ABSTRACT
AIMS/INTRODUCTION: The aim of the present study was to obtain a full view of the changes of urinary complement activation products in the development of diabetic nephropathy and explore their possible significance in the disease process. MATERIALS AND METHODS: A total of 62 patients at different stages of diabetic nephropathy, 20 diabetes patients without nephropathy and 20 healthy persons were enrolled. Urinary complement activation products, including C3a, C5a and C5b-9, were measured, and their associations with the progression of the disease were analyzed. RESULTS: The urinary complement activation products increased markedly since the proteinuria stage, and were parallel with the progression of diabetic nephropathy. More severe renal tubular damage was observed in patients with higher levels of urinary complement activation products. The urinary complement activation products levels correlated closely with renal tubulointerstitial injury score and relative tubular interstitial volume. Multivariate regression analysis showed that elevated urinary complement activation products were independent risk factors for tubular injury in diabetic nephropathy patients. CONCLUSIONS: Urinary complement activation might have a role in renal tubular interstitial injury in patients with diabetic nephropathy, especially in patients at a later stage of the disease.
Subject(s)
Biomarkers/urine , Complement Activation , Complement C3a/urine , Complement C5a/urine , Complement Membrane Attack Complex/urine , Diabetic Nephropathies/pathology , Kidney Tubules/pathology , Biomarkers/blood , Case-Control Studies , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/etiology , Diabetic Nephropathies/urine , Disease Progression , Female , Follow-Up Studies , Humans , Kidney Tubules/injuries , Kidney Tubules/metabolism , Male , Middle Aged , PrognosisABSTRACT
BACKGROUND: Complement has been suggested to be involved in diabetic nephropathy (DN), but the exact significance and underlying mechanisms remain unclear. Data about renal local complement activation in DN patients is scarce. The purpose of the study was to clarify the significance and mechanism of renal local complement activation in DN. METHODS: Sixty-two biopsy-proven DN patients were recruited. Renal expression of C1Q, factor B, C5b-9, MBL and MBL-associated serine protease 1 (MASP1) were detected and associated with the kidney damage. RESULTS: C5b-9, MBL and MASP1 was found to increase with the progression of DN. Especially, the level of C5b-9, MBL and MASP1 in tubular interstitium was closely associated with the damage degree of tubular interstitium. In addition, MBL and MASP1 co-localized and their levels in tubular interstitium correlated with the levels of C5b-9 in tubules and tubular interstitium. CONCLUSION: Increased renal local complement activation was present in DN patients and might contribute to the kidney damage, especially tubular interstitial damage. MBL pathway might play an important role in renal tubular interstitial complement activation. Methods against complement activation or MBL pathway might be effective in reducing renal tubular interstitial damage in DN patients.
