Search

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/1.73m 2 . All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPI Cys was not significantly different from mGFR (p = 0.38). The CKD-EPI Cys exhibited lowest bias [mean bias: -3.53 ± 14.70 ml/min/1.73m 2 (95% CI: -0.608 to -0.98)] and highest accuracy (P 30 : 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90-134.50) ml/min/1.73m 2 ., 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.

Background: Recently, Tsuda et al. reported that high HbA1C or high glycated albumin (GA) level is a major factor in overestimation of GFR by Japanese GFR equation based on serum creatinine (Eq-cr). They developed a modified equation of Eq-cr (M-Eq-cr) using GA or HbA1c. Therefore, effect of GA levels on the estimated GFR (eGFR) by Eq-cr was evaluated in Japanese subjects. We validated the accuracy of the modified equation using GA by Tsuda et al. (M-Eq-cr) and new equations that we developed in the present study., Methods: Seven hundred and fifteen Japanese subjects were included. GFR was measured by inulin renal clearance (Cin). The subjects were divided into two groups by upper limit of the GA reference range (GA-1: GA < 16.3 % and GA-2: GA > 16.4 %). Factors affecting the ratio of eGFR to Cin (eGFR/Cin) were evaluated using multivariate analysis. New equations based on creatinine and albumin (Eq-cr-alb) and based on creatinine, albumin and GA were developed from development dataset (382 subjects). Performances of the equations were validated in validation dataset (333 subjects)., Results: Correlation coefficients between eGFR by Eq-cr and Cin were 0.839 and 0.914 in GA-1 and GA-2, respectively. Slopes (95 % confidential interval) of the regression lines with zero intercepts were 1.013 (0.991 to 1.036) and 0.997 (0.951 to 1.043), respectively. Both slopes were not significantly different from 1.0. Biases were -2.3 ± 19.0 and 0.2 ± 11.7 ml/min/1.73 m(2), respectively. Accuracy (p30; percentage of subjects within 30 % of Cin) (95 % CI) were 78 % (75, 81) and 71 % (62, 78), respectively. There was no significant difference in bias and accuracy between the two groups, indicating a reasonable accuracy of Eq-cr in GA-1 and GA-2. Multiple regression analysis showed that lower serum albumin and higher GA were associated with higher eGFR/Cin. Albumin was a more potent factor affecting eGFR/Cin than GA. M-Eq-cr significantly underestimated GFR and had significantly larger bias compared with Eq-cr in subjects with GA > 20 %, suggesting that the modification of Eq-cr using GA by Tsuda et al. was too much compensation in our subjects. Precisions of Eq-cr-alb were significantly better compared with Eq-cr., Conclusion: Eq-cr has a reasonable accuracy in GA-1 and GA-2. Lower serum albumin and higher GA were significantly associated with higher eGFR/Cin. The former was a more potent factor affecting eGFR/Cin. Eq-cr-alb showed better performance compared with Eq-cr. M-Eq-cr using GA showed too much compensation and did not improve the accuracy of the equation in our subjects.

Background: Creatinine clearance (Ccr) overestimates glomerular filtration rate (GFR) due to the tubular secretion of creatinine. It is known that fractional excretion of creatinine (FE-Cr) increases with decreasing GFR. Association of serum albumin level with the tubular secretion of creatinine was also reported previously. Alteration of FE-Cr may affect the performance of GFR estimating equations based on serum creatinine. Therefore, we analyzed the factors influencing FE-Cr and compared the performance of GFR equations in subjects stratified by serum albumin levels., Methods: Seven hundred and fifty-seven Japanese subjects were included. GFR was measured by inulin renal clearance. GFR and Ccr were measured simultaneously. FE-Cr was calculated as the ratio of Ccr to GFR. Multivariate analysis was performed to evaluate the factors influencing FE-Cr. Age, gender, GFR, body mass index (BMI), body weight, height and serum albumin level were analyzed as the parameters. Estimated GFR was calculated by Japanese GFR equations based on serum creatinine (Eq-cr), serum cystatin C (Eq-cys) and 5 variables including serum albumin (Eq-5var)., Results: FE-Cr in subjects with serum albumin <3.0, 3.0-3.9 and ≥4.0 g/dl were 1.63 ± 0.48, 1.53 ± 0.55, and 1.40 ± 0.36, respectively. FE-Cr in subjects with serum albumin <3.0 or 3.0-3.9 g/dl were significantly higher than the value in subjects with serum albumin ≥4.0 g/dl. Multivariate analysis showed that GFR (p < 0.0001) and serum albumin level (p = 0.004) were independent parameters affecting FE-Cr. Biases of Eq-cr, Eq-cys and Eq-5var in subjects with serum albumin <3.0 g/dl were -9.5 ± 17.5, -0.7 ± 17.1 and -0.6 ± 14.8 ml/min/1.73 m(2), respectively. Eq-cr significantly overestimated GFR compared with Eq-cys or Eq-5var. Biases in subjects with serum albumin ≥4.0 g/dl were 6.4 ± 18.8, 2.0 ± 18.1 and 3.0 ± 18.3 ml/min/1.73 m(2), respectively. Eq-cr significantly underestimated GFR compared with Eq-cys or Eq-5var., Conclusion: GFR and serum albumin level were independent parameters affecting FE-Cr. Alteration of FE-Cr according to the serum albumin levels may be one of the reasons of the bias of GFR equation based on serum creatinine.

