Prognosis of chronic kidney disease with normal-range proteinuria: The CKD-ROUTE study

PLOS ONE, Nov 2019

Background Although lower estimated glomerular filtration rate (eGFR) and higher proteinuria are high risks for mortality and kidney outcomes, the prognosis of chronic kidney disease (CKD) in patients with normal-range proteinuria remains unclear. Methods In this prospective cohort study, 1138 newly visiting stage G2–G5 CKD patients were stratified into normal-range and abnormal-range proteinuria groups. Study endpoints were CKD progression (>50% eGFR loss or initiation of dialysis), cardiovascular events, and all-cause death. Results In total, 927 patients who were followed for >6 months were included in the analysis. The mean age was 67 years, and 70.2% were male. During a median follow-up of 35 months, CKD progression, cardiovascular events, and mortality were observed in 223, 110, and 55 patients, respectively. Patients with normal-range proteinuria had a significantly lower risk for CKD progression (hazard ratio, 0.20; 95% confidence interval, 0.10–0.38) than those with abnormal-proteinuria by multivariate Cox proportional hazard analysis. We also analyzed patients with normal-range proteinuria (n = 351). Nephrosclerosis was the most frequent cause of CKD among all patients with normal-range proteinuria (59.7%). During a median follow-up of 36 months, CKD progression, cardiovascular events, and mortality were observed in 10, 28, and 18 patients, respectively. The Kaplan–Meyer analysis demonstrated that the risks of CKD progression and cardiovascular events were not significantly different among CKD stages, whereas the risk of death was significantly higher in patients with advanced-stage CKD. Multivariate Cox proportional hazard analysis showed that the risk of three endpoints did not significantly differ among CKD stages. Conclusion Newly visiting CKD patients with normal-range proteinuria, who tend to be overlooked during health checkups did not exhibit a decrease in kidney function even in advanced CKD stages under specialized nephrology care.

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Prognosis of chronic kidney disease with normal-range proteinuria: The CKD-ROUTE study

January Prognosis of chronic kidney disease with normal-range proteinuria: The CKD-ROUTE study Soichiro Iimori 0 1 Shotaro Naito 0 1 Yumi Noda 0 1 Hidehiko Sato 0 1 Naohiro Nomura 0 1 Eisei Sohara 0 1 Tomokazu Okado 0 1 Sei Sasaki 0 1 Shinichi Uchida 0 1 Tatemitsu Rai 0 1 0 Editor: Tatsuo Shimosawa, The University of Tokyo , JAPAN 1 Department of Nephrology, Tokyo Medical and Dental University , Bunkyo-ku, Tokyo , Japan , 2 Department of Nephrology, Nitobe Memorial Nakano General Hospital , Nakano-ku, Tokyo , Japan Although lower estimated glomerular filtration rate (eGFR) and higher proteinuria are high risks for mortality and kidney outcomes, the prognosis of chronic kidney disease (CKD) in patients with normal-range proteinuria remains unclear. In this prospective cohort study, 1138 newly visiting stage G2±G5 CKD patients were stratified into normal-range and abnormal-range proteinuria groups. Study endpoints were CKD progression (>50% eGFR loss or initiation of dialysis), cardiovascular events, and all-cause death. In total, 927 patients who were followed for >6 months were included in the analysis. The mean age was 67 years, and 70.2% were male. During a median follow-up of 35 months, CKD progression, cardiovascular events, and mortality were observed in 223, 110, and 55 patients, respectively. Patients with normal-range proteinuria had a significantly lower risk for CKD progression (hazard ratio, 0.20; 95% confidence interval, 0.10±0.38) than those with abnormal-proteinuria by multivariate Cox proportional hazard analysis. We also analyzed patients with normal-range proteinuria (n = 351). Nephrosclerosis was the most frequent cause of CKD among all patients with normal-range proteinuria (59.7%). During a median follow-up of 36 months, CKD progression, cardiovascular events, and mortality were observed in 10, 28, and 18 patients, respectively. The Kaplan±Meyer analysis demonstrated that the risks of CKD progression and cardiovascular events were not significantly different among CKD stages, whereas the risk of death was significantly higher in patients with advanced-stage CKD. Multivariate Cox proportional hazard analysis showed that the risk of three endpoints did not significantly differ among CKD stages. - Competing interests: The authors have declared that no competing interests exist. Background Methods Results Conclusion Newly visiting CKD patients with normal-range proteinuria, who tend to be overlooked during health checkups did not exhibit a decrease in kidney function even in advanced CKD stages under specialized nephrology care. Introduction Higher levels of albuminuria are widely demonstrated to precede and predict a faster rate of renal functional decline and to be associated with increased risk of end-stage kidney disease (ESKD), both in general population and in those with various pathophysiologic conditions such as diabetes, hypertension, and primary glomerular diseases [ 1 ]. Large meta-analyses also showed that lower estimated glomerular filtration rate (eGFR) and higher albuminuria were associated with several adverse outcomes [ 2, 3 ]. Findings from experimental and clinical studies suggest an important role for proteinuria in the pathogenesis of disease progression in chronic kidney disease (CKD) [4]. In Japan, the Industrial Safety and Health Law requires employees to undergo medical examination at least once a year. Furthermore, specific health checkups are available to medical insurance subscribers aged 40±74 years. These health checkups involve a dipstick urinary test; however, measurements for urinary protein, urinary albumin, or serum creatinine levels are not included. In a study including data from 574,024 participants (240,594 males and 333,430 females) over the age of 20 years that were from the Japanese general adult population, prevalence of patients with a eGFR of less than 60 ml/min/1.73 m2 and a negative proteinuria by dipstick urinary test was about 10%; such patients will be overlooked by only using dipstick test [ 5 ]. This finding raises a clinical question. Although lower eGFR and higher proteinuria indicate a high risk for mortality and worse kidney outcomes, the prognosis of CKD patients with normal-range proteinuria who may be overlooked during a health checkup, remains uncertain. Therefore, we aimed in this study to characterize the renal prognosis of CKD in patients with normal-range proteinuria under specialized nephrology care. Materials and methods Study design and cohort participants The Chronic Kidney Disease Research of Outcomes in Treatment and Epidemiology (CKD-ROUTE) was a prospective, observational cohort study of a representative Japanese population with stage G2±G5 CKD according to the Kidney Disease Improving Global Outcomes (KDIGO) classification who were not undergoing dialysis [ 6 ]. Details of the study design were previously reported [ 7, 8 ]. Over 1,000 participants were enrolled at the Tokyo Medical and Dental Un (...truncated)


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Soichiro Iimori, Shotaro Naito, Yumi Noda, Hidehiko Sato, Naohiro Nomura, Eisei Sohara, Tomokazu Okado, Sei Sasaki, Shinichi Uchida, Tatemitsu Rai. Prognosis of chronic kidney disease with normal-range proteinuria: The CKD-ROUTE study, PLOS ONE, 2018, Volume 13, Issue 1, DOI: 10.1371/journal.pone.0190493