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PubMed1996

Effective surface cooling of the kidney during vascular anastomosis decreases the risk of delayed kidney function after transplantation.

The aim of the prospective study was to assess the exact kidney temperature and the effect of surface cooling of the kidney during the time of vascular anastomosis. Twenty-two renal graft recipients were incorporated into our study. We used an electronic temperature measurer provided with a needle-shaped probe pierced into the body of the kidney. The temperature was recorded every 5 min. The mean temperature of the kidney at the beginning of anastomosis (T0) was 8.87 +/- 3.97 degrees C and 17.95 +/- 5.1 degrees C at the end (Tend). The striking finding of this study was that the mean Tend delayed kidney function-negative in [ATN(-)] recipients was significantly lower than in the ATN(+) group; respectively, 14.86 +/- 3.6 degrees C and 19.71 +/- 5.07 degrees C. Therefore, we have divided all recipients according to Tend (< 15 degrees C and > 15 degrees C) in an attempt to assess the direct influence of kidney temperature on early graft function. In nine cases, a temperature below 15 degrees C was recorded and in 13 cases it exceeded 15 degrees C at the end of anastomosis. The mean cold ischemia time and anastomosis time were not different in these recipients. Delayed graft function occurred in 14 recipients; in 3 of 9 (33.3%) recipients from group Tend < 15 degrees C; and in 11 of 13 (85%) from group Tend > 15 degrees C. One case of primary non-function was observed (Tend > 15 degrees C). This study documents the value of effective cooling of the kidney during the time of vascular anastomosis. Since in most clinical reports the significance of the second warm ischemia was assessed only by the duration of the anastomosis, without measurement of the actual organ temperature, this may explain the different findings in our studies.

Adult↗
PubMed2005

Long-term follow-up of double kidney transplantation using a score for evaluation of marginal donors*.

To face the problem of organ shortage, marginal grafts from 36 donors which had been refused for single transplantation were used for double-kidney transplantation (D-KTX). The residual kidney function was evaluated by the Muenster double kidney score. In a 5-year period kidneys from 57 marginal donors were transferred to our center. According to the Muenster double kidney score, the kidneys were distributed to single, double or refusal of transplantation. Sixteen male and 20 female donors were used for D-KTX (70+/-9.3 years, range 53-86). Thirty-six recipients (23 male, 13 female; 60.5+/-6.9 years) were double-grafted within a mean cold ischemic time of 19.3+/-3.4 h. Immunosuppression varied according to human leukocyte antigen (HLA)-mismatch. Graft and patient survival was observed up to 5 years. Initial graft function rate was 69%. Two recipients had a primary nonfunction (5.5%) and nine recipients suffered from delayed graft function (DGF; 25%). One-, 2-, 3-year creatinine values were 1.6 +/- 0.5, 1.9 +/- 0.6 and 2.2 +/- 0.7 mg/dl, respectively. One-, 2-, 3-, 4- and 5-year function rate was 93.7%, 93.5%, 81.8%, 76.4% and 55%, respectively (n = 32, 31, 22, 17 and 9). Acute rejection rate was 19%. 4 grafts were lost to chronic rejection (months 22, 25, 28, 48). Six (16%) died in long-term follow-up because of pneumonia (n = 2), carcinoma of the lung (n = 1), cardial complications (n = 2) and multiorgan failure (n = 1). D-KTX is a safe way to face the problem of organ shortage. However, a score for preoperative evaluation of marginal kidneys for single, dual or refusal of transplantation is essential.

Acute Disease↗
PubMed2005

Laparoscopic live donor nephrectomy: a risk factor for delayed function and rejection in pediatric kidney recipients? A UNOS analysis.

