Iohexol Clearance Research Articles

The Impact of the Glomerular Filtration Rate on the Human Plasma Proteome.

The application of proteomics in chronic kidney disease (CKD) can potentially uncover biomarkers and pathways that are predictive of disease. Within this context, this study examines the relationship between the human plasma proteome and glomerular filtration rate (GFR) as measured by iohexol clearance in a cohort from Sweden (n = 389; GFR range: 8-100 mLmin-1 /1.73m2 ). A total of 2893 proteins are quantified using a modified aptamer assay. A large proportion of the proteome is associated with GFR, reinforcing the concept that CKD affects multiple physiological systems (individual protein-GFR correlations listed here). Of these, cystatin C shows the most significant correlation with GFR (rho = -0.85, p = 1.2 × 10-97 ), establishing strong validation for the use of this biomarker in CKD diagnostics. Among the other highly significant protein markers are insulin-like growth factor-binding protein 6, neuroblastoma suppressor of tumorigenicity 1, follistatin-related protein 3, trefoil factor 3, and beta-2 microglobulin. These proteins may indicate an imbalance in homeostasis across a variety of cellular processes, which may be underlying renal dysfunction. Overall, this study represents the most extensive characterization of the plasma proteome and its relation to GFR to date, and suggests the diagnostic and prognostic value of proteomics for CKD across all stages.

A Simple Method to Measure Renal Function in Swine by the Plasma Clearance of Iohexol.

There is no simple method to measure glomerular filtration rate (GFR) in swine, an established model for studying renal disease. We developed a protocol to measure GFR in conscious swine by using the plasma clearance of iohexol. We used two groups, test and validation, with eight animals each. Ten milliliters of iohexol (6.47 g) was injected into the marginal auricular vein and blood samples (3 mL) were collected from the orbital sinus at different points after injection. GFR was determined using two models: two-compartment (CL2: all samples) and one-compartment (CL1: the last six samples). In the test group, CL1 overestimated CL2 by ~30%: CL2 = 245 ± 93 and CL1 = 308 ± 123 mL/min. This error was corrected by a first-order polynomial quadratic equation to CL1, which was considered the simplified method: SM = −47.909 + (1.176xCL1) − (0.00063968xCL12). The SM showed narrow limits of agreement with CL2, a concordance correlation of 0.97, and a total deviation index of 14.73%. Similar results were obtained for the validation group. This protocol is reliable, reproducible, can be performed in conscious animals, uses a single dose of the marker, and requires a reduced number of samples, and avoids urine collection. Finally, it presents a significant improvement in animal welfare conditions and handling necessities in experimental trials.

Measured GFR in Routine Clinical Practice-The Promise of Dried Blood Spots.

Accurate determination of glomerular filtration rate (GFR) is crucial for the diagnosis of kidney disease. Estimated GFR (eGFR) calculated by serum creatinine and/or cystatin C is a mainstay in clinical practice and epidemiologic research but lacks precision and accuracy until GFR <60mL/min/1.73m2. Furthermore, eGFR may not precisely and accurately represent changes in GFR longitudinally. The lack of precision and accuracy is of concern in populations at high risk for kidney disease, as the dissociation between changes in eGFR and GFR may lead to missed diagnoses of early kidney disease. Therefore, improved methods to quantify GFR are needed. Whereas direct measures of GFR have been too cumbersome for screening and ambulatory care, a practical method of measuring GFR by iohexol clearance using dried capillary blood spots exists. In this review, we examine the current literature and data addressing GFR measurements by dried capillary blood spots and its potential application in high-risk groups.

Urinary Markers of Oxidative Stress Are Associated With Albuminuria But Not GFR Decline

