Estimated glomerular filtration rate in clinical practice: Consensus positioning of the Brazilian Society of Nephrology (SBN) and Brazilian Society of Clinical Pathology and Laboratory Medicine (SBPC/ML) / Estimativa da taxa de filtração glomerular na prática clínica: posicionamento consensual da Sociedade Brasileira de Nefrologia (SBN) e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial (SBPC/ML)

ABSTRACT Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.

RESUMO A doença renal crônica (DRC) representa um dos principais problemas de saúde pública da atualidade. A dosagem da creatinina sérica e a estimativa da taxa de filtração glomerular (TFG) são as principais ferramentas para avaliação da função renal. Para a estimativa da TFG, existem diversas equações, sendo a mais recomendada a CKD-EPI (Chronic Kidney Disease - Epidemiology). Existem ainda algumas controvérsias com relação à dosagem da creatinina sérica e da estimativa da TFG, uma vez que vários fatores podem interferir nesse processo. Uma importante mudança recente foi a retirada da correção por raça das equações para estimativa da TFG, que superestimavam a função renal, e consequentemente retardavam a implementação de tratamentos como diálise e transplante renal. Neste documento de consenso da Sociedade Brasileira de Nefrologia e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial são revisados os principais conceitos relacionados à avaliação da função renal, possíveis controvérsias existentes e recomendações para a estimativa da TFG na prática clínica.

Changes in Alzheimer's disease blood biomarkers in kidney failure before and after kidney transplant.

INTRODUCTION: Alzheimer's disease (AD) blood biomarkers show promise for clinical diagnosis but their reliability in chronic kidney disease (CKD) is debated. This study investigates the impact of kidney transplant (KT) on AD biomarkers in CKD. METHODS: We assessed AD biomarkers in 46 CKD patients pre-KT, at 12 weeks and 12 months post-KT, with baseline measures from 13 non-CKD controls. Using linear mixed models, we examined associations with participant groups, estimated glomerular filtration rate (eGFR) and cognition. RESULTS: CKD patients showed elevated levels of neurofilament light (117 ± 72 vs. 11 ± 5 pg/mL), phosphorylated tau 181 (75 ± 42 vs. 13 ± 8 pg/mL), glial fibrillary acidic protein (193 ± 127 vs. 94 ± 39 pg/mL), amyloid ß 42 (17 ± 5 vs. 5 ± 1 pg/mL), and amyloid ß 40 (259 ± 96 vs. 72 ± 17 pg/mL) compared to controls. Post-KT, biomarker levels approached normal with improved eGFR, paralleled by enhanced cognitive function. DISCUSSION: AD blood biomarker elevations in CKD are reversible with improved kidney function through KT. Highlights: AD biomarker levels are extremely high in severe CKD.AD biomarker levels are higher in patients with kidney failure on dialysis when compared to CKD patients not on dialysis.These elevations in AD biomarker levels in kidney failure are reversable and decrease dramatically after kidney transplantation.The change in biomarker levels after transplantation align with changes in kidney function.The change in biomarker levels after transplantation align with changes in cognitive function.

Urine Epidermal Growth Factor and Kidney Function Decline in Middle-Aged Adults.

