Does infiltration of neutrophils in peritubular capillaries indicate humoral rejection? A case displaying a characteristic lesion of a significantly high amount of neutrophils in peritubular capillaries at 1-h graft biopsy during transplant operation

Inagaki H, Takeda A, Sato T, Watanabe I, Katayama A, Haba T, Tominaga Y, Uchida K, Oikawa T, Morozumi K. Does infiltration of neutrophils in peritubular capillaries indicate humoral rejection? A case displaying a characteristic lesion of a significantly high amount of neutrophils in peritubular capillaries at 1-h graft biopsy during transplant operation. Clin Transplantation 2001: 15 (Supplement 5): 35–40. ©Munksgaard, 2001
We present a case report of a 50-yr-old Japanese woman with a significant accumulation of neutrophils in the peritubular capillaries (PTC) and severe acute tubular necrosis (ATN) at 1-h allograft biopsy during transplant operation from cadaver donor after a cardiac death. Significant accumulation of neutrophils in the PTC is usually valuable diagnostically for acute humoral rejection. However, the patient showed no clinical signs of acute rejection. A second graft biopsy performed on the fifth postoperative day (POD) revealed that both infiltration of neutrophils in PTC and ATN lesions were more aggravated. Neither clinical course nor other morphological findings were compatible with humoral rejection. After the third biopsy of POD 27 revealing acute vascular rejection of moderate degree, acute rejection therapy using methylprednisolone pulse therapy and OKT-3 therapy was performed. Consequently, after a period of delayed graft function requiring haemodialysis for approximately 4 wk, graft function was restored and serum creatinine decreased to 2 mg/dL. Later, we were able obtain information from a paired graft from the same donor. Significant accumulation of neutrophils in the PTC similar to our recipient was also noted in a 1-h biopsy specimen of the paired kidney. This confirmed that the accumulation of neutrophils in the PTC noted in two recipients was transmitted from the donor kidney. The pathogenesis and clinical significance of neutrophils in the PTC has been shrouded in mystery.     

Sequential use of Minnesota antilymphoblast globulin and cyclosporine in cadaveric renal transplantation

The use of Cyclosporine (CsA) immediately after renal transplantation may be associated with an increased incidence and duration of acute tubular necrosis (ATN) and permanent primary graft nonfunction. To avoid this potential interaction we treated recipients of primary cadaveric grafts initially with azathioprine (AZA), methylprednisolone (MP), and 5 daily doses of Minnesota antilymphoblast globulin (MAG) (postoperative days 3-7). AZA was discontinued and CsA started on day 6 if the graft was functioning by then. If ATN persisted beyond day 6, AZA and MAG (maximum 12 doses) were continued and CsA withheld until graft function was established (group 1-33 patients). This protocol is compared to our previous regimen of MAG (14 doses over the first 3 weeks), AZA and MP (group 2-68 primary cadaveric graft recipients). Improved one-year graft survival (81% vs. 60%, P less than 0.05) and patient survival (93% vs. 81%, P less than 0.05) were seen in group 1. The incidence and duration of ATN did not differ in the two groups. During the first year after transplantation more patients in group 1 were completely free of rejection episodes (40% vs. 20%, P less than 0.05) and the number of rejection episodes per patient was also lower in this group (1.0 +/- 15 vs. 1.6 +/- 49, P less than 0.05). The incidence of infections was not different in the two groups. No tumors have developed in either group. We conclude that in primary cadaveric renal transplantation the initial administration of a short course of MAG followed by CsA therapy results in excellent graft and patient survival while avoiding the potential adverse effect of CsA on an allograft already subjected to preservation injury.     

