True Glomerular Filtration Rate Research Articles

New developments and future prospects in the field of glomerular filtration rate estimation

Glomerular filtration rate (GFR) is estimated from equations based on serum or plasma concentrations of endogenous markers (creatinine and/or cystatin C), and demographic data (age, sex, ± ethnicity). These equations are accurate at the population level, but often inaccurate at the individual level. The creatinine-based Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation published in 2009 (CKD-EPIcr-2009), and the CKD-EPI equation published in 2012 based on creatinine and cystatin C, were recalibrated in 2021 to remove their dedicated race correction factors for black American subjects. All creatinine-based CKD-EPI equations overestimate true GFR in subjects younger than 30 years. The Full Age Spectrum (FAS) equation, applicable across the entire age spectrum (pediatrics to old age), solved this problem, but remained suboptimal at low GFR values. The European Kidney Function Consortium (EKFC) equation published in 2021 was an improvement of the FAS equation, which also includes the Q factor (median creatinine in the general population). EKFC is applicable across the age spectrum and is efficient at low and normal GFR values. The new creatinine-based CKD-EPI equation (CKD-EPIcr-2021) underestimates GFR in Black Americans and overestimates it in non-Black Americans. In European and African subjects, CKD-EPIcr-2021 overestimates true GFR and should not be adopted. The EKFC equation, which performs well in this population, also performs well in European Black subjects and in African subjects, provided dedicated Q factors are used.

Estimated Glomerular Filtration Rate Using Cystatin C is a More Sensitive Marker for Kidney Dysfunction in Nonweight-bearing Individuals.

Individuals with neuromuscular disorders and neurogenic lower urinary tract dysfunction are commonly nonweight-bearing with lower lean muscle mass than the general population. We sought to compare estimated glomerular filtration rate equations that include creatinine, cystatin C, or both, in nonweight-bearing individuals and matched ambulatory controls. Records were reviewed for individuals with serum creatinine (Cr) and cystatin C (Cys) and diagnosis consistent with nonweight-bearing status, and matched ambulatory controls. The 2021 CKD-EPI (Chronic Kidney Disease-Epidemiology Collaboration) race agnostic equations were used to calculate estimated glomerular filtration rate. Renal function was compared by equation in the overall cohorts and in a patient subset with imaging and/or urinalysis evidence of renal dysfunction. Nonweight-bearing (n = 102) and control populations (n = 204) had similar demographics. In the nonweight-bearing population, estimated glomerular filtration rate differed when calculated using CKD-EPICr, CKD-EPICr+Cys, and CKD-EPICys (107, 93, 80 mL/min/1.73 m2, respectively, P < .001). The differences in estimated glomerular filtration rate were greater in the nonweight-bearing relative to the control group regardless of CKD-EPI equation pairs compared (P < .001). In the patient subset with imaging and/or proteinuria evidence of renal dysfunction, the nonweight-bearing population again had different estimated glomerular filtration rate when calculated using CKD-EPICr, CKD-EPICr+Cys, and CKD-EPICys (P < .001). Fifty-eight percent of nonweight-bearing individuals with evidence of renal dysfunction on imaging or urinalysis were reclassified into a lower estimated glomerular filtration rate category when using estimated glomerular filtration rateCys relative to estimated glomerular filtration rateCr. Estimated glomerular filtration rate equations containing serum creatinine, cystatin C, or both, validated in mostly ambulatory populations, are not equivalently accurate in estimating kidney function in nonweight-bearing individuals. Comparison of these equations against gold standard glomerular filtration rate measurement is needed to determine which most closely approximates true glomerular filtration rate.