Rationale & Objective: The diagnosis and prognostication of chronic kidney disease (CKD) largely rely on glomerular measures that may not reflect tubular damage. We investigated the associations of urine kidney tubule biomarkers with estimated glomerular filtration rate (eGFR) change among middle-aged adults, when chronic diseases typically emerge. Study Design: An observational cohort study. Setting & Participants: A total of 1,145 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study without CKD, hypertension, or cardiovascular disease at the year 20 visit. Exposures: Seven different biomarkers of tubular health: urine epidermal growth factor (EGF), alpha-1-microglobulin (α1m), interleukin-18, kidney injury molecule-1, monocyte chemoattractant protein-1, uromodulin, and chitinase-3-like protein 1. Outcomes: Ten-year eGFR change and incident reduced eGFR (new onset of eGFR < 60 mL/min/1.73 m2). Analytical Approach: We examined associations of tubular health biomarkers with 10-year eGFR change and incident reduced eGFR with linear mixed models and interval-censored proportional hazards regression models, respectively. Both minimally and fully adjusted models were controlled for urine creatinine levels. Results: The mean age of participants was 44.8 ± 3.7 years, with 39% African American and 56% female. The average 10-year change in eGFR was -18.6 mL/min/1.73 m2 (95% CI, -19.4 to -17.8). In contrast to the other tubular biomarkers, which showed conflicting results, EGF demonstrated strong, consistent associations with both kidney outcomes. Each 1-standard deviation (SD) higher EGF was associated with a 2.37 mL/min/1.73 m2 (95% CI, 0.64-4.10) smaller 10-year decrease in eGFR and a 42% (95% CI, 4%-64%) lower risk of incident reduced eGFR in the fully adjusted model. Limitations: Observational design, measurements of eGFR were done only at 5-year intervals during follow-up. Conclusions: In middle-aged, community-dwelling adults without hypertension, cardiovascular disease or CKD, higher urine EGF concentrations are associated with slower eGFR decline, whereas other kidney tubule biomarkers lacked a consistent association with kidney function decline.

Current measures of chronic kidney disease (CKD) rely on markers of glomerular health and function. This approach inadequately captures the role of kidney tubule health, a known histopathological predictor of CKD development. We investigated associations of 7 biomarkers of kidney tubule health with 10-year estimated glomerular filtration rate (eGFR) change and incident reduced eGFR. Among 7 biomarkers, only epidermal growth factor showed persistent and inverse associations with both 10-year eGFR change and incident reduced eGFR. These findings suggest that epidermal growth factor has an association with kidney function changes and might play a protective role in kidney disease development.

Effects of perioperative dexmedetomidine on delayed graft function following renal transplant: a systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects, has been suggested in recent studies to possess renoprotective properties. Dexmedetomidine may reduce the incidence of delayed graft function and contribute to effective pain control post-renal transplantation. The primary objective of this systematic review was to assess whether dexmedetomidine decreases the occurrence of delayed graft function in renal transplant patients. METHODS: Databases including MEDLINE, EMBASE, and CENTRAL were comprehensively searched from their inception until March 2023. The inclusion criteria covered all Randomized Clinical Trials (RCTs) and observational studies comparing dexmedetomidine to control in adult patients undergoing renal transplant surgery. Exclusions comprised case series and case reports. RESULTS: Ten RCTs involving a total of 1,358 patients met the eligibility criteria for data synthesis. Compared to the control group, the dexmedetomidine group demonstrated a significantly lower incidence of delayed graft function (OR = 0.71, 95% CI 0.52-0.97, p = 0.03, GRADE: Very low, I2 = 0%). Dexmedetomidine also significantly prolonged time to initiation of rescue analgesia (MD = 6.73, 95% CI 2.32-11.14, p = 0.003, GRADE: Very low, I2 = 93%) and reduced overall morphine consumption after renal transplant (MD = -5.43, 95% CI -7.95 to -2.91, p < 0.0001, GRADE: Very low, I2 = 0%). The dexmedetomidine group exhibited a significant decrease in heart rate (MD = -8.15, 95% CI -11.45 to -4.86, p < 0.00001, GRADE: Very low, I2 = 84%) and mean arterial pressure compared to the control group (MD = -6.66, 95% CI -11.27 to -2.04, p = 0.005, GRADE: Very low, I2 = 87%). CONCLUSIONS: This meta-analysis suggests that dexmedetomidine may potentially reduce the incidence of delayed graft function and offers a superior analgesia profile as compared to control in adults undergoing renal transplants. However, the high degree of heterogeneity and inadequate sample size underscore the need for future adequately powered trials to confirm these findings.

Clinical validation of the novel fluorescent glomerular filtration rate tracer agent relmapirazin (MB-102).

