Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex.

BACKGROUND: The accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C-based EKFC equation would increase the accuracy of estimated GFR is unknown. METHODS: We used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex. RESULTS: On the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83 + 0.005 × (age - 50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone. CONCLUSIONS: The EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations. (Funded by the Swedish Research Council.).

Incident heart failure in chronic kidney disease: proteomics informs biology and risk stratification.

BACKGROUND AND AIMS: Incident heart failure (HF) among individuals with chronic kidney disease (CKD) incurs hospitalizations that burden patients and health care systems. There are few preventative therapies, and the Pooled Cohort equations to Prevent Heart Failure (PCP-HF) perform poorly in the setting of CKD. New drug targets and better risk stratification are urgently needed. METHODS: In this analysis of incident HF, SomaScan V4.0 (4638 proteins) was analysed in 2906 participants of the Chronic Renal Insufficiency Cohort (CRIC) with validation in the Atherosclerosis Risk in Communities (ARIC) study. The primary outcome was 14-year incident HF (390 events); secondary outcomes included 4-year HF (183 events), HF with reduced ejection fraction (137 events), and HF with preserved ejection fraction (165 events). Mendelian randomization and Gene Ontology were applied to examine causality and pathways. The performance of novel multi-protein risk models was compared to the PCP-HF risk score. RESULTS: Over 200 proteins were associated with incident HF after adjustment for estimated glomerular filtration rate at P < 1 × 10-5. After adjustment for covariates including N-terminal pro-B-type natriuretic peptide, 17 proteins remained associated at P < 1 × 10-5. Mendelian randomization associations were found for six proteins, of which four are druggable targets: FCG2B, IGFBP3, CAH6, and ASGR1. For the primary outcome, the C-statistic (95% confidence interval [CI]) for the 48-protein model in CRIC was 0.790 (0.735, 0.844) vs. 0.703 (0.644, 0.762) for the PCP-HF model (P = .001). C-statistic (95% CI) for the protein model in ARIC was 0.747 (0.707, 0.787). CONCLUSIONS: Large-scale proteomics reveal novel circulating protein biomarkers and potential mediators of HF in CKD. Proteomic risk models improve upon the PCP-HF risk score in this population.

HbA1c variability is independently associated with progression of diabetic kidney disease in an urban multi-ethnic cohort of people with type 1 diabetes.

AIMS/HYPOTHESIS: The role of HbA1c variability in the progression of diabetic kidney disease is unclear, with most studies to date performed in White populations and limited data on its role in predicting advanced kidney outcomes. Our aim was to evaluate if long-term intra-individual HbA1c variability is a risk factor for kidney disease progression (defined as an eGFR decline of ≥50% from baseline with a final eGFR of <30 ml/min per 1.73 m2) in an ethnically heterogeneous cohort of people with type 1 diabetes with a preserved eGFR ≥45 ml/min per 1.73 m2 at baseline. METHODS: Electronic health record data from people attending outpatient clinics between 2004 and 2018 in two large university hospitals in London were collected. HbA1c variability was assessed using three distinct methods: (1) SD of HbA1c (SD-HbA1c); (2) visit-adjusted SD (adj-HbA1c): SD-HbA1c/√n/(n-1), where n is the number of HbA1c measurements per participant; and (3) CV (CV-HbA1c): SD-HbA1c/mean-HbA1c. All participants had six or more follow-up HbA1c measurements. The eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration equation and clinical/biochemical results from routine care were extracted from electronic health records. RESULTS: In total, 3466 participants (50% female, 78% White, 13% African Caribbean, 3% Asian and 6% of mixed heritage or self-reporting as 'other') were followed for a median (IQR) of 8.2 (4.2-11.6) years. Of this cohort, 249 (7%) showed kidney disease progression. Higher HbA1c variability was independently associated with a higher risk of kidney disease progression, with HRs (95% CIs) of 7.76 (4.54, 13.26), 2.62 (1.75, 3.94) and 5.46 (3.40, 8.79) (lowest vs highest HbA1c variability quartile) for methods 1-3, respectively. Increasing age, baseline HbA1c, systolic BP and urinary albumin/creatinine ratio were also associated with kidney disease progression (p<0.05 for all). African Caribbean ethnicity was associated with an increased risk of kidney disease progression (HR [95% CI] 1.47 [1.09, 1.98], 1.76 [1.32, 2.36] and 1.57 [1.17, 2.12] for methods 1-3, respectively) and this effect was independent of glycaemic variability and other traditional risk factors. CONCLUSIONS/INTERPRETATION: We observed an independent association between HbA1c variability, evaluated using three distinct methods, and significant kidney disease progression in a multi-ethnic type 1 diabetes cohort. Further studies are needed to elucidate the mechanisms that may explain our results and evaluate if HbA1c variability is a modifiable risk factor for preventing diabetic kidney disease progression.

