Estimation Of Kidney Function Research Articles

Formulae for estimation of kidney function as an approach to calculating drug doses: A scoping review

Background: The kidneys are the main organ for drug excretion, and it is critical to assess kidney function when designing dosage regimens for drugs that undergo renal elimination. Various formulae have been used to estimate kidney function and safely adjust doses. Objective: This research reviewed studies that assessed patients' kidney function with various approaches to provide appropriate choices of kidney function estimation formulas based on patients' age and clinical conditions. Method: The search involved browsing scientific articles in PubMed and ScienceDirect with the keywords (("assessment") AND ("GFR") AND ("formula")) OR ("renal function") AND ("human")) AND (“Creatinine”). The articles included were those available in full text and English. Thirty articles addressing the formulae for kidney function assessment were reviewed. Result: The Schwartz formula is more appropriate for pediatric and adult patients, whereas the creatinine-based chronic kidney disease epidemiology (CKD-EPI) formula can be used in geriatrics, obese patients, and patients already known to have decreased kidney function. The cystatin C-based CKD-EPI formula is for patients with HIV and post-transplant patients. Conclusion: This study identified that physiological conditions, especially patients’ age and pathology, should be considered in devising formulae to estimate kidney function to accurately calculate safe drug doses.

#1248 Sex specific associations between fat free mass and weight with mortality: sequences of regressions analyses from the UK Biobank cohort

Abstract Background and Aims There is growing evidence that muscle mass (MM) loss, observed in long term conditions (LTCs), including chronic kidney disease (CKD), is associated with mortality. This study aimed to explore the direct association between MM and mortality, having controlled for the combined influence of ageing, long term conditions (LTCs), inflammation, renal function and body weight. Furthermore, we sought to explore whether this association differed between the biological sexes. Method An observational study was conducted using the UK Biobank cohort. Adults were recruited between 2007-2010 at 22 UK centres. MM was estimated using bioimpedance defined whole body fat-free mass (BI-FFM: Tanita BC418). Primary outcome was all-cause mortality (ACM), with the cause / date of death being obtained from the NHS Information Centre (England and Wales) and NHS Central Registry (Scotland). Follow up was defined as the period between the first visit date to either date of death / the latest date for central registry downloads (December 2021). Estimated glomerular filtration rate using creatinine (eGFRCreat) or cystatin-C (eGFRcystatin-C) were calculated (CKD-EPI 2009 equation without ethnicity correction). Participants were excluded if they were on dialysis, died from SARS-CoV-2 infection or withdrew consent. Sequences of regressions analyses (SoRA), a graphical Markov modelling technique which assesses the complexity of direct and indirect pathways of association between blocks of variables which are ordered a-priori to reflect postulated directions of association, were fitted for both sexes. Results There were 500,589 participants eligible for analysis (272,623 females / 227,966 males). There were 33,755 deaths over a median follow up period of 12.58 (IQR 11.85-13.30) yrs. The male model revealed per 5 kg-higher BI-FFM (holding weight constant) was associated with lower odds of ACM in the eGFRCreat (OR 0.827, 95% CI 0.781-0.875) and eGFRCystatin-C (OR 0.425, 95% CI 0.301-0.599) sub-models, whereas a 5 kg-higher weight (holding BI-FFM constant) was associated with higher odds of ACM in the eGFRCreat (OR 1.070, 95% CI 1.027-1.115) and eGFRCystatin-C (OR 1.395, 95% CI 1.170-1.663) sub-models. In contrast, the female model revealed a 5 kg-higher BI-FFM (holding weight constant) was associated with higher odds of ACM in the eGFRCreat (OR 2.016, 95% CI 1.650-2.463) and eGFRCystatin-C (OR 1.729, 95% CI 1.391-2.151: Fig. 1) sub-models, whereas a 5 kg-higher body weight (holding BI-FFM constant) was associated with lower odds of ACM in the eGFRCystatin-C (OR 0.935, 95% CI 0.918-0.952) but not the eGFRCreat (OR 1.020, 0.970-1.072) sub-model. Conclusion Our analysis demonstrates sex-divergent associations between BI-FFM and/or body weight with ACM when estimated kidney function is accounted for. These associations suggest sex-specific explanations as to why MM loss leads to adverse outcomes in multimorbid populations and further characterises the sex-stratified nature of the “obesity paradox” in LTCs.