The fluorescent compound relmapirazin has been rationally designed for use in point-of-care measurement of glomerular filtration rate (GFR), with attributes including negligible protein binding, negligible metabolites in vivo, negligible tubular secretion, and excellent chemical and photo stability. Twenty-four nonclinical assays were performed in accordance with FDA requirements yielding negligible toxicology concerns. Here, a clinical study was performed to validate relmapirazin as a GFR tracer in patients by comparison to iohexol. This was evaluated in 120 adults at three clinical sites with eGFR values ranging from normal to Stage 4 chronic kidney disease. Relmapirazin and iohexol were administered intravenously in consecutive boluses to each subject and serial blood samples obtained over the subsequent 12 hours. Plasma concentrations were measured and the corresponding plasma GFR for each agent was determined using a standard two-compartment pharmacokinetic assessment. Urine from each subject was collected for the entire 12-hour study period to measure the amount of administered dose appearing in the urine. A near perfect linear regression correlation was observed between the GFRs measured by these two tracers (r2=0.99). Bland-Altman analysis confirmed agreement between these two measures of GFR (limits of agreement -7.0 to +5.6 mL/min; mean of -0.7 mL/min). The GFR determined by relmapirazin was independent of GFR stratification by chronic kidney disease stage, and importantly by race. The percent of the administered relmapirazin dose recovered in the urine was greater than or equal to that of iohexol with no reported severe adverse events. Thus, relmapirazin may be used as a GFR tracer agent in humans.

Associations of exposure to organochlorine pesticides and polychlorinated biphenyls with chronic kidney disease among adults: the modifying effects of lifestyle.

Exposure to organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) has been reported to be associated with renal impairment and chronic kidney disease (CKD). Nevertheless, the research results thus far have exhibited inconsistency, and the effect of lifestyle on their association is not clear. In this study, we assessed the correlation between serum OCPs/PCBs and CKD and renal function indicators including estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) among 1721 Chinese adults. In order to further investigate the potential impact of lifestyle, we conducted joint associations of lifestyle and OCPs/PCBs on CKD. We found a negative correlation between p,p'-DDE and eGFR, while logistic regression results showed a positive correlation between PCB-153 and CKD (OR, 1.92; 95% CI, 1.21, 3.06). Quantile g-computation regression analyses showed that the association between co-exposure to OCPs/PCBs and CKD was not significant, but p,p'-DDE and PCB-153 were the main contributors to the negative and positive co-exposure effects of eGFR and CKD, respectively, which is consistent with the regression results. Participants with both relatively high PCB-153 exposure and an unhealthy lifestyle had the highest risk of CKD, in the joint association analysis. The observed associations were generally supported by the FAS-eGFR method. Our research findings suggest that exposure to OCPs/PCBs may be associated with decreased eGFR and increased prevalence of CKD in humans, and a healthy lifestyle can to some extent alleviate the adverse association between PCB-153 exposure and CKD.

Associations of accelerometer-measured physical activity and sedentary time with renal function and chronic kidney disease: a national population-based study.

Introduction: There is limited information about the relationship between physical activity (PA) and sedentary behaviors in chronic kidney disease (CKD). Therefore, this study aims to explore the associations of accelerometer-measured PA and sedentary behaviors with CKD. Methods: A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey in the 2003-2004 and 2005-2006 survey cycles. A uniaxial accelerometer measured physical activity (PA) and sedentary time (ST). The associations of PA and ST with estimated glomerular filtration rate (eGFR) and odds of CKD adopted the generalized linear regression, multivariable logistic regression, and isotemporal substitution models. Results: A total of 5,990 adults with 605 CKD patients were included in this study. Compared with the individuals in the first quartile group, participants in the fourth quartile of low-intensity physical activity (LIPA), moderate to vigorous physical activity (MVPA), and ST were associated with 52% (35%, 65%) and 42% (14%, 62%) lower odds of CKD and 64% (17%, 131%) higher odds of CKD, respectively. Substituting 30 min/day of ST with equivalent LIPA/MVPA contributed to risk reduction in CKD. Discussion: The findings suggest that increased LIPA and MVPA and reduced ST were associated with a lower risk of CKD and that replacing ST with LIPA may decrease the risk of CKD.

Effect of finerenone on nephrotic syndrome in patients with diabetic kidney disease.

