Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis, and diagnosis

Abstract

Diabetic nephropathy constitutes a devastating complication in patients with type 1 diabetes mellitus, and its diagnosis is traditionally based on microalbuminuria. The aim of this review is to update through the medical literature the suggested early natural course of diabetic nephropathy, the theories behind the pathways of its pathogenesis, and its diagnosis. Poor glycemic control, dyslipidemia, smoking, advanced glycation end products, and environmental and genetic clues play an important role in the development of diabetic nephropathy. Microalbuminuria has been traditionally considered as a primary early marker of microvascular complication unraveling the risk for progress to the advanced stages of chronic kidney disease, but because of our inability to make an early diagnosis of diabetic nephropathy in young patients as well as nonalbuminuric diabetic nephropathy, recently, other additional markers of renal injury like serum and urinary neutrophil gelatinase-associated lipocalin, chitinase-3-like protein 1, cystatin C, and plasma growth differentiation factor 15 have been proposed to unmask early renal dysfunction, even before microalbuminuria supervenes. Copyright © 2016 John Wiley & Sons, Ltd.

NGAL as an Early Predictive Marker of Diabetic Nephropathy in Children and Young Adults with Type 1 Diabetes Mellitus

“…In line with this, cohort studies, including prepubertal children with average diabetes duration of 5–8 years, revealed glomerular base membrane thickening and mesangial expansion [16], while they also disclosed that long-standing nonalbuminuric T1D participants might have significant glomerulopathy lesions [17–19, 21]. Moreover, the prevalence of nonalbuminuric CKD in T1D was recently reported to be 2% and was associated with a higher risk of cardiovascular morbidity as well as all-cause mortality in people with T1D [4, 5]. …”

“…Thus, it represents a significant burden to the patients and the society they live in [2, 3]. Moreover, nonalbuminuric DN has been reported to have a prevalence of 2% among people with T1D and chronic kidney disease (CKD) [4, 5]. …”

“…Puberty itself, as well as poor glycaemic control, is an independent risk factor for MA in persons with T1D [9]. However, the diagnostic value of microalbuminuria in DN has recently been challenged by a large number of researchers worldwide, while it has been widely proposed that other biomarkers are needed for the early identification of diabetic renal lesions [2, 5, 10, 11]. Previous studies have provided evidence of several clinical and laboratory predictors for DN, such as increased systolic arterial blood pressure (SAP), even within the prehypertensive range [12], and dyslipidaemia, identifying people at risk for early endotheliopathy and cardiovascular disease (CVD) as well [13].…”

Crosstalk between tubular epithelial cells and glomerular endothelial cells in diabetic kidney disease

“…Based on this, clinical application of novel hypoglycaemic drugs such as daglitazine, a sodium‐glucose cotransporter‐2 (SGLT2) inhibitor, can increase urinary glucose excretion, control blood sugar and reduce glomerular injury, thereby delaying the deterioration of renal function in DKD. Nektaria found that there are many common signalling pathways between TECs and GECs, in which crosstalk plays a vast role (Figure ) . During the occurrence of DKD, abnormal secretion of vascular endothelial growth factor (VEGF), angiopoietin‐1 (Ang‐1) and inflammatory factors and hypoxia promotes injury to GECs.…”

The role of activation of KАTP channels on hydrogen sulfide induced renoprotective effect on diabetic nephropathy

“…The evolution of DN can be explained by the upregulation of angiotensin II (Ang II) receptors in efferent arterioles that are induced by hyperglycemia, with subsequent increases in the sensitivity to Ang II. Efferent arteriolar vasoconstriction leads to increased hydrostatic glomerular capillary pressure, hyperperfusion, hyperfiltration, and microalbuminuria (Papadopoulou‐Marketou, Chrousos, & Kanaka‐Gantenbein, ).…”