Residual urinary volume is a risk factor for primary nonfunction in kidney transplantation

Primary nonfunction is a severe complication after kidney transplantation. Residual renal function could be a risk factor for this complication in the current era of kidney transplantation from extended criteria donors (ECD). This is a single‐center case–control study. Between 2000 and 2012, 1112 patients received a kidney transplant from a deceased donor. We identified 56 cases of early graft loss (kidney that never recover renal function and/or graft thrombosis <48 h after kidney transplantation). As controls we used patients receiving the contralateral kidney. Donor age was 55 ± 17 years with 57% fulfilling ECD criteria. Among the 56 cases, 14 were due to vascular rejection and 42 to primary nonfunction. Risk factors for early graft loss due to vascular rejection were previous transplant, time on dialysis, and HLA sensitization. Risk factors for primary nonfunction were first transplant, short period on dialysis, mainly peritoneal dialysis, and a residual urinary volume ≥500 ml/24 h. Conditional logistic regression analysis showed that residual urinary volume (OR = 20.01) rather than the dialysis modality was a major risk factor for primary nonfunction. In conclusion, residual urinary volume seems to be a risk factor for primary nonfunction in the current era of kidney transplantation.     

Evaluation of hepatocyte growth factor as a sensitive marker for early detection of acute renal allograft rejection

BACKGROUND: It has been shown that hepatocyte growth factor (HGF), besides its well-established hepatotrophic effect in liver regeneration, is involved in the regeneration of the kidney after injury. In the present study we investigated whether HGF can serve as a marker for detection of acute rejection in the early posttransplantation period. METHODS: HGF levels were determined in pre- and posttransplant sera (up to day 21) of 26 recipients with biopsy-proven acute rejection, 30 recipients with acute tubular necrosis (ATN), and 32 recipients without posttransplant complications. RESULTS: Although no association was found between pretransplant HGF and death-censored functional graft survival, receiver operating characteristic (ROC) curves demonstrated that HGF measured during the entire posttransplant study period, and especially on days 3 to 5, was a good marker for differentiating recipients who subsequently developed acute rejection from recipients with an uncomplicated course (P<0.0001, specificity 87%, sensitivity 84%). HGF measured from day 3 until day 21 posttransplantation, and especially on days 7 to 9, was also a sensitive marker for differentiating recipients with ATN from recipients with an uncomplicated course (P<0.0001). If considered in combination with sCD30, the diagnostic value of HGF was further improved. While 73% of samples from patients with impending rejection were positive for both HGF and sCD30, 94% of samples from nonrejecting patients were double-negative and none of the samples from this group fell into the double-positive category (P<0.0001). CONCLUSIONS: Our data suggest that HGF measured during the early posttransplant period might be a useful parameter for early detection of acute renal allograft rejection.     

Posttransplantation acute tubular necrosis: risk factors and implications for graft survival

Previous studies aimed at identifying the causes, risk factors, and outcome of kidney transplant recipients with delayed graft function (DGF) have yielded controversial results. We retrospectively analyzed the causes and risk factors for DGF in 263 cadaveric kidney transplantations from November 1988 to March 1997 in one center. Causes of DGF were assessed by postoperative graft evolution and graft biopsy. Univariate and multivariate analysis were used to investigate the risk factors for DGF induced by acute tubular necrosis (ATN). Seventy-six patients (29%) had DGF, which was caused by ATN in 70 patients (92.1%) and acute rejection (AR) in 6 patients (7.9%). Therefore, we focused on risk factors and consequences for ATN-induced DGF. In monofactorial analysis, ATN was significantly associated with greater weight and presence of an atheromatous disease in both donor and recipient. Other risk factors for ATN were older age of donor, recipient American Society of Anesthesiology (ASA) physical status category IV, cold ischemia time (CIT), and transplantation using the right kidney. The multivariate analysis showed that donor and recipient weight, donor age, transplantation using the right kidney, preservation in Eurocollins solution, ASA score, and CIT were associated with ATN. The incidence of rejection and renal function were not different at 3 months or 1 and 5 years. ATN is the main cause of DGF in kidney transplant recipients. ATN is caused by donor and recipient vascular background, grafting the right kidney, and CIT. ATN does not appear to have an adverse effect on long-term kidney function.     

