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PubMed2007

Immunosuppression for dual kidney transplantation with marginal organs: the old is better yet.

Immunosuppressive protocols in dual kidney transplantation (DKT) are based on calcineurin inhibitors (CNI). We wonder whether a CNI-free immunosuppression can improve outcome in older patients receiving a DKT with marginal donor organs. Thirty-six were treated with CsA, MMF and prednisone (CsA group) and 42 with rATG, SRL, MMF and prednisone (SRL group). Incidence of delayed graft function and acute rejection was 44% and 11% in the CsA group, and 40% and 8% in the SRL group. CMV infection incidence was low in both protocols. Three-year patient survival was 89% in the CsA and 76% in the SRL group. One- and 3-year graft survival after censoring for dead with a functioning allograft was 94.2% and 94% in CsA and 95% and 90% in SRL, respectively. Renal function was similar in both groups whereas proteinuria was higher in the SRL group. Uninephrectomy due to graft thrombosis or urinary-related complications was numerically higher in the SRL (21%) than in the CsA group (8%) (p = 0.13) and it was associated with renal failure and proteinuria. In DKT, a new induction immunosuppressive protocol based on rATG, SRL, MMF and prednisone does not offer any advantage in comparison to the old CsA, MMF and prednisone.

Calcineurin Inhibitors↗

PubMed1996

Recipient body size and cadaveric renal allograft survival.

Transplantation of renal allografts inadequate to meet recipient metabolic demands has been hypothesized to be one cause of chronic allograft failure. This cohort study examined the relationship of each of three measures of recipient body size and one measure of recipient metabolic rate to the rate of allograft failure among 239 recipients of cadaveric renal allografts between 1985 and 1990. All subjects were followed until allograft failure, death, or December 31, 1992, whichever occurred first. Using multivariate Cox proportional hazards analysis, all measures of recipient size and metabolic rate were found to be strong and statistically significant predictors of allograft survival adjusted for other predictors of allograft survival including allograft rejection, delayed allograft function, recipient race, prior renal transplantation, and donor age. The adjusted relative risk (RR) of allograft failure for a 15-kg increase in recipient body weight was 1.47, P < 0.0001 (95% confidence interval (CI), 1.21-1.78); adjusted RR for a 10-U increase in recipient body mass index was 2.34, P < 0.0001 (95% CI, 1.53-3.58); adjusted RR for a 0.5 m2 increase in recipient body surface area was 2.34, P < 0.001 (95% CI, 1.40-3.91); and adjusted RR for a 250 Kcal increase in metabolic rate was 1.49, P < 0.01 (95% CI, 1.17-1.89). These results are consistent with prior research indicating that a renal tissue supply-demand mismatch may accelerate failure of renal allografts. Alternative explanations of this relationship between recipient body size and allograft survival include inadequate immunosuppressive medication administration among recipients with a larger body size. Additional research is warranted to examine more fully the relationship between recipient body size and allograft survival.

Adolescent↗

PubMed1978

Ruptured human renal allograft. Pathogenesis and management.

From January, 1963, to January, 1977, 4 cases of acute allograft rupture occurred in 474 renal transplants performed at the Cleveland Clinic, an incidence of 0.8 per cent. Rupture developed between the fifth and sixteenth day after transplantation during a period when the patients required dialysis because of poor allograft function. All patients had surgical exploration and successful repair of the laceration. Biopsies in each case at the site of laceration revealed findings consistent with acute allograft rejection. The rejections were mild in 2 cases, moderate in one, and severe in another. Two kidneys failed to sustain function, and the patients were returned to chronic hemodialysis two to five months later. None required a nephrectomy. The other two kidneys are functioning well, with serum creatinine values of 1.3 and 1.5 mg./100 ml. one year after allograft rupture. Since rupture of a renal allograft does not appear to increase the intensity of rejection nor does it represent a severe type of rejection, transplant nephrectomy can be avoided unless hemorrhage is uncontrollable from the site of laceration.

Adult↗

PubMed1998

Identification of clinical and histopathologic risk factors for diminished renal function 2 years posttransplant.

