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C4d staining of perioperative renal transplant biopsies
Haas, Mark; Ratner, Lloyd E; Montgomery, Robert A
BACKGROUND: Deposition of C4d in peritubular capillaries (PTCs) has been shown to be a sensitive marker for antibody-mediated (humoral) rejection in renal transplant biopsies. Some studies also suggest that C4d in PTCs is specific for humoral rejection or, at least, for the presence of donor-specific antibodies. However, in other studies, PTC C4d deposits were noted in more than 40% of renal transplant biopsies performed for graft dysfunction and capillary C4d deposition in heart transplants may result from ischemic injury. METHODS: To test the specificity of C4d staining as a marker for acute humoral rejection ACR in renal allografts, indirect immunofluorescence using a monoclonal anti-C4d antibody and a fluorescein-isothiocyanate-conjugated secondary antibody was performed on cryostat sections of 90 renal transplant biopsies, including 35 pairs of preimplantation and 1-hr postreperfusion biopsies of the same graft, postreperfusion biopsies of 12 additional grafts, and 8 positive controls (biopsies with known C4d-positive AHR). Eighteen grafts were cadaveric, 17 grafts were liviing-related, and 12 grafts were living-unrelated (excluding controls). Included in these grafts were 13 grafts that developed AHR 3 to 34 days posttransplantation. RESULTS: Only 2 of 82 perioperative biopsies showed C4d staining in PTCs. Both perioperative biopsies were postreperfusion biopsies of grafts diagnosed with AHR 5 and 34 days posttransplantation, respectively, and, in each case, the recipient had been treated with plasmapheresis before transplantation because of a positive crossmatch (cytotoxic and flow cytometric) and continued to have a weakly positive flow crossmatch at the time of transplantation. In one biopsy, C4d staining was focal, and in the other biopsy, it was diffuse; in both biopsies, C4d staining was relatively mild (1+ on a 0-4+ scale). No C4d staining was noted on preimplantation biopsies of each graft. All biopsies that contained glomeruli showed linear capillary loop or blotchy mesangial staining, or both, which was similar in prereperfusion and postreperfusion biopsies. All positive controls showed diffuse C4d staining in PTCs. CONCLUSIONS: C4d staining in PTCs may be seen as early as 1 hr posttransplantation in some recipients with low levels of antidonor antibodies. However, this was not observed as a feature of ischemic or ischemia-reperfusion injury in perioperative renal transplant biopsies, including those of cadaveric grafts with cold ischemia times of as long as 41 hr.
PMID: 12352891
ISSN: 0041-1337
CID: 1981312
Preemptive therapy with plasmapheresis/intravenous immunoglobulin allows successful live donor renal transplantation in patients with a positive cross-match
Sonnenday, C J; Ratner, L E; Zachary, A A; Burdick, J F; Samaniego, M D; Kraus, E; Warren, D S; Montgomery, R A
PMID: 12176507
ISSN: 0041-1345
CID: 1981322
Immunomodulation and accommodation in kidneys transplanted across positive crossmatch and ABO incompatible barriers. [Meeting Abstract]
Montgomery, RA; Samaniego, MD; Zachary, AA; Sonnenday, CJ; Warren, DS; King, KE; Ratner, LE
ISI:000177757500235
ISSN: 1046-6673
CID: 1982252
Successful ICAM-1 gene inactivation in pluripotent stem cells using RNA interference and in situ expressed antisense/ribozyme transgenes. [Meeting Abstract]
Warren, DS; Sonnenday, CJ; Cooke, SK; Montgomery, RA
ISI:000177757500496
ISSN: 1046-6673
CID: 1983182
Donor horseshoe kidneys for transplantation [Case Report]
Tan, H P; Samaniego, M D; Montgomery, R A; Burdick, J F; Maley, W R; Kraus, E S; Ratner, L E
BACKGROUND: Experience with donor horseshoe kidneys for transplantation is very limited. Currently, horseshoe kidneys may be underutilized for transplantation because of the greater incidence of vascular anomalies, associated renal anomalies, and predisposition to renal disease. METHODS: In this report, we review five transplantations using horseshoe kidneys: the largest reported institutional experience. In addition, a review of all published cases in the English literature is performed. RESULTS: All five patients underwent successful renal transplantations with a median follow-up of 35 months. One patient lost his kidney from recurrent disease soon after transplantation. CONCLUSION: With appropriate reconstruction of the vessels, careful division of the isthmus, and avoidance of ureteral obstruction, long-term data revealed good graft survival of donor horseshoe kidneys in renal transplantation.
