51Cr-EDTA Plasma Clearance Research Articles

#2929 Plasma levels of brain injury markers NfL and GFAP are independently predicted by glomerular filtration rate in patients with chronic kidney disease

Abstract Background and Aims Patients with chronic kidney disease (CKD) have a high prevalence of cerebrovascular disease and cognitive impairment. The aim of the present study was to measure brain injury biomarkers in plasma in a cohort of patients with CKD stages 3 and 4, without a diagnosis of cerebrovascular disease, and to determine factors that independently predicted plasma levels of these biomarkers. Method This was a cross-sectional cohort study including 110 patients with CKD stages 3 and 4, and 55 healthy, matched, controls, recruited from the outpatient clinic at Sahlgrenska university hospital, Gothenburg, Sweden. None of the included study subjects had a diagnosis of cerebrovascular disease, cognitive impairment, or any other neurological disease. Plasma concentrations of neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and phosphorylated Tau (p-Tau231) were analyzed with ultrasensitive single molecule array (SIMOA). Measured GFR (mGFR) was determined by plasma clearance of ⁵¹Cr-EDTA. Values are medians [interquartile range]. For linear regression analyses standardised beta coefficients (β) are presented. Results Characteristics of CKD patients and healthy controls are presented in Table 1. Plasma concentrations of NfL (37.5 [22.1-47.5] vs. 13.4 [10.5-16.7] ng/L, p < 0.001), p-Tau231 (25.7 [19.1-38.7] vs. 13.9 [10.5-16.3] ng/L, p < 0.001) and GFAP (190 [140-281] vs. 153 [116-211] ng/L, p = 0.001) were significantly elevated in patients with CKD vs. controls. In CKD patients, mGFR showed statistically significant inverse correlations to plasma concentrations of NfL, p-Tau231, and GFAP (Table 2). In multiple regression analyses, mGFR was associated with plasma levels of NfL (β = −0.457, p < 0.001) and GFAP (β = −0.322, p < 0.001) independently of diabetes, age, troponin-T, b-hemoglobin, and aortic pulse-wave velocity. However, mGFR was not significantly associated with plasma levels of p-Tau231 in a multiple regression analysis. Conclusion Plasma levels of brain injury markers NfL, p-Tau231 and GFAP were elevated in patients with CKD stages 3 and 4, without a history of cerebrovascular disease, compared to healthy controls. Furthermore, mGFR independently predicted plasma concentrations of NfL and GFAP in multiple regression models. These results raise the possibility that reduced GFR per se may be associated with subclinical brain injury.

Glomerular Filtration Rate Estimation Using β2-Microglobulin and β-Trace Protein in Adults With Solid Tumors: A Prospective Cross-Sectional Study

β2-Microglobulin (B2M) and β-trace protein (BTP) are novel endogenous filtration markers that may improve the accuracy of estimated glomerular filtration rate (eGFR) beyond creatinine and cystatin C (eGFRcr-cys), but they have not been assessed in patients with cancer. Cross-sectional analysis. Prospective cohort of 1,200 patients with active solid tumors recruited between April 2015 and September2017. CKD-EPI equations without race combining B2M and/or BTP with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR). Performance of equations compared with eGFRcr-cys and non-GFR determinants of serum B2M and BTP (SB2M, and SBTP, respectively). Measured GFR (mGFR) was determined using the plasma clearance of chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA). Bias was defined as the median of the differences between mGFR and eGFR, and 1-P30 was defined as the percentage of estimates that differed by more than 30% from the mGFR (1-P30). Linear regression was used to assess association of clinical and laboratory variables with SB2M, and SBTP after adjustment for mGFR. Mean age and mGFR were 58.8±13.2 SD years and 78.4±21.7 SD mL/min/1.73m2, respectively. Performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys (lesser bias and 1-P30). Performance of 2-marker panel equations was as good as eGFRcr-cys (lesser bias and similar 1-P30). SB2M and SBTP were not strongly influenced by cancer site. Participants may have had better clinical performance status than the general population of patients with solid tumors. B2M and BTP can improve the accuracy of eGFR and may be useful as confirmatory tests in patients with solid tumors, either by inclusion in a multimarker panel equation with creatinine and cystatin C, or by substituting for cystatin C in combination with creatinine. The most accurate method to assess estimate kidney function is estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys). We studied whether using β2-microglobulin (B2M) and/or β-trace protein (BTP) with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR) might be useful in patients with active solid tumors. The performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys. Performance of 2-marker panel equations was as good as eGFRcr-cys. We conclude that B2M and BTP can improve the accuracy of eGFR and may be useful as a confirmatory test in patients with solid tumors either by inclusion in multimarker panel equation with creatinine and cystatin C or by substituting for cystatin C in combination with creatinine.

