabetes, albuminuria, body mass index, kidney function level and ethnicity. All equations showed poor (< 63%) sensitivity for detecting patients showing kidney function decline crossing clinically significant thresholds (e.g. a 25% decline in function). Consequently, the additional cost of monitoring kidney function annually using a cystatin C-based equation could not be justified (incremental cost per patient over 10 years = £43.32). Modelling data showed association between higher albuminuria and faster decline in measured and creatinine-estimated glomerular filtration rate. Reference change values for measured glomerular filtration rate (%, positive/negative) were 21.5/-17.7, with lower reference change values for estimated glomerular filtration rate.

Recruitment of people from South Asian and African-Caribbean backgrounds was below the study target.

Prospective studies of the value of cystatin C as a risk marker in chronic kidney disease should be undertaken.

Inclusion of cystatin C in glomerular filtration rate-estimating equations marginally improved accuracy but not detection of disease progression. Our data do not support cystatin C use for monitoring of glomerular filtration rate in stage 3 chronic kidney disease.

This trial is registered as ISRCTN42955626.

This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/103/01) and is published in full in Health Technology Assessment; Vol. 28, No. 35. See the NIHR Funding and Awards website for further award information.

Assessing glomerular filtration rate (GFR) involves collecting timed urine samples for 24 hours, requiring significant time and resources in the clinical setting. Using predictive GFR formulae to assess renal function may be a better alternative. Our goal was to determine which predictive GFR formula had the highest level of concordance with the GFR that has been measured in a resource-poor setting. This is an observational study. We selected fifty (50) individuals diagnosed with type 2 diabetes (T2DM) in Kumasi, Ghana. The sociodemographic and clinical characteristics were obtained using a structured questionnaire. Urine was obtained from each subject over 24 hours. The levels of glucose (FBG) and creatinine in patients' blood, as well as the levels of creatinine in their urine, were measured after the patients had fasted overnight. Participants had a mean age of 57.4 ± 10.7 (years), BMI of 27.8 ± 4.1 (kg/m2), FBG of 9.0 ± 3.1 (mmol/L), and creatinine concentrations of 95.6 ± 29.1 (μmol/L). A Krouwer plot was used to compare the measured GFR with three formulae: Chronic Kidney Disease Epidemiology (CKD-EPI), Modification of Diet in Renal Disease (MDRD), and Cockroft-Gault (CG) for GFR prediction. Among the 3 estimates, CG showed nonsignificance (p > 0.05) with the measured GFR. The primary finding was that the GFR calculated using the CG formula was not different from the GFR measured, suggesting that CG is the most appropriate alternative GFR estimate among a cross-section of T2DM patients in Ghana.

Cognitive impairment and brain atrophy are common in chronic kidney disease patients. It remains unclear whether differences in renal function, even within normal levels, influence hippocampal volume (HCV) and cognition. We aimed to investigate the association between estimated glomerular filtration rate (eGFR), HCV and cognition in outpatients.

This single-center retrospective study enrolled 544 nonrenal outpatients from our hospital. All participants underwent renal function assessment and 3.0 T magnetic resonance imaging (MRI) in the same year. HCV was also measured, and cognitive assessments were obtained. The correlations between eGFR, HCV, and cognitive function were analyzed. Logistic regression analysis was performed to identify the risk factors for hippocampal atrophy and cognitive impairment. Receiver-operator curves (ROCs) were performed to find the cut-off value of HCV that predicts cognitive impairment.

The mean age of all participants was 66.5 ± 10.9 years. The mean eGFR of all participants was 88.5 ± 15.1 mL/min/1.73 m2. eGFR was positively correlated with HCV and with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Univariate and multivariate logistic regression analysis showed Age ≥ 65 years, eGFR < 75 mL/min/1.73 m2, Glucose ≥6.1 mmol/L and combined cerebral microvascular diseases were independent risk factors for hippocampal atrophy and Age ≥ 65 years, left hippocampal volume (LHCV) <2,654 mm3 were independent risk factors for cognitive impairment in outpatients. Although initial unadjusted logistic regression analysis indicated that a lower eGFR (eGFR < 75 mL/min/1.73 m2) was associated with poorer cognitive function, this association was lost after adjusting for confounding variables. ROC curve analysis demonstrated that LHCV <2,654 mm3 had the highest AUROC [(0.842, 95% CI: 0.808-0.871)], indicating that LHCV had a credible prognostic value with a high sensitivity and specificity for predicting cognitive impairment compared with age in outpatients.

Higher eGFR was associated with higher HCV and better cognitive function. eGFR < 75 mL/min/1.73 m2 was an independent risk factor for hippocampal atrophy after adjusting for age. It is suggested that even eGFR < 75 mL/min/1.73 m2, lower eGFR may still be associated with hippocampal atrophy, which is further associated with cognitive impairment. LHCV was a favorable prognostic marker for predicting cognitive impairment rather than age.