#2514 Clinical impact of the CKD-EPI 2021 versus the CKD-EPI 2012 formula on GFR estimation and CKD prevalence: results from a Dutch routine-care cohort

Abstract Background and Aims Quantifying the kidney function is crucial for diagnosing and monitoring kidney disorders in clinical practice. Recently, the CKD-EPI 2021 formula was developed for estimating glomerular filtration rate (eGFR), excluding the ethnicity variable. In this study, we aimed to analyze the impact in a Dutch routine-care cohort of introducing the new serum creatinine-based CKD-EPI 2021 formula on glomerular kidney function estimation and the prevalence of chronic kidney disease (CKD), compared to the now used CKD-EPI 2012 formula. Method All patients of 18 years and older of whom serum creatinine was measured between January 2013 and December 2023 at the University Medical Center Utrecht in the Netherlands, were included. Differences in the eGFR measured with the CKD-EPI 2012 formula and the new CKD-EPI 2021 formula were defined as median difference, stratified by gender, age categories, and CKD stages. Results 251.960 patients with 2.312.313 serum creatinine measurements were included in our analysis. Our findings indicate that the CKD-EPI 2021 formula results in a higher eGFR compared to the CKD-EPI 2012 formula (median +3.6 (Inter quartile range (IQR) 2.4 to 4.5) ml/min/1.73 m2 in men, and median +3.1 (IQR 2.0 to 4.0) ml/min/1.73 m2 in women). In total, 21.1% of the patients with CKD stage 2-5 according to the CKD-EPI 2012 formula were classified as having a better CKD stage using the new CKD-EPI 2021 formula; 26.1%, 20.5%, and 15.1% of the patients classified as having CKD stage 3A, 3B, and 4 were classified as having CKD stage 2, 3A, and 3B, respectively (Table 1). Conclusion The introduction of the CKD-EPI 2021 formula would have significant implications for kidney function estimation in the Dutch clinical setting. It is crucial to consider these differences when interpreting kidney function data and making clinical decisions, especially given the potential impact on diagnosing CKD and dosing medication.

#2031 Exploring the utility of serum proteomics for outcome prediction of autosomal polycystic kidney disease (ADPKD)

Abstract Background and Aims ADPKD is an inherited disorder characterized by the development of cysts in both kidneys, leading to renal enlargement and a gradual decline in renal function. It is the leading cause of end stage renal disease (ESRD) with an estimated prevalence of 1:1000. The estimated glomerular filtration rate (eGFR) is the calculated estimation of kidney function by using different equations. The eGFR equation used in this study is Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI, 2009) equation, which includes serum creatinine level, age, and gender. eGFR is also frequently used for assessing overall health of ADPKD patients, classifying the disease stages, and determining appropriate therapeutic interventions. As in ADPKD, clinical symptoms manifest typically in later disease stages, early diagnosis is crucial to slow the disease progression and improve patients’ life quality. This study has two main objectives: (1) the identification of molecular and clinical parameters associated with the annual eGFR decline and (2) the development of a predictive model for future eGFR in patients with ADPKD using serum proteomics. This research aims to advance more effective strategies for the misdiagnosis, stratification, and treatment of ADPKD by combining proteomic and clinical parameters. Method Utilizing retrospective eGFR values (n = 7187) of patients with ADPKD (n = 1291) recruited from the AD(H)PKD patient cohort, the annual decline in eGFR (slope) was calculated. A minimum of three eGFR values and the absence of tolvaptan use (a medication that inhibits the mechanisms underlying eGFR decline) were inclusion criteria. In order to determine the slope, robust linear regression was applied. Prior to the analyses, patients whose slopes were clinically extreme (−10 & >5 mL/min/1.73 m2 per year) were excluded. Total of 2469 eGFR values from 219 ADPKD patients were included in this study. To derive a feature set (FS) suitable for slope prediction, the least absolute shrinkage and selection operator (LASSO) was applied independently to two subsets of the serum proteome (SP) data: (i) SP alone and (ii) SP in conjunction with key clinical variables: age, gender, eGFR, and MAYO class (SPMC). Linear regression (LR) models were constructed using the acquired FSs individually (SP and SPMC), and cross-validation (CV) was incorporated to prevent overfitting. Following that, prediction models were generated and compared in terms of their ability to predict slopes and were visualized for an overview. Results Using feature selection, four features associated with slope were identified in both SP and SPMC data. Three of those features were proteomic-based and common to both feature sets (SC and SPMC). LR models exhibited stability in R2s in test sets of CV, indicating no sign of overfitting. Therefore, the LR slope prediction models were built with SP and SPMC feature sets by using all available data. The adjusted R2 of SP and SCMP LR models were 0.274 (R2 = 0.287, F(4,213) = 21.48, p = 6.74 × 10−15) and 0.301 (R2 = 0.317, F(5,208) = 19.31, p = 8.94 × 10−16). This step was followed by the slope prediction of the same patients (internal validation) to examine models’ prediction capacity by comparing the predicted to observed slopes. According to comparisons, our LR models predict closer to actual slope if slope is greater than −5 and lower than 0 mL/min/1.73 m2 per year. Most of the observed slopes were in between the specified thresholds, which explains why the model is working well. However, the deviations between predicted and the observed slopes increases as the slopes exceed this range. Conclusion Identified biomarkers could be used for how the disease will progress, however, fine-tuning of the models might be necessary. Even though there were patients with positive and extremely negative eGFR slopes, our model accurately predicts slopes in the previously specified range. These extreme cases might also be responsible for models’ reduced accuracy outside of that range. One possible solution could be to use weighted lasso to reduce the effect of “extreme” slopes on the models.