IntroductionMarkers of oxidative stress increase with age and are prevalent with chronic kidney disease. However, the role of oxidative stress markers as predictors for kidney function decline in the general population is unclear.MethodsWe investigated whether a baseline urinary excretion of oxidative DNA damage (8-oxo-7,8-dihydro-2′-deoxyguanosine [8-oxodG]) and oxidative RNA damage (8-oxo-7,8-dihydroguanosine [8-oxoGuo]) was associated with the age-related glomerular filtration rate (GFR) decline or incident low-grade albuminuria during a median of 5.6 years of follow-up. In the Renal Iohexol Clearance Survey in the Sixth Tromsø Study, we measured GFR using iohexol clearance in 1591 participants without renal disease, diabetes, or cardiovascular disease. Low-grade albuminuria was defined as an albumin-creatinine ratio >1.13 mg/mmol.ResultsThe mean (SD) annual GFR change was −0.84 (2.00) ml/min per 1.73 m2 per year. In linear mixed models, urinary 8-oxodG and 8-oxoGuo levels were not associated with the GFR change rate. In a multivariable adjusted logistic regression model, a baseline urinary 8-oxoGuo in the highest quartile was associated with an increased risk of low-grade albuminuria at follow-up (odds ratio: 2.64; 95% confidence interval: 1.50–4.65). When the highest quartile of urinary 8-oxoGuo was added to the baseline model, the area under the receiver operating characteristics curve for predicting low-grade albuminuria at follow-up improved from 0.67 to 0.71 (P = 0.002).ConclusionOxidative stress measured as urinary 8-oxoGuo excretion was independently associated with incident low-grade albuminuria, but neither 8-oxoGuo nor 8-oxodG predicted an accelerated age-related GFR decline in a cohort representative of the middle-aged general population during almost 6 years of follow-up.

Contribution of symmetric dimethylarginine to GFR decline in pediatric chronic kidney disease

In pediatric chronic kidney disease (pCKD), traditional factors (proteinuria, etiology, and race) do not fully explain disease progression. The levels of methylated arginine derivatives (MADs: asymmetric and symmetric dimethylarginine, respectively) rise in CKD and increase with CKD progression. The impact of MADs on glomerular filtration rate (GFR) decline has not been examined in pCKD. The aim of this study was to examine the additive impact of baseline (BL) levels of MADs on directly measured GFR (mGFR) decline per year (ml/min/1.73 m2/year) for a period of up to 4 years. Plasma and data, including mGFR by plasma iohexol clearance, were provided by the prospective, observational Chronic Kidney Disease in Children study. BL MADs were analyzed by high-performance liquid chromatography-tandem mass spectrometry. For 352 pCKD subjects, the median [interquartile range] BL mGFR was 45 [35, 57] ml/min/1.73 m2. The levels of BL MADs were inversely related to the initial mGFR and its decline over time (p < 0.0005) but not to the rate of decline. Covariates, non-glomerulopathy and Tanner stage of ≥ 3 demonstrated weaker relationships between BL levels and beginning mGFR (p = 0.004 and p = 0.002, respectively). In pCKD, higher concentrations of BL MADs were inversely related to BL mGFR. MADs did not affect the CKD progression rate. Quantification of this relationship is novel to the pCKD literature.

Iohexol plasma clearance simplified by dried blood spot testing.

Renal function can be estimated with formulas, which are inaccurate, or measured with gold standard methods, which are reliable but unpractical. We propose to simplify the plasma clearance of iohexol, a gold standard method to measure renal function, by dried blood spot (DBS) testing. We compared glomerular filtration rate (GFR) values assessed by DBS and the reference plasma analysis technique. We tested in vitro the agreement between non-volumetric and volumetric DBS with the reference technique. Then, we performed a clinical validation in vivo between volumetric DBS and plasma analysis in 203 patients. The agreement was evaluated with the concordance correlation coefficient (CCC), the total deviation index (TDI) and the coverage probability. We defined acceptable agreement as a TDI <10%. In the in vitro studies, the non-volumetric DBS showed moderate agreement, TDI = 26.0%, while the volumetric method showed better but insufficient agreement, TDI = 13.0%, with the reference method in plasma. The non-volumetric DBS was rejected. To improve the agreement of the volumetric DBS, iopamidol was used as an internal standard. This method showed acceptable agreement, TDI = 9.0% with the analysis in plasma, and was selected as the definitive DBS method. In the in vivo studies, the agreement between the final DBS method and the reference technique was acceptable: TDI = 9.5%. This indicates that 90% of the GFR values ranged from -9.5% to + 9.5% compared with the reference method. We simplified the plasma clearance of iohexol using DBS without losing accuracy and precision with respect to the reference technique. This may facilitate the use of a reliable determination of renal function to the medical community.

Estimating Glomerular Filtration Rate in Kidney Transplant Recipients: Comparing a Novel Equation With Commonly Used Equations in this Population.