Diabetic nephropathy (DN) is one of the most prevalent and severe complications of diabetes mellitus (DM) and is associated with increased morbidity and mortality. We aimed to investigate the associations between red, processed, and white meat consumption and the odds of developing kidney damage and DN in women. We enrolled 105 eligible women with DN and 105 controls (30-65 years). A validated and reliable food frequency questionnaire (FFQ) was used to evaluate the consumption of red, processed, and white meat. Biochemical variables and anthropometric measurements were assessed for all patients using pre-defined protocols. Binary logistic regression was conducted to examine possible associations. The results of the present study showed that there was a direct significant association between high consumption of red meat and processed meats and odds of microalbuminuria (red meat 2.30, 95% CI 1.25, 4.22; P-value = 0.007, processed meat: OR 2.16, 95% CI 1.18, 3.95; P-value = 0.01), severe albuminuria (red meat OR 3.25, 95% CI 1.38, 7.46; P-value = 0.007, processed meat: OR 2.35, 95% CI 1.01, 5.49; P-value = 0.04), BUN levels (red meat: OR 2.56, 95% CI 1.10, 5.93; P-value = 0.02, processed meat: OR 2.42, 95% CI 1.04, 5.62; P-value = 0.03), and DN (red meat 2.53, 95% CI 1.45, 4.42; P-value = 0.001, processed meat: OR 2.21; 95% CI 1.27, 3.85; P-value = 0.005). In summary, our study suggests that higher consumption of red and processed meat sources may be associated with microalbuminuria, severe albuminuria, higher BUN level, and higher odds of DN.

Estimated glomerular filtration rate is considered the principal measure of kidney function and, together with albuminuria, is a relevant prognostic factor for the development of end-stage kidney disease. Due to the strong association between estimated glomerular filtration rate and clinical events, such as commencement of dialysis, cardiovascular outcomes and all-cause death, estimated glomerular filtration rate is crucial for clinical decision-making in terms of scheduling follow-up and pharmacological interventions, and planning renal replacement therapies in advanced chronic kidney disease. In this review we discuss the available methods for measuring glomerular filtration rate and for estimating it through mathematical equations developed over the last few decades. We summarize the prognostic association of different percentages of estimated glomerular filtration rate decline and the main clinical outcomes, and how treatments modify estimated glomerular filtration rate decline and the risk of future endpoints. We also examine the role of pre-clinical trial slope and that of estimated glomerular filtration rate as a useful biomarker when evaluating patients for inclusion into both observational and interventional studies.

Black adults in the United States have 2-4 times higher incidence of kidney failure than White adults. Yet, the reasons underlying this disparity remain poorly understood. Among 547,188 US veterans with new-onset CKD, according to a new race-free GFR equation, Black veterans had a 2.5-fold higher cumulative incidence of kidney failure, compared with White veterans, in any follow-up period from CKD onset. This disparity resulted from a combination of higher hazards of progression to kidney failure and lower hazards of competing-risk death in Black veterans. Both, in turn, were largely explained by the younger age at CKD onset in Black veterans, underscoring an urgent need to prevent early onset and slow progression of CKD in younger Black adults.

The Black adult population is well known to have higher incidence of kidney failure than their White counterpart in the United States, but the reasons underlying this disparity are unclear. We assessed the racial differences in kidney failure and death from onset of CKD on the basis of the race-free 2021 CKD Epidemiology Collaboration equation and examined the extent to which these differences could be explained by factors at the time of CKD onset.

We analyzed a national cohort consisting of 547,188 US veterans (103,821 non-Hispanic Black and 443,367 non-Hispanic White), aged 18-85 years, with new-onset CKD between 2005 and 2016 who were followed through 10 years or May 2018 for incident kidney failure with replacement therapy (KFRT) and pre-KFRT death.

At CKD onset, Black veterans were, on average, 7.8 years younger than White veterans. In any time period from CKD onset, the cumulative incidence of KFRT was 2.5-fold higher for Black versus White veterans. Meanwhile, Black veterans had persistently >2-fold higher hazards of KFRT throughout follow-up (overall hazard ratio [95% confidence interval], 2.38 [2.31 to 2.45]) and conversely had 17%-48% decreased hazards of pre-KFRT death. These differences were reduced after accounting for the racial difference in age at CKD onset.

The 2.5-fold higher cumulative incidence of kidney failure in Black adults resulted from a combination of higher hazards of progression to kidney failure and lower hazards of the competing risk of death, both of which can be largely explained by the younger age at CKD onset in Black compared with White adults.

