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Radhakrishnan J.,Columbia University | Remuzzi G.,Azienda Ospedaliera Papa Giovanni XXIII | Saran R.,University of Michigan | Williams D.E.,Centers for Disease Control and Prevention | And 18 more authors.
Kidney International | Year: 2014

Chronic kidney disease is now recognized to be a worldwide problem associated with significant morbidity and mortality and there is a steep increase in the number of patients reaching end-stage renal disease. In many parts of the world, the disease affects younger people without diabetes or hypertension. The costs to family and society can be enormous. Early recognition of CKD may help prevent disease progression and the subsequent decline in health and longevity. Surveillance programs for early CKD detection are beginning to be implemented in a few countries. In this article, we will focus on the challenges and successes of these programs with the hope that their eventual and widespread use will reduce the complications, deaths, disabilities, and economic burdens associated with CKD worldwide. © 2014 International Society of Nephrology. Source


Imai E.,Nakayamadera Imai Clinic | Haneda M.,Asahikawa University | Chan J.C.N.,Chinese University of Hong Kong | Yamasaki T.,Daiichi Sankyo | And 3 more authors.
Nephrology Dialysis Transplantation | Year: 2013

BackgroundProteinuria is a major predictor for progression of renal disease, including diabetic nephropathy. In a post hoc analysis of the ORIENT, a double-blinded randomized trial of 566 type 2 diabetic patients with nephropathy, we examined the risk association of composite renal outcome [end-stage renal disease, ESRD, doubling of serum creatinine (SCr) and death] with baseline, change and residual urinary protein/creatinine ratio (UPCR).MethodsWe estimated the hazard ratios (HRs) with 95% confidence interval (CI) of composite renal outcome with baseline UPCR (low <1.0 g/gCr; moderate ≥1.0 g/gCr, <3.0 g/gCr and high ≥3.0 g/gCr) as well as percentage reduction of UPCR (Δ) (worsening: <0%; moderate: ≥0%, <30% and high ≥30%) and residual UPCR at 24 weeks (remission <1.0 g/gCr; moderate ≥1.0 g/gCr, <3.0 g/gCr and heavy ≥3.0 g/gCr).ResultsCompared with the low group with baseline UPCR < 1.0g/gCr, the respective HRs with 95% CI in the moderate and high UPCR groups were 3.02 (1.76-5.19) and 9.24 (5.43-15.73). Compared with patients with a worsening UPCR (<0%) at 24 weeks, the HR was 0.54 (0.39-0.74) in those with ≥0%, <30% ΔUPCR and 0.43 (0.31-0.61) in those with ≥30% ΔUPCR. Compared with the remission at 24 weeks, the HR was 2.12 (1.28-3.49) in moderate residual proteinuria and 4.59 (2.74-7.69) in heavy residual proteinuria. Compared with patients with residual UPCR ≥1.0 g/gCr and ΔUPCR <30%, the HR in those with ΔUPCR≥30% and residual UPCR<1.0 g/gCr was 0.38 (0.22-0.64).ConclusionsIn patients with type 2 diabetes and overt nephropathy, over 30% reduction of UPCR compared with baseline and/or residual UPCR<1.0 g/gCr at 24 weeks predicted renoprotection. These values may be used as targets to guide anti-proteinuric and renoprotective therapy in diabetic nephropathy.Trial registrationClinicalTrials. gov NCT00141453. © 2013 The Author. All rights reserved. Source


Horio M.,Osaka University | Imai E.,Nakayamadera Imai Clinic | Yasuda Y.,Nagoya University | Watanabe T.,Fukushima Medical University | Matsuo S.,Nagoya University
Clinical and Experimental Nephrology | Year: 2014

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 m2, 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 m2, 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. © 2013 Japanese Society of Nephrology. Source


Imai E.,Nakayamadera Imai Clinic | Haneda M.,Asahikawa University | Yamasaki T.,Daiichi Sankyo | Kobayashi F.,Daiichi Sankyo | And 4 more authors.
Hypertension Research | Year: 2013

