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PubMed2006

[A case report of simultaneous liver, pancreas-duodenum, and kidney transplantation in a patient with post-hepatitic cirrhosis combined with uremia and insulin-dependent diabetes related to chronic pancreatitis].

OBJECTIVE: To study the effect of triple organ transplantation (liver, kidney, and pancreas) in patient of end-stage liver disease with renal failure and diabetes, and to explore the optimal surgical procedure. METHODS: Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation was performed on a 43-year-old male patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to chronic pancreatitis (CP) who developed hepatic and renal failure. The pancreatic exocrine secretions were drained enterically to the jejunum. Prednisone, tacrolimus, mycophenolate mofetil, and ATG were used as immunosuppression therapy. RESULTS: Good liver and pancreas allograft function recovery was achieved within 7 days after the operation. And the recovery of renal allograft function was delayed. The renal allograft was removed because of break-down of renal blood flow 16 days after the transplantation. A new renal transplantation was performed at the same position. The second kidney graft recovered its normal function 3 days later. Up to the writing of this paper no acute rejection of organs and such complications as pancreatitis, thrombosis, and localized infection occurred. The patient became insulin independent with normal liver and renal function. CONCLUSION: Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation can be a good method for the patients with exocrine pancreatic insufficiency and insulin-dependent diabetes combined with hepatic and renal failure.

Adult↗

PubMed2005

First living related kidney transplantation results in excellent outcomes for small children.

OBJECTIVE: The aim of this study was to evaluated the outcomes of living related kidney transplantation in small children. MATERIALS AND METHODS: Ten pediatric patients with body weights less than 10 kg received parental kidney transplants (five mothers and five fathers). An intra-abdominal approach was used in nine children and a retroperitoneal approach in one child. Bilateral, left, or right nephrectomy was performed in seven, two, and one child, respectively. Immunosuppression consisted of either cyclosporine (n = 7) or tacrolimus (n = 3) with either mizoribine (n = 4) or mycophenolate mofetil (MMF) (n = 5) or azathioprine (n = 1), and methylprednisolone (n = 10). Antilymphocyte globulin was used in the first series of four children; basiliximab in the most recent five children. RESULTS: All renal allografts functioned immediately after transplantation despite the mismatched size of the large renal allografts. Nine of 10 children were alive with a functional allograft at 6 to 196 months posttransplantation. One child died of intra-abdominal bleeding 5 days posttransplantation. One child has suffered chronic allograft nephropathy 11 years posttransplantation (serum creatinine 3.3 mg/dL). The remaining eight children display good renal function (serum creatinine = 0.2 to 1.43 mg/dL). Steroids were withdrawn in eight of nine children; one child continues on alternative-day therapy. One child (LD55) exceeded the mean standard height. The most recent height standard deviation (SD) scores were superior (-1.75 +/- 1.39 [-3.83 to 0.54]; P < .0082) to those at transplantation (-2.91 +/- 0.79 [-2.00 to -4.14]). CONCLUSIONS: The outcomes of living related kidney transplantation in small children were excellent despite the operative risks and the difficulty of cardiovascular and fluid management. Transplantation for small children appears to result in much better quality of life and growth than dialysis.

Antibodies, Monoclonal↗

PubMed1977

Long-term results of renal transplantation in children.

Of 81 children at risk for 5 to 11 yrs following an initial renal allograft, 62 (77%) are alive and 54 (67%) have a functioning allograft. Growth retardation remains a significant problem following transplantation in children; however, rehabilitation is excellent with 94% of recipients surviving with a functioning allograft engaged in age appropriate activities.

Adolescent↗

PubMed1998

Treatment of hypertension after renal transplantation: long-term efficacy of verapamil, enalapril, and doxazosin.

