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PubMed1994

[Color Doppler ultrasound of kidney transplants. Does the resistance index facilitate diagnosis of chronic kidney failure?].

The retrospective study under report assessed the diagnostic capability of colour Doppler sonography (CDS) with measurement of the resistive index (RI) in the long-term follow-up of patients with renal allografts. 210 CDS examinations were performed in 115 patients. The time since transplantation ranged from 6 months to 22 years. The RI was correlated to laboratory parameters of renal allograft function (serum creatinine, urinary protein levels and serum-cyclosporine). In 97 of 210 examinations, serum creatinine was elevated (> 1.5 mg% or an increase of more then 0.3 mg% within the last 6 months). In 35 out of these examinations RI was > 70%, in 62 RI was < or = 70%. Thus, with a threshold RI of 70%, sensitivity of the RI in the diagnosis of renal allograft dysfunction is 36% and specificity 62%, respectively. There was no significant difference in the RI between examinations of allografts with normal function (68.2% +/- 7.5%) and those with dysfunction (68.5% +/- 8.5%). Furthermore, there was no significant correlation between the RI and any of the laboratory parameters. CDS with calculation of the RI cannot differentiate in the long-term follow-up between allografts with normal function and those with dysfunction.

Adolescent↗
PubMed1989

Plasma atrial natriuretic factor and graft function in renal transplant recipients.

In order to determine the relationships between allograft function and the recipient's plasma concentrations of atrial natriuretic factor (ANF), plasma ANF was measured by radioimmunoassay for 14 days after cadaveric renal transplantation in 9 patients aged 19-64 years. All received immunosuppression with prednisolone, azathioprine, and cyclosporine. No patient was in heart failure. During the study period, six grafts functioned, and three were nonfunctioning--two due to rejection and one to acute tubular necrosis. Plasma ANF concentration at the time of transplantation was 48 +/- 16 pmol/L (mean +/- SEM) range 15-145 pmol/L. In the six patients with functioning grafts, ANF declined in parallel with the fall in serum creatinine (658 +/- 35 to 210 +/- 34 mumol/L). In the three with nonfunctioning grafts, serum creatinine and plasma ANF concentration both increased. There was overall a significant linear relation between serum creatinine and plasma ANF (r = 0.527, P less than 0.001). The changes in plasma ANF after renal transplantation bore no relationship to changes in body weight or blood pressure. However, plasma ANF concentration was related to allograft fractional sodium excretion (r = 0.687, p less than 0.001). We conclude that elevated plasma ANF concentrations in end-stage renal disease are restored to normal by successful renal transplantation, implying that renal function is a determinant of plasma ANF concentration. Circulating plasma ANF may also have a direct effect on allograft sodium excretion.

Adult↗
PubMed2004

Metastable tolerance to rhesus monkey renal transplants is correlated with allograft TGF-beta 1+CD4+ T regulatory cell infiltrates.

Approaches that prevent acute rejection of renal transplants in a rhesus monkey model were studied to determine a common mechanism of acceptance. After withdrawal of immunosuppression, all 14 monkeys retained normal allograft function for >6 mo. Of these, nine rejected their renal allograft during the study, and five maintained normal function throughout the study period. The appearance of TGF-beta 1(+) interstitial mononuclear cells in the graft coincided with a nonrejection histology, whereas the absence/disappearance of these cells was observed with the onset of rejection. Analysis with a variety of TGF-beta 1-reactive Abs indicated that the tolerance-associated infiltrates expressed the large latent complex form of TGF-beta 1. Peripheral leukocytes from rejecting monkeys lacking TGF-beta 1(+) allograft infiltrates responded strongly to donor Ags in delayed-type hypersensitivity trans-vivo assays. In contrast, allograft acceptors with TGF-beta 1(+) infiltrates demonstrated a much weaker peripheral delayed-type hypersensitivity response to donor alloantigens (p < 0.01 vs rejectors), which could be restored by Abs that either neutralized active TGF-beta 1 or blocked its conversion from latent to active form. Anti-IL-10 Abs had no restorative effect. Accepted allografts had CD8(+) and CD4(+) interstitial T cell infiltrates, but only the CD4(+) subset included cells costaining for TGF-beta 1. Our data support the hypothesis that the recruitment of CD4(+) T regulatory cells to the allograft interstitium is a final common pathway for metastable renal transplant tolerance in a non-human primate model.

