#ToughTxCase I am going to start an educational series for #transplant professionals/trainees on complex cases I have the privilege to see @UWHealth Patients have provided informed consent for us to discuss their condition in order to help other similar cases @uw_nephrology
#ToughTxCase #1 is the story of Tom, a 73 year old man, who received a living unrelated #kidney tx for #ESRD due to an unknown etiology. Low immunological risk, VXM (-), #CMV D+/R-, basiliximab induction, standard TAC/MPA/P maintenance Rx on Valgan prophylaxis x 6M @TxPharmD
At his 3M visit, Tom complains of #diarrhea, weight loss (4 lbs in 1 month) and poor energy. His kidney fxn is at baseline Scr 1.3 mg/dL. What is the most likely diagnosis? Please feel free to discuss! @uw_IMresidency @askrenal @Nephro_Sparks
#ToughTxCase follow-up: Tom’s stool studies are negative but his outside lab #CMV viral load comes back at 58,000 copies/mL confirming the Dx of breakthrough CMV infection. Tom is admitted to our hospital for IV Ganciclovir and MPA is discontinued, TAC maintained at level 6-8...
Tom’s been volume contracted and relatively hypotensive. Scr increases from 2 to 3.8 within a week. A biopsy is performed inpatient. What do you think we found @NSMCInternship @accpimtrprn @ldcornell @TxPharmD @uw_IMresidency @uw_nephrology
#ToughTxCase day 3: okay here is the update: Tom’s biopsy ahowed segmental intracapillary #CMV-positive cells with or without segmental endocapillary hypercellularity. No tubulitis. @TxPharmD @uw_IMresidency 
#ToughTxCase continued: CMV viral load at our hospital was 251K copies/mL (Log 5.4 IU/mL). Resistance panel negative. We continued with IV GCV, further reduced TAC (level 4-6), and added IVIG 500 mg/kg/week for passive and active immunomodulation @EdoardoMelilli @hswapnil
#ToughTxCase continued: one month later, Tom was discharged home, CMV was down 720 copies/mL, but no improvement in Scr still at 4.1. E repeat biopsy was performed. What do you expect to find? @uw_nephrology @accpimtrprn @NSMCInternship @askrenal @
#ToughTxCase day 4: biopsy findings were consistent with T cell mediated #rejection Banff IA with a chronicity score of 6/12. No CMV. See below PAS courtesy of Dr. Weixiong Zhong 👇 @TxPharmD @uw_IMresidency @uw_nephrology @pathpouneh @accpimtrprn @Renalpathsoc
#ToughTxCase day 4 continued: How would you treat this episode of rejection (CMV VL at 724 copies/mL)?
We have also been using donor derived cell-free DNA (#ddcfDNA) #Allosure for non-invasive monitoring of Tom’s kidney function. Which of the following do you think fits best with the course of his disease (baseline -> CMV nephritis -> TCMR)? #askrenal @TransplantPulse
#ToughTxCase day 5: We treated TCMR as voted by the majority with steroids and IVIG. Tom’s #AlloSure and #CMV readings declined nicely👇 but his kidney function did not improve. Nuclear medicine and MRA/MRI showed lower pole #infarct 🤦🏻♂️ @TxPharmD @uw_IMresidency @accpimtrprn
#ToughTxCase day 5 continued. Repeat #biopsy is scheduled next week (I will report on it) but Tom has mild uremic symptoms and will probably need to return on #dialysis. Break-through CMV nephritis + TCMR + renal infarct -> 🤦🏻♂️🌪🔥@uw_nephrology @ChangUCanSpare @NSMCInternship
#ToughTxCase1: Teaching point #1: should we implement PCR surveillance during universal prophylaxis in CMV D+/R- patients? @csaddler7 @Transplant_ID @jeannina_smith #askrenal #CMV #TxID
#ToughTxCase1 Teaching point #2: Is there high value in non-invasive testing (e.g. #ddcfDNA) for the monitoring kidney allograft injury in patients with #transitional immune systems?
