The factor V Leiden mutation and risk of renal vein thrombosis in patients with nephrotic syndrome

Background: Acquired abnormalities of coagulation and fibrinolysis in nephrotic syndrome have been implicated in the pathogenesis of renal vein thrombosis (RVT). Whether resistance to activated Protein C due to a mutation in the gene for factor V (FV Leiden/FV506Q, the commonest inherited risk factor for venous thrombosis) could contribute to risk of RT in patients with nephrotic syndrome is unknown. Method: Genotyping for the factor V Leiden mutation was undertaken in a retrospective study of 35 patients with a history of nephrotic syndrome, 10 of whom had suffered clinically significant and radiologically proven RVT. Results: Two patients (6%) were heterozygous for the FV506Q mutation, a prevalence similar to studies within the general population. One heterozygote had suffered a RVT, whilst the other without a native RVT subsequently had a primary renal allograft thrombosis. Conclusion: In a retrospective study the prevalence of the FV Leiden mutation was not increased in patients with nephrotic syndrome nor associated with prevalence of clinically significant RVT. Whilst this study was insufficiently powerful to fully exclude an association, it suggests acquired rather than inherited alterations in the coagulation/fibrinolytic balance associated with nephrosis may be of greater importance in venous thrombotic risk, and that routine screening of patients with nephrosis for this mutation will not identify the majority of patients at risk for RVT. Confirmation of these results and determining whether the natural history of thrombosis or underlying renal disease in carriers of the FV Leiden mutation differs from those without this mutation, will require a large prospective study.     

Role of cold ischemia in acute rejection: characterization of a humoral-like acute rejection in experimental renal transplantation

The aim of the study was to characterize the role of cold ischemia in the process of acute rejection using an experimental renal transplant model. Syngeneic renal transplants were performed between Wistar Agouti rats and allogeneic grafts using Wistar-Agouti rats as recipients of Brown-Norway kidneys. For cold ischemia (CI), kidneys were preserved in Euro-Collins (4 degrees C/ 2.5 hours). Rats were bilaterally nephrectomized at the moment of renal transplant and did not receive any immunosuppressant. The groups were NoAR (n = 6): immediate syngeneic transplant; CI-NoAR (n = 6): syngeneic transplant with CI; AR (n = 13): immediate allogeneic graft; CI-AR (n = 6): allogeneic graft with CI. Allogeneic rats were followed for the survival study. Syngeneic rats, with mean survival time beyond 6 months, were sacrificed on the day 7 to compare grafts with those in the allogeneic groups. H&E- and PAS-stained grafts were evaluated using the Banff criteria. Tissue INF-gamma and TNF-alpha were quantified by RT-real time-PCR on the kidney grafts. Renal insufficiency did not appear in the NoAR group, but it did from the posttransplant day 5 in both acute rejection groups. While NoAR kidneys showed well-conserved renal architecture, then AR group displayed variable degrees of tubular necrosis with scarce cellular infiltration, interstitial hemorrhage, vascular damage with fibrinoid necrosis, perivascular edema, and nuclear disruption. Cold ischemia in rejecting animals increased the mortality rate due to renal insufficiency and accelerated acute rejection. Independently of CI, the proinflammatory cytokines TNF-alpha and INF-gamma were increased in both rejection groups. In conclusion, addition of CI overactivates the acute rejection process via a humoral component.     

Resistance to activated protein C caused by factor V Leiden mutation and orthotopic liver transplantation

