Transplant Clinician Opinions on Use of Race in the Estimation of Glomerular Filtration Rate

Background and objectivesCurrent race-based eGFR calculators assign a higher eGFR value to Black patients, which could affect the care of kidney transplant candidates and potential living donors.Design, setting, participants, & measurementsWe conducted a survey of staff at adult kidney transplant centers in the United States (December 17, 2020 to February 28, 2021) to assess opinions on use of race-based eGFR equations for waitlisting and living donor candidate evaluation, availability of serum cystatin C testing and measured GFR, and related practices.ResultsRespondents represented 57% (124 of 218) of adult kidney transplant programs, and the responding centers conducted 70% of recent kidney transplant volume. Most (93%) programs use serum creatinine–based eGFR for listing candidates. However, only 6% of respondents felt that current race-based eGFR calculators are appropriate, with desire for change grounded in concerns for promotion of health care disparities by current equations and inaccuracies in reporting of race. Most respondents (70%) believed that elimination of race would allow more preemptive waitlisting for Black patients, but a majority (79%) also raised concerns that such an approach could incur harms. More than one third of the responding programs lacked or were unsure of availability of testing for cystatin C or measured GFR. At this time, 40% of represented centers did not plan to remove race from eGFR calculators, 46% were planning to remove, and 15% had already done so. There was substantial variability in eGFR reporting and listing of multiracial patients with some Black ancestry. There was no difference in GFR acceptance thresholds for Black versus non-Black living donors.ConclusionsThis national survey highlights a broad consensus that extant approaches to GFR estimation are unsatisfactory, but it also identified a range of current opinions.

Development and Validation of Creatinine-Based Estimates of the Glomerular Filtration Rate Equation from 99mTc-DTPA Imaging in the Malaysian Setting

Introduction. Accurate assessment of glomerular filtration rate (GFR) is very important for diagnostic and therapeutic intervention. Clinically, GFR is estimated from plasma creatinine using equations such as Cockcroft–Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations. However, these were developed in the Western population. To the best of our knowledge, there was no equation that has been developed specifically in our population. Objectives. We developed a new equation based on the gold standard of 99mTc-DTPA imaging measured GFR. We then performed an internal validation by comparing the bias, precision, and accuracy of the new equation and the other equations with the gold standard of 99mTc-DTPA imaging measured GFR. Methods. This was a cross-sectional study using the existing record of patients who were referred for 99mTc-DTPA imaging at the Nuclear Medicine Centre, International Islamic University Malaysia. As this is a retrospective study utilising routinely collected data from the existing pool of data, the ethical committee has waived the need for informed consent. Results. Data of 187 patients were analysed from January 2016 to March 2021. Of these, 94 were randomised to the development cohort and 93 to the validation cohort. A new equation of eGFR was determined as 16.637 ∗ 0.9935Age ∗ (SCr/23.473)−0.45159. In the validation cohort, both CKD-EPI and the new equation had the highest correlation to 99mTc-DTPA with a correlation coefficient of 0.81 ( p < 0.0001 ). However, the new equation had the least bias and was the most precise (mean bias of −3.58 ± 12.01) and accurate (P30 of 64.5% and P50 of 84.9%) compared to the other equations. Conclusion. The new equation which was developed specifically using our local data population was the most accurate and precise, with less bias compared to the other equations. Further study validating this equation in the perioperative and intensive care patients is needed.