The impact of laparoscopic (vs. open) donor nephrectomy on early graft function and survival in pediatric kidney recipients (< or =18 years) is unknown. We studied 995 pediatric live donor txs reported to UNOS from January 2000 to June 2002, in two recipient age groups: 0-5 years (n = 212, 44% laparoscopic donors [LapD]) and 6-18 years (n = 783, 50% LapD). Delayed graft function (DGF) rates were higher for LapD versus open donor (OpD) txs (0-5 years, 12.8% vs. 2.5% [p = 0.004]; 6-18 years, 5.9% vs. 2.8% [p = 0.03]). Acute rejection incidence for LapD versus OpD txs was higher at 6 months for recipients 0-5 years (18.6% vs. 5.9%, p = 0.01) and 6-18 years (22.5% vs. 15.6%, p = 0.03), and 1 year for recipients 0-5 years (24.3% vs. 7.9%, p = 0.004). In multivariate analyses, significant independent risk factors for rejection at 6 months and 1 year were recipient age 6-18 years, pretx dialysis, LapD nephrectomy and DGF. Graft survival was similar for LapD versus OpD txs. In this retrospective UNOS database analysis, LapD procurement was associated with increased DGF and an independent risk factor for rejection during the first year, particularly for recipients 0-5-years old. Future investigations must confirm these findings and identify strategies to optimize procurement and pediatric recipient outcome.

Adolescent↗
PubMed2006

Immediate graft function positively affects long-term outcome of renal allografts from older but not from younger donors.

There is disagreement about the impact of delayed graft function (DGF) on renal allograft outcome. This may depend on several variables including the age of the donor. We evaluated whether DGF could have different effects in recipients of kidneys from donors aged more than 60 years versus well-matched recipients of younger kidney donors. Patients were retrospectively subdivided into 3 groups. Immediate graft function (IGF), DGF without dialysis (DGF-ND), DGF requiring dialysis (DGF-D). DGF-ND and DGF-D occurred more frequently among 198 older than 198 younger donors (P = .016 and P = .044, respectively). The 5-year patient (96% vs 93%) and pure graft (96% vs 89%) survivals were significantly better in younger recipients, while the incidence of acute rejection was similar. After a mean follow-up of 66 +/- 44 months in older donor recipients, the graft survival was significantly better among IGF than patients in the DGF-ND (P = .046) or DGF-D (P = .003) groups. Instead, in younger recipients there was no difference in graft survival between IGD and DGF-ND. Only patients with DGF-D showed a significantly worse outcome. Upon multivariate analysis of older donors, their recipients, showed the pattern of graft function recovery to be the only variable associated with allograft outcome. Instead in younger donor recipients, acute rejection and time on dialysis were the main variables associated with a poor outcome. In older donor recipients, DGF was an independent variable associated with a poor graft outcome. In younger donor recipients, duration of dialysis and rejection were the most important predictors of poor graft outcomes.

Adult↗
PubMed2004

Kidney transplantation from non-heart-beating donors: analysis of organ procurement and outcome.

INTRODUCTION: Most donors in Japan have been non-heart-beating donors (NHBD), so-called "marginal donors." In Western countries kidney transplants from NHBD have also been increasing. We analyzed 120 kidneys harvested from NHBD with regard to organ procurement, renal function, graft survival, and the donor factors that affected graft survival. METHODS: Donors were moved into the operating room after cardiac arrest. A double-balloon catheter was inserted into the abdominal aorta via laparotomy. In situ cooling by Euro-Collins solution was started at 500 mL/min. We did not performed cannulation into the femoral artery or vein prior to cardiac arrest. RESULTS: Warm ischemia time (WIT) was 18.6 minutes. Among 108 kidneys (90%) used for transplantation, 102 kidneys functioned. There were no cases of bilateral nonfunctioning kidneys. The delayed graft function (DGF) rate was 86%; however, the death-censored graft survival was 80.0% at 5 years and 62.9% at 10 years. Kidneys implanted after more than 24 hours of total ischemia time required a significantly longer period of hemodialysis. Donor risk factors that affected graft survival included WIT >/= 20 minutes, donor age >/= 50 years, and serum creatinine level at admission > 1.0 mg/dL. CONCLUSIONS: Organ procurement without cannulation prior to cardiac arrest entailed a long WIT and a high DGF rate. However, the graft survival was good. It has been necessary to use grafts from NHBD despite the inherent risk factors. It is important to reduce kidney damage both at the organ procurement and during the posttransplant management.