BACKGROUND: Factor V (FV)-dependent resistance to activated protein C (APCR) is most likely caused by a point mutation in the FV gene, the so-called FV Leiden mutation (FV:Q506), which is a common risk factor predisposing to venous thromboembolism. Little is known about the role of FV:Q506 in recipients of human liver grafts and the significance of acquired APCR caused by orthotopic liver transplantation (OLT). METHODS: We screened blood samples of 720 patients who underwent OLT by genotyping for FV:Q506 and by testing for APCR with two highly FV-specific tests. Apart from the existing medical records, we obtained clinical data from 551 patients on thromboembolic events (TEs) by means of a questionnaire. RESULTS: We found 49 (6.8%) heterozygous carriers of FV:Q who did not show APCR after OLT. One patient, heterozygous for FV:Q506, displayed APCR after OLT. In 35 (4.9%) noncarriers of FV:Q we detected APCR after OLT. In comparison with noncarriers, carriers of FV:Q506 demonstrated more TE before transplantation (7% vs. 28%, P<0.0005; relative risk 4.0 [95% confidence interval, 2.3-6.9]); this was also true for Budd-Chiari syndrome (1.8% vs. 10%, P<0.005). At a median follow-up of 5 years (0, 13-12 years), we found a higher incidence of TE after transplantation in patients with "acquired" APCR (16.7% vs. 4,3%; P=0.01; relative risk 3.9 [95% confidence interval, 1.7-9.0]), which included one patient with life-threatening TE during the early postoperative phase. CONCLUSIONS: APCR caused by FV:Q506 before OLT is a risk factor for TE. OLT-related "acquired" APCR should be considered a risk factor for venous thromboembolism.     

Transplantation of adult living donor kidneys into infants and small children

HYPOTHESIS: We hypothesized that improved outcomes following renal transplantation in high-risk infants and small children primarily are due to advances in immunosuppression and accurate diagnosis of rejection. Optimizing renal allograft perfusion is critical to achieving good early graft function and decreasing early graft loss. DESIGN: Twenty-eight consecutive recipients (weighing <20 kg) of adult living donor kidneys transplanted at our center from 1984 to 1999 were reviewed. Two groups were identified based on differing immunosuppression protocols and clinical surveillance. Actuarial graft and patient survival reported at 1, 3, and 5 years were compared for group 1 (1984-1991) and group 2 (1992-1999). Graft losses, categorized as immunologic or nonimmunologic, and the incidences of delayed graft function, vascular thrombosis, and rejection were compared. RESULTS: Graft and patient survival in group 1 (n = 13) at 1, 3, and 5 years was 77% and 92%, 54% and 85%, and 54% and 85%, respectively. In group 2, all 15 patients are alive with functioning grafts to date. Immunologic graft loss occurred in 5 of 13 patients in group 1 who developed chronic rejection. Nonimmunologic causes (vascular thrombosis [2 patients]) and patient death [1]) resulted in early graft failure within 2 weeks in 3 of 13 patients in group 1. The overall incidences of delayed graft function (10.7%) and thrombosis (7.1%) were low and did not differ between groups. Percutaneous renal biopsy was used more frequently in group 2 to evaluate graft dysfunction and guide treatment. CONCLUSIONS: We conclude that improved overall graft and patient survival in group 2 is owing to advances in immunosuppression and better treatment of rejection. Percutaneous renal biopsy allows prompt and accurate histological diagnosis of graft dysfunction. Surgical technique and aggressive fluid management aimed at maximizing renal allograft perfusion is critical in optimizing early graft function and decreasing vascular complications.     

A prospective randomized trial comparing the efficacy of tacrolimus versus cyclosporine in black recipients of primary cadaveric renal transplants.

BACKGROUND: We performed a prospective randomized trial to compare the efficacy and safety of tacrolimus (FK506) versus cyclosporine (CSA) in black primary cadaveric renal transplant (CRT) recipients. METHODS: Between December 1994 and February 1997, 35 black primary CRT recipients were enrolled in this trial. All patients received 7 days of induction therapy with OKT3. Fourteen patients received FK506 and prednisone only. Twenty-one patients received CSA, azathioprine, and prednisone. The two groups were comparable in terms of age, gender, plasma renin activity, human leukocyte antigen mismatches, and cause of renal failure. RESULTS: Patient and graft survival were 12 of 14 (86%) for the FK506 group and 20 of 21 (95%) for the CSA group (P = 0.71). Three patients died owing to cardiac events with functioning grafts. Acute rejection was 2 of 14 (14%) for the FK506 and 8 of 21 (38%) for the CSA group (P = 0.25). Two other patients on CSA were converted to FK506 as rescue for OKT3-resistant rejection. Mean serum cholesterol at 1 year was 198 +/- 45 mg/dL for the FK506 group and 244 +/- 49 mg/dL for the CSA group (P = 0.03). Mean serum creatinine at 1 year was 1.39 +/- 0.38 mg/dL for the FK506 group and 1.94 +/- 0.64 mg/dL for the CSA group (P = 0.02). CONCLUSION: Patient and graft survival were similar in both groups at 1 year posttransplant. Although statistically not significant, the incidence of acute rejection was lower in the FK506 group. Furthermore, FK506-treated patients had significantly lower serum creatinine and cholesterol levels at 1 year posttransplant.     

