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RENAL TRANSPLANTATION

Q.726. What future ABOI & HLA desensitization (Dsz) protocols available?

  

RENAL TRANSPLANTATION

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Renal Transplantation- Allograft.




Q.726. What future ABOI & HLA desensitization (Dsz) protocols available?

A.Excellentlong-term results(é accepted high rate of AMRin HLAincomepatible Tx. & early graft loss will be likely be greater thn in nonsensitized recip.) are needed to justify financial cost & resource utilization, esp. é low dose IVIG protocols. If long-term allog. func. is maintained financial benefit will be realized. Comparative studies between high & low dose IVIG protocols are needed. Further information regarding what level of A.B. titer amenable to T.x. with or without Dsz is also needed. For ptn é option of continuing H.DX. or P.D., any long-term survival benefit fr.Tx. using intensive Dsz protocol remains to be determined.

 

“DONOR EXCHANGE”: Alternative to ABOI or HLA Dsz is  paired exchange program (PEP). Although fraught é ethical & legal concerns, willing participants can choose to allow either an ABO or HLA incompatible donor in one case to donate their kidney to an alternate recipient. also éABO or HLA incompatible donor tht’s agreeable to donating to their kid. to remaining recipient.

PEP: avoids need for Dsz & provides LDA to each recipient. Both parties must be in full agreement & understanding of potential post-T.X. ramifications & making decision on whether or not parties should remain anonymous to one another. PEP can help provide allograft to selected No. of individuals. However, this’s unlikely to have significant impact on🠋wait list time if PEP is confined to one Tx. center. Although fraught é logistical problems, incr. PEP to a regional or national level would 🠝No. of suitable donor pairs . A national kidney paired donation is considered in U.S.

Use of “donor exchange programs to perform wait list exchange (wherein incompatible donor donates to individual on waiting list & incompatible recipient moves to front of the wait list) as compared to PEP is controversial. This process may result in even further delays for wait times, esp. 

 blood group O recip.. Such a strategy may not be acceptable to some ptns, esp. blood group O.

Acceptable mismatch” programEurope: an acceptable mismatch program is in place that assists in providing DDA to highly sensitized ptn. through: enhanced distribution& immunologic screening protocol. But: there’s no statistically significant difference in graft survival in highly sensitized recipient vs non-HLA sensitized recipient.

Summary: Despite success in increase likelihood of an acceptable DDA being offered to a potential recip. highly sensitized to HLA Ag., some authors note  pool of ptn remain non-transplantable 2ndry to broad immunogenicity. 

Q.727. What are the “global recommendations” for chronic renal allograft nephropathy (CAN)?      

A. CAN: the 2nd most common cause of allog. failure after the most common cause, death with a functioning graft. Clinical Dgx: [Gradual decline of graft function, i.e slowly rising pl. cr., incr. proteinuria & worsening H.T.]. Pathologic changes involve whole R. parenchyma: (B.V., glomeruli, interstitium & tubules). G. cpll. walls are thickened é double-contour app. resembling MPGN but without👉dense deposits. [Interstitial fibrosis+ tubular atrophy+ this type of👉double-contour] 🠞the most ch.ch. findings for ch. Np. é Banff system .

Evaluation of CANbegins é {R. U/S. & estimation of proteinuria}. Alth. there’s variability concerning need for histologic analysis, we perform allog. biopsy to confirm Dgx. & provide prognostic information & to exclude other processes such as Ac, Rj. or recurrent G.N.. D.D. of CAN involves distinguishing among many f.s that cause progressive allograft dysfunction and/or associated é similar histologic findings

Prevention & management of CAN remains one of the mj. challenges facing Tx. nephrologists. To prevent general immunologic Rj., we maintain ptn. on triple im/m. thpy:[CALI, prednisone & antimetabolite]. Despite possible increase risk of CAN due to CALI, im/m. benefits might outweigh its possible adverse effects.

Changes in im/m. have largely been ineffective in changing prognosis of established CAN. However, consideration of CALI minimization or withdrawal, or conversion fr. Csp. to tacrolimus. For ptn. on Aza, conversion to MMF may be helpful. Finally, for those without proteinuria & GFR >50mL/min, conversion fr. CALI to sirolimus may be associated é improvement in GFR. Non-im/m. intervenetions for CAN. shd be focused primarily on: aggressive control of B.P. & hyperlipidemia.

Q.728. What are the diagnostic recommendations of C4d staining (C4d-st) in R. allografts?

A. Staining for C4 d = marker of A.B.-mediated Rj., should be incl. é all biopsies obtained for allog. dysf..This “complement component” may be detected in either Ac. or ch. allograft dysfunction & presence of C4d-st of PTC strongly suggest👉AMR. Pres. of DSA should be assessed anytime C4d is +ve or é concern for AMR. Recomm. differ based on either é susp. AMR or é abscnce of Dsz prior Tx.:

(A) No Dsz prior to Tx.: Advent of C4d-st & improved ability to detect DSA & description of typical hist. findings🠞recognition of AMR, either alone or + cell mediated Rj. This recognition🠞Banff system wch incl.: AMR criteria. An algorithm for AMR Dgx was formulated by “A.B. Workgroup for AMR.

Consider: (high vs low risk), pres. or abs. of clinical allograft dysfction, +ve C4d-st, L.M.: of AMR and/or DSA . High risk incl.:[husband/wife or child/mother-donor recip. pairs, P.H.: pregnancy, Bld Tx, or T.x. & known HLA-sp. AB.] (current or historic). Diagnostic criteria for AMR: dependent upon C.P. & pres. or abs. of the triad of:  👌

(1)  Detectable DSA.                                                     

(2)  Histologic evidence of AMR.   

(3) Diffuse intense peritub. cpll.” C4d deposition.

*      In allog. dysf., pres. of both C4d + DSA shd be considered as strong evidence for AMR requiring ttt. Histologic findings including:[Vasculitis, glomerulitis é neutrophils or lymphcytes é G. cpll. & peritub. cpll., fibrin thrombi, fibrinoid necrosis & interstitial hge rather thn tubulitis]. However, such findings may be absent, ttt and/or repeat biopsy shd also be considered in other settings:

1.    Ac. decline in graft func., presence of C4d +ve but absence of DSA and/or signif. hist. findings 🠞 indication for either initiating ttt for AMR or repeating biopsy. In the appropriate clinical setting and in abs. of another identifiable cause of graft dysfuction, strong consideration should be given to instituting thpy tht targets AMR on basis of C4d positivity alone.

2.    High possibility of AMR based on P.H or é Ac. decline of allograft function🠞initiate ttt targeting A.B. pathways even if only 👆one of triads is present.

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