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PubMed1977

Cellular components of allograft rejection: identity, specificity, and cytotoxic function of cells infiltrating acutely rejecting allografts.

Functioning mononuclear cells have been harvested from heterotopic rat cardiac allografts during maximal transplant cellular infiltration. T cells, identified by a T cell-specific absorbed rabbit anti-rat brain serum, constituted two-thirds of the total cells recovered. Approximately 20% of the infiltrating cells bear and synthesize surface immunoglobulin. Macrophages, identified by latex ingestion and morphologic and cytochemical techniques, comprise 9% of the graft infiltrate. Donor-specific cytotoxic T lymphocytes are concentrated within the graft. A separate population of Fc receptor-positive recovered cells mediate antibody-dependent LMC (Ab-LMC). Neither effector cell was adherent or phagocytic. These studies have conclusively established that cytotoxic T lymphocytes accumulate within rejecting allografts; however, the enriched presence of cytotoxic T cells within the grafts is not fully dependent upon antigen recognition per se, since Lew animals grafted with both BN and BUF hearts have Lew anti-BN and Lew anti-BUF killer cells in each graft.

Animals↗

PubMed1998

Renographic indices for evaluation of changes in graft function.

Radionuclide renal diagnostic studies play an important role in assessing renal allograft function, especially in the early post-transplant period. In the past two decades various quantitative parameters have been derived from the radionuclide renogram to evaluate changes in perfusion and/or function of the kidney allograft. In this review article we discuss the quantitative parameters that have been used to assess graft condition, with emphasis on the early postoperative period. These quantitative methods are divided into parameters used for assessing renal graft perfusion and parameters used for evaluating parenchymal function. The blood flow in renal transplants can be quantified (a) by measuring the rate of activity appearance in the kidney graft, (b) by calculating the ratio of the integral activity under the transplanted kidney and arterial curves and (c) by calculating the renal vascular transit time. In this article we review a number of parenchymal uptake and excretion indices, such as the accumulation index, the graft uptake capacity at 2 and 10 min, the excretion index and the elimination index. The literature on these parameters shows that they have some practical disadvantages. In addition, values suffer from significant overlap when various graft pathologies coexist. A retrospective study was designed in our institution to evaluate the clinical usefulness of some of the frequently used previously published methods in which the graft function is quantitatively assessed in the early post-transplant period. The quantitative parameters studied which were reasonably reproducible in our hands included: global perfusion index (GPI), cortical perfusion index (CPI), vascular transit time, and the parenchymal parameters uptake capacity at 2 min (UC2) and elimination index (K3/20). The patient population in this study consisted of 43 patients with 157 technetium-99m mercaptylacetyltriglycine renograms. The perfusion indices GPI and CPI did not allow differentiation of the acute tubular necrosis (ATN) group from the acute rejection (AR) group; however, they were of value in monitoring the improvement in the condition of the graft dysfunction in both the AR and ATN groups. As for the parenchymal parameters, both UC2 and K3/20 were able to differentiate stable graft function (SGF) versus AR and ATN groups but were unable to separate AR from ATN dysfunction. The ability of these parenchymal parameters to detect improvement in the graft function was poor and statistically non-significant. From the literature data and our own findings it is concluded that radionuclide scintigraphy of renal transplants has assumed an important role, especially if performed serially, in monitoring graft function in the post-transplant period. Many quantitative parameters have been derived from the radionuclide renogram to evaluate changes in perfusion and/or function of the kidney allograft. It appears that these quantitative numerical values are unable to differentiate unequivocally between grafts with ATN and AR cases. The real value of these parameters lies in the follow-up of the dysfunction processes, which helps the clinician to determine the appropriate therapeutic regimen.

Humans↗

PubMedDate not supplied

Impact of long-term cyclosporine immunosuppressive therapy on native kidneys versus renal allografts: serial renal function in heart and kidney transplant recipients.