Estimated glucose disposal rate for predicting cardiovascular events and mortality in patients with non-diabetic chronic kidney disease: a prospective cohort study.

BACKGROUND: Evidence suggests that insulin resistance (IR) is an autonomous risk factor for cardiovascular disease (CVD). Nevertheless, the association between estimated glucose disposal rate (eGDR), a novel indicator of IR, and incident CVD and mortality in chronic kidney disease (CKD) patients without diabetes remains uncertain. METHODS: The study included 19,906 participants from the UK Biobank who had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or a urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and no history of CVD and diabetes. Individuals were divided into three categories based on tertiles of eGDR. The outcome was a composite CVD (coronary heart disease (CHD) and stroke) and mortality (all-cause, non-accidental, and cardiovascular mortality). Furthermore, a cohort of 1,600 individuals from the US National Health and Nutrition Examination Survey (NHANES) was applied to validate the association between eGDR and mortality. The Cox proportional hazards regression models were used to examine the association between eGDR and event outcomes. RESULTS: During a follow-up of around 12 years, 2,860 CVD, 2,249 CHD, 783 stroke, 2,431 all-cause, 2,326 non-accidental and 492 cardiovascular deaths were recorded from UK Biobank. Higher eGDR level was not only associated with lower risk of CVD (hazard ratio [HR] 0.641, 95% confidence interval [CI] 0.559-0.734), CHD (HR 0.607, 95% CI 0.520-0.709), stroke (HR 0.748, 95% CI 0.579-0.966), but also related to reduced risk of all-cause (HR 0.803, 95% CI 0.698-0.923), non-accidental (HR 0.787, 95% CI 0.682-0.908), and cardiovascular mortality (HR 0.592, 95% CI 0.423-0.829). Validation analyses from NHANES yielded consistent relationship on mortality. CONCLUSIONS: In these two large cohorts of CKD patients without DM, a higher eGDR level was associated with a decreased risk of CVD and mortality.

Limitations of Parenchymal Volume Analysis for Estimating Split Renal Function and New Baseline Glomerular Filtration Rate After Radical Nephrectomy.

PURPOSE: Accurately predicting new baseline glomerular filtration rate (NBGFR) after radical nephrectomy (RN) can improve counseling about RN vs partial nephrectomy. Split renal function (SRF)-based models are optimal, and differential parenchymal volume analysis (PVA) is more accurate than nuclear renal scans (NRS) for this purpose. However, there are minimal data regarding the limitations of PVA. Our objective was to identify patient-/tumor-related factors associated with PVA inaccuracy. MATERIALS AND METHODS: Five hundred and ninety-eight RN patients (2006-2021) with preoperative CT/MRI were retrospectively analyzed, with 235 also having NRS. Our SRF-based model to predict NBGFR was: 1.25 × (GlobalGFRPre-RN × SRFContralateral), where GFR indicates glomerular filtration rate, with SRF determined by PVA or NRS, and with 1.25 representing the median renal functional compensation in adults. Accuracy of predicted NBGFR within 15% of observed was evaluated in various patient/tumor cohorts using multivariable logistic regression analysis. RESULTS: PVA and NRS accuracy were 73%/52% overall, and 71%/52% in patients with both studies (n = 235, P < .001), respectively. PVA inaccuracy independently associated with pyelonephritis, hydronephrosis, renal vein thrombosis, and infiltrative features (all P < .03). Ipsilateral hydronephrosis and renal vein thrombosis associated with PVA underprediction, while contralateral hydronephrosis and increased age associated with PVA overprediction (all P < .01). NRS inaccuracy was more common and did not associate with any of these conditions. Even among cohorts where PVA inaccuracy was observed (22% of our patients), there was no significant difference in the accuracies of NRS- and PVA-based predictions. CONCLUSIONS: PVA was more accurate for predicting NBGFR after RN than NRS. Inaccuracy of PVA correlated with factors that distort the parenchymal volume/function relationship or alter renal functional compensation. NRS inaccuracy was more common and unpredictable, likely reflecting the inherent inaccuracy of NRS. Awareness of cohorts where PVA is less accurate can help guide clinical decision-making.

