Non-proteinuric diabetic nephropathy is the main cause of chronic kidney disease: Results of a general population survey in Spain

Abstract

Background

Diabetic nephropathy traditionally produces significant proteinuria prior to the development of renal impairment. However, this clinical paradigm has recently been questioned. The current study evaluated the impact of diabetes mellitus on the prevalence of renal disease in general population.

Methodology

Data from of the HERMEX survey, an observational, cross sectional, population based study were used. The final sample included 2813 subjects (mean age 51.2 years, 53.5% female). Four hundred patients have diabetes. Urinary albumin excretion (UAE) rate was analyzed and glomerular filtration rate (GFR) was estimated using the CKD-EPI formula.

Results

Among participants without diabetes, 2.9%(2.2–3.6) had a GFR < 60 ml/min. Prevalence of abnormal UAE in population without diabetes was 3.3% (2.6–4.0). The global prevalence of renal disease was 5.6%(4.8–6.6). Prevalence of GFR < 60 ml/min in subjects with diabetes was 8.8%(6.4–11.9)(p < 0.001,Chi-square test). Prevalence of abnormal UAE in population with diabetes was 14.1%(7.7–19.8)(p <  0.001,Chi-square test). CKD prevalence was 20.3%(16.6–24.6)(p < 0.001,Chi-square test). The logistic regression analysis showed a positive independent association of CKD with age, high blood pressure and albuminuria. No significant relationship was found with diabetes mellitus

Conclusions

CKD is more prevalent in population with diabetes. Nevertheless, most of patients with diabetes and CKD have no albuminuria. An increased cardiovascular burden seems to produce this clinical presentation.

Introduction

Diabetic nephropathy (DN) is already the most common cause of end-stage renal disease (ESRD) in developed nations [1]. Typically, patients proceed through five stages [12–15], i.e. renal hypertrophy and hyperfiltration, renal structural changes without microalbuminuria, microalbuminuria with preserved renal function, significant proteinuria (overt nephropathy) and progressive renal impairment and finally, the development of ESRD [2], [3]. Overt nephropathy is characterized by persistent proteinuria (> 500 mg/24 h) that usually precedes a fall in glomerular filtration rate (GFR). Thereafter, proteinuria tends to increase and GFR commences an inexorable decline. Significant proteinuria has therefore long been regarded as the hallmark of DN [4].

Despite this clearly defined pathway, there have now been reports that in both type 1 and type 2 diabetes mellitus, a proportion of patients may have renal impairment without significant proteinuria or albuminuria, with a variable percentage of patients in these reports having advanced (stage 3–5) kidney disease [5], [6], [7], [8], [9], [10], [11], [12]. It could be interpreted as an accelerated kidney sclerosis due to the interaction of diabetes with other cardiovascular risk factors, but superimposed renovascular disease, senile nephrosclerosis, cholesterol emboli and concomitant additional renal disease have been all suggested to explain this situation [13]. The potential role of episodes of acute kidney injury in these patients at high risk of cardiovascular disease also needs to be elucidated. Drug therapy, in particular the widespread usage of agents blocking the renin-angiotensin system (RAS), such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin 2 receptor blockers (ARBs) may also be exerting an effect [14], [15].

We have evaluated the prevalence of renal disease associated to diabetes mellitus in a Spanish general population sample and the effects of classic cardiovascular risk factors in the pathogenesis of this phenomenon.