Absolute GFR Research Articles

#501 Evaluation of the accuracy of serum creatinine-based GFR calculations across the different levels of renal function among Filipinos

Abstract Background and Aims Chronic kidney disease (CKD) is a worldwide health concern which continues to increase in prevalence. Early studies have evaluated kidney function by measuring serum creatinine (sCr) and/or the estimated glomerular filtration rate (eGFR). To date, there are limited studies that correlate nuclear GFR scans and eGFR by equations that include the Cockroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) 2021 in Asians, specifically in a Filipino population. This study aims to compare the accuracy of GFR scan results and GFR estimated from the formulas across different levels of kidney functions, age groups, gender, and co-morbidities among a Filipino subset. Method A cross-sectional study was done among 2986 patients who underwent Nuclear GFR scan in a single kidney center. Results obtained were compared to estimated GFR results. Weighted Kappa and Bland-Altman Analyses were used to test for agreement between the measured and estimated GFR results. Results Absolute GFR values derived from the three equations demonstrated moderate reliability with results from nuclear scan when intraclass correlation coefficients were calculated with CKD-EPI 2021 being the highest. When further categorized into GFR levels, there was substantial level of agreement between each equation and GFR scan, with all weighted kappa coefficients being at least 0.700 with CG having the highest result (Table 1). Furthermore, when subgroup analysis was done according to age group, gender, and comorbidities, CG was found to be the most accurate per category (Table 2). Conclusion CKD-EPI 2021 was the most accurate in the actual GFR values however we cannot fully eliminate the utility of CG due to its categorical accuracy and in monitoring the deterioration of renal function.

Performance of creatinine-based equations for estimating glomerular filtration rate changes over time.

Glomerular filtration rate (GFR) is commonly used to monitor chronic kidney disease (CKD) progression, but its validity for evaluating kidney function changes over time has not been comprehensively evaluated. We assessed the performance of creatinine-based equations for estimating GFR slope according to patient characteristics and specific CKD diagnosis. In the NephroTest cohort study, we measured GFR 5324 times by chromium 51-labeled ethylenediamine tetraacetic acid renal clearance in 1955 adult patients with CKD Stages 1-4 referred to nephrologists (Stages 1-2, 19%) and simultaneously estimated GFR with both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations for isotope dilution mass spectrometry traceable creatinine; absolute and relative GFR slopes were calculated using a linear mixed model. Over a median follow-up of 3.4 [interquartile range (IQR) 2.0-5.6] years, the decline in mean absolute and relative measured GFR (mGFR) and CKD-EPI and MDRD estimated GFR (eGFR) was 1.6 ± 1.2, 1.5 ± 1.4 and 1.3 ± 1.3 mL/min/1.73 m2/year and 5.9 ± 5.3, 5.3 ± 5.3 and 4.8 ± 5.2%/year, respectively; 52% and 55% of the patients had MDRD and CKD-EPI eGFR slopes within 30% of mGFR slopes. Both equations tended to overestimate the GFR slope in the youngest patients and underestimate it in the oldest, thus producing inverse associations between age and mGFR versus eGFR slope. Other patient characteristics and specific CKD diagnoses had little effect on the performance of the equations in estimating associations. This study shows little bias, but poor precision in GFR slope estimation for both MDRD and CKD-EPI equations. Importantly, bias strongly varied with age, possibly due to variations in muscle mass over time, with implications for clinical care and research.

Minimal Improvement in Glomerular Filtration Rate in the First Year After Liver Transplantation.

