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.

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.

Recent Update on Acute Kidney Injury-to-Chronic Kidney Disease Transition.

Acute kidney injury (AKI) is characterized by an abrupt decline of excretory kidney function. The incidence of AKI has increased in the past decades. Patients diagnosed with AKI often undergo diverse clinical trajectories, such as early or late recovery, relapses, and even a potential transition from AKI to chronic kidney disease (CKD). Although recent clinical studies have demonstrated a strong association between AKI and progression of CKD, our understanding of the complex relationship between AKI and CKD is still evolving. No cohort study has succeeded in painting a comprehensive picture of these multi-faceted pathways. To address this lack of understanding, the idea of acute kidney disease (AKD) has recently been proposed. This presents a new perspective to pinpoint a period of heightened vulnerability following AKI, during which a patient could witness a substantial decline in glomerular filtration rate, ultimately leading to CKD transition. Although AKI is included in a range of kidney conditions collectively known as AKD, spanning from mild and self-limiting to severe and persistent, AKD can also occur without a rapid onset usually seen in AKI, such as when kidney dysfunction slowly evolves. In the present review, we summarize the most recent findings about AKD, explore the current state of biomarker discovery related to AKD, discuss the latest insights into pathophysiological underpinnings of AKI to CKD transition, and reflect on therapeutic challenges and opportunities that lie ahead.

Risk factors for lower renal compensation after nephrectomy: an analysis of living kidney donors in an Amazonian cohort.

INTRODUCTION: Living donor kidney transplantation is considered the ideal renal replacement therapy because it has a lower complication rate and allows an efficient response to the high demand for grafts in the healthcare system. Careful selection and adequate monitoring of donors is a key element in transplantation. Individuals at greater risk of developing kidney dysfunction after nephrectomy must be identified. OBJECTIVE: To identify risk factors associated with a renal compensation rate (CR) below 70% 12 months after nephrectomy. METHODS: This observational retrospective longitudinal study included living kidney donors followed up at the Lower Amazon Regional Hospital between 2016 and 2022. Data related to sociodemographic variables, comorbid conditions and kidney function parameters were collected. RESULTS: The study enrolled 32 patients. Fourteen (43.75%) had a CR < 70% 12 months after kidney donation. Logistic regression found obesity (Odds Ratio [95%CI]: 10.6 [1.7-65.2]), albuminuria (Odds Ratio [95%CI]: 2.41 [1.2-4.84]) and proteinuria (Odds Ratio [95%CI]: 1.14 [1.03-1.25]) as risk factors. Glomerular filtration rate was a protective factor (Odds Ratio [95% CI]: 0.92 [0.85-0.99]). CONCLUSION: Obesity, albuminuria and proteinuria adversely affected short-term renal compensation rate. Further studies are needed to uncover the prognostic implications tied to these risk factors. Our findings also supported the need for careful individualized assessment of potential donors and closer monitoring of individuals at higher risk.

Circulating TNF receptor levels are associated with estimated glomerular filtration rate even in healthy individuals with normal kidney function.

The association between serum tumor necrosis factor receptor (TNFRs: TNFR1, TNFR2) levels and estimated glomerular filtration rate (eGFR) observed in patients with diabetes has not been comprehensively tested in healthy subjects with normal kidney function. It also remains unclear whether TNFR levels differ by age and sex, and between healthy subjects and diabetics. We measured serum TNFR levels in 413 healthy subjects and 292 patients with type 2 diabetes. In healthy subjects, TNFR levels did not differ between men and women. Additionally, TNFR2, but not TNFR1, levels increased with age. In multivariate analysis, TNFR1 was associated only with cystatin C-based eGFR (eGFR-CysC), whereas TNFR2 was associated with systolic blood pressure in addition to eGFR-CysC. Both TNFRs were associated with lower eGFR (eGFR-Cys < 90 mL/min/1.73 m2) even after adjustment for relevant clinical factors. Upon combining healthy subjects and patients with diabetes, the presence of diabetes and elevated glycated hemoglobin level were significant factors in determining TNFR levels. TNFR levels were associated with eGFR-CysC, but were not affected by age and sex in healthy subjects with normal kidney function. TNFR levels in patients with diabetes appeared to be higher than in healthy subjects.

Development of a formula for estimated glomerular filtration rate in pregnant women from physiological hyperfiltration of serum creatinine.

