Comparison of the new and traditional CKD-EPI GFR estimation equations with urinary inulin clearance: A study of equation performance.

BACKGROUND: Diagnosis, prognostication and treatment in chronic kidney disease is often informed by an estimate of the glomerular filtration rate (GFR). Commonly used GFR estimation (eGFR) equations are based on serum creatinine (Cr) concentrations and display suboptimal precision and accuracy. Newer equations incorporating additional endogenous markers such as ß-Trace Protein (BTP), ß2-Microglobulin (B2M) and cystatin C (cysC) have been developed but require validation. METHODS: This prospective cohort study evaluated the performance of 6 eGFR equations developed by the chronic kidney disease - epidemiology collaboration group (CKD-EPI) against urinary inulin clearance GFR in patients recruited from outpatient nephrology clinics. RESULTS: Mean biases were negligible and similar between equations. The eGFR-EPI Cr/cysC had the best precision and accuracy of all the equations and the best agreement with inulin mGFR when classifying participants into GFR categories. The BTP and B2M equations displayed the worst precisions and accuracies and showed the least consistent performance across levels of GFR. Thus, the eGFR-EPI Cr/cysC is the least biased, most precise and has the highest accuracy as compared to other eGFR-EPI equations. CONCLUSIONS: The BTP and B2M equations are the worst performing of the eGFR-EPI equations, and no benefit is observed with the addition of BTP or B2M to Cr/cysC.

Combining GFR estimates from cystatin C and creatinine-what is the optimal mix?

BACKGROUND: Combining estimated glomerular filtration rate (eGFR) equations based on creatinine and cystatin C has been shown to improve the accuracy of GFR estimation. This study aims to optimize this strategy for height-independent GFR estimation in children. METHODS: Retrospective study of 408 inulin clearance tests with simultaneous International Federation of Clinical Chemistry-calibrated measurements of creatinine, cystatin C, and urea in children (mean age 12.5 years, GFR 91.2 ml/min/1.73m2) comparing the arithmetic (meanarith) and geometric means (meangeom) of a height-independent creatinine-based (full age spectrum, based on age (FASage)) and a cystatin C-based equation (FAScys), with the complex height-dependent CKiD3 equation incorporating gender, height, cystatin C, creatinine, and urea. RESULTS: Meangeom had a P30 accuracy of 89.2% compared to meanarith 87.7% (p = 0.030) as well as lower bias and %precision error and performed almost as well as CKiD3 (P30 accuracy 90.9%). Modifying the weight of FASage and FAScys when calculating the means showed that an equal contribution was most accurate in most patients. In spina bifida patients, FAScys alone outperformed any combination. Malignancy or nephritis patients had slightly higher accuracy with weighted means favoring cystatin C or creatinine, respectively. Disagreement between FAScys and FASage was inversely correlated with the accuracy of meangeom. When disagreement exceeded 40%, application of weighted means based on diagnosis improved the performance of eGFR. CONCLUSIONS: In the absence of height data, the optimal strategy for estimating GFR in children is by using the geometric mean of FASage and FAScys. When there is large disagreement between the two, weighted means based on diagnosis improve accuracy.

Alteration of renal excretion pathways in gentamicin-induced renal injury in rats.

The kidney plays a major part in the elimination of many drugs and their metabolites, and drug-induced kidney injury commonly alters either glomerular filtration or tubular transport, or both. However, the renal excretion pathway of drugs has not been fully elucidated at different stages of renal injury. This study aimed to evaluate the alteration of renal excretion pathways in gentamicin (GEN)-induced renal injury in rats. Results showed that serum cystatin C, creatinine and urea nitrogen levels were greatly increased by the exposure of GEN (100 mg kg-1 ), and creatinine concentration was increased by 39.7% by GEN (50 mg kg-1 ). GEN dose-dependently upregulated the protein expression of rOCT1, downregulated rOCT2 and rOAT1, but not affected rOAT2. Efflux transporters, rMRP2, rMRP4 and rBCRP expressions were significantly increased by GEN(100), and the rMATE1 level was markedly increased by GEN(50) but decreased by GEN(100). GEN(50) did not alter the urinary excretion of inulin, but increased metformin and furosemide excretion. However, GEN(100) resulted in a significant decrease of the urinary excretion of inulin, metformin and p-aminohippurate. In addition, urinary metformin excretions in vivo were significantly decreased by GEN(100), but slightly increased by GEN(50). These results suggested that GEN(50) resulted in the induction of rOCTs-rMATE1 and rOAT3-rMRPs pathway, but not changed the glomerular filtration rate, and GEN(100)-induced acute kidney injury caused the downregulated function of glomerular filtration -rOCTs-rMATE1 and -rOAT1-rMRPs pathway.

