A New Modified CKD-EPI Equation for Chinese Patients with Type 2 Diabetes

Objective

To improve the performance of glomerular filtration rate (GFR) estimating equation in Chinese type 2 diabetic patients by modification of the CKD-EPI equation.

Design and patients

A total of 1196 subjects were enrolled. Measured GFR was calibrated to the dual plasma sample ^99mTc-DTPA-GFR. GFRs estimated by the re-expressed 4-variable MDRD equation, the CKD-EPI equation and the Asian modified CKD-EPI equation were compared in 351 diabetic/non-diabetic pairs. And a new modified CKD-EPI equation was reconstructed in a total of 589 type 2 diabetic patients.

Results

In terms of both precision and accuracy, GFR estimating equations all achieved better results in the non-diabetic cohort comparing with those in the type 2 diabetic cohort (30% accuracy, P≤0.01 for all comparisons). In the validation data set, the new modified equation showed less bias (median difference, 2.3 ml/min/1.73 m² for the new modified equation vs. ranged from −3.8 to −7.9 ml/min/1.73 m² for the other 3 equations [P<0.001 for all comparisons]), as was precision (IQR of the difference, 24.5 ml/min/1.73 m² vs. ranged from 27.3 to 30.7 ml/min/1.73 m²), leading to a greater accuracy (30% accuracy, 71.4% vs. 55.2% for the re-expressed 4 variable MDRD equation and 61.0% for the Asian modified CKD-EPI equation [P = 0.001 and P = 0.02]).

Conclusion

A new modified CKD-EPI equation for type 2 diabetic patients was developed and validated. The new modified equation improves the performance of GFR estimation.     

Kidney Function,Endothelial Activation and Atherosclerosis in Black and White Africans with Rheumatoid Arthritis

Objective

To determine whether kidney function independently relates to endothelial activation and ultrasound determined carotid atherosclerosis in black and white Africans with rheumatoid arthritis (RA).

Methods

We calculated the Jelliffe, 5 Cockcroft-Gault equations, Salazar-Corcoran, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (EGFR) equations in 233 (112 black) RA patients.

Results

The CKD-EPI eGFR was <90 ml/min/1.73m² in 49.1% and 30.6% of black and white patients, respectively (odds ratio (95% confidence interval) = 2.19 (1.28–3.75), p = 0.004). EGFRs were overall consistently associated with monocyte chemoattractant protein-1 and angiopoietin 2 concentrations in white patients, and with carotid intima-media thickness and plaque in black participants. Amongst black patients, plaque prevalence was 36.7% and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was not associated with plaque presence for the MDRD equation (p = 0.3), whereas the respective relationship was significant or borderline significant (p = 0.003 to 0.08) and of similar extent (p>0.1 for comparisons of AUC (SE)) for the other 8 equations. Based on optimal eGFR cutoff values with sensitivities and specificities ranging from 42 to 60% and 70 to 91% respectively, as determined in ROC curve analysis, a low eGFR increased the odds ratio for plaque 2.2 to 4.0 fold.

Conclusion

Reduced kidney function is independently associated with atherosclerosis and endothelial activation in black and white Africans with RA, respectively. CKD is highly prevalent in black Africans with RA. Apart from the MDRD, eGFR equations are useful in predicting carotid plaque presence, a coronary heart disease equivalent, amongst black African RA patients.     

Multicenter Study of Creatinine- and/or Cystatin C-Based Equations for Estimation of Glomerular Filtration Rates in Chinese Patients with Chronic Kidney Disease

Objective

To establish equations for the estimation of glomerular filtration rates (eGFRs) based on serum creatinine (SCr) and/or serum cystatin C (SCysC) in Chinese patients with chronic kidney disease (CKD), and to compare the new equations with both the reference GFR (rGFR) and the literature equations to evaluate their applicability.

Methods

The 788 Chinese CKD patients were randomly divided into two groups, the training group and the testing group, to establish new eGFR-formulas based on serum CysC and to validate the established formulas, respectively. ^99mTc-DTPA clearance (as the rGFR), serum Cr, and serum CysC were determined for all patients, and GFR was calculated using the Cockcroft-Gault equation (eGFR1), the MDRD formula (eGFR2), the CKD-EPI formulas (eGFR3, eGFR4), and the Chinese eGFR Investigation Collaboration formulas (eGFR5, eGFR6). The accuracy of each eGFR was compared with the rGFR.