Introduction: Serum cystatin C was recently proposed as an alternative marker of glomerular filtration rate (GFR), with a suggested better performance than creatinine. However, detailed studies are limited. We evaluated the performance of cystatin C as a GFR marker., Methods: GFR was measured by inulin clearance in 763 Japanese subjects. Factors other than GFR influencing serum cystatin C or serum creatinine were analyzed by multivariate analyses., Results: After adjustment for GFR, the value of serum creatinine was 25.2% lower in females than males, and decreased by 5.2% for every 20 years of age. Serum cystatin C was 8.2% lower in females, and did not change significantly with aging. Creatinine but not cystatin C was significantly affected by body weight, height and body mass index after adjustment for GFR, gender and age. The correlation coefficient between GFR and 1/cystatin C was significantly higher than that of 1/creatinine in total subjects (0.866 and 0.810, respectively, p < 0.001). Unlike serum creatinine, serum cystatin C did not increase in association with the reduction of GFR in subjects with very low GFR. The regression line of 1/cystatin C against GFR showed a significantly negative intercept of about -8 ml/min/1.73 m(2)., Conclusion: The performance of serum cystatin C was not good in the subjects with very low GFR. Non-renal elimination of cystatin C may contribute to the result. The correlation between reciprocal cystatin C and GFR suggested its superiority in predicting GFR compared to creatinine in subjects with normal and mildly reduced GFR.

Background: Estimation of glomerular filtration rate (GFR) is limited by differences in creatinine generation among ethnicities. Our previously reported GFR-estimating equations for Japanese had limitations because all participants had a GFR less than 90 mL/min/1.73 m2 and serum creatinine was assayed in different laboratories., Study Design: Diagnostic test study using a prospective cross-sectional design. New equations were developed in 413 participants and validated in 350 participants. All samples were assayed in a central laboratory., Setting & Participants: Hospitalized Japanese patients in 80 medical centers. Patients had not participated in the previous study., Reference Test: Measured GFR (mGFR) computed from inulin clearance., Index Test: Estimated GFR (eGFR) by using the modified isotope dilution mass spectrometry (IDMS)-traceable 4-variable Modification of Diet in Renal Disease (MDRD) Study equation using the previous Japanese Society of Nephrology Chronic Kidney Disease Initiative (JSN-CKDI) coefficient of 0.741 (equation 1), the previous JSN-CKDI equation (equation 2), and new equations derived in the development data set: modified MDRD Study using a new Japanese coefficient (equation 3), and a 3-variable Japanese equation (equation 4)., Measurements: Performance of equations was assessed by means of bias (eGFR - mGFR), accuracy (percentage of estimates within 15% or 30% of mGFR), root mean squared error, and correlation coefficient., Results: In the development data set, the new Japanese coefficient was 0.808 (95% confidence interval, 0.728 to 0.829) for the IDMS-MDRD Study equation (equation 3), and the 3-variable Japanese equation (equation 4) was eGFR (mL/min/1.73 m2) = 194 x Serum creatinine(-1.094) x Age(-0.287) x 0.739 (if female). In the validation data set, bias was -1.3 +/- 19.4 versus -5.9 +/- 19.0 mL/min/1.73 m2 (P = 0.002), and accuracy within 30% of mGFR was 73% versus 72% (P = 0.6) for equation 3 versus equation 1 and -2.1 +/- 19.0 versus -7.9 +/- 18.7 mL/min/1.73 m(2) (P < 0.001) and 75% versus 73% (P = 0.06) for equation 4 versus equation 2 (P = 0.06), respectively., Limitation: Most study participants had chronic kidney disease, and some may have had changing GFRs., Conclusion: The new Japanese coefficient for the modified IDMS-MDRD Study equation and the new Japanese equation are more accurate for the Japanese population than the previously reported equations.