Estimated glomerular filtration rate equations in people of self-reported black ethnicity in the United Kingdom: Inappropriate adjustment for ethnicity may lead to reduced access to care

Assessment in African populations suggest adjustment for ethnicity in estimated glomerular filtration rate (eGFR) equations derived from African Americans lead to overestimation of GFR and failure to determine severity in chronic kidney disease (CKD). However, studies in African Europeans are limited. We aimed to assess accuracy of eGFR equations, with and without ethnicity adjustment compared with measured GFR in people of Black ethnicity in the United Kingdom. Performance of MDRD, CKD-EPI (with and without ethnicity adjustment), Full Age Spectrum (FAS), revised Lund Malmö (LM Revised), and European Kidney Function Consortium (EKFC) eGFR equations were assessed compared to 51Cr-EDTA GFR studies extracted from hospital databases. Participants with albumin <30g/l, liver disease, <18 years, of non-Black or non-White self-reported ethnicity were excluded. Agreement was assessed by bias, precision and 30%-accuracy and was stratified for ethnicity and GFR. 1888 51Cr-EDTA studies were included (Mean age-53.7yrs; 43.6% female; 14.1% Black ethnicity). Compared to White participants, eGFR-MDRD and eGFR-CKD-EPI equations in Black participants significantly overestimated GFR (bias 20.3 and 19.7 ml/min/1.73m2 respectively, p<0.001). Disregarding the ethnicity adjustment significantly improved GFR estimates for Black participants (bias 6.7 and 2.4ml/min/1.73m2 for eGFR-MDRD and eGFR-CKD-EPI respectively, p<0.001). The LM Revised equation had the smallest bias for both White and Black participants (5.8ml and -1.1ml/min/1.73m2 respectively). 30%-accuracy was superior for GFR≥60ml/min/1.73m2 compared to <60ml/min/1.73m2 using eGFR-CKD-EPI equation for both White and Black participants (p<0.001). Multivariate regression methodology with adjustment for age, sex and log(serum creatinine) in the cohort yielded an ethnicity coefficient of 1.018 (95% CI: 1.009–1.027). Overestimation of measured GFR with eGFR equations using ethnicity adjustment factors may lead to reduced CKD diagnosis and under-recognition of severity in people of Black ethnicity. Our findings suggest that ethnicity adjustment for GFR estimation in non-African Americans may not be appropriate for use in people of Black ethnicity in the UK.

The evaluation of kidney function in living kidney donor candidates

Living kidney donors incur a small increased risk of end-stage kidney disease (ESKD), of which pre-donation glomerular filtration rate (GFR) is an important determinant. As a result, kidney function assessment is central to the donor candidate evaluation and selection process. This article reviews the different methods of GFR assessment including estimated GFR, creatinine clearance and measured GFR, and the current guidelines on GFR thresholds for donor acceptance. Estimated GFR obtained using the 2009 Chronic Kidney Disease Epidemiology Collaboration equation, while the best of estimating estimations, tends to underestimate and has limited accuracy, especially near normal GFR values. In the United States, the Organ Procurement and Transplantation Network policy on living donation mandates either measured GFR or creatinine clearance as part of evaluation. Measured GFR is considered the gold standard, although there is some variation in performance characteristics depending on the marker and technique used. Major limitations of creatinine clearance are dependency on accuracy of timed collection, and overestimation as a result of distal tubular creatinine secretion. GFR declines with healthy aging, and most international guidelines recommend use of age-adapted selection criteria. The 2017 Kidney Disease: Improving Global Outcomes Guideline for the Evaluation and Care of Living Kidney Donors diverges from other guidelines and recommends using absolute cut-off of <60 ml/min/1.73m2 for exclusion and of ≥90 ml/min/1.73m2 for acceptance, and determination of candidacy with intermediate GFR based on long-term ESKD risk. However, several concerns for this strategy exist, including inappropriate acceptance of younger candidates due to underestimation of risk, and exclusion of older candidates whose kidney function is in fact appropriate for age. Role of cystatin C and other newer biomarkers, as well as data on impact of pre-donation GFR on not just ESKD risk but also advanced chronic kidney disease risk and cardiovascular outcomes are needed.