Rescaling creatinine makes GFR estimation equations generally applicable across populations - validation results for the Lund-Malmö equation in a French cohort of sub-Saharan ancestry.

To make glomerular filtration rate (GFR) estimating equations applicable across populations with different creatinine generation by using rescaled serum creatinine (sCr/Q) where sCr represents the individual creatinine level and Q the average creatinine value in healthy persons of the same population. GFR measurements (mGFR, plasma clearance of 51Cr-EDTA) were conducted in 964 adult Black Europeans. We established the re-expressed Lund-Malmö revised equation (r-LMR) by replacing serum creatinine (sCr) with rescaled creatinine sCr/Q. We evaluated the r-LMR equation based on Q-values of White Europeans (r-LMRQ-white; Q-values females: 62 μmol/L, males: 80 μmol/L) and Black Europeans (r-LMRQ-Black; Q-values females: 65 μmol/L, males: 90 μmol/L), and the European Kidney Function Consortium equation (EKFCQ-White and EKFCQ-Black) regarding bias, precision (interquartile range, IQR) and accuracy (percentage of estimates within ±10 % [P10] and ±30 % [P30] of mGFR). Median bias of r-LMRQ-White/r-LMRQ-Black/EKFCQ-White/EKFCQ-Black were -9.1/-4.5/-6.3/-0.9 mL/min/1.73 m2, IQR 14.7/14.5/14.5/15.6 mL/min/1.73 m2, P10 25.1 %/34.8 %/30.3 %/37.2 % and P30 74.2 %/84.1 %/80.6 %/83.6 %. The improvement of bias and accuracy when using proper Q-values was most pronounced in men. Similar improvements were obtained above and below mGFR 60 mL/min/1.73 m2 and at various age and BMI intervals, except for BMI<20 kg/m2 where bias increased, and accuracy decreased. GFR estimating equations may be re-expressed to include rescaled creatinine (sCr/Q) and used across populations with different creatinine generation if population-specific average creatinine concentrations (Q-values) for healthy persons are established.

#2948 β-2-MICROGLOBULIN AND β-TRACE-PROTEIN DO NOT IMPROVE ESTIMATION OF GFR IN KIDNEY TRANSPLANT RECIPIENTS COMPARED TO CREATININE AND CYSTATIN C

Abstract Background and Aims Precise estimates of glomerular filtration rate (eGFR) are important in kidney transplant recipients (KTRs). Current eGFR formulas based on plasma creatinine and/or cystatin C are associated with significant bias. We investigated whether race free formulas based on plasma values of β-trace-protein and β-2-microglobulin performed better than formulas based on creatinine and cystatin C in a Scandinavian cohort of KTRs. Method We included samples and data from the randomised, controlled trial CONTEXT. GFR was measured by plasma clearance of 51Cr-EDTA or iodothalamate. eGFR was calculated using the new race-free CKD-EPI eGFR-creatinine and/or cystatin C(2021) formulas as well as the CKD-EPI eGFR-β-trace-protein and/or eGFR-β-2-microglobulin formulas. GFR estimates were evaluated at 3 (n = 82) and 12 (n = 64) months post-transplant using mean bias, precision, and accuracy. Also, formulas were analysed for their ability to correctly classify changes in measured GFR from 3 to 12 months. Results At 12 months eGFR-creatinine-cystatin C performed best according to mean bias (−4.54 ml/min/1.73 m2), precision (SD = 8.18 ml/min/1.73 m2) and accuracy (P10 = 47%) among creatinine and cystatin C based formulas (Table 1). Among the β-trace-protein and β-2-microglobulin based formulas, eGFR-β-trace-protein-β-2-microglobulin performed best according to precision (SD = 7.64 ml/min/1.73 m2) and accuracy (P10 = 36%) (Table 1). eGFR-β-trace-protein-β-2-microglobulin and eGFR-creatinine-cystatin C performed similar when comparing residuals (p = 0.481). eGFR-β-trace-protein, eGFR-β-trace-protein-β-2-microglobulin and eGFR-creatinine-cystatin C performed best in correctly classifying changes in mGFR from 3 to 12 months. Conclusion β-trace-protein and β-2-microglobulin do not improve the measurement of GFR compared to creatinine and cystatin C based formulas in KTRs.