血清肝炎病毒标志物阳性肾移植患者临床用药特点

目的 探讨血清肝炎病毒标志物阳性。肾移植患者术后临床用药特点。方法 40例同种异体。肾移植患者，男22例，女18例。年龄30～56岁。其中乙型肝炎感染29例、丙型肝炎感染9例、乙型肝炎合并丙型肝炎感染2例。患者肝功能正常，随机分为普乐可复组（n=20），环孢素A组（n=20）。观察患者术后肝、肾功能情况及人／。肾存活率。结果 40例患者术后随访2年，普乐可复组肝功能异常发生率、急性排斥反应发生率明显低于环孢素A组（分别为15％vs30％，5％vs20％），2组2年人／肾存活率均为100％。结论 血清肝炎病毒标志物阳性患者接受肾移植术后首选普乐可复作为基础免疫制剂方案，可减少排斥反应发生率，对肝脏的损害程度轻。     

Kidney retransplants after initial graft loss to vascular thrombosis

BACKGROUND: Vascular thrombosis early after a kidney transplant is an infrequent but devastating complication. Often, no cause is found. These recipients are generally felt to be good candidates for a retransplant. However, their ideal care at the time of the retransplant and their outcomes have not been well documented. We studied outcomes in 16 retransplant recipients who had lost their first graft early posttransplant (< 1 month) to vascular thrombosis. METHODS: Of 2,003 kidney transplants between I January 1984 and 30 September 1998, we identified 32 recipients who had lost their first graft early posttransplant to vascular thrombosis. Of these 32 recipients, 16 were subsequently retransplanted and detailed chart reviews were done. RESULTS: Of the 16 retransplant recipients, 12 lost their first graft to renal vein thrombosis and 4 to renal artery thrombosis. Thrombosis generally occurred early (mean, 3.6 d). Five recipients underwent a complete hematologic workup to rule out a thrombophilic disorder before their retransplant: 4 had a positive result (presence of antiphospholipid antibodies, n = 3; increased homocysteine levels, n = 1). These 4 recipients, along with 1 other recipient who had a strong family history of thrombosis, underwent thrombosis prophylaxis at the time of their retransplant. Prophylaxis consisted of low-dose heparin for the first 3-5 d posttransplant, followed by acetylsalicylic acid or Coumadin. Of the 16 retransplant recipients, none developed thrombosis. Of the 5 who underwent thrombosis prophylaxis, none had significant bleeding complications. At a mean follow-up of 5.4 yr, 10 (63%) recipients have functioning grafts. Causes of graft loss in the remaining 6 recipients were death with function (n = 5, 31%) and acute rejection (n = 1.6%). Graft and patient survival rates after these 16 retransplants were equivalent to results after primary transplants. The incidence of acute and chronic rejection was also no different (p = ns). CONCLUSION: Vascular thrombosis in the absence of obvious technical factors should prompt a workup for a thrombophilic disorder before a retransplant. Recipients with an identified disorder should undergo prophylaxis at the time of the retransplant. Results in these retransplant recipients are equivalent to those seen in primary transplant recipients.     

Allograft Rejection of Small Bowel Transplantation in Pigs

n = 9): nonimmunosuppressed recipients; (2) group 2 (n = 8): FK506-immunosuppressed recipients; (3) group 3 (n = 2): autotransplant controls; and (4) donors (n = 17). Orthotopic small bowel transplantations were performed with Thiry-Vella loops for daily biopsies. The survival rate of group 2 was significantly longer than that of group 1 (P < 0.05). One best survivor in group 2 was killed at postoperative day (POD) 365. Treatment by FK506 prevented rejection, but most of the pigs died of pneumonia. In group 1, rejection began on POD 3 and progressed to severe rejection rapidly within 7 days. In group 2, rejection began from POD 6 to POD 8, but either remained mild or spontaneously improved. The differences in the routine laboratory data and the tumor necrosis factor-α level were not evident between the groups. Histological studies of repeated graft biopsies are thus considered to be essential for detecting signs of graft rejection. (Received for publication on Mar. 26, 1997; accepted on Jan. 6, 1998)     