Introduction: Diabetic kidney disease (DKD) is an important complication of diabetes as it results in end-stage renal disease; hence, several drugs have been developed for its treatment. However, even with treatment with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, the residual risk of DKD remains. While this risk is an issue, the renoprotective effects of finerenone, a novel non-steroidal mineralocorticoid receptor antagonist, are becoming evident. High proteinuria increases the risk of cardiovascular death as well as renal failure. Hence, it is especially important to address cases of urine protein to nephrotic levels in DKD, however, no previous studies have assessed the safety and efficacy of finerenone in patients with DKD and nephrotic syndrome. Therefore, this study aimed to assess whether finerenone has a renoprotective effect in advanced DKD complicated by nephrotic syndrome. Methods: Nine patients with DKD and nephrotic syndrome who received 10-20 mg/day of finerenone were retrospectively analyzed. The average observation period was 9.7 ± 3.4 months. Patients with serum potassium levels greater than 5.0 mEq/L at the start of finelenone were excluded. Changes in urinary protein levels, estimated glomerular filtration rate (eGFR), and serum potassium levels were studied before and after finerenone administration. Results: The mean changes in the urinary protein creatinine ratio (UPCR) at baseline were 6.6 ± 2.0. After finerenone treatment, the mean UPCR decreased to -0.6 ± 3.9; however, this change was not statistically significant.The eGFR decline slope also tended to decrease with finerenone treatment (before vs. after: 3.1 ± 4.9 vs. -1.7 ± 3.2 mL/min/1.73 m2. Furthermore, finerenone did not increase serum potassium levels. Conclusions: Patients treated with finerenone showed decreased UPCR; hence, it is suggested that finerenone may be effective in treating nephrotic syndrome in patients with DKD. These findings may be applicable to real-world clinical settings. Nonetheless, it is important to note that this study was a retrospective analysis of a single-center cohort and had a limited sample size, highlighting the need for additional large-scale investigations.

Risk factors for chronic kidney disease progression over 20 years for primary prevention in Japanese individuals at a preventive medicine research center: Focus on the influence of plasma glucose levels.

AIMS/INTRODUCTION: Chronic kidney disease (CKD) is a very important issue globally because of the risk of its progressing to end-stage renal disease. We aimed to identify factors contributing to long-term estimated glomerular filtration rate (eGFR) decline to determine an early diagnosis and prevent CKD progression. MATERIALS AND METHODS: From January 2003 to December 2006, 5,507 individuals underwent health checkups at our hospital's Preventive Medicine Research Center. We ultimately enrolled 2,175 individuals. The eGFR was ≥60 mL/min/1.73 m2 at the start of observation period, which was 20 years. The event onset time was the day that the eGFR became <30 mL/min during the 20-year period. Baseline risk factors - in particular, the effect of plasma glucose levels on the eGFR - were extracted and evaluated by using Fine and Gray analysis. RESULTS: During the 20-year observation, the hazard ratio (HR) of CKD progression was examined. A fasting plasma glucose (FPG) level ≥105 mg/dL was significantly associated with the risk of CKD progressing to an eGFR <30 mL/min. This trend was similar in the slope of eGFR. An FPG ≥105 mg/dL or an glycated hemoglobin level ≥6.5% was useful for intervening in CKD progression. Multivariate analysis showed that independent risk factors were an FPG level ≥105 mg/dL (HR 1.9; P < 0.001), age ≥60 years (HR 3.86; P < 0.001), obesity (HR 1.61; P < 0.01) and urinary protein (HR 1.55; P < 0.01). CONCLUSIONS: For early intervention against a reduction in the eGFR, detecting mild increases in FPG ≥105 mg/dL in patients with CKD with or without diabetes is useful.

Comparison of Glomerular Filtration Rate Equations in a Rural New Mexico Cohort: Results from the COMPASS Study.

