Morrissey Pe

Excess risk of renal allograft loss and early mortality among elderly recipients is associated with poor exercise capacity.

BACKGROUNDnSuccessful renal transplantation in the elderly offers substantial benefits in quality and life expectancy. However, in this group of patients there is an early increased risk of death compared with those remaining on dialysis.nnnMATERIALS AND METHODSnGraft and patient outcomes in 64 older transplant recipients were compared with 338 patients aged 18 - 59 years. We identified potential risk factors that may predict clinical outcomes in older transplant recipients. A log-rank test and Cox regression analyses were performed to assess the impact of various patient characteristics on graft and patient survival.nnnRESULTSnAmong older patients, graft survival was 76.6% and 67% at 1 and 3 years, respectively. When graft survival was censored for death with functioning graft, the 1- and 3-year graft survival was 83% and 82%, respectively. Patient survival was 78% and 71% at 1 and 3 years, respectively. These survival rates were significantly lower than those of younger recipients. Pretransplant inactivity, delayed graft function, smoking history and longer waiting time predicted poor graft and patient survival. A history of chronic obstructive pulmonary disease, and peripheral vascular disease also predicted a higher mortality among older recipients.nnnCONCLUSIONnOlder kidney transplant recipients are at high risk for allograft failure and early death. Poor functional capacity predicts a poor outcome for older patients undergoing renal transplantation. Therefore, careful patient selection is paramount, and every effort should be made to initiate timely interventions aimed at increasing physical activity in those with low fitness level.

Correlation of clinical outcomes after tacrolimus conversion for resistant kidney rejection or cyclosporine toxicity with pathologic staging by the Banff criteria.

BACKGROUNDnRefractory rejection and cyclosporine (CsA)-induced nephropathy remain important causes of renal allograft loss. Previous studies demonstrated that 70-85% of the episodes of refractory acute rejection (AR) occurring in renal allograft recipients on a CsA-based immunosuppressive regimen could be salvaged by conversion to tacrolimus. No data are available regarding the correlation between allograft histology at the time of conversion and the response to tacrolimus. We examined the response to tacrolimus conversion in relation to preconversion biopsies stratified by the Banff criteria.nnnMETHODSnSince May 1992, we have converted 22 patients from CsA to tacrolimus as part of a rescue protocol. We report on 18 patients in whom 6-month follow-up was available after conversion for biopsy-proven AR (n=13) or CsA toxicity (n=5). Sixteen patients were recipients of renal allografts, including three second transplants, and two were recipients of kidney-pancreas transplants. All patients with AR were treated with one or more courses of methylprednisolone and OKT3 before conversion. Renal allograft biopsies were interpreted by a transplant pathologist blinded to the clinical history, and graded according to the Banff criteria. Responses to tacrolimus were scored as improved (creatinine returned to within 150% of baseline), stabilized (creatinine rise arrested), or failed (returned to dialysis). RESULTS; Mean follow-up was 17.3+/-8 months. Fourteen of 18 patients (78%) showed improvement or stabilization in renal function as assessed by creatinine at 6 months or 1 year (when available). Of the 13 patients with histological AR, nine (69%) improved, including five of six with borderline AR, two of three with grade I AR, and two of four with grade II AR. Of the four other patients with AR, two stabilized and two failed. Three of five patients with severe clinical rejection requiring dialysis (range 2-16 weeks) recovered renal function after conversion. Of five patients with CsA toxicity, two (40%) improved. Seven of eight patients who were converted to tacrolimus less than 90 days after transplantation improved, compared with only 4 of 10 who were converted more than 90 days after transplantation. No grafts were lost in patients with a creatinine <3.0 mg/dl at the time of conversion versus two of seven grafts lost when the creatinine was 3.1-5.0 mg/dl and two of eight grafts lost when the creatinine was >5.0 mg/dl.nnnCONCLUSIONnThe majority of steroid and antilymphocyte antibody (OKT3 or ATGAM) unresponsive rejections in patients on CsA-based immunosuppression will improve or stabilize after conversion to tacrolimus. There was no correlation with allograft histology stratified by the Banff criteria and the response to tacrolimus. Although there was a trend toward a poorer response with more severe histological rejection, higher serum creatinine at the time of conversion, and longer time from transplantation to conversion, favorable responses were noted in all groups. This indicates that a trial of conversion is warranted, irrespective of the histological severity of injury.

Cryptosporidium infection in renal transplant patients.

Cryptosporidium parvum, an intracellular protozoan parasite, is a significant cause of gastrointestinal disease worldwide. Transmission can occur from an infected person, animal or fecally contaminated environment. The clinical manifestations of cryptosporidiosis are dependent on the immunologic state of the host. Infection among immunocompetent hosts results in diarrhea that is typically self-limited. In immunocompromised hosts, however, the infection may be protracted and life-threatening with no reliable antimicrobial therapy. In transplant patients, a course of antimicrobial therapy along with concurrent reduction in immunosuppression optimize immunologic status and may potentially lead to resolution of the infection.

