Lymphedema of the Transplanted Kidney and Abdominal Wall with Ipsilateral Pleural Effusion Following Kidney Biopsy in a Patient Treated with Sirolimus: A Case Report and Review of the Literature

Abstract

Patient: Female, 32Final Diagnosis: Sirolimus induced congestion of kidney and overlying abdominal wallSymptoms: Abdominal pain • abdominal swelling • dyspneaMedication: —Clinical Procedure: Improvement of symptoms with drug withdrawalSpecialty: NephrologyObjective:Adverse events of drug therapyBackground:Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor, which is used in immunosuppressive treatment regimens in organ transplant recipients. Although mTOR inhibitors are well tolerated, their adverse effects have been reported. Sirolimus treatment in transplant recipients has been reported to be associated with lymphedema of the skin and subcutaneous tissues, and with pleural effusion, but edema of internal organs and organomegaly have not been previously reported. A case is presented lymphedema of the transplanted kidney and abdominal wall with ipsilateral pleural effusion following kidney biopsy in a patient treated with sirolimus.Case Report:A 32-year-old woman with a history of end-stage renal disease of unknown etiology had undergone right renal transplantation from an unrelated living donor, eight years previously. She was referred to our hospital with dyspnea, localized abdominal pain, and swelling of the transplanted kidney. The symptoms appeared following a kidney biopsy and the replacement of cyclosporin with sirolimus four months previously. On examination, she had localized swelling of the abdominal wall overlying the transplanted kidney, and a right pleural effusion. Hydronephrosis and nephrotic syndrome were excluded as causes of kidney enlargement. Following the withdrawal of sirolimus therapy her symptoms resolved within three months.Conclusions:A case is described of lymphedema of the transplanted kidney and abdominal wall with ipsilateral pleural effusion following kidney biopsy attributed to her change in anti-rejection therapy to sirolimus. This case report should raise awareness of this unusual complication of sirolimus anti-rejection therapy and its possible effects on the lymphatic system.

Drug‐induced peripheral oedema: An aetiology‐based review

“…148 In a review of 26 cases, the time from sirolimus initiation to lymphedema onset ranged from 1 to 30 months. 2 Sirolimus-induced lymphedema is usually unilateral or asymmetrical, especially when located in upper extremities. 2 Diuretics are ineffective and it may progress to permanent scleroderma-like lesions 121 when the dosage is not reduced or the drug is not interrupted early.…”

“…Drug-induced peripheral oedema represents a polymorphic iatrogenic entity in terms of mechanisms, severity and to a lesser extent clinical presentation. Although most often pitting and bilateral, some drug-induced peripheral oedema may present as erythematous (eg, pemetrexed), 1 unilateral (e.g., sirolimus) 2 or may be associated with a nonblanching petechial rash [calcium channel blockers (CCBs)]. 3 The aim of this review is to raise awareness of the mechanisms involved in drug-induced peripheral oedema.…”

Drug-induced peripheral edema: an etiology-based review

“…Various drugs can induce or worsen peripheral edema by disrupting the delicate homeostasis between transcapillary flow, edema safety factors and lymphatic drainage capacity (Figure 2 ). Although most often pitting and bilateral, some drugs are involved in the development of peripheral edema that is readily erythematous (e.g., dopaminergic agonists (Wood, 2010), pemetrexed (D'Angelo, Kris, Pietanza, Rizvi, & Azzoli, 2011)) or unilateral (e.g., sirolimus (Rashid-Farokhi & Afshar, 2017)). In addition to aggressive fluid resuscitation and preparation providing a significant amount of sodium, drug-induced edema entails four mechanisms, namely precapillary arteriolar vasodilation (vasodilatory edema), sodium and water retention (renal edema), lymphatic insufficiency (lymphedema) and increased capillary permeability (permeability edema).…”

“…To such an extent that sirolimus is used to treat lymphatic malformations related to PI3K/AKT/mTOR upregulation (Fereydooni, Dardik, & Nassiri, 2019). In a review of 26 cases, the time from sirolimus initiation to lymphedema onset ranged from 1 to 30 months (Rashid-Farokhi & Afshar, 2017). Sirolimus-induced lymphedema is usually unilateral or asymmetrical especially when located in upper extremities (Rashid-Farokhi & Afshar, 2017).…”

“…In a review of 26 cases, the time from sirolimus initiation to lymphedema onset ranged from 1 to 30 months (Rashid-Farokhi & Afshar, 2017). Sirolimus-induced lymphedema is usually unilateral or asymmetrical especially when located in upper extremities (Rashid-Farokhi & Afshar, 2017). Diuretics are ineffective and it may progress to permanent scleroderma-like lesions (E. Mahé et al, 2005) when the dosage is not reduced or drug is not interrupted early (Gharbi et al, 2014).…”