Measurement and Estimation of Glomerular Filtration Rate in Children With Neurogenic Bladder: A Prospective Study

ObjectiveTo evaluate the performance of different equations used to estimate glomerular filtration rate (GFR) in children with neurogenic bladder (NB). MethodsThe GFR measured with the technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) dual-plasma sample clearance method was defined as the true GFR (tGFR). The Chronic Kidney Disease in Children (CKiD) equation for serum creatinine (Scr) and/or cystatin C (Cys C) was used for GFR calculation. Estimated GFR (eGFR) using CKiDScr, CKiDCys C, and CKiDScr+Cys C equations was compared with tGFR in children with NB. ResultsIn total, 458 children with NB were prospectively enrolled in this study. The mean tGFR was 73.84 ± 18.54 ml/min/1.73 m2, mean eGFRScr was 77.94 ± 18.38 ml/min/1.73 m2, mean eGFRCys C was 74.20 ± 17.64 ml/min/1.73 m2, and mean eGFRScr+Cys C was 75.70 ± 18.07 ml/min/1.73 m2. The correlation between the Scr-based equation and 99mTc-DTPA clearance method was low (r = 0.648). The Cys C-based equations exhibited the strongest correlations: CKiDCys C (r=0.891) and CKiDScr+Cys C (r = 0.879). The overall prevalence of chronic kidney disease (CKD) was 20.7%, 19.7%, 17.5%, and 12.4% according to tGFR, eGFRCys C, eGFRCys C+Scr and eGFRScr, respectively. The area under the curve (AUC) for the Receiver operating characteristic (ROC) curve of the CKiDCys C equation was the highest (AUCCKiDcys = 0.956). ConclusionThe Cys C-based CKiD equation was the most accurate for estimating GFR compared with 99mTc-DTPA clearance method in children with NB. The CKiDScr equation overestimated the GFR. The CKiDCys C equation can be used to detect initial stages of CKD in children with NB.

Should Estimated Glomerular Filtration Rate Be Adjusted for Race?

Should Estimated Glomerular Filtration Rate Be Adjusted for Race?

Extracellular fluid volume: A suitable indexation variable to assess impact of bariatric surgery on glomerular filtration rate in patients with chronic kidney disease.

BackgroundBariatric surgery (BS) might be a nephroprotective treatment in obese patients with chronic kidney disease (CKD), and the non-linear relation between body surface area (BSA) and extracellular fluid volume (ECFV) in obese people raises the question of the most relevant way to scale glomerular filtration rate (GFR) for assessing renal function changes after BS.MethodsWe screened 1774 BS candidates and analysed 10 consecutive participants with CKD stage 3. True GFR (mGFR), measured by the renal clearance of 51Cr-ethylenediaminetetraacetic acid (EDTA), was scaled either to BSA (mGFRBSA) or to ECFV measured by 51Cr-EDTA distribution volume (mGFRECFV) before and one year after BS.ResultsThe 10 candidates for BS had a mean body mass index of 43.3 ± 3.6 kg/m2 and a mean GFR of 48 ± 8 mL/min/1.73 m2. Six participants had a sleeve gastrectomy and four had a Roux-en-Y gastric bypass. One year after BS, ECFV decreased (23.2 ± 6.2 to 17.9 ± 4.3 L, p = 0.001), absolute mGFR was not significantly modified (74 ± 23 versus 68 ±19 mL/min), mGFRBSA did not change significantly (53 ± 18 versus 56 ± 17 mL/min/1.73 m2) whereas mGFRECFV significantly increased (42 ± 13 versus 50 ± 14 mL/min/12.9 L, p = 0.037). The relation between mGFRECFV and mGFRBSA was different from the identity line before (p = 0.014) but not after BS (p = 0.09).ConclusionThere is a difference between mGFRBSA and mGFRECFV following BS and the latter might better reflect the adequacy between renal function and corpulence.