#377 Assessment of kidney function by creatinine and cystatin C and cardiovascular outcomes in patients with atrial fibrillation

Abstract Background and Aims Atrial fibrillation (AF) in patients with chronic kidney disease are at an increased risk for ischemic and bleeding events and all-cause mortality. Accurate kidney function estimation is key for risk assessment. Creatinine is commonly used to calculate the Glomerular Filtration Rate (GFR). However, cystatin C has been described to be more sensitive than creatinine independent of muscle mass, autoimmune disease, inflammation or consuming diseases. Our aim was to evaluate the associations between kidney function, assessed by creatinine and cystatin C, and cardiovascular events (CVE), its individual components, and major bleedings. Method We enrolled 326 AF patients into two prospective, multicenter cohort studies. Creatinine and cystatin C were measured at baseline and clinical outcome events were assessed yearly. We calculated GFR using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula based on either creatinine (GFRcr), cystatin C (GFRcy) or both (GFRc2). Primary outcome was major CVE, defined as a composite of stroke or systemic embolism, myocardial infarction and cardiovascular death. Secondary outcomes were the individual components of major CVE and major bleeding. Multivariable adjusted Cox regression analyses were built to evaluate the associations between kidney function and outcome events. Results Mean age was 56 ± 9 years and 37% were female. Mean creatinine and cystatin С levels were 112 ± 21 μmol/l and 1.6 ± 0.3 mg/l, respectively, translating to a GFRc2 of 58.2 ± 16.8 ml/min/1.73 m2. Over a median follow-up of 2 years, the incidence rates for major CVE (per 100 person-years) across quartiles (Q1-Q4) of GFRc2 were 23.1, 20.3, 17.6 and 14.7, respectively. When using multivariable adjusted Cox regression analysis, major CVE was significantly associated with GFRcr (per 1 standard deviation: HR 0.89 (95% CI 0.79; 0.98) p = 0.01), GFRcy (HR 0.65 (CI 0.53; 0.72), p < 0.001) and GFRc2 (HR 0.74 (CI 0.63; 0.82), p < 0.001). This association was mainly driven by cardiovascular death. Major bleeding was associated with GFRcy (HR 0.78 (0.64-0.93) p = 0.001) and GFRc2 (HR 0.82 (0.69-0.97), p = 0.01), but not with GFRcr (HR 0.93 (95% CI 0.83-1.1) p = 0.33). Conclusion Among AF patients, GFR equations including cystatin C were associated both with major CVE and bleeding events, while creatinine based GFR equations were only associated with major CVE. Therefore, Cystatin C based GFR equations might offer more comprehensive risk stratification in patients with AF.

Assessment of estimated kidney function based on creatinine in indonesian adult populations: Calling for validation of performance

Assessment of estimated kidney function based on creatinine in indonesian adult populations: Calling for validation of performance

464 Creating Pragmatic Tools for Reliable Kidney Function Measurement in Patients with Kidney Impairment

OBJECTIVES/GOALS: Estimating kidney function for drug dosing poses safety and efficacy concerns with critical medications. This study aims to develop a pragmatic method for measuring kidney function, ensuring that critical clinical decision points based on kidney function are universally applicable to all patients, leading to improved health outcomes. METHODS/STUDY POPULATION: This is a single-dose pharmacokinetic (PK) study to evaluate the concordance between iopamidol- and iohexol-measured glomerular filtration rate (mGFR), as determined by their respective serum clearances, in a cohort of 24 adults with varying kidney function. Participants with estimated glomerular filtration rates (CKD-EPI eGFRcr) ranging from >30 to 120 mL/min will be recruited from the Michigan Medicine health system. Enrolled participants will be stratified into 3 kidney function groups based on conventual kidney dosing considerations. IV micro doses of iohexol and iopamidol will be administered, followed by blood sampling. PK analysis will be used to compare the clearance of these substances. The agreement between iohexol and iopamidol in measuring GFR will be assessed via bioequivalence analysis. RESULTS/ANTICIPATED RESULTS: We expect no statistically significant difference between iopamidol and iohexol CL due to the high similarity of iopamidol and iohexol molecular and PK properties. We also expect that the ordinary least square regression analysis of iopamidol mGFRand iohexol mGFR will show limited variability across GFR measurements. These expected results will support the use of iopamidol as a marker of mGFR and its interchangeability with the gold standard iohexol. DISCUSSION/SIGNIFICANCE: Addressing eGFR errors is crucial for accurately dosing critical medications. This study aims to develop a novel mGFR methodology that accommodates various kidney function levels. This will enable precision dosing and streamline clinical trials. It also eliminates biological variability, enhancing generalizability and health outcomes.