Liver transplantation (LT) is an effective and lifesaving treatment for patients with end-stage liver disease and hepatocellular carcinoma. Significant improvement in intermediate and long-term survival has been possible due to advancements in immunosuppressive therapy, perioperative care, and surgical techniques. Despite these advances, metabolic complications, including diabetes mellitus, cardiovascular diseases, malignancies, and renal dysfunction, are challenging issues after LT. Acute kidney injury (AKI) and chronic kidney disease (CKD) after LT are common and result in significant morbidity and mortality. Early diagnosis of kidney injury after LT is challenging, and no technique has yet proven effective in prediction of renal dysfunction. The methods for assessing renal function range from formulas that predict glomerular filtration rate to non-invasive biomarkers. The universal adoption of the model for end-stage liver disease has a direct impact on the incidence of peri-transplant AKI and development of CKD in the long-term. Post-LT renal dysfunction is multifactorial and is usually a result of pre-transplantation comorbidities, occurrence of renal dysfunction on the waiting list, perioperative events, and post-transplant nephrotoxic immunosuppressive medication use. Early identification of patients at risk for renal dysfunction and adoption of preventive measures are crucial in the pre-transplant period. No data are currently available to suggest a surgical technique that reliably demonstrates renal protection. Nephroprotective strategies during LT follow accepted surgical practice guidelines, such as maintenance of intravascular volume and mean arterial pressure. The management of kidney disease following LT is challenging, as by the time the serum creatinine is significantly elevated, few interventions impact the course of progression. Early nephroprotective measures are strongly advised and they mostly center on delaying the administration of calcineurin inhibitors (CNIs) during the initial postoperative period, lowering CNI dosage and combining CNI with mycophenolate mofetil and everolimus. The reasons for renal failure following LT, the techniques used to diagnose it, and the therapies designed to preserve renal function both immediately and late after LT are all critically evaluated in this review.

Dapagliflozin was recently approved for use in adults with chronic heart failure with reduced ejection fraction (HFrEF) with/without type 2 diabetes mellitus (T2DM). The objectives of this analysis were to characterize dapagliflozin pharmacokinetics in patients with HFrEF and to compare dapagliflozin systemic exposure between adults with HFrEF with/without T2DM and adults with T2DM. A nonlinear mixed-effects modelling approach was applied; the population-pharmacokinetic model was developed using 9735 dapagliflozin plasma concentrations from 2744 patients. The final two-compartmental model adequately described the observed dapagliflozin concentrations, with a similar estimated apparent clearance compared with a previous estimate in patients with T2DM without HF and in healthy subjects (23.0 [95% CI: 22.6-23.9] L/h vs. 22.9 [95% CI: 22.1-23.7] L/h). The model-predicted median area under the dapagliflozin concentration-time profile was ≤1.2-fold higher in patients with HFrEF vs. those with T2DM without HFrEF, which is not considered clinically relevant. Dapagliflozin exposure was similar between patients with HFrEF with/without T2DM and T2DM patients without HFrEF.

The impact of aortoiliac occlusive disease on kidney transplantation remains unclear. This study aims to investigate the clinical outcomes of kidney transplant patients with aortoiliac atherosclerotic stenosis.

Retrospective data from our transplant center were used to identify patients undergoing kidney transplantation between January 2010 and December 2020. Aortoiliac atherosclerotic stenosis was screened and stratified by the Trans-Atlantic Inter-Society Consensus (TASC) II classification. The primary outcome was patient survival. Secondary outcomes were 90-day mortality, death-censored graft survival, graft function, and arterial complications. Propensity score matching was used to match all patients in the stenosis group with patients without stenosis sharing similar characteristics.

The analysis included 655 patients, 524 without stenosis and 131 with aortoiliac stenosis (95 with TASC A/B stenosis and 36 with TASC C/D stenosis). Recipient age [median (IQR), 66 (60-70) vs. 66 (59-71) years; P =0.47], sex [male: 87 (66%) vs. 355 (68%), P =0.85], and comorbidities were comparable between the stenosis and no-stenosis groups. Forty-six (35%) patients with stenosis were symptomatic. Patient survival was significantly lower in the stenosis group compared with the no-stenosis group (TASC A/B: 30.6% vs. no-stenosis: 44.1%, P =0.013; TASC C/D: 11.4% vs. no-stenosis: 44.1%, P <0.001). The incidence rates of artery dissection, lower extremity ischemia, and acute thrombosis were significantly higher in the stenosis group ( P <0.001). However, death-censored graft survival (TASC A/B: 73.6% vs. no-stenosis: 72.9%, P =0.62; TASC C/D: 58.1% vs. no-stenosis: 72.9%, P =0.16) and graft function were comparable between the groups.

Aortoiliac atherosclerotic stenosis significantly impacts patient survival but not graft survival. Our analyses suggest that patients with TASC A/B stenosis have prolonged survival and enhanced quality of life through kidney transplantation. However, for patients with TASC C/D stenosis, kidney transplantation improves quality of life without bringing survival benefits.

Current demographic change leads to higher number of elderly patients admitted to an ICU. Among other organs also the kidneys show age-related changes, which are associated with a decline in various aspects of renal function. The purpose of this review is to provide an overview of structural and functional changes in elderly and also to specifically address the increased risk of acute kidney injury (AKI) in this population.