Animals↗
PubMed1977

Human renal allograft blood flow and early renal function.

Renal allograft blood flow (RBF) was measured at operation by electromagnetic flow meter and probes in 45 patients (34 cadaver donors and 11 living related donors). Mean RBF in 26 patients without acute tubular necrosis (ATN), was 412 +/- 80 ml/min and in 19 patients with ATN, 270 +/- 100 ml/min (p less than .001). Only two of 24 transplants (8%) with RBF greater than 350 ml/min had ATN; whereas, 17 of 21 transplants (81 per cent) with RBF less than 350 ml/min had ATN (p less than .001). In cadaver donor transplants, RBF did not correlate with duration of ATN, warm ischemia time, total ischemia time, pulsatile perfusion time or renal vascular resistance during perfusion. Measurement of renal allograft blood flow can predict presence or absence of postoperative ATN in 87% of patients.

Adolescent↗
PubMed1988

Kidney retransplantation in the cyclosporine era.

The results of kidney retransplantation in the cyclosporine era remain to be determined. Over a 42-month period, 76 nonprimary renal transplants (66 second, 7 third, 3 fourth allografts) were performed in 73 recipients under cyclosporine immunosuppression. The patient population was predominantly white (90.4%) with a mean age of 32.3 years. Twenty-one recipients (28.8%) were diabetic, and 36 (49.3%) were highly sensitized (panel-reactive antibody [PRA] greater than 50%). Sixty-two patients received cadaver donor grafts while the remaining donations were living-related (12) or living-unrelated (2). A sequential antilymphocyte globulin/cyclosporine protocol was employed, with cyclosporine therapy delayed until adequate renal function occurred. Overall patient and graft survival is 92.1% and 60.5%, respectively, after a mean follow-up of 20.0 months. The mean serum creatinine is 1.64 mg/dl in the 46 functioning allografts. Graft survival is 63.6% for secondary grafts, 28.6% for tertiary grafts, and 66.7% for fourth kidney transplants. In second transplants, recipients of cadaver donor kidneys have a graft survival of 58.5%, while living-related donor graft survival is 84.6% (P = 0.07). In the cadaver retransplant population, duration of previous transplant function greater than one year and HLA-DR matching were associated with increased graft survival, while age over 39 and presence of diabetes mellitus with reduced graft survival. However, these trends were not significant. Peak PRA above 50% did demonstrate a significant negative impact on graft survival both in the univariate and multivariate analyses of risk factors. Acute rejection occurred in 50 patients (65.8%), and was successfully reversed 50% of the time. Of the 30 grafts lost, 25 (83.3%) occurred within four months of retransplantation. Transplant nephrectomy was performed in 20 patients. Cyclosporine was not administered in 21 (70%) of these early graft failures, negating any potential beneficial effect. Retransplantation can be performed safely, with living-donor graft survival superior to cadaver retransplant rates. Rejection and early graft loss are common, especially in the highly sensitized patient. The impact of cyclosporine immunosuppression in renal retransplantation is much less dramatic than in primary transplantation in a protocol that delays cyclosporine therapy until allograft function is demonstrated.

Blood Transfusion↗
PubMed2004

Transplanted liver: consequences of denervation for liver functions.

Following liver transplantation, all hepatic nerves are transected; thus, liver allografts are completely isolated from neural control of their hosts. Despite this absolute denervation, liver allograft function does not appear to be significantly impaired after successful transplantation. In experimental animal models, hepatic denervation has no major effects on bile acid production and biotransformation, while it increases blood pressure and salt retention; decreases the number of hepatic progenitor cells, cholangiocyte proliferation, and liver regeneration; and influences the hepatic microcirculation, diet behavior, and glycemic control. In humans, hepatic denervation after liver transplantation has no major deleterious effects on bile secretion, liver regeneration, and hepatic blood flow. Insulin resistance and postprandial hyperglycemia, changes in ingestion behavior, and reduced stimulation of hepatic progenitor cells in the canals of Hering are the major side effects of absent liver innervation. Despite these abnormalities, patients can lead a new life with improved quality of life.

