How To Prevent And Treat BK Polyomavirus After Kidney Transplantation?
Apr 25, 2024
BK polyomavirus infection is a major challenge after kidney transplantation and can lead to premature failure of the transplanted kidney. There are currently no clinically available vaccines or effective antiviral drugs, but significant advances related to pathophysiology, diagnosis, and treatment may optimize the management of BK polyomavirus infection after kidney transplantation. These advances may improve ultimate outcomes for kidney transplant recipients.
In April 2024, the Global Transplantation Society announced guidelines for the diagnosis and treatment of BK polyomavirus after kidney transplantation. Based on its information, this article is divided into recommendations for renal biopsy examinations, diagnostic criteria, practical guidance on reducing immunosuppressants, and management recommendations for BK polyomavirus. , PK and PD discussion, cost-effectiveness recommendations, and timing of retransplantation.
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Kidney biopsy recommendations
If BK polyomavirus DNA monitoring is positive, the patient should be judged whether to undergo renal biopsy based on the patient's clinical indications (proteinuria, hematuria, etc.) (strong, A);
Patients who are BK polyomavirus DNA-positive, have stable renal function, and are at higher immunological or virological risk (e.g., higher DNA titers) should undergo renal biopsy (weak, D);
Interpret the current biopsy results of the transplanted kidney with reference to clinical, laboratory, and virological data, and previous biopsies (weak, C);
BK polyomavirus DNA should be scored semi-quantitatively and classified according to the Banff working group method (strong, C);
Using the American Society of Transplantation (AST) classification, after collecting inflammatory and tabular data, BK polyomavirus patients were divided into five categories: PyVAN-A, -B1, -B2, -B3, and -C (strong, C) ;
For patients with detectable BK polyomavirus DNAemia and meeting Banff diagnostic criteria, we recommend the diagnosis of antibody-mediated rejection (strong, C);
We recommend against diagnosing combined interstitial TCMR (Banff grade IA/B) on the basis of inflammation and tubulitis; instead, the discussion should use an interdisciplinary approach (strong, B).
We recommend immunohistology (clonal PAb 416 against the SV40 large t antigen) to confirm biopsy-proven BK polyomavirus infection (strong, A);
BK polyomavirus infection should be considered in SV40-positive patients (strong, B);
For patients whose BK polyomavirus DNAemia status is unknown but whose renal biopsy shows inflammatory changes, SV40 should be tested (weak, D);
It is recommended not to routinely use SV40 (LTag) immunohistochemical staining in patients who are BK polyomavirus DNA negative (weak, C);
We recommend against performing allograft biopsy during the course or resolution of BK polyomavirus DNAemia/nephropathy unless rejection or other renal disease is a concern and its detection would alter treatment (weak, D).
diagnosis
Kidney transplant recipients should be regularly screened for BK polyomavirus DNA positivity to promptly diagnose BK polyomavirus infection (strong, A);
BK polyomavirus DNA screening should be performed monthly for the first 9 months after kidney transplantation, then every 3 months until 2 years after kidney transplantation (Strong, B);
In resource-limited settings, urine cytometry can be used as a minimum screening method for BK polyomavirus (strong, B);
If blood cannot be collected or a blood test cannot be used, determine the BK polyomavirus DNA load in urine by the QNAT method at the corresponding time point (weak, D);
If urine bait cells are detected or the urine BK polyomavirus DNA load is ≥10 million copies/mL, we recommend measuring the plasma BK polyomavirus DNA load to guide clinical treatment (strong, B);
For combined kidney/solid organ transplants including pancreas, we recommend extending BK polyomavirus DNA load screening every 3 months to 36 months after transplantation (weak, C);
For nonrenal solid organ transplant recipients, BK polyomavirus DNA load screening may not be routinely performed (strong, B);
The same diagnostic laboratory uses a unified method to determine BK polyomavirus DNA load to avoid heterogeneity between examination methods (strong, B);
We recommend using QNAT to detect BK polyomavirus genome sequences, allowing detection of all genotypes and variants (strong, C);
We recommend using short amplicons of <150 bp for QNAT detection to avoid significant underquantification (strong, C);
Laboratory parameters and quantitation should be calibrated regularly to ensure the quality of BK polyomavirus testing (strong, C).