Ageing in the kidneys is affected by many different factors, such as low grade chronic inflammation, called inflammageing, and various comorbidities. Nevertheless, a decrease of glomerular filtration rate (GFR) occurs independent of the presence of comorbidities and a steady decline of GFR has been reported in both healthy men and women. Pharmacodynamic of many drugs is altered by these changes. Additionally the rate of diuretic resistance appears to be increased. The cause of AKI occurrence in older age is, multifactorial and includes preventable triggers (hypovolemia, hypotension, nephrotoxins) as well as changes associated with aging.

Age-related alterations of the kidneys were found at microscopic and macroscopic levels of the cell. These changes lead to a reduced renal reserve and subsequently to an increased vulnerability of aged kidneys when an additional stressor is added. Age is an independent risk factor for developing AKI. Physicians should take into account the altered renal function in elderly patients and take renal protective measures at an early stage.

Cardiovascular risk assessment beyond traditional risk factors in subjects with prediabetes is not well-established. Here, we evaluated the utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in predicting incident adverse cardiovascular outcomes in prediabetic subjects.

NT-proBNP was analyzed in 3,235 stable subjects with prediabetes undergoing cardiovascular risk evaluation and followed for both 3-year major adverse cardiac events (MACE; death, myocardial infarction, stroke), and 5-year all-cause mortality.

Using Cox proportional hazard models, we found that plasma NT-proBNP was associated with incident (3-year) MACE risk (Q4 vs Q1, HR 6.04 [95%CI 4.17-8.76], P < 0.001) and 5-year mortality risk (HR 8.64 [95%CI 5.78-12.9], P < 0.001). These associations remained significant after adjustments for traditional cardiovascular risk factors, multiple indices of glycemic control, cardiovascular disease (CVD), left ventricular ejection fraction (LVEF), and medication (e.g. diuretic) use (adjusted HR for 3-year MACE 2.65 [95% CI 1.16-6.05], P < 0.05; and adjusted HR for 5-year mortality 3.45 [95% CI 1.42-8.39], P < 0.01). NT-proBNP significantly improved the clinical prognostic value (C-statistic, NRI, IDI) for both 3-year MACE and 5-year death when added to models.

NT-proBNP independently predicts increased long-term MACE and mortality risks in prediabetic subjects, and may help identify those for whom more aggressive global preventive efforts are indicated.

Patients undergoing peritoneal dialysis (PD) are prone to dyslipidemia. However, studies concerning remnant cholesterol (RC) in such patients are limited.

We aimed to investigate the association between RC and cardiovascular (CV) mortality in patients on PD.

Patients who initiated PD at our center (2006-2018) were retrospectively enrolled. Adjusted Cox models were used to evaluate the independent association between baseline RC levels and CV mortality. We classified patients into 4 concordant/discordant categories according to their baseline lipid profiles. Cox models were then used to determine the association between different low-density lipoprotein cholesterol (LDL-C) and RC levels and CV mortality risk.

The study enrolled 2333 individuals, with a mean RC of 33.4 mg/dL. RC levels were positively associated with CV mortality risk independent of LDL-C in patients on PD (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 1. 00-1.10). In the concordant/discordant categories, patients with high LDL-C and RC levels had a higher CV mortality risk (HR: 1.52; 95% CI: 1.01-2.28) than those with low LDL-C and RC levels in the entire cohort. Moreover, in older patients, a higher RC level increased CV mortality risk regardless of the LDL-C level (HR: 2.41, 95% CI: 1.22-4.74; HR: 2.15, 95% CI: 1.12-4.14).

RC levels are elevated in patients on PD and can predict CV mortality beyond LDL-C levels. RC levels should be considered alongside LDL-C levels when assessing prognostic lipid levels in these patients. More attention should be given to RC than to LDL-C in older patients undergoing PD.

Decreased postdonation eGFR is associated with a higher risk of ESRD after living kidney donation, even when accounting for predonation characteristics. The Toulouse-Rangueil model (TRM) estimates 12 month postdonation eGFR (eGFR12) to inform counseling of candidates for living donation. The TRM was validated in several single-center European cohorts but has not been validated in US donors. We assessed the TRM in living kidney donors in the US using SRTR data 1/2000-6/2021. We compared the 2021 CKD-EPI equation eGFR12 observed estimates to the TRM eGFR12 predictions. Median (IQR) bias was -3.4 (-9.3, 3.4) mL/min/1.73 m2. Bias was higher for males vs. females (bias [IQR] -4.4 [-9.9, 1.8] vs. -2.9 [-8.8, 4.1]) and younger (31-40) vs. older donors (>50) (bias -4.9 [-10.6, 3.0] vs. -2.1 [-7.5, 4.0]). Bias was also larger for Black vs. White donors (bias (-6.7 [-12.1, -0.3], p < 0.001) vs. (-3.4 [-9.1, 3.1], p < 0.001)). Overall correlation was 0.71. In a sensitivity analysis using the 2009 CKD-EPI equation, results were generally consistent with exception to a higher overall bias (bias -4.2 [-9.8, 2.4]). The TRM overestimates postdonation renal function among US donors. Overestimation was greatest for those at higher risk for postdonation ESRD including male, Black, and younger donors. A new equation is needed to estimate postdonation renal function.