Association between fibrosis markers and kidney function following peptide receptor radionuclide therapy in patients with neuroendocrine tumours

Peptide receptor radionuclide therapy (PRRT) is a treatment for neuroendocrine tumours (NET). Renal impairment is a known side effect due to kidney fibrosis. We investigated the association between novel specific fibrosis markers and kidney function following PRRT. We included 38 patients who had all finished PRRT. In serum and urine, we analysed levels of three different fibrosis markers, PRO-C6 (type VI collagen formation), PRO-C3 (type III collagen formation) and C3M (type III collagen degradation). We determined kidney function by the 51Cr-EDTA plasma clearance. We used Wilcoxon rank sum test and Spearman’s rank correlation to evaluate the association between the fibrosis markers and kidney function. We included 38 NET patients, 25 small-intestinal NET, 6 pancreatic NET, 2 pulmonary NET and 5 other types of NET. Median age was 69 years (IQR: 61–73). Median time from last PRRT to inclusion was 8 months (IQR: 3–20). We found significantly increased levels of serum PRO-C6 (p = .007) and urinary PRO-C6 (p = .033) and significantly decreased levels of urinary C3M (p = .035) in patients with impaired kidney function. Further, we observed a negative association between serum PRO-C6 and kidney function (rho = −0.33, p = .04) and a positive association between urinary C3M and kidney function (rho = 0.37, p = .02). We showed an association between the three fibrosis markers, serum PRO-C6, urinary PRO-C6 and urinary C3M and kidney function. These markers may help to improve the understanding of potential pathological tissue turnover and potentially improve monitoring of kidney function after PRRT in NET patients.

A comparison of four established GFR formulas to estimate measured GFR and changes in GFR in adult kidney transplant recipients

The accurate assessment of glomerular filtration rate (GFR) is important in the follow-up of kidney transplant recipients in order to identify graft dysfunction. A number of formulas have been proposed to calculate GFR from endogenous plasma markers such as creatinine or cystatin C since measuring GFR using exogenous markers is troublesome. This study compares and evaluates the ability of four different GFR formulas to estimate kidney graft function and to detect changes in GFR in kidney transplant recipients. The study included patients from the prospective, multicenter CONTEXT trial in kidney transplant recipients. GFR was measured using plasma clearance of 51Cr-EDTA and estimated using the MDRD, CKD-EPI Creatinine, CKD-EPI Cystatin C and CKD-EPI Cystatin C + Creatinine equations at three (n = 83) and twelve (n = 65) months post-transplantation. For each formula mean bias, precision, and accuracy were evaluated. The MDRD equation had the lowest mean bias (0.2 ml/min/1.73 m2), whereas the CKD-EPI Cystatin C + Creatinine equation had the highest precision (8 ml/min/1.73 m2). Accuracy at three months were similar for all equations (P30 > 80%) except for the CKD-EPI Cystatin C equation, which performed poorer (P30 = 55%). None of the formulas evaluated avoided misclassification of changes in GFR. The most optimal combination of precision and accuracy suggests the use of CKD-EPI Creatinine + Cystatin C equation in kidney transplant recipients.

Performance of the 2021 CKD-EPI equations without a race coefficient in a multi-racial population of adults with solid tumors: A prospective cross-sectional study.

12064 Background: We previously showed that estimated glomerular filtration rate (eGFR) based on serum creatinine (Scr)(eGFRcr) using the 2009 CKD-EPI equation performed better than Cockroft-Gault equation (CG) in solid tumor patients in Brazil (Onco-GFR Study). In that study, eGFR based on Scr and cystatin C (Scys)(eGFRcr-cys) using the 2012 CKD-EPI was the most accurate equation and suitable for use as a confirmatory test. The CKD-EPI 2009 eGFRcr and 2012 eGFRcr-cys equations include a term for race (Black vs. non-Black). The 2021 CKD-EPI eGFRcr and eGFRcr-cys equations do not include race and are now recommended in the US, but have not been assessed in a multi-racial population or in cancer patients. The aim of this study is to evaluate the performance of the 2021 CKD-EPI equations in the Onco-GFR Study. Methods: Measured GFR (mGFR) was determined using the plasma clearance of 51Cr-EDTA. Scr and Scys assays were traceable to international standards. Results: A group of 1,200 patients recruited between April 2015 and September 2017 were included for analysis. Patients were 58.8±13.2 years, 50.8% male. Race distribution was Black participants 12.8% and non-Black participants 81.2%. Mean (SD) mGFR was 78.5±21.7 ml/min/1.73 m2. For eGFRcr, the overestimation of mGFR was larger for the 2021 vs. 2009 equation -10.0 vs. 8.1 ml/min/1.73m2, resulting in lesser accuracy 1-P30 of 22.3 vs. 19.1, but still more accurate than CG equation (1-P30 of 24.9, P = 0.05). For eGFRcr-cys, the overestimation of mGFR was larger for the 2021 vs. 2012 equation (-4.1 vs. -2.0 ml/min/1.73m2). eGFRcr-cys using the 2021 equation was more accurate than eGFRcr using the 2021 equation and eGFRcys using the 2012 equation (1-P30 9.8 vs. 22.3 and 12.3, p-values &lt; 0.001 and 0.01, respectively) (Table). Conclusions: 2021 CKD-EPI eGFRcr equation race performed better than CG. 2021 CKD-EPI eGFRcr-cys performed better than 2021 eGFRcr and 2012 eGFRcys equations. Removing race from eGFR equations represents an advance and should be incorporated in cancer care. [Table: see text]

