Mean mGFR Research Articles

The Utility of Combined Urine Urea and Creatinine Clearance for Pretransplant Renal Function Assessment

Evaluation of donor renal function as glomerular filtration rate (GFR) is a crucial part of pretransplant workup. Most guidelines recommend measured GFR (mGFR) using exogenous markers with creatinine clearance (CrCl) as an alternative. However, exogenous markers are difficult to obtain and perform, and CrCl may overestimate GFR. We explore the use of CrCl and combined urea and creatinine clearance as an alternative for GFR assessment. A retrospective study involving 81 kidney donors from 2007 to 2020, with mGFR collected by chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) and CrCl and combined urea and creatinine clearance. We analyzed the performance of CrCl and combined urea and creatinine clearance against 51Cr-EDTA. Adequacy of urine volume was taken into consideration. A total of 81 candidates with a mean age of 44.80 ± 10.77 years were enrolled. Mean mGFR from 51Cr-EDTA was 123.66 ± 26.91 mL/min/1.73 m2, and combined urea and creatinine clearance and CrCl were 122.13 ± 47.07 and 133.40 ± 36.32 mL/min/1.73 m2, respectively. CrCl overestimated 51Cr-EDTA. Though combined urea and creatinine clearance had minimal bias, it had a lower correlation coefficient (0.25 vs 0.43), lower precision (49.51 vs 38.10), and slightly lower accuracy within 30% of 51Cr-EDTA (74.07% vs 76.54%). Combined urea and creatinine clearance did not improve the performance of CrCl. Nevertheless, it can potentially be used as first-line GFR assessment, followed by mGFR in selected donors, to ascertain threshold of safe kidney donation. A stringent urine collection method is essential to ensure accurate measurement.

13-LB: Measured vs. Estimated GFR in Young Adults with Uncomplicated T1D

Background: eGFR equations are used to monitor progression of kidney disease, but their performance is incompletely understood in young adults with T1D and preserved GFR. To address this deficit, we compared two eGFR equations (creatinine-based CKD-EPI and modified Schwartz) to mGFR in this population. Methods: GFR based on plasma iohexol clearance was measured in 53 patients (24 males) with T1D, as part of the CAN-SOLVE CKD study Results: Mean age was 20.6±2.1 yrs with mean diabetes duration of 13.1±3.3 yrs. Mean HbA1c and ACR were 8.1±1.3 and 1.6±1.9 mg/mmol, respectively. Mean mGFR was 107.6±15.9 ml/min/1.73 m2. The Schwartz eGFR had a smaller mean bias (5.6 vs. 27.4 ml/min/1.73m2), better accuracy, and overall correlation compared to the CKD-EPI eGFR, while the latter had slightly superior precision. However, both equations were in poor agreement with mGFR. Examination of the Bland Altman plots reveals that, in the lower normal range, the CKD-EPI equation overestimated mGFR. The modified Schwartz equation showed no discernible tendencies. Conclusion: In young adults with T1D and preserved GFR, the modified Schwartz eGFR performed slightly better than CKD-EPI eGFR. Overall, however, both were in poor agreement with mGFR suggesting caution about the use of eGFR as a surrogate outcome in longitudinal studies and emphasizing the need to develop novel equations for this population. Disclosure K. Gaebe: None. C. A. White: None. F. H. Mahmud: Advisory Panel; Self; Insulet Corporation, Lilly Diabetes. J. W. Scholey: None. L. Motran: None. M. Palaganas: None. Y. T. Elia: None. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Scientific Affairs, LLC., Lilly Diabetes, Merck & Co., Inc., Mitsubishi-Tanabe, Maze Inc, Prometic, Novo Nordisk, Sanofi. E. B. Sochett: None. Funding Canadian Institutes of Health Research (20R26070); JDRF

MO512THE RENAL CONSEQUENCES OF LUNG TRANSPLANTATION IN ADULT CYSTIC FIBROSIS PATIENTS

Abstract Background and Aims Cystic fibrosis patients are at high risk for chronic kidney disease (CKD), because of chronic aminoglycoside exposure, high protein and dietary salt intake, and Cystic Fibrosis Related Diabetes. Lung transplantation also entails a high renal burden in the long run because of calcineurin inhibitors exposure. We aimed at studying kidney function by gold standard glomerular filtration rate (mGFR) before and 1 year after lung transplantation, as well as identify risk factors for kidney function impairment. Method Patients from the Cystic Fibrosis reference center in Lyon, France were systematically referred to the nephrology department before lung transplantation. mGFR (iohexol or inulin clearance) was performed before and 12-18 months after lung transplantation. Risk factors for a worse nephrological outcome (i.e. post transplantation mGFR < 60mL/min/1.73m²) were searched for. Results 28 patients (10 males), mean age 32 yr, underwent pre transplantation mGFR. Three died following lung transplantation and two progressed to end stage renal disease rapidly thereafter. 23 patients benefited from both pre and post transplantation mGFR. Mean mGFR was 105±21mL/min/1.73m² and 67±19 mL/min/1.73m² before and after transplant respectively. Factors associated with a worse renal outcome in both univariate and multivariate analysis were age at transplantation (p=0.03) and the occurrence of acute kidney injury in the post-operative period (p=0.005). Cumulated aminoglycoside exposure and time spent under cardiopulmonary bypass were not associated with renal outcome. Conclusion Lung transplantation is associated with a high renal burden in adult Cystic Fibrosis patients. We advise a clinical referral to a nephrologist as part of the systematic evaluation in lung transplantation candidates even if GFR is in the normal range.

