AKI-to-CKD transition is a potential mechanism for non-albuminuric diabetic kidney disease

Abstract

Although albuminuria development is considered the natural course of diabetic kidney disease (DKD), increasing evidence indicate that the disease can present as non-albuminuric DKD (NA-DKD), characterized by prominent tubulointerstitial injury and fibrosis without obvious glomerulopathy. However, the pathogenic mechanisms underlying NA-DKD remain unclear. As diabetic patients are more susceptible to acute kidney injury (AKI), and the maladaptive repair of kidney tubules following AKI occurs more frequently in diabetic than non-diabetic patients, the enhanced AKI-to-CKD transition may be a significant contributor of NA-DKD. Recent studies indicate that endoplasmic reticulum (ER) stress is a key pathogenic driver of AKI-to-CKD transition, and that the tubular expression of ER-resident protein reticulon 1A (RTN1A) correlates with human DKD progression and AKI-to-CKD transition. Experimental studies showed that RTN1A indeed mediates tubular cell injury and AKI-to-CKD transition in diabetic mice via concomitant activation of ER stress and mitochondrial dysfunction as a mediator of ER-mitochondrial crosstalk. Further understanding of the pathogenesis of tubular injury in DKD will help us to develop sensitive and specific biomarkers or diagnostic tools to distinguish between injury-related AKI, pre-renal AKI from hemodynamic changes, and the progression of DKD in order to better manage patients with DKD.

Update sulla malattia renale diabetica (DKD): focus sulla DKD non albuminurica e il rischio cardiovascolare

“…Pertanto, ripetuti episodi di AKI nei pazienti con diabete sono probabilmente responsabili della transizione alla DKD. È anche probabile che la transizione da AKI a CKD sia responsabile del declino dell'eGFR nei pazienti con DKD non albuminurica, che è caratterizzata principalmente da danno tubulointerstiziale e fibrosi (36).…”

Update on Diabetic Kidney Disease (DKD): Focus on Non-Albuminuric DKD and Cardiovascular Risk

“…Thus, episodes of AKI in patients with diabetes are likely responsible for the DKD transition. It is also likely that the AKI-to-CKD transition is responsible for the decline of eGFR in patients with non-albuminuric DKD, which is characterized mostly by tubulointerstitial injury and fibrosis [36].…”

Magnetic Resonance Imaging in Clinical Trials of Diabetic Kidney Disease

“…Moreover, dysfunction of one organ, such as the kidney, can negatively impact other organs and lead to further organ failure, for example, the heart [23]. Episodes of acute kidney injury (AKI) in patients with DM and DKD are also thought to contribute to disease progression and eGFR decline [24]. Clinical AKI is defined by Episodes of acute kidney injury (AKI) in patients with DM and DKD are also thought to contribute to disease progression and eGFR decline [24].…”

“…Episodes of acute kidney injury (AKI) in patients with DM and DKD are also thought to contribute to disease progression and eGFR decline [24]. Clinical AKI is defined by Episodes of acute kidney injury (AKI) in patients with DM and DKD are also thought to contribute to disease progression and eGFR decline [24]. Clinical AKI is defined by KDIGO as an increase in serum creatinine of >0.3 mg/dL (>26 µmol/L) within 48 h or an increase to more than 1.5 times the baseline serum creatinine within 7 days [25].…”

“…Clinical AKI is defined by KDIGO as an increase in serum creatinine of >0.3 mg/dL (>26 µmol/L) within 48 h or an increase to more than 1.5 times the baseline serum creatinine within 7 days [25]. Many, but not all, patients eventually recover their baseline kidney function over days or weeks; however, even a seemingly recovered episode of AKI carries an increased risk of developing CKD later, the so-called "AKI to CKD transition", especially in patients already known to have some impairment of kidney function with or without pre-existing albuminuria [24,26,27].…”