The aim of this study was to identify early clinical and pathologic variates that independently predict diminished renal allograft function at 24 mo posttransplant. A clinical pathologic data base was prospectively derived from 71 patients in whom protocol renal biopsies were performed at 1, 2, 3, 6, and 12 mo posttransplant. The major end point was the 24-mo serum creatinine. Variates correlating independently (r2 = 0.67) with the 24-mo serum creatinine were the chronic biopsy scores (months 3 and 6), late rejections (months 4 to 6), cyclosporin A (CsA) levels (months 1 to 2), and delayed graft function. The adjusted odds ratio (OR) and 95% confidence interval (CI) for having a serum creatinine > or = 130 mumol/L at 24 mo increased for every year the donor age increased (OR = 1.07; 95% CI, 1.02 to 1.13; range, 9 to 55) or for each late rejection episode (OR = 5.9; 95% CI, 1.7 to 20.1), whereas a mean CsA level > 300 micrograms/L from months 1 to 3 was protective (OR = 0.07; 95% CI, 0.01 to 0.43). Variates correlating independently (r2 = 0.53) with the change in serum creatinine from 6 to 24 mo (delta Cr6-24) were the chronic biopsy scores at months 3 and 6. The adjusted OR of the delta Cr6-24 rising > or = +20 mumol/L increased for every year the donor age increased (OR = 1.09; 95% CI, 1.02 to 1.16; range 9 to 56) or when the 6-mo chronic biopsy score was > or = 2 (OR = 6.6; 95% CI, 1.2 to 36.4). An estimate of the relative risk for diminished renal function at 2 yr can be assigned within 6 mo of transplant based on chronic pathology, late acute rejections, CsA levels, and donor age.

Adult↗

PubMed1994

Treatment of chronic hepatitis B and C with interferon-alpha in renal allograft recipients: preliminary results.

We evaluated the effects of treatment with interferon (IFN) on liver disease and renal allograft function in ten immunosuppressed cadaver kidney recipients. Two females and eight males (mean age 39 years) with biopsy-proven chronic active hepatitis (n = 8) or persistent hepatitis (n = 2) and serum positive for hepatitis B surface antigen (HBsAg) and HBe antigen (n = 5) or serum positive for anti-HCV antibodies (n = 3) or serum positive for HBsAg, anti-HCV and anti-HDV antibodies (n = 2) received 3 million units IFN thrice weekly of 6 months. All patients responded with a reduction in serum aminotransferase activity and in five of them liver function completely normalized. Three patients among five infected with HBV cleared HBeAg. During the follow-up period liver function remained stable in 9 patients after discontinuation of IFN therapy. Three patients lost their grafts due to rejection 1, 2, and 4 months after IFN therapy, respectively. In six patients renal function remained stable during and after IFN therapy. We conclude that in selected groups of renal allograft recipients IFN can be used safely and effectively for the treatment of chronic viral hepatitis.

Adult↗

PubMed2001

Conversion from cyclosporine to FK506 in adult liver transplant recipients: a combined North American and European experience.

BACKGROUND: Although cyclosporine (CsA) made clinical liver transplantation possible, side effects and development of rejection have limited its use. In some patients, conversion to tacrolimus has been necessary to abrogate side effects and to preserve allograft function. METHODS: The results of conversion from CsA to tacrolimus were studied retrospectively in 94 liver allograft recipients from a North American and a European transplant center (Duke University Medical Center, Durham, NC, and Hopital Beaujon, Clichy, France). RESULTS: Forty-seven of 94 patients (50%) were converted for steroid-resistant acute rejection. Conversion was successful in 91% of these patients, whereas 9% of patients developed chronic rejection. A further nine patients were converted for chronic allograft rejection with positive results in eight of nine grafts. Mean serum bilirubin in these nine patients was 8.7 mg/dl before conversion and 2.1 mg/dl 6 months after conversion (P=0.02). Nine patients were converted due to inability to wean steroid. Of these, six patients remains steroid free 1 year after conversion. Twenty-three patients (24%) were converted for nephrotoxicity with a reduction in serum creatinine from 167+/-36 mmol/L to 119+/-28 mmol/L 1 year after conversion (P=0.006). Eight of 11 patients converted for neurotoxicity improved after conversion. Conversion to tacrolimus had no effect on seizure frequency or memory loss. CONCLUSIONS: These results suggest that conversion to tacrolimus from CsA is an appropriate paradigm for graft rescue and treatment of a variety of side effects after liver transplant. However, some situations such as memory loss and hypertension may require other strategies.