BackgroundAssessment of glomerular filtration rate (GFR) is important in kidney transplantation. The aim was to develop a kidney transplant specific equation for estimating GFR and evaluate against published equations commonly used for GFR estimation in these patients.MethodsAdult kidney recipients (n = 594) were included, and blood samples were collected 10 weeks posttransplant. GFR was measured by 51Cr-ethylenediaminetetraacetic acid clearance. Patients were randomized into a reference group (n = 297) to generate a new equation and a test group (n = 297) for comparing it with 7 alternative equations.ResultsTwo thirds of the test group were males. The median (2.5-97.5 percentile) age was 52 (23-75) years, cystatin C, 1.63 (1.00-3.04) mg/L; creatinine, 117 (63-220) μmol/L; and measured GFR, 51 (29-78) mL/min per 1.73 m2. We also performed external evaluation in 133 recipients without the use of trimethoprim, using iohexol clearance for measured GFR. The Modification of Diet in Renal Disease equation was the most accurate of the creatinine-equations. The new equation, estimated GFR (eGFR) = 991.15 × (1.120sex/([age0.097] × [cystatin C0.306] × [creatinine0.527]); where sex is denoted: 0, female; 1, male, demonstrating a better accuracy with a low bias as well as good precision compared with reference equations. Trimethoprim did not influence the performance of the new equation.ConclusionsThe new equation demonstrated superior accuracy, precision, and low bias. The Modification of Diet in Renal Disease equation was the most accurate of the creatinine-based equations.

Iohexol plasma clearance in children: validation of multiple formulas and single-point sampling times

BackgroundThe non-ionic agent iohexol is increasingly used as the marker of choice for glomerular filtration rate (GFR) measurement. Estimates of GFR in children have low accuracy and limiting the number of blood-draws in this patient population is especially relevant. We have performed a study to evaluate different formulas for calculating measured GFR based on plasma iohexol clearance with blood sampling at only one time point (GFR1p) and to determine the optimal sampling time point.MethodsNinety-six children with chronic kidney disease (CKD) stage 1–5 (median age 9.2 years; range 3 months to 17.5 years) were examined in a cross-sectional study using iohexol clearance and blood sampling at seven time points within 5 h (GFR7p) as the reference method. Median GFR7p was 66 (range 6–153) mL/min/1.73 m2. The performances of six different single time-point formulas (Fleming, Ham and Piepsz, Groth and Aasted, Stake, Jacobsson- and Jacobsson-modified) were validated against the reference. The two-point GFR (GFR2p) was calculated according to the Jødal and Brøchner–Mortensen formula.ResultsThe GFR1p calculated according to Fleming with sampling at 3 h (GFR1p3h-Fleming) had the best overall performance, with 82% of measures within 10% of the reference value (P10). In children with a GFR ≥ 30 mL/min/1.73 m2 (n = 78), the GFR1p3h-Fleming had a P10 of 92.3%, which is not significantly different (p = 0.29) from that of GFR2p (P10 = 96.2%). Considerable differences within and between the different formulas were found for different CKD stages and different time points for blood sampling.ConclusionsFor determination of mGFR in children with CKD and an assumed GFR of ≥ 30 mL/min/1.73 m2 we recommend GFR1p3h-Fleming as the preferred single-point method as an alternative to GFR2p. For children with a GFR < 30 mL/min/1.73 m2, we recommend the slope-GFR with at least two blood samples.Clinical Trial Registration: ClinicalTrials.gov, Identifier NCT01092260, https://clinicaltrials.gov/ct2/show/NCT01092260?term=tondel&rank=2

Renal Function Influences Diagnostic Markers in Serum and Urine: A Study of Guanidinoacetate, Creatine, Human Epididymis Protein 4, and Neutrophil Gelatinase-Associated Lipocalin in Children.

