Q.729.What are the treatment recommendations of C4d staining in R. allografts & AMR?

KIDNEY TRANSPLANTATION 

Q.729.What are the treatment recommendations of C4d staining in R. allograft & AMR?

A.Non-Dsz:  AMR ptns who hvn’t Dsz: either daily or alternate d. Pph. é either centrifugal or membrane pl. separation. Initial ttt: one & 1/2 vol. exchange & subsequent éone vol. exchange of albumin, é fff as indicated. An alternate d. exchange protocol may be preferable, as albumin alone cn often be given for replacement é interval recovery of PT, PTT  & fibrinogen to acceptable levels é no need for fff. This avoids risk of Ag. Ssz; however, 1-2 u. of fff shd be used for replacement é end of Pph. ttt if indicated (by pre-procedure lab. values or é same d.R. biopsy). 100mg/kg of IVIG is given after each exch.& 500 mg/kg/d. for 1-2 d. after final exch., é total cumulative target dose of 1000mg/kg of IVIG. Pph is continued until s. Cr.➤20-30 % of baseline/minimum 4 sessions. If ptn. is not on tcrol./MMFØswitch to them. If already on tcrol./MMF ➤🠉 dose if necessary. MPd 300-500mg/d./3-5 d. given foll. By rapid taper to maintenance pred. dose.

Refractory👳Ac. AMR: Rituximab 375mg/m2 given one time dose added + Pph, MPd & IVIG. Concurrent severe hist. evid.of cell. Rj. (Banff 2A or more) ➤ combin. of Pph, IVIG, MPd &TG.. So, us. performed Pph &IVIG(100mg/kg) on E.O.D.(Mon.,Wed.,Frid.& Sun.)/minimum 4ttt.s + TG(1.5-3.0mg/kg) E.O.D. é interve-ning d. (Tues.,Thurs. & Sat.)/total of 3 doses. However, one analysis suggest: suppl.TG given post Pph🠞 necessary to maintain equivalent s. levels, compared to TG doses é abs. of Pph. IVIG 500mg/kg is again given for 1-2 d. foll. final planned exch. é total goal of at least 1000 mg/kg of IVIG dur. ttt course.

 

Detection of DSA: é AMR, check for DSA (with titer if present) prior to ttt, during ttt. course (if s. Cr. is not decr.) & after final pl. exchange. é successful ttt. Achieving 50 %🠟 in DSA in AMR hs bn ass. é improved graft survival, supporting use of DSA monitoring to assess response to ttt. If cell-based testing for DSA is used, ttt é TG, rituximab, or IVIG⮞ false +ve results, necessitating these A.B. be adsorbed prior to testing.TG adsorption doesn’t affect in-vitro DSA testing. DSA (ELISA) é recent A.B. preparations 🠟 likelihood of interference é results in abs. of mono- or polyclonal A.B. adsorption. Donor lysate samples(ELISA)➤simplify getting serial DSA titers to monitor ttt response or suggestion of recurrent AMR foll. successful initial ttt.

If there’s evidence for DSA by ELISA, obtain a titer. In case of +ve C4d staining or other concern for AMR based é histological findings or lack of good clinical resp. to ttt for presumed CMR despite -ve ELISA, a more sensitive Luminex assay is per-formed to further evaluate evidence of DSA. Following successful ttt of AMR, a R. panel is obtained twice/w. for one m. & then weekly/3 m.. In case of Tx. into a recip. at high risk of AMR or following successful ttt of AMR, DSA assays are often obtained weekly /1^st4-12 w., then monthly times 3. Newly evident or 🠉 titer DSA despite pres. of stable s.Cr. shd prompt a biopsy & consideration of ttt targeting AMR.

 

Titer of certain DSA (DR52, DR53 &DQ group), may not 🠟 significantly despite ttt. This hs bn most commonly encountered é CAG, é biopsy ➤+ve C4d staining. Persistence of these A.B. has been rep. é setting of HLA Dsz. Significant of persistent🠝A.B. titers in abs. of graft dysfunction or histological evidence of Rj. (biopsy) is unclear.

Aggressive ttt may not be required é mild Rj. Just as some mild CMR episodes resolve without 🠝 intensity of im/m., the same may occur é relatively mild AMR In case of stable graft function é incidental finding of C4d +ve biopsy with or without evidence for DSA& abs. of hist. find., changing to or 🠝 dose of tcrol. & MMF &🠋threshold for repeat biopsy é graft dysfunction may be warranted.

Ch. allograft G.pathy: (CAG=CAN): Although significant of +ve C4d st. or +ve DSA é ch. setting is unclear, this may represent a chronic process of AMR tht might be fore-stalled through augmentation of im/m. regimen. We convert to or augment dose of tcrol. & MMF in case of CAG & +ve C4d st., é or without DSA. In case of graft dysfunction & +ve C4d st. alone without histological evidence of CAG in late Tx. period, follow the same protocol. Consideration may be given to 🠉maintenance dose of steroids to 10mg/d.if other measures is ineffective or not tolerated. If present, we repeat DSA titers after changes in im/m. regimen. Use of IVIG or other adjunctive measures, e.g. rituximab, é CAGé apparent AMR may be considered.    ♠♠

Q.730. What are the possible risk factors for graft failure in R. Tx.? 

A.There’re multiple f. of short- & long-term graft survival; most f. can affect both. Mj. f. tht dcr. short-term graft survival incl.:[Delayedallog. func. & pres. of HLAA.B.]. In addition, living donor Tx. hv a greater short-term survival rate than deceased donor kid.. Expanded criteria donor kid.(i.e, fr. brain-dead donors >60 y.  or é history of H.T. or stroke as a cause of death) are also assciated🠟 short-term graft survival. Donor illness, CMV seropositivity & f. related to Tx. medical center also play a role. Early allograft survival may vary é maint. DX & perhaps type of DX prior to Tx.

Late allograft failure is increase é [Delayed graft function, HLA mismatching, cold isch. time, dev. of anti-HLA A.B., & inadequate im/m. thpy]. Beneficial effect of HLA matching outweighs the detrimental effect of prolonging cold ischemia time in Tx. Kid.. Preformed HLA donor-specific A.B. are associated é 🠟allograft survival & may represent non-HLA immunity in some cases. AlloAg. independent f. contribute to 🠟 graft survival, which. incl.: {Inadequate R. mass, prior & ongoing tissue inj., noncompliance, post-transplant H.T., hyperlipidemia, a more marginal kid., CNI toxicity, CMV. seropositivity & recurrent or de novo G. disease.}.

Q.731. Why it is necessary to withdraw immunosuppressant after renal transplant failure? 👉

The reasons to withdraw im/m. medications in DX ptn. é  failed R.Tx. are : {The incr. risk of infection & malignancy if such agents are continued, S.E. of long-term steroid therapy, and tht dosing of some im/m. ag. is difficult in ptn é R.F.}.

The withdrawal of im/m. may be ass. é significant complications.  (see below).