Aggregate analyses of the impact of long-term cyclosporine administration in kidney transplant recipients have reported generally impaired but stable allograft function. In contrast, experience in extrarenal transplantation has suggested that treatment with cyclosporine for periods in excess of 12 months causes a progressive native nephropathy often leading to dialysis dependence. The extent of this apparent discrepancy between native kidneys and renal allografts is the subject of this study, which examines the evolution of renal function in 119 kidney and 100 heart transplant recipients receiving 12 or more months of cyclosporine immunosuppressive therapy administered in uniform protocols by affiliated clinical transplantation programs. The evolution of renal function in both study cohorts was analyzed retrospectively on the basis of serial serum creatinine (Crs) determinations. Assessment of group mean Crs, reciprocal Crs (1/Crs), and slopes of the curves obtained by plotting 1/Crs versus time in individual patients revealed a significant decline of native kidney function over the first 6 posttransplant months in the cardiac allograft group. Thereafter, however, native kidney function stabilized in these patients, and the aggregate trend was suggestive of no further decline in function over a 3- to 4-year follow-up period. Kidney transplant recipients had an aggregate trend of slowly declining allograft function consistent with the effects of chronic immunologic injury. The data were not consistent with a uniform pattern of a progressive, cyclosporine-induced loss of renal function in either cohort. Long-term use of cyclosporine was found to be associated with impaired but generally stable aggregate renal function in both the heart and the kidney transplant cohorts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1984

Experience with cyclosporine and steroids in clinical renal transplantation.

We have reviewed the results of patient survival and transplant function of the last 100 recipients of renal allografts treated with cyclosporine (CyA) plus low-dose steroids since November 1981; the follow-up varies between 3 months and 2 years. A group of 56 individuals transplanted between January 1980 and October 1982 and immunosuppressed with azathioprine (Aza) and steroids were used as comparison. There were five deaths among 100 patients treated with CyA and two among 56 treated with Aza. There were, however, marked differences in allograft function. Using actuarial curves, 2-year allograft survival from 24 living, related, one haplotype matched donors was 83%, as compared to an unsatisfactory 60% graft function among 24 nonrandomized, comparable, Aza-treated recipients. The 2-year actuarial survival of 76 allografts from cadaver donors was 76%; that of 36 grafts in patients treated with Aza, 48%. Interestingly, function of first cadaver allografts was 84% at 2 years, far better (p less than 0.002) than cadaver graft function (58%) in patients who had been previously transplanted; these latter results are comparable to Aza-treated cadaver recipients. Side effects and complications of this difficult drug, as well as its benefits, have been stressed in this article.

Actuarial Analysis↗

PubMed2006

Possible relations between thyroid function, endothelium, and kidney and liver function in kidney allograft recipients.

BACKGROUND: Renal function affects the thyroid gland in many ways. Disturbances in hemostasis and endothelial damage are common complications of kidney disease. Endothelial dysfunction may link these two processes. AIM AND METHODS: This cross-sectional study examined thyroid hormones in relation to markers of endothelial damage and inflammation among 80 kidney allograft recipients and 29 healthy volunteers. Thyroid hormones, markers of endothelial damage (vWF, thrombomodulin, intracellular adhesion molecule [ICAM] vascular adhesion molecule [VCAM], CD146), markers of inflammation (hsCRP), other hemostatic parameters (thrombin-antithrombin complexes [TAT], prothrombin fragments 1 + 2 [F1 + 2], plasmin-antiplasmin complexes, tissue plasminogen activator and its inhibitor, platelet glycoprotein [V-GPV]) as well as P-selectin were measured using commercially available kits. RESULTS: Total T3 was significantly lower among kidney allograft recipients, whereas markers of endothelial dysfunction and inflammation were significantly elevated over controls. In kidney allograft recipients total T3 was independently related to PAI-1, ICAM, and eGFR, whereas free T3 was independently related to thrombomodulin, aspartate, and alanine aminotransferases, hemoglobin, urea, eGFR, dose of cyclosporine and treatment with mycophenolate mofetil/azathioprine. Total T4 was related to aspartate and alanine aminotransferases, dose of cyclosporine, PAI-1, and ICAM. In multiple regression analysis the only correlates of T3 were PAI-1 and ICAM, whereas the only correlates of free T3 were thrombomodulin, aspartate aminotransferase, eGFR, and cyclosporine dose. In healthy volunteers GPV was related only to TSH. CONCLUSIONS: We described novel relations between thyroid hormones and markers of endothelial dysfunction in kidney transplant recipients. In kidney transplant recipients thyroid function metrics were associated with endothelial damage, immunosuppressive treatment, liver and kidney function. Therefore, the relations between thyroid axis and endothelium in kidney allograft recipients merit additional studies.