Adult↗

PubMed2003

Infectious etiology of bronchiolitis obliterans: the respiratory viruses connection - myth or reality?

A variety of viruses, such as the influenza viruses A and B, the human respiratory syncytial virus, the parainfluenza viruses, and the adenoviruses, cause seasonal respiratory tract infections in young children and adults. Also, studies indicate that these viruses are an important group of pathogens in pediatric and adult lung transplant recipients. More importantly, accumulating data on these infections among lung transplant patients suggest that these illnesses may have immediate and long-term implications for the function of the transplanted lung, including the development of bronchiolitis obliterans. This is important because patient survival and allograft function in lung transplantation remain limited by the development of bronchiolitis obliterans. Models of lung transplantation indicate that respiratory viral infections cause acute and chronic airway damage after transplantation. The mechanism leading to allograft damage by respiratory viruses may be related to the production of alloreactive cytokines such as interleukin (IL)-1, tumor necrosis factor, IL-6 and IL-8 during viral replication. Current clinical data are suggestive of a possible role for respiratory viruses in the development of bronchiolitis obliterans, but further control studies are required to evaluate the significance of respiratory virus infections as a causal factor in the development of bronchiolitis obliterans in lung transplantation.

Bronchiolitis Obliterans↗

PubMed1993

Transplant aspirative cytology: analysis of morphological and immunocytochemical parameters in renal allograft dysfunction.

We have analyzed 245 transplant aspirative cytologies (TACs) from 96 renal allograft patients. TACs were divided in two chronological groups: Early (TACs performed during the first 3-mo posttransplantation) and late (TACs performed after the third month post-transplantation), in order to assess the effect of allograft tolerance on TAC features. Both morphological and immunocytochemical aspects were evaluated, including CD4, CD8, IL2-R, and HLA-DR immunolabeling. A final diagnosis for each case of allograft dysfunction was achieved by other independent diagnostic means. Four diagnostic groups were considered in the present study: acute rejection (AR), chronic rejection (CR), acute tubular necrosis (ATN), and Cyclosporin A toxicity (CsA-T). In addition, a control group (C) was established from patients with stable allograft function. We found that immunocytochemical analysis of TACs is particularly helpful in the diagnosis of late allograft dysfunction, a time period when the simple cytological study of renal infiltrate is not informative enough to help take therapeutic decisions.

Cytological Techniques↗

PubMed1996

A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection. A report of the Tacrolimus Kidney Transplantation Rescue Study Group.

A multicenter trial was conducted to evaluate the efficacy and safety of tacrolimus in the treatment of refractory renal allograft rejection. Renal transplant recipients experiencing biopsy-proven recurrent acute allograft rejection were eligible if the current rejection episode was refractory to corticosteroids. A total of 73 patients were enrolled, of whom 59 (81%) had previously received at least one course of antilymphocyte antibody as rejection therapy. One-year follow-up was available in 93% of patients. Median time to tacrolimus rescue therapy was 75 days after transplantation (range, 18-1448 days). Therapeutic responses to tacrolimus included improvement in 78% of patients, stabilization in 11%, and progressive deterioration in 11%. The risk of experiencing progressive deterioration was related to the pretacrolimus serum creatinine level: serum creatinine < or = mg/dl, 3%; 3.1-5 mg/dl, 16% (P < 0.04); > 5 mg/dl, 23% (P < 0.02). Twelve-month (from the time of initiation of tacrolimus therapy) actuarial patient and graft survival rates were 93% and 75%. Graft loss occurred in 19 patients (25%) at a median time of 108 days. Fourteen episodes of recurrent rejection were diagnosed in 10 patients (14%), at a median time of 101 days. Eleven episodes of recurrent rejection were treated (three patients underwent transplant nephrectomy), with resolution achieved in nine patients. Antilymphocyte antibody therapy was not used to treat recurrent rejection. Serum creatinine values improved during tacrolimus therapy: median serum creatinine level before tacrolimus, 3.2 mg/dl; median at 1 year after tacrolimus, 1.8 mg/dl. Twelve infections were documented in 11 patients (15%), including cytomegalovirus infection in three patients (4%). Posttransplant lymphoproliferative disorder was diagnosed in a single patient. Tacrolimus whole blood levels averaged 15.0 +/- 9.9 ng/ml at day 7 of tacrolimus therapy and 9.4 +/- 5.1 ng/ml at 1 year, and were consistent among individual centers. Treatment outcome did not correlate with tacrolimus blood levels. The most commonly observed adverse events were neurological and gastrointestinal. Seventy-four percent of patients received tacrolimus for at least 1 year. Tacrolimus therapy was discontinued in 18% of patients for rejection (11% for progressive, unrelenting rejection, and 7% for recurrent rejection). Tacrolimus therapy was discontinued in 8% of patients due to adverse events. In conclusion, tacrolimus rescue therapy provides (1) prompt, effective reversal of refractory renal allograft rejection, (2) good long-term renal allograft function, (3) a low incidence of recurrent rejection, and (4) an acceptable safety profile in renal allograft recipients experiencing refractory rejection.