POS-230 COMPARISON OF MEASURED GLOMERULAR FILTRATION RATE BY PLASMA IOHEXOL CLEARANCE WITH EXISTING EQUATIONS OF ESTIMATING GLOMERULAR FILTRATION RATE IN INDIAN SUBJECTS

Glomerular filtration rate (GFR) is a basis of diagnosis and severity of renal diseases. Currently used estimating GFR equations are ethnicity- specific and have not been validated in Indian population. We evaluated the performance of the existing eGFR equations for assessment of GFR in Indians using plasma clearance of Iohexol method. We measured GFR in 208 subjects who were being evaluated as healthy prospective kidney donors (HPKDs) or diagnosed as chronic kidney disease (CKD). The demographic details, anthropometric measurements and clinical data were recorded and baseline blood sample was collected. 3-5ml Iohexol was intravenously injected and blood sampling was done at 60, 120, 180 and 240 mins. The Iohexol were analysed using UHPLC. Serum creatinine was measured by Jaffe’s kinetic Assays and serum Cystatin C using ELISA kit. The GFR was measured by plasma disappearance rate of Iohexol. The dietary protein intake was measured using 24-hour diet recall method. The precision and accuracy of estimating GFR equations was calculated against measured GFR. The bias was expressed as mean difference between measured GFR and estimated GFR and precision was expressed as 95% confidence interval of bias. The accuracy (P30) was calculated as number of subjects with eGFR within ±30% of mGFR. Study participants with mean age 48.4±11.1 years included 130 CKD patients and 78 prospective renal donors. 52% were male and half of the total subjects were vegetarian. The average daily protein intake was 49.9±14.0 g/day. The mean mGFR was 49.0±25.0 ml/min/1.73m2. The mean estimated GFR was 64.6±36.1 ml/min/1.73m2, 46.9±22.2 ml/min/1.73m2and 64.1±40.7 ml/min/1.73m2by CKD-EPIcr, CKD-EPIcys and MDRD, respectively. Barring CKD-EPIcys equation, a significant difference was observed between mGFR and other two eGFR equations (CKD-EPIcr: p<0.001 and MDRD: p<0.001). The mean bias was -15.6±22.4 ml/min/1.73m2(95% CI: -18.6 to -12.5), 2.1±16.8 ml/min/1.73m2(95% CI: -0.1 to 4.4) and -15.1±26.4 ml/min/1.73m2 (95% CI: -18.7 to -11.8) for CKD-EPIcr, CKD-EPIcys and MDRD equations. The P30 was 46.2% for CKD-EPIcr, 57.7% for CKD-EPIcys and 45.2% for MDRD equation. When data were stratified by CKD and HPKD groups, the mean mGFR was 35.1±14.4 ml/min/1.73m2 in CKD and 72.3±21.4 in HPKD. 32% of HPKDs had measured GFR <60ml/min/1.73m2. The mean bias for CKD-EPICr, CKD-EPICys and MDRD were -5.6±14.4 ml/min/1.73m2 (95%CI: -8.1 to -3.1), 1.6±12.9 ml/min/1.73m2 (95%CI: -0.62to 3.9) and -3.2 ± 14.5 ml/min/1.73m2 (95%CI: -5.7 to -0.6) in CKD patients and it was -32.2±23.6 ml/min/1.73m2(95% CI: -37.4 to -26.8), 3.0±21.9 ml/min/1.73m2 (95% CI: -1.9 to 7.9) and -35.0±29.9 ml/min/1.73m2 (95% CI: -41.7 to -28.3 in HPKD. In CKD group, P30 for CKD-EPIcr, CKD-EPICys and MDRD was 53.8%, 51.5% and 55.3% whereas it was 33.3%, 67.9% and 28.2% in HPKDs. Creatinine-based eGFR equations overestimated GFR. However, eGFR by CKD-EPIcys was close to mGFR; exhibited lowest bias and highest accuracy. The accuracy of eGFR equations against mGFR in Indians will become clear in future study in healthy general population to assess the actual GFR.

Hypothermia During Partial Nephrectomy for Patients with Renal Tumors: A Randomized Controlled Trial.