Rationale and Objective: The NKF-ASN Task Force recommends accurate kidney function estimation avoiding biases through racial adjustments. We explored the use of multiple kidney function biomarkers and hence estimated glomerular filtration rate (eGFR) equations to improve kidney function calculations in an ethnically diverse patient population. Study design: Prospective community cohort study. Setting and Participants: rural New Mexico clinic with patients > 18 yo. Methods: Markers of kidney function, IDMS-Creatinine (SCr), chemiluminescence Beta-2 Microglobulin (B2M), Nephelometry-calibrated ELISA Cystatin C (CysC), inflammation, glucose tolerance, demographics, BUN/UACR from the baseline visit of the COMPASS cohort, were analyzed by Kernel-based Virtual Machine learning methods. Results: Among 205 participants, the mean age was 50.1, 62% were female, 54.1% Hispanic American and 30.2% Native American. Average kidney function biomarkers were: SCr 0.9 mg/dl, B2M 1.8 mg/L, and CysC 0.7 mg/dl. The highest agreement was observed between SCr and B2M-based eGFR equations [mean difference in eGFRs: (4.48 ml/min/1.73m2], and the lowest agreement between B2M and CysC-based eGFR equations (-24.75 ml/min/1.73m2). There was no pattern of association between the differences in eGFR measures and gender. In the continuous analyses, the absolute eGFR value (p<2 x 10-16) and serum albumin (p =6.4 x 10-5) predicted the difference between B2M- and SCr-based e-GFR. The absolute eGFR value (p<2 x 10-16) and age (p =7.6 x 10-5) predicted the difference between CysC- and SCr-based e-GFR. Limitations: Relatively small sample size, elevated inflammatory state in majority of study participants and no inulin excretion rate measurements. Conclusion: B2M should be strongly considered as a kidney function biomarker fulfilling the criteria for the NKF-ASN. B2M's eGFR equation does not need adjustment for gender or race and showed the highest agreement with SCr-based eGFR equations.

Favorable changes in the eGFR slope after dapagliflozin treatment and its association with the initial dip.

BACKGROUND: Renoprotective effects of sodium glucose transporter 2 (SGLT2) inhibitors, including dapagliflozin, were observed in randomized controlled trials (RCTs). The suspected underlying mechanism is a correction of hyperfiltration, observed as an "initial dip". Whether SGLT2 inhibitors can attenuate the rate of decline in the estimated glomerular filtration rate (eGFR) in clinical settings, even when considering the pre-treatment decline rate, is unknown. Although several RCTs identified an association between the initial dip and long-term renal prognoses, a conclusion has not been reached. METHODS: We collected the eGFR data of patients for whom dapagliflozin was initiated in our hospital and then calculated their eGFR slopes before and after the start of the treatment. We investigated the changes in the eGFR slopes (ΔeGFR slope) and the association between the ΔeGFR slope and the initial dip. Risks for rapid eGFR decliners (eGFR slope < - 3 mL/min/1.73 m2/year) were also examined. RESULTS: The eGFR slope was significantly milder after dapagliflozin treatment (p < 0.01). A deeper initial dip was associated with a milder rate of eGFR decline (adjusted beta: - 0.29, p < 0.001). Dapagliflozin treatment reduced the proportion of rapid eGFR decliners from 52.9 to 14.7%, and a smaller initial dip was identified as a significant risk for post-treatment rapid eGFR decline (adjusted odds ratio: 1.73, p < 0.05). CONCLUSIONS: Compared to before the administration of dapagliflozin, the rate of eGFR decline was significantly milder after its administration. The initial dip was significantly associated with long-term renoprotective effects and may be a useful predictor of treatment response.

Early and late assessment of renal allograft dysfunction using intravoxel incoherent motion (IVIM) and diffusion-weighted imaging (DWI): a prospective study.