FC 053RATIO OF MEASURED GFR TO ESTIMATED GFR MAY PREDICT EARLY DEATH AND REQUIREMENT FOR DIALYSIS

Background and Aims It has been suggested that, in patients with CKD stage 5, measured GFR (mGFR), defined as the mean of urea and creatinine clearance as measured by a 24-hour urine collection, is a better measure of renal function than estimated GFR (eGFR), based on the CKD-EPI formula. This could be due to reduced muscle mass in this group. Its use is recommended in the ERBP guidelines. Unplanned dialysis initiation (UDI) is associated with increased morbidity, mortality, and reduced modality choice. It is generally considered undesirable. We hypothesized that the ratio mGFR/eGFR (R) aids prediction of death and end stage kidney disease (ESKD), as defined by permanent dialysis requirement or transplantation. Method All 24-hour measurements of urea and creatinine excretion were extracted from the clinical biochemistry databases in Zealand. Data concerning renal diagnosis, comorbidity, biochemistry, medical treatment, mortality and date of ESKD, were extracted from patient notes, the National Patient Registry and the Danish Nephrology Registry. Patients were included if their eGFR was &lt;30 ml/min/1.73m2. The last available value for each patient was included. Results 1265 patients were included. In 519, body surface area (BSA) was available, and the corrected ratio (RBSA) could be calculated. The urea clearance was 49 ±24% of creatinine clearance. R was median 0.88 (IQR 0.63-1.15), RBSA 0.87 (0.68-1.06). R was not related to eGFR. Comorbidity was associated with lower R, e.g. atherosclerosis (0.90 ±0.41 vs. 0.97 ±0.49*), heart failure (0.80 ±0.37 vs. 0.95 ±0.44*), pulmonary disease (0.80 ±0.37 vs. 0.94 ±0.44***), hepatic disease (0.67 ±0.41 vs. 0.92 ±0.43***), but not diabetes mellitus. It was related to albumin (r=0.24***), C-reactive protein (-0.22***) and biochemical markers of uraemia, e.g. bicarbonate (-0.19***). Medical treatment data was available in 137 patients. R was higher in patients treated with ACE inhibitors (1.20 ±0.50 vs. 1.01 ±0.36*) and diuretics (1.09 ±0.40 vs. 0.94 ±0.35*), but no other treatment groups. Patients were grouped as high R (H, &gt;1.25), medium (M, 0.75-1.25) or low (L, &lt;0.75). R was not associated with prognosis at one year, but L patients had a significantly higher ESKD and mortality incidence at 3 months. For patients with eGFR 10-15 ml/min/1.73m2, ESKD incidence was L 22%, M 15%, H 5%, mortality 19, 5, and 2% respectively. Similar findings were seen in other groups, e.g. eGFR 15-20 ml/min/1.73m2: ESKD 11, 2, and 0%; death 11, 5, and 1%. UDI was higher for L patients. For patients with eGFR 10-15 ml/min/1.73m2, UDI occurred in L: 47%, M:27%, H:25%. For patients with eGFR 10-15 ml/min/1.73m2 the figures were 51, 38 and 12% respectively. Findings for the subgroup of patients with RBSA measurements were similar. *:p&lt;0.05; **:p&lt;001;***:p&lt;0.001 Conclusion A low mGFR/eGFR ratio is associated with comorbidity, malnutrition, inflammation and biochemical uraemia. It a marker of early ESKD, death and unplanned dialysis initiation, independently of eGFR. Particular attention paid to patients with a low R may lower the incidence of unplanned dialysis requirement.