Potential utility of renal functional reserve testing in clinical nephrology.

PURPOSE OF REVIEW: The aim of this review is to discuss the concept of renal functional reserve (RFR) and its potential relevance in clinical practice. RECENT FINDINGS: The RFR is a measure of the change in glomerular filtration rate (GFR) from baseline to a peak value when the kidney is stimulated to increase its function. This concept has a strong physiologic basis in nephrology and the presence, magnitude or absence of RFR capacity may have prognostic significance in many clinical scenarios where individuals are at risk of hyperfiltration or kidney dysfunction. Unlike in other medical specialties, where organ reserve function is reliably measurable and used routinely, measurement of RFR in nephrology has not been integrated into clinical care. Methodologic challenges including standardization of methods to stimulate GFR and the ability of measures of GFR to discriminate acute dynamic changes in GFR upon kidney stimulation have hampered the robustness and use of RFR measurements in research and clinical care. SUMMARY: Given the emergence of many new disease-modifying therapies in nephrology, it is imperative that we move forward and develop more robust tools to further our understanding of kidney physiology and pathophysiology, such as the RFR, which should be integrated into research and clinical care to support optimal personalization of therapeutic kidney care strategies.

Glomerular Filtration Rate Estimation Using ß2-Microglobulin and ß-Trace Protein in Adults With Solid Tumors: A Prospective Cross-Sectional Study.

RATIONALE & OBJECTIVE: ß2-Microglobulin (B2M) and ß-trace protein (BTP) are novel endogenous filtration markers that may improve the accuracy of estimated glomerular filtration rate (eGFR) beyond creatinine and cystatin C (eGFRcr-cys), but they have not been assessed in patients with cancer. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: Prospective cohort of 1,200 patients with active solid tumors recruited between April 2015 and September 2017. EXPOSURE: CKD-EPI equations without race combining B2M and/or BTP with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR). OUTCOME: Performance of equations compared with eGFRcr-cys and non-GFR determinants of serum B2M and BTP (SB2M, and SBTP, respectively). Measured GFR (mGFR) was determined using the plasma clearance of chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA). ANALYTICAL APPROACH: Bias was defined as the median of the differences between mGFR and eGFR, and 1-P30 was defined as the percentage of estimates that differed by more than 30% from the mGFR (1-P30). Linear regression was used to assess association of clinical and laboratory variables with SB2M, and SBTP after adjustment for mGFR. RESULTS: Mean age and mGFR were 58.8±13.2 SD years and 78.4±21.7 SD mL/min/1.73m2, respectively. Performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys (lesser bias and 1-P30). Performance of 2-marker panel equations was as good as eGFRcr-cys (lesser bias and similar 1-P30). SB2M and SBTP were not strongly influenced by cancer site. LIMITATIONS: Participants may have had better clinical performance status than the general population of patients with solid tumors. CONCLUSIONS: B2M and BTP can improve the accuracy of eGFR and may be useful as confirmatory tests in patients with solid tumors, either by inclusion in a multimarker panel equation with creatinine and cystatin C, or by substituting for cystatin C in combination with creatinine. PLAIN-LANGUAGE SUMMARY: The most accurate method to assess estimate kidney function is estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys). We studied whether using ß2-microglobulin (B2M) and/or ß-trace protein (BTP) with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR) might be useful in patients with active solid tumors. The performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys. Performance of 2-marker panel equations was as good as eGFRcr-cys. We conclude that B2M and BTP can improve the accuracy of eGFR and may be useful as a confirmatory test in patients with solid tumors either by inclusion in multimarker panel equation with creatinine and cystatin C or by substituting for cystatin C in combination with creatinine.

Associations of Baseline and Longitudinal Serum Uromodulin With Kidney Failure and Mortality: Results From the African American Study of Kidney Disease and Hypertension (AASK) Trial.