Results

The training and testing groups'' mean GFRs were 50.84±31.36 mL/min/1.73 m² and 54.16±29.45 mL/min/1.73 m², respectively. The two newly developed eGFR formulas were fitted using iterative computation: and . Significant correlation was observed between each eGFR and the rGFR. However, proportional errors and constant errors were observed between rGFR and eGFR1, eGFR2, eGFR4, eGFR5 or eGFR6, and constant errors were observed between eGFR3 and rGFR, as revealed by the Passing & Bablok plot analysis. The Bland-Altman analysis illustrated that the 95% limits of agreement of all equations exceeded the previously accepted limits of <60 mL/min •1.73 m², except the equations of eGFR7 and eGFR8.

Conclusion

The newly developed formulas, eGFR7 and eGFR8, provide precise and accurate GFR estimation using serum CysC detection alone or in combination with serum Cr detection. Differences in detection methods should be carefully considered when choosing literature eGFR equations to avoid misdiagnosis and mistreatment.     

Determining Glomerular Filtration Rate in Homozygous Sickle Cell Disease: Utility of Serum Creatinine Based Estimating Equations

Background

Various estimating equations have been developed to estimate glomerular filtration rate (GFR) for use in clinical practice. However, the unique renal physiological and pathological processes that occur in sickle cell disease (SCD) may invalidate these estimates in this patient population. This study aims to compare GFR estimated using common existing GFR predictive equations to actual measured GFR in persons with homozygous SCD. If the existing equations perform poorly, we propose to develop a new estimating equation for use in persons with SCD.

Methods

98 patients with the homozygous SS disease (55 females: 43 males; mean age 34±2.3 years) had serum measurements of creatinine, as well as had GFR measured using ^99mTc-DTPA nuclear renal scan. GFR was estimated using the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and the serum creatinine based CKD-EPI equations. The Bland-Altman limit of agreement method was used to determine agreement between measured and estimated GFR values. A SCD-specific estimating equation for GFR (JSCCS-GFR equation) was generated by means of multiple regression via backward elimination.

Results

The mean measured GFR±SD was 94.9±27.4 mls/min/1.73 m² BSA, with a range of 6.4–159.0 mls/min/1.73 m². The MDRD and CG equations both overestimated GFR, with the agreement worsening with higher GFR values. The serum creatinine based CKD-EPI equation performed relatively well, but with a systematic bias of about 45 mls/min. The new equation developed resulted in a better fit to our sickle cell disease data than the MDRD equation.

Conclusion

Current estimating equations, other than the CKD-EPI equation, do not perform very accurately in persons with homozygous SS disease. A fairly accurate estimating equation, suitable for persons with GFR >60 mls/min/1.73 m² has been developed from our dataset and validated within a simulated dataset.     

Plasma Lipoprotein(a) Levels Are Associated with Mild Renal Impairment in Type 2 Diabetics Independent of Albuminuria

Background

CKD, an independent risk factor for CV disease, increases mortality in T2DM. Treating modifiable CV risk factors decreases mortality in diabetics with microalbuminuria, but the role of early CV prevention in diabetics with mild CKD by GFR criteria alone remains unclear. The purpose of this study was to probe whether T2DM patients with mild GFR impairment have atherogenic lipid profiles compared to diabetic counterparts with normal renal function.

Methods

In the Penn Diabetes Heart Study (PDHS), a single-center observational cohort of T2DM patients without clinical CVD, cross-sectional analyses were performed for directly measured lipid fractions in 1852 subjects with eGFR>60 mL/min/1.73 m² determined by the CKD-EPI equation (n = 1852). Unadjusted and multivariable analyses of eGFR association with log-transformed lipid parameters in incremental linear and logistic regression models (with eGFR 90 mL/min/1.73 m² as a cut-point) were performed.

Results

Mild GFR impairment (eGFR 60–90 mL/min/1.73 m², median urinary ACR 5.25 mg/g) was associated with higher log-transformed Lp(a) values (OR 1.17, p = 0.005) and with clinically atherogenic Lp(a) levels above 30 mg/dL (OR 1.35, p = 0.013) even after full adjustment for demographics, medications, metabolic parameters, and albuminuria. Logistic regression demonstrated a trend towards significance between worse kidney function and apoB (p = 0.17) as well as apoC-III (p = 0.067) in the fully adjusted model.

Conclusions

Elevated Lp(a) levels have a robust association with mild GFR impairment in type 2 diabetics independent of race, insulin resistance, and albuminuria.     