Practical guidance on reducing immunosuppressants
01 Summary
First confirm that the doses and concentrations of all immunosuppressive drugs are within the target range (weak, C);
We recommend monitoring BK polyomavirus DNA load every 2-4 weeks until clearance (strong, B) or stabilization at a plasma viral load <1000 copies/mL (or equivalent) (weak, C);
For rare patients who have reached the lowest dose of immunosuppression and have a BK polyomavirus DNA load <1000 copies/mL, it is recommended to follow up the BK polyomavirus DNA load and serum creatinine concentration every 3 months (weak, D).
02 Reduce antimetabolites first
① First reduce the dose of antimetabolite drugs by at least 50%:
If after 4 weeks of treatment the BK polyomavirus DNA load decreases 10-fold or falls below the lower limit of detection, the immunosuppressive agent should be further reduced (weak, C):
②Discontinue the antimetabolite and gradually reduce the corticosteroid dose to 5 to 10 mg/d of prednisone or equivalent (if applicable)
③We recommend adding prednisone (or equivalent) 5-10 mg/d to patients not taking corticosteroids to avoid CNI monotherapy (Weak, C)
If further reduction in immunosuppression is required, we recommend stepwise reduction of the calcineurin inhibitor (CNI) dose (tacrolimus trough target concentration 5 ng/mL; cyclosporine trough target concentration 100 ng/mL) (Weak, C).
03 Reduce CNI dose first
① Reduce the CNI dose by 25% to 50% in 1 to 2 steps. Specifically, the trough concentration of tacrolimus is 3 to 5 ng/mL, and the trough concentration of cyclosporine is 75 to 125 ng/mL.
If after 4 weeks of treatment the BK polyomavirus DNA load decreases 10-fold or falls below the lower limit of detection, the immunosuppressive agent should be further reduced (weak, C):
② Reduce antimetabolites by 50% and corticosteroids to 5 to 10 mg/d of prednisone or equivalent (if applicable)
③Discontinue antimetabolite drugs
We recommend adding prednisone (or equivalent) 5 to 10 mg/day to patients not taking corticosteroids to avoid CNI monotherapy (weak, C).
management advice
For kidney transplant patients who are not at high immune risk or complicated by acute rejection, we recommend reduced maintenance immunosuppression as the primary treatment option for persistent BK polyomavirus DNAemia/nephropathy (strong, B);
When BK polyomavirus DNAemia is between 1000 and 10 000 copies/mL (or equivalent) on two occasions within 2 to 3 weeks, we recommend reducing immunosuppression (weak, B);
We recommend reducing immunosuppressants in patients with BK polyomavirus DNAemia or biopsy-proven BK polyomavirus nephropathy based on 1 determination of BK polyomavirus DNA >10,000 copies/mL (or equivalent) (Strong, B);
We recommend reducing immunosuppression in biopsy-proven BK polyomavirus nephropathy even while awaiting BK polyomavirus DNA load results (strong, B);
We recommend that each transplant center develop institutional algorithms and standard operating procedures for reducing immunosuppression in patients with BK polyoma viremia (weak, D);
After confirming that the BK polyomavirus DNA test is negative, immunosuppressive therapy should be restarted based on the patient's individual immune risk, and BK polyomavirus DNA should be appropriately screened (weak, D);
If renal dysfunction is present, we recommend de novo donor-specific antibody (DSA) testing in patients with persistent BK polyomavirus DNAemia on the minimally acceptable immunosuppressive regimen to aid decisions about kidney transplant biopsy (weak, D);
For multiorgan transplant recipients, including renal or nonrenal solid organ transplant recipients with BK polyomavirus DNAemia or biopsy-proven BK polyomavirus nephropathy, we recommend careful reduction of immunosuppression as described above and close clinical and Laboratory monitoring, weighing the risks and benefits of rejection and graft loss (Weak, D).
PK and PD discussion
When treating patients with BK polyomavirus DNAemia/nephropathy, we recommend interpreting immunosuppression in the context of PK/PD, drug-drug interactions (including all other drugs, any alternative and complementary medicines, and over-the-counter drugs), and liver and kidney function Drug dose and trough plasma concentration (strong, B).
