Association between mannose-binding lectin, high-sensitivity C-reactive protein and the progression of diabetic nephropathy in type 1 diabetes

Abstract

Aims/hypothesis Diabetic nephropathy has been associated with low-grade inflammation and activation of the complement system in cross-sectional studies. Data from prospective studies are sparse. We investigated the associations of the complement activator mannose-binding lectin (MBL) and the inflammatory marker high-sensitivity C-reactive protein (hsCRP) with the development of nephropathy in a large prospective study of patients with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study. Methods Baseline MBL and hsCRP were measured in 1,564 type 1 diabetes patients from the FinnDiane study, of whom 1,010 had a normal albumin excretion rate, 236 had microalbuminuria and 318 had macroalbuminuria. The main outcome was progression in renal disease during follow-up. Results Both baseline MBL (p=0.038) and hsCRP (p<0.001) increased with increasing level of albuminuria. During 5.8± 2.2 years of follow-up, progression to a higher albuminuria level or end-stage renal disease (ESRD) occurred in 201 patients. MBL levels were higher in progressors compared with non-progressors at all steps of progression, and in a covariate adjusted multivariate Cox-regression analysis MBL levels above the median were significantly associated with progression from macroalbuminuria to ESRD (hazard ratio 1.88, 95% CI 1.06-3.32, p=0.030). In a univariate analysis, hsCRP levels above the median were significantly associated with progression from normal albumin excretion rate to microalbuminuria, but the association was only borderline significant after adjustment for covariates (hazard ratio 1.56, 95% CI 0.97-2.51, p=0.068). Conclusions/interpretation This study demonstrates that concentrations of both MBL and hsCRP are associated with the progression of renal disease in type 1 diabetes.

Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

“…The association between MBL and diabetic nephropathy has been observed in several clinical studies (2)(3)(4)(5)(6)(7)(8). Also, the MBL2 genotype in the present cohort was marginally unequally distributed between patients with or without diabetic nephropathy.…”

“…Several studies have demonstrated the close association between the lectin pathway of complement activation and diabetic nephropathy. In particular, high concentrations of the carbohydrate pattern-recognition molecule mannan-binding lectin (MBL), which initiates complement activation, are linked to diabetic nephropathy defined by urinary albumin excretion rate (2)(3)(4)(5)(6)(7)(8). In the present cohort, we previously showed the cross-sectional association between MBL2 genotype and diabetic nephropathy (2).…”

Distinct Longitudinal Associations of MBL, MASP-1, MASP-2, MASP-3, and MAp44 With Endothelial Dysfunction and Intima–Media Thickness

“…7,27 This is supported by studies in ischemia-reperfusion injury, rheumatoid arthritis, or diabetic nephropathy, in which high MBL was associated with cardiovascular and renal damage. 10,13,14,30,31 We observed that participants with high plasma MBL had lower cIMT. This confirms a previously reported beneficial role of MBL in vascular integrity in a large study.…”

Pathogenic role of mast cells in the development of diabetic nephropathy: a study of patients at different stages of the disease

“…In vitro studies have demonstrated that C3a is the [35,36]. Activation of complement, which can lead to the generation of C3a, has also been demonstrated to increase in diabetic nephropathy [37]. Thus, we suggest that increased complement activation might contribute to the recruitment and activation of MCs.…”