Impaired renal function may affect the level of diagnostic disease markers. The aim of the study was to investigate the effect of measured glomerular filtration rate (GFR) on 4 diagnostic markers in blood and urine-guanidinoacetate (GAA), creatine (CRE), human epididymis protein 4 (HE4), and neutrophil gelatinase-associated lipocalin (NGAL)-and how this could affect the decision and reference limits. We examined 96 children (median age 9.2 years, range 0.25-17.5) with different stages of chronic kidney disease (CKD). GFR [median 65.9 mL · min-1 · (1.73 m2)-1, range 6.3-153] was measured by iohexol clearance using 7 venous blood samples after iohexol injection. Fasting serum and urinary GAA, CRE, HE4, NGAL, and creatinine (crn) were analyzed. After appropriate transformation of the markers, a multiple linear regression analysis examined the influence of age, sex, and measured GFR. The level of GFR significantly affected S-GAA (P = 2 × 10-4) and U-GAA/crn (P = 5 ×10-11), leading to decreased values in renal impairment. GFR did not correlate significantly with the level of CRE and to a minor degree did the U-CRE/crn ratio (P = 0.54 and 0.01, respectively). The level of GFR significantly affected S-HE4 (P = 4 × 10-31) and U-HE4/S-HE4 ratio (P = 2 × 10-21) with increased serum values and decreased U-HE4/S-HE4 ratio in renal impairment. S-NGAL increased with decreasing kidney function (P = 2 × 10-19). Diagnostic disease markers may be influenced by the renal function, and this must be taken into account when interpreting test results. Decreased renal function could change the level of the marker above or below decision limits, leading to diagnostic misinterpretation. ClinicalTrials.gov, Identifier NCT01092260, https://clinicaltrials.gov/ct2/show/NCT01092260?term=tondel&rank=2.

Skeletal impairment in Pierson syndrome: Is there a role for lamininβ2 in bone physiology?

IntroductionPierson syndrome is caused by a mutation of LAMB2, encoding for laminin β2. Clinical phenotype is variable but usually associates congenital nephrotic syndrome (CNS) and ocular abnormalities. Neuromuscular impairment has also been described. MethodsWe report on a 15-year old girl, suffering from Pierson Syndrome, who developed severe bone deformations during puberty.This patient initially displayed CNS and microcoria, leading to the clinical diagnosis of Pierson syndrome. Genetic analysis revealed a truncating mutation and a splice site mutation of LAMB2. The patient received a renal transplantation (R-Tx) at the age of 3. After R-Tx, renal evolution was simple, the patient receiving low-dose corticosteroids, tacrolimus and mycophenolate mofetil. At the age of 12, bone deformations progressively appeared. At the time of bone impairment, renal function was subnormal (glomerular filtration rate using iohexol clearance 50mL/min per 1.73m2), and parameters of calcium/phosphate metabolism were normal (calcium 2.45mmol/L, phosphorus 1.30mmol/L, PTH 81ng/L, ALP 334U/L, 25OH-D 73nmol/L). Radiographs showed major deformations such as scoliosis, genu varum and diffuse epiphyseal abnormalities. A high resolution scanner (HR-pQCT) was performed, demonstrating a bone of “normal low” quantity and quality; major radial and cubital deformations were observed. Stainings of laminin β2 were performed on bone and renal samples from the patient and healthy controls: as expected, laminin β2 was expressed in the control kidney but not in the patient's renal tissue, and a similar pattern was observed in bone. ConclusionThis is the first case of skeletal impairment ever described in Pierson syndrome. Integrin α3β1, receptor for laminin β2, are found in podocytes and osteoblasts, and the observation of both the presence of laminin β2 staining in healthy bone and its absence in the patient's bone raises the question of a potential role of laminin β2 in bone physiology.

GFR estimation based on standardized creatinine and cystatin C: a European multicenter analysis in older adults.

Although recommended by the Kidney Disease Improving Global Outcomes, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICR) creatinine equation was not targeted to estimate glomerular filtration rate (eGFR) among older adults. The Berlin Initiative Study (BIS1CR) equation was specifically developed in older adults, and the Lund-Malmö revised (LMRCR) and the Full Age Spectrum (FASCR) equations have shown promising results in older adults. Our aim was to validate these four creatinine equations, including addition of cystatin C in a large multicenter cohort of Europeans ≥70 years. A total of 3226 individuals (2638 with cystatin C) underwent GFR measurement (mGFR; median, 44 mL/min/1.73 m2) using plasma iohexol clearance. Bias, precision (interquartile range [IQR]), accuracy (percent of estimates ±30% of mGFR, P30), eGFR accuracy diagrams and probability diagrams to classify mGFR<45 mL/min/1.73 m2 were compared. The overall results of BIS1CR/CKD-EPICR/FASCR/LMRCR were as follows: median bias, 1.7/3.6/0.6/-0.7 mL/min/1.73 m2; IQR, 11.6/12.3/11.1/10.5 mL/min/1.73 m2; and P30, 77.5%/76.4%/80.9%/83.5% (significantly higher for LMR, p<0.001). Substandard P30 (<75%) was noted for all equations at mGFR<30 mL/min/1.73 m2, and at body mass index values <20 and ≥35 kg/m2. LMRCR had the most stable performance across mGFR subgroups. Only LMRCR and FASCR had a relatively constant small bias across eGFR levels. Probability diagrams exhibited wide eGFR intervals for all equations where mGFR<45 could not be confidently ruled in or out. Adding cystatin C improved P30 accuracy to 85.7/86.8/85.7/88.7 for BIS2CR+CYS/CKD-EPICR+CYS/FASCR+CYS/MEANLMR+CAPA. LMRCR and FASCR seem to be attractive alternatives to CKD-EPICR in estimating GFR by creatinine-based equations in older Europeans. Addition of cystatin C leads to important improvement in estimation performance.