Acute Disease↗

PubMed1985

Altered distribution pattern of Na+-K+-ATPase and succinate dehydrogenase activities along the nephron in human acute post-transplant renal failure.

The catalytic activities of Na+-K+-ATPase and succinate dehydrogenase, marker enzymes for active salt reabsorptive capacity of renal basolateral plasma membranes and for respiratory capacity of mitochondrial cristae membranes, were studied in the maintenance phase of human acute post-transplant renal failure. Biopsies of 4 kidney-allografts taken at transplantation operation and additionally at different post-transplantation periods, either with good function or in various stages of dysfunction, were compared with the unaffected part of a human kidney nephrectomized due to hypernephroma. In single nephron segments, Na+-K+-ATPase activity was determined after microdissection by microfluorometry, and succinate dehydrogenase activity was determined by a microphotometric procedure in stained cryosections. In intraoperative and postoperative biopsies of a well-functioning allograft, both Na+-K+-ATPase and succinate dehydrogenase activities did not differ from those of normal renal tissue. In contrast, the catalytic activities were found to be decreased in the distal tubules of 2 anuric allografts when compared with their intraoperative controls. In addition, succinate dehydrogenase activity was reduced in distal tubules of a recovering allograft. Catalytic activities appeared to be unaffected in glomeruli, proximal tubules, and collecting ducts. It is suggested that the predominant distal tubular alterations with regard to these parameters are a consequence of increased distal tubular vulnerability due to circulatory and metabolic conditions.

Acute Kidney Injury↗

PubMed2004

[Investigation of sexual function rehabilitation of 11 male heart transplant recipients].

OBJECTIVE: To investigate the rehabilitation of the sexual function of male patients after heart transplantation. METHODS: Eleven discharged adult male cardiac transplant recipients (ranging 32-54 years) with a normally functioning allograft for at least 9 months were questioned on their pre- and post-operative sexual function. RESULTS: All the recipients complained of a significant pretransplantive decrease and 10 stated a significant posttransplantive increase in sexual function. CONCLUSION: The sexual function of the male recipients was significantly improved after cardiac transplantation. Psychosocial factors affecting the rehabilitation of sexual function should not be neglected.

Adult↗

PubMed2004

Duffy antigen receptor and genetic susceptibility of African Americans to acute rejection and delayed function.

BACKGROUND: The unique distribution of the alleles for the Duffy antigen receptor complex (DARC) that binds to chemokines may be associated with the rates of acute rejection and delayed allograft function (DGF) among African Americans. METHODS: A prospective, multicenter cohort study enrolled 222 African American recipients of cadaveric renal allografts from eight adult transplant centers. Subjects were typed by allele-specific polymerase chain reaction (ASPCR) for the polymorphism at position 535 that determines the level of transcription. Associations of DARC genotypes were examined in Cox hazards models with episodes of acute rejection and in logistic regression models with the development of DGF. RESULTS: FyB Null homozygosity was observed among 67% of the recipients. Fifteen percent of the study cohort experienced at least one episode of acute rejection, and the incidence of DGF was 42.5%. The number of FyB Null alleles and FyB Null homozygosity had no detectable association with the rate of acute rejection (P > 0.50) or with the development of DGF (P > 0.50). CONCLUSION: The susceptibility of African American recipients to acute rejection and to DGF was not confirmed to be associated with DARC alleles or genotype. Future studies should exclude a potential role of donor-related DARC in transplant outcomes.