Existing creatinine-based equations overestimate glomerular filtration rate in Indians.

BACKGROUND: Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians. METHODS: GFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe's and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations. RESULTS: A total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m2. All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPICys was not significantly different from mGFR (p = 0.38). The CKD-EPICys exhibited lowest bias [mean bias: -3.53 ± 14.70 ml/min/1.73m2 (95% CI: -0.608 to -0.98)] and highest accuracy (P30: 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90-134.50) ml/min/1.73m2. CONCLUSION: Existing creatinine-based GFR estimating equations overestimate GFR in Indians. An appropriately powered study is needed to develop either a correction factor or a new equation for accurate assessment of kidney function in the Indian population.

Clinical benefits of using inulin clearance and cystatin C for determining glomerular filtration rate in HIV-1-infected individuals treated with dolutegravir.

INTRODUCTION: Dolutegravir may inhibit creatinine transporters in renal tubules and elevate serum creatinine levels. We investigated the usefulness of glomerular filtration rate (GFR) measured using inulin clearance (Cin), creatinine clearance (Ccr), and estimated GFR based on both serum creatinine (eGFRcre) and serum cystatin C (eGFRcys). PATIENTS & METHODS: HIV-1-infected Japanese patients with suppressed viremia and whose antiretroviral drug was switched to dolutegravir from other drugs were included (n = 108, Study 1). We compared eGFRcre and eGFRcys at the start and after 48 weeks of dolutegravir administration. For the patients providing consent, we measured Cin and Ccr (n = 15, Study 2). We assessed biases and accuracy and compared Cin with eGFRcre, eGFRcys, and Ccr. RESULTS: There were no differences in serum cystatin C and eGFRcys between baseline and at 48 weeks. Moreover, eGFRcre was significantly less accurate (within 30% of measured GFR) than both eGFRcys and Ccr (40% accuracy compared to 93% and 93%, respectively). eGFRcys was significantly less biased than eGFRcre and Ccr (p < 0.0001, p = 0.00036, respectively). No significant difference between Cin and eGFRcys was observed. eGFRcys was significantly correlated with Cin (γ = 0.85, p < 0.0001). CONCLUSIONS: eGFRcys provided the most precise estimate and most closely approximate Cin in HIV-1-infected Japanese patients with suppressed viremia treated with dolutegravir. We demonstrated clinical benefits of inulin clearance and eGFRcys. This is the first study performing inulin clearance for HIV-1-infected individuals and to show data for eGFRcys from a large cohort following a switch to dolutegravir from other antiretroviral agents.

How to evaluate renal function in stable cirrhotic patients.

Chronic kidney disease (CKD) is a disorder frequently suffered by cirrhotic patients, and therefore it is crucial to perform an accurate renal assessment in this population. This assessment should be based on the integral evaluation of the clinical exam, glomerular filtration rate (GFR), serum electrolytes, hemoglobin, and parathyroid hormone values, as well as urinalyses and renal imaging. GFR assessment can be performed by different methods, such as serum creatinine, serum cystatin C, GFR equations (based on creatinine, cystatin C or both), endogenous and exogenous markers clearance, and renal functional imaging. All these evaluating methods have their particular characteristics, advantages and disadvantages. Even though Cr-51 EDTA clearance seems to be the best gold standard method, creatinine-based equation (RFH cirrhosis) and cystatin C based-equations (CKD-EPI and Stevens) seem to be the most inexpensive and accurate equations, respectively, for evaluating GFR in this population. In conclusion, renal assessment in cirrhotic patients is a complex task that should not be based on a single renal functional marker.

Measuring and estimating glomerular filtration rate in children.

Glomerular filtration rate (GFR) is the best index for kidney function in health and disease. Knowledge of the GFR is essential for the detection (diagnosis) and monitoring of renal function during disease progression and for ensuring correct medication doses. Inulin clearance (plasma or urine) is currently considered to be the gold standard for measuring GFR, but in clinical practice the measurement of other exogenous filtration markers from the plasma often replaces that of inulin clearance. Different protocols can be used to determine the area under the plasma disappearance curve, and an understanding of these methods is important. GFR can also be estimated by GFR equations (eGFR), which are most often used in clinical practice because they only require a knowledge of the serum creatinine or cystatin C level and demographic information. eGFR equations are easy to use but they do have their limitations, and it is important to know how these equations were derived and in which circumstances they can be used most accurately. The aim of this review is to explain how GFR can be measured using the renal clearance and the plasma clearance method and which eGFR equations can be applied to children, as well as how and when these equations can be used in clinical practice.