Clinical implications of the estimated glomerular filtration rate

A correct determination of the glomerular filtration rate (GFR) is necessary and at the same time difficult. Using gold standard methods, such as measurement of inulin clearance, are not feasible in clinical practice raising the need for methods to estimate GFR using easy to measure endogenous biomarkers. Plasma concentrations of the filtration markers creatinine and cystatin C alone are not adequate to easily calculate kidney function. This is mainly due to anon-linear relationship between plasma concentrations and GFR and GFR-independent factors influencing the plasma concentrations. Therefore, formulae have been developed to estimate GFR using easily available variables. Currently, the most useful formulae are those developed by the modification of diet in renal disease (MDRD) study and more recently by the chronic kidney disease epidemiology (CKD-EPI) collaboration. For older individuals some specifically validated formulae were developed some years ago, among them the Berlin initiative study 1 (BIS-1) and BIS‑2 formulae. The accuracy of the estimated filtration rate (eGFR) with respect to the true GFR depends on various factors. The accuracy of the formula is especially low in the GFR range above 60 ml/min · 1.73 m2, during recent or rapid changes of GFR and in the case of extreme physical traits, especially a very high or low muscle mass. In older individuals an eGFR around 60 ml/min · 1.73 m2 alone is not sufficient to discriminate between age-related and disease-related decline in GFR. Nonetheless dosing of medications with predominantly renal excretion should be made according to the eGFR.

MELD-GRAIL-Na: Glomerular Filtration Rate and Mortality on Liver-Transplant Waiting List.

Among patients with cirrhosis awaiting liver transplantation, prediction of wait-list (WL) mortality is adjudicated by the Model for End Stage Liver Disease-Sodium (MELD-Na) score. Replacing serum creatinine (SCr) with estimated glomerular filtration rate (eGFR) in the MELD-Na score may improve prediction of WL mortality, especially for women and highest disease severity. We developed (2014) and validated (2015) a model incorporating eGFR using national data (n=17,095) to predict WL mortality. Glomerular filtration rate (GFR) was estimated using the GFR assessment in liver disease (GRAIL) developed among patients with cirrhosis. Multivariate Cox proportional hazard analysis models were used to compare the predicted 90-day WL mortality between MELD-GRAIL-Na (re-estimated bilirubin, international normalized ratio [INR], sodium, and GRAIL) versus MELD-Na. Within 3months, 27.8% were transplanted, 4.3% died on the WL, and 4.7% were delisted for other reasons. GFR as estimated by GRAIL (hazard ratio [HR] 0.382, 95% confidence interval [CI] 0.344-0.424) and the re-estimated model MELD-GRAIL-Na (HR 1.212, 95% CI 1.199-1.224) were significant predictors of mortality or being delisted on the WL within 3months. MELD-GRAIL-Na was a better predictor of observed mortality at highest deciles of disease severity (≥ 27-40). For a score of 32 or higher (observed mortality 0.68), predicted mortality was 0.67 (MELD-GRAIL-Na) and 0.51 (MELD-Na). For women, a score of 32 or higher (observed mortality 0.67), the predicted mortality was 0.69 (MELD-GRAIL-Na) and 0.55 (MELD-Na). In 2015, use of MELD-GRAIL-Na as compared with MELD-Na resulted in reclassification of 16.7% (n=672) of patients on the WL. Incorporation of eGFR likely captures true GFR better than SCr, especially among women. Incorporation of MELD-GRAIL-Na instead of MELD-Na may affect outcomes for 12%-17% awaiting transplant and affect organ allocation.

Proenkephalin Compared to Conventional Methods to Assess Kidney Function in Critically Ill Sepsis Patients.