RATIONALE & OBJECTIVE: Uromodulin (UMOD) is the most abundant protein found in urine and has emerged as a promising biomarker of tubule health. Circulating UMOD is also detectable, but at lower levels. We evaluated whether serum UMOD levels were associated with the risks of incident kidney failure with replacement therapy (KFRT) and mortality. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: Participants in AASK (the African American Study of Kidney Disease and Hypertension) with available stored serum samples from the 0-, 12-, and 24-month visits for biomarker measurement. PREDICTORS: Baseline log-transformed UMOD and change in UMOD over 2 years. OUTCOMES: KFRT and mortality. ANALYTICAL APPROACH: Cox proportional hazards and mixed-effects models. RESULTS: Among 500 participants with baseline serum UMOD levels (mean age, 54y; 37% female), 161 KFRT events occurred during a median of 8.5 years. After adjusting for baseline demographic factors, clinical factors, glomerular filtration rate, log-transformed urine protein-creatinine ratio, and randomized treatment groups, a 50% lower baseline UMOD level was independently associated with a 35% higher risk of KFRT (adjusted HR, 1.35; 95% CI, 1.07-1.70). For annual UMOD change, each 1-standard deviation lower change was associated with a 67% higher risk of KFRT (adjusted HR, 1.67; 95% CI, 1.41-1.99). Baseline UMOD and UMOD change were not associated with mortality. UMOD levels declined more steeply for metoprolol versus ramipril (P<0.001) as well as for intensive versus standard blood pressure goals (P = 0.002). LIMITATIONS: Small sample size and limited generalizability. CONCLUSIONS: Lower UMOD levels at baseline and steeper declines in UMOD over time were associated with a higher risk of subsequent KFRT in a cohort of African American adults with chronic kidney disease and hypertension. PLAIN-LANGUAGE SUMMARY: Prior studies of uromodulin (UMOD), the most abundant protein in urine, and kidney disease have focused primarily on urinary UMOD levels. The present study evaluated associations of serum UMOD levels with the risks of kidney failure with replacement therapy (KFRT) and mortality in a cohort of African American adults with hypertension and chronic kidney disease. It found that participants with lower levels of UMOD at baseline were more likely to experience KFRT even after accounting for baseline kidney measures. Similarly, participants who experienced steeper annual declines in UMOD also had a heightened risk of kidney failure. Neither baseline nor annual change in UMOD was associated with mortality. Serum UMOD is a promising biomarker of kidney health.

Quantitatively Predicting Effects of Exercise on Pharmacokinetics of Drugs Using a Physiologically Based Pharmacokinetic Model.

Exercise significantly alters human physiological functions, such as increasing cardiac output and muscle blood flow and decreasing glomerular filtration rate (GFR) and liver blood flow, thereby altering the absorption, distribution, metabolism, and excretion of drugs. In this study, we aimed to establish a database of human physiological parameters during exercise and to construct equations for the relationship between changes in each physiological parameter and exercise intensity, including cardiac output, organ blood flow (e.g., muscle blood flow and kidney blood flow), oxygen uptake, plasma pH and GFR, etc. The polynomial equation P = ΣaiHRi was used for illustrating the relationship between the physiological parameters (P) and heart rate (HR), which served as an index of exercise intensity. The pharmacokinetics of midazolam, quinidine, digoxin, and lidocaine during exercise were predicted by a whole-body physiologically based pharmacokinetic (WB-PBPK) model and the developed database of physiological parameters following administration to 100 virtual subjects. The WB-PBPK model simulation results showed that most of the observed plasma drug concentrations fell within the 5th-95th percentiles of the simulations, and the estimated peak concentrations (Cmax) and area under the curve (AUC) of drugs were also within 0.5-2.0 folds of observations. Sensitivity analysis showed that exercise intensity, exercise duration, medication time, and alterations in physiological parameters significantly affected drug pharmacokinetics and the net effect depending on drug characteristics and exercise conditions. In conclusion, the pharmacokinetics of drugs during exercise could be quantitatively predicted using the developed WB-PBPK model and database of physiological parameters. SIGNIFICANCE STATEMENT: This study simulated real-time changes of human physiological parameters during exercise in the WB-PBPK model and comprehensively investigated pharmacokinetic changes during exercise following oral and intravenous administration. Furthermore, the factors affecting pharmacokinetics during exercise were also revealed.