Animals↗
PubMedDate not supplied

[Effect of exogenous zinc deficiency on the duration of skin graft functioning].

The influence of alimentary zinc deficiency on duration of skin allograft functioning was studied in experiments on guinea pigs. Feeding the animals with a ration deprived of zinc results in significant prolongation of the skin graft functioning period. Thus, in the test group animals that received the ration deprived of zinc the mean time of the graft functioning comprised 24.0 +/- 1.4 days, while in the guinea pigs of the control group that were fed with full value ration, this parameter was 9.9 +/- 0.42 days. At the same time the number of circulating lymphocytes was decreased and their capacity for spontaneous rosette-formation was suppressed in the peripheral blood of the test group animals, as well as manifest inhibition of zinc-dependent enzymes (lactate dehydrogenase, alkaline phosphatase, carbonic anhydrase) in the blood was recorded. Zinc deficiency in the ration induces significant diminution of this trace element content in the muscles, bones, liver, skin and blood, under conditions of its daily negative balance in the body.

Animals↗
PubMed2000

Allogenicity of cryopreserved human fibroblasts: cryopreservation does not downregulate the allogenicity of fibroblasts making up the matrices of allografts.

BACKGROUND: Although cryopreserved tissue allografts are being widely used, long-term degeneration of implanted cryopreserved allografts has become a problem. Although immunologic rejection has been suggested to play a part in this degeneration, cryopreserved allografts are considered to be less immunogenic than fresh allografts. OBJECTIVE: We investigated the effect of cryopreservation on the allogenicity of the fibroblasts that make up the matrices of allografts. METHODS: Fibroblast cell strains obtained from surgically resected lung specimens were used. Allogenicity-related antigens expressed on the cell surface (human leukocyte antigen 1, human leukocyte antigen 2, and intercellular adhesion molecule 1), stimulation indices during 1-way mixed lymphocyte-fibroblast cell culture, and proliferation indices of freshly passaged fibroblasts and cryopreserved fibroblasts stored for 1, 4, and 24 weeks were examined. Flow cytometric analysis with monoclonal antibodies was used to test for cell surface antigens, and a colorimetric methyl-thiazol-diphenyl-tetrazolium assay was used to assess stimulation indices and fibroblast proliferation indices. The effect of exogenous interferon-gamma on the degree of expression of human leukocyte antigen 1, human leukocyte antigen 2, and intercellular adhesion molecule 1 was examined simultaneously. RESULTS: The proliferation indices of fibroblasts were well maintained by cryopreservation. Expression of human leukocyte antigen 1, human leukocyte antigen 2, and intercellular adhesion molecule 1 by fibroblasts was significantly upregulated by interferon-gamma, and cryopreservation did not downregulate this expression. CONCLUSION: Our study suggests that although the fibroblast cell component may be beneficial in restoring allograft function properties initially, it may render the implanted allograft more immunogenic, ultimately resulting in greater rejection and inflammatory responses by the host and, in turn, degeneration of the graft.

Analysis of Variance↗
PubMed2006

Deceased donor renal transplantation--does side matter?