Surgeons induce renal hypothermia during partial nephrectomy to preserve kidney function, without strong evidence of benefit. This trial examined the effectiveness and safety of renal hypothermia during partial nephrectomy. We conducted a parallel randomized controlled trial of hypothermia versus no hypothermia (control group) during partial nephrectomy at 6 academic hospitals. Eligible patients had a planned open partial nephrectomy for the treatment of a renal tumor. During surgery, after clamping the renal hilum, patients were randomized to the intervention or control arm in a 1:1 ratio using permuted blocks of variable lengths (2 and 4), stratified by institution, using a computer-based program. Surgeons and study coordinators were masked to treatment allocation until the renal hilum was clamped. Overall glomerular filtration rates were determined before, and 1-year after, surgery. The primary outcome was measured glomerular filtration rate (mGFR) assessed by the plasma clearance of 99mTc-DTPA. The trial (NCT01529658) was designed with 90% power to detect a minimal clinically important difference in mGFR of 10 ml/minute/1.73 m2 at a 5% significance level. Of the 184 patients randomized, hypothermia and control patients had similar baseline mean mGFR (87.1 vs 81.0 ml/minute/1.73 m2). One hundred and sixty-one (79 hypothermia, 82 control) were alive with primary outcome data 1 year after surgery. The change in mGFR 1 year after surgery was -6.6 ml/minute/1.73 m2 in the hypothermia group and -7.8 ml/minute/1.73 m2 in the control group (mean difference 1.2 ml/minute/1.73 m2, 95% CI -3.3 to 5.6). Operated-kidney change in mGFR was similar between groups (-5.8 vs -6.3 ml/minute/1.73 m2; mean difference 0.5 ml/minute/1.73 m2, 95% CI -2.9 to 3.8). No clinically significant difference in the mGFR was observed when patients were stratified by pre-planned subgroups. Renal hypothermia did not impact the secondary outcomes of surgical complications and patient reported quality of life. Renal hypothermia during partial nephrectomy does not preserve kidney function in patients with normal or mildly impaired renal function.

Performance of 4 Creatinine-based Equations in Assessing Glomerular Filtration Rate in Adults with Diabetes.

To evaluate diagnostic performance of glomerular filtration rate (GFR) estimated by modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI), full age spectrum (FAS), and revised Lund-Malmö (r-LM) equations in adults with diabetes. Individuals were included in this cross-sectional study if they had at least 1 measurement of technetium-99m diethylenetriamine-pentaacetic acid (99mTc-DTPA) GFR (mGFR) and serum creatinine (1487 patients with 2703 measures). GFR calculated by estimation equations was compared with mGFR. Diagnostic performance was assessed using concordance correlation coefficient (CCC), bias, precision, accuracy, reduced major axis regression (RMAR), and Bland-Altman plot. Analysis was repeated in subgroups based on sex, diabetes type, Hemoglobin A1C, and GFR level. Of all patients, 1189 (86%) had type 2 diabetes. Mean mGFR, MDRD, CKD-EPI, FAS, and revised Lund-Malmö eGFR were 66, 72, 74, 71, and 67 mL/min/1.73m2, respectively. Overall, the r-LM had the highest CCC (0.83), lowest bias (-1.4 mL/min/1.73 m2), highest precision (16.2 mL/min/1.73 m2), and highest accuracy (P10 = 39%). The RMAR (slope, intercept) in r-LM, FAS, MDRD, and CKD-EPI was 1.18, -13.35; 0.97, -2.9; 1, -6.4, and 1.04, -11.3, respectively. The Bland-Altman plot showed that r-LM had the lowest mean difference and the narrowest 95% limit of agreement (-1.0, 54.1 mL/min/1.73 m2), while mean difference was more than 5-fold higher in FAS, MDRD, and CKD-EPI (-5.2, -6.3, and -8.2, respectively). In adults with diabetes the revised Lund-Malmö performs better than MDRD, CKD-EPI, and FAS in calculating point estimates of GFR.

TA COMPARISON OF THE CREATININE CLEARANCE BY GFR ESTIMATING EQUATIONS WITH MEASURED GFR BY ISOTOPE SCAN IN VOLUNTARY LIVING KIDNEY DONOR

Background: Glomerular filtration rate (GFR) is essential for renal function evaluation. The need for estimating GFR stems from the shortcomings of interpreting plasma creatinine alone, the cost and complexities of determining a gold standard GFR with either inulin or radionuclides like iothalamate, and the inaccuracies associated with the measurement of a 24 h urine creatinine clearance. It is of special concern in Voluntary Kidney Donor(VKD) in living donor transplantation. Equations like Cockcroft- Gault formula (CGF), Modified Diet in Renal Disease (MDRD) and the Chronic kidney disease- Epidemiology Collaboration equation (CKD-EPI) are useful in estimating GFR. This study is to validate the different GFR estimating equations, and their correlation with measured GFR by nuclear Isotope scan in VKD. Methods: We measured GFR with double-sample plasma clearance of 99mTc-DTPA (mGFR) in 814 healthy adult (=>18yrs) individuals. Using mGFR as the gold standard, we evaluated the efficiency of three different GFR estimation equations (CGF, MDRD and CKD-EPI) and calculated their precision and correlation. Result: In our population, the mean mGFR was 81.46 ± 14.35 mL/min/1.73m2. In correlation analysis, the three equations have significant linear correlation with mGFR (p<0.01), and the linear regression demonstrated moderate explanatory capacity of eGFR produced by CKD-EPI (R2 = 0.22), CGF (R2 = 0.15) and MDRD (R2 = 0.12). The slopes in the Bland-Altman analysis of CGF, MDRD and CKD-EPI are -0.68, -0.41 and -0.18. Intraclass coefficients was highest for CKD-EPI (0.63), followed by CGF (0.51) and MDRD (0.49). Thus, The CGF, MDRD and CKD-EPI formula produced eGFR with strong correlation with mGFR, moderate explanation capacity of variance in mGFR, small bias, satisfactory performance in Bland-Altman analysis and high intra-class correlation coefficients. Conclusion: This study concludes significant correlation between measured GFR and the GFR estimating equations: CGF, CKD EPI and MDRD. Of the three, CKD -EPI has the highest precision of GFR prediction in VKD.