Using Mathematical Algorithms to Modify Glomerular Filtration Rate Estimation Equations

Background

The equations provide a rapid and low-cost method of evaluating glomerular filtration rate (GFR). Previous studies indicated that the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease-Epidemiology (CKD-EPI) and MacIsaac equations need further modification for application in Chinese population. Thus, this study was designed to modify the three equations, and compare the diagnostic accuracy of the equations modified before and after.

Methodology

With the use of ^{99 m}Tc-DTPA renal dynamic imaging as the reference GFR (rGFR), the MDRD, CKD-EPI and MacIsaac equations were modified by two mathematical algorithms: the hill-climbing and the simulated-annealing algorithms.

Results

A total of 703 Chinese subjects were recruited, with the average rGFR 77.14±25.93 ml/min. The entire modification process was based on a random sample of 80% of subjects in each GFR level as a training sample set, the rest of 20% of subjects as a validation sample set. After modification, the three equations performed significant improvement in slop, intercept, correlated coefficient, root mean square error (RMSE), total deviation index (TDI), and the proportion of estimated GFR (eGFR) within 10% and 30% deviation of rGFR (P₁₀ and P₃₀). Of the three modified equations, the modified CKD-EPI equation showed the best accuracy.

Conclusions

Mathematical algorithms could be a considerable tool to modify the GFR equations. Accuracy of all the three modified equations was significantly improved in which the modified CKD-EPI equation could be the optimal one.     

Long-Term Follow-Up of Proteinuria and Estimated Glomerular Filtration Rate in HIV-Infected Patients with Tubular Proteinuria

Objective

The objective of this prospective observational study was to describe the evolution of tubular proteinuria detected in HIV-infected patients, and to evaluate the impact of tenofovir disoproxil fumarate (TDF) discontinuation.

Methods

Proteinuria and estimated glomerular filtration rate (eGFR) were followed during a median duration of 32 months, in 81 HIV-infected patients with tubular proteinuria and eGFR ≥ 60 ml/min/1.73 m² (determined using the Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation). Tubular proteinuria was defined by urine protein to creatinine ratio (uPCR) ≥200 mg/g and albumin to protein ratio (uAPR) <0.4.

Results

Twenty per cent of patients had persistence of tubular proteinuria: TDF continuation was the main factor associated with this persistence [OR 9.0; 95%CI: 1.9–41.4; p = 0.01]. Among the 23 patients who discontinued TDF, uPCR returned below the threshold of 200 mg/g in 11 patients. Overall, eGFR decreased with a mean rate of decline of 3.8 ml/min/1.73m²/year. The decline in eGFR was lesser after discontinuation of TDF (5.8 ml/min/1.73m²/year during TDF exposure versus 3 ml/min/1.73m²/year after TDF discontinuation; p = 0.01).

Conclusions

The continuation of TDF was the main factor associated with the persistence of proteinuria. Moreover, proteinuria was normalized in only half of the patients who discontinued TDF. The clinical significance of TDF-related low level of proteinuria as a factor associated with renal disease progression and bone loss remains poorly understood.     

Prevalence of kidney disease in HIV-infected and uninfected Rwandan women

Background

In the United States, HIV-related kidney disease disproportionately affects individuals of African descent; however, there are few estimates of kidney disease prevalence in Africa. We evaluated the prevalence of kidney disease among HIV-infected and uninfected Rwandan women.

Methods

The Rwandan Women''s Interassociation Study and Assessment prospectively enrolled 936 women. Associations with estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m² and proteinuria were assessed in separate logistic regression models.

Results

Among 891 non-pregnant women with available data, 2.4% had an eGFR<60 mL/min/1.73 m² (calculated by the Modification of Diet in Renal Disease equation, MDRD eGFR) and 8.7% had proteinuria ≥1+. The prevalence of decreased eGFR varied markedly depending on the estimating method used, with the highest prevalence by Cockcroft-Gault. Regardless of the method used to estimate GFR, the proportion with decreased eGFR or proteinuria did not differ significantly between HIV-infected and -uninfected women in unadjusted analysis. After adjusting for age and blood pressure, HIV infection was associated with significantly higher odds of decreased MDRD eGFR but not proteinuria.

Conclusion

In a well-characterized cohort of Rwandan women, HIV infection was associated with decreased MDRD eGFR. The prevalence of decreased eGFR among HIV-infected women in our study was lower than that previously reported in African-Americans and in other Central and East African HIV populations, although there was substantial variability depending on the equation used to estimate GFR. Future studies are needed to optimize GFR estimates and to determine the impact of antiretroviral therapy on kidney disease in this population.     