51Cr-EDTA plasma clearance in children: One, two, or multiple samples?

Plasma disappearance curves using multiple blood samples are a recognized reference method for measuring glomerular filtration rate (GFR). However, there is no consensus on the protocol for this type of measurement. A two-compartment model is generally considered acceptable for the mathematical description of the concentration–time decay curve. The impact of the fitting procedure on the reported GFR has not been questioned.We defined 8 different fitting procedures to calculate the area under the curve, and from this area under the curve, the GFR. We applied the 8 fitting methods (all considering a full concentration–time curve) on the multiple sample data (8 samples) of 20 children diagnosed with Duchenne muscular dystrophy. We evaluated the effect (variability) on the reported GFR from the different fitting methods and compared these results with GFR-values calculated from late samples only (samples after 120 minutes) and from one-sample methods.In 6 out of 20 cases, the fitting methods on the full concentration–time curve resulted in very different reported GFR-values, mainly because some methods were not able to fit the data, or methods resulted in GFR-values ranging from 0 to 120 mL/min. The reported GFR-result therefore strongly depends on the fitting method, making the full concentration–time method less robust than expected. Compared with a consensus reference GFR, the late sample models did not show fitting issues and may therefore be considered as more robust. Also the one-sample methods showed acceptable accuracy.The late sample methods (using 3 time-points) provide robust and reliable methods to determine GFR.

A prospective cross-sectional study estimated glomerular filtration rate from creatinine and cystatin C in adults with solid tumors

Current guidelines recommend estimating glomerular filtration rate (eGFR) using creatinine (eGFRcr) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation as the first test for GFR evaluation, but the Cockcroft-Gault (CG) equation is still commonly used in oncology practice and clinical trials despite increasing evidence of its inaccuracy compared to measured GFR (mGFR). Guidelines recommend eGFR using cystatin C (eGFRcys) or both markers (eGFRcr-cys) as a confirmatory test, but neither was carefully evaluated in cancer patients. Therefore, we compared performance of the CKD-EPI equations and others to the CG equation in adults with a variety of solid tumors. The mGFR was determined by plasma clearance of 51Cr-EDTA. Bias was defined as the median of the differences between mGFR and eGFR while accuracy was defined as the percentage of estimates that differed by more than 30% from the measured GFR (1-P30). We prospectively recruited 1,200 patients between April 2015 and September 2017 with a mean age and mGFR of 58.8 years and 78.4 ml/min/1.73m2, respectively. Bias among eGFRcr equations varied from -8.1 to+6.1 ml/min/1.73 m2. CG was the least accurate, 1-P30 (95% confidence interval) was 24.9 (22.4- 27.3)%; CKD-EPI had 1-P30 of 19.1 (16.8-21.2)% while eGFRcr-cys had the best performance: bias -2.0 (-2.6 to -1.1) ml/min/1.73m2 and 1-P30 7.8 (6.3-9.4)%. Thus, the CG equation should not be preferred over CKD-EPI equation, and eGFRcr-cys can be used as a confirmatory test in adults with solid tumors. Hence, a major policy implication would be to adopt general practice guideline-recommended methods for GFR evaluation in oncology practice and clinical trials.