低龄婴儿双供肾移植给成人22例报道

目的总结单中心低龄婴儿双供肾移植给成人的临床效果。方法回顾性纳入2013年7月至2017年10月华中科技大学同济医学院附属同济医院实施的所有儿童双供肾移植给成人受者共22例临床资料和随访数据。22例供者年龄(2.9±1.7)个月,体重(4.9±1.4)kg,其中15例小于3月龄。受者多为低体重女性成人,体重(46.3±5.6)kg。总结早期移植失败及随访期间移植肾失功或受者死亡原因。根据是否发生单侧移植肾血栓,移植肾功能恢复者又进一步分为双肾存活组和单肾存活组,比较移植肾中-长期功能。结果4例受者在术后早期出现移植失败,包括双肾血栓2例、移植肾破裂切除1例和受者多器官功能衰竭死亡1例。18例受者移植肾功能恢复出院,随访期间因移植肾新生肿瘤切除双肾1例、因复杂全身原因死亡1例、因间质性肺炎死亡1例,余15例受者双肾均存活者10例(中位随访59个月),单肾存活者5例(中位随访48个月)。移植1年时双肾存活组估算肾小球滤过率为(95±27)ml/(min·1.73 m2),显著高于单肾存活组(61±24)ml/(min·1.73 m2)(P<0.05),但3年时分别为(95±21)ml/(min·1.73 m2)和(69±31)ml/(min·1.73 m2),差异缩小,差异无显著统计学意义(P=0.12)。结论低龄婴儿双供肾移植虽然可以扩大供肾来源,但发生早期移植失败和单肾栓塞的风险较高。在单肾存活的情况下,受者仍具有相对满意的中-长期移植效果。     

Short- and long-term outcomes of kidney transplants with multiple renal arteries.

OBJECTIVE: The authors determined whether the use of kidney allografts with multiple renal arteries adversely effects post-transplant graft and patient outcome or increases the incidence of vascular and urologic complications. BACKGROUND: Kidney grafts with multiple renal arteries have been associated with an increased incidence of early vascular and urologic complications. Kidney transplants with single versus multiple renal arteries have not been compared in regard to long-term graft and patient outcome or post-transplant incidence of hypertension, acute tubular necrosis, rejection, and late vascular and urologic complications. METHODS: We analyzed 998 adult kidney transplants done from December 1, 1985 through June 30, 1993, in which only the recipient's external or internal iliac artery was used for anastomosis. We divided the study population into 3 groups: Group A-1 renal artery, 1 arterial anastomosis (n = 835), Group B-->1 renal artery, 1 arterial anastomosis (n = 112), Group C-->1 renal artery, > 1 arterial anastomosis (n = 51). We compared the incidence of post-transplant hypertension, acute tubular necrosis, acute rejection, and vascular and urologic complications; mean creatinine levels at 1, 3, and 5 years post-transplant; and patient and graft survival. Univariate and multivariate analyses were done to identify risk factors for vascular complications. RESULTS: We found no significant differences among the three groups for the following variables: post-transplant hypertension, acute tubular necrosis, acute rejection, creatinine levels, early vascular and urologic complications, and graft and patient survival. In kidneys with single arteries, the presence (vs. absence) of an aortic patch and the type of the arterial anastomosis (end-to-end to the hypogastric vs. end-to-side to the external iliac artery) did not have an impact on the incidence of early or late vascular complications. In kidneys with multiple arteries, only the rate of late renal artery stenosis was higher, the rate of early vascular and urologic complications was not different. Our multivariate analysis identified acute tubular necrosis as a risk factor for renal artery and vein thrombosis; graft placement on the left side for arterial thrombosis; and preservation time > or = 24 hours and multiple renal arteries for renal artery stenosis. CONCLUSIONS: Results of kidney transplants using allografts with multiple versus single arteries are similar.     