We evaluated the performance of creatinine-based equations that are currently used to estimate glomerular filtration rate (GFR) in people with type 2 diabetes compared to measured GFR using gold-standard methods.

In this post-hoc analysis, 32 participants underwent repeated measurement of GFR by inulin clearance (mGFR). GFR was estimated by serum creatinine using the MDRD (eGFRMDRD) and CKD-EPI (eGFRCKD-EPI) equations four times over the course of one month. Performance was evaluated using measurements of bias (mean difference), precision (SD), and inaccuracy (proportion of eGFR that differed by >20 % of mGFR). Treatment and time effects on bias were evaluated using linear mixed effects models.

At baseline, participants (38 % female) were age 60 ± 8 years, had diabetes duration of 9 ± 7 years, HbA1c 56 ± 9 mmol/mol (7.2 ± 0.8 %), and BMI 31.0 ± 6.2 kg/m2. Mean mGFR was 113 ± 24, mean eGFRMDRD was 93 ± 12, and mean eGFRCKD-EPI was 94 ± 9 mL/min/1.73 m2. When 128 observations (32 participants measured 4 times) were evaluated, both equations substantially underestimated mGFR. For eGFRMDRD, mean bias was -21.5 mL/min/1.73 m2, precision was 22.7 mL/min/1.73 m2, and 46 % of observations differed by >20 %. Results were similar for eGFRCKD-EPI. No time or treatment effects on bias were observed.

In adults with type 2 diabetes and preserved renal function, eGFR equations underestimated mGFR, lacked precision and accuracy, and performance was lower at higher ranges of mGFR. Current eGFR equations by serum creatinine are inaccurate in adults with type 2 diabetes with preserved renal function, highlighting the necessity to develop new methods to measure kidney function at earlier stages of diabetic kidney disease.

In patients undergoing percutaneous coronary intervention (PCI), contrast-induced acute kidney injury (CIAKI) is a frequent complication, especially in diabetics, and is connected with severe mortality and morbidity in the short and long term. Therefore, we aimed to develop a CIAKI predictive model for diabetic patients.

3514 patients with diabetes from four hospitals were separated into three cohorts: training, internal validation, and external validation. We developed six machine learning (ML) algorithms models: random forest (RF), gradient-boosted decision trees (GBDT), logistic regression (LR), least absolute shrinkage and selection operator with LR, extreme gradient boosting trees (XGBT), and support vector machine (SVM). The area under the receiver operating characteristic curve (AUC) of ML models was compared to the prior score model, and developed a brief CIAKI prediction model for diabetes (BCPMD). We also validated BCPMD model on the prospective cohort of 172 patients from one of the hospitals. To explain the prediction model, the shapley additive explanations (SHAP) approach was used.

In the six ML models, XGBT performed best in the cohort of internal (AUC: 0.816 (95% CI 0.777-0.853)) and external validation (AUC: 0.816 (95% CI 0.770-0.861)), and we determined the top 15 important predictors in XGBT model as BCPMD model variables. The features of BCPMD included acute coronary syndromes (ACS), urine protein level, diuretics, left ventricular ejection fraction (LVEF) (%), hemoglobin (g/L), congestive heart failure (CHF), stable Angina, uric acid (umol/L), preoperative diastolic blood pressure (DBP) (mmHg), contrast volumes (mL), albumin (g/L), baseline creatinine (umol/L), vessels of coronary artery disease, glucose (mmol/L) and diabetes history (yrs). Then, we validated BCPMD in the cohort of internal validation (AUC: 0.819 (95% CI 0.783-0.855)), the cohort of external validation (AUC: 0.805 (95% CI 0.755-0.850)) and the cohort of prospective validation (AUC: 0.801 (95% CI 0.688-0.887)). SHAP was constructed to provide personalized interpretation for each patient. Our model also has been developed into an online web risk calculator. MissForest was used to handle the missing values of the calculator.

We developed a novel risk calculator for CIAKI in diabetes based on the ML model, which can help clinicians achieve real-time prediction and explainable clinical decisions.

Aortic pulse wave velocity (Ao-PWV) predicts cardiovascular and kidney disease in type 2 diabetes (T2D). Klotho is a circulating antiaging hormone (sKlotho) with putative cardiorenal protective effects. The relationship between sKlotho and Ao-PWV in diabetic kidney disease (DKD) is unknown.

In a cross-sectional cohort study, the correlation of sKlotho measured by a validated immunoassay, and Ao-PWV measured by applanation tonometry, was investigated in 172 participants with T2D and early stage DKD (all had estimated glomerular filtration rate [eGFR] >45 ml/min) on stable renin angiotensin system (RAS) inhibition. In cultured human aortic smooth muscle cells (HASMCs) stimulated with angiotensin II (AngII), the effects of recombinant human sKlotho pretreatment were assessed on intracellular calcium ([Ca²⁺]_i) responses and expression of proteins associated with proosteogenic HASMC phenotypes.

