Serum Creatinine-based Glomerular Filtration Rate Research Articles

A quantitative assessment of renal function utilizing albuminuria in pediatric heart transplant recipients.

Kidney disease is common after pediatric heart transplantation. Serum creatinine-based glomerular filtration rate is the most frequently reported measure of kidney function. Albuminuria is an additional marker of kidney dysfunction and is not well described in this population. In this study, we evaluate the prevalence and degree of albuminuria and describe clinical factors associated with albuminuria in a cohort of pediatric heart transplant recipients. This was a cross-sectional study of pediatric heart transplant recipients. Albuminuria was assessed using spot urine albumin-to-creatinine ratio collected at the most recent annual screening cardiac catheterization through August 2019. In 115 patients at a median duration of 10.2 years post-transplant, 39% had albuminuria. Stage 3 or greater chronic kidney disease was present in 6%. The immunosuppressive regimen at the time of measurement contained a calcineurin inhibitor (CNI) in 88% and a proliferation signal inhibitor (PSI) in 62%. In multivariable modeling, lower eGFR, PSI use, and younger age at transplant were associated with higher levels of albuminuria, whereas CNI use was associated with lower levels of albuminuria. Albuminuria is a prevalent finding in medium-term follow up of pediatric heart transplant recipients, reflecting kidney injury, and is associated with other markers of kidney dysfunction, such as low eGFR. Younger age at transplant, lower eGFR, and PSI use were among the associations with albuminuria.

Utility of cystatin C and serum creatinine-based glomerular filtration rate equations in predicting vancomycin clearance: A population pharmacokinetics analysis in elderly Chinese patients.

Renal function is an important factor affecting the pharmacokinetics of vancomycin. The renal function in elderly patients gradually decreases with age. An accurate estimated glomerular filtration rate (GFR) is essential in drug dosing. The study aimed to determine the most appropriate renal function estimation equations to describe vancomycin pharmacokinetics in elderly patients using population pharmacokinetic analysis. Data were obtained retrospectively from elderly patients aged ≥65years who received vancomycin for infection from September 2016 to January 2022. Renal function was estimated using the Cockcroft-Gault equation (CG), Modification of Diet in Renal Disease equation (MDRD), three Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPIcys-scr , CKD-EPIscr , and CKD-EPIcys ) and two Berlin Initiative Study equations (BIS-1 and BIS-2). The CKD-EPIcys-scr and BIS-2 equations were based on cystatin C (Cys C) and serum creatinine (Scr). The others were based on Cys C or Scr. A nonlinear mixed effects model (NONMEM) was used to develop the population pharmacokinetic model. A total of 471 serum concentrations from 313 elderly patients were used to develop the population pharmacokinetic model. Weight and GFR were identified as significant covariates affecting the pharmacokinetics of vancomycin. Cys C and Scr-based GFR (CKD-EPIcys-scr and BIS-2) yielded significant improvement performance compared with the other equations in model building. The interindividual variability of CL was reduced from 49.4% to 23.6% and 49.4% to 23.7% in CKD-EPIcys-scr and BIS-2 based models, respectively. However, greater interindividual variabilities of CL (from 26.6% to 29.0%) were represented in the other five models which were based on either Cys C or Scr. The GFR estimated by EPIcys-scr and BIS-2 equations and vancomycin CL exhibited a good correlation (r=0.834 and 0.833). In the external validation with 124 serum concentrations, the predictive performances of the CKD-EPIcys-scr and BIS-2 based models (the mean relative prediction errors were less than 1%, the mean relative absolute prediction errors were about 23%) were also superior to the other five models (the mean relative prediction errors were about 2%, the mean relative absolute prediction errors were greater than 25%) which are based on either Cys C or Scr. In this study, we determined that the equation used to estimate GFR can affect the population pharmacokinetic model fitting result. Population pharmacokinetics model with CKD-EPIcys-scr or BIS-2 can be used to optimize vancomycin dosage in elderly Chinese patients.

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

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

Evaluation of Renal Function and Stent Durability Following Resonance Stent Placement for Benign Disease.

