Risk Factor For Graft Loss Research Articles

Use of Recombinant Factor VIIA as a Risk Factor for Graft Loss after Orthotopic Liver Transplantation Due to Hepatic Artery Thrombosis

Background: The genetically engineered recombinant activated factor VII (rFVIIa) was primarily developed for the treatment of bleeding episodes in haemophilia patients with inhibitors. Different outcomes have been described in a number of studies evaluating the off-label use in patients with liver disease and consequently with complex coagulopathies. We here evaluated the use of rFVIIa in patients undergoing orthotopic liver transplantation (OLT). The aim of this study was to determine the safety within this patient population. Methods: Overall, 1343 OLTs were performed at Hannover Medical School between 2002 and 2014. Out of this group we selected patients having received rFVIIa in the early phase after OLT. We retrospectively analyzed the outcome of patients treated with rFVIIa and compared our findings to those from other transplant centers. Results: In a single center retrospective analysis we identified eight patients after OLT who received treatment with rFVIIa (0.59%). Five out of eight (62.5%) patients suffered graft loss due to hepatic artery thrombosis (HAT). None of these patients had a history of thrombosis or signs of hypercoagulopathy. 60% of the patients who developed HAT had a primary graft non-function. Interestingly, rFVIIa administration was the only risk factor for HAT and consequently for graft loss in our cohort. Other known risk factors such as cold ischaemic time, number of anastomoses, donor age of > 60 years and CMV status could be excluded. Conclusion: This study shows that rFVIIa treatment is a highly likely risk factor for the development of HAT and consequently graft loss in patients after OLT. Thus, usage of rFVIIa in this patient population should be avoided.

Negative Impact of Underlying Non–Insulin-dependent Diabetes Mellitus Nephropathy on Long-term Allograft Survival in Kidney Transplantation: A 10-Year Analysis From a Single Center

IntroductionWe analyzed the relationship between underlying nephropathy and long-term outcomes in kidney transplant recipients. MethodsWe retrospectively analyzed data from 678 patients who underwent kidney transplantation (KTx) between 1998 and 2011. Recipients with 13 major nephropathies were evaluated for graft and patient survival, and causes of graft loss. ResultsThe best 10-year graft survival rates (100%) were in the patients with autosomal-dominant polycystic kidney disease, preeclampsia, Alport syndrome, and purpura nephritis. The worst rate (50.8%) was in patients with non–insulin-dependent diabetes mellitus nephropathy (NIDDMN; P = .039). Causes of graft-loss in the NIDDM patients included chronic rejection (6 cases), acute rejection (3 cases), infection (2 cases), and cardiovascular event (2 cases). Significant risk factors for graft loss were donor age (P < .01) and NIDDMN (P < .01). ConclusionUnderlying NIDDMN before KTx was a significant risk factor for long-term graft function. Immunologic factors and nonimmunologic factors influenced the long-term outcomes in patients with underlying NIDDMN.

Impaired Kidney Allograft: How Long Can It Function? A Single-Center Study of the Transplantation Population

Impaired renal graft function is a matter of particular concern during post-transplantation care because low estimated glomerular filtration rate (eGFR) is a risk factor for graft loss. The aim of the study was to assess risk factors for inferior outcomes of kidney transplantations with low eGFRs. We identified 72 patients who underwent transplantation between 1999 and 2005 who had chronic renal graft dysfunction after 6 months post-transplantation (eGFR < 40 mL/min/1.73 m2), received a kidney transplant between 1999 and 2005, and were treated in one center through the entire post-transplantation course. Three patients who were lost for follow up after 6.4, 6.7, and 8.5 years are not included in this analysis. A group of 23 patients (33%) had chronic kidney disease stage 4 (eGFR < 30 mL/min/1.73 m2) at 6 months. In 39 patients (56%), delayed graft function was diagnosed. Forty-eight patients (70%) had at least one episode of acute graft rejection. Results were confirmed using biopsy in 39 patients. Eight patients (12%) died and 35 patients (51%) lost their grafts between 1.6 and 14 years (median, 6.3 years). The remaining 26 (38%) patients have still functioning allografts 11 years after transplantation (median). The initial immunosuppression included calcineurin inhibitor (CNI) in all cases. At the end of study, 6 (8.3%) patients received mammalian target of rapamycin inhibitor plus steroids, whereas the remaining were treated with CNIs. Improvement of kidney function by 15% was observed in 23% of the studied population between 6 and 24 months. This satisfactory outcome was a result of the careful follow-up examinations and comprehensive medical care provided by our dedicated staff of nurses and physicians. Improvement of kidney function may reflect a state of immune quiescence in some patients which allows them to sustain a functioning kidney despite injury.