Effect of obesity, age and gender on glomerular filtration rate measured in normal adults

This was a retrospective study of 120live kidney donors (75females, 45males). GFR was evaluated from 51Cr-EDTA plasma clearance using blood samples taken at 3, 4 and 5hours. The slope-intercept GFR was corrected for body surface area using the Dubois & Dubois and for the fast exponential using the Brochner-Mortensen equation. Scatter plot of DFG against age in live kidney donors was plotted and the 98% range limits have been defined. The median GFR obtained for kidney donors was 88mL/min/1.73m2 [68-130]. No significant difference with gender was found. 51Cr-EDTA clearance was strongly correlated with patient age (r =-0.62, P <0,0001). GFR decreased by approximately 8mL/min/1.73m2 per decade. Based on these results, a nomogram for GFR is presented. The interpretation of GFR requires age-adjusted normal values. These standards need not be adjusted to the patient's sex or BMI.

No Race-Ethnicity Adjustment in CKD-EPI Equations Is Required for Estimating Glomerular Filtration Rate in the Brazilian Population.

Background Glomerular filtration rate (GFR) is usually estimated from equations using serum creatinine (sCr), with adjustment for gender, age, and race (black or nonblack). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is the preferred equation for adults, but it was validated for the United States population. We intended to evaluate if the race-ethnicity adjustment proposed for the sCr-based CKD-EPI equations is appropriate for the Brazilian population. Methods CKD outpatients had blood samples collected for determination of sCr and serum cystatin C (sCys) levels. GFR was measured (mGFR) by plasma clearance of 51Cr-EDTA and used as the reference. We compared values of mGFR and estimated GFR (eGFR) by CKD-EPI equations based on sCr (eGFRCr) and on the combination of sCr and sCys (eGFRCr-Cys). For African Brazilian patients, eGFR was calculated either without or with race adjustment. Accuracy was considered acceptable if the difference between the values of eGFR and mGFR was ≤30% (P30). Results 100 patients were enrolled (58 ± 14 years, 46% male, 39% white and 61% African Brazilian). Mean mGFR was 46.7 ± 29.2 ml/min/1.73 m2. Mean eGFRCr and eGFRCr-Cys without race adjustment were 47.8 ± 30.1 ml/min/1.73 m2 and 46.4 ± 30.3 ml/min/1.73 m2, respectively. The corresponding P30 accuracy values were 79.0% and 83.0%. In the African Brazilian subgroup, values for mean mGFR and eGFRCr either without or with race adjustment were 49.8 ± 32.2 ml/min/1.73 m2, 50.4 ± 32.7 ml/min/1.73 m2, and 58.4 ± 37.9 ml/min/1.73 m2 (P < 0.001 vs. mGFR), respectively. P30 accuracy values for eGFRCr either without or with race adjustment were 75.4% and 67.2%, respectively. Conclusions The use of CKD-EPI equations without race-ethnicity adjustment seems more appropriate for the Brazilian population.

Determination of the glomerular filtration rate in patients with type 2 diabetes: An assessment of the agreement between 51Cr-EDTA plasma clearance and 99mTc-DTPA plasma clearance, 99mTc-DTPA renography and plasma creatinine prediction equation

AimsTo investigate the agreement of glomerular filtration rate (GFR) determination between 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) plasma clearance (GFREDTA) and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) plasma clearance (GFRDTPA), the Gates 99mTc-DTPA renographic method (GFRGates) and the serum creatinine Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI, GFRSCr) in patients with type 2 diabetes mellitus (T2DM). MethodsNinety-nine T2DM patients underwent GFR determinations simultaneously with 51Cr-EDTA and 99mTc-DTPA (using the slope-intercept technique and the Brochner-Mortensen correction) and also with GFRGates and GFRSCr. ResultsIn the comparison between GFREDTA versus GFRDTPA, GFRGates and GFRSCr, the Bland-Altman statistic provided 0.0 ± 13.2, 17.4* ± 28.8 and −5.9* ± 30.1 (*p < 0.001 for the difference from 0). Lin’s concordance correlation coefficient showed substantial (0.976), poor (0.737) and poor (0.872) agreement, respectively. The proportion of the index results within the 30% and 10% of GFREDTA measurements were 95% and 74% for GFRDTPA, 53% and 19% for GFRGates, and 83% and 26% for GFRSCr, respectively. ConclusionIn T2DM patients, a clinically acceptable agreement is demonstrated between 51Cr-EDTA and 99mTc-DTPA plasma clearance for GFR measurements, suggesting conditional interchangeability between those compounds. Both the CKD-EPI prediction equation and the Gates’ renographic method cannot assess GFR reliably, the latter appearing less unfailing than the former.