Triglyceride Levels Are Closely Associated with Mild Declines in Estimated Glomerular Filtration Rates in Middle-Aged and Elderly Chinese with Normal Serum Lipid Levels

Objective

To investigate the relationship between lipid profiles [including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)] and a mild decline in the estimated glomerular filtration rate (eGFR) in subjects with normal serum lipid levels.

Design and Methods

In this study, we included 2647 participants who were ≥40 years old and had normal serum lipid levels. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to estimate the GFR. A mildly reduced eGFR was defined as 60–90 mL/min/1.73 m². First, multiple linear regression analysis was used to estimate the association of lipid profiles with the eGFR. Then, the levels of each lipid component were divided into four groups, using the 25th, 50th and 75th percentiles as cut-off points. Finally, multiple logistic regression analysis was used to investigate the association of different lipid components with the risk of mildly reduced eGFR.

Results

In the group with a mildly reduced eGFR, TG and LDL-C levels were significantly increased, but HDL-C levels were significantly decreased. After adjusting for age, gender, body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin (HbA_1c), smoking and drinking, only TC and TG were independently related to the eGFR. Additionally, only TG showed a linear relationship with an increased risk of a mildly reduced eGFR, with the highest quartile group (TG: 108–150 mg/dl [1.22–1.70 mmol/L]) having a significantly increased risk after adjusting for the above factors.

Conclusions

Triglyceride levels are closely associated with a mildly reduced eGFR in subjects with normal serum lipid levels. Dyslipidemia with lower TG levels could be used as new diagnostic criteria for subjects with mildly reduced renal function.     

Longitudinal Study of the Decline in Renal Function in Healthy Subjects

Background

Chronic kidney disease is an important concern in preventive medicine, but the rate of decline in renal function in healthy population is not well defined. The purpose of this study was to determine reference values for the estimated glomerular filtration rate (eGFR) and rate of decline of eGFR in healthy subjects and to evaluate factors associated with this decline using a large cohort in Japan.

Methods

Retrospective cross-sectional and longitudinal studies were performed with healthy subjects aged ≥18 years old who received a medical checkup. Reference values for eGFR were obtained using a nonparametric method and those for decline of eGFR were calculated by mixed model analysis. Relationships of eGFR decline rate with baseline variables were examined using a linear least-squares method.

Results

In the cross-sectional study, reference values for eGFR were obtained by gender and age in 72,521 healthy subjects. The mean (±SD) eGFR was 83.7±14.7ml/min/1.73m². In the longitudinal study, reference values for eGFR decline rate were obtained by gender, age, and renal stage in 45,586 healthy subjects. In the same renal stage, there was little difference in the rate of decline regardless of age. The decline in eGFR depended on the renal stage and was strongly related to baseline eGFR, with a faster decline with a higher baseline eGFR and a slower decline with a lower baseline eGFR. The mean (±SD) eGFR decline rate was ‒1.07±0.42ml/min/1.73m²/year (‒1.29±0.41%/year) in subjects with a mean eGFR of 81.5±11.6ml/min/1.73m².

Conclusions

The present study clarified for the first time the reference values for the rate of eGFR decline stratified by gender, age, and renal stage in healthy subjects. The rate of eGFR decline depended mainly on baseline eGFR, but not on age, with a slower decline with a lower baseline eGFR.     

Estimated Glomerular Filtration Rate,All-Cause Mortality and Cardiovascular Diseases Incidence in a Low Risk Population: The MATISS Study

Background

Chronic kidney disease (CKD) independently increases the risk of death and cardiovascular disease (CVD) in the general population. However, the relationship between estimated glomerular filtration rate (eGFR) and CVD/death risk in a general population at low risk of CVD has not been explored so far.

Design

Baseline and longitudinal data of 1465 men and 1459 women aged 35-74 years participating to the MATISS study, an Italian general population cohort, were used to evaluate the role of eGFR in the prediction of all-cause mortality and incident CVD.

Methods

Bio-bank stored sera were used to evaluate eGFR at baseline. Serum creatinine was measured on thawed samples by means of an IDMS-calibrated enzymatic method. eGFR was calculated by the CKD-EPI formula.