Abstract 6381: Long-term kidney function after treatment for unilateral, non-metastatic, non-syndromic Wilms tumor. A report from the St. Jude Lifetime Cohort Study

Abstract Background: We previously reported that the estimated glomerular filtration rate (eGFR) was decreased among survivors of unilateral, non-metastatic, non-syndromic Wilms tumor (WT) treated with whole abdomen radiation therapy (WART) compared to controls, but not compared to unirradiated WT survivors (Pediatr Blood Cancer 2020;67:e28271). The impact of sex on estimates of kidney function among adult survivors of WT has not been well-documented. Methods: We clinically evaluated male and female WT survivors with creatinine and cystatin C, calculated eGFR using the Chronic Kidney Disease - Epidemiology (CKD-EPI) equations with and without cystatin C and measured 99mTc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. WT survivors consisted of 20 treated with unilateral nephrectomy (UN), non-nephrotoxic chemotherapy (NNC) and whole abdomen radiation therapy (WART) (mean - 20.2 Gray (Gy); standard deviation (SD) - 9.12 Gy), and 20 treated with UN, no radiation therapy, and NNC. Correlations between 99mTc DTPA clearance and eGFR were calculated. Results: Among female WT survivors, none of the eGFR calculations was statistically significantly correlated with 99mTc DTPA clearance. Among male WT survivors, 99mTc DTPA clearance correlated well with eGFR calculations that included creatinine. Results are shown in the Table. Conclusions: Among female survivors of unilateral, non-metastatic, non-syndromic WT who have undergone UN, eGFR is poorly correlated with 99mTc DTPA clearance. Evaluation of treatment-related changes in body composition may provide insight into these results. Correlation between eGFR and 99mTc DTPA clearance Females eGFR(CKD-EPI) 99mTc DTPA clearance No radiation therapy (n=13) Whole abdomen radiation therapy(n=12) Pearson correlation coefficient p-value Pearson correlation coefficient p-value Creatinine only 0.109 0.723 -0.295 0.352 Cystatin C only 0.311 0.301 0.094 0.782 Creatinine and cystatin C 0.348 0.244 -0.028 0.935 Males No radiation therapy (n=6) Whole abdomen radiation therapy(n=6) Pearson correlation coefficient p-value Pearson correlation coefficient p-value Creatinine only 0.827 0.043 0.859 0.028 Cystatin C only 0.811 0.050 0.592 0.216 Creatinine and cystatin C 0.878 0.021 0.866 0.026 Citation Format: Daniel M. Green, Mingjuan Wang, Matthew J. Krasin, Andrew M. Davidoff, DeoKumar Srivastava, Dennis W. Jay, Kirsten K. Ness, Barry L. Shulkin, Jennifer Q. Lanctot, Kyla C. Shelton, Rachel C. Brennan, Matthew J. Ehrhardt, Stephanie Dixon, Beth A. Kurt, Leslie L. Robison, Melissa M. Hudson, Sheri L. Spunt. Long-term kidney function after treatment for unilateral, non-metastatic, non-syndromic Wilms tumor. A report from the St. Jude Lifetime Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6381.

Cystatin C Outperforms Creatinine in Predicting Cefepime Clearance in Pediatric Stem Cell Transplant Recipients

