Thread by @Emilia_Nunez_

1/Hello everyone! Welcome to this month’s #ASPNFOAM group Tweetorial, featuring BK polyomavirus (BKV) & #BKNephropathy
🚨Spoiler alert: BK does not stand for Burger King🍔. But hopefully this 🧵 has been cooked up to your liking😉.
#Medtwitter #NephTwitter #PedNeph @ASPNeph

2.1/ So what’s “BK” & why can’t you have it with a side of🍟?
“BK” actually stands for B.K., the initials of the Sudanese🇸🇩 kidney transplant (KT) patient in whom the virus was 1st identified back in 1971! Not that long ago if you think about it 🤔
(PMID: 4104714, 33319201)

2.2/Also:
➤BKV is a non-enveloped double-strand DNA virus.
➤Primary infection occurs through respiratory secretions, mainly asymptomatic.
➤It infects urothelial and tubular cells in a non-replicative latent phase.

3.1/What % of the healthy adult population is seropositive for BKV due to primary infection?

3.2/That’s right! >80% of the healthy adult population has BKV latent infection. In fact, primary infection usually happens before adolescence, with an IgG seroprevalence of >90% in healthy 5-9 yr olds
(PMID: 31273924, 33510329)

3.3/Problem is that in the setting of immunosuppression -like after organ transplantation- BKV can reactivate, potentially leading to kidney dysfunction and/or graft failure in KT recipients😓

4.1/Pop quiz! What are common viral infections that can adversely affect kidney graft survival?

4.2/Yep, All the above. But in contrast to CMV, there's no effective antiviral therapy for BKV
Interestingly, studies show that the usual universal Valganciclovir prophylaxis for CMV entails a ↑ risk of BK viremia and BKV-associated nephropathy (BKVN). Yikes!😬

(PMID:31220412)

5.1/ This next infographic is 🔑 (trust me):
Early after transplantation when immunosuppression level is at its highest, BKV intracellular reactivation starts a cascade of events…

(PMID: 33510329, 31273924, 31858227)

5.2/📝Even though BKV-related disease is commonly seen in KT and hematopoietic stem cell transplant recipients, it can also occur in nonkidney solid organ transplant, and/or other types of immunodeficiency

(PMID: 23465010, 3331920)

6.1/When does BK viremia tends to appear in pediatric and adult KT recipients:

6.2/Yes! BK viremia can usually be detected in the early post-transplantation period (<6 mo after transplant), which can then lead to BKVN

(PMID: 30539254).

7/Some BKVN stats to keep in🧠:
➤BKVN will develop in 1–10% of all KT recipients
➤10–80% of KT patients with BKVN will have allograft loss
➤>15% of patients are expected to lose their allograft kidney within 1 yr of BKVN diagnosis

(PMID:30539254, 12138148)

8/Regarding pediatric KT recipients:
➤BK viremia rates > in the adult KT recipients (30.2% vs 11.5-12.8%)
➤BKVN is associated with acute rejection (32%) & graft failure (40%) 24 months after diagnosis

(PMID:33510329, 29626241)

9/In the pediatric KT population, some of the risk factors for developing graft loss from BKV include
➤Male gender
➤Younger age of transplantation
➤HLA mismatch
➤Rejection in 1st year
➤Tacrolimus use at discharge
➤Urological cause of ESKD

(PMID: 33245596,30539254,33245596)

10.1/What is the screening recommendation for BKV reactivation and BKVN?

10.2/🚨SERUM BKV PCR TESTING IS THE CURRENT SCREENING RECOMMENDATION🚨
➤Many post-transplant patients have BK viruria which is mostly self-limited and doesn’t necessarily progress to viremia
➤Plasma PCR/Viremia has a better correlation with BKVN than Viruria

(PMID:10793163)

10.3/Fun Fact!🔬
Though detection of virally infected uroepithelial cells (also known as “decoy cells”) in urinary cytology was the 1st diagnostic test for BKV reactivation and BKVN, it's NOT currently used in screening because...

