Q.732. What are the complications of withdrawal?kidney transplant complications kidney transplant requirements kidney transplant rejection symptoms ki

Solid-organ transplant (SOT) TR are immunocompromised  and may be at higher risk for severe COVID-19 disease as compared to general population. Two large observational studies of SOT recipients with COVID-19, about 80-90 % of ptns required hospitalization; of those, nearly 40 % required intensive care & 30 % required mechanical ventilation. At one month, mortality (MR) exceeds > 20 %. These findings suggest: TR are at a higher risk for poor outcomes, multivariate analyses in both studies reported that age & chronic co-morbidities were the primary drivers of MR rather than immunosuppression.

@ Kates OS, Haydel BM, Florman SS, et al. COVID-19 in solid organ transplant: A multi-center cohort study. Clin Infect Dis 2020.

@ Leeaphorn N, Thongprayoon C, Chon WJ, et al. Outcomes of kidney retransplantation after graft loss as a result of BK virus nephropathy in the era of newer immunosuppressant agents. Am J Transplant 2020; 20: 1334. 

RENAL TRANSPLANTATION

Q.732. What are the complications of withdrawal?

A. Complications of withdrawal: Continued  immunosuppression (im/m.) administration to ptn é R. allograft failure would, at first glance, appear to be unnecessary, since such agent increase risk of infection without providing obvious benefits. However, withdrawal of im/m. may be ass. é significant complications:

1)   Precipitation of rejection, requiring Tx. nephrectomy.

2)   Secondary adrenal insufficiency.

3)   Loss of residual renal function (Kru).

4)   Potentially adverse immunologic effects é those pursuing another Tx.

Q.733. What are the indications of nephrectomy?

A.Indications for Tx. nephrectomy: onset of Sm and/or complications rel. to Rj. after withdrawal of im/m., and P.H. of early graft failure(with or without Sm and/or complications): Sm resulting fr. Rj. & necrosis incl.:[graft tenderness, fever, hematuria, localized edema & occasionally infection]. Less fulminant Rj. may present é unusual Sm, such as [wt loss, anemia, fatigue, G.I. complaints, neurologic disturbances & resistance to Epo.].  Ptn. who have early graft failure (= return to DX é one y. of Tx.) are much more likely to development graft-related complication requiring nephrictomy thn are those é late allograft failure, independent of whether im/m. medications are withdrawn. Alth. such complications may be obs. in ptns in whom withdrawal is not initiated, abruptwithdrawal of im/m. among those é early graft failure⮞increase risk of ppt Rj. tht requires nephrectomy. In addition, morbidity & mortality fr. nephrectomy hs improved markedly over the last 3 decades. These obs. hv led most centers to adopt a policy of immediate withdrawal of im/m. combined é + preemptive nephrectomy for ptns é early allograft failure.

Indications for Tx. nephrectomy in late allog. failure after initiation of DX are not clearly defined, but may be considered in ptns é Sn & Sm of a ch. inflmm. state . Some clinicians, advocate allog. removalé features of such an inflmm. state, while others sugg. nephrectomy only é Sm.  Analysis based éU. S. Renal Data System suggest.: survival is improved after Tx nephrectomy. Among nearly 11,000 DX ptns with a failed kidney allograft, 32%underwent nephrectomy between 1994 &2004. The relative risk for all-cause death was signif. Lower for those é Tx nephrectomy. Although nephrectomy is the conventional approach to removing failed R. allografts, some centers have rep. some success é vascular embolization. Further study is required to clarify the role for this technique, é some concern related to M.R. & absence of data é hematologic & biochemical outcomes.

Q.734.What are the methods of withdrawal?