Results

At baseline, less than 2% of enrolled persons had eGFR < 60 mL/min/1.73m² and more than 70% had a 10-year cardiovascular risk score < 10%. In people 60 or more years old, the first and the last eGFR quintiles (<90 and ≥109 mL/min/1.73m², respectively) were associated to an increased risk for both all-cause mortality (hazard ratio 1.6, 95% confidence interval 1.2-2.1 and 4.3, 1.6-11.7, respectively) and incident CVD (1.6, 1.0-2.4 and 7.0, 2.2-22.9, respectively), even if adjusted for classical risk factors.

Conclusions

These findings strongly suggest that in an elderly, general population at low risk of CVD and low prevalence of reduced renal filtration, even a modest eGFR reduction is related to all-cause mortality and CVD incidence, underlying the potential benefit to this population of considering eGFR for their risk prediction.     

Kidney Function Decline and Apparent Treatment-Resistant Hypertension in the Elderly

Background

Cross-sectional studies show a strong association between chronic kidney disease and apparent treatment-resistant hypertension, but the longitudinal association of the rate of kidney function decline with the risk of resistant hypertension is unknown.

Methods

The population-based Three-City included 8,695 participants older than 65 years, 4265 of them treated for hypertension. We estimated the odds ratios (OR) of new-onset apparent treatment-resistant hypertension, defined as blood pressure ≥ 140/90 mmHg despite use of 3 antihypertensive drug classes or ≥ 4 classes regardless of blood pressure, associated with the mean estimated glomerular filtration rate (eGFR) level and its rate of decline over 4 years, compared with both controlled hypertension and uncontrolled nonresistant hypertension with ≤ 2 drugs. GFR was estimated with three different equations.

Results

Baseline prevalence of apparent treatment-resistant hypertension and of controlled and uncontrolled nonresistant hypertension, were 6.5%, 62.3% and 31.2%, respectively. During follow-up, 162 participants developed apparent treatment-resistant hypertension. Mean eGFR decline with the MDRD equation was 1.5±2.9 mL/min/1.73 m² per year: 27.7% of the participants had an eGFR ≥3 and 10.1% ≥ 5 mL/min/1.73 m² per year. After adjusting for age, sex, obesity, diabetes, and cardiovascular history, the ORs for new-onset apparent treatment-resistant hypertension associated with a mean eGFR level, per 15 mL/min/1.73m² drop, were 1.23 [95% confidence interval 0.91–1.64] compared to controlled hypertension and 1.10 [0.83–1.45] compared to uncontrolled nonresistant hypertension; ORs associated with a decline rate ≥ 3 mL/min/1.73m² per year were 1.89 [1.09–3.29] and 1.99 [1.19–3.35], respectively. Similar results were obtained when we estimated GFR with the CKDEPI and the BIS1 equations. ORs tended to be higher for an eGFR decline rate ≥ 5 mL/min/1.73m² per year.

Conclusion

The speed of kidney function decline is associated more strongly than kidney function itself with the risk of apparent treatment-resistant hypertension in the elderly.     

A New Equation to Estimate Glomerular Filtration Rate in Chinese Elderly Population

Background

We sought to develop a new equation to estimate glomerular filtration rate (GFR) in Chinese elderly population.

Methods

A total of 668 Chinese elderly participants, including the development cohort (n = 433), the validation cohort (n = 235) were enrolled. The new equation using the generalized additive model, and age, gender, serum creatinine as predictor variables was developed and the performances was compared with the CKD-EPI equation.

Results

In the validation data set, both bias and precision were improved with the new equation, as compared with the CKD-EPI equation (median difference, −1.5 ml/min/1.73 m² vs. 7.4 ml/min/1.73 m² for the new equation and the CKD-EPI equation, [P<0.001]; interquartile range [IQR] for the difference, 16.2 ml/min/1.73 m² vs. 19.0 ml/min/1.73 m² [P<0.001]), as were accuracies (15% accuracy, 40.4% vs. 30.6% [P = 0.02]; 30% accuracy, 71.1% vs. 47.2%, [P<0.001]; 50% accuracy, 90.2% vs. 75.7%, [P<0.001]), allowing improvement in GFR categorization (GFR category misclassification rate, 37.4% vs. 53.2% [P = <0.001]).

Conclusions

A new equation was developed in Chinese elderly population. In the validation data set, the new equation performed better than the original CKD-EPI equation. The new equation needs further external validations. Calibration of the GFR referent standard to a more accurate one should be an useful way to improve the performance of GFR estimating equations.     