Background: In patients with adult minimal change disease (MCD), proteinuria relapse is a problem to solve. However, the optimal relapse treatment regimen remains unclear regarding steroid dose. We described the treatment pattern of adult MCD patients and evaluated the appropriate steroid dose for relapse treatment. Methods: This retrospective multicenter cohort study included 192 patients with adult biopsy-proven MCD from 14 hospitals in Japan. The prescription pattern of immunosuppressive drugs in relapse was reviewed. To assess the association between steroid dose used for relapse and subsequent outcomes, data of patients with tapered prednisolone (PSL) dosage to <10 mg/day before the first relapse in whom the dose was subsequently increased to ≥10 mg/day were extracted and assigned to the High-PSL or Low-PSL groups, based on the median dose of 20 mg/day. Multivariate Cox proportional hazard model and propensity score analysis with multiple imputations were conducted to compare their clinical course. Results: During a median observation period of 37.6 months, 186/192 (96.9%) patients achieved complete remission (CR) and 100 (52.1%) relapsed. The median urinary protein level at the first relapse was 3.12 g/gCr or g/day. The proportion of non-steroidal immunosuppressant use increased with relapses; cyclosporine was the most common. No significant differences were found in the second relapse, frequent relapses, or adverse events between High-PSL (n = 34) and Low-PSL (n = 36) groups. A multivariate Cox proportional hazard model revealed that the hazard ratios adjusted with propensity score for the second relapse were 0.94 (High-PSL vs. Low-PSL; 95% confidence interval, 0.42–2.10; P = 0.88) and 0.82 (PSL dose per 10 mg/day; 95% confidence interval, 0.58–1.16; P = 0.25). Conclusions: Among patients in CR with PSL dose <10 mg/day, higher steroid dose (PSL >20 mg/day) was not associated with favorable outcomes after the first relapse as compared to lower dose (10–20 mg/day). [ABSTRACT FROM AUTHOR]

Background: Japanese GFR equation was developed from mainly chronic kidney disease (CKD) subjects. Only a small number of healthy subjects were included in the development and validation of the GFR equation. We assessed the performance of the equation in potential kidney donors. Methods: A total of 113 potential kidney donors was included. The data of CKD subjects that were previously reported were also included for comparison. GFR (mGFR) was measured by inulin clearance. The estimated GFR (eGFR) was calculated by the Japanese GFR equation. Bias of the equation (eGFR − mGFR) and urinary creatinine excretion were evaluated. Results: There was no significant difference between eGFR and mGFR in 340 CKD subjects (54.2 ± 31.6 and 55.7 ± 33.2 ml/min/1.73 m, respectively). Contrarily, the eGFR was significantly lower than mGFR in 113 potential kidney donors (78.9 ± 16.2 and 93.6 ± 19.2 ml/min/1.73 m, respectively). The biases in potential kidney donors with eGFR 30-59 and 60-89 ml/min/1.73 m were significantly greater than those in CKD subjects (−19.2 ± 12.2 and −18.3 ± 16.4 ml/min/1.73 m in potential kidney donors and −3.8 ± 15.6 and −3.4 ± 17.6 ml/min/1.73 m in CKD subjects, respectively). Creatinine excretion per body weight of potential kidney donors was significantly higher than that of CKD subjects, suggesting higher creatinine generation in potential kidney donors. Conclusion: The Japanese GFR equation underestimated GFR in potential kidney donors. Higher creatinine generation compared with CKD subjects may contribute to the underestimation of GFR by the Japanese GFR equation in potential kidney donors. [ABSTRACT FROM AUTHOR]

Accurate estimation of the glomerular filtration rate (GFR) is crucial for the detection of chronic kidney disease (CKD). In clinical practice, GFR is estimated from serum creatinine using the Modification of Diet in Renal Disease (MDRD) study equation or the Cockcroft-Gault (CG) equation instead of the time-consuming method of measured clearance for exogenous markers such as inulin. In the present study, the equations originally developed for a Caucasian population were tested in Japanese CKD patients, and modified with the Japanese coefficient determined by the data. The abbreviated MDRD study and CG equations were tested in 248 Japanese CKD patients and compared with measured inulin clearance (Cin) and estimated GFR (eGFR). The Japanese coefficient was determined by minimizing the sum of squared errors between eGFR and Cin. Serum creatinine values of the enzyme method in the present study were calibrated to values of the noncompensated Jaffé method by adding 0.207 mg/dl, because the original MDRD study equation was determined by the data for serum creatinine values measured by the noncompensated Jaffé method. The abbreviated MDRD study equation modified with the Japanese coefficient was validated in another set of 269 CKD patients. There was a significant discrepancy between measured Cin and eGFR by the 1.0 × MDRD or CG equations. The MDRD study equation modified with the Japanese coefficient (0.881 × MDRD) determined for Japanese CKD patients yielded lower mean difference and higher accuracy for GFR estimation. In particular, in Cin 30–59 ml/min per 1.73 m2, the mean difference was significantly smaller with the 0.881 × MDRD equation than that with the 1.0 × MDRD study equation (1.9 vs 7.9 ml/min per 1.73 m2; P < 0.01), and the accuracy was significantly higher, with 60% vs 39% of the points deviating within 15%, and 97% vs 87% of points within 50%, respectively (both P < 0.01). Validation with the different data set showed the correlation between eGFR and Cin was better with the 0.881 × MDRD equation than with the 1.0 × MDRD study equation. In Cin less than 60 ml/min per 1.73 m2, the accuracy was significantly higher, with 85% vs 69% of the points deviating within 50% ( P < 0.01), respectively. The mean difference was also significantly smaller ( P < 0.01). However, GFR values calculated by the 0.881 × MDRD equation were still underestimated in the range of Cin over 60 ml/min per 1.73 m2. Although the Japanese coefficient improves the accuracy of GFR estimation of the original MDRD study equation, a new equation is needed for more accurate estimation of GFR in Japanese patients with CKD stages 3 and 4. [ABSTRACT FROM AUTHOR]