Mean (range) age of the cohort was 61.3 years (40-82) and 65% were male. Mean (±SD) Ao-PWV was 11.4 (±2.3) m/s, eGFR 78.8 (±23.5) and median (interquartile range) sKlotho of 358.5 (194.2-706.3) pg/ml. In multivariable linear regression analyses, we observed a statistically significant inverse relationship between sKlotho and Ao-PWV, which was independent of clinical risk factors for cardiorenal disease. Pretreatment of cultured HASMC with sKlotho significantly attenuated AngII-stimulated [Ca²⁺]_i transients and reduced osteogenic collagen (Col1a2) expression.

In individuals with T2D and early DKD, lower levels of sKlotho are associated with increased Ao-PWV. Taken together with the direct effect of sKlotho on mediators of aortic wall stiffness in vitro, these findings may explain the enhanced risk of cardiorenal disease in DKD.

Tolvaptan slows kidney function decline in patients with autosomal dominant polycystic kidney disease (ADPKD) who are at risk of rapid progression. Given that treatment requires commitment to long-term use, we evaluated the effects of tolvaptan discontinuation on the trajectory of ADPKD progression.

This was a post hoc analysis of pooled data from two clinical trials of tolvaptan (TEMPO 2:4 [NCT00413777] and TEMPO 3:4 [NCT00428948]), an extension trial (TEMPO 4:4 [NCT01214421]), and an observational study (OVERTURE [NCT01430494]) that enrolled patients from the other trials. Individual subject data were linked longitudinally across trials to construct analysis cohorts of subjects with a tolvaptan treatment duration > 180 days followed by an off-treatment observation period of > 180 days. For inclusion in Cohort 1, subjects were required have ≥ 2 outcome assessments during the tolvaptan treatment period and ≥ 2 assessments during the follow-up period. For Cohort 2, subjects were required to have ≥ 1 assessment during the tolvaptan treatment period and ≥ 1 assessment during the follow-up period. Outcomes were rates of change in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). Piecewise-mixed models compared changes in eGFR or TKV in the on-treatment and post-treatment periods.

In the Cohort 1 eGFR population (n = 20), the annual rate of eGFR change (in mL/min/1.73 m2) was -3.18 on treatment and -4.33 post-treatment, a difference that was not significant (P = 0.16), whereas in Cohort 2 (n = 82), the difference between on treatment (-1.89) and post-treatment (-4.94) was significant (P < 0.001). In the Cohort 1 TKV population (n = 11), TKV increased annually by 5.18% on treatment and 11.69% post-treatment (P = 0.06). In Cohort 2 (n = 88), the annual TKV growth rates were 5.15% on treatment and 8.16% post-treatment (P = 0.001).

Although limited by small sample sizes, these analyses showed directionally consistent acceleration in measures of ADPKD progression following the discontinuation of tolvaptan.

Lower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), High-Mobility Group Box-1 (HMGB-1), Osteoprotegerin (OPG), Sortilin and Omentin-1- at baseline, with cardiovascular outcomes (MACE and MALE) after LER in diabetic patients with CLTI.

In this prospective non-randomized study, 264 diabetic patients with CLTI undergoing endovascular revascularization were enrolled. Serum levels of each biomarker were collected before revascularization and outcomes' incidence was evaluated after 1, 3, 6 and 12 months.

During the follow-up period, 42 cases of MACE and 81 cases of MALE occurred. There was a linear association for each biomarker at baseline and incident MACE and MALE, except Omentin-1 levels that were inversely related to the presence of MACE or MALE. After adjusting for traditional cardiovascular risk factors, the association between each biomarker baseline level and outcomes remained significant in multivariable analysis. Receiver operating characteristics (ROC) models were constructed using traditional clinical and laboratory risk factors and the inclusion of biomarkers significantly improved the prediction of incident events.

Elevated IL-1, IL-6, CRP, TNF-α, HMGB-1, OPG and Sortilin levels and low Omentin-1 levels at baseline correlate with worse vascular outcomes in diabetic patients with CLTI undergoing LER. Assessment of the inflammatory state with this panel of biomarkers may support physicians to identify a subset of patients more susceptible to the procedure failure and to develop cardiovascular adverse events after LER.

Tolvaptan is indicated for treatment of patients with autosomal dominant polycystic kidney disease (ADPKD) at risk of rapid progression. Participants aged 56-65 years constituted a small proportion of the Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trial population. We assessed effects of tolvaptan on estimated glomerular filtration rate (eGFR) decline in participants aged >55 years.

This was a pooled data analysis from 8 studies of tolvaptan or non-tolvaptan standard of care (SOC).

Participants aged >55 years with ADPKD were included. Data on participants in >1 study were linked longitudinally for maximum follow-up duration, with matching for age, sex, eGFR, and chronic kidney disease (CKD) stage to minimize confounding.

Tolvaptan or non-tolvaptan SOC.

Treatment effects on annualized eGFR decline were compared using mixed models with fixed effects for treatment, time, treatment-by-time interaction, and baseline eGFR.

