Abstract
BackgroundDiabetic nephropathy, a major complication of diabetes, is characterized by progressive renal injury and increased cardiovascular mortality. An increased urinary albumin excretion due dysfunction of the glomerular barrier is an early sign of diabetic nephropathy. An increased urinary excretion of higher molecular weight proteins such as IgM appears with progression of glomerular injury. We aim here to study the prognostic significance of urine IgM excretion in patients with type 1 diabetes mellitus (type 1 diabetic nephropathy).MethodsThis is an observational study of 139 patients with type1 diabetes mellitus (79 males and 60 females) under routine care at the diabetic outpatient clinic at the Lund University Hospital. The median follow-up time was 18 years (1 to 22) years. Urine albumin and urine IgM concentration were measured at time of recruitment.ResultsOverall 32 (14 male and 18 female) patients died in a cardiovascular event and 20 (11 male and 9 female) patients reached end-stage renal disease. Univariate analysis indicated that patient survival and renal survival were inversely associated with urine albumin excretion (RR = 2.9 and 5.8, respectively) and urine IgM excretion (RR = 4.6 and 5.7, respectively). Stratified analysis demonstrated that in patients with different degrees of albuminuria, the cardiovascular mortality rate and the incidence of end-stage renal disease was approximately three times higher in patients with increased urine IgM excretion.ConclusionAn increase in urinary IgM excretion in patients with type 1 diabetes is associated with an increased risk for cardiovascular mortality and renal failure, regardless of the degree of albuminuria.
Highlights
Diabetic nephropathy, a major complication of diabetes, is characterized by progressive renal injury and increased cardiovascular mortality
Univariate Cox-regression analysis identified the following predictors of CV mortality: age (HR = 11.5, 95% confidence intervals (95% CI) 3.5 to 38, P < 0.001), duration of diabetes (HR = 7.8, 95% CI 3 to 20, P < 0.001), mean arterial blood pressure (HR = 3.6, 95% CI 1.6 to 8.1, P = 0.002), serum creatinine (HR = 3.3, 95% CI 1.5 to 7.3, P = 0.004), eGFR (HR = 9.3, 95% CI 3.3 to 27.0, P < 0.001), urinary albumin excretion (HR = 2.9, 95% CI 1.7 to 5.0, P < 0.001) and urinary IgM excretion (HR = 4.6, 95% CI 2.0 to 10.7, P < 0.001)
The predictors of End-stage renal disease (ESRD) were: duration of diabetes (HR = 4.3, 95% CI 1.6 to 12, P =0.005), mean arterial blood pressure (HR = 3.9, 95% CI 1.4 to 10.8, P = 0.009), serum creatinine (HR = 23.3, 95% CI 3.1 to 174, P = 0.002), Glomerular filtration rate (GFR) (HR = 12.4, 95% CI 2.9 to 54.0, P = 0.001), urinary albumin excretion (HR = 5.8, 95% CI 2.4 to 14, P < 0.001) and urinary IgM excretion (HR = 5.7, 95% CI 1.9 to 17, P = 0.002)
Summary
A major complication of diabetes, is characterized by progressive renal injury and increased cardiovascular mortality. An increased urinary albumin excretion due dysfunction of the glomerular barrier is an early sign of diabetic nephropathy. An increased urinary excretion of higher molecular weight proteins such as IgM appears with progression of glomerular injury. Development of DN is associated with an increased risk of cardiovascular (CV) complications and mortality [4,5]. A large interindividual variation in the rate of decline in kidney function and mortality has been reported [3,6]. This highlights the need for identification of risk factors and early predictors of progression. An increased urinary albumin excretion is an early sign of (page number not for citation purposes)
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