Comparison of MDRD equations and the old equations CKD-EPI against new equations CKD-EPI in patients with kidney transplantation when used 51Cr-EDTA to measure glomerular filtration

BackgroundWhen estimating the glomerular filtration rate (GFR) in kidney transplant patients, significant differences have been found between MDRD and the 2009 CKD-EPI equations, and reference techniques. ObjectiveTo analyse and compare the performance of MDRD and the 2009 and 2012 CKD-EPI equations against 51Cr-EDTA plasma clearance in measuring GFR in 270 kidney transplant patients after one year. ResultsThe mean measured GFR was 43.0 ± 11.4 (18.2–79.4) ml/min/1.73 m2, with creatine levels of 1.42 ± 0.46 (0.60–4.33) mg/dl and cystatin C levels of 1.45 ± 0.53 (0.42–3.48) mg/l. This correlated moderately with creatinine (r=–0.61, p < 0.001) and cystatin C (r=–0.52, p < 0.001). Using linear regression techniques, it was found that creatinine, cystatin C, gender and age only explained 52% of GFR total variance. All equations overestimated GFR, with a mean bias of +11.1 ml/min/1.73 m2 for MDRD, +16.4 ml/min/1.73 m2 for 2009-CKD-EPI, +15 ml/min/1.73 m2 for CKD-EPI with cystatin C and +14.1 ml/min/1.73 m2 for 2012-CKD-EPI with creatinine and cystatin C. eGFR by MDRD and the 2009 CKD-EPI equation correlated better with 51Cr-EDTA than CKD-EPI with creatinine and/or cystatin C. The overestimations were negatively correlated with creatinine and cystatin C levels, most significantly for CKD-EPI with creatinine and/or cystatin C when GFR was greater than 60 ml/min/1.73 m2. ConclusionsThe 2012 CKD-EPI equations with creatinine and/or cystatin C significantly overestimate GFR in stage 1 and 2 chronic kidney disease. The MDRD equation is therefore recommended in these cases. The reference method used to measure GFR seems to heavily influence the bias of the equations.

Comparación de las ecuaciones MDRD y de las antiguas ecuaciones CKD-EPI frente a las nuevas ecuaciones CKD-EPI en pacientes con trasplante renal cuando se emplea 51Cr-EDTA para medir el filtrado glomerular

BackgroundWhen estimating the glomerular filtration rate (GFR) in kidney transplant patients, significant differences have been found between MDRD and the 2009 CKD-EPI equations, and reference techniques. ObjectiveTo analyse and compare the performance of MDRD and the 2009 and 2012 CKD-EPI equations against 51Cr-EDTA plasma clearance in measuring GFR in 270 kidney transplant patients after one year. ResultsThe mean measured GFR was 43.0±11.4 (18.2–79.4)ml/min/1.73m2, with creatinine levels of 1.42±0.46 (0.60-4.33)mg/dl and cystatin C levels of 1.45±0.53 (0.42-3.48)mg/l. This correlated moderately with creatinine (r=–0.61, P<.001) and cystatin C (r=–0.52, P<.001). Using linear regression techniques, it was found that creatinine, cystatin C, gender and age only explained 52% of GFR total variance. All equations overestimated GFR, with a mean bias of +11.1ml/min/1.73m2 for MDRD, +16.4ml/min/1.73m2 for 2009-CKD-EPI, +15ml/min/1.73m2 for CKD-EPI with cystatin C, and +14.1ml/min/1.73m2 for 2012-CKD-EPI with creatinine and cystatin C. eGFR by MDRD and the 2009 CKD-EPI equation correlated better with 51Cr-EDTA than CKD-EPI with creatinine and/or cystatin C. The overestimations were negatively correlated with creatinine and cystatin C levels, most significantly for CKD-EPI with creatinine and/or cystatin C when GFR was greater than 60ml/min/1.73m2. ConclusionsThe 2012 CKD-EPI equations with creatinine and/or cystatin C significantly overestimate GFR in stage 1 and 2 chronic kidney disease. The MDRD equations is therefore recommended in these cases. The reference method used to measure GFR seems to heavily influence the bias of the equations.

Comparison of simultaneous plasma clearance of 99mTc-DTPA and 51Cr-EDTA: can one tracer replace the other?

