Thrombotic Microangiopathy After Kidney Transplantation

Thrombotic microangiopathy (TMA) is a severe complication of kidney transplantation that often causes graft failure. TMA may occur de novo, often triggered by immunosuppressive drugs and acute antibody‐mediated rejection, or recur in patients with previous history of hemolytic uremic syndrome (HUS). Recurrent TMA is very rare in patients who had developed end‐stage renal failure following HUS caused by Shiga‐toxin producing E. scherichia coli, whereas disease recurrence is common in patients with atypical HUS (aHUS). The underlying genetic defect greatly impacts the risk of posttransplant recurrence in aHUS. Indeed recurrence is almost the rule in patients with mutations in genes encoding factor H or factor I, whereas patients with a mutation in membrane‐cofactor‐protein gene have a good transplant outcome. Prophylactic and therapeutic options for posttransplant TMA, including plasma therapy, combined kidney and liver transplantation and targeted complement inhibitors are discussed in this review.     

Recovery from Pure Red Cell Aplasia Caused by Anti-Erythropoietin Antibodies After Kidney Transplantation

The use of recombinant human erythropoietin (rHuEPO) is a major advance in the treatment of patients with anemia caused by chronic renal failure (CRF). The development of antierythropoietin (anti-EPO) antibodies following treatment with rHuEPO has been observed in an increasing number of patients. This causes pure red cell aplasia (PRCA) and requires the definitive withdrawal of rHuEPO. Many patients require immunosuppressive therapy before anti-EPO antibodies disappear completely. We report a case of PRCA owing to anti-EPO in a 20-year-old hemodialyzed man who was receiving immunosuppressive therapy for a liver transplantation carried out in childhood. He required repeated red cell transfusions until a kidney transplantation was performed. He received an induction therapy with antithymocyte globulins and a maintenance regimen consisting of steroids, tacrolimus and mycophenolate mofetil. This new immunosuppressive treatment led to the complete disappearance of anti-EPO antibodies within a few weeks after the kidney transplantation. Erythropoiesis and endogenous erythropoietin synthesis were restored following transplantation, without leading to an increase in the titer of anti-EPO antibodies.     

Effect of Teriparatide on Early Bone Loss After Kidney Transplantation

Kidney transplantation is associated with bone loss and a high risk of fractures. Prophylactic treatment of bone is therefore recommended in the early posttransplant period. As a large number of transplant recipients develop adynamic renal osteodystrophy, recombinant parathyroid hormone (rPTH) could be a promising therapeutic option.
In a 6-month double-blind, randomized trial, 26 kidney transplant recipients were treated with daily subcutaneous injections of 20 μg teriparatide (PTH 1–34) or placebo. Bone mineral density (BMD) of the femoral neck, lumbar spine and radial bone was measured at transplantation and after 6 months. Paired bone biopsies for histomorphometric analysis were obtained in six, and for measurement of bone matrix mineralization in five patients of each group. Serologic bone markers were measured at baseline and every 3 months.
A total of 24 out of 26 patients completed the study. Femoral neck BMD was stable in the teriparatide group, but decreased significantly in the placebo group. Lumbar spine and radial BMD, histomorphometric bone volume and bone matrix mineralization status remained unchanged in both groups. Serologic bone markers were similarly reduced in both groups throughout the study.
We conclude that teriparatide does not improve BMD early after kidney transplantation. Neither histological analysis nor bone markers provide evidence of improved bone turnover or mineralization.     

肾移植术后肺部感染致ARDS的治疗

目的：总结。肾移植术后重度肺部感染致急性呼吸窘迫综合征（ARDS）的治疗经验。方法：回顾性分析2000年7月-2009年1月期间24例肾移植术后重症肺部感染致ARDS患耆的临床资料：肺部感染致ARDS多在肾移植术后1～12个月发生。尤以术后2～6个月多见．且大剂量激素冲击多为诱因。24例患者均采用综合治疗方案,并按照抗排斥反应药物治疗方案分为三个阶段进行治疗。结果：24例患者中。9例死亡,2例放弃治疗．死亡率为37．5％;其中两个或两个以上器官障碍者死亡8例,最多见于上消化道出血和肾功能衰竭。1例最长呼吸机辅助呼吸达33灭．最终痊愈出院。本组患者肺部感染多为混合性感染,多以巨细胞病毒、真菌、耐药菌群和条件致病菌感染为主。结论：移植肾功能的保护或替代是治愈的决定因素;合理、及时调整抗生素是治愈的关键;肠内营养支持是治愈的基础;早期有利的呼吸功能支持是主要手段。     