Adult↗

PubMed1998

Outcome of renal transplantation in ninety-seven cyclosporine-era patients with systemic lupus erythematosus and matched controls.

OBJECTIVE: To evaluate the effectiveness of renal transplantation in systemic lupus erythematosus (SLE). METHODS: A total of 97 SLE patients who underwent renal transplantation between January 1984 and September 1996 were selected for study and were matched with a group of non-SLE controls (1 control for each SLE patient) who also received transplants during that period. SLE patients and controls were matched on 6 covariates: age, sex, race, type of allograft (cadaveric versus living-related), number of previous transplants, and year of transplantation. All study subjects received either cyclosporine or FK-506/tacrolimus as part of their immunosuppressive regimen. In a rigorous medical records review, the status of each allograft and the cause of each graft loss was determined. Using a stratified Cox proportional hazards model, the transplantation outcomes of the SLE patients were compared with those of the controls. The effects of 9 individual variables on transplantation outcomes were also examined, and the statistically significant variables were compared in a stratified, multivariate Cox proportional hazards model. RESULTS: The control group included patients with 20 different causes of end-stage renal disease (ESRD). The mean followup times for the SLE patients and controls were 323 weeks and 320 weeks, respectively. During the followup period, 52 SLE patients and 37 controls lost their allografts. The 1-, 2-, 5-, and 10-year allograft survival probabilities for the 2 groups (SLE versus controls) were as follows: 81.7% versus 88.2% (1-year); 74.7% versus 84.4% (2-year); 45.9% versus 75.0% (5-year); and 18.5% versus 34.8% (10-year). In the multivariate model, the relative hazard of allograft loss associated with SLE as the cause of ESRD was 2.1 (95% confidence interval 1.06-4.06, P = 0.0328). The total number of HLA mismatches, smoking status, and delayed allograft function were also associated with allograft loss in the multivariate model. CONCLUSION: Compared with matched controls, renal transplant patients with SLE had inferior transplantation outcomes, with more than twice the risk of allograft loss.

Adult↗

PubMed1994

Comparison of FK-506 and cyclosporine regimens in pediatric renal transplantation.

Clinical aspects of FK-506 or cyclosporine immunosuppression regimens were evaluated in 48 consecutive pediatric renal transplant recipients. Tapering and discontinuation of prednisone was employed only in children receiving FK-506 who experienced minor or no rejection episodes during the 1st posttransplant month. At 1 year follow-up, 17 of 22 (77%) of all children with functioning allografts were receiving no prednisone (n = 13) or a mean dosage of 0.07 mg/kg per day (n = 4). During the 1st month, acute cellular rejection was more common in the FK-506 group (0.58 vs. 0.21 rejections per patient, P < 0.05) but allograft survival (92%) and renal function at 1 year posttransplant were identical in both groups. Compared with the cyclosporine regimen, FK-506 immunosuppression may be associated with a higher incidence of cytomegalovirus or reversible Epstein-Barr virus-induced lymphoproliferative disease. However, the FK-506 group had less hirsutism and gingival hypertrophy and required fewer antihypertensive medications independent of steroid use. Height standard deviation scores and weight-for-height index improved only in pre-adolescents receiving FK-506 but no prednisone (P < 0.02 and P < 0.05, respectively), but did not differ between children on FK-506 plus prednisone and those in the cyclosporine group. We conclude that the major advantages of FK-506 over cyclosporine immunosuppression are a reduced severity of hypertension and an improved cosmetic appearance which may improve long-term medical compliance. When used as monotherapy, FK-506 also shows promise in relieving the growth retardation associated with cyclosporine regimens that include prednisone.