Transplantation of kidneys harvested from non-heart-beating donors: early and long-term results

Abstract  The purpose of this retrospective study was to evaluate results of non-heart-beating donor (NHBD) kidney transplantation. Between Jan 1986 and Dec 1994,80 out of 582 cadaveric kidneys were harvested from NHBD (31.9 min ± 24 after cardiac arrest). The results in the NHBD group (76 recipients) were compared with those obtained after transplantation of kidneys harvested from heart-beating donors (HBD) with respect to early graft function, and the graft and recipient's survival. Both groups were matched for sex, age, PRA level, number of HLA mismatches, and cold ischemia time. Triple immunosuppression therapy was used in both groups. Acute tubular necrosis (ATN) was observed significantly more frequently in the NHBD group (50 of 76 recipients vs 33 of 100 in the HBD group). The striking finding of this study was that the occurrence of primary non-function was the same in both groups and that the main cause of it was acute rejection. The 1-year patient and graft survival rates were 98.7 % and 81.6 % for the NHBD group and 99 % and 90 % for the HBD group, respectively. There was also no statistical difference in the serum creat-inine concentration in both groups. We concluded that despite an increased incidence of ATN in the NHBD kidney recipients, the long-term results are good and comparable with those in the HBD group.     

Increased major histocompatibility complex antigen expression in unilateral ischemic acute tubular necrosis in the mouse

In many studies of renal transplant recipients, acute tubular necrosis has been shown to predispose to a higher rate of graft loss, apparently due to rejection, but the mechanism of this effect is unknown. One possibility is an increased immunogenicity of the graft. To study this possibility, we examined the expression of major histocompatibility complex antigens in kidneys damaged by ischemia, using a mouse model of ischemic ATN. ATN was produced in the left kidney of male CBA mice by temporary clamping of the vascular pedicle for up to 60 min. Class I and II MHC expression was quantified by the extent of binding of monoclonals in radioimmunoassay, after 1 to 35 days in both kidneys. MHC induction was localized by indirect immunoperoxidase staining. Specific steady state mRNA for beta 2 microglobulin and class II were quantified by northern blotting using 32P-labeled probes. Changes in MHC expression were assessed by comparing the ischemically injured left kidney to the control right kidney. By day 1, ATN was evident by histology but there was no change in MHC expression. By day 3, class I was increased in the left kidney by 3-6-fold over the right. In tissue sections, the class I increase was localized to tubular epithelial cells. Starting on day 7 and persisting to day 35, class II was increased by 1.5 to 3 times for the ischemic kidney over the control, primarily in interstitial cells but also in tubular cells. This increase in class II was associated with the appearance of Thy 1.2-positive cells in the interstitial areas. Increased antigen expression was preceded by increased steady state mRNA. Thus unilateral ischemic ATN causes increased MHC expression in tubular cells and the accumulation of an inflammatory infiltrate, both of which may contribute to the increased rate of rejection and graft loss in ischemically injured kidneys.     

Hepatic ischemia/reperfusion injury can be modulated with thymoglobulin induction therapy

BACKGROUND: Thymoglobulin induction therapy has been shown to ameliorate delayed graft function and possibly decrease ischemia reperfusion injury in cadaver renal transplant recipients. This controlled randomized trial was designed to assess whether thymoglobulin also protects liver transplant recipients from ischemia reperfusion injury. PATIENTS AND METHODS: Twenty-two cadaver liver transplant recipients were randomized to receive either thymoglobulin (1.5 mg/kg per dose) during the anhepatic period and two doses every other day or no thymoglobulin. No differences in recipient or donor demographics were present. Maintenance immunosupression consisted of tacrolimus (or cyclosporine) and steroids for both groups. Donor biopsies were obtained during organ procurement, cold storage, and 1 hour after revascularization. Postoperative liver function tests were monitored. Early graft function, length of stay, patient and graft survival rates, incidence of primary nonfunction, and rate of rejection were assessed. RESULTS: Patient and graft survival at 3 months was 100%. There was no incidence of primary graft nonfunction and no need for retransplantation. The incidence of acute rejection was similar between the two groups. Although donor livers randomized to thymoglobulin had less optimal preimplantation biopsies, these recipients had significant decreases in ALT at day 1 compared to the control group (P = .02), near significant decreases of total bilirubin at day 5, and shorter length of hospitalization. CONCLUSION: Thymoglobulin allowed for more compromised liver grafts to be transplanted with less clinical evidence of ischemia reperfusion injury and improved function.     