BACKGROUND: The aim of the present study was to determine whether the deceased donor kidney side (left or right kidney) was predictive of subsequent kidney transplant outcomes. METHODS: A retrospective analysis was undertaken of the left-right deceased donor kidney pairs transplanted into recipients with end-stage renal failure in Queensland between 1 April 1994 and 31 March 2004. RESULTS: A total of 201 left-right deceased donor kidney pairs were transplanted into 402 patients. The baseline characteristics of the recipients in the two groups were comparable, except that the patients receiving right kidneys had lower body mass indices and shorter cold ischaemic times. No differences were seen between the left and right kidney recipient groups with respect to operative duration (3.02 +/- 0.67 vs 3.12 +/- 0.72 h, P = 0.16), warm ischaemic time (0.62 +/- 0.18 vs 0.65 +/- 0.21, P = 0.09), delayed graft function (4 vs 6%, respectively, P = 0.26) or a composite vascular, haemorrhagic, ureteric and infective post-operative complication end-point (22 vs 22%, P = 0.90). Estimated glomerular filtration rates were almost identical at 1 month (52.7 +/- 39.6 vs 51.0 +/- 24.0 ml/min/1.73 m(2), P = 0.34) and remained comparable thereafter. Respective death-censored graft survival rates for left and right kidney recipients were 100 and 100% at 1 year, 99.4 and 96.4% at 3 years and 96.3 and 95.5% at 5 years, respectively (P = 0.67). CONCLUSIONS: Although left and right deceased donor kidneys present different operative challenges, the present results suggest that the probability of early post-operative complications, delayed graft function, impaired early and medium-term renal allograft function or death-censored graft failure is comparable between left and right kidney recipients.

Adult↗
PubMed1999

Donor G protein beta3 subunit 825TT genotype is associated with reduced kidney allograft survival.

Recent studies have identified a novel polymorphism (C825T) of the gene encoding the beta3 subunit of heterotrimeric G proteins (Gbeta3), associated with enhanced activation of G proteins, which appears to be more common in hypertensive patients. In the present study, the relationship between this genetic variant and kidney allograft survival was examined over the first 3 yr after transplantation, in 320 consecutive Caucasian patients recruited from the Berlin-Steglitz transplantation center between 1988 and 1993. Clinical parameters, transplantation data, and details of graft survival were retrieved from clinical records. After multivariate adjustment for covariates (Cox hazard regression), the Gbeta3 825TT donor-genotype was associated with a significantly decreased graft survival representing a relative risk of graft loss of 2.2 (95% confidence interval, 1.1 to 4.8) compared to TC and CC grafts within the observation period. This association between donor TT genotype and graft survival remained stable even after stepwise exclusion of covariates from the multivariate model. In contrast, there was no significant relationship between recipient genotype and allograft function. These findings indicate that individuals receiving renal allografts from donors homozygous for the Gbeta3-825T allele may have an increased risk of developing allograft failure. Additional studies on the role of this genetic marker as well as the role of pertussis toxin-sensitive G proteins in the development of chronic rejection appear warranted.

Adult↗
PubMed1993

Initial nonfunction in cadaveric renal transplantation.

Patients who receive a kidney transplant that does not function immediately have more complications and decreased graft survival than patients whose allografts function immediately. To determine the causes of initial nonfunction (INF), the authors reviewed 188 consecutive cadaveric kidney transplants performed between 1985 and 1988 at the University Hospital, London, Ont. Data were collected on 16 putative risk factors for INF, which were divided into three categories: donor, recipient and technical. INF was defined as the need for dialysis within 7 days of transplantation. Forty-eight (26%) of the 188 allografts had INF, 6 of which never functioned. Univariate analysis identified five variables associated with increased risk of INF: no donor dopamine use, back-table flush, single-organ retrieval, exchanged kidney and prolonged cold ischemic time. Multivariate analysis, however, identified only three variables associated with INF: cerebrovascular accident as the cause of donor death, no donor dopamine use and single-organ retrieval. The authors recommend (a) low-dose dopamine therapy for all donors and (b) multiorgan retrieval to produce quality kidneys for transplantation.

Cadaver↗
PubMed2004

Effects of parathyroidectomy on renal allograft survival.