Effects of Bariatric Surgery on Renal Function in Obese Patients: A Systematic Review and Meta Analysis.

BACKGROUND: Obesity is an independent risk factor of development and progression of chronic kidney disease (CKD). Data on the benefits of bariatric surgery in obese patients with impaired kidney function have been conflicting. OBJECTIVE: To explore whether there is improvement in glomerular filtration rate (GFR), proteinuria or albuminuria after bariatric surgery. METHODS: We comprehensively searched the databases of MEDLINE, Embase, web of science and Cochrane for randomized, controlled trials and observational studies that examined bariatric surgery in obese subjects with impaired kidney function. Outcomes included the pre- and post-bariatric surgery GFR, proteinuria and albuminuria. In obese patients with hyperfiltration, we draw conclusions from studies using measured GFR (inulin or iothalamate clearance) unadjusted for BSA only. Study quality was evaluated using the Newcastle-Ottawa Scale. RESULTS: 32 observational studies met our inclusion criteria, and 30 studies were included in the meta-analysis. No matter in dichotomous data or in dichotomous data, there were statistically significant reduction in hyperfiltration, albuminuria and proteinuria after bariatric surgery. LIMITATIONS: The main limitation of this meta-analysis is the lack of randomized controlled trials (RCTs). Another limitation is the lack of long-term follow-up. CONCLUSIONS: Bariatric surgery could prevent further decline in renal function by reducing proteinuria, albuminuria and improving glomerular hyperfiltration in obese patients with impaired renal function. However, whether bariatric surgery reverses CKD or delays ESRD progression is still in question, large, randomized prospective studies with a longer follow-up are needed.

The relationship between estimated GFR based on the CKD-EPI formula and renal inulin clearance in potential kidney donors.

It is not yet clear whether or not renal function in the living donor can be sufficiently assessed by estimated glomerular filtration rate (GFR) using creatinine-based equations. The present paper investigates the relationship between GFR values determined using renal inulin clearance (Cin) and those estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Our study was performed in 287 potential kidney donors with a mean age of 48 ± 10 years. Mean Cin was 1.47 ± 0.28 (1.10 - 2.50) mL/s/1.73 m2. Total bias when using the CKDEPI formula was -0.0183 mL/s/1.73 m2, precision 0.263 mL/s/1.73 m2, and accuracy 90.6% within ± 30% of Cin. The sensitivity of CKD-EPI to estimate a decrease in Cin below 1.33 mL/s/1.73 m2 was 50.5%, with an 85% specificity of detecting a value above the cutoff. Receiver-operating curve analysis for the above produced an area under the curve of 0.766 ± 0.0285 (CI 0.712 - 0.813). For donor screening purposes, CKD-EPI should be interpreted with great caution.

Prospective study of methods of renal function evaluation in patients with neurogenic bladder dysfunction.

OBJECTIVE: To evaluate the precision of methods used to assess renal function in patients with neurogenic voiding dysfunction. MATERIALS AND METHODS: This multicenter prospective study, which was set in Toulouse and Lyon, France, included 60 patients (mean age, 48.9 ± 15.2 years) with neurogenic bladder and sphincter dysfunction. The correlation and the concordance with the inulin clearance of each method of renal function evaluation were assessed. RESULTS: The correlation of serum creatinine with inulin clearance was low when using serum creatinine-based equations such as the Modification of Diet in Renal Disease (simplified and complete) and Cockcroft-Gault equations. The r and r(2) coefficients were higher for creatinine-based methods, such as 24-hour (r = 0.72) and 3-hour creatinine clearance (r = 0.78). The strongest correlation was found for serum cystatin C-based equations: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine/cystatin C combined equation (r = 0.78) and the CKD-EPI cystatin C equation (r = 0.80). Mean bias of serum creatinine-based equations estimating glomerular filtration rate, the Cockcroft-Gault, and the simplified and complete Modification of Diet in Renal Disease equations, was 27.5 ± 28.6, 17.48 ± 29.40, and 21.98 ± 30.40 mL/min, respectively. Mean bias of creatinine clearance was 19.89 ± 15.30 mL/min at 3 hours and 19.00 ± 31.08 mL/min at 24 hours. Mean bias of the CKD-EPI cystatin C and the CKD-EPI creatinine/cystatin C combined equations was 11.98 ± 17.68 mL/min and 18.62 ± 17.85 mL/min, respectively. Limitations are the numerous types of neurologic diseases. CONCLUSION: The CKD-EPI equation using cystatin C was the most precise method of renal function evaluation in patients with neurogenic bladder.