PURPOSE: To evaluate the ability of the Intravoxel Incoherent Motion (IVIM) and monoexponentially ADC in renal allograft function in the early and late phases of transplantation, and to predict their effectiveness in discrimination of the graft pathology. METHODS: This is a prospective study included participants scanned with quantitative diffusion and perfusion sequences on a 3-T MR scanner (Philips, Ingenia); the ADC and IVIM parameters; were calculated. Correlations and regression analysis with the eGFR, transplantation periods, and pathology were assessed. RESULTS: This study included 105 renal allograft recipients (85 males, and 20 females with mean age = 32.4 ± 11.9 years and age range = 22-61 years). There was a significant positive correlation between the whole parameters of the ADC and IVIM with eGFR however, the cortical parameters showed higher significant correlation coefficients (p < 0.001). Regression analysis revealed the most significant model can predict eGFR groups included cortical pseudo diffusion (D*) and cortical ADC (p < 0.001). In graft dysfunction eGFR was 61.5 ml/min and normal graft was 64 ml/min. This model demonstrates a high performance of an AUC 96% [0.93-0.97]. In the late transplantation, there is a higher correlation with D* compared to ADC, p-values = 0.001. CONCLUSION: IVIM and ADC Values are significant biomarkers for renal allograft function assessment, cortical ADC, and D* had the highest performance even in situations with mild impairment that is not affect the eGFR yet as cases of proteinuria with normal eGFR. Furthermore, D* is superior to ADC in the late assessment of the renal transplant.

Persistent albuminuria and chronic kidney disease in adults with sickle cell anaemia: Results from a multicenter natural history study.

Clinical and laboratory correlates of chronic kidney disease (CKD) in sickle cell anaemia remain incompletely defined. In a multicenter cohort study, we evaluated the prevalence of persistent albuminuria (PA) and characteristics associated with PA, albumin-creatinine ratio (ACR) and decreased estimated glomerular filtration rate (eGFR) using logistic, linear and multinomial regression models, respectively. Of 269 participants (median age: 30 years; 57.2% females), the prevalence of PA was 35.7%. Using baseline ACR values of <100 and ≥100 mg/g, the probabilities of PA were 30.0% and 94.6%, respectively. In multivariable logistic regression analyses, male sex (ß = 0.80 [SE = 0.36], p = 0.024) and ACE inhibitors/ARBs use (ß = 1.54 [SE = 0.43], p < 0.001) were associated with higher likelihoods of PA, while higher haemoglobin (ß = -0.33 [SE = 0.13], p = 0.009) and HbF (ß = -0.04 [SE = 0.02], p = 0.041) were associated with lower likelihoods of PA. In multivariable multinomial regression analyses, older age (ß = 0.06 [SE = 0.02], p = 0.004) and higher alkaline phosphatase (ß = 0.01 [SE = 0.00], p = 0.004) were associated with higher odds of having eGFR 60-90 versus eGFR>90 mL/min/1.73 m2 using the cystatin C-based CKD-EPI-2012 equation. Additionally, higher systolic blood pressure (ß = 0.11 [SE = 0.03], p = 0.001) and blood urea nitrogen (ß = 0.45 [SE = 0.12], p < 0.001) were associated with higher odds, while higher haemoglobin (ß = -1.22 [SE = 0.43], p = 0.004) was associated with lower odds of having eGFR<60 versus eGFR>90 mL/min/1.73 m2. PA and decreased eGFR are associated with measures of disease severity and comorbid conditions (Clinicaltrials.gov Identifier: NCT03277547).

Early reduction in albuminuria is associated with a steeper 'dip' in initial estimated glomerular filtration rate but favourable long-term kidney outcomes in people with diabetes receiving sodium-glucose cotransporter-2 inhibitors.