Normal blood pressure is a good marker of graft survival after renal transplantation, and effective antihypertensive treatment reduces the progression of graft damage. We conducted a long-term follow-up study of 88 hypertensive renal transplant recipients, all of whom were taking sustained cyclosporine A (CsA) immunosuppression. The patients were treated for at least three years, and initially received 240 mg/day of verapamil (N = 24, group I), 5 mg/day of enalapril (N = 24, group II) or 1 mg/day of doxazosin (N = 40, group III). Baseline creatinine did not differ in the three groups, but proteinuria was higher in the enalapril group (7 patients had proteinuria > 1.5 g/day). Treatment was withdrawn in 5 patients in the verapamil group, 5 in the enalapril group and 2 in the doxazosin group due to drug-related side effects. Blood pressure (BP) control at three years was equivalent in the three groups (systolic BP, group I 157 +/- 12; group II 149 +/- 19; group III 154 +/- 21; diastolic BP, group I 90 +/- 8.7, group II 84 +/- 9.8, group III 90.5 +/- 16; mean BP, group I 113 +/- 7, group II 106 +/- 10, group III 106 +/- 29). Two patients in group I, 3 in group II and 15 in group III required additional antihypertensive drugs. CsA levels increased in the verapamil-treated patients, allowing for an early decrease in CsA doses (1 year doses, 3.3 +/- 1 mg/kg body wt/day in group I, 4.3 +/- 1.6 in group II, 3.7 +/- 1.6 in group III). Six cardiovascular events occurred, 3 in group I, 1 in group II, and 2 in group III patients. One patient died in the enalapril group and another in the doxazosin group. Eight verapamil-treated patients, 8 enalapril-treated patients and 4 doxazosin-treated patients lost their grafts due to biopsy-proven chronic transplant nephropathy. In conclusion, the three antihypertensive agents are effective in reducing blood pressure, with no clear advantage of one above any other. Verapamil allows the CsA dose to be reduced, thus decreasing the cost of immunosupression. Enalapril can be a more effective antiproteinuric agent, but hyperkalemia or impaired allograft function may occur in patients with non-optimal allograft function. Doxazosin offers an excellent safety and efficacy profile, and when not efficient by itself in controlling blood pressure, is an ideal concomitant agent in hypertensive renal transplant patients.

Adult↗

PubMed2002

Sequential monitoring of intragraft cytokine mRNA expression in relation to diastolic left ventricular wall thickness and function early after heart transplantation.

Because production of immune regulatory proteins may play a role in early graft dysfunction after heart transplantation, we analyzed whether intragraft cytokine messenger RNA (mRNA) expression levels are associated with diastolic left ventricular function in cardiac allografts. We intensively monitored 16 cardiac allograft recipients during the first 3 months after transplantation. The mRNA expression levels of tumor necrosis factor (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), transforming growth factor (TGF-beta), platelet derived growth factor (PDGF-A), and basic fibroblast growth factor (bFGF) were measured in endomyocardial biopsies (n = 123) by quantitative RT-PCR. To determine diastolic allograft function, concurrent M-mode and two-dimensional Doppler echocardiograms were analyzed for the following parameters: left ventricular total wall thickness, maximal early and atrial mitral flow velocity, deceleration time of maximal early mitral flow velocity, and isovolumetric relaxation period. During the first 3 months post-transplant an overall decrease in mRNA expression levels of almost all measured cytokines was observed, which paralleled an improvement in diastolic left ventricular wall thickness and function. However, no straightforward relationship could be found between a specific cytokine mRNA expression pattern and the studied echocardiographic parameters. Our data suggest that the improvement in diastolic left ventricular function is associated with a general reduction of inflammation within the allograft, rather than related to a specific cytokine expression pattern.

Adult↗

PubMed1981

Skin autografts to cover exposed renal allografts.

Exteriorized renal allografts that protrude abnormally after dehiscence of transplant wounds pose a rare but formidable surgical problem. If good renal allograft function is present and wound sepsis is controlled, the renal allograft need not be removed even if the wound cannot be approximated. The exposed kidney behaves like other body soft tissues, and resurfacing the renal cortex with skin autografts can be performed successfully. We present four cases demonstrating that split-thickness autografts can be successfully utilized to cover an exposed renal allograft with salvage of allograft function. The incidence of this situation was 0.62% in a series of 641 consecutive renal transplants. We also observed, incidentally, that there was no apparent linkage between the HL-A complex and the tendency for keloid formation.

Adult↗

PubMed2006

Effects of the molecular weight of peg molecules (8, 20 and 35 KDA) on cell function and allograft survival prolongation in pancreatic islets transplantation.