Trajectory of extracellular fluid volume over time and subsequent risks of end-stage kidney disease and mortality in chronic kidney disease: a prospective cohort study.

Extracellular fluid volume (ECF) is independently associated with chronic kidney disease (CKD) progression and mortality in patients with CKD, but the prognostic value of the trajectory of ECF over time beyond that of baseline value is unknown. To characterize ECF trajectory and evaluate its association with the risks of end-stage kidney disease (ESKD) and mortality. From the prospective tricentric NephroTest cohort, we included 1588 patients with baseline measured glomerular filtration rate (mGFR) ≥15mLmin-1 /1.73m2 and ECF measurement. ECF and GFR were measured repeatedly using the distribution volume and clearance of 51 Cr-EDTA, respectively. ESKD and mortality were traced through record linkage with the national registries. Adjusted shared random-effect joint models were used to analyse the association between the trajectory of ECF over time and the two competing outcomes. Patients were mean age 58.7years, 66.7% men, mean mGFR of 43.6±18.6mLmin-1 /1.73m2 and mean ECF of 16.1±3.6L. Over a median follow-up of 5.3 [IQR: 3.0;7.4] years, ECF increased by 136 [95%CI 106;167] mL per year on average, whilst diuretic prescription and 24-hour urinary sodium excretion remained stable. ESKD occurred in 324 (20.4%) patients, and 185 (11.6%) patients died before ESKD. A higher current value of ECF was associated with increased hazards of ESKD (adjusted hazard ratio [aHR]: 1.12 [95%CI 1.06;1.18]; P<0.001 per 1 L increase in ECF), and death before ESKD (aHR: 1.10 [95%CI 1.04;1.17]; P=0.002). The current value of ECF was associated with the risks of ESKD and mortality, independent of multiple potential confounders, including kidney function decline. This highlights the need for a close monitoring and adjustment of treatment to avoid fluid overload in CKD patients.

Cystatin C and Urine Albumin to Creatinine Ratio Predict 5-Year Mortality and Cardiovascular Events in People Living With HIV.

Identifying people with HIV (PWH) at risk for chronic kidney disease, cardiovascular events, and death is crucial. We evaluated biomarkers to predict all-cause mortality and cardiovascular events, and measured glomerular filtration rate (mGFR) slope. Biomarkers were measured at enrollment. Baseline and 5-year mGFR were measured by plasma iohexol clearance. Outcomes were a composite criterion of all-cause mortality and/or cardiovascular events, and mGFR slope. Of 168 subjects, 146 (87.4%) had undetectable HIV load. Median follow-up was 59.1 months (interquartile range, 56.2-62.1). At baseline, mean age was 49.5 years (± 9.8) and mean mGFR 98.9 mL/min/1.73m2 (± 20.6). Seventeen deaths and 10 cardiovascular events occurred during 5-year follow-up. Baseline mGFR was not associated with mortality/cardiovascular events. In multivariable analysis, cystatin C (hazard ratio [HR], 5.978; 95% confidence interval [CI], 2.774-12.88; P < .0001) and urine albumin to creatinine ratio (uACR) at inclusion (HR, 1.002; 95% CI, 1.001-1.004; P < .001) were associated with mortality/cardiovascular events. Area under receiver operating curve of cystatin C was 0.67 (95% CI, .55-.79) for mortality/cardiovascular event prediction. Biomarkers were not associated with GFR slope. uACR and cystatin C predict all-cause mortality and/or cardiovascular events in PWH independently of mGFR.

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.