Renal allograft loss due to proximal extension of ileofemoral deep venous thrombosis

Renal allograft recipients with thrombophilic (hypercoagulable) states are at higher risk for early allograft loss. Presumably, the combination of endothelial injury at surgery and thrombophilia predisposes to arterial or venous thrombosis. Of 270 consecutive renal transplants at our center one allograft failed secondary to renovascular thrombosis. At exploration the iliac and renal veins were thrombosed. Thrombectomy and re‐implantation were attempted, but unsuccessful. Also noted at surgery was extensive clot in the femoral vein that could not be removed by embolectomy catheters. Post‐operatively, a Doppler ultrasound confirmed the presence of extensive deep venous thrombosis (DVT) in the femoral and popliteal veins. The adherent nature of this clot, the extent of clot found less than 12u2003h after renal transplantation and the absence of leg edema suggested that the DVT existed prior to surgery. This case demonstrates that a pre‐existing, asymptomatic DVT can precipitate allograft thrombosis and highlights the importance of diagnosing thrombophilia in patients undergoing renal transplantation. Current practices in our unit have evolved to include screening for thrombophilia in all patients with a suggestive history. As thrombophilic states are increasingly appreciated in the end‐stage renal disease population, effective management of these patients while on hemodialysis and at the time of renal transplantation presents an ongoing challenge.

The utility of 6-month protocol renal biopsy under modern immunosuppression.

BACKGROUNDnProtocol biopsies after renal transplantation are useful in detecting subclinical rejection. In earlier studies, the incidence of subclinical rejection was high among renal transplant recipients on a cyclosporine-based immunosuppression. However, recent data show that subclinical rejection is low under tacrolimus-based immunosuppression. This study evaluates the utility of 6-month protocol biopsy in renal transplant recipients under induction with rabbit antithymocyte globulin and maintenance immunosuppression with tacrolimus, mycophenolate mofetil (MMF) and corticosteroids.nnnMETHODSn6-month protocol biopsies on 40 transplant recipients were analyzed for borderline and subclinical rejections. Allograft injury at biopsy was evaluated using the chronic allograft damage index score system (CADI) and was compared with initial scores obtained at implantation.nnnRESULTSnBorderline rejection was detected in 1 out of 40 patients. No case of subclinical rejection was detected at protocol biopsy. In 31 patients with corresponding implantation biopsies, mean CADI score increased from 1.1 +/- 1.4 to 2.8 +/- 2.1 at 6 months despite stable graft function. In the subgroup of patients with a 6-month CADI score of 2 or less (n = 11), graft function remained stable at 12 months post transplant (65.3 +/- 16.9 ml/min/1.73 m2 at 6 months vs. 65.2 +/- 16.7 ml/min/1.73 m2 at 12 months, p = 0.96). In contrast, allograft function declined significantly at 12 months in those with a 6-month CADI score of > 2 (n = 20) (64.3 +/- 13.5 ml/min/1.73 m2 at 6 months vs. 51 +/- 9.8 ml/min/1.73 m2 at 12 months, p = 0.0006).nnnCONCLUSIONSnWhile the incidence of borderline and subclinical is low under antilymphocyte antibody induction and tacrolimus-based immunosuppression, chronic allograft damage is highly prevalent at 6 months post transplantation. Our findings suggest that protocol biopsies under current immunosuppression may be more useful in the early detection of chronic allograft nephropathy (CAN).

Allorecognition and Tissue Typing in Organ Transplantation

The beginning of solid-organ transplantation can be traced back to the technical achievement of Alexis Carrel. In 1902, he described the techniques of vascular anastomosis, thus ushering in accounts of autograft and homograft transplantation. Although a number of animal-to-human kidney transplants were reported in the ensuing three decades, a human donor organ was not used until 1933, by the Russian surgeon Voronoy. This and other attempts at using human kidneys for transplantation failed owing to acute tubular necrosis and rejection.

Ponyclonal Antilymphocyte Antibodies

Polyclonal antilymphocyte antibodies (henceforth ALS/ALG or ATS/ATG) was the first biological immunosuppressive agent introduced into clinical transplantation with the exception of ionizing radiation. Indeed, ALS was the first heterologous antibody used for immunosuppressive effects in man. There now exist over thirty years experience in the clinical use of antilymphocyte antibodies in solid organ transplantation and in selected autoimmune disorders. An enormous literature exists which has established clear-cut and widely accepted indications for the use of ALS in man. A number of commercially manufactured antilymphocyte (ALS/ALG) and antithymocyte (ATS/ATG) preparations are currently available. In addition, many large transplant programs still manufacture their own preparations for use in their own programs. It is conservatively estimated that between 300,000 and 400,00 transplant patients have been treated with various forms of ALG or ATG. Thus polyclonal antilymphocyte preparations have had and continue to have a significant impact in clinical transplantation.