Management of proteinuria in the transplanted patient.

Proteinuria is a relatively frequent complication in children after renal transplantation (40-80 %). It is usually mild and non-nephrotic in nature and predominantly tubular in origin. The major causes of post-transplant proteinuria are recurrence of primary glomerulonephritis [mostly focal segmental glomerulosclerosis (FSGS)], rejection (acute and chronic), mTOR inhibitors or hypertension. Proteinuria is a risk factor for graft loss and patient death in adults, and even a mild proteinuria (0.1-0.2 g/day) is associated with impaired graft and patient survival. In children, proteinuria seems to be associated with graft but not patient survival. Proteinuria (protein/creatinine ratio) should be assessed regularly in all children. In children with prior chronic kidney disease due to idiopathic FSGS, proteinuria should be assessed daily during the first month after transplantation to enable early diagnosis of recurrence. The cause of proteinuria should be identified, and graft biopsy should be considered in children with unexplained proteinuria, especially with new onset proteinuria or deterioration of previously mild proteinuria. Treatment must be primarily targeted at the cause of proteinuria, and in normotensive children symptomatic antiproteinuric therapy with angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists should also be initiated. Other antihypertensive drugs should be used to achieve target blood pressure of <75th percentile. Target proteinuria should be <20 mg/mmol creatinine.

Effects of obesity on kidney transplantation outcomes: a systematic review and meta-analysis.

The effects of obesity on outcomes reported after kidney transplantation have been controversial. The purpose of this systematic review and meta-analysis was to elucidate this issue. MEDLINE, EMBASE, Cochrane Library, and gray literature were searched up to August 6, 2013. Studies that compared obese and nonobese patients who underwent kidney transplantation and evaluated one of these outcomes-delayed graft function (DGF), acute rejection, graft or patient survival at 1 or 5 years after transplantation, or death by cardiovascular disease (CVD)-were included. Two independent reviewers extracted the data and assessed the quality of the studies. From 1,973 articles retrieved, 21 studies (9,296 patients) were included. Obesity was associated with DGF (relative risk, 1.41; 95% confidence interval, 1.26-1.57; I=8%; Pheterogeneity=0.36), but not with acute rejection. Graft loss and death were associated with obesity only in the analysis of studies that evaluated patients who received a kidney graft before year 2000. No association of obesity with graft loss and death was found in the analysis of studies that evaluated patients who received a kidney graft after year 2000. Death by CVD was associated with obesity (relative risk, 2.07; 95% confidence interval, 1.17-3.64; I=0%; Pheterogeneity=0.59); however, most studies included in this analysis evaluated patients who received a kidney graft after year 2000. In conclusion, obese patients have increased risk for DGF. In the past years, obesity was a risk factor for graft loss, death by CVD, and all-cause mortality. However, for the obese transplanted patient today, the graft and patient survival is the same as that of the nonobese patient.

Influence of Post Transplant De Novo Anti-MHC Antibody On The Outcomes After Simultaneous Kidney and Pancreas Transplantation.

We evaluated the influence of development of post transplant de novo anti-MHC antibodies on the outcomes after simultaneous kidney and pancreas transplantation. Since 1/1/2002, 285 patients underwent primary simultaneous kidney and pancreas transplantations at our center. Of these patients, 90 developed de novo anti-MHC class I or class II antibodies (30 were DSA by Luminex single bead analyses). 174 patients were tested and remained negative for post transplant anti-MHC antibodies. The remaining 21 patients were not tested and were excluded from this study. We compared the outcomes between the antibody positive and negative groups regarding: acute rejection, kidney and pancreas graft survivals using Kaplan-Meier survival curve analysis as well as Cox proportional hazard model regression analyses. Results: There were no significant differences between groups in regards to age or sex of the recipients however; there were significantly (p<0.01) more African Americans in the antibody positive group (19 out of 90, 21.1%) than in the antibody negative group (17 out of the 174, 9.8%). The antibody positive group had significantly a higher incidence of acute rejection, and a lower 1, 3 and 5 year death censored kidney and pancreas graft survivals when compared to the antibody negative group (table). Multivariate analysis identifies anti MHC antibody (hazard ratio HR: 4.1, 95% CI 2.2-4.7) and acute rejection (HR 2.8, 95% CI 1.5-5.2) as significant risk factors for kidney graft loss. For the pancreas, only anti-MHC antibodies were significant risk factor for graft loss (HR 2.3, 95% CI 1.3-4.3. We conclude that post transplant de novo anti MHC antibodies are associated with worse outcomes after simultaneous kidney and pancreas transplantation.Table: No Caption available.