The normopotassic solution SCOT (Macopharma, France) used for the isolation of the islets of Langerhans may improve both graft function and survival. We believe that this is due to the immunoprotective properties of polyethyleneglycol (PEG) (20 kDa; 1.5 mM/L), which is contained in this solution. However, the optimal PEG chain length remains to be determined. Three extracellular type solutions (SCOT without PEG) containing various PEG-8 kDa, 20 kDa, or 35 kDa- at 1.5 mM/L were compared in vitro for viscosity and osmolarity as well as in vivo using a murine model of pancreatic islet allotransplantation. We compared the effects of the various solutions on functional cell recovery (primary nonfunction rate, PNF) and immunoprotection (allograft survival time). We showed that the viscosity of PEG 35 kDa solutions was too high for physiological use. PEG 20 kDa solution provided the best graft function (0% PNF, P < .05). PEG 8 kda and 20 kDa solutions significantly increased allograft survival time compared to the PEG 35 kDa solution (P < .05). Graft survival was similar with PEG 20 kDa and PEG 8 kDa solutions: 27.50 +/- 3.70 days versus 23.13 +/- 4.39 days (NS). However, the number of PNF with PEG 8 kDa solution (50%) was significantly higher (P < .01) than that with the PEG 20 kDa solution (0%). These preliminary results indicated that the optimal chain length at 1.5 mM/L of PEG is 20 kDa.

Animals↗

PubMed2001

Cytotoxic effector molecule gene expression in acute renal allograft rejection: correlation with clinical outcome; histopathology and function of the allograft.

BACKGROUND: Cytotoxic effector molecule expression in human renal allograft biopsies has been closely associated with acute rejection. Here we studied whether intragraft expression of perforin, granzyme B, and Fas ligand correlates with long-term clinical outcome of acute rejection episodes. Furthermore, we examined the relation to histopathology and function of the allograft during rejection. METHODS: Twenty-two human renal biopsies were quantified for mRNA expression of perforin, granzyme B, Fas ligand, and Fas with reverse transcription-polymerase chain reaction. Expression levels were correlated with clinical outcome after 12 months, Banff rejection grades, and allograft function in the course of acute rejection. RESULTS: Only Fas ligand, but not perforin or granzyme B, showed significantly higher up-regulation in seven samples with therapy-resistant acute rejections versus eight samples with therapy-sensitive acute rejection. We found no relation between cytotoxic marker expression and Banff rejection grades or serum creatinine peak levels. CONCLUSIONS: Fas ligand may be useful as an early marker of therapy-resistant acute rejection. Cells that express Fas ligand but not classical soluble cytotoxic molecules might influence clinical outcome of acute rejection episodes.

Acute Disease↗

PubMed1997

Analysis of functional renal allograft tolerance with single-dose rapamycin based induction immunosuppression.

The induction of transplantation tolerance is one of the primary goals following solid organ transplantation. The combination of a single dose of rapamycin (RAPA) with a short course of cyclosporine (CsA) has been shown to induce transplantation tolerance in the nonfunctional rat heterotopic cardiac transplant model. The purpose of this study was to assess this effective induction protocol in a functional renal transplant model. Male ACI (RTl(a)) and Lewis (RT1(1)) rats were used as donor and recipients respectively. Allografts received a single RAPA dose of (1.5 mg/kg) combined with CsA (10 mg/kg) 12-14 hr prior to transplantation. CsA (5 mg/kg) was given daily on days +1 - +7. Untreated Lewis to Lewis isografts served as histological controls. Chimerism, assessed in recipient skin, and intragraft interleukin (IL) 10 expression was determined utilizing PCR and RT-PCR techniques respectively. Treated animals and isografts were sacrificed 120-130 days posttransplant for functional and histological evaluation. Allografts (n=9) were functionally tolerant with serum creatinine (0.77+/-0.1 vs. 0.88+/-0.1; P=0.275), blood urea nitrogen (37.6+/-4.6 vs. 23.3+/-1.9; P=0.123), and 24 hr protein excretion (27.0+/-4.4 vs. 17.9+/-5.2; P=0.131) similar to single kidney ACI controls. Histologically, 45% (4/9) allografts were indistinguishable from isografts with no evidence of rejection, and were considered immunologically tolerant. Donor/recipient chimerism was not detected. All immunologically tolerant allografts had evidence of intragraft IL-10 expression. Rejecting allografts and isografts did not express intragraft IL-10. This study confirms the efficacy of pre-engraftment single-dose RAPA combined with CsA in inducing true immunologic tolerance in this stringent functional renal transplant model. The expression of intragraft IL-10 in tolerant recipients suggests a Th-2 shift as the mechanism of tolerance in this model.

Actins↗

PubMed2005

Allogeneic hematopoietic stem-cell transplantation, mixed chimerism, and tolerance in living related donor renal allograft recipients.