In the pooled studies, 230 tolvaptan-treated and 907 SOC participants were aged >55 years at baseline. Ninety-five participant pairs from each treatment group were matched, all in CKD G3 or G4, ranging from 56.0 to 65.0 years (tolvaptan) or from 55.1 to 67.0 years (SOC). The eGFR annual decline rate was significantly reduced by 1.66 mL/min/1.73 m² (95% CI, 0.43-2.90; P = 0.009) in the tolvaptan group compared with SOC (-2.33 versus -3.99 mL/min/1.73 m²) over 3 years.

Limitations include potential bias because of study population differences (bias risk was reduced through matching and multiple regression adjustment); vascular disease history data was not uniformly collected, and therefore not adjusted; and natural history of ADPKD precludes evaluating certain clinical endpoints within the study time frame.

In individuals aged 56-65 years with CKD G3 or G4, compared to a SOC group with mean GFR rate of decline ≥3 mL/min/1.73 m²/year, tolvaptan was associated with efficacy similar to that observed in the overall indication.

Otsuka Pharmaceutical Development & Commercialization, Inc (Rockville, MD).

TEMPO 2:4 (NCT00413777); phase 1 tolvaptan trial (no NCT number; trial number 156-06-260); phase 2 tolvaptan trial (NCT01336972); TEMPO 4:4 (NCT01214421); REPRISE (NCT02160145); long-term tolvaptan safety extension trial (NCT02251275); OVERTURE (NCT01430494); HALT Progression of Polycystic Kidney Disease (HALT-PKD) study B (NCT01885559).

Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-fibroblast growth factor 23 (FGF23) axis is associated with endothelial injury and cardiovascular risk. We aimed to analyze the relationship between Klotho and FGF23 serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI. Baseline levels of Klotho and FGF23, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population of diabetic patients with PAD and CLTI requiring LER. A total of 220 patients were followed for 12 months after LER. Sixty-three MACE and 122 MALE were recorded during follow-up period. Baseline lower Klotho serum levels (295.3 ± 151.3 pg/mL vs. 446.4 ± 171.7 pg/mL, p < 0.01), whereas increased serum levels FGF23 (75.0 ± 11.8 pg/mL vs. 53.2 ± 15.4 pg/mL, p < 0.01) were significantly associated with the development of MACE. Receiver operating characteristic (ROC) analysis confirmed the predictive power of Klotho and FGF23 baseline levels. Furthermore, decreased Klotho levels were associated with the occurrence of MALE after LER (329.1 ± 136.8 pg/mL vs 495.4 ± 183.9 pg/mL, p < 0.01). We found that Klotho and FGF23 baseline levels are a potential biomarker for increased cardiovascular risk after LER in diabetic patients with PAD and CLTI.

Optimal preparation is recommended for patients with advanced chronic kidney disease to minimize complications during dialysis initiation. This study evaluated the effects of planned dialysis initiation on survival in patients undergoing incident hemodialysis and peritoneal dialysis. Patients newly diagnosed with end-stage kidney disease who started dialysis were enrolled in a multicenter prospective cohort study in Korea. Planned dialysis was defined as dialysis therapy initiated with permanent access and maintenance of the initial dialysis modality. A total of 2892 patients were followed up for a mean duration of 71.9 ± 36.7 months and 1280 (44.3%) patients initiated planned dialysis. The planned dialysis group showed lower mortality than the unplanned dialysis group during the 1st and 2nd years after dialysis initiation (1st year: adjusted hazard ratio [aHR] 0.51; 95% confidence interval [CI] 0.37-0.72; P < 0.001; 2nd year: aHR 0.71; 95% CI 0.52-0.98, P = 0.037). However, 2 years after dialysis initiation, mortality did not differ between the groups. Planned dialysis showed a better early survival rate in hemodialysis patients, but not in peritoneal dialysis patients. Particularly, infection-related mortality was reduced only in patients undergoing hemodialysis with planned dialysis initiation. Planned dialysis has survival benefits over unplanned dialysis in the first 2 years after dialysis initiation, especially in patients undergoing hemodialysis. It improved infection-related mortality during the early dialysis period.

The relationship between obesity and nonalcoholic fatty liver disease and renal hyperfiltration is controversial. This study aimed to assess the correlations of body mass index and fatty liver index, respectively, with renal hyperfiltration in non-diabetic subjects, considering age, sex, and body surface area.

This cross-sectional study assessed the Japanese health check-up data (FY2018) of 62,379 non-diabetic individuals from a health insurance database. Renal hyperfiltration is the ≥ 95th percentile of estimated glomerular filtration rate (derived by Chronic Kidney Disease Epidemiology Collaboration formula) by gender and age in healthy subjects. After adjusting for potential confounders, multiple logistic regression models were applied to evaluate the correlation of renal hyperfiltration with body mass index categories and fatty liver index (10 equal parts).