Renal function is an important predictor of liver transplantation (LT) outcome. This study examines the change in glomerular filtration rate (GFR, mL/min per m) in the first year after LT, with subgroup analysis by baseline GFR, model for end-stage liver disease (MELD), age, sex, race, and diabetes/hypertension. The records of 1275 consecutive deceased donor, liver, and liver/kidney transplants were reviewed retrospectively, with the liver/kidney data analyzed separately. Glomerular filtration rate was calculated using the modification of diet in renal disease equation. Among liver only patients, 25% had GFR less than 60 (mL/min per 1.73 m) at LT, and this increased to 39% at 1 year. There were 42% of patients with normal renal function (GFR > 90) at baseline, and this decreased to 18% at 1 year. Only patient subgroups with MELD > 25 experienced any 1-year improvement in GFR, whereas all lower MELD groups experienced a significant decline in GFR. At 1 year after transplantation, there were 42% of recipients that had an absolute GFR decrease greater than 20 mL/min per 1.73 m, and 39% that decreased greater than 25% from their transplant baseline. Only 22% had an absolute improvement in GFR greater than 5 mL/min per 1.73 m. Sixty-four percent of liver transplant recipients overall experience a decrease in GFR 1 year after transplantation. Recipients with severe kidney disease at transplant (GFR < 30) are the group most likely to experience improvement in GFR after transplantation. However, at 1 year, as a group, they remain at GFR less than 60 (stage III chronic kidney disease). These results suggest that severe renal dysfunction may be marginally reversible after LT, but only 22% of the recipients in this cohort experienced any post-LT improvement in renal function.

Accounting for individual body surface area does improve estimation of absolute GFR using the CKD-EPI equation

<h3>Aims</h3> To compare estimated glomerular filtration rate (eGFR) according to the CKD-EPI equation, with (CKD-EPI, mL/min/1.73m²) and without body surface area (BSA)-normalisation (CKD-EPI_;BSA, mL/min), against measured Tc-DTPA GFR (mL/min). <h3>Methods</h3> The CKD-EPI and CKD-EPI_;BSA equations were compared in 222 individuals with Tc-DTPA GFR for bias, proportion within 30% of GFR (P30) and area under the receiver-operator curve (ROC) for detecting GFR<90mL/min. In 80 oncology patients and 78 obese subjects, we also evaluated concordance in relation to carboplatin dosing. <h3>Results</h3> Chi-square indicated differences in P30s between CKD-EPI_;BSA and CKD-EPI: in those with BMI ≥30kg/m² (32%), in those with BMI>25.0–29.9kg/m² (18%) and in those with BMI ≥18.5–25.0kg/m² (2%) (<i>p</i><0.0001). The ROC area under curve (AUC) for CKD-EPI_;BSA equation to detect GFR<90mL/min (0.85) and>125mL/min (0.81) was greater than for the CKD-EPI (0.80 and 0.71, respectively). Concordance for carboplatin dosing using the CKD-EPI_;BSA equation was 71% and 56.% by the CKD-EPI equation (<i>p</i>=0.07). <h3>Conclusion</h3> Estimation of absolute Tc-DTPA GFR using the CKD-EPI equation was improved by removal of BSA normalisation, reflected by higher proportion of results within 30% of GFR and less underestimations of GFR, with implications for drug dosing.

The body composition and excretory burden of lean, obese, and severely obese individuals has implications for the assessment of chronic kidney disease

Obesity could affect associations between creatinine generation, estimated body surface area, and excretory burden, with effects on chronic kidney disease assessment. We therefore examined the impact of obesity on the performances of estimated glomerular filtration rate (eGFR), the urine albumin:creatinine ratio (ACR), and excretory burden in 3611 participants of the Chronic Renal Insufficiency Cohort. Urine creatinine excretion significantly increased with body mass index (BMI) (34 and 31% greater at 40 kg/m(2) or more versus the normal of 18.5-25 kg/m(2)) in men and women, respectively, such that patients with a normal BMI and an ACR of 30 mg/g had the same 24-h albuminuria as severely obese patients with ACR 23 mg/g. The bias of eGFR (referenced to body surface area-indexed iothalamate (i-)GFR) had a U-shaped relationship to obesity in men but progressively increased in women. Nevertheless, obesity-associated body surface area increases were accompanied by a greater absolute (non-indexed) iGFR for a given eGFR, particularly in men. Two men with eGFRs of 45 ml/min per 1.73 m(2), height 1.76 m, and BMI 22 or 45 kg/m(2) had absolute iGFRs of 46 and 62 ml/min, respectively. The excretory burden, assessed as urine urea nitrogen and estimated dietary phosphorus, sodium, and potassium intakes, also increased in obesity. However, obese men had lower odds of anemia, hyperkalemia, and hyperphosphatemia. Thus, for a given ACR and eGFR, obese individuals have greater albuminuria, absolute GFR, and excretory burden. This has implications for chronic kidney disease management, screening, and research.

