Everolimus worsening chronic proteinuria in patient with diabetic nephropathy post liver transplantation

• Published in: Saudi journal of kidney diseases and transplantation Vol. 30; no. 4; pp. 989 - 994
• Main Authors: Hanna, Rami M., Yanny, Beshoy, Arman, Farid, Barsoum, Marina, Mikhail, Mira, al-Baghdadi, Maha, Rastogi, Anjay, Wallace, William, Sab, Sami
• Format: Journal Article
• Language: English
• Published: Riyadh, Saudi Arabia Saudi Center for Organ Transplantation 01.07.2019; Wolters Kluwer India Pvt. Ltd; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Wolters Kluwer Medknow Publications
• Subjects: Aged; Angiogenesis inhibitors; Bevacizumab; Diabetes; Diabetic nephropathies; Diabetic Nephropathies - complications; Diabetic Nephropathies - diagnosis; Diabetic Nephropathies - urine; Diabetic nephropathy; Disease Progression; Endothelial growth factors; Endothelium; Everolimus; Everolimus - adverse effects; Humans; Immunosuppressive Agents - adverse effects; Immunotherapy; Inhibitor drugs; Kidney diseases; Kinases; Liver; Liver failure; Liver Failure, Acute - complications; Liver Failure, Acute - diagnosis; Liver Failure, Acute - surgery; Liver transplantation; Liver Transplantation - adverse effects; Liver transplants; Male; Mammals; Organ transplantation; Patients; Proteins; Proteinuria; Proteinuria - diagnosis; Proteinuria - etiology; Proteinuria - urine; Risk Factors; Stem cell transplantation; Stem cells; Transplants & implants; Treatment Outcome; Urine; Vascular endothelial growth factor; اعتلال الكلى السكري; البروتين البولي; الكبد; المرضى; المضاعفات; زرع الأعضاء
• ISSN: 1319-2442; 2320-3838
• DOI: 10.4103/1319-2442.265481

Mammalian target of rapamycin (mTOR) inhibitors are used in renal sparing protocols and transplant immunosuppression in patients with solid organ and stem cell transplants. They cause various side effects, including proteinuria, which is mediated by blockade of the vascular endothelial growth factor receptor pathway. There have been various reports of mTOR inhibitors causing proteinuria or worsening proteinuria form preexisting renal glomerulopathies. We report a 73-year old male with diabetic glomerulosclerosis, acute liver failure due to Budd–Chiari syndrome, chronic low platelets, and worsening proteinuria from 0.46 g protein/g creatinine to 2.2 g protein/g creatinine. Workup revealed no thrombotic microangiopathy through skin biopsy, and a renal biopsy confirmed only clinically suspected diabetic and hypertensive glomerulosclerosis and possible calcineurin inhibitors. On discontinuation of everolimus urine protein decreased back to 0.6 g/g creatinine. We review the mechanism of mTOR-induced proteinuria and how this may affect diabetic nephropathy secondarily. We also consider the clinical implications of this in transplant patients receiving these agents.