Beta Trace Protein does not outperform Creatinine and Cystatin C in estimating Glomerular Filtration Rate in Older Adults

Despite intense research the optimal endogenous biomarker for glomerular filtration rate (GFR) estimation has not been identified yet. We analyzed if ß-trace protein (BTP) improved GFR estimation in elderly. 566 participants aged 70+ from the population-based Berlin Initiative Study were included in a cross-sectional validation study. BTP, standardized creatinine and cystatin C were measured in participants with iohexol clearance measurement as gold standard method for measured GFR (mGFR). In a double logarithmic linear model prediction of mGFR by BTP was assessed. Analyses with BTP only and combined with creatinine and cystatin C were performed. Additionally, performance of GFR estimating equations was compared to mGFR. We found that the combination of all three biomarkers showed the best prediction of mGFR (r2 = 0.83), whereat the combination of creatinine and cystatin C provided only minimally diverging results (r2 = 0.82). Single usage of BTP showed worst prediction (r2 = 0.67) within models with only one biomarker. Subgroup analyses (arterial hypertension, diabetes, body mass index ≤23 and >30) demonstrated a slight additional benefit of including BTP into the prediction model for diabetic, hypertensive and lean patients. Among BTP-containing GFR equations the Inker BTP-based equation showed superior performance. Especially the use of cystatin C renders the addition of BTP unnecessary.

Losartan therapy decreases albuminuria with stable glomerular filtration and permselectivity in sickle cell anemia

Sickle cell nephropathy begins with hyperfiltration and microalbuminuria and may progress to renal failure. The aim of this study was to determine the effects of losartan on glomerular function and albumin excretion in sickle cell anemia (SCA). Individuals with SCA on hydroxyurea with persistent albuminuria were enrolled in a 1-year study of losartan. Glomerular filtration rate (GFR) measured by iohexol clearance, albumin excretion rate (AER), and fractional clearance of dextran were assessed at baseline, short-term (1–2month), and long-term (≥12month) intervals. Twelve subjects (6 microalbuminuria, 6 macroalbuminuria) completed short-term studies; 8 completed long-term studies. Baseline GFR was 112ml/min/1.73m2 (71–147ml/min/1.73m2). AER decreased significantly at the short-term (median decrease –134 mcg/min, p=0.0063). GFR was not significantly-different at short-term or long-term intervals. Dextran clearance improved for diameters smaller than albumin (<36Å) but not larger sizes. Losartan therapy for ≥1year in sickle nephropathy results in lower albumin excretion with stable GFR. Filtration of neutral molecules ≥36Å was not changed by losartan, suggesting that the effect of losartan is a mechanism other than alteration of glomerular filtration size-selectivity.

Reduced renal function in patients with Myotonic Dystrophy type 1 and the association to CTG expansion and other potential risk factors for chronic kidney disease

Myotonic dystrophy type 1 (DM1) affects several organs. Disease severity and age at onset are correlated to the CTG repeat expansion. The aim of this study was to assess renal function and the association to numbers of CTG repeat expansion in patients with DM1. Ninety-eight patients with DM1 were included. Glomerular filtration rate (measured GFR) was measured using iohexol clearance. Data on CTG repeats were available in 83/98 (85%) patients. The overall mGFR was 74 (16) ml/min/1.73 m2 (range 38–134). Sixty-four patients (69%) had a mild and sixteen patients (17%) a moderate decrease in renal function (mGFR 60–89 and 30–59 ml/min/1.73 m2, respectively). No correlations were found between CTG repeats and mGFR (r = 0.10, p = 0.4) or between CTG repeats and serum cystatin C (r = 0.12, p = 0.29). CTG repeats was positively correlated to creatinine-based estimates of GFR (eGFR) (modified diet in renal disease r = 0.49, p < 0.001, CKD-EPI creatinine equation; r = 0.50, p < 0.001), but analyses using Structural Equation Modeling showed no correlation. The correlation was explained by an indirect effect via serum creatinine and skeletal muscle mass index. In conclusion, patients with DM1 seem to have a slight decrease in renal function but there is no association between renal function and the number of CTG repeats, a marker of disease severity.