Plasma oxalate following kidney transplantation in patients without primary hyperoxaluria

Patients with primary hyperoxaluria may need repeated kidney transplants due to damage from oxalic acid (oxalate) deposits. However, oxalate may also be potentially harmful in all transplant recipients. Determinants of oxalate following transplantation have not been well studied. Two hundred and twelve recipients admitted for transplantation were included in the study. Blood samples for measurement of oxalate and other relevant laboratory parameters were collected at baseline and subsequently 10 weeks after transplantation. For oxalate determination, samples were obtained in 99, 167 and 54 patients out of the 212 at baseline, at follow-up and at both time points, respectively. We examined the bivariate association between plasma oxalate at transplantation and preemptive transplantation, time on dialysis, recipient age, creatinine, urea, phosphate, haemoglobin, PTH, albumin and calcium. Oxalate 10 weeks after transplantation was tested likewise including also laboratory parameters at baseline, primary non-function, rejection episodes, live versus deceased donor, donor age and GFR at follow-up. Median plasma oxalate concentration at transplantation was 35.0 micromol/L [95% confidence interval (95% CI) = 10.4-93.9] and 98% of the values were above normal limits (2.6-11.0). Oxalate concentration after 10 weeks was 9.0 micromol/L (4.0-25.5), still 37% being above the upper normal value. Multiple regression analysis revealed established dialysis treatment (P = 0.002) and creatinine (P < 0.000001) as independent positive determinants of oxalate at transplantation. Oxalate at 10 weeks was negatively associated to (51)Cr-EDTA absolute GFR (P = 0.023) and positively associated to donor age (P = 0.027) and plasma creatinine at 10 weeks (P = 0.03). At transplantation, plasma oxalate was on average three times increased and above the upper normal limit in 98% of patients and were still above normal in 37% after 10 weeks. The reduction after 10 weeks is determined by GFR and donor age. Whether increased plasma oxalate following kidney transplantation may have long-term consequences needs further study.

Estimated one‐yr glomerular filtration rate is an excellent predictor of long‐term graft survival in pediatric first kidney transplants

Acute rejection episodes following pediatric renal transplantation have been progressively reduced by recent immunosuppressive regimens. Nevertheless, grafts continue to fail over time and surrogate parameters for long-term RGS are lacking. We investigated post-transplant renal function within the first yr as an independent predictor of long-term RGS in 104 pediatric first kidney transplant recipients (mean age 11.1 +/- 3.9 yr; mean follow-up 8.3 +/- 3.5 yr) transplanted between January 1989 and December 2000. GFR was assessed by use of the Schwartz formula at 30 days and six and 12 months after transplantation, respectively. Patients were further stratified at all times according to GFR: (i) GFR<45 mL/min/1.73 m(2), (ii) GFR 45-80 mL/min/1.73 m(2), and (iii) GFR>80 mL/min/1.73 m(2). Cox regression analysis including factors potentially influencing long-term RGS, e.g., age, gender, transplant yr, HLA-mismatch, underlying renal disease, clinical acute rejection, absolute GFR as well as the change in GFR within the first yr was performed. Graft failure occurred in 24 out of 104 patients (23%) 6.2 yr (mean) after transplantation corresponding to a cumulative five-yr graft survival of 87.5%. GFRs at 30 days and six and 12 months were significantly associated with long-term RGS in the univariate cox regression analysis (GFR at 30 days, p = 0.045; GFR at six months, p = 0.004; GFR at 12 months, p < 0.001). None of the other variables were significant parameters of correlation. Multivariate cox analysis revealed a GFR below 45 mL/min/1.73 m(2) at 12 months after transplantation as the only independent predictor of long-term RGS (hazard ratio 55.9, 95% CI 5.29-591, p = 0.001). GFR at 12 months post-transplant is an excellent surrogate parameter for long-term RGS in children. This parameter might be useful as a primary end-point in short-term pediatric clinical trials.