#ToughTxCase1 final questions: any other thoughts? Would you have managed this case differently? Thank you all for sticking with me through this first #ToughTxCase “tweetorial”. Let me know how I can improve content! 🙏🙂🙏 @TxPharmD @accpimtrprn @uw_IMresidency @NSMCInternship
#ToughTxCase2 I would like to thank Kurt our patient #2 for his informed consent to share his case: Kurt is 54 when he is called for his third #transplant. Original ESRD due to #nephrocalcinosis. He is highly sensitized (cPRA 100%) and on the waitlist x 10 years 👇@TxPharmD
He has a positive virtual crossmatch (DSA sum ~ 4,000 MFI all against class I HLA). He undergoes peri-Tx #desensitization with Thymo/Ritux/PLEX/IVIG and is discharged home with TAC/MPA/P. Nadir Scr 1.4 mg/dL. He is doing well x 3 months 👇@uw_IMresidency
At his third month visit Kurt complains of diarrhea and fatigue. His routine BK viral load is positive at 1200 copies/mL (Log 3). What do you do next: @accpimtrprn #askrenal
#ToughTxCase2 We went with option D. A month later Kurt presented with #AKI (Scr 1.4->2.3 mg/dL). His #BK viral load had increased (1,200->549,000 copies/mL) despite reducing MPA dose 🤦🏻♂️ We biopsied. What did it show? @NSMCInternship @RenalFellowNtwk @TxPharmD @uw_nephrology
#ToughTxCase2 okay... The majority was right I guess! Here is what we observed on the biopsy: tubular #SV40 staining positive-> #BKVN. Courtesy of the incredible Dr. Weixiong Zhong #renalpathrules #lovepathology @TxPharmD @Renalpathsoc @RenalFellowNtwk 👇
Your next step in this highly sensitized patient with a third transplant who now has #BKVN?
#ToughTxCase3 I have received requests to continue the series so here it is (with the explicit written approval from patient!) 47 year old woman with SLE nephritis receives an offer for deceased donor kidney transplant KDPI 83% cPRA 99% VXM (+) DQ9+DR9 MFI ~1000. What next?
Evidence supports desensitization instead of waiting (N Engl J Med 2011; 365:318-326) Patient was transplanted and underwent peri-Tx desensitization with rATG/PLEX/IVIG -> TAC/MPA/P. What was the first complication?
#ToughTxCase3 continued: The risk of DGF in this patient is ~ 30-40% (PMID: 29314286). She did present with DGF which was managed in the outpatient setting (PMID: 26700736) At her 3M visit Scr nadir 1.2, TAC level 10, HLA increased to 47,000 MFI, and AlloSure 1.2%. What next?
Majority wins! Biopsy done showing subclinical ABMR with i1g1ptc1ct1 Banff lesions. How would you treat? @TxPharmD @RenalFellowNtwk @uw_nephrology @ToniSabbouh @wisit661 @NSMCInternship
Once again the majority wins! Our studies suggest that treatment is subclinical ABMR is associated with better graft outcomes PMID 30507740 although risk of pneumonia (not CMV or BK) is increased PMID 33335983 @TxPharmD @RenalFellowNtwk @uw_nephrology @wisit661 @NSMCInternship
One month later patient presents with diarrhea and weight loss of 4 lbs What was the culprit? @TxPharmD @RenalFellowNtwk @uw_nephrology @ToniSabbouh @wisit661 @NSMCInternship @abregman42
She actually had both C-Diff and Norovirus diarrhea. @sandeshParaj @stacey_rolak have shown that these infectious complications are associated with worse long-term graft survival PMID 30689283. We reduced MPA dose and treated C-Diff with oral vanco. Diarrhea resolved 👇
MPA had to be discontinued altogether because of COVID pneumonia, which fully resolved but 9M after transplant patient presented with a rise in Scr 3.2, circulating HLA DSA (-) but AT1R ab (+), and AlloSure increase from 0.2% to 0.9%. What is happening? Thank you @aishaikh :-)
Indication biopsy showed mixed rejection and early transplant glomerulopathy with t3 i2 g2 ptc1 cg1a ti2 iIFTA3 ci1 ct1 cv1 Banff lesions. The change in AlloSure >0.5% would suggest poor outcomes in TCMR grade 1A or borderline (PMID 32056331). What next?
Patient was treated with Thymo/losartan/IVIG for mixed chronic active ABMR and TCMR IB rejection. Saw her yesterday 18M after transplant. Scr down to 1.6, UPC 0.7, AlloSure 0.55% feeling great but still not out of it. Planning a repeat surveillance biopsy in 4M 🙂
#ToughTxCase3 Transplanting highly sensitized patients across HLA barrier is challenging but rewarding. Without multidisciplinary and multimodality monitoring the risk of graft failure at 12M is high. Should CMS replace the benchmark of 12M graft survival with patient survival?
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