FK 506 versus cyclosporin in the prevention of renal allograft rejection — European pilot study: six-week results

FK 506 was compared with cyclosporin in a randomised trial in good-risk cadaveric renal transplant recipients. The objective was to evaluate whether oral FK 506 dosing was viable and whether blood concentrations in the range 10–20 ng/ml would prove to be practical. Thirty-one adult patients were randomised to FK 506 and 16 to cyclosporin. Both groups received an identical regimen of azathioprine and corticosteroids. Serum creatinine concentrations decreased rapidly in both groups with mean values below 200 mol/l within 2 weeks. One graft in the cyclosporin group was lost due to renal vein thrombosis. During the 6-week study period, 19.4% of patients on FK 506 and 31.3% on cyclosporin experienced acute rejection. One patient in each group experienced corticosteroidresistant rejection that responded to anti-lymphocyte therapy. Infections were reported in 51.6% of the FK 506 group compared with 37.5% of the cyclosporin group. The spectrum of adverse events was similar in both groups. However, minor neurological disorders were more common in the FK 506 group (54.8% versus 6.3%) whereas hypertension was less common (48.8% versus 75.0%). The results indicate that oral FK 506 rapidly achieves therapeutic blood concentrations and is an effective immunosuppressant for the initial treatment of renal allograft recipients.     

环孢素A和他克莫司在高危肾移植患者中的应用比较

目的　比较高危肾移植患者术后应用环孢素 A(CsA)和他克莫司(FK506)的疗效和安全性。方法　将58例高危肾移植患者随机分为CsA组(30例)和FK506组(28 例),观察肾移植后 1年内两组的急性排斥发生率和药物逆转率、药物毒副作用及感染发生情况。结果　 FK506组和 CsA组的人/肾存活率分别为100%/100%和93.3%/86.7%;急性排斥反应发生率分别为14.3%和16.7%;抗排斥治疗的逆转率分别为100%和60%。FK506组药物毒副作用也较 CsA组小。结论　在高危肾移植患者的免疫抑制治疗中FK506应为首选。     

Activated protein C resistance in patients with peripheral vascular disease

Purpose: The frequency of activated protein C (APC) resistance, caused by factor V R506Q gene mutation and abnormal APC ratio, in patients with peripheral vascular diseases was analyzed. Methods: All patients electively admitted to the vascular ward unit of our tertiary care academic medical center from January 1995 through October 1996 (n = 679) were prospectively analyzed using an APC-resistance screening test to determine the frequency of abnormal APC ratio (≤2.6). Baseline activated partial thromboplastin time (APTT) and its prolongation after the addition of a standard amount of APC were determined. The factor V R506Q gene mutation (Leiden) was analyzed in patients with an APC ratio less than 3.0. Statistical comparisons were made to an age-matched control population (n = 278). Results: The factor V Leiden gene mutation or abnormal APC ratio was detected in 154 of the patients (22.7%), compared with 34 of 278 the control subjects (12.2%; t = 13.65; P < .001). The factor V Leiden gene mutation was found in 102 patients (15.2%), compared with 29 control subjects (10.4%; t = 4.64; P < .05); an abnormal APC ratio was found in 132 patients (19.8%), compared with 26 (9.8%) of controls (t = 14.56; P <.001). The frequency of the factor V Leiden gene mutation was significantly increased in patients with femoro-popliteal occlusive disease (n = 126), to 21.6% (t = 16.94; P<.001), and venous disease (n = 50), to 36.0% (t = 20.93; P < .001). Overall, 63% of the patients with abnormal APC ratios tested positive for the factor V Leiden gene mutation. A significantly increased frequency of APC resistance was demonstrated in patients undergoing aorto-iliac (n = 37) or femoro-crural graft reconstructions (n = 72); it was found in 41% and 35%, respectively (P < .001). In addition, a significantly increased frequency of APC resistance was found in patients who suffered from occlusion after reconstruction; 13 of 41 (32%) had the factor V Leiden gene mutation (P < .001), and 19 of 39 (49%) had an abnormal APC ratio (P < .001). Conclusion: The factor V Leiden gene mutation and abnormal APC ratios are significantly increased in patients with lower extremity peripheral vascular disease and failed reconstructions. An abnormal APC ratio was seen without factor V Leiden gene mutation in 37% of patients with peripheral vascular diseases, suggesting additional causes of an abnormal APC ratio, exclusive of gene mutation. (J Vasc Surg 1998;28:624-9.)     