Risk Factors for Development of Acute Renal Failure After Liver Transplantation

Background.?Acute renal failure (ARF) is a common complication after liver transplantation (LTx). Identification of risk factors may prevent the development and attenuate the impact of ARF on patients outcome after LTX. Methods.?Retrospective analysis of variables in the pre, intra, and postoperative periods of 92 patients submitted to LTx was performed in order to identify risk factors for development of ARF after LTx. ARF was defined as serum creatinine ≥2.0 mg/dL in the first 30 days after LTx. Univariate and multivariate analysis by logistic regression were performed. Results.?ARF group comprised 56 patients (61%). Preoperative serum creatinine was higher in ARF group. During the intraoperative period, ARF group required more blood transfusions, developed more episodes of hypotension and presented longer anesthesia time. In the postoperative period, ARF group presented higher serum bilirubin and more episodes of hypotension. Dialysis was required in 10 patients (11%). The identified risk factors for development of ARF were: preoperative serum creatinine >1.0 mg/dL, more than five blood transfusions in the intraoperative period, hypotension during intra and postoperative periods. The identified mortality risk factors were hypotension in the postoperative period and no recovery of renal function after 30 days. Conclusions.?Several factors are involved in the pathogenesis of ARF after LTx and may influence patients outcome and mortality. Pretransplant renal function and hemodynamic conditions in the operative and postoperative periods were identified as risk factors for development of ARF after LTx. Nonrenal function recovery and postoperative hypotension were identified as mortality risk factors after LTx.     

Literature Review of Passenger Lymphocyte Syndrome Following Renal Transplantation and Two Case Reports

Passenger lymphocyte syndrome (PLS) is an immune‐mediated hemolysis. It occurs following ABO blood group mismatched solid organ and/or bone marrow transplantation between donor and recipient. We report two cases of PLS occurring after renal transplantation. Both recipients received live related kidney transplants; one from his mother and the other from his brother. The direction of blood group transfer, from donor to recipient, was O Rh D+ to A Rh D+ in both cases. Approximately 12 days after transplantation, both recipients showed a rapid fall in their hemoglobin levels with no identifiable bleeding source. DAT positive hemolysis was confirmed and anti‐A antibodies were detected in recipient sera, confirming a diagnosis of PLS. Both cases required blood transfusion support to maintain their hemoglobin and both had good renal outcomes. We have identified 99 PLS cases following renal transplant in the English literature. Previous ABO sensitization, donor blood group O to recipient blood group A or B transfer, and ciclosporin treatment have been identified as risk factors for PLS. Clinical outcomes in general are good; nonetheless, cases of graft failure and deaths have been reported. Early diagnosis and appropriate treatment are important in at risk individuals.     

雷公藤多苷对移植肾长期存活率的影响

目的:探讨雷公藤多苷(TW)作为免疫抑制剂对肾移植患者长期存活率的疗效及副作用.方法:104例患者在肾移植术后采用TW 泼尼松(Pred) 环孢霉素(GsA) 硫唑嘌呤(AZa)免疫抑制剂治疗,48例患者在肾移植术后采用Pred GsA 骁悉(MMF)免疫抑制剂治疗,就以下方面对两组患者进行观察比较:(1)术后5年内发生排斥反应及临界改变情况;(2)外周血白细胞下降、肝功能异常的发生率;(3)严重感染情况;(4)出现尿蛋白情况;(5)术后5年内肾功能变化情况及移植肾5年存活率.结果:5年内AZa TW组急性排斥反应及临界改变的发生率较MMF组低,分别为11.5%、16.7%和4.8%、6.3%(P＞0.05);GPT高于正常的发生率分别为7.7%、16.6%(P＞0.05);外周血白细胞低于正常的发生率分别为0.96%、18.8%(P＜0.01);严重感染的发生率分别为1.9%、18.8%(P＜0.05),5年内出现蛋白尿的患者例数分别为17.3%、29.2%(P＞0.05),两组移植肾5年存活率相似,分别为89.6%、85.4%(P＞0.05).结论:在肾移植术后应用CsA Pred AZa TW免疫抑制方案是可行的,既可以使肾移植术后急性排斥反应减少,同时还能减少蛋白尿及慢性排斥反应的发生率下降,为国内提高移植肾长期存活率提供了一条新的途径.     