BackgroundPediatric hematopoietic stem cell transplant (HSCT) patients are at risk of developing both sepsis and altered kidney function. Cefepime is used for empiric coverage post-HSCT and requires dose adjustment based on kidney function. Since cefepime's anti-microbial efficacy is determined by the time free concentrations exceed bacterial minimum inhibitory concentration (MIC), it is important to assess kidney function accurately to ensure adequate concentrations. Serum creatinine (SCr) is routinely used to estimate glomerular filtration rate (eGFR) but varies with muscle mass, which can be significantly lower in HSCT patients, making SCr an inaccurate kidney function biomarker. Cystatin C (CysC) eGFR is independent of muscle mass, though steroid use increases CysC. ObjectivesTo describe how eGFR impacts cefepime pharmacokinetic/pharmacodynamic (PK/PD) target attainment in pediatric HSCT patients, to investigate which method of estimating GFR (SCr, CysC, combined) best predicts cefepime clearance, and to explore additional predictors of cefepime clearance. Study DesignPatients admitted to the pediatric HSCT unit who received ≥2 cefepime doses were prospectively enrolled. We measured total cefepime peak/trough concentrations between the 2nd-4th cefepime doses and measured SCr and CysC if not already obtained clinically within 24h of cefepime samples. eGFRs were calculated with Chronic Kidney Disease in Children U25 equations. Bayesian estimates of cefepime clearance were determined with a pediatric cefepime PK model and PK software MwPharm++. Simple linear regression was used to compare cefepime clearance normalized to body surface area (BSA) to BSA-normalized SCr-, CysC-, and SCr-/CysC-eGFRs, while multiple linear regression was used to account for additional predictors of cefepime clearance. For target attainment, we assessed the percentage of time free cefepime concentrations exceeded 1x MIC (%fT>1x MIC) and 4x MIC (%fT>4x MIC) using a susceptibility breakpoint of 8 mg/L for Pseudomonas aeruginosa. ResultsWe enrolled 53 patients (ages 1-30 years, median 8.9 years). SCr- and CysC-eGFRs were lower in patients who attained 100% fT>1xMIC compared to those who did not attain this target: 115 vs 156 mL/min/1.73m2 (p=0.01) for SCr-eGFR and 73.5 vs 107 mL/min/1.73m2 (p<0.001) for CysC-eGFR. SCr-eGFR was weakly positively correlated with cefepime clearance (adjusted [a]r2=0.14), while CysC-eGFR and SCr-/CysC-eGFR had stronger positive correlations (ar2=0.30 CysC, ar2=0.28 combo. There was a weak, significant linear association between increasing CysC-eGFR and decreased %fT>1xMIC (ar2=0.32) and %fT>4xMIC (ar2=0.14). No patients with a CysC-eGFR >120 mL/min/1.73 m2 achieved 100% fT>1xMIC or 50% fT>4x MIC. In multiple regression models, underlying diagnosis of hemoglobinopathy (in all models) and being pre-transplant (in SCr and combined models) were associated with increased cefepime clearance, while concomitant use of calcineurin inhibitors was associated with decreased cefepime clearance in all models. Overall, the combo-eGFR model with timing pre-transplant, hemoglobinopathy, and use of calcineurin inhibitors had the best performance (ar2=0.63). ConclusionsCysC-based eGFRs (CysC alone and combined) predicted cefepime clearance better than SCr-eGFR, even after considering steroid use. Increasing CysC eGFR correlated with decreased probability of PD target attainment, raising concerns for underdosing at high eGFRs. CysC should be included when estimating kidney function to provide adequate dosing of cefepime in pediatric HSCT patients.

Toward Equitable Kidney Function Estimation in Critical Care Practice: Guidance From the Society of Critical Care Medicine's Diversity, Equity, and Inclusion in Renal Clinical Practice Task Force.

Accurate glomerular filtration rate (GFR) assessment is essential in critically ill patients. GFR is often estimated using creatinine-based equations, which require surrogates for muscle mass such as age and sex. Race has also been included in GFR equations, based on the assumption that Black individuals have genetically determined higher muscle mass. However, race-based GFR estimation has been questioned with the recognition that race is a poor surrogate for genetic ancestry, and racial health disparities are driven largely by socioeconomic factors. The American Society of Nephrology and the National Kidney Foundation (ASN/NKF) recommend widespread adoption of new "race-free" creatinine equations, and increased use of cystatin C as a race-agnostic GFR biomarker. Literature review and expert consensus. English language publications evaluating GFR assessment and racial disparities. We provide an overview of the ASN/NKF recommendations. We then apply an Implementation science methodology to identify facilitators and barriers to implementation of the ASN/NKF recommendations into critical care settings and identify evidence-based implementation strategies. Last, we highlight research priorities for advancing GFR estimation in critically ill patients. Implementation of the new creatinine-based GFR equation is facilitated by low cost and relative ease of incorporation into electronic health records. The key barrier to implementation is a lack of direct evidence in critically ill patients. Additional barriers to implementing cystatin C-based GFR estimation include higher cost and lack of test availability in most laboratories. Further, cystatin C concentrations are influenced by inflammation, which complicates interpretation. The lack of direct evidence in critically ill patients is a key barrier to broad implementation of newly developed "race-free" GFR equations. Additional research evaluating GFR equations in critically ill patients and novel approaches to dynamic kidney function estimation is required to advance equitable GFR assessment in this vulnerable population.