Heart Arrest↗
PubMed1990

The role of cold ischemia in a provincial organ-sharing program in the cyclosporine era.

Prolonged cold ischemia has been associated with impaired early cadaver renal allograft function. The role of CsA in potentiating these effects is not well understood, but CsA has been implicated in promoting delayed graft function and potentiating renal ischemic injury. In order to establish whether CsA is safely tolerated by kidneys subjected to protracted cold ischemia, we examined patient and graft outcome in a series of 1081 patients receiving cadaver-kidney transplants over an 8-year period (1981-1988). All patients received a standard immunosuppressive regimen that included CsA. Overall actuarial 1-year patient and graft survival rates were 96% and 80%, respectively. Renal preservation was achieved either by pulsatile perfusion (n = 261, 24%) or simple cold storage (n = 820, 76%). Results were analyzed according to total cold ischemic time as follows: 0-23 hr (n = 512; range, 0-23.9 hr); 24-35 hr (n = 380; range, 24.0-35.9 hr); 36-47 hr (n = 161; range, 36.0-47.7 hr); greater than or equal to 48 hr (n = 28; range, 48.0-70.6 hr). These groups did not differ significantly in recipient age, sex, incidence of diabetes, number of pretransplant blood transfusions, level of presensitization, or HLA match. There were no differences in overall actuarial 1-year patient or graft survival rates, incidence of rejection, or renal function at 1 year. There was a higher incidence of impaired early graft function for kidneys preserved greater than or equal to 48 hr, but eventual graft outcome, including serum creatinine at 1 year, was unchanged. Delayed introduction of CsA resulted in improved 1-year graft survival (84.4% vs. 74.7%, P less than 0.05) compared to CsA treatment begun at the time of transplantation ("initial CsA"). This improvement was present regardless of total cold ischemia time. The incidence of permanent graft nonfunction, which has been previously reported to increase with CsA therapy, was influenced by the timing of CsA therapy (initial: 12%; delayed: 3%, P less than 0.05) but was not affected by duration of cold ischemia. Thus, safe preservation of cadaver kidneys for up to 70 h can be achieved by standard techniques even when CsA is incorporated into the immunosuppressive regimen. The most important determinants of graft survival in these patients are the timing of CsA therapy and the presence of early graft function, not the duration of renal preservation.

Blood Group Incompatibility↗
PubMed2005

Induction therapy with basiliximab versus Thymoglobulin in African-American kidney transplant recipients.

BACKGROUND: It has been suggested that the use of antilymphocyte induction therapy in African-American (AA) renal transplant recipients reduces the risk of acute rejection (AR) and improves graft survival. It is not clear whether the efficacy of basiliximab (BSX) is different from that of Thymoglobulin (ATG) in this regard. METHODS: We retrospectively assessed the effect of induction therapy with BSX versus ATG in 88 AA renal allograft recipients receiving transplants at our center between July 2001 and June 2003 and followed for 19+/-7 months. All patients were maintained on mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus. Study endpoints included patient and graft survival, graft function, and incidence of AR and cytomegalovirus infection. Regression models were used to evaluate the independent effect of each induction agent on these endpoints. RESULTS: Thirty-six patients received ATG, and 52 received BSX. The groups were comparable with regard to donor race and age, and recipient sex, body mass index, human leukocyte antigen (HLA) matching, and hepatitis C virus serostatus. The ATG group was younger, more likely to receive retransplant, had longer duration of end-stage renal disease and higher panel reactive antibody, and was less likely to receive live-donor organs. However, after adjusting for all these variables, graft outcomes, as well as renal function, were comparable between the two induction groups. We found that the degree of HLA mismatch, delayed graft function, and AR were the only significant predictors of graft loss. CONCLUSION: The results of our study suggest that the choice of induction agent may not have a major impact on graft outcomes in AA renal-allograft recipients.