MO504LOW BIRTH WEIGHT ASSOCIATES WITH SMALLER KIDNEY SIZE IN MIDDLE-AGED WOMEN

Background and Aims Low birth weight is associated with increased risk of kidney disease due to lower nephron endowment leading to hyperfiltration and subsequent nephron loss. Nephron number is thought to associate with kidney size. We compared kidney size measured by magnetic resonance imaging (MRI) with ultrasonography and measured glomerular filtration rate (mGFR) in adults with normal versus low birth weight. Method Healthy individuals aged 42-52 years with Low birth weight (LBW – 1100-2300g) and normal birth weight (NBW - 3500-4000g) were invited. GFR was measured using plasma clearance of iohexol. Kidney volume was measured on MRI images using axial T2 images and coronal T1 images with fat saturation without contrast enhancement, calculations were performed according to the ellipsoid formula - π/6 x Length x Width x Depth. Ultrasonographic imaging was done using a dorsal approach. In the maximal longitudinal view the parenchymal area was calculated subtracting the area of a manual tracing around the renal pelvis from the area of a manual tracing of the whole kidney. Volume and area from the two kidneys were added and total value was used for analyses. Kidney size measurements were compared between the two groups of LBW vs NBW, and analysis using Pearson’s correlation coefficient R between kidney volume and measured GFR and parenchymal area was performed. Results We included 102 individuals (54 LBW, 48 NBW). Total kidney volume was 302 ± 51 ml for female NBW vs 258 ± 48 ml for female LBW (p=0.002). For men, total kidney volume was 347 ± 51 ml vs 340 ± 65 ml (p=0.7). Measured GFR was significantly associated with kidney volume with R=0.52 (p&lt;0.001) for women and R=0.39 (p=0.007) for men. Kidney parenchymal area measurements using ultrasonography showed similar results with an R=0.77 between the MRI and the ultrasonography measurement and similar differences for sex and birth weight were seen. Conclusion Healthy middle-aged females born with LBW have smaller kidneys than healthy middle-aged females born with NBW, no difference were seen for males. Kidney volume associate with measured GFR.

Comparative study of various glomerular filtration rate estimating equations in Egyptian patients with hepatitis C virus-related liver cirrhosis: a single-center observational study

Background Accurate assessment of GFR is critical in patients with chronic liver disease for early detection of renal disease. Cystatin C is a marker of GFR that seems to be more accurate than creatinine. The aim of the study is to assess of the performance of creatinine and cystatin C-based GFR equations in Egyptian patients with hepatitis C virus (HCV)-related liver cirrhosis as compared to measured creatinine clearance. GFR was estimated using five equations; three that were based on serum creatinine, another that was based on serum cystatin C, and a third that was based on both in 120 patients with HCV-related liver cirrhosis as well as 60 age- and sex-matched healthy controls. The bias, precision, and accuracy of each equation were determined as compared to measured creatinine clearance using the traditional equation U*V/P. Results The mean measured creatinine clearance was 51.39 ± 16.05 ml/min per 1.73 m2. The CKD-EPI creatinine-cystatin C equation had the greatest precision (7.5 ml/min per 1.73 m2), and highest accuracy (68 and 93% within 10% and 30% of measured GFR, respectively), but not the lowest bias (5.4 ml/min per 1.73 m2). The CKD-EPI creatinine-cystatin C equation remained accurate even in both males (69 and 90% within 10% and 30% of measured GFR, respectively) and females (68 and 97% within 10% and 30% of measured GFR, respectively). The CKD-EPI creatinine-cystatin C equation remained accurate even when the measured GFR was ≥ 60 ml/min per 1.73 m2 (60 and 90% within 10% and 30% of measured GFR, respectively with precision 10.5 ml/min per 1.73 m2). Conclusion CKD-EPI creatinine-cystatin C equation is more accurate at predicting GFR in HCV-related liver cirrhosis than creatinine- and cystatin-C alone based equations.

Evaluating chronic kidney disease in rural South Africa: comparing estimated glomerular filtration rate using point-of-care creatinine to iohexol measured GFR