OBJECTIVE: We designed a prospective, randomized, and controlled clinical trial to evaluate the efficacy and safety of achieving a mixed chimerism-associated tolerance protocol for recipients of living related donor (LRD) renal allografts. PATIENTS AND METHODS: Sixty-six consecutive patients were divided into two equal groups of 33 patients with end-stage renal disease. They were enrolled for transplantation after negative lymphocytotoxicity cross-matching (LCM). Both groups (treated [Tn] and control [Cn]) showed similar clinical and laboratory parameters and donor HLA match profiles. The Tn group underwent thymic transplantation of donor renal tissue, two donor-specific transfusions, low-intensity conditioning, and high-dose hematopoietic stem-cell transplantation (HSCT) before renal transplantation. The conditioning regimen included low-dose, target-specific irradiation (to abdominal and inguinal lymph nodes, bone marrow [BM] from thoracolumbar vertebrae and part of the pelvis on alternate days, 100 rad x 4), anti-T-cell antibodies (1.5 mg/kg body weight [BW]), cyclophosphamide (10 mg/kg BW x 2 consecutive days), and cyclosporine (CyA; >3 mg/kg BW/d). Unfractionated HSCT procured from the donor marrow was administered into the BM, portal and peripheral circulations, within 24 hours of achieving CD 4+/CD 8+ T-cell count less than 10% of normal. This infusion was supplemented with a dose of peripherally mobilized stem cells (mean total dose of 20 x 10(8) cells/kg recipient BW) administered peripherally. Renal transplantation was performed after negative LCM. Donor-specific cytotoxic antibodies were eliminated with intravenous immunoglobulins and plasmapheresis before renal transplantation. Mixed chimerism was evaluated before and after transplantation at monthly intervals in patients with donors of opposite gender by the FISH technique. Both groups received CyA and prednisolone for immunosuppression; Cn subjects also received mycophenolate mofetil/azathioprine. Rejection was treated with standard treatment. Immunosuppression was withdrawn 6 months after renal transplantation for patients with consistently positive chimerism. Clinical tolerance was defined as stable allograft function for more than 100 days without immunosuppression and confirmed by allograft biopsy. RESULTS: Over a mean follow-up of 210 days, all Tn patients showed stable allograft function with mean serum creatinines (SCr) of 1.20 mg/dL, no rejection/CMV infections/graft or patient loss. A low-level donor-specific cytotoxic antibody was observed in all Tn patients. The CyA toxicity was noted in 10 (30.3%) patients. Persistent mixed hematopoietic chimerism was seen in all 21 patients irrespective of donor-recipient HLA matching (mean 0.5% before and 1 +/- 0.3% after transplantation). All four patients on drug withdrawal have shown donor-specific tolerance at a mean follow-up of 129.8 days. Other Tn patients are in the process of being weaned off immunosuppression. Mean SCr of controls was 1.45 mg/dL over a mean follow-up of 216 days. Acute rejection was observed in 17 (51.5%) patients; no CMV infection/patient loss was noted and one (3.03%) graft was lost in controls. No patient was lost in controls. No graft-versus-host disease was observed in Tn patients. CONCLUSION: We have achieved mixed hematopoietic chimerism-associated tolerance with high-dose HSCT, intrathymic donor renal tissue transplantation, and minimal conditioning without any adverse effects.

Adolescent↗

PubMed2003

Angiotensinogen M235T genotype predicts progression in chronic renal allograft dysfunction.

BACKGROUND: Genotypes of the renin-angiotensin system have been implicated in essential hypertension and in progression of native kidney diseases, but gene effects on progression in chronic renal allograft dysfunction are unclear. METHODS: To examine gene effects on long-term renal allograft function, we conducted a prospective cohort study of 210 nondiabetic renal allograft recipients younger than 36 years of age who underwent transplantation between 1980 and 1993 and were followed up through 1999. All grafts survived more than 1 year and all subjects received cyclosporine-based immunosuppression. DNA was analyzed by polymerase chain reaction for the angiotensin-converting enzyme insertion/deletion and angiotensinogen (AGT) M235T polymorphisms. Linear regression multivariate modeling of the slope of the inverse creatinine-versus-time, survival analyses for time-to-sustained doubling of baseline serum creatinine, time-to-graft loss, and a composite endpoint including patient death were performed. RESULTS: Mean follow-up time was 8.4+/-3 years. Genotype frequencies for each marker system did not deviate significantly from the Hardy-Weinberg equilibrium. The slope of the inverse creatinine-versus-time for AGT 235T/T and M/T was significantly increased compared with M/M ( <0.0001). The AGT 235T/T genotype was also associated with a shorter time-to-sustained doubling of serum creatinine ( =0.001). When subjects were divided into quartiles based on slope magnitude, the frequency of the AGT 235T/T genotype was overrepresented in the fastest progressing group compared with the slowest ( =0.001). The AGT 235T/T genotype was also associated with shorter time-to-graft loss ( =0.007) and the composite endpoint ( =0.001). CONCLUSION: The AGT 235 T allele independently influences long-term decline in renal allograft function.