How accurate is dynamic contrast‐enhanced MRI in the assessment of renal glomerular filtration rate? A critical appraisal

To evaluate the current literature to see if the published results of MRI-glomerular filtration rate (GFR) stand up to the claim that MRI-GFR may be used in clinical practice. Claims in the current literature that Gadolinium (Gd) DTPA dynamic contrast enhanced (DCE) MRI clearance provides a reliable estimate of glomerular filtration are an overoptimistic interpretation of the results obtained. Before calculating absolute GFR from Gd-enhanced MRI, numerous variables must be considered. We examine the methodology in the published studies on absolute quantification of MRI-GFR. The techniques evaluated included the dose and volume of Gd-DTPA used, the speed of injection, acquisition sequences, orientation of the subject, re-processing, conversion of signal to concentration and the model used for analysis of the data as well as the MRI platform. Claims in the current literature that using DCE MRI "Gd DTPA clearance provides a good estimate of glomerular filtration" are not supported by the data presented and a more accurate conclusion should be that "no MRI approach used provides a wholly satisfactory measure of renal GFR function." This study suggests that DCE MRI-GFR results are not yet able to be used as a routine clinical or research tool. The published literature does not show what change in DCE MRI-GFR is clinically significant, nor do the results in the literature allow a single DCE MRI-GFR measurement to be correlated directly with a multiple blood sampling technique.

Factors affecting graft function in pediatric and adult recipients of adult live donor kidney transplants

The aims of this investigation were to compare changes of function of adult living kidney grafts transplanted into adult and child recipients and to analyze factors associated with graft function during the first post-transplant year. The study involved 53 adult and 23 pediatric recipients with immediate graft function and without complications that could influence graft function. In comparison to children, adult recipients and their donors were older, and having been longer on hemodialysis they had received more transfusions. Although similar baseline graft function--GFR(0) was transplanted in both groups, absolute and relative GFR in adults rose and maintained stable, while in children absolute GFR decreased and remained similar to the GFR(0) until the end of the study. Significant predictors of kidney function in both adult and child recipients were donor age, ratio between GFR(0) and recipient BSA, induction immunosuppression, and systolic hypertension. In conclusion, the function of adult live kidney grafts changed differently in children and adults because of different functional requirements of recipients but donor age, induction immunosuppression and hypertension are significant predictor of graft function in both adults and children.

Glomerular filtration rate what is the rationale and justification of normalizing GFR for body surface area?

80 ml/min/1.73 m 2 and 75 ml/min/1.73 m 2 respectively for a 55-year-old prospective kidney donor. The 9.1 ml/min difference between the absolute GFR and the GFR indexed for BSA prompted further consideration of the validity and rationale for indexing GFR to BSA. There are several formulae that estimate BSA from measures of height and weight in the literature and in this man, with height 1.65 m and weight 86 kg, we found that the application of six previously published height–weight formulae to estimate BSA [3–8] gave a range of indexed GFR of 72.0 to 77.9 ml/min/1.73 m 2 . In other words, indexing GFR for BSA in this man reduced the value for GFR by between 9.1 and 15 ml/min depending on which BSA formula was used and greatly influenced the decision about his suitability as a kidney donor. Several authors have questioned the validity of indexing GFR for BSA and the generalizability of the supporting studies from the last century to the increasingly obese population [9–12]. The purpose of this review is to explore the physiological plausibility of using BSA as an appropriate way to index measured GFR, the validity of the methods that