Introduction: The metal-based Resonance stent (RS) has traditionally been placed in patients with malignant ureteral obstruction; as such, the long-term utility of RS among patients with benign ureteral obstruction (BUO) remains underinvestigated. Methods: We retrospectively reviewed our database for patients with BUO who underwent RS placement between 2010 and 2020. The impact of chronic RS placement on renal function was evaluated by estimated serum creatinine-based glomerular filtration rate (eGFR), furosemide renal scan, and CT-based renal parenchymal volume measurement. The number of and reason for RS stent exchanges during the follow-up period, incidence of encrustation, and the average indwell time were recorded. A cost analysis of placing the RS vs a polymeric stent was performed. Results: Among 43 RS patients with BUO, at a mean follow-up of 26 months, there was no change in eGFR (p = 0.99), parenchymal volume (p = 0.44), or split renal function of the stent-bearing side on renal scan (p = 0.48). The mean RS indwell time was 9.7 months. Eleven patients (26%) underwent premature stent replacement (6 cases) or removal (5 cases). Stents in 9 patients (32%) were encrusted, of which 4 (44%) required laser lithotripsy. Overall, 25 patients (58%) and 12 patients (28%) had a mean stent indwell time of ≥6 months and ≥12 months, respectively. Placing an RS resulted in a 52%, 37%, and 5.6% cost reduction compared with a regular polymeric stent placement, where it was exchanged every 6, 4, or 3 months, respectively. Conclusions: RS deployment in the patient with a BUO results in cost-effective maintenance of renal function and of renal parenchymal volume at a mean follow-up of 2 years; however, only 28% of patients fulfilled the 1-year criterion for RS indwell time.

A Prospective Evaluation of Novel Renal Biomarkers in Patients With Lymphoma Receiving High-Dose Methotrexate

Methotrexate (MTX)-associated acute kidney injury (AKI) occurs in 3% to 60% of patients at some point during treatment.1,2 The standard of care for MTX dose derivation and postdose monitoring centers around serum creatinine level as a surrogate for glomerular filtration rate (GFR).3 As the terminal byproduct of skeletal muscle metabolism, nonrenal determinants, including altered muscle mass, deconditioning, and malnutrition, can decrease the accuracy of serum creatinine-based GFR estimation in patients with cancer.

Comparability of serum creatinine-Based glomerular filtration rate equations in West African adult communities.

The clinical diagnosis of chronic kidney disease (CKD) is based on estimated glomerular filtration rate (GFR) using serum creatinine-based equations. Many formulas are used in estimating GFR. We set out to determine the degree of agreement between the Cockcroft-Gault (CG), 4-variable Modification of diet in renal disease (MDRD). Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in our indigenous population. Adult participants were recruited across all sectors of life, education, and occupation. Blood pressure, fasting blood glucose, lipid profile, urinalysis, serum creatinine, and anthropometry were measured. Estimated GFR (eGFR) was computed using CG, MDRD, and CKD-EPI equations with and without the race factor. The Lin's concordance index (rho_c) and Bland-Altman analysis were used to determine the degree of agreement between various pairs of creatinine-based eGFR equations [MDRD with the race factor (MDRDw)]; MDRD without the race factor (MDRD); CKD-EPI with race factor (CKD-EPIw); CKD-EPI without the race factor (CKD-EPI), and the CG equation. Two hundred and sixty-one adults, mean age 47.5 ± 9.9 years, 45.2% females participated in the study. Hypertension prevalence in the study population was 41.4 (95% CI 35.3-47.6%) while diabetes mellitus was 8.1% (95% CI 5.0-12.0%). The proportion of individuals with eGFRCKD-EPI less than 60 ml/min/1.73 m2 was 17.6 (95% CI 13.2-22.8%). All pairs of rho_c were lower than the threshold of 0.9 except for eGFRCKD-EPI versus eGFRCKD-EPw. There is significant discordance in the eGFR obtained from the various serum creatinine-based GFR equations in our population suggesting the need to validate these equations and determine the best equation for our general population.

Correlation between vancomycin clearance and cystatin C-based glomerular filtration rate in paediatric patients.

Because of limitations with the serum creatinine-based glomerular filtration rate (GFRcr), estimates of the serum cystatin C-based glomerular filtration rate (GFRcys) are getting attention to predict vancomycin clearance (CLvan). We evaluated the correlations between (i) CLvan and GFRcr, and (ii) CLvan and GFRcys in paediatric patients. We evaluated a retrospective cohort of patients between 1 and 19 years old admitted to a tertiary hospital between 2017 and 2019. CLvan was estimated using measured vancomycin trough concentrations. We conducted Spearman's correlation analyses between CLvan and 1/creatinine, GFRcr, 1/cystatin C and GFRcys. Subgroup analyses were conducted for the young child, child, adolescent subgroups, intensive care unit patients and low body weight (<10th percentile) patients. We analysed 40 patients. GFRcys correlated with CLvan better than GFRcr did (ρ = 0.731, P < 0.001 vs ρ = 0.504, P = 0.001). In the subgroup analyses, the correlation between GFRcys and CLvan was stronger than that between GFRcr and CLvan (child subgroup ρ = 0.712, P = 0.002 vs ρ = 0.282, P = 0.289; intensive care unit patients ρ = 0.772, P < 0.001 vs ρ = 0.540, P = 0.004; low body weight patients ρ = 0.671, P < 0.001 vs ρ = 0.464, P = 0.022). Serum cystatin C-based GFR strongly correlates with vancomycin clearance, suggesting the possibility of better prediction models than creatinine-based GFR. Further prospective studies are required for the validation of the prediction model in a large paediatric population.