Comparison of the Schwartz and CKD-EPI Equations for Estimating Glomerular Filtration Rate in Children,Adolescents, and Adults: A Retrospective Cross-Sectional Study

Background

Estimating kidney glomerular filtration rate (GFR) is of utmost importance in many clinical conditions. However, very few studies have evaluated the performance of GFR estimating equations over all ages and degrees of kidney impairment. We evaluated the reliability of two major equations for GFR estimation, the CKD-EPI and Schwartz equations, with urinary clearance of inulin as gold standard.

Methods and Findings

The study included 10,610 participants referred to the Renal and Metabolic Function Exploration Unit of Edouard Herriot Hospital (Lyon, France). GFR was measured by urinary inulin clearance (only first measurement kept for analysis) then estimated with isotope dilution mass spectrometry (IDMS)–traceable CKD-EPI and Schwartz equations. The participants’ ages ranged from 3 to 90 y, and the measured GFRs from 3 to 160 ml/min/1.73 m². A linear mixed-effects model was used to model the bias (mean ratio of estimated GFR to measured GFR). Equation reliability was also assessed using precision (interquartile range [IQR] of the ratio) and accuracy (percentage of estimated GFRs within the 10% [P10] and 30% [P30] limits above and below the measured GFR). In the whole sample, the mean ratio with the CKD-EPI equation was significantly higher than that with the Schwartz equation (1.17 [95% CI 1.16; 1.18] versus 1.08 [95% CI 1.07; 1.09], p < 0.001, t-test). At GFR values of 60–89 ml/min/1.73 m², the mean ratios with the Schwartz equation were closer to 1 than the mean ratios with the CKD-EPI equation whatever the age class (1.02 [95% CI 1.01; 1.03] versus 1.15 [95% CI 1.13; 1.16], p < 0.001, t-test). In young adults (18–40 y), the Schwartz equation had a better precision and was also more accurate than the CKD-EPI equation at GFR values under 60 ml/min/1.73 m² (IQR: 0.32 [95% CI 0.28; 0.33] versus 0.40 [95% CI 0.36; 0.44]; P30: 81.4 [95% CI 78.1; 84.7] versus 63.8 [95% CI 59.7; 68.0]) and also at GFR values of 60–89 ml/min/1.73 m². In all patients aged ≥65 y, the CKD-EPI equation performed better than the Schwartz equation (IQR: 0.33 [95% CI 0.31; 0.34] versus 0.40 [95% CI 0.38; 0.41]; P30: 77.6 [95% CI 75.7; 79.5] versus 67.5 [95% CI 65.4; 69.7], respectively). In children and adolescents (2–17 y), the Schwartz equation was superior to the CKD-EPI equation (IQR: 0.23 [95% CI 0.21; 0.24] versus 0.33 [95% CI 0.31; 0.34]; P30: 88.6 [95% CI 86.7; 90.4] versus 29.4 [95% CI 26.8; 32.0]). This study is limited by its retrospective design, single-center setting with few non-white patients, and small number of patients with severe chronic kidney disease.

Conclusions

The results from this study suggest that the Schwartz equation may be more reliable than the CKD-EPI equation for estimating GFR in children and adolescents and in adults with mild to moderate kidney impairment up to age 40 y.     

Comparisons between the 2012 New CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Equations and Other Four Approved Equations

Objective

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) reported two equations in 2012: one based on cystatin C concentration (CKD-EPI_2012cys) and the other using both serum creatinine and cystatin C concentrations (CKD-EPI_2012Scr-cys). We compared the adaptability of new formulae with other four equations.

Methods

Participants (n = 788; median age, 54 [range, 19–94] years) were recruited from the First Affiliated Hospital of Nanjing Medical University. The reference glomerular filtration rate (rGFR) was measured by a ⁹⁹mTc-DTPA renal dynamic imaging method, and the estimated glomerular filtration rate (eGFR) was calculated separately by the Chinese adapted Modification of Diet in Renal Disease equation (C-MDRD), MacIsaac, Ma, serum creatinine-based CKD-EPI equation (CKD-EPI_2009Scr), CKD-EPI_2012cys and CKD-EPI_2012Scr-cys equations. We compared the performance of six equations with rGFR.

