Update on pathogenesis and diagnosis flow of normoalbuminuric diabetes with renal insufficiency

Abstract

In recent decades, the prevalence of diabetic kidney disease has remained stable and appears to be a wide heterogeneity. Normoalbuminuric diabetes with renal insufficiency, which is characterized by a decline in the glomerular filtration rate in the absence of albuminuria, has been identified as an albuminuria-independent phenotype of diabetic kidney disease. Epidemiological data demonstrate that normoalbuminuric phenotype is prevalent. Compared to albuminuric phenotype, normoalbuminuric phenotype has distinct clinical characteristics and a wide heterogeneity of pathological features. Currently, the pathogenesis of normoalbuminuric phenotype remains unclear. Additionally, the flow of diagnosing normoalbuminuric phenotype is not perfect. In this article, we review the latest studies addressing the epidemiology, clinical characteristics, and pathology of normoalbuminuric phenotype. Based on the studies of clinical features and renal histopathologic changes, we attempt to propose an underlying pathogenesis model and a flow chart for diagnosing normoalbuminuric phenotype.

New strategies to improve clinical outcomes for diabetic kidney disease

“…Increasing permeability to albumin, marked by high levels of albuminuria, results from progressive glomerular injury [ 15 ]. Albuminuria typically develops prior to loss of filtration, but eGFR decline may also occur without the occurrence of albuminuria in DKD [ 16 – 18 ]. In people who experience a decline in eGFR without albuminuria, the kidney tissue typically shows prominent vascular lesions and interstitial fibrosis [ 18 ].…”

“…Albuminuria typically develops prior to loss of filtration, but eGFR decline may also occur without the occurrence of albuminuria in DKD [ 16 – 18 ]. In people who experience a decline in eGFR without albuminuria, the kidney tissue typically shows prominent vascular lesions and interstitial fibrosis [ 18 ]. Table 1 provides a description of typical findings of glomerular lesion biopsies common in DKD.…”

Non Proteinuric Diabetic Kidney Disease: A Narrative Review

“…In diabetic patients with proteinuria, hyperglycaemia can lead to activation of inflammatory pathways and reactive oxygen species that cause inflammation, fibrosis, and vascular permeability [4,25].…”

“…Approximately 40% of all patients diagnosed with type 2 diabetes mellitus (T2DM) eventually develop diabetic kidney disease (DKD); this condition may lead to end-stage renal failure (ESRF), cardiovascular disease and premature death [1][2][3][4][5][6][7][8][9][10]. Albuminuria followed by a decline in glomerular filtration rate (GFR), has been long considered to be the pathognomonic sign of DKD [4][5][6][7]11].…”

“…Approximately 40% of all patients diagnosed with type 2 diabetes mellitus (T2DM) eventually develop diabetic kidney disease (DKD); this condition may lead to end-stage renal failure (ESRF), cardiovascular disease and premature death [1][2][3][4][5][6][7][8][9][10]. Albuminuria followed by a decline in glomerular filtration rate (GFR), has been long considered to be the pathognomonic sign of DKD [4][5][6][7]11]. However, this notion has been recently challenged, as it has been recognized that some patients with T2DM develop chronic kidney disease without albuminuria [1][2][3][4][5][6][7][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26].…”