ABSTRACTBackground:The assessment of renal function in clinical practice remains challenging. Using creatinine to assess the glomerular filtration rate (GFR) is notoriously inaccurate, and determination of the true GFR, e.g., using inulin or iohexol, is laborious and not feasible in daily practice. Proenkephalin (PENK) is a novel candidate biomarker for kidney function that is filtrated in the glomerulus, has shown to represent steady-state GFR in patients with different severities of renal insufficiency. In this pilot study in non-steady-state critically ill patients, we compared plasma PENK concentrations with creatinine-based GFR assessments and validated both against the “true GFR” measured using a gold standard method: iohexol plasma clearance.Methods:Twenty-three critically ill patients with septic shock were included. Kidney function was determined using the Modification of Diet in Renal Disease formula (eGFRMDRD), Endogenous Creatinine Clearance (GFRECC), and iohexol plasma clearance (GFRiohexol) during a 6-h window. Plasma PENK concentrations were measured using the penKid immunoassay.Results: The eGFRMDRD and GFRECC correlated with the GFRiohexol (R2 = 0.82, P < 0.0001 and R2 = 0.82, P < 0.0001 respectively); however, bias and variability were considerable: the eGFRMDRD overestimated the true GFR with 31 ± 35% (95% limits of agreement: −37% to 100%) and the GFRECC with 37 ± 49% (95% limits of agreement: −59% to 133%). Plasma PENK concentrations showed a very strong inverse correlation with the GFRiohexol (R2 = 0.90, P < 0.0001) which tended to be better compared with the correlation of eGFRMDRD (P = 0.06) and GFRECC (P = 0.08) with the GFRiohexol.Conclusions:In this pilot study in non-steady-state critically ill sepsis patients, GFR appears to be more accurately reflected by plasma PENK concentrations compared to conventional creatinine-based methods. Therefore, PENK holds promise as an accurate and feasible biomarker to determine kidney function during non-steady-state conditions in the critically ill.

The significance of C-reactive protein to albumin ratio in patients with decompensated cirrhosis.

BackgroundPrognostic indicators in patients with decompensated cirrhosis are vital for the estimation of death risk. The ratio of C-reactive protein to albumin (CAR) has been verified as a prognostic marker in patients with hepatocellular carcinoma and decompensated cirrhosis related to hepatitis B virus. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and gamma globulins have been separately studied in cirrhosis. We evaluated the predictive role of CAR and other inflammatory markers in decompensated patients.MethodsWe prospectively studied 159 patients with stable decompensated cirrhosis, calculating the following indexes: CAR, NLR, LMR, Child-Turcotte-Pugh (CTP), and model for end-stage liver disease (MELD).ResultsMELD (area under the curve [AUC] 0.814) and CTP score (AUC 0.752) were superior to the other markers above in predicting patients’ mortality (P<0.05). Patients with CAR<2.17 (median value) presented better times of survival: 20 months (12-27) vs. 14 months (10-17) (log rank P=0.015). NLR and LMR barely discriminated patients’ prognosis. In multivariate analysis, only MELD and CTP scores were significant risk factors, whether using the proposed cutoff of 1.3 (hazard ratio [HR] 1.17 [1.106-2.44], P<0.001) or the median 2.17 CAR categorical variable (HR 1.17 [1.104-1.243], P<0.001). When patients who underwent liver transplantation were excluded, apart from the MELD and CTP scores CAR 2.17 was the only significant factor associated with the outcome (HR 3.61 [0.96-13.6], P=0.05) and detected different survival times: 10 (1-48) vs. 11 (2-38) months, log rank P=0.003. Patients with LMR≥1.9 presented significantly better renal function, in terms of true glomerular filtration rate (80±34 vs. 64±33 mL/min, P=0.004) and creatinine levels: 0.84 (0.1-1.8) vs. 0.98 (0.59-3.3) mg/dL (P=0.001).ConclusionOur findings demonstrate the significance of CAR and LMR in the outcome and renal function of decompensated patients.

Measured and estimated glomerular filtration rate: current status and future directions

Evaluation of glomerular filtration rate (GFR) is central to the assessment of kidney function in medical practice, research and public health. Measured GFR (mGFR) remains the reference standard, but the past 20 years have seen major advances in estimated GFR (eGFR). Both eGFR and mGFR are associated with error compared with true GFR. eGFR is now recommended by clinical practice guidelines, regulatory agencies and public health agencies for the initial evaluation of GFR, with measured GFR (mGFR) typically considered an important confirmatory test, depending on how accurate the assessment of GFR needs to be for application to the clinical, research or public health setting. Our approach is to use initial and confirmatory tests as needed to develop a final assessment of true GFR. We suggest that GFR evaluation might be improved by more complete implementation of current recommendations and by further research to improve the accuracy of mGFR and eGFR.