[Relationship between glomerular filtration rate, uric acid, and parathyroid hormone in children]. / Relation entre débit de filtration glomérulaire, parathormone et acide urique chez l'enfant.

INTRODUCTION: Parathyroid hormone (PTH) and uric acid (UA) levels increase early during chronic kidney disease (CKD). The objective of this study was to evaluate the relationship between these two parameters at different stages of pediatric CKD. PATIENTS AND METHODS: One hundred patients (range, 5-18 years) were included in this retrospective study: they had undergone renal exploration with a direct measurement of the glomerular filtration rate (GFR) using the reference standard (i.e., inulin clearance, Cin) and presented with increased circulating levels of PTH and/or UA. RESULTS: GFR was normal in 39% of patients, with UA increased in 44% and PTH in 75% of them. Interestingly, 29% of the children with increased PTH levels had a strictly normal GFR (i.e., above 90 mL/min/1.73 m(2)). An inverse association was found between UA and GFR (r=-0.452, P ≤ 0.0001) as well as between PTH and GFR (r=-0.226, P=0.024). The same negative relationships were found between UA and PTH (r=-0.266, P=0.007), and between UA and the phosphate reabsorption rate (r=-0.415, P<0.001). DISCUSSION: Since hyperuricemia was found at all stages of CKD, an early silent tubular impairment can be discussed to explain these findings. The early increase in PTH levels during CKD has not been described by all authors, with North American studies describing rather late increased PTH levels during CKD. Prospective studies are required to confirm these data and evaluate the role of UA in the pathophysiology of the mineral disorders observed during CKD.

Prediction of glomerular filtration rate in cancer patients by an equation for Japanese estimated glomerular filtration rate.

BACKGROUND: Assessment of renal function is important for safe cancer chemotherapy, and eligibility criteria for clinical trials often include creatinine clearance. However, creatinine clearance overestimates glomerular filtration rate, and various new formulae have been proposed to estimate glomerular filtration rate. Because these were developed mostly in patients with chronic kidney disease, we evaluated their validity in cancer patients without kidney disease. METHODS: Glomerular filtration rate was measured by inulin clearance in 45 Japanese cancer patients, and compared with creatinine clearance measured by 24-h urine collection as well as that estimated by the Cockcroft-Gault formula, Japanese estimated glomerular filtration rate developed in chronic kidney disease patients, the Modification of Diet in Renal Disease study equation and the Chronic Kidney Disease Epidemiology Collaboration equation. The Modification of Diet in Renal Disease study and Chronic Kidney Disease Epidemiology Collaboration equations were adjusted for the Japanese population by multiplying by 0.808 and 0.813, respectively. RESULTS: The mean inulin clearance was 79.2 ± 18.7 ml/min/1.73 m(2). Bias values to estimate glomerular filtration rate for Japanese estimated glomerular filtration rate, the Cockcroft-Gault formula, creatinine clearance measured by 24-h urine collection, the 0.808 × Modification of Diet in Renal Disease study equation and the 0.813 × Chronic Kidney Disease Epidemiology Collaboration equation were 0.94, 9.75, 29.67, 5.26 and -0.92 ml/min/1.73 m(2), respectively. Precision (root-mean square error) was 14.7, 22.4, 39.8, 16.0 and 14.1 ml/min, respectively. Of the scatter plots of inulin clearance versus each estimation formula, the Japanese estimated glomerular filtration rate correlated most accurately with actual measured inulin clearance. CONCLUSION: The Japanese estimated glomerular filtration rate and the 0.813 × Chronic Kidney Disease Epidemiology Collaboration equation estimated glomerular filtration rate with lower bias and higher precision than the other formulae. We therefore propose Japanese estimated glomerular filtration rate for the estimation of glomerular filtration rate in Japanese cancer patients.

