Monique E Cho1, Carol Sweeney2, Nora Fino2, Tom Greene2, Nirupama Ramkumar3, Yufeng Huang3, Ana C Ricardo4, Tariq Shafi5, Rajat Deo6, Amanda Anderson7, Katherine T Mills7, Alfred K Cheung3. 1. Division of Nephrology and Hypertension, University of Utah, Salt Lake City, Utah, USA, Monique.Cho@hsc.utah.edu. 2. Division of Epidemiology, University of Utah, Salt Lake City, Utah, USA. 3. Division of Nephrology and Hypertension, University of Utah, Salt Lake City, Utah, USA. 4. Department of Medicine, University of Illinois, Chicago, Illinois, USA. 5. Division of Nephrology, University of Mississippi, Jackson, Mississippi, USA. 6. Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 7. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
Abstract
INTRODUCTION: Prorenin, a precursor of renin, and renin play an important role in regulation of the renin-angiotensin system. More recently, receptor-bound prorenin has been shown to activate intracellular signaling pathways that mediate fibrosis, independent of angiotensin II. Prorenin and renin may thus be of physiologic significance in CKD, but their plasma concentrations have not been well characterized in CKD. METHODS: We evaluated distribution and longitudinal changes of prorenin and renin concentrations in the plasma samples collected at follow-up years 1, 2, 3, and 5 of the Chronic Renal Insufficiency Cohort (CRIC) study, an ongoing longitudinal observational study of 3,939 adults with CKD. Descriptive statistics and multivariable regression of log-transformed values were used to describe cross-sectional and longitudinal variation and associations with participant characteristics. RESULTS: A total of 3,361 CRIC participants had plasma available for analysis at year 1. The mean age (±standard deviation, SD) was 59 ± 11 years, and the mean estimated glomerular filtration rate (eGFR, ± SD) was 43 ± 17 mL/min per 1.73 m2. Median (interquartile range) values of plasma prorenin and renin at study entry were 4.4 (2.1, 8.8) ng/mL and 2.0 (0.8, 5.9) ng/dL, respectively. Prorenin and renin were positively correlated (Spearman correlation 0.51, p < 0.001) with each other. Women and non-Hispanic blacks had lower prorenin and renin values at year 1. Diabetes, lower eGFR, and use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, and diuretics were associated with higher levels. Prorenin and renin decreased by a mean of 2 and 5% per year, respectively. Non-Hispanic black race and eGFR <30 mL/min/1.73 m2 at year 1 predicted a steeper decrease in prorenin and renin over time. In addition, each increase in urinary sodium excretion by 2 SDs at year 1 increased prorenin and renin levels by 4 and 5% per year, respectively. DISCUSSION/ CONCLUSIONS: The cross-sectional clinical factors associated with prorenin and renin values were similar. Overall, both plasma prorenin and renin concentrations decreased over the years, particularly in those with severe CKD at study entry.
INTRODUCTION: Prorenin, a precursor of renin, and renin play an important role in regulation of the renin-angiotensin system. More recently, receptor-bound prorenin has been shown to activate intracellular signaling pathways that mediate fibrosis, independent of angiotensin II. Prorenin and renin may thus be of physiologic significance in CKD, but their plasma concentrations have not been well characterized in CKD. METHODS: We evaluated distribution and longitudinal changes of prorenin and renin concentrations in the plasma samples collected at follow-up years 1, 2, 3, and 5 of the Chronic Renal Insufficiency Cohort (CRIC) study, an ongoing longitudinal observational study of 3,939 adults with CKD. Descriptive statistics and multivariable regression of log-transformed values were used to describe cross-sectional and longitudinal variation and associations with participant characteristics. RESULTS: A total of 3,361 CRIC participants had plasma available for analysis at year 1. The mean age (±standard deviation, SD) was 59 ± 11 years, and the mean estimated glomerular filtration rate (eGFR, ± SD) was 43 ± 17 mL/min per 1.73 m2. Median (interquartile range) values of plasma prorenin and renin at study entry were 4.4 (2.1, 8.8) ng/mL and 2.0 (0.8, 5.9) ng/dL, respectively. Prorenin and renin were positively correlated (Spearman correlation 0.51, p < 0.001) with each other. Women and non-Hispanic blacks had lower prorenin and renin values at year 1. Diabetes, lower eGFR, and use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, and diuretics were associated with higher levels. Prorenin and renin decreased by a mean of 2 and 5% per year, respectively. Non-Hispanic black race and eGFR <30 mL/min/1.73 m2 at year 1 predicted a steeper decrease in prorenin and renin over time. In addition, each increase in urinary sodium excretion by 2 SDs at year 1 increased prorenin and renin levels by 4 and 5% per year, respectively. DISCUSSION/ CONCLUSIONS: The cross-sectional clinical factors associated with prorenin and renin values were similar. Overall, both plasma prorenin and renin concentrations decreased over the years, particularly in those with severe CKD at study entry.
Authors: Rajat Deo; Wei Yang; Abigail M Khan; Nisha Bansal; Xiaoming Zhang; Mary B Leonard; Martin G Keane; Elsayed Z Soliman; Susan Steigerwalt; Raymond R Townsend; Michael G Shlipak; Harold I Feldman Journal: Hypertension Date: 2014-04-21 Impact factor: 10.190
Authors: Harold I Feldman; Lawrence J Appel; Glenn M Chertow; Denise Cifelli; Borut Cizman; John Daugirdas; Jeffrey C Fink; Eunice D Franklin-Becker; Alan S Go; L Lee Hamm; Jiang He; Tom Hostetter; Chi-Yuan Hsu; Kenneth Jamerson; Marshall Joffe; John W Kusek; J Richard Landis; James P Lash; Edgar R Miller; Emile R Mohler; Paul Muntner; Akinlolu O Ojo; Mahboob Rahman; Raymond R Townsend; Jackson T Wright Journal: J Am Soc Nephrol Date: 2003-07 Impact factor: 10.121