Clinical Studies on Diabetic and Non- Diabetic Patients with Respect to Lipid Profile Test

Introduction; Dyslipidemia is one of the major cardiovascular disease (CVD) risk factors and plays an important role in the progress of atherosclerosis. The prevalence of Dyslipidemia in type 2 diabetes is double with respect to the general population. These are more complex abnormalities that are caused by the interrelation among obesity, insulin resistance and hyper insulin. It is worth to emphasize that the fatty tissue is exclusively related to risk factors, such as the altered insulin and lipid profile, which can contribute to the development of the insulin resistance syndrome, which comprises several risk factors for the emergence of cardiovascular complications. In patients with type 2 diabetes, which is equivalent most commonly characterized by elevated TG and reduced HDL-C. These abnormalities can be present alone or in combination with other metabolic disorders. Material and Method : This project was conducted by the department of Biochemistry at Asian Diagnostic lab from two month period of time on 300 patients belongs Bangalore urban district (kalasipalya) were Selected. Blood glucose, lipid profile, kidney function and liver function estimation was done by Uv test of Enzymatic reference method. COBASc311 ANALYSE Roche/Hitachi Cobas c 311 analyzer is an automated software controlled system for clinical chemistry analysis both qualitative and quantitative analysis determination

Comparing five equations to estimate glomerular filtration rate or creatinine clearance and assign individuals to KDIGO categories across the full age spectrum using real world data

AbstractFive equations are commonly used by biopharma companies to estimate glomerular filtration rate (GFR) or creatinine clearance (CrCl) based on regulatory and stakeholder recommendations. Changes observed in GFR and/or CrCl can be challenging to interpret as participants transition between age strata, prompting changes in equations. This manuscript explores how GFR, CrCl, and the resulting Kidney Disease Improving Global Outcomes (KDIGO) categories of kidney function can change when different equations are used. We analyzed descriptively real‐world data (RWD) from 48 health care organizations in the United States to identify patients with data (age, sex, height, weight, serum biomarkers such as creatinine [Scr] and/or cystatin C [Scys]) sufficient to estimate GFR and/or CrCl. Five equations (Bedside Schwartz, Modified Schwartz, Cockcroft‐Gault, 2021 Chronic Kidney Disease‐Epidemiology Collaboration [CKD‐EPI] Scr, and 2021 CKD‐EPI Scr/Scys) were used to estimate GFR and/or CrCl and assign individuals to KDIGO categories (G1–G5). We identified 32,728 patients, including 378 infants (&lt;2 years), 1191 younger children (2 to &lt;6 years), 1891 older children (6 to &lt;12 years), 3174 adolescents (12 to &lt;18 years), 16,367 younger adults (18 to &lt;65 years), and 9727 older adults (65+ years) with sufficient information to estimate kidney function. For patients greater than or equal to 2 years, estimated GFR and/or CrCl and KDIGO categories based on the 2021 CKD‐EPI Scr/Scys equation appeared similar to those based on currently recommended equations. RWD suggests the 2021 CKD‐EPI Scr/Scys equation could potentially be used to estimate GFR in individuals aged 2 years and older; more research is needed to confirm these findings.

Novel equations for estimating renal function: significance for drug dose adjustment

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. 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 cystatinC in assessing kidney function. Particularly in patients with significantly reduced or increased muscle mass, creatinine is not suitable for determining GFR, and cystatinC should be used. Currently recommended GFR estimating equations are described, illustrating for which patient groups they can be used. Alarge 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. Estimated GFR (eGFR) is only arough 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.

Glomerular filtration rate measurement during platinum treatment for urothelial carcinoma: optimal methods for clinical practice