Increased body fluids during pregnancy complicates the application of estimated glomerular filtration rate (eGFR) formulas that are based on body surface area. Furthermore, gestational renal dysfunction cannot be identified if the serum creatinine (SCr) concentration is within the non-pregnant reference interval (RI) despite inadequate pregnancy-related renal hyperfiltration. 1484 SCr measurements from 957 healthy pregnant women were collected. The average SCr value of gestational week (GW) 0-3 was the representative SCr value of non-pregnant status. While the distribution of SCr measurements varied across GWs, it was transformed into a normal distribution using the bootstrap resampling method. A polynomial linear regression method was applied to achieve a continuous and smooth transformation of values. The normally distributed SCr values of each GW were compared to the non-pregnant status, leading to the calculation of SCr hyperfiltration. The final equation, (2 - SCr (µmol/L) / 55.25) × 103.1 × 55.25/(56.7 - 0.223 × GW - 0.113 × GW2 + 0.00545 × GW3 - 0.0000653 × GW4), and reference intervals for both SCr and eGFR for each GW were obtained. These RIs and novel equations can be effectively used to monitor renal dysfunction in pregnant women.

Urinary Prostaglandin E2 Excretion and the Risk of Cardiovascular and Kidney Disease.

BACKGROUND: Inhibition of prostaglandin synthesis by nonsteroidal anti-inflammatory drugs is associated with cardiovascular mortality and kidney disease. This study hypothesizes that urinary prostaglandin E2 (PGE2) and PGE2 metabolite (PGEM) excretions are markers of cardiovascular and kidney health, because they reflect both systemic and kidney-derived PGE2 production. METHODS AND RESULTS: PGE2 and PGEM were measured in spot urine samples from 2291 participants (≥55 years old) of the population-based Rotterdam Study. Urinary PGE2 and PGEM excretions were analyzed using linear regression analyses to identify cross-sectional associations with cardiovascular risk factors and baseline estimated glomerular filtration rate (eGFR). Longitudinal associations with cardiovascular mortality and kidney outcomes (eGFR <60 or <45 mL/min per 1.73 m2 and the composite outcome 40% eGFR loss or kidney failure) were assessed with Cox regression. Urinary PGE2 and PGEM excretions were higher with increasing age, lower eGFR, smoking, diabetes, and albuminuria. A 2-fold higher urinary PGE2 and PGEM excretion was associated with a higher risk of cardiovascular mortality (28 825 patient-years; 160 events; PGE2 hazard ratio [HR], 1.27, [95% CI, 1.06-1.54]; PGEM HR, 1.36 [95% CI, 1.10-1.67]). Higher PGE2 excretions were also associated with a higher risk of incident eGFR <60 mL/min per 1.73 m2 (31 530 person-years; 691 events; HR, 1.13 [95% CI, 1.02-1.25]) with similar HRs for the other kidney outcomes. CONCLUSIONS: Urinary PGE2 and PGEM excretions are novel markers for the presence and progression of cardiovascular and kidney disease. Future studies should address whether these associations are causal and can be targeted to improve cardiovascular and kidney outcomes.

Cumulative blood pressure load and hypertensive nephropathy in Han Chinese hypertensive patients.

The study aims to assess the relationship between cumulative blood pressure load (cBPL) and the risk of renal function decline in hypertensive patients and determine the blood pressure (BP) threshold required to prevent hypertensive nephropathy. A single-center prospective cohort study was conducted on hypertensive patients. The cBPL was defined as the proportion of area beyond variable BP cutoffs under ambulatory BP monitoring. Renal events were defined as > 25% (minor) or > 50% (major) decline of baseline estimated glomerular filtration rate (eGFR). Cox regression analysis was conducted between cBPL, other ambulatory BP parameters, and renal events. The results revealed a total of 436 Han Chinese hypertensive patients were eligible for enrollment. During an average follow-up period of 5.1 ± 3.3 years, a decline of > 25% and > 50% in eGFR was observed in 77 and eight participants, respectively. Cox regression analysis revealed that cSBPL140 (hazard ratio [HR], 1.102; 95% confidence interval [CI], 1.017-1.193; p = .017), cSBPL130 (HR, 1.076; 95% CI, 1.019-1.137; p = .008), and cSBPL120 (HR, 1.054; 95% CI, 1.010-1.099; p = .015) were independently associated with minor renal events. Similarly, cSBPL140 (HR, 1.228; 95% CI, 1.037-1.455; p = .017), cSBPL130 (HR, 1.189; 95% CI, 1.045-1.354; p = .009), and cSBPL120 (HR, 1.155; 95% CI, 1.039-1.285; p = .008) were independently associated with major renal events. In conclusion, cBPL is associated with renal function decline in hypertensive patients. Minimizing cBPL120 may decrease the risk of hypertensive nephropathy.