Impact of Immunosuppressive Treatment on Endothelial Biomarkers After Kidney Transplantation

Endothelial dysfunction occurs in hemodialysis and kidney‐transplanted patients and can be enhanced by immunosuppressive therapy. Circulating endothelial cells (CEC), endothelial microparticles (EMP) and sVCAM‐1 provide information on endothelium activation and damage. We compared the impact of two immunosuppressive regimens (CsA/Aza vs. Tac/MMF) on the kinetics of CEC, EMP and sVCAM‐1 levels in 52 patients, both before graft and 3, 6, 9 and 12 months after graft, in reference to 50 healthy controls. CEC, EMP and sVCAM‐1 levels were significantly decreased 1 year after transplantation (M12) as compared to pretransplant values. At M12, CEC and sVCAM‐1 levels were significantly higher than those of controls whereas EMP reached normal values. Nine months postgraft, lower CEC and normalized EMP levels were found in patients receiving cyclosporine microemulsion/ azathioprine (CsA/Aza) when compared to patients treated with tacrolimus/ mycophenolate mofetil (Tac/MMF). Multivariate analysis evidenced positive correlations between CEC and history of cardiovascular diseases and between EMP and cytomegalovirus infection at M12. In conclusion, our combined analysis of endothelial injury markers confirms the favorable impact of renal transplantation on endothelium, and show that CEC levels discriminate treatment‐associated endothelial toxicity. These results enlighten the potential of these noninvasive blood biomarkers in indexing vascular injury and optimize therapeutic options.     

Donor-Estimated GFR as an Appropriate Criterion for Allocation of ECD Kidneys into Single or Dual Kidney Transplantation

It has been suggested that dual kidney transplantation (DKT) improves outcomes for expanded criteria donor (ECD) kidneys. However, no criteria for allocation to single or dual transplantation have been assessed prospectively. The strategy of DKT remains underused and potentially eligible kidneys are frequently discarded. We prospectively compared 81 DKT and 70 single kidney transplant (SKT) receiving grafts from ECD donors aged >65 years, allocated according to donor estimated glomerular filtration rate (eGFR): DKT if eGFR between 30 and 60 mL/min, SKT if eGFR greater than 60 mL/min. Patient and graft survival were similar in the two groups. In the DKT group, 13/81 patients lost one of their two kidneys due to hemorrhage, arterial or venous thrombosis. Mean eGFR at month 12 was similar in the DKT and SKT groups (47.8 mL/min and 46.4 mL/min, respectively). Simulated allocation of kidneys according to criteria based on day 0 donor parameters such as those described by Remuzzi et al., Andres et al. and UNOS, did not indicate an improvement in 12-month eGFR compared to our allocation based on donor eGFR.     

Hyperlipidemia Is Associated With Accelerated Chronic Kidney Disease Progression After Lung Transplantation