肾移植急性肾小管坏死的单光子发射计算机断层评价研究

肾移植术后急性肾小管坏死（ＡＴＮ）发生率高，鉴别诊断困难。本研究对６８例肾移植病人作了８３次单光子发射计算机断层（ＳＰＥＣＴ）检测，发现ＡＴＮ和急性排斥反应均表现摄取慢而少伴皮质滞留，但后者同时有明显肾肿大及灌注异常；超排和急性加速性排斥肾不显影、显影不清或为“负影”，严重ＡＴＮ时也可显影不清，但血流灌注尚可；灌注期及摄取早期肾实质内放射性稀疏区是上尿路梗阻的典型特征；ＣｓＡ肾中毒则以摄取障碍为主，伴有一定排泄障碍。     

Outcomes of Delayed Graft Function in Kidney Transplant Recipients Stratified by Histologic Biopsy Findings

Delayed graft function (DGF) after kidney transplantation is associated with an increased risk of graft failure. We studied the histologic findings among adult kidney transplant recipients transplanted between January 2000 and June 2015 who had DGF and had a kidney biopsy within 14 days of transplant. Death censored graft failure (DCGF) and death at 1 and 3 years after transplant were examined. A total of 269 transplant recipients fulfilled our selection criteria, of which 152 (56.51%) had acute tubular necrosis (ATN), 44 (16.4%) had acute rejection (AR), mainly T-cell mediated rejection (n = 31), 35 (13%) had ATN with AR (mainly T-cell mediated rejection, n = 26), and 38 (14.1%) had other pathology. Compared with those with ATN alone, kidney transplant recipients with AR alone had a significantly higher risk of DCGF at 1 year post transplant (adjusted hazard ratio = 3.70; 95% confidence interval 1.5-9.5; P = .006). Those with AR alone had an increased risk of DCGF at 3 years post transplant (hazard ratio = 3.10; 95% confidence interval 1.3-8.5; P = .01) in crude analyses. There was no association between DGF etiology and mortality. Early renal biopsy can be used to distinguish AR, which has protocolized treatments, from other etiologies. This could potentially alter allograft survival within 1 year of transplant complicated by DGF.     

Conversion from cyclosporine to azathioprine in renal allograft recipients

Fifty seven recipients of renal allografts initially treated with CsA and low-dose prednisone were switched to azathioprine and low-dose steroids. Ten had prolonged (greater than 28 days) allograft nonfunction after transplantation (group 1), 8 had ongoing, poorly controlled rejection (group 2), and 39 had stable functioning grafts (group 3). With a mean follow-up period of 5 +/- 3 months after conversion, 50 grafts remained functional including 6 of 10 in group 1, 6 of 8 in group 2, and 38 of 39 in group 3. Thirty-seven (65%) had improved function, 12 (21%) had stable function, and 8 (14%) experienced declining renal function. Three of these latter 8 patients required reinstitution of CsA therapy. There were 20 episodes of acute rejection in 18 patients; one graft lost function because of acute rejection unresponsive to therapy. Reasons for the 6 other graft losses were persistent primary nonfunction in 3 patients from group 1, untreated rejection in 2 patients who had multiple prior rejection episodes while on CsA, and chronic rejection in one patient. Although renal function has improved or stabilized in the majority (86%) of individuals changed to azathioprine therapy, there was substantial risk of acute rejection (32%) complicating this procedure. Patients most likely to benefit from conversion to azathioprine therapy are those with prolonged graft nonfunction after transplantation and those with serum creatinines greater than 2.0 mg/dl.     