Adult↗
PubMed2004

Periarterial application of papaverine during laparoscopic donor nephrectomy improves early graft function after kidney transplantation in pigs.

BACKGROUND: Laparoscopic donor nephrectomy (LDN) increases incentives to donation by subjects who might refuse an open operation. However, the incidence of delayed graft function is higher after LDN than after open operation. This may be caused by the reduction of renal perfusion as a result of the raised intraabdominal pressure and mechanically induced renal angiospasm during the operation. We conducted experiments to find out whether the application of papaverine around the renal artery during LDN could improve early graft function after transplantation. METHODS: Renal function was studied in 10 male pigs (weight approximately 25 kg). The left kidney was harvested laparoscopically (intraabdominal pressure 8 mmHg). Five animals were randomly selected to have perivascular application of 50 mg papaverine (treatment group) before preparation of the vessels. In controls no papaverine was used. After LDN and open right nephrectomy the left kidney was autotransplanted. The main outcome measures were volume of urine produced and creatinine clearance during the first 20 h after the transplant. RESULTS: The groups were comparable in respect of body weight, hemodynamic values, amount of infusions, warm and cold ischemia time, and duration of anastomosis. Urine output and creatinine clearance were significantly higher in pigs treated with papaverine than in controls. CONCLUSIONS: Papaverine substantially improved early graft function in pigs when applied around the renal artery during LDN. Whether this is applicable to procurement of human kidneys remains to be evaluated.

Animals↗
PubMed2001

Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years.

BACKGROUND: A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years. METHODS: Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years. RESULTS: The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P=0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF. CONCLUSIONS: All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.

Administration, Oral↗
PubMed2003

Two doses of daclizumab in conjunction with low-dose cyclosporine, mycophenolate mofetil and steroids resulted in a low incidence of acute rejection after renal transplantation.

Five doses of daclizumab, given initially after kidney transplantation, reduce the rate of acute rejection (AR). Without cyclosporin A (CsA), a protocol, including daclizumab, mycophenolate mofetil (MMF) and corticosteroids (CSs), has recently shown efficacy in terms of graft function and survival. The rate of AR was relatively high, however. In this single-centre study, a CsA low-dose regimen was combined with two doses of daclizumab (1 mg/kg day 0 and 14), plus MMF (2 g) and CS. Forty-three cadaver donor renal recipients were included. Following the onset of graft function, target trough levels of CsA were 150-200 ng/ml for 90 days, then 100-150 ng/ml. One year AR rate was 23% (n = 10) and events occurred at a median of 2.9 months (range from 9 days to 9.6 months). Delayed graft function (DGF) (absent spontaneous reduction of serum creatinine day 1) was 51%. Graft survival was 95% and patient survival 98% after 1 year. With respect to our previous experience, we used CsA, azathioprine and CSs (n = 223) from 1988 to 1995, and the rate of AR was 57%. From 1996 to 1998, standard CsA doses, MMF and CS (n = 67) resulted in 31% AR. Median time to AR was 0.8 and 1.0 month, and the rate of DGF was 20 and 22%, respectively. This CsA low-dose protocol, including two doses of daclizumab, MMF and CS, resulted in a reduction and delay of AR episodes and excellent graft function, graft survival and patient survival, despite an increase in DGF.

Acute Disease↗
PubMed1995

Renal transplantation: current status, complications and prevention.

Renal transplantation is the ideal mode of renal replacement therapy. One-, 5- and 10-year graft survival rates are currently > 85%, 60-70% and 40-50%, respectively. Graft loss in the first year is predominantly due to vascular complications, acute rejection, and death with a functioning graft. Other significant causes of early graft dysfunction are urological complications, delayed graft function and drug-induced nephrotoxicity. Subsequently, graft loss is due to chronic rejection or death with a functioning graft secondary to cardiovascular disease, malignancy and infection. Renal artery stenosis, chronic cyclosporin nephrotoxicity and recurrent disease also contribute to late graft dysfunction. The immunosuppressed renal transplant recipient is at long term risk of infection and neoplasia.

