Richard Schechner

Prevention of Bone Loss in Renal Transplant Recipients: A Prospective, Randomized Trial of Intravenous Pamidronate

Renal transplant recipients are at risk of developing bone abnormalities that result in bone loss and bone fractures. These are related to underlying renal osteodystrophy, hypophosphatemia, and immunosuppressive treatment regimen. Although bisphosphonates are useful in ameliorating bone mineral loss after transplantation, it is not known whether their use in renal transplant patients leads to excessive suppression of bone turnover and increased incidence of adynamic bone disease. A randomized, prospective, controlled, clinical trial was conducted using the bisphosphonate pamidronate intravenously in patients with new renal transplants. Treatment subjects (PAM) received pamidronate with vitamin D and calcium at baseline and at months 1, 2, 3, and 6. Control (CON) subjects received vitamin D and calcium only. During months 6 to 12, the subjects were observed without pamidronate treatment. Biochemical parameters of bone turnover were obtained monthly and, bone mineral density (BMD) was obtained at baseline and months 6 and 12. Bone biopsies for mineralized bone histology were obtained at baseline and at 6 mo in a subgroup of subjects who underwent scheduled living donor transplantation. PAM preserved bone mass at 6 and 12 mo as measured by bone densitometry and histomorphometry. CON had decreased vertebral BMD at 6 and 12 mo (4.8 +/- 0.08 and 6.1 +/- 0.09%, respectively). Biochemical parameters of bone turnover were similar in both groups at 6 and 12 mo. Bone histology revealed low turnover bone disease in 50% of the patients at baseline. At 6 mo, all of PAM had adynamic bone disease, whereas 50% of CON continued to have or developed decreased bone turnover. Pamidronate preserved vertebral BMD during treatment and 6 mo after cessation of treatment. Pamidronate treatment was associated with development of adynamic bone histology. Whether an improved BMD with adynamic bone histology is useful in maintaining long-term bone health in renal transplant recipients requires further study.

Successful rescue therapy with plasmapheresis and intravenous immunoglobulin for acute humoral renal transplant rejection

Plasmapheresis (PP) and intravenous immunoglobulin (IVIg) remove donor-specific antibodies, a cause of acute humoral rejection (AHR). We describe the use of PP and IVIg as rescue therapy for AHR. The records of 143 renal transplants performed between October 1, 2000 and April 1, 2002 were reviewed. Patients who underwent PP and IVIg therapy for AHR were identified. The data reviewed included age, sex, source of transplant, number of human leukocyte antigen mismatches, transplant number, number of PP and IVIg treatments, dose of IVIg, time of AHR, serum creatinine (SCr) level at AHR, SCr level after PP and IVIg at 3 months, days to achieve 30% decline in SCr, and graft survival. Immunosuppression included basiliximab induction, tacrolimus, and prednisone (± sirolimus or mycophenolate mofetil [CellCept, Roche Pharmaceutical, Nutley, NJ]). PP was followed by IVIg infusion. Nine patients were treated for AHR with PP and IVIg. All nine patients demonstrated biopsy-proven AHR. One graft was lost. Mean 3-month and 1-year SCr levels were 1.9 and 1.8, respectively, in the remaining eight patients. AHR in renal transplantation can be effectively treated with PP and IVIg.

Chronic renal allograft rejection: no response to mycophenolate mofetil.

BACKGROUNDnMycophenolate mofetil (MMF) has been previously shown to prevent functional deterioration in an experimental model of chronic renal allograft rejection.nnnMETHODSnIn this retrospective case-control study, patients with chronic rejection who were receiving cyclosporine or tacrolimus and who had MMF added to their immunosuppressive regimen were compared with patients with chronic rejection who were not receiving MMF. Patients were matched for serum creatinine levels and transplant duration at the time MMF was begun.nnnRESULTSnIn the MMF group, the average dose of MMF was 1482 mg/day with an average duration of 19.3 months. Over 36 months, including 12 months before MMF and up to 24 months on MMF, there was no difference in serum creatinine levels between the two groups. Cyclosporine levels and dose were no different.nnnCONCLUSIONSnIn this small, retrospective, preliminary study, adding MMF to maintenance immunosuppression provided no clear benefit to renal allograft recipients with established chronic rejection. Larger prospective randomized studies are needed.

