ReviewThe emerging concept of chronic kidney disease without clinical proteinuria in diabetic patientsNéphropathie diabétique sans protéinurie: apparition d’un concept nouveau
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.
References (37)
- et al.
Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus
Lancet
(1982) - et al.
Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64)
Kidney Int
(2003) - et al.
In patients with type 1 diabetes and new-onset microalbuminuria the development of advanced chronic kidney disease may not require progression to proteinuria
Kidney Int
(2010) - et al.
Histopathology of diabetic nephropathy
Semin Nephrol
(2007) - et al.
for the DEMAND investigators. Prevalence and risk factors for microalbuminuria in a referred cohort of type II diabetic patients: A global perspective
Kidney International
(2006) - et al.
Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion
Acta Endocrinol
(1982) - et al.
Predicting diabetic nephropathy in insulin-dependent patients
N Engl J Med
(1984) - et al.
Incipient nephropathy in type 1 (insulin-dependent) diabetes
Diabetologia
(1984) - et al.
Similar risks of nephropathy in patients with type I or type II diabetes mellitus
Nephrol Dial Transplant
(1989) - et al.
Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74
Diabetes
(2006)
Microalbuminuria and the risk for early progressive renal function decline in type 1 diabetes
J Am Soc Nephrol
Epidemiology of Diabetes Interventions and Complications Study Group. Development and progression of renal insufficiency with and without albuminuria in adults with type 1 diabetes in the diabetes control and complications trial and the epidemiology of diabetes interventions and complications study
Diabetes Care
Normoalbuminuric renal-insufficient diabetic patients: a lower-risk group
Diabetes Care
Initial angiotensin receptor blockade-induced decrease in albuminuria is associated with long-term renal outcome in type 2 diabetic patients with microalbuminuria: a post hoc analysis of the IRMA-2 trial
Diabetes Care
Renal changes in long-term type 1 (insulin-dependent) diabetic patients with and without clinical nephropathy: a light microscopic, morphometric study of autopsy material
Diabetologia
Low glomerular filtration rate in normoalbuminuric Type 1 diabetic patients. An indicator of more advanced glomerular lesions
Diabetes
Renal Pathology Society Pathologic classification of diabetic nephropathy
J Am Soc Nephrol
Renal endpoints in renal and cardiovascular randomized clinical trials: time for a consensus?
Fundam Clin Pharmacol
Cited by (71)
The potential use of urinary transferrin, urinary adiponectin, urinary Retinol Binding Protein, and serum zinc alpha 2 glycoprotein levels as novel biomarkers for early diagnosis of diabetic nephropathy: A case-control study
2022, Diabetes and Metabolic Syndrome: Clinical Research and ReviewsCitation Excerpt :The four biomarkers' levels were significantly higher in microalbuminuric patients compared to control subjects and normoalbuminuric patients. Glomerular damage in DN leads to proteinuria [33]. Some patients with T2DM may have progressive nephropathy with decreased eGFR, leading to ESRD without significant proteinuria [34].
SGLT2 inhibitors: A new era for our patients
2021, Nephrologie et TherapeutiqueThe Role of Glomerular Epithelial Injury in Kidney Function Decline in Patients With Diabetic Kidney Disease in the TRIDENT Cohort
2021, Kidney International ReportsUse of ACEi/ARBs, SGLT2 inhibitors and MRAs can help us reach the therapeutic ceiling in CKD
2024, Clinical Kidney Journal