Knowing your GFR—when is the number not (exactly) the number?

All methods used to measure and estimate glomerular filtration rate (GFR) are associated with systematic or random error, which leads to differences in measured GFR (mGFR) and estimated GFR (eGFR) from "true GFR." In this issue of Kidney International, Rowe etal. evaluate time-to-time variability using repeated assessments of mGFR and eGFR within a short time frame. They show that biological variability is larger for mGFR than eGFR, and the magnitude of reference change values when interpreting changes in mGFR and eGFR.

Effect of renal function on homeostasis of asymmetric dimethylarginine (ADMA): studies in donors and recipients of renal transplants.

Asymmetric dimethylarginine (ADMA) is a methylated form of arginine and an endogenous nitric oxide synthase inhibitor. Renal function decline is associated with increase of plasma ADMA in chronic kidney disease populations. It is yet unknown how isolated renal function impairment affects ADMA homeostasis in healthy humans. Here, we measured plasma concentrations and urinary excretion of ADMA using GC-MS/MS in 130 living kidney donors before and at 1.6 (1.6-1.9) months after donation. We additionally analyzed 201 stable renal transplant recipients (RTR) that were included > 1year after transplantation, as a model for kidney disease in the context of single kidney state. We measured true glomerular filtration rate (mGFR) using 125I-iothalamate. To study enzymatic metabolism of ADMA, we also measured L-citrulline as primary metabolite. Mean age was 52 ± 10years in donors and 54 ± 12years in RTR. Renal function was significantly reduced from pre- to post-donation (mGFR: 104 ± 17 vs. 66 ± 10ml/min per 1.73m2 BSA, - 36 ± 7%, P < 0.001). Urinary ADMA excretion strongly and significantly decreased from pre- to post-donation (60.6 ± 16.0 vs. 40.5 ± 11.5µmol/24h, - 31.5 ± 21.5%, P < 0.001), while plasma ADMA increased only slightly (0.53 ± 0.08 vs. 0.58 ± 0.09µM, 11.1 ± 20.1%, P < 0.001). Compared to donors post-donation, RTR had significantly worse renal function (mGFR: 49 ± 18ml/min/1.73m2, - 25 ± 2%, P < 0.001) and lower urinary ADMA excretion (30.9 ± 12.4µmol/24h, - 23.9 ± 3.4%, P < 0.001). Plasma ADMA in RTR (0.60 ± 0.11µM) did not significantly differ from donors post-donation (2.9 ± 1.9%, P = 0.13). Plasma citrulline was inversely associated with mGFR (st. β: - 0.23, P < 0.001), consistent with increased ADMA metabolism to citrulline with lower GFR. In both groups, the response of urinary ADMA excretion to renal function loss was much larger than that of plasma ADMA. As citrulline was associated with GFR, our data indicate that with renal function impairment, a decrease in urinary ADMA excretion does not lead to a corresponding increase in plasma ADMA, likely due to enhanced metabolism, thus allowing for lower renal excretion of ADMA.

Validity of current equations to estimated glomerular filtration rate in geriatric population

Background Despite the estimation of glomerular filtration rate (GFR) being the best index of kidney function, and estimated glomerular filtration rate (eGFR) being limited by differences in creatinine generation among different age groups, the data regarding the accuracy of serum creatinine-based formulae on the geriatric population is still scarce. Aim Our aim is to investigate the accuracy of the eGFR equations to predict renal function in geriatric population versus the measurement of true GFR by diethylenetriaminepentaacetic acid (99mTc-DTPA). Patients and methods The study included 160 elderly persons, with 93 (58%) females. All persons were from Minia Governorate, Egypt. GFR was estimated using Modification of Diet in Renal Disease, abbreviated Modification of Diet in Renal Disease, Walser, Nankivell, Cockcroft–Gault, Mayo Clinic, and Chronic Kidney Disease Epidemiology Collaboration. The true GFR was determined for all participants with 99mTc-DTPA. Results All the seven eGFR estimations correlated with 99mTc-DTPA clearance (P Conclusion In the geriatric population, the overall performance of these seven prediction equations did not give a precise assessment of kidney function, that is, all analyzed formulae lacked the precision to estimate true GFR.