AIM: To assess if early change in albuminuria was linked to an initial change in estimated glomerular filtration rate (eGFR) and long-term kidney outcomes in people with type 2 diabetes (T2D) receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors. METHODS: Using a medical database from a multicentre healthcare institute in Taiwan, we retrospectively enrolled 8310 people receiving SGLT2 inhibitors from 1 June 2016 to 31 December 2021. We compared the risks of initial eGFR decline, major adverse renal events (MARE; >50% eGFR reduction or development of end-stage kidney disease), major adverse cardiovascular events (MACE), or hospitalization for heart failure (HHF) using a Cox proportional hazards model. RESULTS: In all, 36.8% (n = 3062) experienced a >30% decrease, 21.0% (n = 1743) experienced a 0%-30% decrease, 14.4% (n = 1199) experienced a 0%-30% increase, and 27.7% (n = 2306) experienced a >30% increase in urine albumin-to-creatine ratio (UACR) after 3 months of SGLT2 inhibitor treatment. Greater acute eGFR decline at 3 months correlated with greater UACR reduction: -3.6 ± 10.9, -2.0 ± 9.5, -1.1 ± 8.6, and -0.3 ± 9.7 mL/min/1.73 m2 for the respective UACR change groups (p < 0.001). Over a median of 29.0 months, >30% UACR decline was associated with a higher risk of >30% initial eGFR decline (hazard ratio [HR] 2.68, 95% confidence interval [CI] 1.61-4.47]), a lower risk of MARE (HR 0.66, 95% CI 0.48-0.89), and a comparable risk of MACE or HHF after multivariate adjustment (p < 0.05). The nonlinear analysis showed early UACR decline was linked to a lower risk of MARE but a higher risk of initial steep eGFR decline of >30%. CONCLUSION: Physicians should be vigilant for the potential adverse effects of abrupt eGFR dipping associated with a profound reduction in UACR, despite the favourable long-term kidney outcomes in the population with T2D receiving SGLT2 inhibitor treatment.

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.

Association between consumption of flavonol and its subclasses and chronic kidney disease in US adults: an analysis based on National Health and Nutrition Examination Survey data from 2007-2008, 2009-2010, and 2017-2018.

Background: There is little research on the relationship between flavonol consumption and chronic kidney disease (CKD). This study aimed to examine the link between flavonol consumption and the risk of CKD among US adults, using data from the 2007-2008, 2009-2010 and 2017-2018 National Health and Nutrition Examination Survey (NHANES). Methods: A cross-sectional approach was used, drawing on data from three NHANES cycles. The flavonol consumption of the participants in this study was assessed using a 48 h dietary recall interview. CKD was diagnosed based on an estimated glomerular filtration rate below 60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio of 30 mg/g or higher. Results: Compared to the lowest quartile of flavonol intake (Q1), the odds ratios for CKD were 0.598 (95% CI: 0.349, 1.023) for the second quartile (Q2), 0.679 (95% CI: 0.404, 1.142) for the third quartile (Q3), and 0.628 (95% CI: 0.395, 0.998) for the fourth quartile (Q4), with a p value for trend significance of 0.190. In addition, there was a significant trend in CKD risk with isorhamnetin intake, with the odds ratios for CKD decreasing to 0.860 (95% CI: 0.546, 1.354) in the second quartile, 0.778 (95% CI: 0.515, 1.177) in the third quartile, and 0.637 (95% CI: 0.515, 1.177) in the fourth quartile (p for trend = 0.013). Conclusion: Our analysis of the NHANES data spanning 2007-2008, 2009-2010, and 2017-2018 suggests that high consumption of dietary flavonol, especially isorhamnetin, might be linked to a lower risk of CKD in US adults. These findings offer new avenues for exploring strategies for managing CKD.

Performance of Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration Equations Versus 99Tc-DTPA-Renogram in Assessing Kidney Function.

Objectives: To evaluate the performance of measurement of glomerular filtration rate (GFR) using Modification of Diet in Renal Disease equations (MDRD186, MDRD175) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in comparison with technetium-99m diethylenetriaminepentaacetic acid (99Tc-DTPA) renogram method, the gold standard. A related aim was to correlate the three equations to estimate GFR and their impact on reclassifying the stages of CKD in adult Omani patients. Methods: This cross-sectional study recruited two groups of patients diagnosed with CKD during a 10-month period from January to October 2021. The first group comprised 48 patients who underwent a 99Tc-DTPA renogram procedure for GFR measurement, and the second group comprised 30 348 adult patients who did not undergo the same procedure; estimated GFR was calculated using the three equations. Results: The median of the reference GFR was 106.0 mL/min/1.73 m2, whereas the median estimated GFR for the MDRD175, MDRD186, and CKD-EPI equations were 92.5, 98.3, and 102.1, respectively. All three equations correlated moderately with the reference GFR (0.428, 0.428, 0.523, respectively; p < 0.010). The CKD-EPI showed lesser bias (3.7 vs. 12.9 and 7.5 for MDRD175 and MDRD186, respectively) and more accuracy (95.8% vs. 91.7% and 93.8%); however, it was the least precise (25.1 vs. 22.3 and 23.8). The MDRD186 performed similarly to the CKD-EPI equation at CKD stages 3a-5 and differed significantly at stages 1-2. Whereas the MDRD175 differed significantly with both equations at stages 1-3b and was similar to them at stages 4-5. Conclusions: The CKD-EPI equation had the highest accuracy and the least bias and precision in the general population. The MDRD186 CKD classification differed significantly from the CKD-EPI equation at CKD-stages 1-2 only. The CKD-EPI equation is preferred to MDRD for the detection and classification of early CKD stages.