Both 99mTc-DTPA and 51Cr-EDTA are widely used to determine glomerular filtration rate (GFR), but few direct comparative studies exist. The shortage of 51Cr-EDTA makes a direct comparison highly relevant. The aim of the study was to investigate if there is any clinically relevant difference between plasma clearance of 99mTc-DTPA and 51Cr-EDTA. Patients ≥18 years of age referred for routine GFR measurement by 51Cr-EDTA were prospectively enrolled. The two tracers (10 MBq 99mTc-DTPA (CaNa3-DTPA) and 2.5 MBq 51Cr-EDTA) were intravenously injected at time zero. A standard 4-sample technique was applied with samples collected at 180, 200, 220 and 240 min, if the estimated GFR (eGFR) was ≥30 mL/min. A comparison of single-sample GFR based on the 200 min sample was also conducted. Fifty-six patients were enrolled in the study. All patients had an estimated GFR >30 mL/min/1.73 m2. No patients suffered from ascites or significant oedema. The mean 51Cr-EDTA plasma clearance was 82 mL/min (range 16–226). The plasma clearances determined by the two methods were highly correlated (r = 0.993). The plasma clearance was significantly higher when measured by 99mTc-DTPA than by 51Cr-EDTA (p = 0.01), but the numerical difference was minimal (mean difference 1.4 mL/min; 95% limits of agreement (LOA) –6.6 to 9.4). The difference between the two methods was independent of the level of renal function. Similar results were found for one-sample GFR. No clinically relevant differences were found between the plasma clearance of 99mTc-DTPA and that of 51Cr-EDTA. Therefore, 99mTc-DTPA can replace 51Cr-EDTA when needed.

Short-term effects of liraglutide on kidney function and vasoactive hormones in type 2 diabetes: a randomized clinical trial.

To investigate the effects of a single dose of 1.2 mg liraglutide, a once-daily glucagon-like peptide-1 (GLP-1) receptor agonist, on key renal variables in patients with type 2 diabetes. The study was a placebo-controlled, double-blind, crossover trial in 11 male patients with type 2 diabetes. Measurements included (51) Cr-EDTA plasma clearance estimated glomerular filtration rate (GFR) and MRI-based renal blood flow (RBF), tissue perfusion and oxygenation. Liraglutide had no effect on GFR [95% confidence interval (CI) -6.8 to 3.6 ml/min/1.73 m(2) ] or on RBF (95% CI -39 to 30 ml/min) and did not change local renal blood perfusion or oxygenation. The fractional excretion of lithium increased by 14% (p = 0.01) and sodium clearance tended to increase (p = 0.06). Liraglutide increased diastolic and systolic blood pressure (3 and 6 mm Hg) and heart rate (2 beats per min; all p < 0.05). Angiotensin II (ANG II) concentration decreased by 21% (p = 0.02), but there were no effects on other renin-angiotensin system components, atrial natriuretic peptides (ANPs), methanephrines or excretion of catecholamines. Short-term liraglutide treatment did not affect renal haemodynamics but decreased the proximal tubular sodium reabsorption. Blood pressure increased with short-term as opposed to long-term treatment. Catecholamine levels were unchanged and the results did not support a GLP-1-ANP axis. ANG II levels decreased, which may contribute to renal protection by GLP-1 receptor agonists.

Forty-five-year follow-up on the renal function after spinal cord injury.

Retrospective chart review. To investigate the extent of renal deterioration in patients with spinal cord injury (SCI) and to identify risk indicators associated with renal deterioration. Clinic for Spinal Cord Injuries, Rigshospitalet, Hornbæk, Denmark. This study included 116 patients admitted to our clinic with a traumatic SCI sustained between 1956 and 1975. Results from renography and (51)Cr-EDTA plasma clearance were collected from medical records from time of injury until 2012, and the occurrence of renal deterioration was analysed by cumulative incidence curves. The impact of demographics, neurological level and completeness of SCI, urinary tract stones, dilatation of the upper urinary tract (UUT) and bladder-emptying methods were analysed with Cox proportional hazard ratios. The bladder-emptying methods used for the longest period were reflex triggering (63%), bladder expression (22%), indwelling catheter (5%), normal voiding (4%), ileal conduit (3%) and clean intermittent catheterisation (2%). The cumulative risk of moderate renal deterioration (functional distribution outside 40-60% on renography or relative glomerular filtration rate (GFR) ⩽75% of expected according to age and gender) was 58%. The cumulative risk of severe renal deterioration (functional distribution outside 30-70% on renography or relative GFR⩽51%) was 29% after 45 years postinjury. Only dilatation of UUT and renal/ureter stone requiring removal significantly increased the risk of moderate and severe renal deterioration. Renal deterioration occurs at any time after injury, suggesting that lifelong follow-up examinations of the renal function are important, especially in patients with dilatation of UUT and/or renal/ureter stones.

Monitoring Kidney Function in Neuroendocrine Tumor Patients Treated with (90)Y-DOTATOC: Associations with Risk Factors.