Immunologic factors: the major risk for decreased long-term renal allograft survival

BACKGROUND: Both antigen-dependent (immunologic) and non-antigen-dependent (nonimmunologic) factors have been implicated in long-term renal allograft loss. Differentiating between these two factors is important because prevention strategies differ. METHODS: To isolate the importance of these 2 factors, we studied long-term actuarial graft survival in a cohort of adult kidney recipients who underwent transplants at a single institution between January 1, 1984 and October 31, 1998. Excluded were recipients with graft loss as a result of death with function, technical failure, primary nonfunction, and recurrent disease, leaving 1587 recipients (757 cadaver [CAD], 830 living donor [LD]) who would be at risk for graft loss secondary to both immunologic and nonimmunologic factors. These recipients were analyzed in the following 2 groups: those treated for a previous episode of acute rejection (AR) (Group1; n = 588; 328 CAD, 260 LD) and those with no AR (Group 2: n = 999; 429 CAD, 570 LD). Actuarial graft survival and causes of graft loss were determined for each group. Presumably, graft loss in Group 1 would be caused by immunologic and nonimmunologic factors; graft loss in Group 2 would be caused primarily by nonimmunologic factors. RESULTS: The 10-year graft survival rate (censored for death with function, technical failure, primary nonfunction, and recurrent disease) in Group 2 was 91%. In contrast, the 10-year graft survival rate in Group 1 was 45% (P<0.001 vs. Group 2). Causes of graft loss in Group 2 were chronic rejection in 1.8% (3.0% CAD, 0.9% LD), de novo disease, 0.4%; sepsis, 0.2%; discontinuation of immunosuppressive therapy, 0.3%; and unknown, 0.6%. In contrast, 23.8% (29.9% CAD, 16.2% LD) of recipients in Group 1 had graft loss caused by chronic rejection (P = 0.001 vs. Group 2). CONCLUSIONS: This very low incidence of chronic rejection in recipients without previous AR suggests that immunologic factors are the main determinants of long-term kidney transplant outcome; nonimmunologic factors in isolation may have only a minimal impact on long-term graft survival.     

A 100% 2-year graft survival can be attained in high-risk 15-kg or smaller infant recipients of kidney allografts

BACKGROUND: Infants make up the most high-risk, difficult to care for subgroup undergoing kidney transplantation, with the lowest 1- and 2-year graft survival rates of any other age group. The principal causes of graft loss have been graft thrombosis, primary nonfunction, technical error, and irreversible acute rejection. HYPOTHESIS: Infants undergoing kidney transplantation can achieve near 100% graft survival at 2 years following surgery, despite their very high-risk status. DESIGN: Analysis of 45 consecutive kidney transplants performed in patients weighing less than or equal to 15 kg during an 8-year period beginning August 1991. Patients included complex referrals from throughout the United States and all received transplants and were cared for by the same pediatric kidney transplantation team. RESULTS: Mean weight at transplantation was 11. 2 kg. Renal failure was due to congenital or urologic causes in the majority (53%) of cases. Size-discrepant adult-sized kidney grafts were transplanted in 80% of patients; 64% received live-donor grafts; 78% were receiving dialysis prior to transplantation; and 27% had extremely small bladders (<20 cm(3)) requiring modification of the ureteral implantation. Excluding 1 transplant-unrelated death, graft and patient survival at 2 years was 100%. Eight-year patient and graft survival rates (for our combined live and cadaver donor series) were 89.6% and 84.6%, respectively. This compares favorably with much lower graft survival in low-risk adult recipients. Delayed graft function occurred in only 1 patient (2%). Rate of incidence of rejection was 9.3% within 2 years of transplantation and the overall rejection rate was 15.5%. No graft was lost to vascular thrombosis, primary nonfunction, technical error, or acute rejection. The mean creatinine level was 53.04 micromol/L (0.6 mg/dL) and 61.9 micromol/L (0.7 mg/dL) at 1 and 2 years, respectively, and 88.4 micromol/L (1.0 mg/dL) at 3, 4, and 5 years after transplantation. CONCLUSION: One hundred percent 2-year and excellent 8-year graft survival rates can be achieved in what has historically been the highest-risk and most difficult to care for patient subgroup undergoing kidney transplantation.     