Augmented renal clearance in pediatric intensive care: are we undertreating our sickest patients?

Many critically ill patients display a supraphysiological renal function with enhanced renal perfusion and glomerular hyperfiltration. This phenomenon described as augmented renal clearance (ARC) may result in enhanced drug elimination through renal excretion mechanisms. Augmented renal clearance seems to be triggered by systemic inflammation and therapeutic interventions in intensive care. There is growing evidence that ARC is not restricted to the adult intensive care population, but is also prevalent in critically ill children. Augmented renal clearance is often overlooked due to the lack of reliable methods to assess renal function in critically ill children. Standard equations to calculate glomerular filtration rate (GFR) are developed for patients who have a steady-state creatinine production and a stable renal function. Those formulas are not reliable in critically ill patients with acutely changing GFR and tend to underestimate true GFR in patients with ARC. Tools for real-time, continuous, and non-invasive measurement of fluctuating GFR are most needed to identify changes in kidney function during critical illness and therapeutic interventions. Such devices are currently being validated and hold a strong potential to become the standard of practice. In the meantime, urinary creatinine clearance is considered the most reliable method to detect ARC in critically ill patients. Augmented renal clearance is clearly associated with subtherapeutic antimicrobial concentrations and subsequent therapeutic failure. This warrants the need for adjusted dosing regimens to optimize pharmacokinetic and pharmacodynamic target attainment. This review aims to summarize current knowledge on ARC in critically ill children, to give insight into its possible pathophysiological mechanism, to evaluate screening methods for ARC in the pediatric intensive care population, and to illustrate the effect of ARC on drug exposure, therapeutic efficacy, and clinical outcome.

Effects of crizotinib on creatinine clearance and renal hemodynamics

ObjectivesThe tyrosine kinase inhibitor crizotinib may affect renal function. The mechanism of this effect is not understood. We aimed to get more insight by measuring renal hemodynamics in patients treated with crizotinib. Materials and methodsRenal hemodynamics (i.e. glomerular filtration rate and effective renal plasma flow) were measured with radioactive tracers in three patients with stage IV non small-cell lung cancer during treatment with crizotinib. The results were compared with simultaneous creatinine based renal function measurements in the same patients. ResultsPatients had been treated with crizotinib between 155 and 320 days at the first measurement. In one patient the measurement was repeated after a total of one year and two months of treatment. All patients had been treated with chemotherapy containing cisplatin before. In these patients true glomerular filtration rate was 64–83% higher than estimated by creatinine based measurements. Filtration fraction, a measure of glomerular pressure, was increased in all three patients. The glomerular pressure was even further increased in a follow-up measurement. ConclusionCreatinine-based estimates of GFR on crizotinib may underestimate the true GFR. However, evidence of increased glomerular pressure may increase risk of long term true nephrotoxicity.

Cystatin C Is a More Reliable Biomarker for Determining eGFR to Support Drug Development Studies.

Glomerular filtration rate (GFR) is routinely used as a surrogate endpoint for the development of investigational drugs in clinical trials. GFR and staging of chronic kidney disease are typically assessed by measuring the concentration of endogenous serum biomarkers such as albumin and creatinine. However, creatinine is subject to high biological variability, and levels of creatinine do not rise until nearly 50% of kidney function is damaged, leading to inaccurate chronic kidney disease staging and false negatives. A newer biomarker for GFR, cystatin C, has been shown to be subject to less biological interference and more sensitive to early declines in kidney function. Cystatin C has also been shown to outperform creatinine as an indicator of true GFR and to add information about the occurrence of acute kidney injury. Comparison studies of cystatin C and creatinine continue to demonstrate its increased accuracy and sensitivity for changes in true GFR. While challenges remain for use of cystatin C, international agencies and working groups continue to validate cystatin C as a biomarker and accompanying GFR estimating equations for diagnostic and drug development use. In this review, we summarize these comparison studies, regulatory and industry guidelines, and clinical trial case studies for use of cystatin C in drug development.