P0654INTEREST OF SCREENING FOR CKD AFTER AKI IN ICU AND THE PLACE OF CYSTATIN C IN THIS POPULATION

Abstract Background and Aims Acute Kidney Injury (AKI) is one of the most frequent complications in Intensive Care Unit (ICU). It’s now clearly established that AKI may be associated with the installation and/or worsening of Chronic Kidney Disease (CKD). However, few patients are currently screened for CKD after hospitalization in the ICU. In addition, ICU patients often have changes in their volume of distribution and muscle mass that may interfere with plasma Creatinine (pCreat) dosing and thus the estimated GFR (eGFR) value using CKD-Epi equation. Method Since 2019, we are prospectively screening for CKD patients who developed moderate-to-severe AKI (KDIGO 2 and 3) in ICU. Patients are referred to Nephrology consultation within 2 to 3 months after discharge from the ICU. The screening for CKD is performed according to the GFR estimation using the CKD-Epi equation. In this cohort, we will assess the incidence of CKD after ICU discharge and factors associated with CKD installation and worsening (univariate and multivariate analysis). In addition, for some patients, we planned to measure GFR using Iohexol clearance to compare measured GFR (mGFR) to eGFR using both CKD-Epi equation and Cystatin C-based equations. Results So far, 43 patients have been referred in Nephrology consultation, 72% of male and a mean age of 62 (±16) years. The time between the ICU discharge and the consultation was 55 (±21) days. The main co-morbidities were diabetes (37%) and hypertension (58%). The mean eGFR before the ICU (basal renal function) was 78 (±24) ml/min/1.73m2 and the pCreat was 89 (±21) µmol/l. At baseline, twenty-one percent of the patients had an eGFR &amp;lt; 60 ml/min/1.73m2. The length of stay in the ICU was 14 (±14) days. Nearly half of the patients (47%) were ventilated and 56% received vasopressive drugs. Most of the patients (74%) developed KDIGO Stage 3 AKI and 26% developed Stage 2 AKI. The mean entry pCreat was 252 (± 178) µmol/l, reaching a maximum of 382 (± 198) µmol/l during the hospitalization. Sixty percent of the patients underwent renal replacement therapy. The patients lost in average 10 kgs during the hospitalization. The pCreat at discharge was 175 µmol/l (± 175). At the time of the consultation, the eGFR was 70 (± 27) ml/min/1.73m2 with 35% of the patients with an eGFR &amp;lt; 60 ml/min/1.73m2. Univariate and multivariate analysis will be performed to evaluate the mains factors associated with CKD. At this time, 8 patients had a GFR measure using Iohexol. Mean mGFR was 32,8 (±14) ml/min/1,73m2, lower than the CKD-Epi (57±19), the CKD-Epi Cystatin (35±13) and the CKD-Creatinine-Cystatin (43±14). Compared to the mGFR, the CKD-Epi Cystatin equation appears to perform better with a bias of 4 ml/min/1.73m2 versus a bias of 24 ml/min/1.73m2 for the CKD-Epi equation and 12.7 ml/min/1.73m2 for the CKD-Epi Creatinine-Cystatin equation. Based on the Iohexol measure and the CKD-Epi Cystatin equation, all the patients (100%) had a GFR &amp;lt; 60 ml/min/1,73m2 against only 33% with the CKD-Epi equation. Conclusion In this analysis on the first 43 patients of our cohort, AKI seems to be associated with an increase of CKD 2 months after ICU discharge with 35% of patients with an eGFR below 60 ml/min/1,73m2. This proportion of CKD patients may be underestimated by the GFR estimation based on pCreat. Given the results of the analysis of our first 8 patients who have benefited from GFR measurement, Cystatin C-based equations may be an interesting tool to better assess renal function in this specific population.

P1679HYPOMAGNESAEMIA AND HYPERGLYCAEMIA AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims Hypomagnesaemia has been associated with increased insulin resistance and decreased insulin secretion. Recent data suggest that early post-engraftment hypomagnesaemia may play a role in development of post-transplant diabetes mellitus (PTDM). This single-centre study investigated the association between hypomagnesaemia 8 weeks post-engraftment and glucose metabolism changes 1 year after kidney transplantation. Method The study included 425 renal transplantation recipients, transplanted at Oslo University Hospital between March 2015 and May 2018. All included patients had functioning grafts with valid blood sampling and oral glucose tolerance tests 8 weeks and 1 year after transplantation. Patients with known pretransplant diabetes and those developing PTDM the first 8 weeks after transplantation were excluded. The association between plasma magnesium 8 weeks after transplantation and HbA1c, fasting plasma glucose and 2-hr glucose after 1 year was tested using both unadjusted and multiple linear regression, adjusted for: gender, age, body mass index (BMI), systolic blood pressure (SBP), tacrolimus (trough), measured glomerular filtration rate (mGFR; iohexol clearance) and plasma triglycerides. Results Patients had a median age of 54 (range 18-83) years, 65% were men and mean mGFR 1 year after transplantation was 56 (SD±14) ml/min/1.73m2. Median plasma magnesium was 0.72 (0.46-0.94) mmol/L 8 weeks after Tx and patients with hypomagnesaemia (Mg&amp;lt; 0.7 mmol/L) (n=169) were not different compared to patients with normal plasma magnesium (n=256) regarding age, gender, BMI, tacrolimus, mGFR, SBP or plasma triglycerides after 1 year. In unadjusted linear regression 1 mmol/L higher plasma magnesium at 8 weeks was associated with the following glycaemic endpoints 1 year after transplantation (β-coefficient, CI 95%, p-value); fasting glucose: HbA1c: +9 mmol/mol (1;16, P=0.02); +0.5 mmol/L (-0.7;1.7, P=0.39); 2-hour glucose: +0.74 mmol/L (-2.5;3.9, P=0.65). In multiple linear regression the following numbers were: Fasting glucose: HbA1c: +8 mmol/mol (0.3;16, P=0.042); +0.7 mmol/L (-0.5;2.0, P=0.26); 2-hour glucose: +2.8 mmol/L (-0.6;6.2, P=0.11). Conclusion In both unadjusted and multiple linear regression there was a positive correlation between 8-week plasma magnesium and HbA1c 1 year after transplantation. A similar trend was found for fasting and 2-hour glucose, although this was not statistically significant.