Results

Median rGFR was 76.35 (interquartile range, 59.03–92.50) mL/min/1.73 m². Compared with CKD-EPI_2009Scr, CKD-EPI_2012Scr-cys formula had better diagnostic value with larger area under the receiver operating characteristic curve (ROC^AUC, 0.879, p = 0.006), especially in young participants (ROC^AUC, 0.883, p = 0.005). CKD-EPI_2012cys equation did not perform better than other available equations. Accuracy (the proportion of eGFR within 30% of rGFR [P₃₀]) of the CKD-EPI_2012Scr-cys equation (77.03%) was inferior only to MacIsaac equation (80.2%) in the entire participants, but performed best in young participants with normal or mildly-injured GFR. Neither of the two new CKD-EPI equations achieved any ideal P₃₀ in the elderly participants with moderately-severely injured GFR. Linear regression analysis demonstrated a consistent result. In this study, CKD-EPI_2012Scr-cys had a relatively better diagnosis consistency of GFR stage between the eGFR and rGFR in the whole cohort.

Conclusion

CKD-EPI_2012Scr-cys appeared less biased and more accurate in overall participants. Neither of the new CKD-EPI equations achieved ideal accuracy in senior participants with moderately-severely injured GFR. A large-scale study with more subjects and cooperating centers to develop new formulae for the elderly is assumed to be necessary.     

Adherence with Dosing Guideline in Patients with Impaired Renal Function at Hospital Discharge

Objectives

To determine the prevalence, determinants, and potential clinical relevance of adherence with the Dutch dosing guideline in patients with impaired renal function at hospital discharge.

Design

Retrospective cohort study between January 2007 and July 2011.

Setting

Academic teaching hospital in the Netherlands.

Subjects

Patients with an estimated glomerular filtration rate (eGFR) between 10-50 ml/min/1.73m² at discharge and prescribed one or more medicines of which the dose is renal function dependent.

Main Outcome Measures

The prevalence of adherence with the Dutch renal dosing guideline was investigated, and the influence of possible determinants, such as reporting the eGFR and severity of renal impairment (severe: eGFR<30 and moderate: eGFR 30-50 ml/min/1.73m²). Furthermore, the potential clinical relevance of non-adherence was assessed.

Results

1327 patients were included, mean age 67 years, mean eGFR 38 ml/min/1.73m². Adherence with the guideline was present in 53.9% (n=715) of patients. Reporting the eGFR, which was incorporated since April 2009, resulted in more adherence with the guideline: 50.7% vs. 57.0%, RR 1.12 (95% CI 1.02-1.25). Adherence was less in patients with severe renal impairment (46.0%), compared to patients with moderate renal impairment (58.1%, RR 0.79; 95% CI 0.70-0.89). 71.4% of the cases of non-adherence had the potential to cause moderate to severe harm.

Conclusion

Required dosage adjustments in case of impaired renal function are often not performed at hospital discharge, which may cause harm to the majority of patients. Reporting the eGFR can be a small and simple first step to improve adherence with dosing guidelines.     

Comparison of Various Equations for Estimating GFR in Malawi: How to Determine Renal Function in Resource Limited Settings?

Background

Chronic kidney disease (CKD) is a probably underrated public health problem in Sub-Saharan-Africa, in particular in combination with HIV-infection. Knowledge about the CKD prevalence is scarce and in the available literature different methods to classify CKD are used impeding comparison and general prevalence estimates.

Methods

This study assessed different serum-creatinine based equations for glomerular filtration rates (eGFR) and compared them to a cystatin C based equation. The study was conducted in Lilongwe, Malawi enrolling a population of 363 adults of which 32% were HIV-positive.

Results

Comparison of formulae based on Bland-Altman-plots and accuracy revealed best performance for the CKD-EPI equation without the correction factor for black Americans. Analyzing the differences between HIV-positive and –negative individuals CKD-EPI systematically overestimated eGFR in comparison to cystatin C and therefore lead to underestimation of CKD in HIV-positives.

Conclusions

Our findings underline the importance for standardization of eGFR calculation in a Sub-Saharan African setting, to further investigate the differences with regard to HIV status and to develop potential correction factors as established for age and sex.     

Estimated Glomerular Filtration Rate and Proteinuria Are Separately and Independently Associated with the Prevalence of Atrial Fibrillation in General Population

Background

Both, proteinuria and a decline in glomerular filtration rate (GFR) are associated with greater cardiovascular mortality. However, few studies have explored that proteinuria and lower GFR are related with prevalent atrial fibrillation (AF).

Methods

This cross-sectional study was based on annual health check-up program of community-based population in Gunma, Japan from April 2011 to March 2012. A total of 20,019 adult participants were included. AF was ascertained by a standard 12-lead electrocardiogram. Cross-sectional association and correlates with prevalent AF were examined using multivariable logistic regression analysis.