Age and estimated glomerular filtration rate in Chinese older adults: a cohort study from 2014 to 2020.

Objectives: This study aimed to fill the data gap of the course of renal function decline in old age and explore changes in renal function across different health states with increasing age. Methods: This observational, retrospective, single-center cohort study included 5,112 Chinese older adults (3,321 men and 1,791 women, range 60-104 years). The individual rate of estimated glomerular filtration rate (eGFR) decline was analyzed using linear mixed-effects model to account for repeated measures over the years. Results: The median age was 66 years, median BMI was 24.56 kg/m2, and median eGFR was 89.86 mL/min.1.73 m2. For every 1-year increase in age, women's eGFR decreased by 1.06 mL/min/1.73 m2 and men's by 0.91 mL/min/1.73 m2. We observed greater age-related eGFR decline in men and women with high systolic blood pressure (SBP). Men with high triglyceride (TG), high low-density lipoprotein cholesterol (LDL-C), and low high-density lipoprotein cholesterol (HDL-C), had greater age-related eGFR decline. In women, different BMI groups showed significant differences in age-related eGFR decline, with the highest decline in those with obesity. Additionally, participants with normal baseline eGFR had a faster age-related decline than those with low baseline eGFR. Conclusion: The eGFR declined linearly with age in Chinese older adults, with women exhibiting a slightly faster decline than men. Both men and women should be cautious of SBP. Older adults with normal baseline renal function experienced a faster eGFR decline. Men with high TG, LDL-C, and low HDL-C levels, as well as obese women, should be vigilant in monitoring renal function.

Preexisting Hyperuricemia Before High-Altitude Ascent is Associated with a Slower Recovery of Estimated Glomerular Filtration Rate Following Descent.

Zhao, Linggong, Yujie Huang, and Xiaoling Tan. Preexisting hyperuricemia before high-altitude ascent is associated with a slower recovery of estimated glomerular filtration rate following descent. High Alt Med Biol. 00:00-00, 2024. Objectives: Hypoxia at high altitudes results in elevated uric acid (UA) and reduced estimated glomerular filtration rate (eGFR). However, the impact of a prolonged high-altitude sojourn on UA levels and renal function in patients with preexisting hyperuricemia warrants further exploration. The study was to investigate the eGFR and related factors in patients with preexisting hyperuricemia following exposure to high altitude. Methods: The study included 345 participants, who worked at a high altitude for 1 year. Anthropometric and laboratory indices were collected before ascent (i.e., baseline), as well as 20 and 80 days after descent. The participants were categorized into individuals with hyperuricemia (HUA) or normal uric acid (NUA) group based on the presence or absence of hyperuricemia at baseline. Results: No difference in baseline eGFR was observed between the two groups before ascend or on day 20 after descent (p > 0.05). However, on day 80, eGFR of the HUA group was lower compared with the NUA group (p < 0.05). Correlations existed between post-descent eGFR levels and variables, including sampling time, UA levels, total and direct bilirubin, and baseline grouping. Conclusions: After high-altitude exposure, the recovery of eGFR was delayed in participants with preexisting hyperuricemia. Preexisting hyperuricemia and high-altitude hypoxia jointly contribute to renal impairment.