Evolution of renal function in patients with severe intestinal failure on home parenteral nutrition.

BackgroundKidney disease is a frequent but underestimated complication in patients suffering from intestinal failure (IF) treated by long-term home parenteral nutrition (HPN). The evolution in glomerular filtration rate (GFR) over time is poorly characterized. The current equations for estimating GFR have limited precision. No study has specifically investigated the reliability of recent creatinine-based estimated GFR (eGFR) equations in this population. The aim of this study was to evaluate the renal function decline under home parenteral nutrition (HPN) with a gold standard method and compare the performances of routinely used eGFR equations.MethodsForty patients with HPN and two or more GFR measurements were retrospectively studied. The renal function decline was calculated by the slope drawn between the successive measured GFRs (mGFRs). The performances of the Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, full age spectrum and revised Lund–Malmö equations were compared with reference methods (inulin or iohexol clearance).ResultsThe mean mGFR was 78 ± 28 mL/min/1.73 m2. The annual decline of mGFR was −1.9 mL/min/1.73 m2/year. No predisposing factor was identified to predict impairment in renal function. eGFR formulas grossly overestimated mGFR and had a low level of accuracy.ConclusionsPatients with IF are at significant risk for impaired renal function. In this population, the tested eGFR equations were inaccurate. However, monitoring kidney function with mGFR remains important in these patients, as their GFR regularly declines and no specific risk factor has yet been identified.

Measurement of glomerular filtration rate in lung transplant recipients highlights a dramatic loss of renal function after transplantation.

BackgroundChronic kidney disease (CKD) after lung transplantation (LT) is underestimated. The aim of the present study was to measure the loss of glomerular filtration rate (GFR) 1 year after LT and to identify the risk factors for developing Stage ≥3 CKD.MethodsLT patients in the University Hospital of Lyon had a pre- and post-transplantation measurement of their GFR (mGFR), and GFR was also estimated using the Chronic Kidney Disease Epidemiology Collaboration equation.ResultsDuring the study period, 111 patients were lung transplant candidates, of which 91 had a pre-transplantation mGFR, and 29 had a mGFR at 1 year after LT. Six patients underwent maintenance haemodialysis after transplantation. Mean mGFR was 106 mL/min/1.73 m2 before LT and 58 mL/min/1.73 m2 1 year after LT (P < 0.05) with a mean loss of 48 mL/min/1.73 m2 per patient. The risk of developing Stage ≥3 CKD after LT was higher in patients with lower pre-LT mGFR (odds ratio for each 1 mL/min/1.73 m2 increase: 0.94, 95% confidence interval 0.88–0.99). Receiver operator characteristics curves for the sensitivity and specificity of eGFR and mGFR for the prediction of CKD Stage ≥3 after LT found that pre-LT mGFR of 101 mL/min/1.73 m2 and pre-LT eGFR of 124 mL/min/1.73 m2 were the optimal thresholds for predicting Stage ≥3 CKD after LT.ConclusionThe present study underlines the value of mGFR in the pre-LT stage and found major renal function loss after LT, and consequently two-thirds of patients have Stage ≥3 CKD at 1 year. All patients with a pre-LT mGFR <90 mL/min/1.73 m2 warrant particular attention.

Estimation of GFR in Patients With Cystic Fibrosis: A Cross-Sectional Study.

Background:Patients with cystic fibrosis (CF) have frequent infectious complications requiring nephrotoxic medications, necessitating monitoring of renal function. Although adult studies have suggested that cystatin C (CysC)-based estimated glomerular filtration rate (eGFR) may be preferable due to reduced muscle mass of patients with CF, pediatric patients remain understudied.Objective:Our objective was to determine which eGFR formula is best for estimating glomerular filtration rate (GFR) in pediatric patients with CF.Methods:A total of 17 patients with CF treated with nephrotoxic antibiotics were recruited from the Children’s Hospital at London Health Sciences Centre, London, Ontario, Canada. 99Tc DTPA GFR (measured GFR [mGFR]) was measured with 4-point measurements starting at 120 minutes using a 2-compartmental model with Brøchner-Mortensen correction, with simultaneous measurement of creatinine, urea, and CysC. The eGFR was calculated using 16 known equations based on creatinine, urea, CysC, or combinations of these. Primary outcome measures were correlation with mGFR, and agreement within 10% for various eGFR equations.Results:Mean mGFR was 136 ± 21 mL/min/1.73 m2. Mean creatinine, CysC, and urea were 38 ± 10 μmol/L, 0.72 ± 0.08 mg/L, and 3.9 ± 1.4 mmol/L, respectively. The 2014 Grubb CysC eGFR had the best correlation coefficient (r = 0.75, P = .0004); however, only 35% were within 10%. The new Schwartz formula with creatinine and urea had the best agreement within 10%, but a relatively low correlation coefficient (r = 0.63, P = .0065, 64% within 10%).Conclusions:Our study suggests that none of the eGFR formulae work well in this small cohort of pediatric patients with CF with preserved body composition, possibly due to inflammation causing false elevations of CysC. Based on the small numbers, we cannot conclude which eGFR formula is best.