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.

[Novel equations for estimating renal function: significance for drug dose adjustment]. / Neue Formeln zur Schätzung der Nierenfunktion ­ Bedeutung für die Dosierung nierengängiger Arzneimittel.

BACKGROUND: Important therapeutic decisions depend on kidney function, which is why its correct assessment is of great importance. It also plays an important role for drug dose adjustments in patients with impaired kidney function. OBJECTIVES: In clinical practice, kidney function is almost always estimated using mathematical glomerular filtration rate (GFR) equations. To estimate GFR, the patient's age and gender as well as kidney-specific endogenous biomarkers are required. This work aims to provide an overview of the advantages and disadvantages of the biomarkers serum creatinine and cystatin C in assessing kidney function. Particularly in patients with significantly reduced or increased muscle mass, creatinine is not suitable for determining GFR, and cystatin C should be used. Currently recommended GFR estimating equations are described, illustrating for which patient groups they can be used. CURRENT DATA: A large number of high-ranking publications are available investigating the validity of GFR estimating equations and the optimal choice of endogenous biomarkers. However, there are still large gaps when it comes to drug approval studies in older patients and children. CONCLUSION: Estimated GFR (eGFR) is only a rough estimate of kidney function and should not be interpreted as an exact number. Drug dose adjustments may be necessary in patients with an eGFR of < 50 ml/min and should be verified particularly in severely impaired GFR (< 30 ml/min). There are tools available online for this purpose.

Long-Term Renal Involvement in Association with Fontan Circulation.

Multiorgan dysfunction is a concern of Fontan patients. To clarify the pathophysiology of Fontan nephropathy, we characterize renal disease in the long-term observational study. Medical records of 128 consecutive Fontan patients [median age: 22 (range 15-37) years old] treated between 2009 and 2018 were reviewed to investigate the incidence of nephropathy and its association with other clinical variables. Thirty-seven patients (29%) showed proteinuria (n = 34) or < 90 mL/min/1.73 m2 of estimated glomerular filtration rate (eGFR) (n = 7), including 4 overlapping cases. Ninety-six patients (75%) had liver dysfunction (Forns index > 4.21). Patients with proteinuria received the Fontan procedure at an older age [78 (26-194) vs. 56 (8-292) months old, p = 0.02] and had a higher cardiac index [3.11 (1.49-6.35) vs. 2.71 (1.40-4.95) L/min/m2, p = 0.02], central venous pressure [12 (7-19) vs. 9 (5-19) mmHg, p < 0.001], and proportion with > 4.21 of Forns index (88% vs. 70%, p = 0.04) than those without proteinuria. The mean renal perfusion pressure was lower in patients with a reduced eGFR than those without it [55 (44-65) vs. 65 (45-102) mmHg, p = 0.03], but no other variables differed significantly. A multivariable analysis revealed that proteinuria was associated with an increased cardiac index (unit odds ratio 2.02, 95% confidence interval 1.12-3.65, p = 0.02). Seven patients with severe proteinuria had a lower oxygen saturation than those with no or mild proteinuria (p = 0.01, 0.03). Proteinuria or a decreased eGFR differentially occurred in approximately 30% of Fontan patients. Suboptimal Fontan circulation may contribute to the development of proteinuria and reduced eGFR.

Predicting complex kidney drug handling using a physiologically-based pharmacokinetic model informed by biomarker-estimated secretory clearance and blood flow.