Animals↗
PubMedDate not supplied

Renal matrix metalloproteinase activity is unaffected by experimental ischemia-reperfusion injury and matrix metalloproteinase inhibition does not alter outcome of renal function.

BACKGROUND: Ischemia-reperfusion injury can lead to organ damage, such as delayed graft function in kidney transplantation. Reactive oxygen species that play a key role in this disorder may directly activate latent matrix metalloproteinases (MMP). In the kidney, little is known about the role of MMP in ischemia-reperfusion. Therefore, the aim of our study was to analyze activity/expression of MMP and to assess their functional role by the use of the MMP inhibitor BB-94 (Batimastat). METHODS: Renal ischemia was induced by left renal pedicle occlusion for 60 min, preceded by right nephrectomy. Thirty-two female Sprague-Dawley rats were analyzed: sham-operated rats (n = 8), treated sham-operated rats (n = 4), ischemic rats (n = 12), and treated ischemic rats (n = 8). Batimastat therapy (30 mg/kg body weight/day) was initiated 2 days prior to induction of ischemia. Animals were sacrificed 12 h (n = 8) and 24 h (n = 24) after ischemia for analyses of MMP activity/expression and of plasma creatinine levels. RESULTS: We found no evidence for an alteration in the activity or expression of MMP as a result of renal ischemia-reperfusion. Importantly, plasma creatinine levels significantly increased to a mean of 374 +/- 61 micromol/l in ischemic rats after 24 h, almost identical to the BB-94-treated ischemic rats (384 +/- 36 micromol/l). The creatinine levels in sham-operated rats remained within normal limits. CONCLUSION: MMP play no role during the early phase of experimental renal ischemia-reperfusion injury.

Animals↗
PubMedDate not supplied

Prostaglandin E1 improves pulsatile preservation characteristics and early graft function in expanded criteria donor kidneys.

Unlike simple cold storage, machine preservation allows dynamic assessment and manipulation of the donor organ before transplantation. The effects of four pharmacologic agents added to the perfusate during machine preservation of expanded criteria donor (ECD) kidneys were prospectively compared to 1) describe their influence on perfusion parameters and 2) determine their influence on early graft outcome. Between 1 January 1995 and 1 October 1997, 125 consecutive ECD kidneys were preserved in the authors' laboratory. A definition of ECD was assigned to kidneys requiring pretransplant biopsy. The ECD kidneys were randomized to receive prostaglandin E1 (PGE1), trifluoperazine (TFP), verapamil (VER), mannitol (MAN), or no intervention (control) during machine preservation. All kidneys were preserved by continuous hypothermic pulsatile perfusion (CHPP) using Belzer II solution, and perfusion parameters were measured every 2 hours during pulsatile perfusion. The addition of PGE1 to the perfusate increased renal flow and decreased renal resistance. Moreover, the PGE1 treated group was associated with improved early graft function when compared with all other groups. The addition of VER, TFP, and MAN influenced neither the perfusion characteristics nor the incidence of early graft function. Treatment with PGE1 during machine preservation enhances hydrostatic perfusion parameters (renal flow and renal resistance) and reduces the incidence of delayed graft function in ECD kidneys.

Alprostadil↗
PubMed1999

Prostaglandin E1 influences pulsatile preservation characteristics and early graft function in expanded criteria donor kidneys.