Estimated Glomerular Filtration Rate Bias in Participants with Severe Obesity Regardless of Deindexation.

Morbid obesity is associated with a higher independent risk of chronic kidney disease (CKD). Estimated glomerular filtration rate (eGFR) has been evaluated in a limited number of studyparticipants with severe obesity. A total of 706 measured GFR (mGFR) results from 598 participants with obesity (BMI ≥ 35 kg/m2 )were retrospectively collected. The performanceof the Modification of Diet in Renal Disease (MDRD)equation, Chronic Kidney Disease-Epidemiology (CKD-EPI)equation, and deindexed eGFR were compared with mGFRfrom thegold standard technique (inuline or iohexol), adjusted (mGFRr) or nonadjusted (mGFR) to body surface area. Absolute bias, precision, and accuracy were calculated. Mean mGFRr (58 ± 31 mL/min/1.73m2 ) was significantly different from CKD-EPI and MDRD (P < 0.001). Mean mGFR (nonindexed) (70 ± 40 mL/min) was significantly higher than mGFRr (P < 0.001). eGFR showed important biases and low accuracies for CKD-EPI and MDRD (10.7 ± 10.7 and 12.2 ± 13.7 mL/min/1.73m2 ; 78% vs. 75% respectively). Deindexation worsened bias and accuracy 30% (percentage of GFR estimates within 30% of mGFRr or mGFR) between eGFR and mGFR. eGFR overestimates mGFR and is associated with important biases and inaccuracies in patients with severe obesity, and deindexing eGFR worsens the overestimation. These findings may have important implications in examining kidney function inpatients with obesity.

Estimated glomerular filtration rate using a point of care measure of creatinine in patients with iohexol determinate GFR

IntroductionDetermination of creatinine and estimation of Glomerular Filtration Rate (GFR) rapidly before injection of contrast media provides early detection of high-risk patients for acute kidney failure. Hence, a rapid point-of-care (POC) device (result in 30 s) allowing creatinine measurement and eGFR could be of interest. To validate this method, we considered a population referred for measuring GFR. MethodsIohexol plasma clearance was used to measure GFR. For each subject, enzymatic creatinine was quantified with two different devices: in plasma with the Roche Cobas analyzer and in capillary blood with the Nova Biomedical POC device. Both values of creatinine were used in the CKD-EPI equation for estimated glomerular filtration rate (eGFR). eGFR using POC was compared to eGFR using Cobas and to mGFR by Passing Bablok regression, calculation of bias, precision and accuracy (or concordance) within 30%. Also, we calculated the rate of discrepant staging (eGFR >60 or ≤ 60 when mGFR is actually ≤60 and > 60) with both creatinine methods. Results120 subjects (52 ± 13 years, 49% of women) were included. Mean mGFR was 77 ± 27 mL/min/1.73m2 with 29 patients presenting mGFR <60 mL/min/1.73m2. Passing- Bablok regression comparing eGFR obtained with the POC and the Cobas was: eGFRPOC = −0.1 (95% CI: −7.4; 3.0) + 1.06 (95% CI: 1.00; 1.15) x eGFRCOBAS. Mean bias was 3.7 ± 14.1 mL/min/1.73m2. Concordance within 30% was 82%. Compared to mGFR, Passing-Bablok with POC was: eGFRPOC = −11.5 (95% CI: −22.9; −0.7) + 1.15 (95% CI: 1.02; 1.29) x mGFR. Mean bias was 0.1 ± 17.6 mL/min/1.73m2. Accuracy within 30% was 81%. Between eGFRCOBAS and mGFR, mean bias was −3.7 ± 12.5 mL/min/1.73m2. Accuracy within 30% was 95%. With POC (and Cobas), 3.3% (0.8%) of patients would have been considered with GFR > 60 mL/min/1.73m2 whereas mGFR it was ≤60 and 10% (9.2%) of them would have been considered with GFR ≤60 mL/min/1.73m2 when mGFR was >60. ConclusionCreatinine measured with the POC has an acceptable performance when used with the CKD-EPI equation to estimate GFR. Its ability to detect GFR <60 mL/min/1.73m2 is not significantly different from the classical Roche assay. StatSensor Creatinine (Nova Biomedical) can be used for GFR screening before contrast media injection.