Decline in measured glomerular filtration rate is associated with a decrease in endurance, strength, balance and fine motor skills.

Physical performance in chronic kidney disease affects morbidity and mortality. The aim was to find out which measures of physical performance are important in chronic kidney disease (CKD) and if there are associations with declining measured glomerular filtration rate (GFR). Endurance was assessed by 6 min walk test (6-MWT) and stair climbing, muscular endurance by 30 s sit to stand, heel rises and toe lifts, strength by quadriceps- and handgrip-strength, balance by functional reach and Berg's balance scale, and fine motor skills by Moberg's picking-up test. GFR was measured by Iohexol clearance. The study comprised 101 patients with CKD 3b-5 not started dialysis, 40 women and 61 men, with a mean age of 67 ± 13 (range: 22 - 87) years. All measures of physical performance were impaired. A decrease in GFR of 10 mL/min per 1.73 m2 corresponded to a 35 metre shorter walking distance in the 6-MWT. Multivariable linear regression analysis showed significant relationships between decline in GFR and the 6-MWT (P = 0.04), isometric quadriceps strength left (P = 0.04), balance measured as functional reach (P = 0.02) and fine motor skills in the left hand as measured by Moberg's picking-up test (P = 0.01), respectively, after sex, age, comorbidity and the interaction between sex and age had been taken into account. Endurance, muscular endurance, strength, balance and fine motor skills were impaired in patients with CKD 3b-5. Walking capacity, isometric quadriceps strength, balance, and fine motor skills were associated with declining GFR. The left extremities were more susceptible to GFR, ageing and comorbidities and seem thus to be more sensitive.

Workflow sensitivity of post-processing methods in renal DCE-MRI

Objective: Estimation of renal filtration using dynamic contrast-enhanced imaging (DCE-MRI) requires a series of analysis steps. The possible number of distinct post-processing chains is large and grows rapidly with increasing number of processing steps or options. In this study we introduce a framework for systematic evaluation of the post-processing chains. The framework is later used to highlight the workflow processing chain sensitivity towards accuracy in estimation of glomerular filtration rate (GFR).Methods: Twenty healthy volunteers underwent DCE-MRI examinations as well as iohexol clearance for reference GFR measurements. In total, 692 different combinations of post-processing steps were explored for analysis, including options for kidney segmentation, B1 inhomogeneity correction, placement of arterial input function, gadolinium concentration estimation as well as handling of motion-corrupted volumes and breathing motion. The evaluation of various processing chains is presented using a classification tree framework and random forest ensemble learning.Results: Among the processing steps subject to testing, methods for calculating the gadolinium concentration as well as B1 inhomogeneity correction had the largest impact on accuracy of GFR estimations. Different segmentation methods did not play an important role in the post-processing of the MR data except from one processing chain where the automated segmentation outperformed the manual segmentation.Conclusion: The proposed classification trees were efficiently used as a statistical tool for visualization and communication of results to distinguish between important and less influential processing steps in renal DCE-MRI. We also identified several crucial factors in the processing chain.

Estimating glomerular filtration rate (GFR) in children. The average between a cystatin C- and a creatinine-based equation improves estimation of GFR in both children and adults and enables diagnosing Shrunken Pore Syndrome

Estimating glomerular filtration rate (GFR) in adults by using the average of values obtained by a cystatin C- (eGFRcystatin C) and a creatinine-based (eGFRcreatinine) equation shows at least the same diagnostic performance as GFR estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparison of eGFRcystatin C and eGFRcreatinine plays a pivotal role in the diagnosis of Shrunken Pore Syndrome, where low eGFRcystatin C compared to eGFRcreatinine has been associated with higher mortality in adults. The present study was undertaken to elucidate if this concept can also be applied in children. Using iohexol and inulin clearance as gold standard in 702 children, we studied the diagnostic performance of 10 creatinine-based, 5 cystatin C-based and 3 combined cystatin C-creatinine eGFR equations and compared them to the result of the average of 9 pairs of a eGFRcystatin C and a eGFRcreatinine estimate. While creatinine-based GFR estimations are unsuitable in children unless calibrated in a pediatric or mixed pediatric-adult population, cystatin C-based estimations in general performed well in children. The average of a suitable creatinine-based and a cystatin C-based equation generally displayed a better diagnostic performance than estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparing eGFRcystatin and eGFRcreatinine may help identify pediatric patients with Shrunken Pore Syndrome.