Determination of Glomerular Filtration Rate with CT Measurement of Renal Clearance of Iodinated Contrast Material versus 99mTc-DTPA Dynamic Imaging "Gates" Method: A Validation Study in Asymmetrical Renal Disease.

Purpose To validate a computed tomographic (CT) glomerular filtration rate (GFR) measurement and compare it with renal dynamic imaging GFR obtained by using the "Gates" method, with dual plasma sampling technetium 99m (99mTc) diethylenetriaminepenta-acetic acid (DTPA) clearance ("true GFR") as the reference standard. Materials and Methods This prospective study was approved by the institutional review board, and written informed consent was obtained from all patients. Forty-two patients with unilateral renal disease were included. Single-kidney CT GFR was calculated as excretory phase whole-kidney CT number enhancement divided by the area under the time-attenuation curve for the aorta, multiplied by (1 - hematocrit level). The CT GFR was then obtained by summing the result of the two sides. The true GFR and the Gates GFR were measured by using a single injection of 99mTc-DTPA. The CT GFR and Gates GFR were respectively compared with the true GFR by using a paired t test and linear regression analysis. Results The difference between CT GFR (mean ± standard deviation, 96.02 mL/min ± 23.11) and true GFR (90.50 mL/min ± 21.46) was 5.51 mL/min ± 6.96 (P < .001), demonstrating 6.09% systemic overestimation. The difference between Gates GFR (93.93 mL/min ± 26.97) and true GFR was 3.42 mL/min ± 16.10 (P = .176). Linear regression findings confirmed the association between CT GFR (y-axis) and true GFR (x-axis) and between Gates GFR (y-axis) and true GFR (x-axis) (P < .001 for both). Both regression lines paralleled the diagonal (intercept = 0 and slope = 1) (P = .599 and P = .945, respectively). The 95% confidence interval of the former was above the diagonal, confirming the systemic overestimation. The standard deviations of residuals of both linear regressions were 7.02 mL/min and 16.30 mL/min, respectively, demonstrating smaller deviation of the CT GFR (P < .001). Conclusion The proposed CT GFR measurement was validated in this study and was proved to be more accurate than the Gates method despite slight (6.09%) systemic overestimation. © RSNA, 2016 Online supplemental material is available for this article.

The chronic kidney disease epidemiology collaboration equation combining creatinine and cystatin C accurately assesses renal function in patients with cirrhosis.

BackgroundAccurate measurement of renal function in cirrhotic patients is still challenging. To find the best test for the determination of the true glomerular filtration rate (GFR) in cirrhotic patients this study prospectively compared measured (m)GFR, the gold standard, with estimated (e)GFR using equations based on serum levels of creatinine and cystatin C.MethodsGFR was measured by sinistrin clearance using the bolus method in 50 patients with cirrhosis (Child Turcotte Pugh score A, B and C) and 24 age-matched healthy subjects as controls. Measured (m)GFR was compared to eGFR using bias, accuracy 10 % and 30 %, as well as correlation coefficients.ResultsCreatinine-based equations generally overestimated GFR in patients with cirrhosis and showed a bias (average difference between mGFR and eGFR) of −40 (CG), −12 (MDRD) and −9 (CKD-EPI-Cr) ml/min/1.73 m2. Cystatin C-based equations underestimated GFR, especially in patients with Child Turcotte Pugh score C (bias 17 ml/min/1.73 m2for CKD-EPI-CysC). Of these equations, the CKD-EPI equation that combines creatinine and cystatin C (CKD-EPI-Cr-CysC) showed a bias of 0.12 ml/min/1.73 m2 as compared to measured GFR.ConclusionsThe CKD-EPI equation that combines serum creatinine and cystatin C measurements shows the best performance for accurate estimation of GFR in cirrhosis, especially at advanced stages.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-015-0188-0) contains supplementary material, which is available to authorized users.