Results

The overall prevalence of AF was 0.6% (2.2 % in participants with eGFR < 60 mL▪min^-1･1.73m^-2, 0.4% and 0.2% in those with eGFR 60 to 89 and ≧90 mL▪min^-1･1.73m^-2, p for trend <0.001). The multivariable odds ratio (OR) for AF was 2.86 (95 % CI 1.16 - 7.08, p<0.001) for eGFR< 60 mL▪min^-1▪1.73m^-2 versus eGFR≧ 90 mL▪min^-1▪1.73m^-2. This association remained significant with further adjustment for proteinuria. In addition, proteinuria was also strongly associated with increased prevalence of AF (OR 2.96, 95 % CI 1.55-5.68, p<0.001), an association that remained significant after adjustment for eGFR.

Conclusions

Proteinuria and lower eGFR are separately and significantly associated with prevalence of AF independent of well-established risk factors for AF in general population.     

Short and Long-Term Effects of Telaprevir on Kidney Function in Patients with Hepatitis C Virus Infection: A Retrospective Cohort Study

Background

Recent reports suggest that telaprevir, a protease inhibitor used to treat hepatitis C infection, is associated with decline in kidney function during therapy, particularly in patients with baseline renal impairment.

Methods

Patients treated with telaprevir in a single healthcare network were retrospectively reviewed. Kidney function was determined at baseline, during therapy, and twelve weeks and twelve months after telaprevir discontinuation. Significant creatinine rise during therapy was defined as an increase in serum creatinine ≥ 0.3mg/dL from baseline during treatment with telaprevir.

Results

Between July 2011 to January 2013,seventy-eight patients began treatment. The majority completed the prescribed twelve weeks of telaprevir therapy; 32% discontinued due to side effects. The average rise in serum creatinine during therapy was 0.22mg/dL (standard deviation 0.22mg/dL). Thirty-one percent experienced a significant creatinine rise during therapy. Decline in estimated glomerular filtration rate (eGFR) was lower in those with baseline eGFR < 90 mL/min/1.73m² compared to the group with baseline eGFR ≥ 90 mL/min/1.73m² (12 vs. 18 mL/min/1.73m², P = 0.047). Serum creatinine fully normalized by twelve weeks after cessation of telaprevir in 83% of patients, however experiencing a significant creatinine rise during telaprevir use was associated with a 6.6mL/min/1.73m² decrease in estimated glomerular filtration rate at twelve months in an adjusted model.

Conclusions

Decline in kidney function during therapy with telaprevir is common and is not associated with baseline eGFR < 90mL/min/1.73m² as previously reported.     

Estimating Kidney Function in HIV-Infected Adults in Kenya: Comparison to a Direct Measure of Glomerular Filtration Rate by Iohexol Clearance

Background

More than two-thirds of the world''s HIV-positive individuals live in sub-Saharan Africa, where genetic susceptibility to kidney disease is high and resources for kidney disease screening and antiretroviral therapy (ART) toxicity monitoring are limited. Equations to estimate glomerular filtration rate (GFR) from serum creatinine were derived in Western populations and may be less accurate in this population.

Methods

We compared results from published GFR estimating equations with a direct measure of GFR by iohexol clearance in 99 HIV-infected, ART-naïve Kenyan adults. Iohexol concentration was measured from dried blood spots on filter paper. The bias ratio (mean of the ratio of estimated to measured GFR) and accuracy (percentage of estimates within 30% of the measured GFR) were calculated.

Results

The median age was 35 years, and 60% were women. The majority had asymptomatic HIV, with median CD4+ cell count of 355 cells/mm³. Median measured GFR was 115 mL/min/1.73 m². Overall accuracy was highest for the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation. Consistent with a prior report, bias and accuracy were improved by eliminating the coefficient for black race (85% of estimates within 30% of measured GFR). Accuracy of all equations was poor in participants with GFR 60–90 mL/min/1.73 m² (<65% of estimates within 30% of measured GFR), although this subgroup was too small to reach definitive conclusions.

Conclusions

Overall accuracy was highest for the CKD-EPI equation. Eliminating the coefficient for race further improved performance. Future studies are needed to determine the most accurate GFR estimate for use in individuals with GFR <90 mL/min/1.73 m², in whom accurate estimation of kidney function is important to guide drug dosing. Direct measurement of GFR by iohexol clearance using a filter paper based assay is feasible for research purposes in resource-limited settings, and could be used to develop more accurate GFR estimates in African populations.