PMID: 11571452
ISSN: 0041-1337
CID: 1981332
Liver transplantation in patients with severe portopulmonary hypertension treated with preoperative chronic intravenous epoprostenol [Case Report]
Tan, H P; Markowitz, J S; Montgomery, R A; Merritt, W T; Klein, A S; Thuluvath, P J; Poordad, F F; Maley, W R; Winters, B; Akinci, S B; Gaine, S P
Portopulmonary hypertension (PPHTN) is no longer an absolute contraindication to orthotopic liver transplantation (OLT). The pre-OLT management of patients with PPHTN requires early diagnosis and chronic therapy with intravenous epoprostenol to decrease pulmonary vascular resistance (PVR). Close follow-up is necessary to reassess pulmonary artery pressures (PAPs) and evaluate right ventricular (RV) function. This assists in the optimal timing of OLT. Successful management also necessitates reassessment of pulmonary artery hemodynamics just before OLT, with clearly defined parameters used to determine whether to proceed. Even with the intraoperative and postoperative availability of potent pulmonary vasodilators, clinical management may be suboptimal in reducing PAP. Adequate reduction in PVR and improvement in RV function in response to chronic epoprostenol therapy may facilitate successful OLT. We present a case report and review the limited experience with this treatment.
PMID: 11510023
ISSN: 1527-6465
CID: 1981452
Laparoscopic live donor nephrectomy. A review of the first 5 years
Ratner, L E; Montgomery, R A; Kavoussi, L R
Laparoscopic live donor nephrectomy is technically feasible. The operation has evolved over the last 5 years and is greatly improved compared with the procedure originally described. Advantages to the donor when compared with the standard open operation are decreased postoperative pain, shorter hospitalization, a quicker recuperation, an earlier return to driving, and an earlier return to employment. These improvements have resulted in fewer lost wages and a lower financial burden for donors. Live donor nephrectomy also provides improved cosmetic results. It successfully removes many of the disincentives to live kidney donation and has resulted in an increased willingness of individuals to donate their kidneys. The operative risk seems to be equivalent to that of the open donor operation performed through a flank approach. Although there is no financial advantage of the laparoscopic operation in terms of hospital costs, the increase seen in live donor transplantation may result in long-term cost savings overall. Kidneys procured laparoscopically function well in recipents in the short and long term. There is no increased risk for rejection or technical complications, and the recipent's length of hospitalization is unaffected. The laparoscopic donor operation does not have any apparent deleterious effect on the recipient. The procedure is being adopted rapidly by transplant centers around the world and has been performed at more than 100 centers on five continents. The authors believe that laparoscopic live donor nephrectomy will become the standard of care in the not too distant future.