Acute Disease↗

PubMed2006

Early assessment of renal resistance index after kidney transplant can help predict long-term renal function.

BACKGROUND: Color Doppler ultrasonography of intrarenal arterial resistance index (RI), performed early after kidney transplant, has proven to reliably predict short-term allograft function. The aim of this study was to assess whether it could also predict long-term renal function. METHODS: We retrospectively analysed 76 kidney transplant patients who underwent RI assessment within 1 month after the transplant, subdivided into two groups according to RI values, lower (group A) or higher (group B) than its median value (0.635). RESULTS: Compared with group A subjects, the patients of group B were older at the time of transplant (42 +/- 9 vs 35 +/- 8 years; P = 0.001), the donor age was also older (41 +/- 16 vs 33 +/- 13 years; P = 0.02) and had a slightly higher proteinuria (0.54 +/- 0.5 vs 0.32 +/- 0.2 g/24 h; P = 0.02). Serum creatinine, ciclosporin or tacrolimus trough level, arterial blood pressure, number of human leukocyte antigen (HLA) mismatches, anti-hypertensive medications and incidence of delayed graft function were not significantly different between the two groups. By univariate analysis, RI turned out to directly correlate with the recipient age, donor age and daily proteinuria (P = 0.007, P = 0.0007 and P = 0.02, respectively). Multivariate analysis showed that only donor and recipient age maintained their independent predictive value on RI. Kaplan-Meier analysis, considering a serum creatinine increase >50% as the endpoint of the study, showed a statistically significant different graft survival in the two groups (log-rank test = 5.489; P = 0.01). The univariate relative risk of deterioration of graft function among patients with higher RI was 3.77. Proteinuria and recipient age increased the risk as well. CONCLUSIONS: Our data seem to suggest that early determination of RI can help predict long-term graft function in kidney transplant recipients.

Adult↗

PubMedDate not supplied

Incidence and outcome of transplant renal artery stenosis: single center experience.

Since the incidence of transplant renal artery stenosis (TRAS) in renal allografts varies from 1% to 23%, we sought to examine its incidence, to analyze treatment options, and to ascertain its outcomes. Retrospective analysis of 793 kidney allograft recipients transplanted between 1996 and 2004 revealed an incidence of 0.9% (n = 7). Time from kidney transplantation to the first symptoms varied from 1 week to 3 years (median, 4 months). Three patients experiences refractory hypertension and six patients developed allograft dysfunction. Screening color Doppler ultrasonography showed hemodynamic changes in six patients with the definitive diagnosis confirmed by angiography in all patients. One patient with an anastomotic stenosis was treated with a surgical operation and six patients, percutaneous transluminal angioplasty (PTA), with stenting in three cases. Both surgical as well as PTA treatment were successful in all but one patient, who underwent PTA alone, developed chronic renal insufficiency necessitating hemodialysis and finally lost his allograft. In the other patients all symptoms resolved after treatment and the patients are doing well with functioning allografts. Although TRAS was an uncommon complication, if recognized promptly it could be treated by surgery or PTA with a high success rate.

Adult↗

PubMed1980

Renal transplantation in children with obstructive uropathy.

The outcome of renal transplantation was examined in 52 pediatric patients (mean age 13 years) whose primary renal disease was obstructive uropathy. The bladder was used at transplantation in 45 allograft recipients, 39 of whom had had a previous lower urinary tract operation or bladder defunctionalization. An ileal loop was used in 7 recipients. The 52 patients received 73 renal allografts from 58 cadaver and 15 live-related donors. Presently, 40 patients (77 per cent) have functioning allografts, 4 have returned to dialysis and 8 (15 per cent) have died. The results indicate that the outcome of renal transplantation in patients with obstructive uropathy is similar to that of other transplant recipients. Damaged and defunctionalized bladders may be used successfully in most cases. If necessary an ileal conduit is an effective alternative. Post-transplant urologic complications occur with increased frequency but with appropriate management allograft salvage and patient survival are excellent.

Adolescent↗

PubMed1996

Prospective analysis of HLA immunogenicity of cryopreserved valved allografts used in pediatric heart surgery.