Correction of the slope-intercept method for the measurement of glomerular filtration rate.

Glomerular filtration rate (GFR) is frequently assessed using the slope-intercept method by fitting a single exponential to plasma samples obtained 2-5 h after injection. The body surface area (BSA)-corrected one-pool clearance (CO,BSA) overestimates true GFR (CT,BSA) because it fails to sample the full plasma curve, and values of CT,BSA are usually estimated from CO,BSA using the Brøchner-Mortensen (BM) equation. An improved equation, CT,BSA=CO,BSA/(1+fBSA×CO,BSA), with fBSA a fixed constant, was proposed by Fleming, but subsequently Jødal and Brøchner-Mortensen (JBM) reported that fBSA varies with BSA. We report data for a large group of individuals who underwent GFR investigations with sampling of the full plasma curve. The aims were to validate the JBM equation with independent data and assess whether replacing the BM equation with a BSA-dependent correction based on Fleming's equation can increase the accuracy of the slope-intercept method. Plasma data were analysed for 142 children and adults aged 0.6-56 years who underwent technetium-99m-diethylenetriaminepentaacetic acid GFR investigations with blood samples taken between 5 min and 8 h after injection. Values of CO,BSA were calculated using the 2, 3 and 4 h data. Values of CT,BSA were calculated by integrating the plasma curve between 5 min and 4 h and extrapolating the terminal exponential. Individual values of fBSA were calculated using the relationship fBSA=1/CT,BSA-1/CO,BSA. Nonlinear regression was used to fit the function fBSA=f1×BSA and find the best-fit values for f1 and n. Scatter and Bland-Altman plots were drawn comparing the various formulae for correcting slope-intercept GFR. The trend for fBSA to decrease with increasing BSA was highly significant (Spearman's test: RS=-0.31; P=0.0002). When the data were fitted by nonlinear regression, the best-fit values (95% confidence interval) of the model parameters were n=-0.13 (from -0.21 to -0.04) and f1=0.00191 (from 0.00183 to 0.00200). The results confirm that fBSA varies with BSA and provide independent values of the parameters f1 and n. Differences from GFRs calculated using the original JBM equation were small and not clinically significant. The BM equation also performed well for CT,BSA less than 125 ml/min/1.73 m. However, there was a small number of children with CT,BSA greater than 150 ml/min/1.73 m for whom the JBM formula provided more accurate estimates of true GFR than did the BM equation.

Crizotinib Effects on Creatinine and Non-Creatinine–Based Measures of Glomerular Filtration Rate

Rapid reductions in creatinine-based estimates of the glomerular filtration rate (GFR) have recently been reported secondary to crizotinib use. Whether these reflect drug-induced changes in the true GFR or the validity of creatinine as a measure of kidney function in the presence of crizotinib is unknown. Two anaplastic lymphoma kinase-rearranged non-small-cell lung cancer patients (one with pre-existing renal impairment) were identified during periods of time on and off crizotinib. Creatinine- and iothalamate-based estimates of renal function were conducted in the presence and absence of crizotinib. Crizotinib is associated with both acute and chronic effects on kidney function. Chronic creatinine changes seem to reflect a true reduction in the GFR. In contrast, acute effects include a reduction in creatinine-based estimates of the GFR without a reduction in non-creatinine-based measurements (consistent with, e.g., an acute effect of crizotinib on creatinine secretion), in addition to some reduction in the true GFR (with this latter effect seeming to be more prominent in the presence of pre-existing renal impairment). If crizotinib-associated changes in creatinine-based kidney function suggest a change in dosing with either crizotinib or concomitant medications that are renally excreted, use of a non-creatinine-based assessment of kidney function, such as iothalamate assessments, should be considered before making a final decision.