Adaptive hyperfiltration in the aging kidney after contralateral nephrectomy

We examined the magnitude of adaptive hyperfiltration in the remaining kidney of 16 aging (>57 yr) and 16 youthful (<55 yr) individuals who had undergone a contralateral nephrectomy. Healthy volunteers who were youthful (n = 143) or aging (n = 37) provided control values for the binephric condition. One-kidney glomerular filtration rate (GFR; +42%), renal plasma flow (+38%), plasma oncotic pressure (+2.8 mmHg), and mean arterial pressure (+7.0 mmHg) were all higher in youthful uninephric vs. binephric subjects. Corresponding excesses in aging uninephric vs. binephric subjects were by 38 and 36% and 1.4 and 14.0 mmHg, respectively. Modeling of these data revealed that an isolated increase in either the glomerular ultrafiltration coefficient (K(f)) by 110% or in the transcapillary hydraulic pressure gradient (DeltaP) by 7 mmHg, could account for the observed level of hyperfiltration in youthful uninephric subjects. Corresponding increases for aging uninephric subjects were 61% for K(f) and 5 mmHg for DeltaP. We conclude that the magnitude of adaptive hyperfiltration is similar in aging to that in youthful uninephric subjects, albeit at a lower absolute GFR level. Isolated increases in either K(f) or DeltaP or a combination of smaller increases in both can account for the hyperfiltration. Greater adaptive arterial hypertension in aging than youthful uninephric subjects raises the possibility of a disproportionate role for glomerular hypertension and DeltaP elevation in aging compared with youthful uninephric subjects. Glomerular hypertension could exacerbate the sclerosing glomerulopathy of senescence and lead to renal insufficiency. We recommend that living donors of a kidney transplantation in or beyond the seventh decade be used with caution.

Transplantation of infant en bloc kidneys into paediatric recipients

En bloc renal transplantation (EBT) from infant donors is an option for children with end-stage renal failure. Owing to potential complications, EBT is not performed in all paediatric nephrology centres. We evaluated the perioperative and long-term course of five children undergoing EBT. Primary diagnosis was atypical (diarrhoea-negative) haemolytic uraemic syndrome (n=2), interstitial nephropathy (two siblings) and branchio-oto-renal syndrome (n=1). Recipient and donor ages ranged between 5.9 and 11.1 years and 0.3 and 2.5 years, respectively. Follow-up time after EBT was 2.1-13.2 years. Perioperative complications included (1) a renal artery thrombosis, with immediate intraoperative reconstruction and primary non-functioning of the graft, with recovery after 10 days, and (2) a vesico-ureteric obstruction, successfully managed with temporary insertion of a JJ-catheter. All grafts had good long-term function. Absolute glomerular filtration rate (GFR; millilitres/minute) increased in all patients, whereas relative GFR (millilitres/minute per 1.73 m(2) body surface area) remained stable during the follow-up period in all but one. Kidney size increased significantly, with maximal growth during the first year after EBT; magnetic resonance imaging (MRI) showed normal structure and vasculature. EBT is a safe and effective option for young children with end-stage renal failure. Absolute GFR and graft size increase and adapt to the children's growing body mass.

Better long-term functional adaptation to the child's size with pediatric compared to adult kidney donors