Adolescent↗

PubMed2000

The impact of donor age on living donor liver transplantation.

BACKGROUND: The impact of the age of the donor on the outcome of living related liver transplantation is yet to be clarified. METHODS: During October 14, 1996 and December 20, 1999, 34 living related liver transplantations were performed. Of these, 26 cases were performed using the extended left lobe graft, which were classified into three groups; younger donor group (group Y, donor age < 30, n = 7), middle-aged donor group (group M, 30 < or = donor age <50, n=13), and older donor group (group O, donor age < 50, n = 6). Early allograft function and regeneration were compared between these groups. RESULTS: There was no difference in standard liver volume, and predicted or harvested graft size between the three groups. Although serum transaminase and total bilirubin levels within postoperative day 7 were not different between the groups, the prothrombin time on postoperative day 3 was significantly longer in group O than in group Y. One week after transplantation, group Y had significantly greater graft/standard liver volume ratio than group O, and greater graft volume than group M and O. One month after transplantation, however, there was no significant difference in such graft size parameters between the groups. Graft and patient survival were comparable between the three groups. CONCLUSION: Although function and regeneration of the allografts from older donors in living donor liver transplantation is worse than those of their younger counterparts, the outcome is not affected by the age of the liver.

Adult↗

PubMed2005

Long-term outcome of deceased donor renal transplants correlates with the 30-day creatinine reduction ratio.

A simplified model to correlate early allograft function with long-term allograft survival in recipients of deceased donor renal transplants (DDRT) remains challenging. We propose here a novel approach, using the change from the pretransplant creatinine to the 30-day posttransplant creatinine. The outcomes of 153 consecutive DDRT performed at our center between January 1998 and March 2001 were reviewed. The percentage change in creatinine from the pretransplant to 1 month posttransplant, termed here, the creatinine reduction ratio (CRR), was calculated as follows: (pretransplant creatinine-creatinine at 1 month)/pretransplant creatinine *100%. Patients were divided as follows: group 1 CRR>or=67% and group 2<67%. Group 1 had a graft survival at 1 and 5 years of 100% and 89.1% versus 88% and 69.1% for group 2 (log-rank p=0.0008). The risk ratio for graft loss during the follow-up period was four times lower for the patients on group 1. Using the Cox hazards model to compare CRR>or=67% with determinants of long-term outcome, the risk ratio of graft loss during the observational period was 0.26 (p=0.001). The creatinine reduction ratio, when stratified by a level of >or=67% has a strong correlation with superior long-term allograft survival in recipients of DDRT.

Adult↗

PubMed1999

[Experience of orthotopic liver transplantation from non-heart-beating donors at the University of Pittsburgh Medical Center].

Eight cases of orthotopic liver transplantation (OLT) from non-heart-beating donors (NHBDs) were experienced at the University of Pittsburgh Medical Center. Four cases were from donors whose organs were procured following cardiopulmonary resuscitation (uncontrolled NHBD), and the remaining four hepatic allografts were recovered after sustained cardiopulmonary arrest following extubation in an operating room (controlled NHBD). After OLT from uncontrolled NHBDS, two allografts failed due to preservation injury and hepatic arterial thrombosis, and one showed poor allograft function. In contrast, all four grafts from controlled NHBDs survived and functioned well worked postoperatively. Hepatic allografts from controlled NHBDs is considered to be useful in OLT, especially in Japan where there is a serious brain-dead donor shortage.

Adolescent↗

PubMed2004

Preservation of graft function in low-risk living kidney transplant recipients treated with a combination of sirolimus and cyclosporine.