BACKGROUND: Hyperparathyroidism is a common problem secondary to renal insufficiency and is often not entirely resolved after renal transplantation (TX). METHODS: In this retrospective analysis, the effects of parathyroidectomy (PTX) on allograft function were evaluated and the risk factors involved in allograft deterioration in patients after PTX will be discussed. RESULTS: The rise in creatinine was steeper 1 year after PTX compared to 2 years before PTX in the majority (13 of 22) of patients. Compared to a cohort without PTX, graft survival was significantly decreased by 60% in 6 years (p < 0.0001). After multivariate adjustment, risk factors attributed to graft function included baseline creatinine (p = 0.02), baseline systolic blood pressure (p = 0.04) and time between TX and PTX, but not PTX itself. The peri-PTX drop in serum calcium was significantly more accentuated in patients exhibiting a worsening of graft function after PTX (p = 0.04). CONCLUSIONS: In patients requiring PTX, graft function is in danger of worsening. Since many factors contribute to this negative correlation and no association with parathyroid hormone (PTH) levels before PTX has been observed, we do not recommend prophylactic PTX on the basis of PTH levels only. However, appropriate management of peri-PTX risk factors is highly important. If the clinical situation, e.g. progressive renal osteodystrophy, requires removal of parathyroid glands, the procedure should be performed, if possible, in the presence of stable graft function.

Calcium↗
PubMed1983

The effect of cyclosporine on early graft function in human renal transplantation.

The effect of cyclosporine and steroids on early renal allograft function and eventual graft outcome was analyzed in 100 recipients; 33 recipients of living related donor (LRD) and 67 recipients of cadaveric donor (CAD) allografts were studied. A concurrent population of 47 CAD recipients treated with azathioprine and steroids was used for comparison. Recipients received oral cyclosporine (14 mg/kg) 48 hours (LRD) or 6-12 hours (CAD) pretransplant. No cases of acute tubular necrosis (ATN) were observed in the LRD recipients. The incidence of posttransplant ATN was similar in the cyclosporine-treated (41%) and in the azathioprine-treated (45%) CAD recipients (P = ns). Cyclosporine-treated CAD kidneys preserved less than 24 hr experienced a lower rate of ATN (P less than .01) using simple cold storage (31%), as compared with hypothermic pulsatile perfusion (57%). One-month creatinine nadirs were higher in cyclosporine-treated than in azathioprine-treated recipients, using median values for each group. One-year actuarial patient survival for cyclosporine-treated LRD recipients was 97%; CAD recipients, 94%, and azathioprine-treated CAD recipients, 91%. Graft survival rates in the same groups were 91%, 76%, and 55%, respectively. The major causes of graft loss in cyclosporine-treated patients were nonimmunologic. It is concluded that cyclosporine and prednisone are a safe, efficacious combination for LRD and CAD renal transplantation. The possibility of nephrotoxicity leading to impaired graft function in the early posttransplant period should not preclude the administration of cyclosporine prior to alloantigen presentation.

Acute Kidney Injury↗
PubMed1979

Renal transplantation for patients with type I and type II membranoproliferative glomerulonephritis: serial complement and nephritic factor measurements and the problem of recurrence of disease.

Fourteen patients with membranoproliferative glomerulonephritis as their original kidney disease received 16 renal allografts. All 14 patients are alive, 11 currently have functioning allografts, and one graft was lost to recurrence of membranoproliferative glomerulonephritis. Originally depressed serum complement (C3) concentrations returned to normal soon after transplantation in those patients with no clinical evidence of recurrence. Two patients with type II membranoproliferative glomerulonephritis had recurrence of disease. Nephritic factor (C3NeF) was high in both these patients before they received their transplants and was absent soon thereafter. However, abnormally high levels were again detected in their course. The one recurrence of type I membranoproliferative glomerulonephritis was associated with depressed C3, Clq, C4 and factor B but without C3NeF activity. Despite warnings of "high risks/ and "high mortality" associated with renal transplants in patients with membranoproliferative glomerulonephritis, we, because of these results and a review of the literature, continue to recommend renal transplants from both living related (LRD) and cadaver (CAD) donors in otherwise suitable patients who have renal failure due to membranoproliferative glomerulonephritis.

Adolescent↗
PubMed2003

Long-term experience with simultaneous kidney-pancreas transplantation with portal-enteric drainage and tacrolimus/mycophenolate mofetil-based immunosuppression.