We recommend careful consideration and monitoring of reciprocal PK/PD effects of immunosuppression in promoting or inhibiting viral replication, kinetics, and BK polyomavirus DNAemia (weak, C).
We recommend that patients and caregivers be provided with ongoing medication education about medication compliance and that compliance be routinely assessed (Strong, B).
cost effectiveness advice
We recommend routine screening for BK polyomavirus DNAemia using the strategy proposed in current guidelines, as this is associated with improved clinical outcomes and is cost-effective in a robust model of kidney transplant recipients younger than 70 years of age (Strong, B );
We recommend against reducing screening frequency because it may reduce the effectiveness of the intervention by reducing immunosuppression, thereby increasing overall direct health care costs (weak, B).
Timing of retransplantation
For patients with renal allograft failure due to BK polyomavirus nephropathy, we recommend retransplantation (strong, B);
Before retransplantation, BK polyomavirus testing should be negative (weak, C);
For patients with allograft failure due to BK polyomavirus nephropathy and BK polyomavirus DNA-negative patients, we recommend that allograft nephrectomy not be performed routinely before retransplantation (weak, C).
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How Does Cistanche Treat Kidney Disease?
Cistanche is a traditional Chinese herbal medicine used for centuries to treat various health conditions, including kidney disease. It is derived from the dried stems of Cistanche deserticola, a plant native to the deserts of China and Mongolia. The main active components of cistanche are phenylethanoid glycosides, echinacoside, and acteoside, which have been found to have beneficial effects on kidney health.
Kidney disease, also known as renal disease, refers to a condition in which the kidneys are not functioning properly. This can result in a buildup of waste products and toxins in the body, leading to various symptoms and complications. Cistanche may help treat kidney disease ase through several mechanisms.
Firstly, cistanche has been found to have diuretic properties, meaning it can increase urine production and help eliminate waste products from the body. This can help relieve the burden on the kidneys and prevent the buildup of toxins. By promoting diuresis, cistanche may also help Reduce high blood pressure, a common complication of kidney disease.
Moreover, cistanche has been shown to have antioxidant effects. Oxidative stress, caused by an imbalance between the production of free radicals and the body's antioxidant defenses, plays a key role in the progression of kidney disease. ies help neutralize free radicals and reduce Oxidative stress, thereby protecting the kidneys from damage. The phenylethanoid glycosides found in cistanche have been particularly effective in scavenging free radicals and inhibiting lipid peroxidation.
Additionally, cistanche has been found to have anti-inflammatory effects. Inflammation is another key factor in the development and progression of kidney disease. Cistanche's anti-inflammatory properties help reduce the production of pro-inflammatory cytokines and inhibit the activation of inflammation mandatory pathways, thus alleviating inflammation in the kidneys.
Furthermore, cistanche has been shown to have immunomodulatory effects. In kidney disease, the immune system can be dysregulated, leading to excessive inflammation and tissue damage. Cistanche helps regulate the immune response by modulating the production and activity of immune cells, such as T cells and macrophages. This immune regulation helps reduce inflammation and prevent further damage to the kidneys.
Moreover, cistanche has been found to improve renal function by promoting the regeneration of renal tubes with cells. Renal tubular epithelial cells play a crucial role in the filtration and reabsorption of waste products and electrolytes. In kidney disease, these cells can be damaged, leading to damaged renal function. Cistanche's ability to promote the regeneration of these cells helps restore proper renal function and improve overall kidney health.
In addition to these direct effects on the kidneys, cistanche has been found to have beneficial effects on other organs and systems in the body. This holistic approach to health is particularly important in kidney disease, as the condition often affects multiple organs and systems. che has been shown to have protective effects on the liver, heart, and blood vessels, which are commonly affected by kidney disease. By promoting the health of these organs, cistanche helps improve overall kidney function and prevent further complications.
In conclusion, cistanche is a traditional Chinese herbal medicine used for centuries to treat kidney disease. Its active components have diuretic, antioxidant, anti-inflammatory, immunomodulatory, and regenerative effects, which help improve renal function and protect the kidneys from further damage. , cistanche has beneficial effects on other organs and systems, making it a holistic approach to treating kidney disease.