Prevalence of asymptomatic cholelithiasis and risk of acute cholecystitis after kidney transplantation

Prophylactic cholecystectomy for asymptomatic cholelithiasis is sometimes required before transplantation. However, there is little indication in the literature that transplant recipients are at any greater risk than individuals in the general population. Between January 1990 and December 1993, 211 renal transplant recipients underwent duplex sonography. All were asymptomatic. Twenty-one had positive findings: gallstones were found in 15 patients (7.11%) and sludge was found in 6 (2.84%). Of gallstone patients, seven (3%) were men and eight (4%) were women. One gallstone patient also had diabetes mellitus. The mean age by gender of the patients with calculi was 54 years for men and 38 years for women. Thirteen of the 15 patients with calculi (87%) have remained asymptomatic. Two patients (one diabetic) developed acute cholecystitis and underwent uncomplicated laparoscopic cholecystectomy. Patients with sludge were similar in gender and age to patients with gallstones; one patient had diabetes. No sludge patients became symptomatic. The incidence and morbidity of gallstones after kidney transplantation are low. Prophylactic cholecystectomy in asymptomatic patients before transplantation is not justified.

Basiliximab induction improves the outcome of renal transplants in children and adolescents.

Abstract. Thirty-two children and adolescents received their renal transplant at the Montefiore Medical Center, in New York, between October 1996 and May 2000. Twenty-four patients received basiliximab, in addition to tacrolimus and steroids (basiliximab group). The remaining eight patients received only tacrolimus and steroids (non-basiliximab group). The 1-year patient survival rate was 100% in both groups. The 1-year graft survival rate was 87.5% for the basiliximab group and 75% for the non-basiliximab group (P=0.45). The rates of acute rejection in the basiliximab and non-basiliximab groups were 26% and 43%, respectively (P=0.36). However, in recipients with ≤3 HLA mismatches, the rate of acute rejection was zero in the basiliximab group, and 40% in the non-basiliximab group (P=0.04). The beneficial effect occurred despite the fact that tacrolimus was maintained at below the target levels. There were no adverse events directly attributable to the administration of basiliximab. There were no cases of opportunistic infections or post-transplant lymphoproliferative disease. In summary, addition of basiliximab to tacrolimus and prednisone significantly decreased the rate of acute rejection in well-matched patients. Moreover, this effect was manifest at lower, and therefore less toxic, tacrolimus levels.

Improved Small Intestinal Preservation After Lazaroid U74389g Treatment And Cold Storage In University Of Wisconsin Solution

The small intestine (SI) is highly sensitive to oxygen free radical-induced injury. The most common preservation solution, University of Wisconsin (UW) solution, does not adequately prevent free radical-induced injury. Lazaroids, and U74389G in particular, are a new class of compound that are potent inhibitors of superoxide-mediated lipid peroxidation. We studied the added influence of U74389G to 18-hr cold preservation of rat SI in UW solution. Three groups of rats were studied. In group 1, SI was excised and reperfused immediately. In group 2, SI was stored in UW solution at 4 degrees C for 18 hr. In group 3, U74389G was given to the SI graft before storage and again before reperfusion. Blood reperfusion of the grafts was achieved via connection to the superior mesenteric artery and portal vein of support rats. Functional recovery was assessed using a maltose tolerance test. Weight changes were calculated and histologic studies done. After 30 and 60 min of reperfusion, maltose uptake in group 3 was significantly better than that of the group 2, and returned to control levels. Significantly more tissue swelling was noted in group 3 over control, but the magnitude was less than that of group 2. Less transmural necrosis and villous blunting were noted in group 3 versus group 2; the appearance of the mucosa in group 3 approached that of group 1. We conclude that the use of U74389G treatment in addition to cold storage in UW solution improves recovery of graft function and minimizes morphologic damage to the small intestinal mucosa.