Adolescent↗

PubMed1978

Influenza vaccination in renal transplant recipients.

Renal transplant recipients receiving immunosuppressive therapy are prone to major pulmonary infections. Development of influenza virus infection may lead to renal allograft damage or rejection. These patients should therefore be protected against influenza viruses by vaccination. A satisfactory antibody response was found in 12 (60%) of 20 renal transplant recipients vaccinated. Among 15 control subjects, the antibody response was satisfactory in all participants (100%). Factors that might play a role in suppression of antibody response include use of immunosuppressive drugs and renal allograft function. Immunization is safe and does not appear to affect renal allograft function.

Adolescent↗

PubMed1989

Effects of the thromboxane synthesis inhibitor CGS-12970 on experimental acute renal allograft rejection.

The purpose of this study was to examine the effects and mechanisms of the selective thromboxane synthesis inhibitor CGS-12970 (3-methyl-2[3 pyridyl]-1-indoleoctanoic acid) on renal allograft function and eicosanoid production. Kidneys were transplanted between nonimmunosuppressed outbred mongrel dogs and renal allograft function, renal eicosanoid production and histologic signs of rejection were monitored. In the untreated animals, renal allograft blood flow and allograft glomerular filtration rate declined steadily over the 5-day observation period compared to animals with nonrejecting autotransplanted kidneys. However, renal blood flow and glomerular filtration rate of renal allografts from animals receiving the selective thromboxane synthesis inhibitor CGS-12970 (3 mg/kg p.o. b.i.d.) were significantly higher compared to nontreated allograft animals. Histologic examination of renal allografts harvested 5 days after transplantation revealed rejection with mononuclear infiltration in both the untreated and the CGS-12970-treated animals. In untreated dogs, renal allograft tissue production of thromboxane B2 (TXB2) Prostaglandin E2 (PGE2) and 6-Keto PG F1 alpha (6-K-PGF1 alpha) was significantly elevated 5 days after transplantation compared to normal renal tissue. In animals treated with CGS-12970, renal allograft tissue production of TXB2, PGE2 and 6-K-PGF1 alpha was significantly lower than the untreated allografts and was not different from normal kidneys. In-vitro dose-response experiments revealed that CGS-12970 nonselectively inhibited renal allograft tissue TXB2 and 6-K-PGF1 alpha production in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1997

Clinical correlates to chronic renal allograft rejection.

Chronic rejection is a clinical syndrome characterized by a progressive decline in renal allograft function and nonspecific histologic findings of interstitial fibrosis, glomerulosclerosis, and fibrointimal proliferation of intrarenal arteries. Most late allograft failure that is not due to death with a functioning allograft is caused by chronic rejection. Although the pathogenesis and treatment of chronic rejection are unknown, a number of epidemiological studies have examined clinical correlates for possible clues to its pathogenesis. Clinical correlates for chronic renal allograft rejection can be classified in two broad categories: immune (alloantigen-dependent) and non-immune (alloantigen-independent). The strongest evidence that chronic rejection is immune mediated comes from its association with acute rejection and the degree of histocompatibility mismatching. However, not all acute rejection leads to chronic rejection, and there is little evidence that newer immunosuppression regimens which effectively prevent acute rejection have reduced the incidence and severity of chronic rejection. Therefore, many clinical investigators have also looked for potential non-immune causes of chronic rejection. Putative non-immune risk factors include donor source (living-related vs. cadaveric), cold ischemia time, delayed graft function, size mismatching, donor age, donor and recipient gender, recipient race, hyperlipidemia, and hypertension. Although there is little evidence supporting a cause and effect relationship between any immune or non-immune risk factor and chronic rejection, these clinical associations suggest a number of potentially important areas for further study.

Chronic Disease↗

PubMed1988

Pancreatic islet allograft prevents basement membrane thickening in the diabetic rat retina.

Progressive basement membrane thickening is a characteristic structural abnormality in diabetic tissues including the retina. We examined the effect of pancreatic islet allotransplantation on basement membrane thickening and irregularities in retinal capillaries of the streptozotocin-diabetic rat. Diabetic animals received intraportal or intracerebral pancreatic islet allografts. Animals with functioning allografts demonstrated euglycaemia and a normal body weight gain during the 400-day post-transplantation period. The characteristic thickening of capillary basement membranes was completely prevented in animals with successful transplantation. The present findings suggest that islet allotransplantation may be a rational therapeutic approach in the treatment of diabetes mellitus and the prevention of ensuing secondary complications.