The use of sirolimus (SRL) in combination with full doses of cyclosporin A (CsA) results in reduced one-year kidney allograft function, which is associated with shorter long-term allograft survival. We determined the effect of reduced CsA exposure on graft function in patients receiving SRL and prednisone. Ninety recipients of living kidney transplants receiving SRL (2 mg/day, po) were compared to 35 recipients receiving azathioprine (AZA, 2 mg kg-1 day-1, po). All patients also received CsA (8-10 mg kg-1 day-1, po) and prednisone (0.5 mg kg-1 day-1). Efficacy end-point was a composite of biopsy-confirmed acute rejection, graft loss, or death at one year. Graft function was measured by creatinine, creatinine clearance, and graft function deterioration between 3 and 12 months (delta1/Cr). CsA concentrations in patients receiving SRL were 26% lower. No differences in one-year composite efficacy end-point were observed comparing SRL and AZA groups (18 vs 20%) or in the incidence of biopsy-proven acute rejection (14.4 and 14.3%). There were no differences in mean +/- SD creatinine (1.65 +/- 0.46 vs 1.60 +/- 0.43 mg/dl, P = 0.48) or calculated creatinine clearances (61 +/- 15 vs 62 +/- 13 ml/min, P = 0.58) at one year. Mean +/- SD delta1/Cr (-11 +/- 17 vs -14 +/- 15%, P = 0.7) or the percentage of patients with >20% (26 vs 31%, P = 0.6) or >30% delta1/Cr (19 vs 17%, P = 1) did not differ between the two groups. The use of 2-mg fixed oral doses of SRL and reduced CsA exposure was effective in preventing acute rejection and preserving allograft function.

Adolescent↗

PubMed2001

Peritoneal dialysis in the patient with a failing renal allograft.

BACKGROUND: Patients returning to dialysis treatment after a period with a functioning allograft represent a special case in the integrated care model of renal replacement therapy. They are known to nephrologists--and thus are ideal candidates for a timely commencement of dialysis--but they have had time to accrue additional cardiovascular risk. Furthermore, they have been exposed to prolonged immunosuppression. PURPOSE: The present study aimed to establish the clinical outcomes of patients returning to peritoneal dialysis (PD) with failing allografts [survival, technique survival, longitudinal residual renal function (Kt/V(R)), peritoneal membrane function (solute transport), and plasma albumin] and to compare those outcomes with outcomes in new, contemporary patients. SETTING: The study was conducted in a single center where prospective collection of data now known to be important in determining outcome on peritoneal dialysis (age, comorbidity, albumin, Kt/V(R), and solute transport) has been performed since 1989. METHODS: All patients commencing PD between 1989 and 2001 after failure of an allograft that had functioned for more than 6 months were identified. Outcomes in that group were compared to outcomes in all new PD patients and in all dialysis patients with failed grafts who were returning to hemodialysis (HD) in the same period. RESULTS: The study identified 45 patients with failed allografts: 28 were commencing PD treatment, and 17 were commencing HD treatment.Those patients were significantly younger than the 469 new patients commencing PD [FailedTx-->PD 41.2 years, FailedTx-->HD 38.9 years, NewPD 54.7 years; analysis of variance (ANOVA): p < 0.001]. We saw no significant difference in the survival of failed transplant patients commencing PD as compared with those commencing HD (log rank: p = 0.11). Kaplan-Meier plots of patient survival were better for failed transplant patients as compared with all new PD patients. When corrected using Cox regression, the survival advantage was seen to be due to age and comorbidity at start of PD. Pure technique failure (excluding death) was not different between the groups. Compared with all new PD patients, patients with failed allografts had similar longitudinal plasma albumin and a tendency toward an earlier increase in solute transport, but a more rapid loss of Kt/V(R), (p < 0.05 at 6-48 months). CONCLUSIONS: Peritoneal dialysis would appear to be a good option for patients with failing allografts. Comorbidity is the predominant determinant of survival. That finding underlines the need for attention to factors that might prevent accrual of cardiovascular risk during the post-transplantation period. The earlier loss of Kt/V(R) in those patients might be prevented by developing strategies of continued immunosuppression after commencement of dialysis, although infection risk is an important issue.