The failure of glomerular filtration rate estimating equations among obese population.

BackgroundObesity is a major public health with increasing numbers of obese individuals are at risk for kidney disease. However, the validity of serum creatinine-based glomerular filtration rate (GFR) estimating equations in obese population is yet to be determined.MethodsWe evaluated the performance of the reexpressed Modification of Diet in Renal Disease (MDRD), reexpressed MDRD with Thai racial factor, Thai estimated GFR (eGFR) as well as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations among obese patients, defined as body mass index (BMI) ≥25 kg/m2 with the reference measured GFR (mGFR) determined by 99mTc-diethylene triamine penta-acetic acid (99mTc-DTPA) plasma clearance method. Serum creatinine levels were measured using standardized enzymatic method simultaneously with GFR measurement. The statistical methods in assessing agreement for continuous data including total deviation index (TDI), concordance correlation coefficient (CCC), and coverage probability (CP) for each estimating equation were compared with the reference mGFR. Accuracy within 10% representing the percentage of estimations falling within the range of ±10% of mGFR values for all equations were also tested.ResultsA total of 240 Thai obese patients were finally recruited with mean BMI of 31.5 ± 5.8 kg/m2. In the total population, all eGFR equations underestimated the reference mGFR. The average TDI values were 55% indicating that 90% of the estimates falling within the range of -55 to +55% of the reference mGFR. The CP values averaged 0.23 and CCC scores ranged from 0.75 to 0.81, reflecting the low to moderate levels of agreement between each eGFR equation and the reference mGFR. The proportions of patients achieving accuracy 10% ranged from 23% for the reexpressed MDRD equation to 33% for the Thai eGFR formula. Among participants with BMI more than 35 kg/m2 (n = 48), the mean error of all equations was extremely wide and significantly higher for all equations compared with the lower BMI category. Also, the strength of agreement evaluated by TDI, CCC, and CP were low in the subset of patients with BMI ≥35 kg/m2.ConclusionEstimating equations generally underestimated the reference mGFR in subjects with obesity. The overall performance of GFR estimating equations demonstrated poor concordance with the reference mGFR among individuals with high BMI levels. In certain clinical settings such as decision for dialysis initiation, the direct measurements of GFR are required to establish real renal function among obese population.

Increased Glomerular Filtration Rate in Early Stage of Balkan Endemic Nephropathy.

Background: A previous study indicated that Balkan endemic nephropathy (BEN) patients in the early stage of the disease had significantly higher creatinine clearance (Ccr) than healthy persons. The aim of the study was to assess whether tubular creatinine secretion affects Ccr in early stages of BEN and to check the applicability of serum creatinine-based glomerular filtration rate (GFR) equations in these patients. Methods: The study involved 21 BEN patients with estimated GFR (eGFR) above 60 mL/min/1.73 m2, excluding any conditions that could affect GFR or tubular creatinine secretion, and 15 healthy controls. In all participants Ccr with and without cimetidine and iohexol clearance (mGFR) were measured and eGFR calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease Study (MDRD) equations. Glomerular hyperfiltration cutoff (GFR-HF) was calculated. Results: There was no significant difference between the groups in Ccr before and after cimetidine or for eGFR, but mGFR was significantly higher in BEN patients than in controls (122.02 ± 28.03 mL/min/1.73 m2 vs. 101.15 ± 27.32 mL/min/1.73 m2; p = 0.032). Cimetidine administration reduced Ccr by 10% in both groups. The ratio of Ccr to mGFR was significantly above one in seven BEN patients and five controls and their mGFR values were similar. Seven other patients and eight controls had this ratio equal to one, while values below one were recorded for seven more patients and two controls. mGFR of all these 14 patients was significantly higher than that of healthy controls (129.88 ± 27.52 mL/min/1.73 m2 vs. 107.43 ± 19.51 mL/min/1.73 m2; p = 0.009). Mean GFR-HF was significantly higher than mGFR in controls, but these two values were similar in BEN patients. eGFR underestimated mGFR in both BEN patients and controls. Conclusion: The ratio of Ccr to mGFR and mGFR to GFR-HF indicated that elevated mGFR in early stages of BEN could be explained by increased glomerular filtration, but tubular creatinine secretion augmented Ccr in a smaller proportion of patients, who did not differ from healthy subjects.