Risk of overestimation of kidney function using GFR-estimating equations in patients with low inulin clearance.

BACKGROUND: Accurate estimation of the glomerular filtration rate (GFR) is very important in clinical practice. Although renal inulin clearance (Cin) is the gold standard for measuring GFR, the procedure for Cin measurement is complicated. Use of GFR-estimating equations has been increasing recently due to their simplicity. The objectives of the present study are to analyze the correlation between Cin and other GFR-estimating parameters and to investigate their clinical usefulness and limitation. METHODS: Seventy-two Japanese patients were enrolled in this study. Cin was measured by the continuous infusion method. Serum creatinine (s-Cr), cystatin C, uric acid (UA), and hemoglobin (Hb) were measured. The Japanese formula of estimated GFR (eGFR) was as follows: eGFR (ml/min/1.73m(2) ) = 194 × s-Cr(-1.094) × Age(-0.287) × 0.739 (if female). The endogenous creatinine clearance test was also performed. RESULTS: Levels of Cin were highly correlated with those of endogenous creatinine clearance (Ccr) (R(2) = 0.7585) and eGFR (R(2) = 0.5659). However, patients with lower Cin showed unexpectedly elevated levels of endogenous Ccr and eGFR. Moreover, the levels of eGFR tended to be unexpectedly increased in patients with low body surface area. CONCLUSION: Although GFR-estimating equations are useful for estimating GFR accurately, they pose a risk of overestimation of kidney function in patients with decreased GFRor a poor physique.

[Constant-infusion technique of inulin clearance without urine collection].

Inulin clearance is accepted as the gold standard for estimating the glomerular filtration rate (GFR). However, the method of this examination is troublesome and infants need difficult bladder catheterization. The existence of residual urine results in an inaccurate estimation of GFR and the proceduse requires a large amount of transfusion. In the plasma infusion method, inulin reaches an equilibrium in which the inulin urinary excretion rate is equal to the infusion rate, and urine collection is unnecessary. We estimated GFR in 21 children using both the plasma infusion method and renal infusion method. In the renal infusion method, the loading infusion of 1% inulin was administered over 30 minutes at the dose of 5 mL/kg body weight, followed by maintenance infusion at the constant speed (mL/hour) of 1.5 x estimated GFR (mL/min/1.73 m2) x body surface area (m2)/ 1.73. Three 30-minute urine collections were performed and the plasma inulin levels were measured to estimate GFR. In the plasma infusion method, maintenance infusion was conducted at the speed (mL/hour) of 0.6 x estimated GFR (mL/min/1.73 m2) x body surface area (m2)/1.73. The mean plasma inulin concentrations at 8, 9 and 10 hours were examined and GFR was calculated with the infusion rate. The GFRs for the renal infusion methods (Cin) and plasma infusion methods (e-Cin) were 91.90 +/- 39.61 and 95.33 +/- 38.08 mL/min/1.73 m2, respectively. The values for Cin and e-Cin showed good linear correlation (R2 = 0.81). The value of e-Cin/Cin was 1.069 +/- 0.172 and the mean e-Cin value was only 7% higher than that of Cin. We believe that GFR estimated by the constant infusion method shows a value approximating that estimated by the standard method. This technique is noninvasive for infants and the GFR of children who have vesicoureteral reflux or residual urine in the bladder can be estimated. The method does not need a large amount of transfusion and is suitable for children with heart failure. We believe that this method is clinically useful.

Comparison of plasma clearance of iohexol and urinary clearance of inulin for measurement of GFR in children.

BACKGROUND: Very few studies have been published that compare plasma clearance of iohexol (Cio) with renal clearance of inulin (Cin). STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: 60 children aged 11.6 ± 4.5 years with different kidney disorders were investigated. INDEX TEST: Plasma Cio calculated from the slope and a single point. REFERENCE TEST: Renal Cin with continuous infusion during water diuresis. Results were compared with the correlation coefficients, bias and precision, accuracy percentage, root mean square error, and intraclass correlation. OTHER MEASUREMENTS: Measured creatinine clearance and estimated glomerular filtration rate based on serum creatinine level and height. RESULTS: Mean Cin was 70.7 ± 41.3 (SD) mL/min/1.73 m². Mean differences between Cio and Cin were 2.65 and 2.00 mL/min/1.73 m² for the slope and single-point methods, respectively. Precision was ±16 mL/min/1.73 m² and intraclass correlation was 0.92 in both methods. Proportions of Cio within 30% of Cin were 83.3% and 86.7% for the slope and single-point methods, respectively. LIMITATIONS: A limited number of patients; no adults were studied. CONCLUSIONS: Plasma Cio shows good agreement with renal Cin.

