BACKGROUND: Reliable biomarkers are needed to identify patients with glomerular disease at risk of progression. Transforming growth factor beta 1 (TGF-β1) and monocyte chemotactic protein 1 (MCP-1) play key roles in promoting renal tissue injury. Whether their urinary measurement adds value to current predictors of progression is uncertain. METHODS: We enrolled patients with diabetic (n=53) and nondiabetic (n=47) proteinuric renal disease and retrospectively studied their rate of renal function decline over a defined period of 2 years. We simultaneously measured urinary protein, MCP-1 and TGF-β1, standardized to urinary creatinine. RESULTS: The initial estimated glomerular filtration rate, proteinuria and rate of renal function decline (slope) were 36 ml/min per 1.73 m2, 1.1 g/day and -4.0 ± 7.2 ml/ min per 1.73 m2 year. Median urinary TGF-β1 and MCP- 1 levels were 0.3 (range 0.0-28.1) and 18 (range 3-370) ng/mmol of creatinine, respectively. Urinary protein and MCP-1 to creatinine ratios were associated with slope, and this applied to both diabetic and nondiabetic patients separately. Urinary TGF-β1 showed no relation to slope. However, the majority of its measurements were below the suggested reproducibility threshold. Using linear regression, both normalized urinary protein and MCP-1 were independently associated with the slope. Adding urinary MCP-1 to the model statistically raised the adjusted R2 from 0.35 to 0.40, refining patient risk stratification. Using cutoffs for urinary protein and MCP-1 obtained by receiver operating characteristic curves, the risk of progression was confidently determined in 80% of patients. CONCLUSION: Urinary MCP-1 is a marker of renal function decline in diabetic and nondiabetic proteinuric renal disease, independent of and additive to proteinuria.
BACKGROUND: Reliable biomarkers are needed to identify patients with glomerular disease at risk of progression. Transforming growth factor beta 1 (TGF-β1) and monocyte chemotactic protein 1 (MCP-1) play key roles in promoting renal tissue injury. Whether their urinary measurement adds value to current predictors of progression is uncertain. METHODS: We enrolled patients with diabetic (n=53) and nondiabetic (n=47) proteinuric renal disease and retrospectively studied their rate of renal function decline over a defined period of 2 years. We simultaneously measured urinary protein, MCP-1 and TGF-β1, standardized to urinary creatinine. RESULTS: The initial estimated glomerular filtration rate, proteinuria and rate of renal function decline (slope) were 36 ml/min per 1.73 m2, 1.1 g/day and -4.0 ± 7.2 ml/ min per 1.73 m2 year. Median urinary TGF-β1 and MCP- 1 levels were 0.3 (range 0.0-28.1) and 18 (range 3-370) ng/mmol of creatinine, respectively. Urinary protein and MCP-1 to creatinine ratios were associated with slope, and this applied to both diabetic and nondiabeticpatients separately. Urinary TGF-β1 showed no relation to slope. However, the majority of its measurements were below the suggested reproducibility threshold. Using linear regression, both normalized urinary protein and MCP-1 were independently associated with the slope. Adding urinary MCP-1 to the model statistically raised the adjusted R2 from 0.35 to 0.40, refining patient risk stratification. Using cutoffs for urinary protein and MCP-1 obtained by receiver operating characteristic curves, the risk of progression was confidently determined in 80% of patients. CONCLUSION: Urinary MCP-1 is a marker of renal function decline in diabetic and nondiabetic proteinuric renal disease, independent of and additive to proteinuria.
Authors: Jason H Greenberg; Alison G Abraham; Yunwen Xu; Jeffrey R Schelling; Harold I Feldman; Venkata S Sabbisetti; Joachim H Ix; Manasi P Jogalekar; Steven Coca; Sushrut S Waikar; Michael G Shlipak; Bradley A Warady; Ramachandran S Vasan; Paul L Kimmel; Joseph V Bonventre; Michelle Denburg; Chirag R Parikh; Susan Furth Journal: J Am Soc Nephrol Date: 2021-09-20 Impact factor: 14.978
Authors: Girish N Nadkarni; Veena Rao; Faramarz Ismail-Beigi; Vivian A Fonseca; Sudhir V Shah; Michael S Simonson; Lloyd Cantley; Prasad Devarajan; Chirag R Parikh; Steven G Coca Journal: Clin J Am Soc Nephrol Date: 2016-05-17 Impact factor: 8.237
Authors: Xiangling Wang; John C Lieske; Mariam P Alexander; Muthuvel Jayachandran; Aleksandar Denic; Jerry Mathew; Lilach O Lerman; Walter K Kremers; Joseph J Larson; Andrew D Rule Journal: Am J Nephrol Date: 2016-06-10 Impact factor: 3.754