BackgroundWe assessed the accuracy of four estimated glomerular filtration rate (eGFR) methods: MDRD, Cockcroft–Gault, CKD-EPI, and Wright.MethodThe four methods were compared to measure GFR (mGFR) in patients with urothelial urinary tract cancer (T2-T4bNxMx) receiving platinum-based chemotherapy at Rigshospitalet, Copenhagen, from January 2019 to December 2021. Using standardized assays, creatinine values were measured, and mGFR was determined using Technetium-99 m diethylenetriaminepentaacetic acid (Tc-99 m-DTPA) or Cr-51-ethylenediaminetetraacetic acid (Cr-51-EDTA) plasma clearance. Patients (n = 146) with both mGFR and corresponding creatinine values available were included (n = 345 measurements).ResultsThe CKD-EPI method consistently demonstrated superior accuracy, with the lowest Total Deviation Index of 21.8% at baseline and 22.9% for all measurements compared to Wright (23.4% /24.1%), MDRD (26.2%/25.5%), and Cockcroft–Gault (25.x%/25.1%). Bland Altman Limits of agreement (LOA) ranged from − 32 ml/min (Cockcroft–Gault) to + 33 ml/min (MDRD), with CKD-EPI showing the narrowest LOA (− 27 ml/min to + 24 ml/min and lowest bias (0.3 ml/min). Establishing an eGFR threshold at 85 ml/min—considering both the lower limit of agreement (LOA) and the minimum cisplatin limit at 60 ml/min—allows for the safe omission of mGFR in 30% of patients in this cohort.ConclusionCKD-EPI equation emerged as the most suitable for estimating kidney function in this patient group although not meeting benchmark criteria. We recommend its use for initial assessment and ongoing monitoring, and suggest mGFR for patients with a CKD-EPI estimated GFR below 85 ml/min. This approach could reduce costs and decrease laboratory time for 30% of our UC patients.

Prescription audit of renally excreted drugs and vancomycin dosing for older patients with reduced kidney function

Japan has the largest aging population in the world, and kidney function declines with age. Therefore, when administering renally excreted drugs to older patients, the dosage should be adjusted according to the kidney function. This study addresses the appropriate use of renally excreted drugs in older patients in two topics. The first topic is concerned with the author’s experience with cibenzoline overdose, which led the author to conduct a survey of renally excreted drugs and establish an in-hospital prescription checking system for these drugs. The second topic clarifies the usefulness of serum creatinine-based kidney function estimation equations for predicting the area under the concentration-time curve of vancomycin in bedridden older patients. Based on these findings, the importance of pharmaceutical interventions by pharmacists in the pharmacotherapy of older patients with reduced kidney function is discussed

Clinical and biochemical associations of urinary metabolites: quantitative epidemiological approach on renal-cardiometabolic biomarkers.

Urinary metabolomics has demonstrated considerable potential to assess kidney function and its metabolic corollaries in health and disease. However, applications in epidemiology remain sparse due to technical challenges. We added 17 metabolites to an open-access urinary nuclear magnetic resonance metabolomics platform, extending the panel to 61 metabolites (n = 994). We also introduced automated quantification for 11 metabolites, extending the panel to 12 metabolites (+creatinine). Epidemiological associations between these 12 metabolites and 49 clinical measures were studied in three independent cohorts (up to 5989 participants). Detailed regression analyses with various confounding factors are presented for body mass index (BMI) and smoking. Sex-specific population reference concentrations and distributions are provided for 61 urinary metabolites (419 men and 575 women), together with methodological intra-assay metabolite variations as well as the biological intra-individual and epidemiological population variations. For the 12 metabolites, 362 associations were found. These are mostly novel and reflect potential molecular proxies to estimate kidney function, as the associations cannot be simply explained by estimated glomerular filtration rate. Unspecific renal excretion results in leakage of amino acids (and glucose) to urine in all individuals. Seven urinary metabolites associated with smoking, providing questionnaire-independent proxy measures of smoking status in epidemiological studies. Common confounders did not affect metabolite associations with smoking, but insulin had a clear effect on most associations with BMI, including strong effects on 2-hydroxyisobutyrate, valine, alanine, trigonelline and hippurate. Urinary metabolomics provides new insight on kidney function and related biomarkers on the renal-cardiometabolic system, supporting large-scale applications in epidemiology.

Estimation of kidney function for medication dosing in adult patients with chronic kidney disease: a practice update

AbstractChronic kidney disease (CKD) is a major health concern with a growing disease burden and inequalities in access to treatments. Glomerular filtration rate (GFR) is accepted as the best overall measure of kidney function and is considered the most important measure for medications cleared by the kidneys. In clinical practice, equations that estimate GFR using validated prediction equations are routinely used. This practice update was developed by a Working Group comprising clinical pharmacists representing the Society of Hospital Pharmacists of Australia (SHPA) Specialty Practice streams of Nephrology, Oncology and haematology, Critical care and Infectious diseases. It is intended to provide practical recommendations for clinical pharmacists who use equations to estimate GFR for medication dosing decisions. The limitations of the various equations in use — such as the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI), the Cockcroft–Gault equation and Modification of Diet in Renal Disease — are summarised and compared to direct measures of kidney function using exogenous markers. The CKD‐EPI equation is recommended to be used routinely as a primary measure of kidney function. Dose adjustments should also consider medication‐specific, patient‐related, and disease‐related characteristics. Kidney function and the response to therapy should be continuously assessed by monitoring the signs, symptoms and disease outcomes, the emergence of adverse reactions or medication‐induced disorders and use therapeutic drug monitoring (if available) to adjust doses accordingly.