A. No controlled, prospective studies have been performed to clatify the best method for tapering/withdrawing im/m. following R. allog. failure. Most centers have sp. protocols. The foll. approach⮞stable nephrectomy rate of apprx. 30%: Most Tx. centers have adopted a policy of immediate withdrawal of im/m. combined épreemptive nephrectomy for early allograft failure:[failure occur <one y. after surgery].Withdraw im/m. é later allograft failure, é no one remaining on any type of im/m. for longer thn 6 m. fr. time of allograft failure. A standard protocol is to immediately withdraw {Csp. or Tcrol, and Aza or MMF}; subsequently taper{pred. by 1 mg/m.} until the drug is discontinued, carefully watching for Sm. of adrenal insufficiency. Different appr. if ptn hs continued toproduce urine despite allograft failure: withdraw the anti-metabolite immediately,🠋CNI dose to once/d.in the morning&🠋pred. to 5mg/d.; both remaining im/m. ag. are tapered slowly over 3-6 m..This approach allows ptn to obtain benefits of additional solute & waterclearance& recover nutritionally; this permits the ptn to tolerate a nephrectomy, if necessary, without risking immediate Rj & need for Tx. nephrectomy while balancing the risks of ongoing im/m..Further studies are needed to determine if slower taper of other im/m. ag., such as CNI, can🠋incid. of nephrectomy without untoward S.E. in DX ptn. Patient developing Sm. of allog. Rj é withdrawal, some give 5-7 d., pred.0.3-1.0mg/kg/d.; thenrefere  for surgery. Some nephrologists advocate immediate nephrectomy é even mild Sms of Rj. after im/m. withdrawal.

Q.735.What are the reasons for withdrawal ? 

A.The most compelling reasons to withdraw im/m. medications in DX ptns é failed R.Tx.: [Incresed risk of infection, malignancy & complications ass. é long-term corticosteroid im/m. use]. Infectionis the 2^nd leading cause of death in this setting. Another problem: dosing of some im/m. ag. is difficult in R.F.

Q.736.What is the role of HLA matching in graft survival in R.Tx.?

A. HLA system Ag.s:=Mj. barrier to acceptance of R.Tx.. The Mj. impact comes fr. mismatch of  👉 DR Ag.& to a lesser degree,B Ag., élittle effect fr. A Ag.. Each Ag. exerts its effect at different timespost-Tx: maximal effect of DR&B mismatching occ. é 1^st6 m.s & two y.s post-x., resp.. Degree of mismatching is ass. é long-term graft survival, though not early Rj.. Long-term survival is best in HLA-identical, esp. living related, kid. & worst in randomly matched cadaver kidney. Despite the importance of HLA-DR matching, some seemingly well-matched kid. are still rejected, wch. reflects the incomplete accuracy of routinely used tissue typing methods. Cold isch. time>36 h. No benefit fr. HLA matching. This’s important since if there were no cold ischemic time effects, a strategy of national allocation & shipping of all kidneys (not just zero mismatches) to 🠋 HLA mismatches wd generate the largest graft survival improvement & cost savings. This longer preservation times & 🠝cold ischemic time negatively affects outcome & costs.

 

Distribution of HLA Ag.s in U.S. & frequency of deceased donor donation differs é racial groups, thereby affecting organ allocation. Between 1987&1995, black ptn.s received only 6% of fully matched kid.s despite constituting one 1/3^rdof the national waiting list. Conversely, 30% of partially or fully mismatched kid. go to black recip., approximating frequency é wch blacks appear on waiting list. To address this relative inequity, the national allocation policy of U.S. ws changed to nolonger give priority points for fewer HLA-B mis-matches. Other histocompatability Ag.s incl. MHC class I-related chain A (MICA) & H-Y Ag. A.B. directed agnst MICA may adversely affect allog. function & survival. Some authors hv therefore recomm. universal testing of R.Tx. ptn. for A.B. post-Tx. & careful monitoring of s. cr. if A.B. are detected. However, such testing is not widely performed. We test for such A.B.s in select ptn.s é unexplained Rj.. Reactivity agnst Y chromosome H-Y encoded gene products: Tx. fr. ♂ donor to ♀ recip. 🠝risk of Rj. However, role of gene products in R. Tx. is unclear.