Extracellular fluid volume is associated with incident end-stage kidney disease and mortality in patients with chronic kidney disease

Volume overload has been shown to be an independent risk factor for mortality in patients receiving chronic dialysis, but data in non-dialysis patients are scarce. Therefore we evaluated the prognostic value of extracellular fluid (ECF) volume for chronic kidney disease (CKD) progression and mortality in a prospective hospital-based cohort with CKD stage 1-4 (NephroTest Study). ECF (scaled to body surface area) and the measured glomerular filtration rate (mGFR) were determined using the distribution volume and clearance of 51Cr-EDTA, respectively. Cause-specific Cox and linear mixed-effect regression models were used to analyze the association of ECF with end-stage kidney disease (ESKD) and mortality, and with mGFR decline, respectively. The 1593 patients were mean age 58.8 years, 67% were men, mean mGFR of 43.6 mL/min/1.73m2 and mean ECF 15.1 L/1.73m2. After a median follow-up of 5.3 years, ESKD occurred in 324 patients and 185 patients died before ESKD. In multivariable analysis, ECF was significantly associated with the risk of ESKD (hazard ratio per 1L/1.73m2 increase: 1.14; 95% confidence interval [1.07; 1.21]) and with a faster GFR decline (adjusted mean difference in mGFR slope per 1L/1.73m2 increase -0.14 [-0.23; -0.05] mL/min/year). The relationship of ECF with mortality was non-linear and not significant (per 1L/1.73m2 increase 0.92, [0.73; 1.16]), below 15L/1.73m2, but significant (1.28; [1.14-1.45]) above 15L/1.73m2. Thus, in this large cohort of carefully phenotyped patients with CKD, ECF was an independent risk factor of CKD progression and mortality. Hence, close monitoring and treatment of fluid overload are important for the clinical management of patients with non-dialysis CKD.

Renal function after combined liver-kidney transplantation: A longitudinal study of pediatric and adult patients.

It has been proposed that the liver protects the kidney in CLKT. However, few studies have examined long-term renal function after CLKT and contrasted renal function of CLKT patients to KT patients beyond one year after transplantation. We studied long-term renal function of CLKT patients and compared renal function of CLKT patients to KT patients between one and five years after transplantation. Patients who underwent CLKT between 1993 and 2011 were included (n=34; 11 children and 23 adults). Ninety-six (27 children and 69 adults) KT patients were selected as controls. GFR was estimated (eGFR) and measured (mGFR) with 51 Cr-EDTA clearance. Mean mGFR was 63 at one and 70 at ten years after pediatric CLKT. Mean eGFR was 75 at one and 50 at ten years after adult CLKT. Difference in mean mGFR between pediatric CLKT and KT patients was 8 (95% CI -7 to 23) and 11 (95% CI -4 to 26) at one and five years after transplantation, respectively. Difference in mean eGFR between adult CLKT and KT patients was 8 (95% CI -5 to 20) and 1 (95% CI -10 to 12) at one and five years after transplantation, respectively. Longitudinal changes in GFRs were somewhat similar in CLKT and KT patients in both age-groups but pediatric CLKT patients had on average higher GFRs than pediatric KT patients. In long-term follow-up, renal function remains stable in pediatric CLKT patients but declines in adult CLKT patients.

Relation between invasive hemodynamics and measured glomerular filtration rate by 51Cr-EDTA clearance in advanced heart failure

The interaction between hemodynamics and kidney function in heart failure (HF) is incompletely understood. We investigated the association between invasive hemodynamic parameters and measured glomerular filtration rate (mGFR) by plasma clearance of 51-chromium-labeled ethylenediamine tetra-acetic acid (51Cr-EDTA) in patients with advanced HF and tested the hypothesis that patients with reduced mGFR have lower cardiac index (CI) and mean arterial pressure (MAP) as well as higher central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP). We retrospectively studied 242 patients (mean age 50 ± 13 years) referred for evaluation for heart transplantation or implantation of a left ventricular assist device with a left ventricular ejection fraction < 45% on optimal medical therapy, who underwent right heart catheterization (RHC) and measurement of 51Cr-EDTA clearance. Mean mGFR was 63 ± 21 mL/min/1.73 m2, CI was 2.3 ± 0.7 L/min/m2, PCWP was 21 ± 9 mmHg, and CVP was 10.3 ± 5.2 mmHg. Univariate analysis demonstrated a significant correlation between mGFR and CI (r2 = 0.030, p = .007) and CVP (r2 = 0.017, p = .049) but not between mGFR and MAP or PCWP. In multivariate analyses, none of the hemodynamic variables remained significantly associated with mGFR. While CVP and CI were correlated with mGFR in univariate analysis the results of analyses adjusted for multiple covariates suggest that hemodynamics are only correlated to renal function in advanced HF to a modest degree challenging the hypothesis that renal dysfunction in HF mainly is a consequence of renal congestion.