INTRODUCTION: Unlike simple cold storage, machine preservation allows dynamic assessment and manipulation of the donor organ prior to transplantation. We prospectively compared the effects of five pharmacological agents added to the perfusate during machine preservation of expanded criteria donor (ECD) kidneys in order to (1) describe their influence on perfusion parameters and (2) determine their influence on early graft outcome. METHODS: Two hundred seventy-five consecutive ECD kidneys were preserved in our laboratory between 1/1/94 and 12/31/97 by either machine perfusion (MP) or cold storage (CS). ECD kidneys were defined as those requiring pretransplant biopsy. ECD kidneys were divided by method of preservation and MP kidneys were randomized to receive prostaglandin E1 (MP+PGE1), trifluoperazine (TFP), verapamil (VER), papaverine (PAP), mannitol (MAN), or no intervention during the period of machine perfusion. CS kidneys were randomized to receive PGE1 (CS+PGE1), TFP, VER, PAP, or no intervention. All MP kidneys were preserved by continuous hypothermic pulsatile perfusion using Belzer II solution and perfusion parameters were measured every hour during pulsatile perfusion. All CS kidneys were stored in 1.0 L of University of Wisconsin (UW) solution. RESULTS: The addition of PGE1 to machine perfusate increased renal flow and decreased renal resistance. Moreover, the MP+PGE1-treated group was associated with improved early graft function compared to all other groups. The addition of VER, TFP, PAP, or MAN influenced neither the perfusion characteristics nor the incidence of early graft function in MP kidneys. Similarly, the addition of VER, TFP, or PAP did not influence early graft function in the CS kidneys. The CS+PGE1 group exhibited a significantly lower incidence of early graft function than did the MP+PGE1 group. CONCLUSIONS: PGE1 treatment during machine preservation improves hydrostatic perfusion parameters and reduces the incidence of delayed graft function in ECD kidneys. Moreover, the addition of PGE1, TFP, VER, or PAP to UW does not influence early graft function in the CS kidney.

Alprostadil↗
PubMed2000

Influence of cold-storage conditions on renal function of autotransplanted large pig kidneys.

BACKGROUND: The consequences of ischemia/reperfusion injury (IRI) on delayed graft function (DGF) and graft survival for kidney recipients remain a matter of debate. Several strategies have been proposed to reduce IRI. We have shown that adding the anti-ischemic drug trimetazidine (TMZ) to different preservation solutions had beneficial effects on the function of reperfused rat and pig kidneys. METHODS: We analyzed the renal parameters of reperfused, autotransplanted large pigs following transplantation. The left kidneys were first removed and cold flushed with Euro-Collins (EC) and University of Wisconsin (UW) solutions (with or without 10-6 mol/L TMZ) and were stored for 48 hours at 4 degrees C. The kidney was then autotransplanted, and the contralateral kidneys were removed. Creatinine clearance, natriuresis, proteinuria, the degree of interstitial fibrosis, the number of CD4, CD8, and macrophage-positive cells, and the amount of vascular cell adhesion molecule-1 were analyzed on kidney biopsies taken at 2, 4 to 5, and 10 to 12 weeks after surgery. RESULTS: The functions of the transplanted kidneys were better preserved after cold flushing with TMZ-supplemented solutions than with TMZ-free solutions. Creatinine clearance was higher, and proteinuria was lower in animals transplanted with kidneys cold flushed with TMZ-supplemented solutions than with TMZ-free solutions. The cytoprotective action of TMZ also reduced interstitial fibrosis and the numbers of infiltrating CD4- and CD8-positive cells. CONCLUSION: These results indicate that the condition of cold preservation may influence long-term kidney graft functions and suggest that, to a certain extent, TMZ reduces the degree of interstitial fibrosis.

Animals↗
PubMedDate not supplied

[Effect of preservation of the kidney on the long-term function following autotransplantation].

The consequences of ischaemia-reperfusion injury from kidney recipients on delayed graft function and graft survival still remain a matter of debate. Using an autotransplanted pig kidney model, the influence of trimetazidine added to two standard preservation solutions (Euro-Collins and University of Wisconsin) was studied. The renal parameters were analysed over a period of 12 weeks after transplantation. The degree of interstitial fibrosis, and the number of CD4, CD8 and macrophage positive cells were analysed at 2, 4-5 and 11-12 weeks after the transplantation. Glomerular filtration and sodium reabsorption were significantly more improved after cold-flush and preservation with trimetazidine-supplemented solutions than with trimetazidine-free solutions. The cytoprotective action of trimetazidine also reduced interstitial fibrosis and the number of infiltrating CD4 and CD8-positive cells. These results indicate that the condition of cold preservation may influence long-term kidney graft functions and that trimetazidine reduces to a certain extent the degree of interstitial fibrosis.

