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IVIG 治疗 BK 病毒相关性肾病 (BKVN)

Doctor with an anatomical model of a human kidney

People who have received a kidney transplant often develop a condition called BK virus-associated nephropathy (or BKVN). This is a serious kidney problem that’s caused by the BK virus. If not treated properly, it can contribute to kidney failure or premature graft loss in kidney transplant recipients (a person who received a healthy kidney from a donor). 

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Currently, there isn’t a standard therapy for managing BKVN. The only option is to lower the dose of immunosuppression, which is not always possible or effective in certain patients. 

However, using 免疫球蛋白 can help manage BK virus-associated nephropathy. Read on to learn how IVIG therapy works. 

BK Virus-Associated Nephropathy: Basic Overview

Most people get exposed to the BK virus during childhood, and it usually stays inactive (dormant or latent) in the kidney and urinary tract. In the dormant state, the BK virus does not cause any problems. 

However, the BK virus reactivates (wakes up) in kidney transplant recipients when they take immunosuppressants (or antirejection agents) to prevent organ rejection. Unfortunately, these medications  also weaken the body’s immune system, which creates an ideal environment for the virus to multiply and infect the transplanted kidney cells. 

The infection causes inflammation and injury to kidney tissues (nephropathy), leading to a decline in transplanted kidney function and, eventually, progressing to graft failure.

Standard Treatments for BK Virus-Associated Nephropathy

The standard treatment for BKVN is to reduce the dosage of immunosuppressive medications to allow the patient’s immune system to fight off the BK virus more effectively. However, this strategy is a bit challenging as it can raise the risk of transplant rejection. Also, in some cases, this treatment strategy becomes ineffective in certain patients. 

Researchers are now exploring alternative treatments, like IVIG, to manage the BKVN in kidney transplant recipients. 

IVIG for BK Virus-Associated Nephropathy (BKVN): Research Evidence

Nurse preparing IVIG for BK Virus-Associated Nephropathy (BKVN)

Though the research on IVIG treatment for BKVN is ongoing, various small clinical studies and case reports have reported promising results. For instance, a retrospective single-center study published in the Journal of Kidney Transplantation and Transplant Immunology reported that IVIG effectively clears the BK virus and maintains normal graft function in pediatric kidney transplant recipients. 

Similarly, a case report published in 2024 found that IVIG can effectively treat BKVN when standard treatment fails. A 37-year-old kidney transplant patient showed no improvement after reducing immunosuppressants, but after two doses of IVIG, his viral load dropped from over 2 million to 5,500 copies/ml. This suggests IVIG may be a useful second-line option for managing BKVN.

Another study reported that IVIG is a promising treatment to improve the severity of BKVN, especially in cases where a dose reduction of immunosuppressants was found to be effective. 

Efficacy of IVIG in Combination With Other Drugs

Research has also been done to study the impact of IVIG in combination with other medications  in kidney transplant recipients. For instance, a study published in the Journal of Transplantation Proceedings reported that a high dose of IVIG (1 g/kg) combined with leflunomide significantly decreased BK viral load within 1 month of treatment. 

Likewise, another study involving 50 patients with BKVN showed that 1 g/kg of IVIG in addition to immunosuppression adjustment appears to be more effective in clearing the BK virus from blood and renal transplant tissue.

In other words, IVIG alone or combined with traditional treatment has proven effective in improving kidney function and lowering the BK virus level in recipients. 

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How Does IVIG Manage BK Virus-Associated Nephropathy (BKVN)?

IVIG therapy, which provides patients with antibodies, is thought to manage BKVN in two ways:

1. Direct Neutralization

The antibodies (IgG) provided by IVIG therapy can counteract the different strains of the BK virus. When IgG antibodies bind to the BK virus, they prevent the virus from infecting the kidney cells. 

In fact, an experimental study reported that commercially available IG contains potent neutralizing antibodies , which are capable of neutralizing all major BKV genotypes.

2. Immune System Modulation

It is believed that IVIG can modulate the immune system by boosting the body’s anti-viral response. This also helps calm down the harmful inflammation in the kidney and prevents further tissue damage. 

One significant advantage of IVIG is that its dual action can control virus replication without increasing the risk of transplant rejection. 

Note: IVIG is not a cure but is only used as an adjunctive therapy to manage the BK virus-associated nephropathy condition. 