A4098 Childhood Elevated Blood Pressure Predicts Adult Renal Damage

Objectives: We aimed to investigate the sex-specific association of childhood blood pressure (BP) with adult renal damage and function. Methods: Data were obtained from a population-based cohort of children aged 6–18 years started in 1987. The study comprised 936 subjects who were followed up in 2014 (aged 32–46 years). Renal Damage was assessed using urine albuminuria/creatinine ratio (ACR), and renal function using serum creatinine-based glomerular filtration rate (GFR). Results: Childhood SBP was significantly associated with adult ACR in males (β = 0.60, P = 0.002) but not in females (β = 0.03, P = 0.830), adjusted for age, follow up duration, and adult BMI, diabetes, and other risk factors. After further adjustment for adult SBP, the association of childhood SBP with adult ACR was still significant in males. In addition, childhood SBP was not associated with adult GFR with or without adjustment for covariates for both males and females. Conclusion: Childhood elevated BP predicts adult renal damage only in males but not in females. These findings underscore the importance of early prevention of elevated BP to reduce future risk of renal disease, especially in males.

Carboplatin dosing for adult Japanese patients.

Carboplatin is a platinum-based anticancer drug that has been long used to treat many types of solid cancer. Because the clearance of carboplatin strongly correlates with the glomerular filtration rate (GFR), its dosage is calculated with the Calvert formula on the basis of the patient's GFR to achieve the target area under the plasma drug concentration-time curve (AUC) for each patient. However, many lines of evidence from previous clinical studies should be interpreted with caution because different methods were used to estimate drug clearance and derive the dosage of carboplatin. There is a particularly high risk of carboplatin overdosing when the dosage is determined on the basis of standardized serum creatinine values. When deciding the dose of carboplatin for adult Japanese patients, preferred methods to assess renal function instead of directly measuring GFR include (1) 24-h urinary collection-based creatinine clearance adjusted by adding 0.2 mg/dl to the serum creatinine concentration measured by standardized methods, and (2) equation-based GFR (eGFR) with a back calculation to units of ml/min per subject. Given the limitations of serum creatinine-based GFR estimations, the GFR or creatinine clearance should be directly measured in each patient whenever possible. To ensure patient safety and facilitate a medical-team approach, the single most appropriate method available at each institute or medical team should be consistently used to calculate the dose of carboplatin with the Calvert formula.

Long-term renal function outcomes in bladder cancer after radical cystectomy.

To evaluate postoperative renal function and risk factors for the loss of renal function in patients who had undergone radical cystectomy. A retrospective single institutional study evaluated 70 patients, including 54 men and 16 women who underwent radical cystectomy. The median follow-up period was 34.5 months (range, 12 to 228 months). In this cohort, four types of urinary diversions were studied, including ileal neobladder (n = 24), ileocecal neobladder (n = 12), ileal conduit (n = 25), and cutaneous ureterostomy (n = 9). Postoperative changes in renal function were reviewed, and the estimated serum creatinine-based glomerular filtration rate (eGFR) was calculated. The variables analyzed were age, a prior history of hypertension or diabetes mellitus, pre-operative renal function, type of urinary diversion, the postoperative occurrence of acute pyelonephritis, and the presence of chemotherapy. The mean eGFR was 74.6 (range, 15.2 to 155.1) mL/min/1.73 m² before surgery and 63.6 (range, 8.7 to 111.5) mL/min/1.73 m² at the last follow-up. The 10-year renal deterioration-free interval was 63.8%. Multivariate analysis showed that a postoperative episode of acute pyelonephritis [Odds Ratio (OR), 3.21; 95% Confidence Interval (CI), 1.14 to 9.02; P = .03] and the presence of chemotherapy (OR, 3.27; 95% CI, 1.33 to 8.01; P = .01) were significant adverse factors. Twenty-four (34.2%) patients demonstrated reduced renal function during the follow-up period. Postoperative episodes of acute pyelonephritis and the presence of chemotherapy were found to be significant adverse factors.