Frail hypertensive older adults with prediabetes and chronic kidney disease: insights on organ damage and cognitive performance - preliminary results from the CARYATID study.

BACKGROUND: Hypertension and chronic kidney disease (CKD) pose significant public health challenges, sharing intertwined pathophysiological mechanisms. Prediabetes is recognized as a precursor to diabetes and is often accompanied by cardiovascular comorbidities such as hypertension, elevating the risk of pre-frailty and frailty. Albuminuria is a hallmark of organ damage in hypertension amplifying the risk of pre-frailty, frailty, and cognitive decline in older adults. We explored the association between albuminuria and cognitive impairment in frail older adults with prediabetes and CKD, assessing cognitive levels based on estimated glomerular filtration rate (eGFR). METHODS: We conducted a study involving consecutive frail older patients with hypertension recruited from March 2021 to March 2023 at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, followed up after three months. Inclusion criteria comprised age over 65 years, prior diagnosis of hypertension without secondary causes, prediabetes, frailty status, Montreal Cognitive Assessment (MoCA) score < 26, and CKD with eGFR > 15 ml/min. RESULTS: 237 patients completed the study. We examined the association between albuminuria and MoCA Score, revealing a significant inverse correlation (r: 0.8846; p < 0.0001). Subsequently, we compared MoCA Score based on eGFR, observing a significant difference (p < 0.0001). These findings were further supported by a multivariable regression analysis, with albuminuria as the dependent variable. CONCLUSIONS: Our study represents the pioneering effort to establish a significant correlation between albuminuria and eGFR with cognitive function in frail hypertensive older adults afflicted with prediabetes and CKD.

Which is the best glomerular filtration marker: Creatinine, cystatin C or both?

BACKGROUND: The glomerular filtration rate (GFR) is estimated by the serum or plasma concentration of creatinine and/or cystatin C using equations that include demographic data. The equations worldwide most widely used are those of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) consortium and updated in 2021 to remove the Afro-American racial correction factor. In 2021 and then in 2023, the European Kidney Function Consortium also developed equations based on creatinine and cystatin C, usable across the full age spectrum, and constructed by including the Q value (i.e. the median creatinine or cystatin C in healthy men and women, which is customizable for specific populations). METHODS: The aim of this narrative review is to examine the strengths and weaknesses of each biomarker. RESULTS: Both biomarkers have non-GFR determinants, namely muscle mass, protein intake and tubular secretion for creatinine; dysthyroidism and systemic corticosteroids for cystatin C, as well as other more debated determinants (diabetes, obesity, proteinuria, inflammatory syndrome). These non-GFR determinants are the reason why no equation based on a single endogenous biomarker has an accuracy within 30% greater than 90% over the entire age spectrum (in at least one patient in 10, estimated GFR is at least 30% higher or at least 30% lower than the measured GFR). CONCLUSION: Equations combining the two biomarkers provide a better estimate of GFR, particularly in the subgroup of patients whose estimates based on each of the biomarkers are highly discordant. These patients must also be identified as being at increased risk of morbidity, particularly cardiovascular, and mortality.

Lean body mass in living kidney donors impacts postoperative renal function.

PURPOSE: A living donor kidney transplant is the optimal treatment for chronic renal impairment. Our objective is to assess if lean skeletal muscle mass and donor factors such as body mass index, hypertension, and age impact on renal function following donor nephrectomy. METHODS: Potential donors undergo CT angiography as part of their work-up in our institution. Using dedicated software (Horos®), standardized skeletal muscle area measured at the L3 vertebrae was calculated. When corrected for height, skeletal muscle index can be derived. Skeletal muscle mass index below predefined levels was classified as sarcopenic. The correlation of CT-derived skeletal muscle index and postoperative renal function at 12 months was assessed. Co-variables including donor gender, age, body mass index (BMI), and presence of pre-op hypertension were also assessed for their impact on postoperative renal function. RESULTS: 275 patients who underwent living donor nephrectomy over 10 years were included. Baseline pre-donation glomerular filtration rate (GFR) and renal function at one year post-op were similar between genders. 29% (n = 82) of patients met the criteria for CT-derived sarcopenia. Sarcopenic patients were more likely to have a higher GFR at one year post-op (69.3 vs 63.9 mL/min/1.73 m2, p < 0.001). The main factors impacting better renal function at one year were the presence of sarcopenia and younger age at donation. CONCLUSION: When selecting donors, this study highlights that patients with low skeletal mass are unlikely to underperform in terms of recovery of their renal function postoperatively at one year when compared to patients with normal muscle mass and should not be a barrier to kidney donation.

