. 2021 Sep 21;10(9):2497. doi: 10.3390/cells10092497

Table 1.

Autophagy in kidney physiology and DKD pathophysiology.

Autophagy in Kidney Physiology	Impaired Autophagy in DKD
Essential for kidney’s integrity and proper functioning [47]. Protective role over the kidneys by preventing fibrosis [48]. Protective role preventing inflammation [43]. Regulates GFB integrity [48,49,50,51]. Contributes to renal homeostasis by regulating autophagy flux in kidney cells [52]. May increase glucagon level, which induces autophagy in several tissues.	Generates the accumulation of impaired organelles and misfolded proteins: The accumulation of mitochondria plays a huge part in the formation of reactive oxygen species (ROS) [1]. This activates pro apoptotic signals and may result in podocyte death. [52,53] Induces podocyte damage and hypertrophy [54,53]. Induces apoptosis in podocytes and proximal tubular cells [55]. Mediator of unconventional secretion of pro-inflammatory molecules such as IL-1β [30] and IDE [45]. Develops kidney fibrosis mediated by WISP-1 [56]. Set in motion glomerulosclerosis and damage in the GFB by the deletion of Atg5 [53]. Increases the rate of senescence in PTEC [57,58]. Up-regulates nephrin in the glomeruli through inhibition of mTOR, altering podocytes cytoskeleton [49]. Induces pryoptosis, a highly inflammatory form of programmed cell death due to a high rate of caspase 1 that cleaves IL-1B [59,60]. Produces alterations in ATG genes leading to kidney damage [61]. Inhibition of mTOR may increase protein excretion, which promotes progressive tubular injury [62].

Autophagy in Kidney Physiology

Impaired Autophagy in DKD

Essential for kidney’s integrity and proper functioning [47].
Protective role over the kidneys by preventing fibrosis [48].
Protective role preventing inflammation [43].
Regulates GFB integrity [48,49,50,51].
Contributes to renal homeostasis by regulating autophagy flux in kidney cells [52].
May increase glucagon level, which induces autophagy in several tissues.

Generates the accumulation of impaired organelles and misfolded proteins:
The accumulation of mitochondria plays a huge part in the formation of reactive oxygen species (ROS) [1].
This activates pro apoptotic signals and may result in podocyte death. [52,53]
Induces podocyte damage and hypertrophy [54,53].
Induces apoptosis in podocytes and proximal tubular cells [55].
Mediator of unconventional secretion of pro-inflammatory molecules such as IL-1β [30] and IDE [45].
Develops kidney fibrosis mediated by WISP-1 [56].
Set in motion glomerulosclerosis and damage in the GFB by the deletion of Atg5 [53].
Increases the rate of senescence in PTEC [57,58].
Up-regulates nephrin in the glomeruli through inhibition of mTOR, altering podocytes cytoskeleton [49].
Induces pryoptosis, a highly inflammatory form of programmed cell death due to a high rate of caspase 1 that cleaves IL-1B [59,60].
Produces alterations in ATG genes leading to kidney damage [61].
Inhibition of mTOR may increase protein excretion, which promotes progressive tubular injury [62].