Pretransplant dialysis status and outcome of renal transplantation in North American children: a NAPRTCS Study. North American Pediatric Renal Transplant Cooperative Study

BACKGROUND: There are no large studies of the effect of pretransplant dialysis status on the outcome of renal transplantation (Tx) in children. This study evaluated the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) registry data for the outcome of Tx in pediatric patients who either (1) received their transplants preemptively or (2) were maintained on dialysis before receiving their transplants. METHODS: We compared graft survival and patient survival rates, incidence of acute tubular necrosis (ATN), acute rejection episodes, and causes of graft failure in peritoneal dialysis (PD) patients with those maintained on hemodialysis (HD) and those undergoing preemptive Tx (PTx). RESULTS: Primary Tx was performed in 2495 children (59% male; 61% Caucasian; 1090 PD, 780 HD, 625 PTx) between 1/1/1992 and 12/31/1996. The overall graft survival rates of the PD and HD groups were similar, but were less than that of the PTx group (3-year: 82% PD and HD, 89% PTx, overall P = 0.0003). Improved graft survival in the PTx group was present only in recipients of grafts from living donors. There was no difference in the overall patient survival rate at 3 years, or in time to first acute-rejection episodes in the three groups. The incidence of ATN in the first 7 days post-Tx was higher in PD and HD patients than in PTx patients (11% PD and 12% HD vs. 2% PTx, P<0.001; HD vs. PD, P = NS). The major single cause of graft failure in each group was: PD, vascular thrombosis (200%); HD, chronic rejection (27%); PTx, acute and chronic rejection (21% each). CONCLUSION: NAPRTCS data show that graft survival is improved in patients receiving PTx, compared with those receiving PD and HD. Graft loss resulting from vascular thrombosis is more common in children who receive PD than in those receiving HD.     

Heterozygosity for the factor V Leiden (G1691A) mutation predisposes renal transplant recipients to thrombotic complications and graft loss

BACKGROUND: Heterozygosity for a mutation in the coagulation factor V gene (factor V Leiden; FVL) leads to resistance to activated protein C and represents the most common cause of inherited thrombophilia. FVL is associated with a high risk for thromboembolic events and might be a risk factor for venous thrombosis and early graft loss in renal transplant recipients. METHODS: We studied a cohort of 202 renal allograft recipients to assess the impact of the FVL mutation on thrombotic events and graft loss within 1 year after transplantation. We recorded the occurrence of deep venous thrombosis, pulmonary embolism, early graft perfusion defect, and graft loss. The occurrence of these events was then correlated with the presence or absence of heterozygosity for the FVL mutation. RESULTS: Heterozygosity for FVL was detected in 8 (4%) of 202 patients. The incidence of deep venous thrombosis or pulmonary embolism was higher in heterozygous compared with wild-type patients (25% vs. 5.7%, P=0.09). Furthermore, early graft perfusion defect (25% vs. 2.6%; P=0.03) and graft loss within 7 days after transplantation (2/8 vs. 1/194; P=0.004) were significantly more frequent among heterozygous carriers of FVL. All eight FVL carriers were negative for protein C or S deficiency and antiphospholipid and anticardiolipin antibodies, and were not carriers of the G20210A prothrombin mutation. CONCLUSIONS: Heterozygosity for the FVL mutation predisposes renal allograft recipients to venous thromboembolic complications, graft perfusion defects, and early transplant loss. Screening for the FVL mutation and appropriate peri- and postoperative anticoagulation after renal transplantation might prevent these thromboembolic complications.     

Cohort study of the prognostic significance of acute transplant glomerulitis in acutely rejecting renal allografts.

