Nephrotic syndrome associated with ramucirumab therapy

Abstract

Ramucirumab is a human immunoglobulin G1 monoclonal antibody that binds to vascular endothelial growth factor receptor 2 and is used for the treatment of metastatic or inoperable gastric, colorectal, and non-small cell lung cancers. However, ramucirumab can result in renal adverse events, including nephrotic syndrome, and the clinical course of this event is unclear. This study aimed to investigate the clinical course and pathological findings of patients with nephrotic syndrome after ramucirumab treatment. We evaluated 5 patients with malignancies (2 cases of gastric cancer and 3 cases of colorectal cancer) who developed nephrotic syndrome during treatment with ramucirumab. Two patients were diagnosed based on renal biopsy. We investigated the relationship between ramucirumab treatment and clinical courses, pathological findings, and renal outcomes. Four of 5 patients developed nephrotic syndrome after 1 or 2 doses of ramucirumab. All patients had hypertension, and 2 of 5 patients had renal dysfunction, defined as an increase in serum creatinine levels of ≥50% or ≥0.3 mg/dL. The 2 renal biopsy samples revealed a diffuse glomerular basement membrane double contour, intracapillary foam cell infiltration, and partial foot process effacement. Early drug discontinuation and antihypertensive therapy improved proteinuria, renal dysfunction, and hypertension in all patients. Nephrotic syndrome is a renal adverse event observed in cancer patients after ramucirumab treatment. We suggest that urinalysis, renal function, and blood pressure should be closely monitored in patients undergoing ramucirumab treatment, and treatment should be discontinued if renal adverse events are detected.

A case of ramucirumab-induced renal failure with nephrotic-range proteinuria and its pathological findings

“…Previous studies suggested that RTKI inhibits NF-κB activity, leading to c-mip overexpression, and induces MCD or FSGS. 5 In two previous studies on ramucirumab-induced nephropathy, three cases of renal pathology were reported 3 8 and all of them were reported as TMA. The development of renal impairment characterised the three previous cases after switching from bevacizumab to ramucirumab, as in this case.…”

“… 7 Although other VEGF inhibitory drugs, such as the anti-VEGF monoclonal body (bevacizumab), tyrosine kinase inhibitors (sunitinib, axitinib, sorafenib and cediranib) and VEGF-Trap (aflibercept) have been known to cause nephrotic-range proteinuria and renal dysfunction, ramucirumab has been reported in only one case report 8 and one single-centre case report. 3 …”

“…We present the case of a 71-year-old man who had acute kidney injury with nephrotic-range proteinuria after ramucirumab administration. Past reports showed only thrombotic microangiopathy (TMA) in renal pathological changes, 3 but his pathological findings suggested ramucirumab induced TMA and podocytopathy, which included a crescent-like lesion.…”

“… 1 In the last decade, antiangiogenic agents for solid cancers have caused renal dysfunction. 2 However, renal dysfunction induced by ramucirumab is rarely reported 3 and its specific clinical course is still unknown.…”

Nephrotoxicity of anti-angiogenesis drugs

“…Fujii и соавт. описали 5 случаев нефротического синдрома после введения 1-2 доз рамуцирумаба [44]. Продолжительность лечения до появления нефротического синдрома составила от 21 до 112 (в среднем 46) дней.…”