The ratio of epidermal growth factor to monocyte chemotactic peptide-1 in the urine predicts renal prognosis in IgA nephropathy

Abstract

The production of cytokines by resident and non-resident renal cells during immunoglobulin A nephropathy (IgAN) plays a key role in the progression of renal damage. The aim of this study was to determine if measurements of urinary epidermal growth factor (EGF) and monocyte chemotactic peptide-1 (MCP-1), at the time of renal biopsy, were a predictor of end-stage renal disease (ESRD) in a cohort of 132 patients with biopsy-proven IgAN. Outcome measures were a doubling of the baseline serum creatinine (sCr) and/or ESRD. Patients with ratios of EGF/MCP-1 in the lowest tertile had a significant decline in renal survival, while patients in the highest tertile maintained 100% renal survival at 48 and 84 months of follow-up. Multivariate Cox's regression analysis showed that the urine EGF/MCP-1 ratio was an independent prognostic factor and indirectly correlated with the combined outcome. The predictive value was also measured by the area under the receiver operating characteristic curve (ROC). The area of the EGF/MCP-1 ratio was significantly higher than that of EGF or MCP-1 alone, histologic grade, creatinine clearance, or proteinuria. Our study suggests that the urinary EGF/MCP-1 ratio may be used as a prognostic marker of ESRD for patients with IgAN.

Effect of Protein Kinase Cβ Inhibition on Renal Hemodynamic Function and Urinary Biomarkers in Humans With Type 1 Diabetes: A Pilot Study

“…Our second major finding was that ruboxistaurin was associated with reductions in GFR and filtration fraction without affecting ERPF in hyperfiltration subjects but was not associated with such reductions in normofiltration subjects. Furthermore, the change in the urinary biomarkers in hyperfiltration subjects was consistent with protection against renal injury (a decline in MCP-1 and a rise in the EGF-to-MCP-1 ratio) (12). Although we cannot determine the precise pathway responsible for these hemodynamic and molecular effects, we favor the theory that ruboxistaurin may have inhibited the effects of angiotensin II, leading to vasodilatation and a fall in GFR.…”

Urine Epidermal Growth Factor, Monocyte Chemoattractant Protein-1 or Their Ratio as Biomarkers for Interstitial Fibrosis and Tubular Atrophy in Primary Glomerulonephritis

“…On the other hand, epidermal growth factor (EGF), a peptide growth factor produced by the ascending loop of Henle and the distal convoluted tubule, seem to have a protective role in tubulointerstitial damage. Decreased renal EGF expression has been found in chronic kidney disease [13], and decreased urine EGF levels have been found in IgA nephropathy (IgAN) patients with advanced histopathological lesions [14,15].…”

Association of Urinary Laminin G-Like 3 and Free K Light Chains with Disease Activity and Histological Injury in IgA Nephropathy

“…Interestingly, we previously found that urinary EGF excretion was a strong predictor of disease outcome in IgAN (7,48). Finally, in an animal model of brain ischemia, LG3 was shown to be neuroprotective and antiproliferative in brain endothelial cells (49).…”

“…In the last decade, a few noninvasive diagnostic tests for detecting IgAN and a series of prognostic biomarkers have been suggested (4)(5)(6)(7)(8)(9)(10)(11)(12). However, the ability to accurately predict individual patient-level risk at the time of diagnosis or during early followup remains limited and mainly relies on clinical and histologic features (13).…”