Adenosine↗
PubMed2006

Quantitative detection of promoter hypermethylation as a biomarker of acute kidney injury during transplantation.

Aberrant promoter hypermethylation, also known as epigenetics, is thought to be a promising biomarker approach to diagnose malignancies. Kidney repair after injury is a recapitulation of normal morphogenesis, with similarities to malignant transformation. We hypothesized that changes in urine epigenetics could be a biomarker approach during early kidney transplant injury and repair. We examined urine DNA for aberrant methylation of two gene promoters (DAPK and CALCA) by quantitative methylation-specific polymerase chain reaction from 13 deceased and 10 living donor kidney transplant recipients on postoperative day 2 and 65 healthy controls. Results were compared with clinical outcomes and to results of the kidney biopsy. Transplant recipients were significantly more likely to have aberrant hypermethylation of the CALCA gene promoter in urine than healthy controls (100% vs 31%; P < .0001). There was increased CALCA hypermethylation in the urine of deceased versus living donor transplants (21.60 +/- 12.5 vs 12.19 +/- 4.7; P = .04). Furthermore, there was a trend toward increased aberrant hypermethylation of urine CALCA in patients with biopsy-proven acute tubular necrosis versus acute rejection and slow or prompt graft function (mean: 20.40 +/- 6.9, 13.87 +/- 6.49, 17.17 +/- 13.4; P = .67). However, there was no difference of CALCA hypermethylation in urine of patients with delayed graft function versus those with slow or prompt graft function (16.9 +/- 6.2 vs 18.5 +/- 13.7, respectively; P = .5). There was no aberrant hypermethylation of DAPK in the urine of transplant patients. Urine epigenetics is a promising biomarker approach for acute ischemic injury in transplantation that merits future study.

Adult↗
PubMed1991

Risk factors for second renal allografts immunosuppressed with cyclosporine.

Second renal allograft survival rates are lower than those of primary allografts. For recipients immunosuppressed with azathioprine, prednisone, and Minnesota ALG (conventional immunosuppression), risk factors associated with decreased second graft survival have been identified: age greater than 40, cadaver donor, less than 6 months between primary graft loss and retransplantation, duration of primary graft function (6 months or 1 year, depending on the study), high peak panel-reactive antibody, number of human leukocyte antigen mismatches, and delayed graft function. In this study, we used a multivariate analysis to identify risk factors associated with decreased second graft survival in patients who did or did not receive cyclosporine. Results were compared with primary graft survival rates. Risk factors for patients receiving conventional immunosuppression were: (a) primary graft loss caused by rejection greater than or equal to 6 months (P = 0.01 vs. either rejection less than 6 months or nonimmunologic loss); (b) cadaver donor (P = 0.005 vs. living related); and (c) interval between primary graft loss and retransplantation of greater than or equal to 6 months (P = 0.05 vs. less than 6 months). For CsA, risk factors that most decreased second graft survival were: (a) primary graft loss caused by rejection less than 6 months (P = 0.11 vs. nonimmunologic loss); (b) conventional immunosuppression for the primary graft (P = 0.08 vs. CsA immunosuppression); and (c) a peak PRA of greater than or equal to 21 (P = 0.14 vs. peak PRA of 1-20). For second graft recipients immunosuppressed with CsA, primary graft loss to either rejection greater than 6 months posttransplant or nonimmunologic causes was not a risk factor for second graft survival. These data extend the recent reports of other investigators by identifying risk factors for retransplant recipients treated with CsA and by demonstrating that subgroups of patients in the retransplant population can be retransplanted without additional risk (i.e., their second graft survival rates are similar to primary graft survival rates). This may become more important if, in the future, organ distribution is based on graft survival data. If so, our data would support retransplantation in patients who are immunosuppressed with CsA, especially those who lost their primary graft to either rejection greater than or equal to 6 months posttransplant or nonimmunologic causes; who receive living related grafts; and who have a peak PRA of 1-20.

Adult↗