Retrieved November 12, from www. AKI can lead to sudden kidney failure, kidney damage or even This could lead to a wide range of new treatments that are less onerous for kidney The study signifies a significant milestone in the Print Email Share.
Boy or Girl? Just a Game? Urine test strips and h urine collection tests are commonly used to test proteinuria. UPCR is often substituted because outpatient chemotherapy makes it difficult to collect urine for h [ 14 ].
One of the reasons for this is that the decision of whether or not to administer BEV was based on the proteinuria concentration alone. UPCR has already been reported for its utility in measuring urinary protein, but there are often cases that are ignored in general practice.
Furthermore, in this case, in addition to BEV administration, there were multiple risk factors for the development of proteinuria, such as a history of kidney transplantation and combined use of immunosuppressants. Renal pathology findings indicative of BEV-induced proteinuria include glomerular endothelial cell exfoliation, the collapse of slit membranes formed by glomerular podocytes, and glomerular nephritis caused by renal thrombotic microangiopathy TMA [ 15 ].
In this case, immunosuppressants were continuously used after kidney transplantation. Calcineurin inhibitors tacrolimus and cyclosporine are known to cause nephrotoxicity [ 16 ]. Frequent kidney damage occurs when serum concentrations of calcineurin inhibitors remain high for long periods of time [ 17 ].
Therefore, regular dose adjustment based on serum concentration measurements is recommended. The main cause of tacrolimus-related nephrotoxicity is renal tubule damage, with elevated serum creatinine levels and electrolyte abnormalities [ 18 ].
Furthermore, since tacrolimus is known to be involved in the development of TMA [ 19 ], the combination of tacrolimus and BEV may have caused TMA additively or synergistically, causing tissue damage.
However, details in this case are unknown because a renal biopsy was not performed after the onset of severe proteinuria. They reported severe proteinuria after BEV administration in a patient who underwent kidney transplantation, in which tacrolimus and everolimus were used as immunosuppressive agents. However, the association between serum tacrolimus concentration and proteinuria was not evaluated in that report.
In our case, there were no significant differences in serum tacrolimus concentrations before and after the start of BEV administration. Moreover, there was no correlation between the serum tacrolimus concentration and proteinuria. Therefore, it is indicated that the cause of severe proteinuria is not the effect of tacrolimus concentration.
Thrombocytopenia occurred before the onset of severe proteinuria. Suspected causes of thrombocytopenia were BEV administration, tacrolimus use [ 21 , 22 ], and TMA [ 23 ], but recovery was observed after withdrawal of oxaliplatin.
Therefore, it was speculated that bone marrow suppression by oxaliplatin was a direct causative factor. Previous reports have shown that the increase in blood pressure with BEV use does not correlate with the onset of proteinuria [ 24 ], and the observations in this case may be consistent with this conclusion.
This report has potential limitations. It is unclear whether both kidney transplantation and administration of calcineurin inhibitors could be risk factors of proteinuria caused by BEV. To reveal this clinical question, more case reports and clinical research are required.
The administration of BEV to cancer patients undergoing living kidney transplantation is considered to be important for prolonging survival. In this case, severe proteinuria developed. Patients with risk factors for renal impairment should have their proteinuria measured regularly to carefully assess the risks and benefits of BEV administration. Strategies to improve long-term outcomes after renal transplantation. N Engl J Med.
Article Google Scholar. Risk factors for graft loss and mortality after renal transplantation according to recipient age: a prospective multicentre study.
Nephrol Dial Transplant. Clinical characteristics and treatment outcomes of colorectal cancer in renal transplant recipients in Korea. Yonsei Med. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study.
Gordon MS, Cunningham D. Managing patients treated with bevacizumab combination therapy. Blockade of VEGF accelerates proteinuria, via decrease in nephrin expression in rat crescentic glomerulonephritis. Kidney Int. Most proteins are too large to pass through the glomeruli into the urine. The glomeruli are negatively charged, so they repel the negatively charged proteins.
Thus, a size and charge barrier keeps protein molecules from entering the urine. When the glomeruli are damaged, proteins of various sizes pass through them and are excreted in the urine, resulting in measurable, but usually asymptomatic, proteinuria.
The mechanism of proteinuria is not fully understood, but recent research finds that renal thrombotic microangiopathy secondary to impaired vascular endothelial growth factor VEGF signaling within the glomerulus may be a factor in the development of bevacizumab-associated proteinuria. Note: the patient in that case had ovarian cancer, not CRC.
In most cases, proteinuria improves and usually resolves after bevacizumab is stopped. Comorbid conditions such as hypertension and diabetes increase the risk, independent of bevacizumab exposure. In that study, hypertension toxicity was associated with an increased risk of proteinuria. Secondary edema generally occurs only when proteinuria is in the nephrotic syndrome range.
Proteinuria is assessed and graded based on urine dipstick testing or hour urine collection results Table 1. Nephrotic syndrome is a clinical complex characterized by 14 The presence of proteinuria during bevacizumab therapy is statistically associated with hypertension, although a causative relationship has not yet been established. No temporal relationship was found in an observational study in which it was noted that half the patients developed hypertension first and the other half developed proteinuria.
Otis Brawley, the American Cancer Society's chief medical and scientific officer, who likewise had no involvement with this research. It also doesn't concern year-old Julie Del Giorno, a Pennsylvania woman who took Avastin to treat her ovarian cancer as part of a clinical trial last year.
After reading about the side effects of Avastin and consulting with her doctor, she decided to give it a try. Still, the researchers and other medical experts agree that the results of the study indicate the importance of keeping a close eye on kidney function. Proteinuria places a person at higher risk for blood clots and other complications on top of the risks related to cancer and chemotherapy.
Earlier this week, researchers from Fox Chase Cancer Center presented findings showing that women who took Avastin while they underwent chemotherapy and then continued on the drug by itself lived longer and without any signs of cancer growth.
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