When Is IVIG Used?

Healthcare providers  typically consider IVIG treatment when a BK viral load increases in the patient’s urine and blood, and their kidney function starts to worsen even after lowering the dose of  immunosuppressive medications. 

IVIG Administration and Side Effects

IVIG is usually infused slowly through a vein (intravenous or IV) over several hours in a hospital or clinic setting. The frequency of the IVIG doses can vary among kidney transplant recipients. 

If you’re receiving IVIG treatment, it is possible you may experience some mild side effects like headaches, chills, and fatigue. Your healthcare provider might even give you pre-medications to take before your IVIG dose to help prevent infusion-relation reactions or side effects. These side effects are temporary and resolve over a short period of time. Moreover, serious effects like allergic reactions or blood clot formation occur rarely.

We recommend that you consult your healthcare provider immediately if you experience any of the above side effects. 

The Bottom Line

BK virus-associated nephropathy poses a significant threat to kidney transplant recipients. However, early detection and timely treatment can help prevent this infection and improve the transplant success rate in individuals who receive kidney transplants.

参考:

  1. Mosca, M., Bacchetta, J., Chamouard, V., Rascle, P., Dubois, V., Paul, S., Mekki, Y., Picard, C., Bertholet-Thomas, A., Ranchin, B., & Sellier-Leclerc, A. (2023). IVIg therapy in the management of BK virus infections in pediatric kidney transplant patients. Archives de PéDiatrie, 30(3), 165-171. https://doi.org/10.1016/j.arcped.2023.01.005
  2. Matsumura, S., Kato, T., Taniguchi, A., Kawamura, M., Nakazawa, S., Namba-Hamano, T., Abe, T., Nonomura, N., & Imamura, R. (2020). Clinical Efficacy of Intravenous Immunoglobulin for BK Polyomavirus-Associated Nephropathy After Living Kidney Transplantation. Therapeutics and Clinical Risk Management, 16, 947. https://doi.org/10.2147/TCRM.S273388
  3. Vu, D., Shah, T., Ansari, J., Naraghi, R., & Min, D. (2015). Efficacy of Intravenous Immunoglobulin in the Treatment of Persistent BK Viremia and BK Virus Nephropathy in Renal Transplant Recipients. Transplantation Proceedings, 47(2), 394-398. https://doi.org/10.1016/j.transproceed.2015.01.012
  4. Elizabeth, I. A., & Stanley, P. H. (2014). Intravenous immunoglobulin in BK virus nephropathy. The Open Urology & Nephrology Journal, 7(1), 129–132. https://doi.org/10.2174/1874303×014070100129
  5. Sharma, R., & Zachariah, M. (2020). BK Virus Nephropathy: Prevalence, Impact and Management Strategies. International Journal of Nephrology and Renovascular Disease, 13, 187. https://doi.org/10.2147/IJNRD.S236556
  6. Gorriceta, J. H., Otbo, A. L., Uehara, G., & Posadas Salas, M. A. (2023). BK viral infection: A review of management and treatment. World Journal of Transplantation, 13(6), 309. https://doi.org/10.5500/wjt.v13.i6.309
  7. Pezeshgi, A., Ghods, A., Keivani, H., Asgari, M., & Shatty, M. (2012). Incidence of BK Virus Nephropathy (BKVN) in Renal Transplant Recipients. International Journal of Organ Transplantation Medicine, 3(3), 115. https://pmc.ncbi.nlm.nih.gov/articles/PMC4089294/
  8. Ximenes, C., Cabral, D., & Cavalcanti, F. (2024). Intravenous human immunoglobulin in the treatment of BK virus nephropathy in kidney transplant: a case report. Transplantation Proceedings, 56(5), 1052–1054. https://doi.org/10.1016/j.transproceed.2024.02.003
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医学审核人 Robert Hakim博士,药学博士

Robert Chad Hakim 博士,药学博士,在加州北岭出生长大。他毕业于威斯康星大学麦迪逊分校药学院,获得药学学位。工作中最让他感到自豪的是积极推进临床项目,从而最大限度地提升患者护理的效果。他拥有重症监护委员会认证 (BCCCP),专业领域包括重症监护、药物信息、全科医学和心脏病学。闲暇时,他喜欢旅行。 

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