Dapagliflozin as a cause of acute tubular necrosis with heavy consequences: a case report

Pleros, Christos; Stamataki, E.; Papadaki, Antonia; Damianakis, Nikolaos; Poulidaki, Rafaela; Gakiopoulou, Charikleia; Tzanakis, Ioannis

doi:10.1007/s13730-017-0283-0

Cited by 17 publications

(15 citation statements)

References 9 publications

(9 reference statements)

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“…Features resembling osmotic nephrosis have been previously reported in a patient receiving dapaglifozin. 11 In our case, one could argue that concomitant use of furosemide and enalapril may have caused volume depletion and intrarenal hemodynamic changes predisposing to kidney injury. However, the diffuse osmotic nephropathy was the predominant lesion.…”

Section: Discussionmentioning

confidence: 70%

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Osmotic Nephrosis and Acute Kidney Injury Associated With SGLT2 Inhibitor Use: A Case Report

Phadke

Kaushal

Tolan

et al. 2020

American Journal of Kidney Diseases

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We report a case of a patient who developed dialysis-requiring acute kidney injury (AKI) after the use of canagliflozin. A 66-year-old man with type 2 diabetes who was recovering from left knee septic arthritis at a rehabilitation facility was admitted with oliguric AKI 5 days after starting treatment with canagliflozin, an inhibitor of sodium/glucose cotransporter 2 (SGLT2). The patient presented with hematuria, non-nephrotic-range proteinuria, and serum creatinine level of 6.8 (baseline, 1.1-1.3) mg/dL. There was no recent use of radiocontrast agents or exposure to other nephrotoxins. The patient subsequently required hemodialysis. Due to recent antibiotic use (ampicillin-sulbactam), acute interstitial nephritis was considered in the differential diagnosis. Kidney biopsy was performed, which showed the presence of osmotic nephropathy. The patient's kidney function returned to baseline after 2 weeks of hemodialysis. This case provides evidence of an association of osmotic nephropathy with the use of canagliflozin and discusses potential mechanisms. We recommend kidney biopsy for cases of severe AKI associated with SGLT2 inhibitors to better understand the relationship of this complication with the use of this class of medications. Complete author and article information provided before references.

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Section: Discussionmentioning

confidence: 70%

“…A patient with AKI likely from SGLT2 inhibitor use was reported to have the lesion of osmotic nephrosis. 11 We report another case and discuss its potential pathogenesis.…”

Section: Introductionmentioning

confidence: 92%

Osmotic Nephrosis and Acute Kidney Injury Associated With SGLT2 Inhibitor Use: A Case Report

Phadke

Kaushal

Tolan

et al. 2020

American Journal of Kidney Diseases

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“…Nevertheless, despite good overall clinical tolerability, several harmful effects have been published related to daily intake. Caution is still advised regarding possible adverse events described such as AKI and acute tubular necrosis [3,13]. Under certain circumstances-possibly dehydration of the patient, low blood pressure, or certain co-medications-gliflozin may damage the organ.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, despite overall good clinical tolerability [10], harmful effects also can occur during daily gliflozin intake. Reported adverse events are especially acute kidney injury (AKI) [11,12], acute tubular necrosis [13], genital infections, and bone fractures [3]. Although current evidence supports their safety, additional efforts are needed to elucidate the long-term impact of these compounds on chronic kidney disease, mineral metabolism, and bone health.…”

Section: Introductionmentioning

confidence: 99%

No Cytotoxic and Inflammatory Effects of Empagliflozin and Dapagliflozin on Primary Renal Proximal Tubular Epithelial Cells under Diabetic Conditions In Vitro

Baer

Koch

Freitag

et al. 2020

IJMS

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Gliflozins are inhibitors of the renal proximal tubular sodium-glucose co-transporter-2 (SGLT-2), that inhibit reabsorption of urinary glucose and they are able to reduce hyperglycemia in patients with type 2 diabetes. A renoprotective function of gliflozins has been proven in diabetic nephropathy, but harmful side effects on the kidney have also been described. In the current project, primary highly purified human renal proximal tubular epithelial cells (PTCs) have been shown to express functional SGLT-2, and were used as an in vitro model to study possible cellular damage induced by two therapeutically used gliflozins: empagliflozin and dapagliflozin. Cell viability, proliferation, and cytotoxicity assays revealed that neither empagliflozin nor dapagliflozin induce effects in PTCs cultured in a hyperglycemic environment, or in co-medication with ramipril or hydro-chloro-thiazide. Oxidative stress was significantly lowered by dapagliflozin but not by empagliflozin. No effect of either inhibitor could be detected on mRNA and protein expression of the pro-inflammatory cytokine interleukin-6 and the renal injury markers KIM-1 and NGAL. In conclusion, empa- and dapagliflozin in therapeutic concentrations were shown to induce no direct cell injury in cultured primary renal PTCs in hyperglycemic conditions.

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“…[15][16][17][18][19][20] Examples of these histologic descriptions can be found in included studies. 16,[21][22][23][24][25][26][27]…”

Section: Data Extractionmentioning

confidence: 99%

A Systematic Review of Clinical Characteristics and Histologic Descriptions of Acute Tubular Injury

Wen

Yang

Menez

et al. 2020

Kidney International Reports

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Introduction: The term "acute tubular injury" (ATI) represents histopathologic renal tubular injury and often manifests clinically as acute kidney injury (AKI). Studies systematically summarizing the clinical presentation and histological changes in human ATI are limited. Methods: We used a comprehensive search strategy to search human studies of ATI from 1936 to July 2019. We extracted study characteristics, clinical characteristics, and histologic descriptions of ATI by bright field, immunofluorescence, electron microscopy, and immunohistochemistry. We compared ATI histology as a function of tissue procurement type, timing, and etiologies. Results: We included 292 studies comprising a total of 1987 patients. The majority of studies (222 of 292, 76%) were single-center case reports. The mean age of included patients was 47 years. In native kidney biopsy cases, baseline, peak, and latest creatinine were 1.3 mg/dl, 7.19 mg/dl, and 1.85 mg/dl respectively, and biopsy was performed mostly after peak creatinine (86.7%, 391 of 451). We identified 16 histologic descriptions of tubular injury, including tubular cell sloughing (115 of 292, 39.4%), tubular epithelial flattening/simplification (110 of 292, 37.7%), tubular dilatation (109 of 292, 37.3%), and tubular cell necrosis (93 of 292, 31.8%). There was no difference in tubular injury histology among different tissue procurement types (native kidney biopsy, transplant kidney biopsy, and autopsy), among different etiologies, or between different tissue procurement timing (before or after creatinine peaks in native kidneys). Electron microscopy and immunohistochemistry were used in a minority of studies. Conclusion: ATI manifests with diverse histologic changes. Efforts to establish protocols to harmonize biopsy practices, to handle kidney biopsy for tissue interrogation, and to report results across clinical practice are needed to improve our understanding of this complex disease.

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Dapagliflozin as a cause of acute tubular necrosis with heavy consequences: a case report

Cited by 17 publications

References 9 publications

Osmotic Nephrosis and Acute Kidney Injury Associated With SGLT2 Inhibitor Use: A Case Report

Osmotic Nephrosis and Acute Kidney Injury Associated With SGLT2 Inhibitor Use: A Case Report

No Cytotoxic and Inflammatory Effects of Empagliflozin and Dapagliflozin on Primary Renal Proximal Tubular Epithelial Cells under Diabetic Conditions In Vitro

A Systematic Review of Clinical Characteristics and Histologic Descriptions of Acute Tubular Injury

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