Kidney function by creatinine and cystatin c and adverse cardiovascular outcomes in patients with atrial fibrillation

Abstract Background Atrial fibrillation (AF) patients with chronic kidney disease are at an increased risk for ischemic and bleeding events and all-cause mortality. Accurate kidney function estimation is key for risk assessment. Creatinine is commonly used to calculate the Glomerular Filtration Rate (GFR). However, cystatin c has been described to be more sensitive than creatinine independent of muscle mass, autoimmune disease, inflammation or consuming diseases. Thus, cystatin C might be superior for risk assessment in patients with AF. Aim We aimed to investigate the associations between kidney function, assessed by creatinine and cystatin c, and major adverse cardiovascular events (MACE), its individual components, and major bleedings. Methods We enrolled 3865 AF patients into two prospective, multicenter cohort studies. Creatinine and cystatin c were measured at baseline and clinical outcome events were assessed yearly. We calculated GFR using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula based on either creatinine (GFRcr), cystatin c (GFRcy) or both (GFRc2). Primary outcome was MACE, defined as a composite of stroke or systemic embolism, myocardial infarction and cardiovascular death. Secondary outcomes were the individual components of MACE and major bleeding. Multivariable adjusted Cox regression analyses were built to investigate the associations between kidney function and adverse outcome events. Results Mean age was 71 ± 10 years and 28% were female. Mean creatinine and cystatin levels were 103 ± 32 μmol/l and 1.2 ± 0.4 mg/l, respectively, translating to a GFRc2 of 63.8 ± 21.7 ml/min/1.73 m2. Over a median follow-up of 6 years, the incidence rates for MACE (per 100 person-years) across quartiles (Q1-Q4) of GFRc2 were 22.0, 19.6, 17.4 and 15.9, respectively (Figure). When using multivariable adjusted Cox regression analysis, MACE was significantly associated with GFRcr (per 1 standard deviation: HR 0.87 (95%CI 0.77; 0.97) p=0.01), GFRcy (HR 0.68 (CI 0.58; 0.78), p&amp;lt;0.001) and GFRc2 (HR 0.75 (CI 0.66; 0.86), p&amp;lt;0.001). This association was mainly driven by cardiovascular death (Table). Major bleeding was associated with GFRcy (HR 0.73 (0.60-0.88) p=0.001) and GFRc2 (HR 0.80 (0.67-0.95), p=0.01), but not with GFRcr (HR 0.91 (95% CI 0.78-1.07) p=0.25). Conclusion Among AF patients, GFR equations including cystatin c were associated both with MACE and bleeding events, while creatinine based GFR equations were only associated with MACE. Therefore, Cystatin c based GFR equations might offer more comprehensive risk stratification in AF patients.Figure 1Table 1

Incorporation of Cystatin C in Estimating Kidney Function: Real-World Experience in Sweden

Incorporation of Cystatin C in Estimating Kidney Function: Real-World Experience in Sweden

African American/Black race, apolipoprotein L1 , and serum creatinine among persons with HIV.

Accurate estimation of kidney function is critical among persons with HIV (PWH) to avoid under-dosing of antiretroviral therapies and ensure timely referral for kidney transplantation. Existing estimation equations for kidney function include race, the appropriateness of which has been debated. Given advancements in understanding of race and the necessity of accuracy in kidney function estimation, this study aimed to examine whether race, or genetic factors, improved prediction of serum creatinine among PWH. This cross-sectional study utilized data from the Center for AIDS Research Network of Integrated Clinical Systems cohort (2008-2018). The outcome was baseline serum creatinine. Ordinary least squares regression was used to examine whether inclusion of race or genetic factors [ apolipoprotein-L1 ( APOL1 ) variants and genetic African ancestry] improved serum creatinine prediction. A reduction in root mean squared error (RMSE) greater than 2% was a clinically relevant improvement in predictive ability. There were 4183 PWH included. Among PWH whose serum creatinine was less than 1.7 mg/dl, race was significantly associated with serum creatinine ( β = 0.06, SE = 0.01, P < 0.001) but did not improve predictive ability. African ancestry and APOL1 variants similarly failed to improve predictive ability. Whereas, when serum creatinine was at least 1.7 mg/dl, inclusion of race reduced the RMSE by 2.1%, indicating improvement in predictive ability. APOL1 variants further improved predictive ability by reducing the RMSE by 2.9%. These data suggest that, among PWH, inclusion of race or genetic factors may only be warranted at higher serum creatinine levels. Work eliminating existing healthcare disparities while preserving the utility of estimating equations is needed.