Adult↗

PubMed1997

Peripheral vascular disease after kidney-pancreas transplantation in diabetic patients with end-stage renal disease.

OBJECTIVE: To determine the long-term effect of a functioning pancreas transplant on peripheral vasculopathy. DESIGN: We compared the progression of peripheral vascular disease in 39 recipients of successful kidney-pancreas transplants (KPT) with 65 consecutive diabetic patients who received cadaver kidney transplants alone (KTA) during the same period in a nonrandomized, retrospective control study. The mean duration of follow-up was more than 4 years in both groups. SETTING: Academic subspecialty referral practice. PATIENTS: A consecutive sample of all KPT recipients with more than 6 months of pancreas allograft function performed between May 1, 1988, and April 30, 1995. All patients who received cadaver renal transplants for diabetic nephropathy during the same period and who maintained a functioning renal allograft for more than 6 months were included as controls. INTERVENTION: Kidney-pancreas transplantation. MAIN OUTCOME MEASURE: Progression of peripheral vascular complications (PVC) defined as any midfoot or limb amputation (AMP), any ischemic ulceration requiring treatment (ULCER), and lower-extremity bypass surgery or angioplasty (LEBP). Ulcers leading to amputation were considered as single events (AMP only). RESULTS: Thirty-five (90%) of 39 KPT recipients are insulin-free. The KTA recipients had more atherosclerotic risk factors, including a higher incidence of coronary artery disease (P = .008), higher serum cholesterol levels (P = .03), and higher triglyceride levels (P = .04) than KPT recipients. Peripheral vascular complications before transplantation were comparable (P = .94) between groups. After transplantation, there were 35 new PVC (9 AMP, 11 ulcers, and 15 LEBP) in 18 of 39 KPT recipients vs 32 PVC (10 AMP, 8 ulcers, and 14 LEBP) in 20 of 65 KTA recipients (P = .005), indicating that KPT recipients had more PVC than did KTA recipients, despite a functioning pancreas. Seven bypass grafts failed after KPT, resulting in 6 limb amputations. In contrast, only 3 limb amputations were performed in 14 patients undergoing lower-extremity bypass procedures after KTA. CONCLUSIONS: Despite fewer risk factors for peripheral vasculopathy and the presence of insulin independence, KPT recipients had a higher incidence of PVC than a cohort of uremic diabetic patients undergoing KTA during the same period. These data show that a functioning pancreas allograft performed with a renal transplantation not only does not alter the progression of peripheral vascular disease in patients with renal failure secondary to diabetic nephropathy but also may accelerate PVC.

Adult↗

PubMed1997

Preharvest nitroprusside flush improves posttransplantation lung function.

BACKGROUND: Morbidity as a result of early allograft dysfunction remains a significant problem in clinical lung transplantation. We previously demonstrated that nitroprusside (NP), a potent nitric oxide donor, administered before storage and again during reperfusion, reduced lung reperfusion injury. The purpose of the present study was to determine whether these observations were storage effects, reperfusion effects, or both. MATERIALS AND METHODS: Fifteen dogs underwent left lung allotransplant. Donor lungs were flushed with modified Euro-Collins solution and stored for 21 hours at 1 degree C. Immediately after transplantation, the contralateral right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamics and arterial blood gas analysis (FIO2 1.0) were assessed for 6 hours before sacrifice. Allograft myeloperoxidase (MPO) activity and wet to dry weight (W/D) ratio were assessed. Animals were divided into three groups for timing of NP administration. Group I (n = 5) animals received no NP. In group II (n = 5), donor lungs received NP (10 mg/L) in the flush solution only. In group III (n = 5), recipient animals received NP (0.2 mg/kg) just before reperfusion, as well as a continuous infusion (0.1 mg/kg/hr) during the assessment period. RESULTS: Significant improvement in gas exchange was apparent in groups II and III compared with group I, but there was no significant difference between groups II and III. After 6-hour reperfusion, mean PaO2 values were 85.46 +/- 13.32 mm Hg in group I, 298.74 +/- 61.25 mm Hg in group II (p < 0.05), and 311.12 +/- 43.39 mm Hg in group III (p < 0.05). Systemic vascular resistance was significantly lower in group III than in group I (p < 0.05). MPO activities decreased in groups II (p < 0.05) and III (p < 0.05), indicating reduced neutrophil sequestration. W/D ratio was significantly lower in groups II and III. CONCLUSION: Both methods of NP administration are effective, but NP administration in the recipient is accompanied by a decrease in systemic vascular resistance. From a clinical point of view, NP administration in the flush solution is a sufficiently effective and practical method to reduce lung allograft reperfusion injury.