Better long-term functional adaptation to the child's size with pediatric compared to adult kidney donors.BackgroundPros and cons for pediatric kidney donors have been debated, especially with respect to survival rates. However, the effect of donor age on kidney function remains conflicting. The aim of this study was to compare short and long-term renal function according to the age of the donor, in grafts from adult living related (LRD), adult cadaveric and pediatric cadaveric donors (PedCD) following pediatric transplantation (Tx).MethodsOne hundred and thirty-four children were repeatedly followed for four years, and 44 were followed for eight years. Absolute and relative glomerular filtration rate (GFR; inulin clearance, mL/min and mL/min/1.73 m2, respectively) were determined within 6 months, and yearly thereafter.ResultsAbsolute GFR increased along with body growth in the PedCD group (P < 0.001) during the 4 years following Tx, leading to stable relative GFR, whereas absolute GFR of the LRD group did not change, with a progressive decrease of relative GFR (P < 0.001). Relative GFR did not differ between PedCD and LRD recipients by the sixth month but became higher in PedCD 4 years post-Tx (70 ± 25 vs 52 ± 19 mL/min/1.73 m2, P < 0.001). Among those followed for 8 years, relative GFR showed a slow decrease in both recipient groups from 6 years post-Tx. At 8 years post-Tx, relative GFR was still significantly higher in PedCD than in LRD (57 ± 19 vs. 45 ± 19; P < 0.05).ConclusionsAdult-sized grafts may adapt to pediatric recipients during the first months post-Tx, but graft function cannot improve thereafter along with the increase in body size of the recipient. Interestingly, the absolute GFR of children receiving pediatric grafts increased along with body growth, leading to a stable relative GFR up to 6 years post-Tx. Better long-term functional adaptation to the child's size with pediatric compared to adult kidney donors. Pros and cons for pediatric kidney donors have been debated, especially with respect to survival rates. However, the effect of donor age on kidney function remains conflicting. The aim of this study was to compare short and long-term renal function according to the age of the donor, in grafts from adult living related (LRD), adult cadaveric and pediatric cadaveric donors (PedCD) following pediatric transplantation (Tx). One hundred and thirty-four children were repeatedly followed for four years, and 44 were followed for eight years. Absolute and relative glomerular filtration rate (GFR; inulin clearance, mL/min and mL/min/1.73 m2, respectively) were determined within 6 months, and yearly thereafter. Absolute GFR increased along with body growth in the PedCD group (P < 0.001) during the 4 years following Tx, leading to stable relative GFR, whereas absolute GFR of the LRD group did not change, with a progressive decrease of relative GFR (P < 0.001). Relative GFR did not differ between PedCD and LRD recipients by the sixth month but became higher in PedCD 4 years post-Tx (70 ± 25 vs 52 ± 19 mL/min/1.73 m2, P < 0.001). Among those followed for 8 years, relative GFR showed a slow decrease in both recipient groups from 6 years post-Tx. At 8 years post-Tx, relative GFR was still significantly higher in PedCD than in LRD (57 ± 19 vs. 45 ± 19; P < 0.05). Adult-sized grafts may adapt to pediatric recipients during the first months post-Tx, but graft function cannot improve thereafter along with the increase in body size of the recipient. Interestingly, the absolute GFR of children receiving pediatric grafts increased along with body growth, leading to a stable relative GFR up to 6 years post-Tx.

Better long-term functional adaptation to the child's size with pediatric compared to adult kidney donors

Pros and cons for pediatric kidney donors have been debated, especially with respect to survival rates. However, the effect of donor age on kidney function remains conflicting. The aim of this study was to compare short and long-term renal function according to the age of the donor, in grafts from adult living related (LRD), adult cadaveric and pediatric cadaveric donors (PedCD) following pediatric transplantation (Tx). One hundred and thirty-four children were repeatedly followed for four years, and 44 were followed for eight years. Absolute and relative glomerular filtration rate (GFR; inulin clearance, mL/min and mL/min/1.73 m(2), respectively) were determined within 6 months, and yearly thereafter. Absolute GFR increased along with body growth in the PedCD group (P < 0.001) during the 4 years following Tx, leading to stable relative GFR, whereas absolute GFR of the LRD group did not change, with a progressive decrease of relative GFR (P < 0.001). Relative GFR did not differ between PedCD and LRD recipients by the sixth month but became higher in PedCD 4 years post-Tx (70 +/- 25 vs 52 +/- 19 mL/min/1.73 m(2), P < 0.001). Among those followed for 8 years, relative GFR showed a slow decrease in both recipient groups from 6 years post-Tx. At 8 years post-Tx, relative GFR was still significantly higher in PedCD than in LRD (57 +/- 19 vs. 45 +/- 19; P < 0.05). Adult-sized grafts may adapt to pediatric recipients during the first months post-Tx, but graft function cannot improve thereafter along with the increase in body size of the recipient. Interestingly, the absolute GFR of children receiving pediatric grafts increased along with body growth, leading to a stable relative GFR up to 6 years post-Tx.