In Reply to ‘Secondary Capillary Leak Syndrome Related to Pemetrexed Exposure’

Abstract

Maroz and Weiner report a case of systemic capillary leak syndrome associated with administration of pemetrexed and characterized by peripheral and visceral edema, hypotension, hypoalbuminemia, and acute kidney injury.1Maroz N. Weiner I.D. Secondary capillary leak syndrome related to pemetrexed exposure.Am J Kidney Dis. 2012; 59: 583PubMed Google Scholar This syndrome is a relatively rare condition with 126 cases reported in the literature between 1960 and 2010. It is characterized by unexplained episodes of capillary hyperpermeability manifesting as edema, hypoalbuminemia, and shock.2Druey K.M. Greipp P.R. Narrative review: the systemic capillary leak syndrome.Ann Intern Med. 2010; 153: 90-98Crossref PubMed Scopus (197) Google Scholar Although the authors purport that this is the first report of pemetrexed-related systemic capillary leak syndrome, a number of cases of fluid retention during therapy with pemetrexed have been reported in the literature.3D'Angelo S.P. Kris M.G. Pietanza M.C. et al.A case series of dose-limiting peripheral edema observed in patients treated with pemetrexed.J Thorac Oncol. 2011; 6: 624-626Crossref PubMed Scopus (14) Google Scholar, 4Eguia B. Ruppert A.M. Fillon J. et al.Skin toxicities compromise prolonged pemetrexed treatment.J Thorac Oncol. 2011; 6: 2083-2089Crossref PubMed Scopus (28) Google Scholar, 5Bastos D.A. Calabrich A. Katz A. Pemetrexed-induced fluid retention.J Thorac Oncol. 2010; 5: 752Crossref PubMed Scopus (11) Google Scholar Our group recently reported a case series of 14 patients who developed peripheral edema while receiving pemetrexed. The edema was associated with hypoalbuminemia, with a median serum albumin level of 3.0 (range, 2.3-3.7) g/dL.3D'Angelo S.P. Kris M.G. Pietanza M.C. et al.A case series of dose-limiting peripheral edema observed in patients treated with pemetrexed.J Thorac Oncol. 2011; 6: 624-626Crossref PubMed Scopus (14) Google Scholar Eguia et al also reported a case of peripheral edema, pleural and pericardial effusions, weight gain, and hypoalbuminemia.4Eguia B. Ruppert A.M. Fillon J. et al.Skin toxicities compromise prolonged pemetrexed treatment.J Thorac Oncol. 2011; 6: 2083-2089Crossref PubMed Scopus (28) Google Scholar Bastos et al described 7 patients with fluid retention in the setting of pemetrexed therapy. Two of these patients had generalized edema and pleural effusions.5Bastos D.A. Calabrich A. Katz A. Pemetrexed-induced fluid retention.J Thorac Oncol. 2010; 5: 752Crossref PubMed Scopus (11) Google Scholar All cases showed improvement after discontinuation of pemetrexed. It appears that pemetrexed in certain patients may increase capillary permeability leading to albumin loss and leakage of fluid into extravascular space. The patient described by Maroz and Weiner also developed acute kidney injury during an episode of systemic capillary leak syndrome. The mechanism of kidney injury appears to be prerenal given evidence of hypotension requiring intravenous fluids, low fractional excretion of sodium, and bland urinalysis. We have described different renal toxicity associated with pemetrexed.6Glezerman I.G. Pietanza M.C. Miller V. et al.Kidney tubular toxicity of maintenance pemetrexed therapy.Am J Kidney Dis. 2011; 58: 817-820Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar In our report the toxicity appeared to be intrarenal, with acute, subacute, and chronic tubular injury related to direct tubular toxicity of pemetrexed, which gained entry into tubular cells via folate transporters. Our patients did not have any evidence of fluid retention and increased capillary permeability could not be implicated in development of their kidney disease. Financial Disclosure: The authors declare that they have no relevant financial interests. Secondary Capillary Leak Syndrome Related to Pemetrexed ExposureAmerican Journal of Kidney DiseasesVol. 59Issue 4PreviewWe read the article by Glezerman et al1 with great interest. We would like to report a patient who developed systemic capillary leak syndrome due to pemetrexed. A 74-year-old white man with non–small cell lung cancer had poor response to a carboplatin-paclitaxel chemotherapy regimen, so it was changed to pemetrexed, 500 mg/m2. Within several days he developed moderate-size pericardial and pleural effusion, as well as severe edema of the face, abdominal wall, and lower and upper extremities; he also acutely gained 36 pounds of weight. Full-Text PDF