Urinary monocyte chemotactic protein 1: marker of renal function decline in diabetic and nondiabetic proteinuric renal disease.

BACKGROUND: Reliable biomarkers are needed to identify patients with glomerular disease at risk of progression. Transforming growth factor beta 1 (TGF-ß1) 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-ß1, 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-ß1 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-ß1 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.

Practical considerations for the use of nonsteroidal anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors in hypertension and kidney disease.

BACKGROUND: Selective cyclo-oxygenase (COX)-2 inhibitors (coxibs) produce the beneficial effects of nonsteroidal anti-inflammatory drugs (NSAIDs) while sparing the COX-1-mediated adverse effects on platelets and the gastrointestinal system. However, due to the presence of constitutive COX-2 in the human kidney, coxibs have the same potential for adverse renal effects as traditional NSAIDs. OBJECTIVE: To provide evidence-based guidelines for the use of traditional NSAIDs and coxibs in patients potentially at risk for renal and associated hemodynamic blood pressure effects. METHODS: All pertinent peer-reviewed papers were retrieved with the usual electronic search tools. RESULTS: Both traditional NSAIDs and coxibs compromise the glomerular filtration rate in patients at increased risk. If there are differences in the blood pressure-raising potential of these drugs, these differences do not appear to be clinically significant. CONCLUSIONS: The blood pressure should be monitored for all patients taking chronic NSAID or coxib therapy. If a clinically significant (4 to 5 mmHg or more) increase in blood pressure is detected, the NSAID or the coxib should be discontinued and replaced with acetaminophen, to which codeine might be added. If the NSAID or the coxib is considered necessary, the increase in blood pressure should be treated. In addition, if the glomerular filtration rate reserve is compromised, all patients (including those taking short term therapy) should be closely monitored for the early detection of signs and symptoms of renal failure.