Elsevier

Diabetes & Metabolism

Volume 38, Issue 4, October 2012, Pages 291-297
Diabetes & Metabolism

Review
The emerging concept of chronic kidney disease without clinical proteinuria in diabetic patientsNéphropathie diabétique sans protéinurie: apparition d’un concept nouveau

https://doi.org/10.1016/j.diabet.2012.04.001Get rights and content

Abstract

The natural history of diabetic nephropathy was defined in the 1980s on the basis of longitudinal studies undertaken in patients with type 1 and type 2 diabetes. However, an increasing number of studies have indicated that certain diabetic patients do not present with the same evolution as was then defined: for example, some often have significant initial deterioration of glomerular filtration rate whereas, in others, microalbuminuria is reduced spontaneously. Chronic kidney disease (CKD) may be accompanied, rather than preceded, by macroalbuminuria, or it may develop in patients with microalbuminuria or even in those with albuminuria levels that revert to normal. CKD can also develop in patients whose albuminuria levels remain normal. Progression to macroalbuminuria is, in fact, less frequent than regression to normoalbuminuria or no change in microalbuminuria status in diabetic patients with microalbuminuria, especially in type 1 diabetes. Some experience progressive deterioration of renal function due to diabetes without developing significant proteinuria: this is seen fairly frequently and can affect 50% of patients with renal insufficiency. Such cases are more often older patients treated with renin–angiotensin system blockers who usually have a history of cardiovascular disease. Evolution to end-stage renal disease is slower in this subgroup of patients, although histological analyses may show surprisingly advanced glomerular lesions. The main parameters of surveillance remain regular monitoring of glycaemia, and control of blood pressure and the evolution of initial albuminuria levels. Nevertheless, why some patients exhibit conventional diabetic nephropathy while others have slower declines in renal function associated with normal albuminuria levels or microalbuminuria is unclear. It is hoped that the new pathological classification of diabetic nephropathy will help in our understanding of these discrepancies.

Résumé

L’histoire naturelle de la néphropathie diabétique a été définie dans les années 1980 à partir d’études longitudinales menées chez des patients diabétiques de type 1 et de type 2. Cependant, des études de plus en plus nombreuses indiquent que certains patients diabétiques n’ont pas l’évolution naturelle telle qu’elle a été décrite dans les années 1980. Ils ont souvent une dégradation initiale de leur débit de filtration glomérulaire très importante; chez d’autres, la microalbuminurie peut régresser spontanément. Le développement d’une insuffisance rénale chronique (IRC) peut être accompagnée mais non précédée d’une macroalbuminurie et peut se développer chez un patient qui reste microalbuminurique ou qui peut régresser au stade de normoalbuminurie. L’IRC peut aussi se développer chez un patient initialement normoalbuminurique qui reste normoalbuminurique jusqu’à un stade avancé. Plus généralement, les patients diabétiques microalbuminuriques ont davantage de risque de régresser au stade de normoalbuminurie que de progresser au stade de macroalbuminurie. Certains développent une altération progressive de la fonction rénale dont la cause est bien le diabète sans développement d’une protéinurie importante: cela semble être une situation assez fréquente et peut atteindre 50 % des patients diabétiques en IRC. Ces patients sont souvent plus âgés, ont un diabète ancien et ont souvent un traitement qui comporte un bloqueur du système rénine-angiotensine et des antécédents cardiovasculaires. Leur vitesse d’évolution vers l’IRC terminale est plus faible. L’analyse histologique montre des lésions glomérulaires évoluées. Au-delà des incertitudes nosologiques et physiopathologiques, il reste que les éléments essentiels de surveillance sont les mêmes: contrôle de l’équilibre glycémique, pression artérielle, albuminurie initiale et son évolution.

Introduction

The natural history of diabetic nephropathy was defined in the 1980s on the basis of longitudinal studies of patients with type 1 and type 2 diabetes. These studies identified stages in the evolution of diabetic nephropathy, and led to the development of strategies of detection and guidelines for use in clinical trials and the identification of therapeutic targets in such patients, and also influenced how the natural history of diabetic nephropathy was taught. Evidently, however, a minority of diabetic patients can develop renal disease other than diabetic nephropathy, as occurs in any individual. More disturbingly, a growing number of studies have indicated that many diabetic patients do not present with the natural evolution described in the 1980s, particularly in terms of the relationship between the development of urinary albumin excretion (UAE) and the glomerular filtration rate (GFR), with some developing a progressive deterioration of renal function that is indeed due to diabetes, but with an evolution unlike that described in the 1980s. Also, it was long considered that there were only a few such patients, but recent findings indicate that this is not the case and, thus, raises pathophysiological, nosological and practical questions regarding diabetes surveillance and treatment.

Section snippets

The conventional natural history of diabetic nephropathy

Four major studies on the natural history of diabetic nephropathy were reported between 1982 and 1984 [1], [2], [3], [4]. In these prospective studies, the authors evaluated the predictive value of microalbuminuria in relation to the development of proteinuria in patients with type 1 diabetes monitored for 6–14 years. The definition of microalbuminuria varied according to the studies, but generally corresponded to a UAE of 15–70 μg/min. Proteinuria was defined as a UAE > 150 μg/min or proteinuria > 

Chronic kidney disease (CKD) without clinical proteinuria in diabetic patients

Nevertheless, ever since, the edifice has begun to crack. First, the UKPDS also showed that the risk factors for developing microalbuminuria and renal insufficiency were not the same: some were shared (raised blood pressure, smoking, poor control of diabetes, history of cardiovascular disease), whereas some were specifically related to the development of microalbuminuria (male gender, increased waist size and/or triglyceride levels) and others were specifically related to the development of

Conclusion

Observational studies have identified another natural history of diabetic nephropathy particularly in type 1 and type 2 diabetes patients. However, it is not clear why some patients develop the ‘classical’ diabetic nephropathy with significant proteinuria, while others have impaired renal function associated with very low levels of proteinuria that sometimes persist as late as end-stage renal disease. This phenomenon may be due to renal vascular disease, as the intrarenal resistive index is

Disclosure of interest

The author declares that he has no conflict of interest concerning this article.

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