Hyperlipidemia is associated with faster progression of chronic kidney disease (CKD) in the general public. We sought to investigate this association after lung transplantation. Data was retrospectively collected on 230 lung recipients transplanted between January 1997 and December 2003. Estimated glomerular filtration rates (eGFR) and lipid levels were recorded at regular intervals posttransplant. Independent associations between lipid levels early posttransplant and pertinent renal endpoints were investigated. Baseline LDL was 110 ± 35 mg/dL and remained unchanged at 6 months. A faster decline in eGFR was seen in those with 6 month LDLs > versus < the mean level of 110 mg/dL (p = 0.05). By 6 months posttransplant eGFRs were lower in the 6 month LDL > versus < 110 mg/dL group (53 ± 23 vs. 62 ± 29 mL/min/1.73 m², p = 0.01), a difference that persisted at 60 months (39 ± 24 vs. 73 ± 57 mL/min/1.73 m², p = 0.05). On univariate analysis, a 6 month LDL in the highest quartile, i.e. >140 mg/dL, predicted faster progression to CKD, defined as declining to an eGFR < 30 mL/min/1.73 m² (HR 1.5, p = 0.01). This finding persisted in the multivariate Cox-proportional model (HR 1.4, p = 0.02). Hyperlipidemia predicts faster decline in renal function after lung transplant. Prospective trials are needed to confirm this finding.     

Renal Histopathological Lesions After Orthotopic Liver Transplantation (OLT)

Liver transplant recipients are at risk of chronic renal failure (CRF), customarily considered to be secondary to CsA/FK506 nephrotoxicity. We have examined renal biopsies from 26 liver transplant recipients with CRF. Before OLT, 5 patients had CRF, 8 were diabetic and 9 hypertensive. Renal biopsies were performed at a mean of 5 years after liver transplantation. Mean SCr was then 212 micromol/L, proteinuria was 1 g/24 h. Twelve patients were diabetic and 25 hypertensive. Histology revealed impressive renal destruction, with a mean of 45% interstitial fibrosis and 45% glomerular sclerosis. All biopsies showed severe arteriosclerosis. CRF can be attributed to four associated primary lesions: (i) specific chronic CsA/FK506 arteriolopathy; (ii) typical diabetic nephropathy; (iii) acute or chronic thrombotic microangiopathy attributed to CsA/FK506 or alpha-IFN and (iv) tubular changes related to administration of hydroxyethylstarch. At the end of the follow-up, after a mean of 6.4 years, 12 patients required dialysis, 13 had CRF and only 1 had normal renal function. Thus, CRF in OLT recipients is more complex than originally thought and should not be classified as anti-calcineurin nephrotoxicity without further investigations, including renal histology. These investigations have therapeutic potential, that is, they may lead to a more aggressive treatment of hypertension and/or diabetes.     

Predicting Glomerular Filtration Rate in Kidney Transplantation: Are the K/DOQI Guidelines Applicable?

The kidney disease outcomes quality initiative (K/DOQI) guidelines introduced a classification of chronic kidney disease (CKD) based on the level of kidney function. In order to predict the glomerular filtration rate (GFR), they specifically recommended the use of the modification of diet in renal disease (MDRD) study and Cockcroft-Gault (C-G) equations. Since the performance of these estimates has been questioned, we sought to determine whether these recommendations might be applicable in renal transplantation. Following the K/DOQI methodology, we compared the GFR estimated by the MDRD and C-G equations with 476 inulin clearances performed in 284 renal transplant recipients. Even though the MDRD equations provided a better prediction than C-G formula, none of them reached the level of accuracy required by the K/DOQI standards. At least, 25% of the calculated GFR gave a prediction beyond 30% of the corresponding inulin clearance value. In addition, when classified according to their predicted GFR, less than two-thirds of the transplant patients turned out to be assigned to the correct stage of CKD. We conclude that, in renal transplantation, the predictive performance of both C-G and MDRD study equations appears to be particularly impaired and may potentially compromise the validity of the K/DOQI guidelines if implemented in their current form.     

Proteinuria After Kidney Transplantation, Relationship to Allograft Histology and Survival