Early donor lymph node procurement and local HLA typing reduce cold ischemia time and risk of acute tubular necrosis in cadaveric kidney transplantation

Prolonged cold ischemia time (CIT) is one of the most common causes of acute tubular necrosis (ATN) with consequent delayed graft function after kidney transplantation. The aim of the study was to analyze the impact of early donor lymph nodes (LN) procurement in combination with local or central HLA typing on CIT, on donor-recipient HLA mismatches, and on the early results of grafts. Two hundred six cadaveric procedures were performed from 2001 to 2004 including 86 cases out of 119 recipients who were matched locally and 60 cases out of 87 recipients who were matched centrally, wherein LN were obtained before kidney harvest. CIT was significantly shorter when LN were obtained before kidney harvesting both in local (13.6 vs 20.6 hours) and central (20.1 vs 27.7 hours) matching (both P < .001). ATN frequency was significantly lower in patients with LN obtained earlier (27.9%) when matched locally versus (35.0%) when matched centrally. Kidney graft function estimated at 12 months was similar in both groups. CIT longer than 19.5 hours predicted ATN occurrence with 57.7% sensitivity and 66.4% specificity. Local matching resulted in shortening CIT compared to central matching (15.5 vs 22.4 hours); however, the mismatch in HLA class I and HLA class II were significantly worse (HLA A + B 2.76 vs 2.45, HLA DR 1.21 vs 0.82). These discrepancies did not significantly influence the frequency of ATN (36.1% vs 40.0%) or the kidney graft function at 12 months.     

Technical failure of the pancreas after SPK transplant: are these patients good candidates for later pancreas retransplant?

Abstract:  Technical failure of the pancreas graft after a simultaneous pancreas–kidney (SPK) transplant is not uncommon, affecting roughly 10% of SPK recipients. These patients often recover with good kidney function, but have persistent issues related to their diabetes. The aim of this study was to determine if these patients were good candidates for a later pancreas retransplant. Outcomes were compared between 21 PASPK (pancreas after SPK) recipients and 361 recipients of a primary pancreas after kidney (PAK) transplant. Except for kidney graft source, there was no significant difference in the demographic characteristics between these two groups. In general, early surgical complications were more common in PASPK than PAK recipients (47.6% vs. 35.5%, p = 0.15), although the difference was not statistically significant. The incidence of acute rejection was no different between these two groups (28% vs. 33%, p = NS). At three yr post-transplant, patient and pancreas graft survival rates were also no different between the two groups (p = NS). The most common cause for graft loss in both groups was acute or chronic rejection. In conclusion, pancreas retransplant is a viable option for SPK recipients experiencing early technical failure of the pancreas graft. These recipients are not at higher immunologic risk vs. primary PAK recipients.     

Impact of failed allograft nephrectomy on initial function and graft survival after kidney retransplantation

The management of an asymptomatic failed renal graft remains controversial. The aim of our study was to explore the effect of failed allograft nephrectomy on kidney retransplantation by comparing the outcome of recipients who underwent graft nephrectomy prior to retransplantation with those who did not. Retrospective comparison of patients undergoing kidney retransplantation with (group A, n = 121) and without (group B, n = 45) preliminary nephrectomy was performed, including subgroup analysis with reference to patients with multiple (≥2) retransplantations and patients of the European Senior Program (ESP). Nephrectomy leads to increased panel reactive antibody (PRA) levels prior to retransplantation and is associated with significantly increased rates of primary nonfunction (PNF; P = 0.05) and acute rejection (P = 0.04). Overall graft survival after retransplantation was significantly worse in group A compared with group B (P = 0.03). Among the subgroups especially ESP patients showed a shorter graft survival after previous allograft nephrectomy. On the multivariate analysis, pretransplant graft nephrectomy and PRA >70% were independent and significant risk factors associated with graft loss after kidney retransplantation. Nephrectomy of the failed allograft was not beneficial for retransplant outcome in our series. Patients with failed graft nephrectomy tended to have a higher risk of PNF and acute rejection after retransplantation. The possibility that the graft nephrectomy has a negative impact on graft function and survival after retransplantation is worth studying further.     