BACKGROUND: Acute transplant glomerulitis is a unique lesion in renal allografts, the prognostic significance of which is controversial. We conducted this retrospective cohort study to examine the independent prognostic significance of moderate-to-severe transplant glomerulitis in acute rejection. METHODS: Renal allograft survival for patients with acute rejection were studied, comparing one group with significant glomerulitis (G, n=28) with those with no glomerulitis (NG, n=35). Clinical, biopsy, and demographic data and renal graft survival were compared, and the association of G with graft failure was examined. RESULTS: In the G versus NG group, a greater percentage of patients were highly sensitized (peak panel reactive antibody value >80%; P=0.009), had had a previous renal transplant (40% vs. 11%; P=0.02), or had suffered from delayed graft function (P=0.03). The G group had a trend toward earlier rejection episodes (P=0.07), a significantly higher serum creatinine at the time of index biopsy (P=0.01), a higher prevalence of vascular rejection (P=0.02), and less improvement in mean reciprocal serum creatinine at 1-2 weeks after biopsy (P=0.02). Although there was a trend toward shorter allograft survival in the G group (P=0.09), the level of significance of which increased with adjustment for transplantation time period and the duration of the transplant-biopsy interval (P=0.06), the relative risk for graft loss was no longer significant when additionally adjusted for index biopsy Banff score (relative risk, 0.97; P=0.97). CONCLUSION: In this study, G was significantly more common in highly sensitized patients and was strongly associated with vascular rejection biopsies but was not an independent predictor of graft survival.     

Risk Factors for Graft Loss Due to Acute Vascular Complications in Adult Renal Transplantation Using Grafts Without Vascular Anomalies

BackgroundVascular complications are the main cause of early graft loss in renal transplant (RT). A graft with multiple vessels represents the most validated risk factor. The aim of the present study was to identify potential predictive factors for acute vascular complications causing graft loss when graft vascular anomalies are excluded.MethodsThis is a retrospective case-control (1:3 ratio) study extrapolated from the RT series of the Renal Transplant Unit - Udine University Hospital, during the period 1993-2017. Grafts with multiple vessels and retransplant cases were excluded.ResultsThe overall prevalence of graft loss due to acute vascular complications was 2.6% (25/961). Seventeen complicated recipients had grafts without vascular anomalies (case group). The median time between RT and complication was 6 days (interquartile range, 4-23 days). The following types of vascular complications were recorded: 5 isolated renal artery thromboses (0.5%), 4 isolated renal vein thromboses (0.4%), 4 combined renal artery and vein thromboses (0.3%), 3 renal artery ruptures due to mycotic arteritis (0.3%), and 1 renal artery nonmycotic pseudoaneurysm (0.1%). No differences were recorded between the groups in terms of donors and grafts characteristics. Complicated recipients showed a statistically higher prevalence of thromboembolism history (P = .046) and vascular atherosclerosis (P = .048). During the postoperative course, blood stream infections (P = .02), acute rejection (P = .03), bleeding from a nonmacrovascular source (P = .04), and multiple reintervention because of nonvascular complications (P = .03) were identified as significant risk factors.ConclusionsRecipient characteristics and post-RT complications rather than donor and graft characteristics are relevant risk factors for graft loss due to acute vascular complications when graft vascular anomalies are excluded.     

采用程序化肾活检评估肾移植后低水平和标准水平他克莫司的疗效

目的以程序化肾活检评估低水平与标准水平他克莫司(FK506)的免疫抑制方案的疗效及其安全性。方法采用前瞻性、开放、随机对照研究,将48例首次接受尸体肾移植受者按随机数字分为两组:低水平FK506组(低FK506组,24例)和标准水平FK506组(标准FK506组,24例)。两组患者均采用麦考酚吗乙酯(MMF)+FK506+肾上腺皮质激素(激素)的三联免疫抑制方案,两组的MMF与激素用法相同。标准FK506组的FK506血药谷浓度:在入组后前3个月维持在10～12 ng/ml,3个月后维持在8～10 ng/ml。低FK506组的FK506血药谷浓度:入组后头2个月为8～10 ng/ml,第3个月为3～7 ng/ml,3个月后为3～5 ng/ml。术后定期随访1年,内容包括测定FK506血药谷浓度,检测肾功能[血清肌酐(Scr)、内生肌酐清除率(endogenous creatinine clearancerate,Ccr)]、空腹血糖、糖化血红蛋白、血清白蛋白、血脂。同时于术后3个月和12个月予以程序化移植肾活组织检查(活检),了解急性排斥反应(AR)发生情况、病理损伤指标评分及慢性移植物损伤指数(chronic allograft damage index,CADI)变化。观察术后1年的人、肾存活率及不良事件发生情况。结果移植术后1年,与标准FK506组比较,低FK506组:(1)FK506血药谷浓度较低(P<0.01),且达到目标水平的患者所占比例较高;(2)Ccr水平较高,(83±14)ml/min比(62±16)ml/min,P<0.05;(3)血糖水平较低(P<0.05);(4)根据程序化肾活检的结果,间质纤维化、肾小管萎缩和肾小球硬化评分较低(均为P<0.05);(5)AR发生率及其严重程度相似,术后1年人、肾存活率相近,均为100%(均为P>0.05)(6)术后1年的肺部感染与新发糖尿病的发生率较低(分别为P<0.05和P<0.01)。结论采用程序化肾活检评估疗效结果可靠,并有助于发现移植肾的慢性化改变,移植术后早期适度降低FK506血药谷浓度对于移植肾和患者均有较大益处,且不增加发生排斥反应的风险。     