Reassessment of the Value of Post-Vascularization Biopsy Performed at Renal Transplantation: The Effects of Arteriosclerosis

Between January 1, 1984 and December 31, 1991, 471 cadaver renal transplants were performed. We reviewed 130 transplants, which were biopsied 30 minutes to 1 hour after the establishment of renal allograft blood flow. Analysis showed a significant difference in 2-year graft survival rate between the groups with and without arteriosclerosis (71.8% versus 65.9%, p < 0.05). Arteriosclerotic changes were noted more frequently in biopsies from older donors (37 versus 28 years, p < 0.005). There was also a difference in ischemic time between the groups with and without tubular degeneration (30.1 hours versus 26.7 hours, p < 0.02), which did not correlate with the need for dialysis in the perioperative period (48% versus 49%, p > 0.8).

Excellent outcome using “impaired” standard criteria donors with elevated serum creatinine

Abstract:u2002 Introduction:u2002 To maximize organ utilization, the United Network for Organ Sharing (UNOS) encourages use of Expanded Criteria Donors (ECD). However, Standard Criteria Donors (SCD) may also be under‐utilized, some centers discarding kidneys with serum creatinine (S.Cr) >2.0 at nephrectomy. Our experience with the use of such ``impaired’’ kidneys was reviewed retrospectively.

Evidence that zero antigen−matched cyclosporine-treated renal transplant recipients have graft survival equal to that of matched recipients: reevaluation of points

The value of HLA matching in cadaver renal transplantation (CRT) continues to be debated. It has recently been suggested that increased importance be given to HLA matching for the distribution of cadaver kidneys. Such a policy would add both delay and expense to CRT, which could be justified only by significantly improved results. The results of CRT in 252 cyclosporine treated adult patients transplanted at our institution from November 1984 to April 1989 were reviewed. Kidneys were initially transplanted into crossmatch-negative recipients based on waiting time, regardless of match. From October 1987, a points system, based on United Network for Organ Sharing (UNOS) criteria has been used. Eighty-four pts. with zero antigen match with their donors were compared with 168 pts. sharing 1-6 Ag. Actuarial graft and patient survival were determined by the cumulative life table method and compared using a log rank test. Our results indicated no statistically significant difference in graft survival because of better matching or mismatching. These findings are in keeping with our previously reported long-term results for non-CsA pts. Past predictions of improved graft survival based upon better matching at our institution have not fulfilled expectations, with the exception of 6 Ag matches. In conclusion, increased emphasis on HLA matching with fewer points for poorer matches does not appear justifiable.

Renal allograft rejection in children and young adults : the Banff classification

In the Banff classification, arteritis and tubulitis are regarded as the principal histological lesions indicating acute renal allograft rejection. To test this claim, we examined 51 biopsies obtained from 21 children and young adults with transplant rejection. Two reviewers, blind to the clinical course, graded the biopsies according to the Banff scheme. In patients without significant tubulitis (borderline changes), rejection tended to be reversed easily (88%), often with methylprednisolone pulse (52%). In patients with arteritis or significant tubulitis (Banff I–III), rejection was reversed in only 23% (P < 0.001), in 9% with steroids, and in 14% with OKT3. Salvage of the graft was achieved in 26 of 35 (74%) with a score < 5 but in only 1 of 12 (8%) with a score ≥5 (P < 0.001). All 6 patients with vasculitis lost their grafts despite methylprednisolone pulse and OKT3. We conclude that the Banff classification predicts accurately the outcome of renal allograft rejection in children and may aid in choosing appropriate therapy.