CKD-EPI equation: A suitable Glomerular Filtration Rate estimate for drug dosing in HIV-infected patients

ObjectivesTo evaluate concordance between glomerular filtration rate (GFR) estimates (Cockcroft and Gault, modification of diet in renal diseases, chronic kidney disease epidemiology study group equations) for drug dosing in HIV-infected patients. Patients and methodsWe performed a monocentric study. GFR was measured using the gold standard method (plasma clearance of iohexol) in 230 HIV-infected patients. Concordance rate was evaluated between measured GFR (mGFR) and estimated GFR (eGFR) for different GFR categories (GFR>90 mL/min, GFR<90 mL/min, GFR>70 mL/min, and GFR<70 mL/min). MDRD and CKD-EPI were used with and without indexation to body surface area (BSA). ResultsMean age was 48±10 years, mean mGFR was 101±26 mL/min. Concordance between mGFR and eGFR estimated with CG, CKD-EPI (indexed and not indexed to BSA), or MDRD equations (not indexed to BSA) was similar (73%, 73%, 74%, and 73% respectively) for a breakpoint value of 90 mL/min for GFR. At this value, the concordance rate between mGFR and MDRD indexed to BSA was significantly lower (65%, P<0.05). Using 70 mL/min of GFR as the breakpoint value, all equations had similar concordance rates with mGFR (with or without indexation to BSA). ConclusionCKD-EPI equation has the same concordance with GFR and with CG when used for drug dosing.

Combining Cystatin C and Creatinine Yields a Reliable Glomerular Filtration Rate Estimation in Older Adults in Contrast to β-Trace Protein and β2-Microglobulin

Background: The glomerular filtration rate (GFR) is the most important measure of kidney function and chronic kidney disease (CKD). This study aims to validate commonly used equations for estimated GFR (eGFR) based on creatinine (cr), cystatin C (cys), β-trace protein (BTP), and β2-microglobulin (B2M) in older adults. Method: We conducted a validation study with 126 participants aged between 72 and 98 with a mean measured GFR (mGFR) by iohexol clearance of 54 mL/min/1.73 m². The eGFR equations (CKD-Epidemiology collaboration [CKD-EPI], Berlin Initiative Study [BIS], Full Age Spectrum [FAS], Modification of Diet in Renal Disease [MDRD]_cr, Caucasian-Asian-Pediatric-Adult [CAPA]_cys, Lund-Malmö Revised [LM-REV]_cr, and MEAN-LM-CAPA_cr-cys), were assessed in terms of bias (median difference: eGFR-mGFR), precision (interquartile range of the differences), and accuracy (P30: percentage of estimates ±30% of mGFR). The equations were compared to a benchmark equation: CKD-EPI_cr-cys. Results: All cystatin C-based equations underestimated the GFR compared to mGFR, whereas bias was mixed for the equations based only on creatinine. Accuracy was the highest for CKD-EPI_cr-cys (98%) and lowest for MDRD (82%). Below mGFR 45 mL/min/1.73 m² only equations incorporating cystatin C reached P30 accuracy >90%. CKD-EPI_cr-cys was not significantly more accurate than the other cystatin C-based equations. In contrast, CKD-EPI_cr-cys was significantly more accurate than all creatinine-based equations except LM-REV_cr. Conclusion: This study confirms that it is reasonable to use equations incorporating cystatin C and creatinine in older patients across a wide spectrum of GFR. However, the results call into question the use of creatinine alone below mGFR 45 mL/min/1.73 m². B2M and BTP do not demonstrate additional value in eGFR determination in older adults.

MP22-08 ESTIMATED GLOMERULAR FILTRATION RATE: DO WE MEASURE THE REAL RENAL FUNCTION OR ARE WE STILL GROPING IN THE DARK?

MP22-08 ESTIMATED GLOMERULAR FILTRATION RATE: DO WE MEASURE THE REAL RENAL FUNCTION OR ARE WE STILL GROPING IN THE DARK?