Peptide receptor radionuclide therapy (PRRT) is an established treatment for progressive neuroendocrine tumours with nephrotoxicity as the limiting factor. It is therefore important to monitor kidney function changes after PRRT treatment. We aimed to investigate kidney function by different methods and during a 4-hour and a 24-hour amino acid (AA) infusion protocol. We measured the Glomerular Filtration Rate (GFR) in 28 patients before and 3, 6, 12, and 18 months after (90)YDOTATOC therapy. We used standardized (51)Cr-EDTA plasma clearance (Cr-GFR) and estimated GFR (eGFR) by the simplified 4 variable Modification of Diet in Renal Disease based on serum creatinine values. Further, we determined GFR in 15 patients treated with a 4-hour infusion of AA compared to 13 patients with a 24-hour infusion at 3, 6, 12 and 18 months after therapy. Pre-existing risk factors associated with kidney failure were seen in 82% of the patients. We observed a significant reduction in Cr-GFR up to 12 months after PRRT (mean loss 27 ml/min/1.73 m(2) (32%)). The eGFR continuously overestimated the Cr-GFR with a bias of 8%. There was no significant difference between the two AA protocols, however, the 24-hour AA protocol tended to reduce mean Cr-GFR loss 12 months post therapy. Pre-existing risk factors for kidney failure were highly prevalent in this patient cohort, and kidney function after PRRT treatment is best monitored by (51)Cr-EDTA plasma clearance. Further, the use of a 24-hour AA kidney protection protocol seems to reduce the loss of kidney function in these patients.

Glucagon-like peptide 1 receptor agonist (GLP-1 RA): long-term effect on kidney function in patients with type 2 diabetes

AimsIn a short-term study including 31 patients with type 2 diabetes, glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment was associated with a significant reversible decline in GFR. Twenty-three patients re-initiated GLP-1 RA treatment after the primary study, and the aim was to investigate the long-term effect on kidney function. MethodsWe included 30 patients in a one-year extension study, all initially treated with liraglutide for seven weeks. During follow-up 23 were treated with liraglutide and seven untreated. Primary outcome was change in GFR (51Cr-EDTA plasma clearance). ResultsPatients were 61.5 (10.0) years and HbA1c 60.1 (13.8) mmol/mol. Baseline GFR was 100.6 (24.9) mL/min/1.73m2 and was reduced by 11 (95% CI: 6.6–15.7, p<0.001) mL/min/1.73m2, independent of change in 24-h systolic blood pressure (SBP), weight, UAER or HbA1c (p≥0.33). Geometric mean (IQR) of UAER was 25.5 (9.9–50.9) mg/d and was reduced by 27 (95% CI: 5–44; p=0.020)%, and 24-h SBP was reduced by 8.2 (p=0.048) mmHg. No changes occurred in untreated patients. ConclusionsLong-term treatment with liraglutide was associated with a reduction in measured GFR similar to the effect during short-term treatment, suggesting a metabolic or haemodynamic reversible effect and not structural changes. Moreover, UAER and 24-h SBP were reduced. Trial registrationClinicalTrials.gov identifier: NCT01499108.

Improved prognosis of diabetic nephropathy in type 1 diabetes

The natural history of diabetic nephropathy offered an average survival of only 5-7 years. During the past decades, multiple changes in therapy and lifestyle have occurred. The prognosis of diabetic nephropathy after implementing stricter control of blood pressure (including increased use of long-term renin-angiotensin system inhibition), lipids, and glycemia, along with less smoking and other lifestyle and treatment advancements, is inadequately analyzed. To clarify this, we studied 497 patients with type 1 diabetes and diabetic nephropathy at the Steno Diabetes Center and compared them with previous data, obtained using identical criteria at our hospital. The glomerular filtration rate, measured yearly by 51Cr-EDTA plasma clearance, was a mean of 71 ml/min per 1.73 m2 at baseline. The mean glomerular filtration rate decline was significantly reduced by 19% (95% confidence interval 5-34) from previously 4.0 to 3.3 ml/min per 1.73 m2/year. During a median follow-up of 9.1 years, 29% of participants doubled their plasma creatinine or developed end-stage renal disease. Mortality risk was similar to our prior study (hazard ratio 1.05 (0.76-1.43). However, after age adjustment, as both diabetes and nephropathy onset occurred later in life, mortality was reduced by 30%. Risk factors for decline in glomerular filtration rate, death, and other renal end points were generally in agreement with prior studies. Thus, with current treatment of nephropathy in type 1 diabetes, the prognosis and loss of renal function has improved along with better control of modifiable risk factors.