Comparison of a simple and a standard method for inulin renal clearance.

BACKGROUND: The standard method of renal inulin clearance consists of three sets of 30-min clearances. We previously proposed a simple method with a single urine collection for 1 h and two blood samples. In this study, we compared the two methods. METHODS: The study involved 112 individuals. Three sets of 30-min urine sample collections were started 45 min after inulin infusion , and serum concentrations were measured at the midpoint (60, 90, 120 min) of each clearance period. The mean of the three (Cin-ST) or average of the first two (Cin-ST2) clearances was used for the standard method. Clearance calculated by the simple method (Cin-S) combined the first two collections and the mean of serum concentrations at the beginning (45 min) and end (105 min) of the clearance period. Clearance was also calculated by estimated area under the plasma concentration curve from 45 to 105 min (Cin-A) as a more reliable value. RESULTS: Cin-S correlated highly with Cin-ST (r = 0.992). Bland-Altman plot indicated that Cin-S was lower than Cin-ST at the same rate in all glomerular filtration rate (GFR) ranges. Total Cin-S of all patients was significantly lower (5.9%, 4.8%, and 3.6%) than Cin-ST, Cin-ST2, and Cin-A, respectively. Cin-ST2 was 1.3% higher than Cin-A. The change in serum inulin concentration by time from 45 to 105 min was not linear but concave. This led to the underestimation of clearance by the simple method. CONCLUSION: The simple method of renal inulin clearance gives slightly lower results than the standard method. The difference was small, indicating the simple method is accurate enough for use in clinical practice.

Utility of the Japanese GFR estimation equation for evaluating potential donor kidney function.

BACKGROUND: In Japan, the number of living kidney transplantations has increased each year, and an accurate evaluation of renal function must be conducted before donation to minimize the risk to donors. Recently, the Japanese Society of Nephrology issued a new equation for estimating glomerular filtration rate (eGFR) in Japanese people. This study compared the accuracy of eGFR and creatinine clearance (Ccr) values with that of inulin clearance (Cin) for assessing renal function in kidney donors. METHODS: Clinical data were analyzed for 85 potential living kidney donors who had undergone routine measured GFR (mGFR) and Ccr measurements from October 2006 to November 2008 at a single center. Inulin clearance, representing the mGFR, was determined by standard method. The eGFR was calculated as: eGFR = 194 x Scr(-1.094) x Age(-0.287) (for females, x0.739). RESULTS: Mean mGFR was 96.1 +/- 14.7 (range 67.8-126.8); mean eGFR, 72.6 +/- 12.7 (range 50.1-107.1); and mean Ccr, 117.3 +/- 22.4 (range 35.1-170.1), in units of ml/min/1.73 m(2) for each. Relative to mGFR, the correlation coefficient for Ccr was 0.496, and the mean difference between the two values was 21.1 ml/min/1.73 m(2) (23.2%), with a root-mean square error (RMSE) of 19.6. The correlation coefficient between eGFR and mGFR was 0.502, and the mean difference between the two values was -23.5 (23.7%), with a RMSE of 11.0. Bland-Altman plots showed that Ccr overestimated mGFR in 90.6% of cases, whereas eGFR underestimated mGFR in 95.3% of cases. CONCLUSION: Ccr and eGFR values did not accurately estimate mGFR in Japanese living kidney donors.

Evaluation of a new automated, enzymatic inulin assay using D-fructose dehydrogenase.