A negative and positive correlation, respectively, were noted when the body mass index was < 21 and ≥ 30 in women; however, a positive correlation was noted for BMI < 18.5 and ≥ 30 in men. Renal hyperfiltration prevalence increased when fatty liver index increased for both sexes; the cutoff value for fatty liver index was 14.7 for women and 30.4 for men.

Body mass index and renal hyperfiltration correlated linearly in women; however, in men, the correlation was U-shaped; therefore, differing by sex. However, fatty liver index correlated linearly with renal hyperfiltration in both sexes. Non-alcoholic fatty liver disease might be associated with renal hyperfiltration; Fatty liver index is a simple marker that can be obtained from health check-ups. Since a high fatty liver index correlated with renal hyperfiltration, it may be beneficial to monitor the renal function in such a population.

Introduction Impairment of cognitive functions can commonly develop in patients with chronic kidney disease (CKD) and increase morbidity and mortality. The antioxidant activity of selenium reduces cognitive decline by protecting neurons from free radical damage. We aimed to explore the associations between serum selenium levels, cognitive impairment, and depression in CKD patients in this research. Methods In this prospective cross-sectional research, 100 participants between the ages of 20 and 65 were included, and four groups of 25 patients each were formed (control group, stage 3-4 CKD, peritoneal dialysis [PD], hemodialysis [HD]). The Standardized Mini Mental Test (sMMT) was used to measure cognitive skills, and the Beck Depression Inventory (BDI) was utilized to diagnose depression. Simultaneously, measurements of serum selenium levels were done from collected blood samples. Results Cognitive impairment was detected in 4% of the control group, 16% of CKD patients (n=75), and 30% of the dialysis patients (n=50). Depression was found in 16% of the control group, 40% of the stage 3-4 CKD group, 50% of the PD group, and 44% of the HD group. In the control group, sMMT scores were higher than the other groups (p<0.001 for all), while the BDI score was statistically significantly lower (p=0.003). Serum selenium levels were found to be higher than HD and PD groups in patients with non-dialysis CKD and control groups in the post hoc analyses (p=0.001, p<0.001, p<0.001, p<0.001, respectively). Conclusion Depression and cognitive impairment are particularly prevalent in CKD and dialysis patients. Our results indicate serum selenium insufficiency may be related to depression and cognitive impairment in this patient group. Nonetheless, these findings need to be confirmed by larger-scale studies.

Human epididymis protein-4 (HE-4) is a commonly used biomarker for diagnosing ovarian cancer. Elevated HE-4 has also been observed in various benign conditions including chronic kidney disease (CKD); however, generalizability and statistical power of previous studies have been limited by small sample sizes.

We conducted a retrospective study that included 80 pathologically confirmed ovarian cancer patients, 641 CKD patients, and 2661 healthy controls. Serum HE-4 and several renal function parameters were collected and compared between the three groups. Correlation analysis was conducted to evaluate the relationship between HE-4 and renal function parameters. A receiver operating characteristic curve was established to evaluate its diagnostic performance.

CKD patients had the highest levels of HE-4, with a median of 193.00 pmol/L, while the median in ovarian cancer patients was 90.82 pmol/L. HE-4 levels also increased with CKD progression, and Spearman's rank correlation showed that HE-4 had a strong correlation with renal function parameters in CKD patients. Furthermore, HE-4 exhibited a satisfactory diagnostic performance in both differentiating CKD patients and controls as well as stage 2 CKD patients and controls.

HE-4 can be used as an alternative biomarker for diagnosing CKD as it is less affected by several preanalytical factors. Nevertheless, in clinical practice, elevated HE-4 requires taking both CKD and ovarian cancer into consideration.

Artificial sweeteners are widely used sugar substitutes, but little is known about their long-term effects on cardiometabolic disease risks. Here we examined the commonly used sugar substitute erythritol and atherothrombotic disease risk. In initial untargeted metabolomics studies in patients undergoing cardiac risk assessment (n = 1,157; discovery cohort, NCT00590200 ), circulating levels of multiple polyol sweeteners, especially erythritol, were associated with incident (3 year) risk for major adverse cardiovascular events (MACE; includes death or nonfatal myocardial infarction or stroke). Subsequent targeted metabolomics analyses in independent US (n = 2,149, NCT00590200 ) and European (n = 833, DRKS00020915 ) validation cohorts of stable patients undergoing elective cardiac evaluation confirmed this association (fourth versus first quartile adjusted hazard ratio (95% confidence interval), 1.80 (1.18-2.77) and 2.21 (1.20-4.07), respectively). At physiological levels, erythritol enhanced platelet reactivity in vitro and thrombosis formation in vivo. Finally, in a prospective pilot intervention study ( NCT04731363 ), erythritol ingestion in healthy volunteers (n = 8) induced marked and sustained (>2 d) increases in plasma erythritol levels well above thresholds associated with heightened platelet reactivity and thrombosis potential in in vitro and in vivo studies. Our findings reveal that erythritol is both associated with incident MACE risk and fosters enhanced thrombosis. Studies assessing the long-term safety of erythritol are warranted.