Association of sarcopenia with rapid kidney function decline and chronic kidney disease in adults with normal kidney function.

The association between sarcopenia and kidney function remains poorly investigated. We aimed to evaluate the associations between sarcopenia status and kidney function (rapid kidney function decline and chronic kidney disease (CKD)) in middle-aged and older Chinese population. A total of 9375 participants from the China Health and Retirement Longitudinal Study 2011 were included in the cross-sectional analyses. A total of 5864 participants with eGFRcr-cys ≥ 60 ml/min per 1·73 m2 at baseline were included in the longitudinal analyses and were followed up in 2015. Sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 criteria. In the cross-sectional analyses, possible sarcopenia and sarcopenia were significantly associated with an increased risk of CKD. During the 4 years of follow-up, 359 (6·12 %) participants experienced rapid decline in kidney function and 126 (2·15 %) participants developed CKD. After multivariable adjustment of baseline eGFRcr-cys level and other risk factors, possible sarcopenia (OR, 1·33; 95 % CI 1·01, 2·12) and sarcopenia (OR, 1·49; 95 % CI 1·05, 2·12) were associated with an increased risk of primary outcome (composite of rapid decline in kidney function (annualised decline in eGFRcr-cys ≥ 5 ml/min per 1·73 m2) and progression to CKD (eGFRcr-cys < 60 ml/min per 1·73 m2). Individuals with low muscle mass or low muscle strength alone also had an increased risk of rapid decline in kidney function and progression to CKD.

Mother-child correlation of kidney function: data from the Yamanashi Adjunct Study of Japan Environment and Children's Study (JECS).

BACKGROUND: Individual variation in kidney function can be affected by both congenital and acquired factors, and kidney function in children is possibly correlated with that in their mothers. However, the mother-child correlation in kidney function remains directly unconfirmed. METHODS: We conducted a cross-sectional study of 655 healthy pairs of 7- or 8-year-old children and their mothers as an adjunct study of a nationwide epidemiological study (Japan Environment and Children's Study). RESULTS: Both serum creatinine level (all children, r = 0.324, p < 0.001; girls, r = 0.365, p < 0.001; boys, r = 0.278, p < 0.001) and estimated glomerular filtration rate (eGFR) (r = 0.274, p < 0.001; r = 0.352, p < 0.001; r = 0.195, p < 0.001, respectively) in children were weakly associated with their maternal values. In the single linear regression analyses, maternal values of serum creatinine and eGFR were significantly associated with the children's values. Moreover, several body composition values in children, such as weight-SDS, fat (%), and predicted muscle weight, were also significantly associated with kidney function values in children. In the multiple linear regression analysis for serum creatinine levels in children, in which weight-SDS and predicted muscle weight in children were selected as adjustment factors, maternal serum creatinine level showed a significant positive association (B = 0.214, p < 0.001 in the adjusted model). Moreover, in the multiple linear regression analysis for eGFR value in children, in which fat (%) and predicted muscle weight in children were selected as adjustment factors, maternal eGFR values showed a significant positive association (B = 0.319, p < 0.001). CONCLUSIONS: We directly confirmed mother-child correlations in both serum creatinine levels and eGFR values, particularly in girls. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

To retrieve values of albuminuria to define the size of CKD patients eligible to SGLT-2Is: An explorative analysis using a primary care database.