Adult-size kidneys without acute tubular necrosis provide exceedingly superior long-term graft outcomes for infants and small children: a single center and UNOS analysis. United Network for Organ Sharing

BACKGROUND: Infants with end-stage renal disease are at highest risk for early graft loss and mortality of any subgroup undergoing renal transplantation. This study evaluates the influence of donor tissue mass and acute tubular necrosis (ATN) on graft survival and incidence of acute rejection episodes in infant and small child recipients of living donor (LD) and cadaver (CAD) adult-size kidneys (ASKs), pediatric CAD kidneys and combined kidney-liver transplants. Methods. Kidney transplants in infants and small children at a single center and those reported to the UNOS Scientific Renal Transplant Registry were analyzed. At Stanford, multi-variate analysis was conducted on 45 consecutive renal allograft recipients weighing < or = 15 kg, mean weight 11.2 +/- 2.6 kg. The UNOS Registry results in age groups 0-2.5 (n=548) and 2.5-5 years (n=743) were compared with age groups 6-12, 13-18, and the lowest risk adult group of 19-45 years. STANFORD RESULTS. Graft survival was 97.8 +/- 0.0 at 2 years and 84.6 +/- 0.1% at 8 years. The incidence of biopsy proven rejection was 8.8% in the first 3 months and 15.5% over the 8-year follow-up. None of the pediatric CAD kidneys had ATN. Rejection episodes were restricted to the pediatric CAD kidneys alone (3/3), with no kidney rejections in the combined pediatric CAD kidney-liver transplants (0/6; P=0.003). Four ASK transplants had ATN (1 postoperative and 3 late), and all predisposed to subsequent acute rejection episodes (4/4), whereas there were no rejection episodes in ASK transplants without ATN (0/32; P<0.001). At 3 years posttransplantation, mean serum creatinines were worse in ASKs with ATN (1.5 vs. 0.9 mg/dL; P<0.001) and in all grafts with rejection episodes (1.2 vs. 0.9 mg/dL; P<0.05). UNOS RESULTS: Among the 5 age groups studied, significantly better (P<0.001) long-term graft survival rates were observed in allograft recipients in the 2 youngest age groups with ASKs without ATN: 82 +/- 3% and 81 +/- 3% for LD and 70 +/- 7% and 78 +/- 4% for CAD recipients in the 0-2.5 and 2.5- to 5-year age groups, respectively, at 6 years after transplantation. Moreover, the projected graft half-lives after the 1st year in the LD groups without ATN were at least equivalent to those of HLA-identical sibling recipients ages 19-45 years: 26.3 +/- 5 and 29.3 +/- 6 years for the 0- to 2.5- and 2.5- to 5-year age groups, respectively, and 23.3 +/- 1 years for HLA-identical transplants. The graft half-lives for CAD recipients without ATN ages 0-2.5 and 2.5-5 yearswere equivalent or better than those for LD transplants without ATN in recipients aged 19-45 years: 15.4+/- 7 and 23.7 +/- 8 years versus 15.0 +/- 0.3 years. Mean serum creatinines were superior in the 2 younger recipient age groups compared with older age groups. CONCLUSIONS: Increased donor tissue mass of the ASK or kidney-liver transplants, in the absence of ATN, seems to confer a protective effect to infant and small child recipients of these allografts. This is manifested by a prolonged rejection-free state in the single center experience and enhanced graft survival and function in the UNOS analysis, comparable to HLA identical sibling transplants for LD infant and small child recipients and to LD adult results for CAD infant and small child recipients. To optimize this protective effect by whatever mechanism, absolute avoidance of ATN is essential in infant recipients of ASK or combined kidney-liver transplants.     