BACKGROUND: Inulin clearance (Cin) is widely considered to be a gold-standard assessment of glomerular filtration rate (GFR). Although inulin concentrations are commonly determined by the anthrone method, this method has several disadvantages, including a hazardous heating procedure using a strong acid, as well as a nonspecific reaction and being influenced by other saccharides such as glucose. METHOD: Here, we report the development of a new automated, enzymatic inulin assay. This method uses D: -fructose dehydrogenase (EC1.1.99.11), which does not require NAD or NADP as the electron acceptor, and utilizes oxygen transfer from hydrogen peroxide to an electron acceptor in a sensitive chromophoric system. This method allows rapid and accurate determination of inulin concentrations, and takes only 15 min on automated analyzers. We evaluated this new assay and compared it with the anthrone method. RESULTS: The detection limit value and linearity of the new method were 5 mg/l and up to 300 mg/l, respectively. The within-run precision coefficient of variations (CVs) for serum and for urine were 2.05 +/- 0.79% (mean +/- SEM; n = 3) and 0.92 +/- 0.24%, respectively, and the between-run precision CVs for serum and for urine were 1.91 +/- 0.72% and 1.86 +/- 0.17%, respectively. No influence of glucose was observed with the new method, while a positive influence of 38.7% was observed with the anthrone method. However, neither method was influenced by fructose (3.0 mg/l in serum or 30 mg/l in urine). The analytical recovery rates of inulin were 97.8 +/- 0.7% (mean +/- SEM; n = 6) in serum and 99.0 +/- 0.4% in urine using the enzymatic method. We compared results for the enzymatic method and the anthrone method using 46 serum samples and 46 urine samples. Bland-Altman plots showed no significant difference between the two methods for the serum samples. However, inulin recovery in the urine samples measured by the enzymatic method was about 5% higher than that obtained by the anthrone method. CONCLUSION: The new enzymatic assay offers a more convenient and more accurate measurement of inulin and may be suitable for routine procedures by automated analyzers in clinical laboratories.

Simple sampling strategy for measuring inulin renal clearance.

BACKGROUND: In the standard method of inulin clearance (Cin), three sets of serum and urine samples are collected during a 2-hour clearance period. For a practical use of this method, sampling should be the minimal number allowable while still providing enough accuracy. The aim of this study was to evaluate the validity of inulin renal clearance with assumed single urine collection with a period such as 30, 60 or 90 minutes. METHODS: Inulin clearance data collected by the standard method from 737 individuals were used. Changes of serum inulin concentrations between 45 and 105 minutes after the start of the infusion were analyzed. We used first urine collection to calculate the inulin clearance with single urine collection (Cin-30 min). We assumed single urine collection for 60 or 90 minutes by combining the urine data of the consecutive 30-minute periods. Inulin clearances (Cin-60 min, Cin-90 min) were calculated from the assumed single urine collections, respectively. RESULTS: Serum inulin concentration did not reach equilibrium during the clearance period. It increased in subjects with low glomerular filtration rate (GFR) and decreased in subjects with normal GFR. The amount of the change was small and -0.5 +/- 12.6% in subjects with GFR over 30 ml/min per 1.73 m(2). Cin-30 min, Cin-60 min and Cin-90 min showed high correlation coefficients against Cin-ST (0.962, 0.988 and 0.998, respectively). Systemic biases in these clearances were negligible (under 1 ml/min per 1.73 m(2)). Root mean square error (RMSE) were 10.4, 5.3 and 2.3 ml/min per 1.73 m(2) for Cin-30 min, Cin-60 min and Cin-90 min, respectively. These data indicated that accuracy of inulin clearance depends on the duration of the urine collection period. CONCLUSION: Inulin clearance with a single urine collection is a convenient method. We showed that single urine collection for 30 minutes or a longer period has reasonable accuracy in calculation of inulin clearance. We propose a method of inulin clearance with single urine collection for 60 minutes.

Renal function and cardiopulmonary bypass in pediatric cardiac surgical patients.

We studied prospectively the perioperative changes of renal function in nine children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured with inulin and (131)I-hippuran clearances before CPB, during hypo and normothermic CPB, following sternal closure and 1 h postoperatively. Urinary alpha glutathione S-transferase (alpha GS-T) was measured pre- and postoperatively as a marker for tubular cellular damage. Plasma and urine creatinine and electrolytes were measured. Free water, osmolal and creatinine clearances, as well as fractional excretion of sodium (FeNa) and potassium transtubular gradient (TTKG) were calculated. GFR was normal before and after surgery. ERPF was low before and after surgery; it increased significantly immediately after CPB. Filtration fraction (FF) was abnormally elevated before and after surgery; however, a significant decrease during normothermic CPB and sternal closure was found. Alpha GS-T presented a moderate, but nonsignificant increase postoperatively. FeNa also increased in this period, but not significantly. Creatinine, osmolal, free water clearances, as well as TTKG, were normal in all patients pre- and postoperatively. We conclude that there is no evidence of clinically significant deterioration of renal function in children undergoing repair of cardiac lesions under CPB. Minor increases of alpha GS-T in urine postoperatively did not confirm cellular tubular damage. There was no tubular dysfunction at that time.