PURPOSE: To address missingness of albuminuria values, which establish the eligibility to SGLT-2Is for patients with CKD, using the multiple imputation (MI) method. METHODS: We selected patients aged 18 or older and diagnosed with CKD in a primary care database. Those with severe CKD and/or previously treated with SGLT-2Is were excluded. Then, we collected all available information on albuminuria within 90 days the measure of GFR. A value of albumin-creatinine ratio (ACR) ranging 200-5000 mg/g or otherwise was the response variable on which we ran MI. Using logistic regression, odds ratios (OR) and related 95% confidence intervals (CI) were estimated for each covariate toward the response variable for both full and imputed dataset. RESULTS: The determinants showed consistent estimates between the full and imputed datasets as demonstrated by the overlaps of the CIs and the similar point estimates. As expected, there were some exceptions, such as diabetes (OR of 1.2 vs. 0.5) and use of diabetic medications (OR of 1.0 vs. 2.1) and/or statins (OR of 1.1 vs. 1.8). CONCLUSIONS: Besides being a reminder for GPs to prescribe and register albuminuria in certain patients' categories, these determinants might be translated into an operational algorithm to input ACR values in administrative data sources. Scenarios for the reimbursement criteria regulating SGLT-2Is to treat CKD would be therefore simulated on more inferable estimates.

Association between renal insufficiency and lesion characteristics of posterior reversible encephalopathy syndrome.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is characterized by cerebral blood flow dysregulation and the blood-brain barrier (BBB) disruption. While renal insufficiency has been considered a factor in BBB fragility, the relationship between renal insufficiency and the PRES lesions volume remains unclear. METHODS: This observational study was performed retrospectively. PRES patients were categorized into two groups with renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2 on the day of symptom occurrence. Lesion volume was measured using fluid-attenuated inversion recovery (FLAIR) imaging, and the brain was divided into nine regions. The volume of the parietal-occipital-temporal lobe was considered typical, while the other six regions were labeled as atypical. RESULTS: The study included 200 patients, of whom 94 (47%) had renal insufficiency. Patients with renal insufficiency had a larger lesion volume (144.7 ± 125.2 cc) compared to those without renal insufficiency (110.5 ± 93.2 cc; p = 0.032); particularly in the atypical lesions volume (49.2 ± 65.0 vs. 29.2 ± 44.3 cc; p = 0.013). However, there was no difference in the reversibility of the lesions (35.2 ± 67.5 vs. 18.8 ± 33.4 cc; p = 0.129). Multiple regression analysis revealed that decreases in eGFR (ß = -0.34, 95% CI -0.62-0.05, p = 0.020) were positively associated with total lesion volume. CONCLUSION: Our findings suggest that PRES patients with renal insufficiency experience more severe lesion volumes, likely due to the atypical brain regions involvement. The lesions involving atypical regions may have a similar pathophysiology to typical lesions, as the PRES lesions reversibility was found to be similar between individuals with and without renal insufficiency.

Association of remnant cholesterol with decreased kidney function or albuminuria: a population-based study in the U.S.

BACKGROUND: Dyslipidemia is frequently exhibited in individuals with chronic kidney disease (CKD). Remnant cholesterol (RC), an emerging novel lipid marker, plays an elusive role in CKD progression. This study sought to investigate the association of RC with decreased kidney function or albuminuria in the general population of U.S. METHOD: Data were retrieved from the continuous 2001 to 2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Individuals aged between 18 and 70 years were included. RC was divided into quartiles. Albuminuria was defined by albumin-to-creatinine ratio (ACR) ≥30 mg/g, while reduced kidney function was described as an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2. Using a multivariable regression model, the association of RC with decreased eGFR or albuminuria was examined. The dose‒response relationship between RC and eGFR or ACR was also investigated using a restricted cubic spline (RCS) model. RESULTS: A total of 1551 (10.98%) participants with impaired renal function or albuminuria were identified. After multivariate adjustment, RC was not significantly associated with kidney function decline or albuminuria (odds ratio (OR) 1.24, 95% confidence interval (95% CI): 0.95, 1.61). However, a significantly inverse correlation was observed between RC and eGFR in a dose‒response manner (ß -2.12, 95% CI: -3.04, -1.21). This association remained consistent when stratifying data by gender, age, race, hypertension, diabetes and body mass index (BMI). CONCLUSION: A higher RC was significantly correlated with a lower eGFR in the general population. The role of RC in predicting kidney outcomes needed further investigation in prospective studies.