Analysis of Variance↗

PubMed2005

Functionally significant renal allograft rejection is defined by transcriptional criteria.

Renal allograft acute cellular rejection (ACR) is a T-cell mediated disease that is diagnosed histologically. However, many normally functioning allografts have T-cell infiltrates and histological ACR, and many nonimmune processes cause allograft dysfunction. Thus, neither histological nor functional criteria are sufficient to establish a significant rejection, and the fundamental features of clinical rejection remain undefined. To differentiate allograft lymphocyte infiltration from clinically significant ACR, we compared renal biopsies from patients with ACR to patients with: sub-clinical rejection (SCR, stable function with histological rejection); no rejection; and nontransplanted kidneys. Biopsies were compared histologically and transcriptionally by RT-PCR for 72 relevant immune function genes. Neither the degree nor the composition of the infiltrate defined ACR. However, transcripts up-regulated during effector T(H)1 T-cell activation, most significantly the transcription factor T-bet, the effector receptor Fas ligand and the costimulation molecule CD152 clearly (p = 0.001) distinguished the patient categories. Transcripts from other genes were equivalently elevated in SCR and ACR, indicating their association with infiltration, not dysfunction. Clinically significant ACR is not defined solely by the magnitude nor composition of the infiltrate, but rather by the transcriptional activity of the infiltrating cells. Quantitative analysis of selected gene transcripts may enhance the clinical assessment of allografts.

Adult↗

PubMed2005

Vasodilatation vs. immunotherapy to prevent delayed graft function: delayed graft function as an indication of immune activation.

Delayed renal allograft function (DGF) is a factor for acute rejection and chronic allograft nephropathy. Cold ischemia time (CIT) is associated with an increased in DGF. Twenty patients receiving allografts with CIT>12 were enrolled in a double-blinded, randomized (1:1), placebo-controlled study to assess vasodilatation with fenoldopam (Abbott; dopamine-1 receptor agonist) on DGF. Fenoldopam infusion began at arterial anastomosis at 0.025 microg/kg/min and titrated to 0.1 microg/kg/min continued for 48 h postop (PO). Immunosuppression included steriods, MMF, and calcinurin inhibitors begun 36 h PO. Antibody induction (AI) using antithymocyte globulin (rabbit) (AT-G(r); Sangstat) was added halfway through the study to African-Americans and for PRA>40%. The need for dialysis, cumulative urine output (UOP), and creatinine (Cr) at PO day 7, 14, and 30 were compared. Eighteen patients completed the study drug infusion. Demographics of groups were not different. There was no difference between fenoldopam and controls for dialysis, UOP at 48 and 72 h, or Cr at 7, 14, or 30 days. There was a difference in UOP when AI (n=7) was compared to non-AI (n=11). At 48 h non-AI UOP 4796+/-3284 ml compared to AI UOP 8960+/-5130 ml (p=0.050). At 72 h, non-AI patients had UOP of 6824+/-4547 ml compared to AI patients with UOP of 12196+/-5868 ml (p=0.044). There was a trend to a lower Cr at day 7 for AI 2.7+/-2.1mg/dl compared to 4.9+/-3.0 mg/dl in non-AI (p=0.11). There was no difference in dialysis or Cr at day 14 and 30 between the AI and non-AI patients. AI with AT-G(r) significantly increases UOP in allografts with CIT>12 h, whereas vasodilatation did not. Therapy for DGF may include AT-G(r) AI.