UNLABELLED: Refinements in surgical techniques and advances in clinical immunosuppression have led to steadily improving results in pancreas transplantation (PTX). Although there is renewed interest in enteric exocrine drainage, most PTXs are performed with systemic venous delivery of insulin. To improve the physiology of PTX, we developed a novel technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal-enteric [P-E]). The purpose of the study was to analyse outcomes in patients undergoing PTX with P-E drainage and contemporary immunosuppression. MATERIALS AND METHODS: From January 1997 through September 2002, we performed 67 primary simultaneous kidney-PTXs (SKPT) with P-E drainage. Maintenance immunosuppression consisted of tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids. No antibody induction therapy occurred in 33 patients (49%) with the remainder receiving daclizumab (n = 15), basiliximab (n = 2), or thymoglobulin (n = 14) induction therapy. The patient group included 38 males and 29 females with a mean age of 39.7 year (range 23-58) and a mean duration of pretransplant diabetes of 24.5 year (9-46). Fourteen patients (21%) were African-American. RESULTS: The mean waiting time for SKPT was 3.3 months (range 0.1-10). Mean kidney and pancreas cold ischaemia times were 15.1 and 15.4 h, respectively. Patient, kidney and pancreas graft survival rates were 97%, 92.5% and 82%, respectively, with a mean follow-up of 20 months (range 1-56). Two deaths (one sepsis, one cardiac event) occurred at 1 month after SKPT; both patients died with functioning grafts (DWFG). Three patients (4.5%) had delayed renal allograft function and received temporary dialysis after SKPT. Five kidney graft losses occurred (two DWFG, one thrombosis, two chronic rejection). All but four patients (6%) had immediate PTX function. A total of 12 pancreas graft losses occurred (two DWFG, five thrombosis, five chronic rejection). The incidence of acute rejection was 28%, but no grafts were lost due to isolated acute rejection. The incidence of major infection was 51%, but only five patients (7.5%) developed cytomegalovirus infection. A total of 19 patients (28%) underwent early relaparotomy within 3 months of SKPT. The composite endpoint of no rejection, graft loss, or mortality was attained by 63% of patients. At present, 58 patients (87%) are both dialysis and insulin-independent (including four retransplants). CONCLUSION: These findings suggest that SKPT with P-E drainage and contemporary immunosuppression may result in excellent intermediate-term outcomes.

Adult↗
PubMed2006

Rat cytomegalovirus infection interferes with anti-CD4 mAb-(RIB 5/2) mediated tolerance and induces chronic allograft damage.

In order to assess the role of heterologous immunity on tolerance induction (TI) by signal 1 modification, the influence of rat cytomegalovirus infection (RCMVI) on TI by a non-depleting monoclonal anti-CD4 mAb (monoclonal antibody) (RIB 5/2) in a rat kidney transplant (KTx) model was investigated. Orthotopic rat KTx (Dark Agouty (DA)-->Lewis (LEW)) was performed after TI with RIB 5/2 [10 mg/kg body weight (BW); day -1, 0, 1, 2, 3; i.p. (intraperitoneal route)]. RCMVI (5x10E5 Plaque forming units [PFU] i.p.) was simultaneously conducted to KTx, 50 days after KTx, and 14 days before and after KTx. RIB 5/2 induced robust allograft tolerance even across the high-responder strain barrier. RCMVI broke RIB 5/2-induced tolerance regardless of the time of RCMVI but did not induce acute graft failure during the 120 days follow-up. RCMVI induced a significant chronic deterioration of allograft function (p<0.01) and enhanced morphological signs of chronic allograft damage (p<0.05). Cellular infiltrates and major histo-compatibility complex (MHC)-expression were more pronounced (p<0.05) in the infected groups. RCMVI induced not only RCMV-specific T-cell response but also enhanced the frequency of alloreactive T cells. RCMV interferes with anti-CD4 mAb-induced tolerance and leads to chronic allograft damage. The data we presented suggest a potentially important role of viral infections and their prophylaxis in clinical TI protocols.

Animals↗