Animals↗

PubMed2006

Primary graft dysfunction in lung transplantation.

Following the initial successful lung transplants reported by the Toronto Lung Transplant Group in 1986, lung transplantation has evolved into an effective treatment of isolated pulmonary failure and has been performed in more than 20,000 recipients. Increased experience, adjustments, and additions to the surgical technique and improved perioperative care have combined to decrease morbidity and improve survival in lung transplant recipients. An area in which improvements have been made but that continues to cause major morbidity, mortality, and impact on long-term allograft function is primary allograft dysfunction, which occurs in 11 to 60% transplant patients, depending on the diagnostic criteria applied. The basis of this potentially devastating complication is likely ischemia reperfusion injury of the donor allograft with activation of recipient innate immunity. This article discusses mechanisms of primary graft dysfunction in light of recent International Society for Heart and Lung Transplantation consensus definitions, and considers successful strategies for prevention and treatment of primary graft dysfunction.

Graft Rejection↗

PubMed1998

Liver transplantation for decompensated cirrhosis after jejunoileal bypass: a strategy for management.

BACKGROUND: Although jejunoileal bypass results in end-stage liver disease in up to 100% of patients, little is known about outcome after liver transplantation. METHODS: The clinical courses of six patients who underwent liver transplantation at UCLA for decompensated cirrhosis owing to a jejunoileal bypass were reviewed. Liver function, allograft pathology, renal function, and nutritional status were assessed. RESULTS: Of the four patients with an intact jejunoileal bypass, two of the three who were biopsied had recurrent steatotic liver disease. The two patients whose jejunoileal bypass was reversed at the time of liver transplantation had lower alkaline phosphatase, lower creatinine, higher albumin, and higher cholesterol, and were more obese than their counterparts with intact bypasses. CONCLUSIONS: Patients undergoing liver transplantation for jejunoileal bypass-associated liver disease should, if possible, have their bypass reversed at the time of transplantation; otherwise, they must be followed closely and be biopsied routinely. Recurrent liver disease should prompt reversal of the jejunoileal bypass.

Adult↗

PubMed2004

Cold ischemia and the reduced long-term survival of cadaveric renal allografts.

BACKGROUND: Prolonged cold ischemia time (CIT) is accompanied by delayed cadaveric renal allograft function and early allograft loss, but the effect of CIT on long-term allograft survival is less certain and has not been studied in detail. METHODS: Using data from the United Network for Organ Sharing, we identified 6465 patients who received a kidney-only transplant of cadaveric origin for the first time in 1995. We examined the effect of CIT on the 6-year survival of these kidneys using Cox proportional hazard analysis. RESULTS: The mean CIT of the kidney was 21 +/- 7 hours (mean +/- SD) and correlated with the serum creatinine on discharge (R= 0.20, P < 0.001) and the distance traveled by the kidneys (R= 0.30, P < 0.001). CIT had a significant effect on the 6-year allograft survival (a 10-hour increase in CIT was associated with a hazard risk ratio (RR) of 1.20 for graft failure (P < 0.001) that persisted (RR = 1.40, P= 0.021) after adjusting for donor age, recipient age and race, human leukocyte antigen (HLA) mismatch, panel reactive antibodies, and first 6 months' rejection treatments. Similarly, compared to CIT category of 0 to 10 hours, the 6-year graft survival was progressively worse for 11 to 20 hours (RR = 1.03), 21 to 30 hours (RR = 1.12), and, significantly so, for >30 hours (RR = 1.32; P= 0.011). The gain in HLA match with increasing CIT was not uniform; for instance, HLA match in >30 hours was lower than for 21 to 30 hours (2.4 +/- 1.5 vs. 2.7 +/- 1.6; P < 0.001). CONCLUSION: (1) Cadaveric kidneys continue to undergo prolonged periods of cold ischemia; (2) prolonged cold storage is associated with longer distance traveled by the kidneys, but is not associated with any significant gain in tissue matching; and (3) prolonged cold ischemia is a significant predictor of long-term graft loss. Reducing prolonged cold ischemia by regional distribution of organs and less stringent tissue matching may reduce the persistent high rate of long-term loss of cadaveric renal allografts.

Adult↗