Objectives The prevalence of chronic kidney disease is rising rapidly in low- and middle-income countries. Serum creatinine and estimation of glomerular filtration rate (GFR) are critical diagnostic tools, yet access to centralised laboratory services remains limited in primary care resource-limited settings. The aim of this study was to evaluate point-of-care (POC) technologies for serum creatinine measurement and to compare their performance to a gold standard measurement using iohexol measured GFR (mGFR). Methods POC creatinine was measured using iSTAT® and StatSensor® devices in capillary and venous whole blood, and laboratory creatinine was measured using the compensated kinetic Jaffe method in 670 participants from a rural area in South Africa. GFR estimating equations Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease (CKD-EPI and MDRD) for POC and laboratory creatinine were compared to iohexol mGFR. Results Calculated GFR for laboratory and POC creatinine measurements overestimated GFR (positive bias of 1.9–34.1 mL/min/1.73 m2). However, all POC devices had less positive bias than the laboratory Jaffe method (1.9–14.7 vs. 34.1 for MDRD, and 8.4–19.9 vs. 28.6 for CKD-EPI). Accuracy within 30% of mGFR ranged from 0.56 to 0.72 for POC devices and from 0.36 to 0.43 for the laboratory Jaffe method. POC devices showed wider imprecision with coefficients of variation ranging from 4.6 to 10.2% compared to 3.5% for the laboratory Jaffe method. Conclusions POC estimated GFR (eGFR) showed improved performance over laboratory Jaffe eGFR, however POC devices suffered from imprecision and large bias. The laboratory Jaffe method performed poorly, highlighting the need for laboratories to move to enzymatic methods to measure creatinine.

Assessment of kidney function: clinical indications for measured GFR

In the vast majority of cases, glomerular filtration rate (GFR) is estimated using serum creatinine, which is highly influenced by age, sex, muscle mass, body composition, severe chronic illness and many other factors. This often leads to misclassification of patients or potentially puts patients at risk for inappropriate clinical decisions. Possible solutions are the use of cystatin C as an alternative endogenous marker or performing direct measurement of GFR using an exogenous marker such as iohexol. The purpose of this review is to highlight clinical scenarios and conditions such as extreme body composition, Black race, disagreement between creatinine- and cystatin C–based estimated GFR (eGFR), drug dosing, liver cirrhosis, advanced chronic kidney disease and the transition to kidney replacement therapy, non-kidney solid organ transplant recipients and living kidney donors where creatinine-based GFR estimation may be invalid. In contrast to the majority of literature on measured GFR (mGFR), this review does not include aspects of mGFR for research or public health settings but aims to reach practicing clinicians and raise their understanding of the substantial limitations of creatinine. While including cystatin C as a renal biomarker in GFR estimating equations has been shown to increase the accuracy of the GFR estimate, there are also limitations to eGFR based on cystatin C alone or the combination of creatinine and cystatin C in the clinical scenarios described above that can be overcome by measuring GFR with an exogenous marker. We acknowledge that mGFR is not readily available in many centres but hope that this review will highlight and promote the expansion of kidney function diagnostics using standardized mGFR procedures as an important milestone towards more accurate and personalized medicine.

Concomitant weekly cisplatin-based chemoradiotherapy in head and neck cancer: the value of a second measured glomerular filtration rate during treatment

Objectives: To assess the efficacy of the second measured glomerular filtration rate (GFR) during the course of weekly cisplatin-based chemoradiotherapy in head and neck cancer. Methods: Data was collected on consecutive 221 head and neck cancer patients who underwent cisplatin-based chemoradiotherapy. Results: 68% patients managed to complete at least five out six proposed cycles of cisplatin, with a cumulative dose of ≥200 mg/m 2 . 181 patients underwent second measured GFR and it showed a mean fall in measured GFR by 12.0 ml/min/1.73 m 2 (p < 0.0001). Out of these 181 patients, in 16 patients (9%), the decision to discontinue cisplatin was purely based on a low second measured GFR (below 50 ml/min/1.73 m 2 ). Conclusion: Our study has shown that obtaining a second measured GFR is valuable in 9% of these patients. We propose that this should be considered as a standard procedure in these settings and also should be considered incorporating this additional safety measure, into future clinical trials as a mandatory procedure. Advances in knowledge: To the best of author’s knowledge, this is first study of its kind. The results of our study suggest that it should be a standard procedure of obtaining a second GFR in these settings.