BACKGROUND: The HLA immunogenicity of cryopreserved valved allografts used in the surgical repair of congenital heart defects is unknown. METHODS AND RESULTS: To determine the immunogenicity of these allografts, we measured prospectively the frequency of panel-reactive HLA class I alloantibodies (PRA) before, 1 month after, and 3 months after allograft implantation in 9 children (age, 5.4 +/- 2.1 years) and after open-heart surgery without allograft implantation in 11 age-matched control children (age, 4.0 +/- 1.5 years). PRA was determined against an HLA-select frozen T-lymphocyte panel using the antiglobulin cytotoxicity technique. After allograft implantation, PRA increased from 3.2 +/- 2.7% before surgery to 63.3 +/- 12% at 25 +/- 2 days after surgery and 99.7 +/- 0.3% at 3.4 +/- 0.3 months after surgery. The use of dithiothreitol to remove IgM alloantibodies resulted in a modest decrease in PRA at 1 month (33.2 +/- 13%) but no change at 3 months (93.0 +/- 3.4%), suggesting the initial humoral response is an IgM alloantibody that switches almost exclusively to IgG by 3 months. Control patients showed no increase in PRA over time: 1.6 +/- 1% before surgery, 3.2 +/- 1% at 28 +/- 5 days after surgery, and 1.7 +/- 1% at 2.7 +/- 0.3 months after surgery. CONCLUSIONS: Cryopreserved valved allografts in children induce a marked HLA alloantibody response that increases to broad panel reactivity within 3 months after surgery. This HLA sensitization has potential not only for causing deleterious effects on allograft function but also for limiting the future opportunity of heart transplantation in patients who receive cryopreserved valved allografts.

Adolescent↗

PubMed2000

Progression of renal damage in chronic rejection.

A significant complication in renal transplantation is the progressive decline of allograft function, commonly called chronic rejection. This complication has been regarded as a result of continuous immunological activity against the allograft. However, the role of nonimmunological factors has become increasingly apparent in triggering or exacerbating immunological mechanisms. Although the role of immunological factors is predominant, the correction of nonimmunological factors may contribute in improving the probability of long-term graft function. However, immunosuppressive therapy remains the cornerstone for reducing the risk of chronic rejection and late graft failure.

Animals↗

PubMed2001

Polyoma viral infection in renal transplantation: the role of immunosuppressive therapy.

BACKGROUND: Polyoma virus infection in renal transplant recipients has been observed with increasing frequency in recent years. Renal allograft involvement in this condition may occur as a result of primary infection or secondary to reactivation of the latent virus. Interstitial nephritis, ureteric stenosis, rise in serum creatinine and allograft function loss have been attributed to this viral infection. METHODS: In this study we reviewed our experience with 8 patients who developed polyoma viral infection confirmed by allograft biopsy. All patients were receiving mycophenolate mofetil as part of the immunosuppression and 7 of the 8 patients were on tacrolimus. All patients have biopsy proven polyoma viral infection. The following therapeutic maneuvers were carried out following the diagnosis of polyoma viral infection: 1) stopping mycophenolate and 2) switching tacrolimus to cyclosporine or reducing the tacrolimus dose to adjust it at a lower therapeutic trough level. The clinical course and outcome of our patients were reviewed in relation to manipulation of immunosuppressive medications. RESULTS: The incidence of this infection in our transplant program in the last 3 yr was 5.3%. Seventy-five percent of the patients had at least one rejection episode and 63% had more than one rejection episode. The main risk factor for the development of polyoma viral infection was related to the intensity of immunosuppression. The use of antirejection therapy after histological diagnosis of polyoma virus infection was not associated with improvement of renal function despite the histological appearance of acute rejection. Thus, the interstitial nephritis associated with polyoma viral infection appears to be an inflammatory response to the virus rather than acute rejection. Six out of the 8 patients stabilized renal function with reduction in immunosuppression. CONCLUSIONS: Reduction in immunosuppression was associated with the stabilization of renal function when instituted early. However, these patients were left with a degree of allograft dysfunction and their outcome may be significantly compromised. The lack of effective antiviral therapy for polyoma virus may limit the use of newer and more potent immunosuppressive medications.

Acute Disease↗