Proteinuria is associated with reduced kidney allograft survival. Herein we assessed the association between proteinuria, graft histology and survival. The cohort included 613 kidney allograft recipients who had proteinuria (measured) and surveillance biopsies at 1-year posttransplant. Proteinuria >150 mg/day was detected in 276 patients (45%) and in 182 of these, proteinuria was below 500. In >84% of patients even low levels of proteinuria were associated with albuminuria. Proteinuria was associated with the presence of graft glomerular pathology and the use of sirolimus. Eighty percent of patients with proteinuria >1500 mg/day had glomerular pathology on biopsy. However, lower levels of proteinuria were not associated with specific pathologies at 1 year. Compared to no sirolimus, sirolimus use was associated with higher prevalence of proteinuria (40% vs. 76%, p < 0.0001) and higher protein excretion (378 + 997 vs. 955 + 1986 mg/day, p < 0.0001). Proteinuria was associated with reduced graft survival (HR = 1.40, p = 0.001) independent of other risk factors including, glomerular pathology, graft function, recipient age and acute rejection. The predominant pathology in lost allografts (n = 57) was glomerular, particularly in patients with 1-year proteinuria >500. Thus, proteinuria, usually at low levels (<500 mg/day), is present in 45% of recipients at 1 year. However, and even low levels of proteinuria relate to poor graft survival. Proteinuria and glomerular pathology relate independently to survival.     

Early Graft Loss After Kidney Transplantation: Risk Factors and Consequences

Early graft loss (EGL) after kidney transplantation is a catastrophic outcome that is assumed to be more likely after the use of kidneys from suboptimal donors. We therefore examined its incidence, risk factors and consequences in our center in relation to different donor types. Of 801 recipients who received a kidney‐only transplant from deceased donors, 50 (6.2%) suffered EGL within 30 days of transplantation. Significant risks factors for EGL were donation after circulatory death (DCD) (odds ratio [OR] 2.88; p = 0.006), expanded criteria donor (ECD) transplantation (OR 4.22; p = 0.010), donor age (OR 1.03; p = 0.044) and recipient past history of thrombosis (OR 4.91; p = 0.001). Recipients with EGL had 12.28 times increased risk of death within the first year, but long‐term survival was worse for patients remaining on the waiting list. In comparison with patients on the waiting list but not transplanted, and with all patients on the waiting list, the risk of death after EGL decreased to baseline 4 and 23 months after transplantation, respectively. Our findings suggest that DCD and ECD transplantation are significant risk factors for EGL, which is a major risk factor for recipient death. However, long‐term mortality is even greater for those remaining on the waiting list.     

Immunosuppression for Dual Kidney Transplantation with Marginal Organs: The Old Is Better Yet

Immunosuppressive protocols in dual kidney transplantation (DKT) are based on calcineurin inhibitors (CNI). We wonder whether a CNI-free immunosuppression can improve outcome in older patients receiving a DKT with marginal donor organs. Thirty-six were treated with CsA, MMF and prednisone (CsA group) and 42 with rATG, SRL, MMF and prednisone (SRL group). Incidence of delayed graft function and acute rejection was 44% and 11% in the CsA group, and 40% and 8% in the SRL group. CMV infection incidence was low in both protocols. Three-year patient survival was 89% in the CsA and 76% in the SRL group. One- and 3-year graft survival after censoring for dead with a functioning allograft was 94.2% and 94% in CsA and 95% and 90% in SRL, respectively. Renal function was similar in both groups whereas proteinuria was higher in the SRL group. Uninephrectomy due to graft thrombosis or urinary-related complications was numerically higher in the SRL (21%) than in the CsA group (8%) (p = 0.13) and it was associated with renal failure and proteinuria. In DKT, a new induction immunosuppressive protocol based on rATG, SRL, MMF and prednisone does not offer any advantage in comparison to the old CsA, MMF and prednisone.     

The Evidence of Occult Hypervolemia; Improvement of Cardiac Functions After Kidney Transplantation

The term cardiorenal syndrome (CRS) has been used to define interactions between acute or chronic dysfunction of the heart or kidney. When primary chronic kidney disease contribute to cardiac dysfunction, it is classified as type 4 CRS. Cardiac dilatation, valve regurgitations, and left ventricular dysfunction are observed in end-stage renal failure patients with uremic cardiomyopathy. Because of perioperative risks in these patients, they may not be considered a candidate for kidney transplantation. However, uremic cardiomyopathy can be corrected when volume control is achieved by appropriate dose and duration of ultrafiltration. By presenting two cases with occult hypervolemia in uremic cardiomyopathy whose cardiac functions improved early after kidney transplantation, attention is drawn to the importance of kidney transplantation on cardiac function in such patients primarily and the importance of strict volume control on cardiac function in dialysis patients waiting for kidney transplantation.