Kidney function-adjusted drug dosing is currently based solely on the estimated glomerular filtration rate (GFR), however, kidney drug handling is accomplished by a combination of filtration, tubular secretion, and re-absorption. Mechanistic physiologically-based pharmacokinetic (PBPK) models recapitulate anatomic compartments to predict elimination from estimated perfusion, filtration, secretion, and re-absorption, but clinical applications are limited by a lack of empiric individual-level measurements of these functions. We adapted and validated a PBPK model to predict drug clearance from individual biomarker-based estimates of kidney perfusion and secretory clearance. We estimated organic anion transporter-mediated secretion via kynurenic acid clearance and kidney blood flow (KBF) via isovalerylglycine clearance in human participants, incorporating these measurements with GFR into the model to predict kidney drug clearance. We compared measured and model-predicted clearances of administered tenofovir and oseltamivir, which are cleared by both filtration and secretion. There were 27 outpatients (age 55 ± 15 years, mean iohexol-GFR [iGFR] 76 ± 31 mL/min/1.73 m2 ) in this drug clearance study. The mean observed and mechanistic model-predicted tenofovir clearances were 169 ± 102 mL/min and 163 ± 80 mL/min, respectively; estimated mean error of the mechanistic model was 37.1 mL/min (95% confidence interval [CI]: 24-52.9), compared to a mean error of 41.8 mL/min (95% CI: 25-61.6) from regression model. The mean observed and model-predicted oseltamivir carboxylate clearances were 183 ± 104 mL/min and 179 ± 89 mL/min, respectively; estimated mean error of the mechanistic model was 42.9 mL/min (95% CI: 29.7-56.4), versus error of 48.1 mL/min (95% CI: 31.2-67.3) from the regression model. Individualized estimates of tubular secretion and KBF improved the accuracy of PBPK model-predicted tenofovir and oseltamivir kidney clearances, suggesting the potential for biomarker-informed measures of kidney function to refine personalized drug dosing.

Addition of bioimpedance-derived body cell mass improves performance of serum creatinine-based GFR estimation in a chronic kidney disease cohort.

PURPOSE: Serum creatinine-based glomerular filtration rate (GFR) estimating equations are imprecise and systemic overestimate GFR in chronic kidney disease (CKD) populations with low muscle mass. Bioimpedance devices can measure body cell mass (BCM), a surrogate for muscle mass which has been included in a published GFR estimating equation. This BCM GFR equation is validated and compared with MDRD and CKD-EPI 2021 equations in an Indian CKD population. METHODS: Patients with stable CKD stages 1-5 and voluntary kidney donors underwent measurement of serum creatinine, DTPA GFR and bioimpedance on the same day. BCM GFR was tested for consistency, agreement and performance with respect to DTPA GFR. RESULTS: A total of 125 study participants were enrolled, including 106 patients with CKD (Stage 1: 8; stage 2: 32, stage 3: 42, stage 4: 20 and stage 5: 4 patients) and 19 voluntary kidney donors, with 66% males, and a mean age of 43.3 (± 16.5) years. The median bias of BCM GFR was 5.45 ml/min/1.73 m2 [95% confidence interval (CI) 4.2-8.3], absolute precision was 10.16 ml/min/1.73 m2 [95% CI 4.5-12.6], P30 was 59.1% [95% CI 50.0-67.7] and accuracy was 8.62% [95% CI 6.4-20.0]. Kappa measurement of agreement was the highest for BCM GFR-based staging (0.628 vs 0.545 for MDRD and 0.487 for CKD-EPI). CONCLUSION: BCM-based GFR estimating equation performed better than MDRD and CKD-EPI equations in this Indian CKD population, and BCM GFR-based KDIGO staging was associated with lesser misclassification than the MDRD and CKD-EPI equations. TRIAL REGISTRATION (PROSPECTIVE): Clinical Trials Registry of India (CTRI/2019/11/021850).

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.

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.

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.

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.

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.

Association between serum complements and kidney function in patients with diabetic kidney disease.

Objective: We aimed to explore the association between serum complements and kidney function of diabetic kidney disease (DKD) in Chinese patients. Methods: This is a retrospective study involving 2,441 participants. DKD was diagnosed according to the Kidney Disease: Improving Global Outcomes (KDIGO) categories. Participants were classified as stages G1-G5 by KDIGO glomerular filtration rate (GFR) categories. Effect sizes are expressed as odds ratio (OR) with 95% confidence interval (CI). Results: After balancing age, gender, systolic blood pressure (SBP), hemoglobin A1c (HbA1C), serum triglyceride (TG), and urinary albumin-to-creatinine ratio (UACR) between the G2-G5 and control groups, per 0.1 g/L increment in serum complement C3 was significantly associated with a 27.8% reduced risk of DKD at G5 stage (OR, 95% CI, P: 0.722, 0.616-0.847, <0.001) relative to the G1 stage. Conversely, per 0.1 g/L increment in serum complement C4 was associated with an 83.0-177.6% increased risk of G2-G5 stage (P<0.001). Serum complement C1q was not statistically significant compared to controls at all stages prior to or after propensity score matching. Conclusions: Our results indicate that high concentrations of serum C4 were associated with the significantly elevated risk of kidney function deterioration across all stages, and reduced serum C3 levels with an increased risk of DKD stage G5.