肾移植术后肝细胞生长因子的动态监测及临床意义

目的:探讨肝细胞生长因子(HGF)在急性排斥反应的早期诊断、鉴别诊断中的意义。方法:采用双抗体夹心酶联免疫吸附法,对50例肾移植受者血清HGF水平在手术前后进行动态监测。观察肾移植术后发生急性排斥反应(AR)、急性肾小管坏死(ATN)、环孢素(CsA)中毒时血清HGF的变化。结果:术前组HGF水平与对照组相比有统计学意义(P<0.05)。稳定组术后前3天HGF下降明显,2周左右降至对照组水平。AR组在典型症状出现及血Cr升高前1~3d,HGF即有升高,且峰值出现在抗排斥治疗的当天。经甲基泼尼松龙冲击后AR逆转者HGF迅速下降。ATN组HGF升高,与AR组相比有统计学意义(P<0.05)。CsA中毒组HGF水平升高,与AR相比有统计学意义(P<0.05),但与ATN组相比无统计学意义(P>0.05)。结论:动态监测HGF可能作为急性排斥反应的早期诊断敏感指标,并且对ATN、CsA中毒的鉴别诊断也具有一定临床应用价值。     

Microscopic examination of the urine helps to confirm the recovery of acute tubular necrosis after cadaveric renal transplantation: a case report

INTRODUCTION: Delayed graft function due to acute tubular necrosis (ATN) is frequently seen in kidney transplants from non-heart-beating donors. However, only a biopsy can be used to assess the severity of ATN. Therefore, we studied the validity of microscopic findings in tubular epithelial cells (TECs) from urine as a means to monitor ATN. MATERIALS AND METHODS: The first voided urine in the morning was examined for the appearance and nuclear cytoplasmic (N/C) ratio of the TECs, using a murine staining with URO-3 monoclonal antibody to detect proximal tubular cells (PTCs). CASE: A 58-year-old man underwent cadaveric kidney transplantation in January, 2003 using tacrolimus, mycophenolate mofetil, and prednisone following basiliximab induction therapy. His graft did not function immediately; needle biopsy was performed on day 17. The pathological findings showed severe ATN without evidence of acute rejection. A large quantity of TECs was seen in his urine between days 7 and 14. After day 28, TECs with a large N/C ratio and that were URO-3 antibody-positive were detected. Urine volume increased gradually and hemodialysis was not necessary after day 36. CONCLUSION: The presence of URO-3-positive TECs with large N/C ratios suggests the reconstruction of PTCs. Therefore, it may be useful to monitor TEC findings to assess the severity ATN after cadaveric kidney transplantation.     

Combined pancreas kidney transplantation after isolated kidney transplantation

Simultaneous pancreas kidney transplantation (SPK) is an established therapy for type 1 diabetics with end stage or preterminal renal disease. SPK is superior to isolated kidney transplantation (KTX) in diabetic patients. Even pancreas-re-transplantations are more common in these patients now, mostly after SPK. But Experience with SPK after KTX is rare. Between 1994 and 2003 six Re-SPK 4.5 to 8.5 years after KTX were performed in our department. Average age of the recipients was 40.5 years. They had been suffering from diabetes for an average of 29.3 years. Four recipients were on dialysis again, whereas two had preterminal renal insufficiency. Pancreas transplants were drained through the bladder (n = 1) or into the small intestine (n = 5) with systemic venous anastomosis. After a median observation period of 28 months (8 to 99 months) all six recipients are insulin free. One patient lost his kidney graft due to severe acute rejection. Therefore kidney graft survival is 83 %. Four acute rejections (66 %) were observed in 4 patients. Only one rejection was treated successfully by steroids. Two rejections could be stopped with antibodies. 3 patients had infections in the early postoperative period (sinusitis, urinary tract infection, wound infection). Even after KTX with graft failure, diabetic patients suffering from renal disease can be re-transplanted successfully with SPK.