10.4/...Sadly, the positive predictive value of "decoy cells" in urinary cytology for BKVN is only 5–29% and intraobserver variability is high.

So no microscope🔬 fun time for us #nephnerds 😔

11.1/Most current BKV screening recommendations follow a path similar to the guidelines proposed by AST in 2019 (PMID:30859620):
➤1️⃣First 3-9 mo after transplant→MONTHLY serum BKV PCR testing
➤2️⃣After this period→PCR testing every 3 until the end of the 2nd yr post-transplant

11.2/According to 2019 AST guidelines serum BKV PCR results can be interpreted as:
★ >1000 copies/mL
➤Considered positive for BK viremia & “Probable BKVN”
➤Can be self-limited
➤Repeat Serum PCR within 3 weeks
★ >10,000 copies/ml
➤“Presumptive BKVN”

(PMID:30859620)

12.1/🥇Gold standard for diagnosis of “Definitive BKVN” is a kidney biopsy using immunohistochemistry (SV40 T antigen staining) or in situ hybridization

(PMID:30859620)

12.2/Indications for biopsy in KT recipients with BK viremia:
➤↓ in kidney allograft function
➤Highly sensitized status with panel reactive antibodies
➤​​History of acute rejection

(PMID:30859620)

12.3/🚨BUT, due to the focal nature of BKVN, negative biopsy results don’t necessarily rule it out (probability of sampling error 10–36.5%).

Regardless, here's an image 🔬 of BKVN with its characteristic ‘Decoy Cells’ for the kidney-thirsty #nephverse

13.1/Wait a sec, if there’s no efficient antiviral treatment, then what’s the first strategy for managing high load BK viremia and/or BKVN?

13.2/Answers!
➤Cidofovir: Careful,↑ doses can be nephrotoxic
➤↓IS dose: Yes! #1 strategy for managing high load BK viremia and/or BKVN
➤IVIG: used as adjunctive treatment but efficacy hasn’t been proven
➤Leflunomide: Sometimes used to replace the use of MMF

(PMID:30859620)

13.3/Although there’s a lack of RCTs studying specific ways of lowering IS, the following strategies have been reported:
➤Fluorquinolone prophylaxis (PMID: 20507960)
➤Mammalian target of rapamycin (mTOR) inhibitors (PMID: 32533451, 26994751)

13.4/With reduction of IS in patients with BK viremia of >1000 copies/mL sustained for 3 weeks or increasing to >10 000 copies/mL, clearance of viremia and prevention of BKVN have then been observed in 80–100% of patients

(PMID: 31858227)

14/⚡Call to action!⚡
In the pediatric population there’s a huge lack of RCTs that provide sufficient evidence to design specific treatment guidelines for BK viremia and BKVN…

15.1/Some other BKV-related diseases worth mentioning are:
➤Hemorrhagic cystitis: commonly seen in allogeneic hematopoietic stem cell transplant patients
➤Ureteric stenosis: ↑association with kidney transplant patients

(PMID: 33319201)

15.2/BKV has also been rarely implicated in extrarenal pathologies such as pneumonia, encephalitis, hepatitis, retinitis, capillary-leak syndrome, and cancer

(PMID: 23465010)

16/If all this BK talk made you crave a 🍔, here’s a “whopper” of a summary that may do the trick😉
#ASPNFOAM #Medtwitter #NephTwitter #PedNeph #Transplant #BKNephropathy @ASPNeph

17/And, if you’ve been left wanting more, here’s some additional reading used for this #ASPNFOAM group Tweetorial: shorturl.at/hsE16

18/For a case-based clinical discussion with a pathology expert login to @ASPNeph website. Special thanks to @drM_sudha @swasti_Thinks @mdabdul @nefron1310 @RoshanPGeorgeMD and #ASPNFOAM group

Until next time!
#Medtwitter #NephTwitter #PedNeph #Transplant #BKNephropathy

*18/Typo correction😅:
Special thanks to these amazing doctors @drM_sudha @SwastiThinks @md_abdulqader83 @nefron1310 @RoshanPGeorgeMD and to the #ASPNFOAM group!