Cystatin C as a Marker of Glomerular Filtration Rate in Voluntary Kidney Donors

Cystatin C is emerging as an endogenous marker of glomerular filtration rate. This study sought to assess the usefulness of serum cystatin C as a marker of glomerular filtration rate in comparison with serum creatinine and serum creatinine-based glomerular filtration rate estimations in voluntary kidney donors. Serum cystatin C and serum creatinine were estimated in 35 voluntary kidney donors. Glomerular filtration rate was estimated using: (1) Cockcroft-Gault method normalized to 1.73 m(2) of body surface area, (2) 4-variable Modification of Diet in Renal Diseases formula, and (3) (99m)Tc-DTPA double plasma sampling method. Glomerular filtration rate-double plasma sampling method was used as a reference value. Results were expressed as means ± SD. The mean age of the participants was 44.23 ± 8.61 years old (19 women, 16 men). The mean serum creatinine was 0.83 ± 0.14 mg/dL, and the mean serum cystatin C was 0.71 ± 0.12 mg/L. Serum cystatin C showed significant correlation with serum creatinine (r = 0.864; P < .001). Glomerular filtration rate-MDRD showed the strongest correlation with glomerular filtration rate double plasma sampling method (r = 0.93; P < .001), followed by glomerular filtration rate-Cockcroft-Gault (r = 0.76; P < .001 ), serum creatinine (r = - 0.68; P < .001), and serum cystatin C (r = - 0.59; P < .001). The mean serum cystatin C values were 22.6% higher in men than in women. There was a significant correlation of serum cystatin C with glomerular filtration rate-Cockcroft-Gault (r = - 0.50; P = .002 ), glomerular filtration rate-MDRD (r = - 0.59; P < .001 ), and glomerular filtration rate-double plasma sampling method (r = - 0.59; P < .001 ). Serum cystatin C is an optimal marker of glomerular filtration rate in voluntary kidney donors.

Appraisal of GFR-Estimating Equations Following Kidney Donation

It is not clear which serum creatinine-based glomerular filtration rate (GFR)-estimating model performs best in kidney donors. Study of diagnostic accuracy. From a population of 3,698 kidney donors, 255 donors underwent iohexol GFR measurement (mGFR). INDEX TEST (INTERVENTION): mGFR by means of plasma disappearance of iohexol. GFR was estimated (eGFR) by using the Cockcroft-Gault equation (eGFR(CG)), Mayo Clinic equation (eGFR(MC)), and Modification of Diet in Renal Disease (MDRD) Study equation (eGFR(MDRD)). Mean mGFR was 71.8 +/- 11.8 mL/min/1.73 m(2), and 85.5% had mGFR greater than 60 mL/min/1.73 m(2). eGFR(CG) underestimated mGFR by 3.96 +/- 13.3 mL/min/1.73 m(2) and was within 30% of mGFR 89.4% of the time. eGFR(MC) overestimated mGFR by 8.44 +/- 11.9 mL/min/1.73 m(2) and was within 30% of mGFR in 83.1% of cases. eGFR(MDRD) underestimated mGFR by only 0.43 +/- 11.7 mL/min/1.73 m(2), and the proportion within 30% of mGFR was greatest in the tested model; 94.1% of the time. However, eGFR(MC) was most accurate in classifying donors according to having eGFR less than 60 mL/min/1.73 m(2). Lack of ethnic diversity and response bias. The MDRD Study equation is least biased, and because it is routinely reported by most laboratories, it is the best readily available model for estimating GFR in kidney donors.

Validation of child serum creatinine-based prediction equations for glomerular filtration rate

Equations for estimating glomerular filtration rate (GFR) are vital in caring for patients with renal disease and the current standard, the Schwartz formula, lacks precision. We evaluated several child serum creatinine-based GFR prediction equations. Subjects aged 2-21 years who underwent iothalamate GFR (IoGFR) testing between 1999 and 2004 were studied retrospectively. GFR was estimated using: (1) Schwartz formula (SchwartzGFR), using a local k value; (2) Schwartz model (SchwartzMod) using regression-derived coefficients; (3) Leger GFR (LegerGFR) using original coefficients; and (4) Leger model (LegerMod) using regression-derived coefficients. Bias, precision, and diagnostic characteristics were evaluated. There were 195 subjects [61% male; mean (SD) age 12.4 (4.5) years; mean (SD) IoGFR 78.9 (33.4) ml/min per 1.73 m(2)]. Only the LegerGFR overestimated IoGFR (5.5 ml/min per 1.73 m(2)). Precision for all formulae was poor (95% limits of agreement approximately -40 to 40 ml/min per 1.73 m(2)), but >or=72% of estimates were within 30% of IoGFR. Sensitivities for detecting IoGFR <30 and 90 ml/min per 1.73 m(2) were highest using the SchwartzGFR (80%) and SchwartzMod (90%), respectively. The LegerGFR was most specific. Using local coefficients, the Schwartz and Leger models were imprecise estimates of GFR, but the Schwartz model was most unbiased and sensitive. Future research should derive more precise equations for GFR in children.