Combination therapy with angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors (ACEIs) requires further evaluation in patients with diabetic nephropathy and hypertension. In a post hoc analysis of the Olmesartan Reducing Incidence of Endstage renal disease in diabetic Nephropathy Trial with hypertension, we examined the effects of olmesartan on renal and cardiovascular outcomes in the presence or absence of an ACEI. Among 563 patients randomized to receive either olmesartan (n=280) or placebo (n=283), 73.5% (n=414) received a concomitant ACEI. Compared with placebo, olmesartan significantly reduced proteinuria in both the ACEI-treated and non-ACEI-treated groups. The respective changes in the urinary protein creatinine ratio in the olmesartan-treated and placebo-treated groups were -32.6% and +21.1% without an ACEI (P=0.001) and -17.0% and +2.2% with an ACEI (P=0.028). In the olmesartan group, 115 patients developed primary renal outcomes (41.1%) compared with 129 (45.6%) in the placebo group (hazard ratio (HR): 0.97, P=0.787). The respective HRs in the ACEI-treated and non-ACEI-treated groups were 1.02 (P=0.891) and 0.84 (P=0.450). 40 olmesartan-treated patients (14.3%) and 53 placebo-treated patients (18.7%) developed secondary cardiovascular outcomes (HR: 0.65, P=0.042). The respective HRs in the ACEI-treated and non-ACEI-treated groups were 0.69 (P=0.129) and 0.51 (P=0.129). Olmesartan was well tolerated. Dual blockade treatment caused more hyperkalemia than monotherapy. In patients with diabetic nephropathy and hypertension, olmesartan significantly reduced proteinuria, independent of ACEI treatment and cardiovascular outcome but failed to show additional renal benefit compared with ACEI treatment alone. The cardiovascular benefit of dual treatment requires further evaluation. © 2013 The Japanese Society of Hypertension All rights reserved. Source


Horio M.,Osaka University | Imai E.,Nakayamadera Imai Clinic | Yasuda Y.,Nagoya University | Watanabe T.,Fukushima Medical University | Matsuo S.,Nagoya University
Clinical and Experimental Nephrology | Year: 2013

Background: Japanese GFR equations based on serum creatinine (Scr) (Eq cr), serum cystatin C (Scys) (Eqcys) and average value of Eqcr and Eqcys (Eqaverage), and coefficient-modified CKD-EPI equations based on Scr (CKD-EPIcr), Scys (CKD-EPIcys) and Scys in combination with Scr (CKD-EPI cr-cys) are now available for Japanese subjects. Performance of these equations has not been well evaluated in subjects stratified by GFR. Therefore, the bias, precision and accuracy of the GFR equations were compared in Japanese subjects stratified by measured GFR. Methods: Three hundred fifty Japanese subjects were included for validation. These subjects were stratified by measured GFR (0-29, 30-59, 60-89, 90-119 ml/min/1.73 m2 and total). Japanese equations (Eqcr, Eqcys and Eqaverage) were compared with coefficient-modified CKD-EPI equations (0.813 × CKD-EPIcr, CKD-EPIcys and 0.908 × CKD-EPI cr-cys), respectively. GFR was measured by inulin renal clearance. Standardized Scr was measured by enzymatic method. Standardized Scys was measured by colloidal gold immunoassay. Results: Bias and accuracy were not significantly different between Japanese GFR equations and coefficient-modified CKD-EPI equations in all mGFR ranges. The precision of Eqcr was significantly better in GFR 0-29 ml/min/1.73 m2 and significantly worse in GFR 60-89 and GFR 90-119 ml/min/1.73 m2 compared with 0.813 × CKD-EPIcr. The precision of Eqcys was significantly better in GFR 30-59 and GFR 60-89 ml/min/1.73 m2 compared with CKD-EPIcys. The precision of Eqaverage was significantly better in GFR 30-59 ml/min/1.73 m2 and significantly worse in GFR 90-119 ml/min/1.73 m2 compared with 0.908 × CKD-EPIcr-cys. Conclusion: Japanese GFR equations performed well in subjects with GFR under 60 ml/min/1.73 m2 compared with the coefficient-modified CKD-EPI equations. © 2012 Japanese Society of Nephrology. Source

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