Development of osmotic vacuolization of proximal tubular epithelial cells following treatment with sodium-glucose transport protein 2 inhibitors in type II diabetes mellitus patients-3 case reports

AbstractWe encountered 3 cases of acute kidney injury that occurred after treatment with a SGLT2 inhibitor. In case 1, serum creatinine increased from 1.65 to 3.0 mg/dL, in case 2, serum creatinine increased from 1.03 to 1.21 mg/dL, and in case 3, serum creatinine increased from 0.8 to 1.1 mg/dL. Renal biopsy showed isometric vacuolization on tubules, that was completely negative for Periodic acid-Schiff (PAS) stain in case 1, and was partially negative for PAS stain in case 2 and 3, consistent with osmotic vacuolization. Immunohistochemical analysis showed positive staining for CD138 and CD10 indicating the proximal tubules in the vacuolar lesions. 3 patients were obese with body mass index of more than 30, and showed an increase in serum renin. In conclusion, in type II diabetes mellitus (T2DM), individuals that remain within their standard weight range, SGLT2 inhibitor treatment does not result in osmotic vacuolization of proximal tubular epithelial cells and AKI. However, treatment with a SGLT2 inhibitor may cause damage of the proximal tubules resulting in AKI in T2DM individuals who do not remain within their standard weight range, due to an overdose lavage of sugar in the urine and dehydration.

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FcRn-mediated transcytosis of immunoglobulin G in human renal proximal tubular epithelial cells

AJP Renal Physiology ◽

10.1152/ajprenal.0164.2001 ◽

2002 ◽

Vol 282 (2) ◽

pp. F358-F365 ◽

Cited By ~ 72

Author(s):

Noriyoshi Kobayashi ◽

Yusuke Suzuki ◽

Toshinao Tsuge ◽

Ko Okumura ◽

Chisei Ra ◽

...

Keyword(s):

Epithelial Cells ◽

Proximal Tubules ◽

Transepithelial Transport ◽

Dependent Manner ◽

Tubular Epithelial Cells ◽

Human Igg ◽

Proximal Tubular Epithelial Cells ◽

Proximal Tubular ◽

Ph Dependent ◽

Renal Proximal Tubular

In the kidney, proteins filtered through glomeruli are reabsorbed by endocytosis along the proximal tubules to avoid renal loss of large amounts of proteins. Recently, neonatal Fc receptor (FcRn), which is involved in the transport of IgG across several epithelial and endothelial cells, was reported to be expressed in renal proximal tubular epithelial cells (RPTECs). However, there has been no direct evidence for receptor-mediated endocytosis of IgG in human RPTECs. To explore physiological roles of FcRn in the proximal tubules, we used the human RPTECs to examine IgG transport. FcRn was expressed in RPTECs and physically associated with β2-microglobulin, preserving the capacity of specific pH-dependent IgG binding. Human IgG was bound to the cell surface of RPTECs in a pH-dependent manner. The human IgG transport assay revealed that receptor-mediated transepithelial transport of intact IgG in RPTECs is bidirectional and that it requires the formation of acidified intracellular compartments. With the use of double immunofluorescence, the internalized human IgG was marked in cytoplasm of RPTECs and colocalized with FcRn. These data define the mechanisms of FcRn-associated IgG transport in RPTEC monolayers. It was suggested that the intact pathway for human IgG transepithelial transport may avoid lysosomal degradation of IgG.

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