Abstract
Objective Albuminuria is an early marker of renal impairment and a powerful factor of progression of renal disease in type 2 diabetes (T2D). Approximately, one-third of patients with T2D have micro- or macroalbuminuria and these patients have a high risk of progression toward End Stage Renal Disease (ESRD) as well as increased cardiovascular disease. The aim of this study was to determine the prevalence of remission, regression, persistence, and progression of albuminuria, and to evaluate the impact of change in albuminuria on kidney disease and cardiovascular disease in a prospective cohort of patients with T2D. Methods This is a prospective study. The Ethics Committee of Morocco’s Mohammed V University in Rabat approved the study protocol. Inclusion criteria targeted patients who were type 2 diabetics with albuminuria >30 mg/day, and who had been regularly followed-up in nephrology consultation for at least 36 months. Results Five-hundred twenty-four patients were included. 75.8 and 24.6% of all patients had micro- and macroalbuminuria at enrollment in the study. At the end of the study, 91, 141, 199, and 93 patients had remission, regression, persistence, and progression of albuminuria, respectively. Remission of microalbuminuria to normoalbuminuria was observed in 23.6% of cases. Regression of macroalbuminuria to micro- was observed in 29.9% of cases. Conclusion In our study, the incidence of remission and/or regression of micro- and macroalbuminuria was higher. The incidence of ESRD and the occurrence of cardiac events were greater in the regression, persistence, and progression groups than in the remission of albuminuria group.
Introduction
In type 2 diabetes mellitus (T2D), microalbuminuria is known as an early marker of kidney disease and overt albuminuria is considered as a major risk factor for progression of kidney disease.Citation1–3 Approximately, one-third of the patients with T2D have micro- or macroalbuminuria and these patients have a higher risk of progression towards End Stage Renal Disease (ESRD), as well as increased cardiovascular disease.Citation4 Lowering of the albuminuria is one of the most important elements in the management of diabetic kidney disease. It can be achieved with treatment or spontaneously. While the regression of microalbuminuria is relatively frequent, regression of macroalbuminuria to micro- or normoalbuminuria is rarer in T2D, even with optimized blockage of the renin angiotensin system.Citation5,Citation6 Does the change in albuminuria really influence the evolution of renal disease in T2D? The aim of this study was to determine the prevalence of remission, regression, persistence, and progression of albuminuria and to evaluate the impact of the change in albuminuria on kidney disease and cardiovascular disease in a prospective cohort of patients with T2D.
Methods
This is a prospective study started in January 2008 and conducted at the Reference Center for Chronic Diseases in Oujda, Morocco (Eastern Morocco). The Ethics Committee of Morocco’s Mohammed V University in Rabat approved the study protocol (University Mohamed V Souissi, Rabat). Verbal informed consent was obtained from all participants. Inclusion criteria targeted patients who had confirmed T2D and had been regularly followed in nephrology consultation for at least 36 months. T2D was diagnosed according to the criteria of the World Health Organization.Citation7 All patients included in the study had positive albuminuria (albuminuria > 30 mg/day). Albuminuria was measured from at least two 24-h urine samples and determined as the mean of 24-h urine collections to minimize variability. Excluded from the study were those T2D patients who were pregnant, who had a single kidney, a pathology other than diabetes capable of altering renal function (renal lithiases, Polycystic Kidney Disease, prior long-standing arterial hypertension, a neoplasm, long-term use of nephrotoxic medications), ESRD on admission and/or follow-up of less than 24 months. Patients with type 1 diabetes were excluded from this study.
Cardiac events were defined by history of angina, myocardial infarction, heart failure, and/or coronary revascularization. Remission of albuminuria was defined as returning to normo-albuminuria during the follow-up period; regression of albuminuria was defined as a decrease in urinary excretion of albumin (UEA) of 50% or more from baseline. Persistent albuminuria was defined as a decrease in UEA of less than 50% from baseline or no change from baseline and progression of albuminuria was defined as an increase in UEA of 50% or more from baseline.
Data were analyzed using the Statistical Package for Social Sciences version 13.0 (SPSS, Inc., Chicago, IL). Comparison of quantitative variables between four groups was performed using analysis of variance (ANOVA) if the variable was symmetrically distributed or the Kruskal–Wallis test if the variable was asymmetrically distributed. Comparison of qualitative variables between four groups was performed using the chi-square test. All p-values were two-sided and p < 0.05 was considered statistically significant.
Results
A total of 524 cases of T2D were included. 75.8% and 24.6% of patients had micro- and macroalbuminuria at enrollment in the study. 62.6% and 20.4% of patients had micro and macroalbuminuria at the end of the study. Remission of microalbuminuria to normoalbuminuria was observed in 23.6% of cases. Regression of macroalbuminuria to micro- was observed in 29.9% of cases. The mean of albuminuria in this group was 380 ± 55 mg/day. shows the comparison of clinical and biological parameters between four groups of patients with T2D according to the evolution of albuminuria at the time of enrollment and at the end of the study.
Table 1. Comparison of clinical and biological parameters between the four groups of patients according to the evolution of albuminuria.
Discussion
While remission and/or regression of microalbuminuria has been observed in 40–50% of patients with T2D, regression of macroalbuminuria to microalbuminuria remains less frequent and regression of macroalbuminuria to normoalbuminuria is classically rare.Citation5,Citation8 In our study, among 127 patients with macroalbuminuria at the time of enrollment, only two patients (1.5%) had remission to normoalbuminuria and 38 patients (29.9%) had regression to microalbuminuria. However, in the series of Yokoyama et al.,Citation9 the 5-year cumulative incidence rates of remission of macroalbuminuria to micro- and normoalbuminuria were 58.3 and 18.5%, respectively. This abnormally high incidence was obtained after intensification of treatment for diabetes and the factors associated with progression of albuminuria.
Conclusion
The high incidence of remission and regression of macroalbuminuria to micro- or normoalbuminuria in type 2 diabetes suggests that the concept initially mentioned of the rarity of obtaining remission of macroalbuminuria is not altogether true. This result remains dependent on optimal control of the main factors associated with progression of albuminuria, such as diabetic imbalance, arterial hypertension, hyperlipidemia, smoking, and obesity.
Disclosure statement
The authors declare that they have no conflicts of interest.
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