Adult↗

PubMed1991

Morbidity of pancreas transplantation during cadaveric renal transplantation.

Simultaneous transplantation of the pancreas is an option for diabetic patients undergoing kidney transplantation to attempt to halt progression of diabetic complications, but the additional risk imposed by the procedure is unclear. Our aim was to determine the morbidity attributable to pancreas transplantation during simultaneous pancreas and kidney transplantation. We compared the first posttransplant year of 18 consecutive recipients of combined pancreas and kidney transplantation to 18 consecutive recipients of kidney transplantation alone. All patients received cadaver donor allografts between 1986 and 1989, and had type I diabetes mellitus with chronic renal failure. There were no differences in patient survival (94% both groups) or satisfactory renal allograft function (89% pancreas/kidney group, 83% kidney group) up to 18 months after transplantation. Eighty-eight percent of pancreas allografts were functioning satisfactorily at 18 months. There was a mean (+/- SD) of 1.5 +/- 1.0 acute rejection episodes per patient for the pancreas/kidney group compared to 0.8 +/- 6 for the kidney-only group (P less than 0.02). Cytomegalovirus infection and wound complications were each encountered more often after pancreas/kidney transplantation than kidney transplantation alone, and together with rejection accounted for a difference in days of hospitalization during the first year (71 +/- 34 vs. 27 +/- 13, P less than 0.001). We conclude that simultaneous pancreas transplantation during cadaver donor kidney transplantation accounted for more frequent rejection episodes, CMV infections, and wound complications. These complications resulted in more hospitalization for patients undergoing simultaneous pancreas/kidney transplantation than kidney transplantation alone.

Adult↗

PubMed2003

Nephrogenic fibrosing dermopathy after liver transplantation successfully treated with plasmapheresis.

Nephrogenic fibrosing dermopathy (NFD) is a recently described cutaneous fibrosing disorder associated with renal dysfunction. It appears similar to scleromyxedema but with some notable exceptions, including the lack of involvement of the face and absence of plasma cells on histology, systemic involvement, and paraproteinemia. Patients can present with thickened or edematous skin with indurated papules and plaques involving the extremities and the trunk. We report the first three cases of NFD after liver transplantation successfully treated with plasmapheresis. Two patients underwent liver transplantation for hepatitis C virus-induced cirrhosis and one for hepatitis B virus-induced cirrhosis. All the patients had encephalopathy, refractory ascites, and malnutrition prior to transplantation. Like those patients with NFD, all three of our patients had renal dysfunction and required hemodialysis before and after transplantation. Two were not dependent on dialysis at the time of diagnosis, however. These patients had excellent liver allograft function, but the other patient had allograft failure secondary to recurrent hepatitis C. Immunosuppression therapy consisted of basiliximab, mycophenolate mofetil, calcineurin inhibitor, and prednisone. The patients developed "woody" skin induration of the distal extremities, erythematous papules, and contractures at 1, 2, and 120 months after transplantation. Skin biopsies resembled NFD. No paraproteinemia was evident. One to three 5-day courses of plasmapheresis resulted in moderate to marked clinical improvement. The improvement of the kidney function in two of our patients did not appear to correlate with that of the skin disorder, because the kidney function was improving at the time the diagnosis of NFD was made. In conclusion, we report the first three cases of NFD after liver transplantation. Plasmapheresis was moderately successful in resolving the skin-indurated papules, severe skin induration, and associated joint contractures. Preliminary studies (unpublished data) show that decreasing plasma levels of transforming growth factor-beta1 after plasmapheresis appear to correlate with the amelioration of this clinical condition.

Adult↗