C3D deposition in peritubular capillaries indicates a variant of acute renal allograft rejection characterized by a worse clinical outcome

BACKGROUND: C4d deposition in peritubular capillaries (PTCs) is a sign of humoral renal allograft rejection and an independent predictor of graft survival. Few investigators have focused on the meaning of capillary C3 deposition in rejecting grafts. Because C3 production can result from both classic and alternative pathway activation of the complement cascade, it is not clear whether C3 deposition indicates a distinct entity of acute rejection (AR) or merely represents a separate form of C4d-positive AR. METHODS: We examined the deposition of C3d in the PTCs of recipients with AR in the first year posttransplantation (n=30). Clinical outcome variables and histology were compared with C3d-negative control patients (n=82). RESULTS: C3d-positive patients demonstrated more frequent preexisting T-cell antibodies (57%) and more re-transplants (37%), and they received more blood transfusions (mean 10.3 units). C3d-positive patients experienced more frequent multiple AR episodes (57%) and delayed graft function (36.7%). All nine C3d-positive recipients screened for posttransplantation donor-specific human leukocyte antigen antibodies demonstrated positive results. Graft failure occurred in 23% of C3d-positive recipients (7.3% in the control group) (P=0.03). C3d-positive biopsies showed significantly less tubulitis (P=0.03), whereas congestive PTCs with intraluminal accumulation of polymorphonuclear leukocytes were conspicuous. Thrombi, fibrinoid necrosis, and acute tubular necrosis were not more pronounced. In 19% of rejection biopsies, C3d deposition in PTCs was present without C4d deposition. In the remaining biopsies, C3d and C4d deposition was found simultaneously. CONCLUSIONS: The deposition of complement factor C3d in PTCs indicates a variant type of AR characterized by a worse clinical outcome.     

Adverse effect of donor arteriolosclerosis on graft outcome after renal transplantation.

INTRODUCTION: In recent years less strict criteria for renal graft donors have been applied. Our study was designed to investigate whether the histological picture, with special reference to vascular changes of the donor kidney, has an effect on the development and level of graft function, and on 48-month graft survival. METHODS: Three morphologically distinct groups were formed from 150 consecutive cadaveric kidneys donors transplanted into 290 recipients. A control group (C) consisted of kidneys with a completely normal histological picture. Group M1 included kidneys with mild arteriolosclerosis and group M2 (n=122) was comprised of kidneys showing significant arteriolosclerosis. The onset of graft function was assessed by the need for dialysis treatment post-transplantation and the levels of serum creatinine and creatinine clearance at 6, 12, 24 and 36 months post transplant. RESULTS: The proportion of sclerotic glomeruli (P<0.001) and the incidence and severity of interstitial fibrosis was greater in groups M1 and M2 than in the control group (M1, P<0.01; M2, P<0.001). The incidence of vascular fibrinoid necrosis in M2 was greater than in controls (P<0.001). The onset of graft function did not differ significantly between the groups. Group M2 showed a significantly lower level of graft function (P<0.001). The 4-year graft survival rate of group M2 was 74.2%, significantly lower than in the combined group C+M1 (P=0.03). CONCLUSION: Significant vascular lesions in the donor kidney should be taken into account when predicting graft function and survival.