PMID: 11791488
ISSN: 0094-0143
CID: 492872
Should the indications for laparascopic live donor nephrectomy of the right kidney be the same as for the open procedure? Anomalous left renal vasculature is not a contraindiction to laparoscopic left donor nephrectomy
Mandal, A K; Cohen, C; Montgomery, R A; Kavoussi, L R; Ratner, L E
BACKGROUND: The left kidney is preferred for live donation. In open live donor nephrectomy, the right kidney is selected if the left kidney has multiple renal arteries or anomalous venous drainage. With laparoscopic live donor nephrectomy (LLDN), there is reluctance to procure the right kidney because of the more difficult exposure and further shortening of the right renal vein (RRV) after a stapled transection. An experience with LLDN is reviewed to determine whether the right kidney should be procured laparoscopically. METHODS: From February 1995 to November 1999, 227 patients underwent live donor renal transplants with allografts procured by LLDN. The results of these transplants were analyzed. RESULTS: Of the 227 kidneys transplanted, 17 (7.5%) were right kidneys. In the early experience, three (37.5%) of the eight right renal allografts developed venous thrombosis, two of which had duplicated RRV. Based on these initially unacceptable results, donor evaluation and LLDN techniques were modified. Spiral computerized tomography (CT) replaced conventional angiography to define better the venous anatomy. LLDN was modified in one of three ways: (1) changing the stapler port placement such that the RRV was transected in a plane parallel to the inferior vena cava, (2) relocation of the incision for open division of RRV, or (3) lengthening of the donor RRV with a panel graft constructed of recipient greater saphenous vein. Finally, the recipient operation enjoined complete mobilization of the left iliac vein with transposition lateral to the iliac artery. With these modifications, there were no vascular complications with the subsequent nine right renal allografts (P<0.05). Of the left kidneys transplanted, 31 had multiple renal arteries, 14 had retroaortic or circumaortic veins, 4 had both multiple arteries and venous anomalies, and 1 had a duplicated IVC draining the left renal vein. There were no vascular complications with left renal allografts that had multiple arteries or venous anomalies. CONCLUSIONS: LLDN of the left kidney is technically easier. Left kidneys with multiple arteries or anomalous venous drainage are not problematic. The right kidney can be procured with LLDN; however, a rational approach to preoperative angiographic imaging, donor operation, and recipient operation is crucial.
PMID: 11292298
ISSN: 0041-1337
CID: 493032
Improved recipient results after 5 years of performing laparoscopic donor nephrectomy
Montgomery, R A; Kavoussi, L R; Su, L; Sinkov, V; Cohen, C; Maley, W R; Burdick, J F; Markowitz, J; Ratner, L E
PMID: 11267212
ISSN: 0041-1345
CID: 493052
Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into cross-match-positive recipients
Montgomery, R A; Zachary, A A; Racusen, L C; Leffell, M S; King, K E; Burdick, J; Maley, W R; Ratner, L E
BACKGROUND: Hyperacute rejection (HAR) and acute humoral rejection (AHR) remain recalcitrant conditions without effective treatments, and usually result in graft loss. Plasmapheresis (PP) has been shown to remove HLA- specific antibody (Ab) in many different clinical settings. Intravenous gamma globulin (IVIG) has been used to suppress alloantibody and modulate immune responses. Our hypothesis was that a combination of PP and IVIG could effectively and durably remove donor-specific, anti-HLA antibody (Ab), rescuing patients with established AHR and preemptively desensitizing recipients who had positive crossmatches with a potential live donor. METHODS: The study patients consisted of seven live donor kidney transplant recipients who experienced AHR and had donor-specific Ab (DSA) for one or more mismatched donor HLA antigens. The patients segregated into two groups: three patients were treated for established AHR (rescue group) and four cross-match-positive patients received therapy before transplantation (preemptive group). RESULTS: Using PP/IVIG we have successfully reversed established AHR in three patients. Four patients who were cross-match-positive (3 by flow cytometry and 1 by cytotoxic assay) and had DSA before treatment underwent successful renal transplantation utilizing their live donor. The overall mean creatinine for both treatment groups is 1.4+/-0.8 with a mean follow up of 58+/-40 weeks (range 17-116 weeks). CONCLUSIONS: In this study, we present seven patients for whom the combined therapies of PP/IVIG were successful in reversing AHR mediated by Ab specific for donor HLA antigens. Furthermore, this protocol shows promise for eliminating DSA preemptively among patients with low-titer positive antihuman globulin-enhanced, complement-dependent cytotoxicity (AHG-CDC) cross-matches, allowing the successful transplantation of these patients using a live donor without any cases of HAR.
PMID: 11014642
ISSN: 0041-1337
CID: 1981342