Association between kidney function and Parkinson's disease risk: a prospective study from the UK Biobank.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative influenced by various clinical factors. The potential relationship between renal function and the risk of PD remains poorly understood. This study aims to explore the association between kidney function and the risk of developing PD. METHODS: A population-based cohort study was conducted using data from 400,571 UK Biobank participants. Renal function was assessed using the estimated glomerular filtration rate (eGFR), calculated from serum creatinine and cystatin C levels. The association between eGFR levels and PD risk was evaluated using univariate and multivariate Cox regression analyses, Restricted Cubic Spline (RCS) analysis, and Kaplan-Meier analysis. Additionally, a clinical prediction model was developed and its diagnostic accuracy was evaluated using ROC analysis. A heatmap was also constructed to examine the relationship between clinical factors and gray matter volume in various brain regions. RESULTS: Over a median observation period of 13.8 years, 2740 PD events were recorded. Cox regression and Kaplan-Meier analyses revealed a significant association between decreased eGFR and increased PD risk, particularly in participants with eGFR < 30 ml/min/1.73 m2. This association was confirmed across three adjusted models. RCS analysis demonstrated a nonlinear relationship between decreasing eGFR and increasing PD risk. Furthermore, changes in eGFR were correlated with alterations in subcortical gray matter volume in regions such as the frontal cortex, striatum, and cerebellum. The clinical prediction model showed high diagnostic accuracy with AUC values of 0.776, 0.780, and 0.824 for 4-, 8-, and 16-year predictions, respectively. CONCLUSION: Renal insufficiency is significantly associated with an increased risk of PD, highlighting the importance of maintaining good kidney function as a potential preventive measure against PD.

The Retinal Blood Flow Density Is Related to the Pathological Severity of Diabetic Kidney Disease.

INTRODUCTION: This study aimed to investigate the correlation between fundus blood flow parameters and the severity of pathological biopsy in patients with diabetic kidney disease (DKD). METHODS: Data of patients with type 2 diabetes mellitus who completed renal pathology biopsies and optical coherence tomography angiography (OCTA) examinations, including renal function, 24-h urine protein quantification, and macular flow imaging, were collected. DKD pathology biopsies were graded as stages 1-4, and differences and correlations of the parameters were compared between groups. The grading was transformed into early (stage 1) and late (stages 2-4), and regression analyses were conducted to develop a model, draw a nomogram, and test efficacy. RESULTS: This study included 157 eyes from 157 individuals in total. Urinary microalbumin and to urinary creatinine ratio (mALB/NCR) increased with pathological grading, whereas while glomerular filtration rate was decreased (p < 0.01). Corresponding retinal blood flow in superficial, deep, and full paracentral rings was decreased, which correlated with pathological grading (p < 0.01), with the highest blood flow density in the whole layer (r2 = -0.707). Meaningfully, in the early DKD model (area under the curve = 0.929 [0.889-0.970], p < 0.01), whole-layer blood flow density, mALB/NCR, and diabetes duration were statistically significant. CONCLUSIONS: The decrease in macular retinal blood flow density detected by OCTA is closely associated with the increase in pathological grading of DKD and can be used as a noninvasive parameter for monitoring early changes in DKD.

Assessment of renal function in persons with motor complete spinal cord injury-cystatin C as an accurate single marker.

STUDY DESIGN: Observational cohort. AIM: To show that Cystatin C is an accurate single marker to estimate GFR in motor complete persons with SCI. OBJECTIVES: To assess if Cystatin C is an accurate for estimating GFR in persons with SCI with no preserved motor power. To study if use of Serum creatinine for estimation of GFR in this population significantly overestimates GFR, thereby inaccurate. SETTING: Tertiary care hospital and Medical College, Vellore, South India. METHODS: 30 persons with SCI (ASIA A and B) fulfilling the inclusion criteria were recruited. Serum Creatinine and Serum Cystatin C values were obtained, and eGFR was calculated based on available formulae. 24-h urine for urine creatinine clearance-based eGFR was used as a reference value. RESULTS: Analysis with a Bland-Atman plot showed that eGFR estimated with Serum Cystatin C was more accurate than Serum Creatinine, using 24-h urine creatinine as a reference value. eGFR using Serum Creatinine significantly overestimated GFR by over 50.6%. Estimated GFR using Serum Cystatin C showed a meager mean difference of 0.5% from the reference 24-h urine creatinine clearance (mean difference of -2.56%). CONCLUSION: Serum Cystatin C is a much more accurate marker for estimating GFR in SCI, compared to serum Creatinine which overestimates GFR.