Acute Kidney Injury (AKI) From Hemodynamic Factors Influence Allograft Outcome in Kidney Transplant Recipients.

Background: The clinical course of kidney transplant recipients with one or more episodes of acute kidney injury (AKI), as well as graft-recipient cofactors contributing to allograft susceptibility to AKI are not well characterized. Methods: We studied 447 kidney transplant recipients who were transplanted between September 2004 and December 2010. AKI was defined by both RIFLE (Risk, Injury, Failure, Loss of kidney function and End stage) and AKIN (Acute Kidney Injury Network) criteria. Data were described using appropriate summary measures. Unpaired t-test was used to compare the continuous baseline data according to AKI status while Fisher's exact test was used to compare the categorical data according to AKI status. Graft failure is defined as reaching end stage renal disease (ESRD) or requiring dialysis. Deaths are treated as censored events. Cox regression analysis was performed to assess the association of cofactors with graft survival. Results were reported using hazard ratio (HR) with 95% confidence interval (CI). P-value less than 5% were considered as significant results. Results: The median follow up was 47.48 months. A total of 53 (11.8%) patients had graft failure and 41 (9.1%) patients died during follow up. Out of 447 patients, 55.5% had AKI. Among patients with AKI, rejection at AKI was 18.6%, majority of patients had AKIN stage 1 (64.9%) followed by stage 2 (19%). Death censored graft survival rate was found to be 85% at 5 years. Graft survival correlated with staging of AKIN classification as follows, 88%, 74%, 51%, and 28% for stages 1, 2, 3 and 4 respectively. Recipients with one or more episode of AKI showed inferior death censored graft survival (79% vs.97% at 5 years; p<0.001) compared to none. AKI was an independent risk factor for graft loss in co-variate adjusted risk analysis for graft survival (aHR = 3.68, CI 1.43-9.45, p=0.0068) in addition to cold ischemia time (aHR=1.08, CI 1.04-1.12, p=0.0001). Conclusion: Acute kidney injury may be a modifiable risk factor for graft loss after kidney transplantation and should be better characterized in order to implement optimal treatment and prevention strategies.

Causes of Graft Loss After Kidney Transplantation Following Rabbit-Antithymocyte Gobulin Induction and Steroid-Sparing Maintenance.

Purpose: We analyzed specific factors associated with graft loss in the setting of a steroid-free immunosuppression environment and rabbit-antithymocyte globulin (r-ATG) induction. Methods: 1693 kidney transplants were performed over a 10-year span at our institution. Risk factors for graft loss, defined as loss of kidney function due to patient death or necessitating chronic dialysis, and/or re-transplantation, were evaluated by multivariate analysis. Death-censored data was further stratified by biopsy findings and causes of graft loss. Results: The study group included 1151 patients who underwent kidney transplant from November 2001 to December 2011 under a steroid sparing protocol with r-ATG induction. A total of 215 graft losses occurred (18.7%), with a mean follow up of 51.9 ± 30.6 months. Excluding death with a functioning graft (n=81) as the reason for graft loss, 134 graft losses (11.6%) were included in the final analysis. Table 1 summarizes other factors associated (P < 0.05) with graft loss in the study group. Surgical complications (e.g. hemorrhage, urinary leak, lymphoceles, etc.) required a re-operation. Infection included CMV, BK virus, or other opportunistic infections. All rejection events (n=52) occurred in grafts that were eventually lost. The most significant cause of graft loss was due to acute rejection (n=21, O.R. 29.5 [95% CI: 4.34-200.6], P <0.01), which included ACR, AMR and mixed ACR/AMR. There were no significant correlations between graft loss and patient age, race, gender, donor type (living vs. deceased, ECD vs SCD), or length of time on dialysis.Table: No Caption available.Conclusions: The reasons for graft failure have not been well described in a large cohort of kidney transplants using steroid minimization and r-ATG induction. Despite an acceptable rate of graft loss with this protocol, acute rejection serves as an ominous risk factor for graft loss. Infections, which may be related to over-treatment of rejection, as well as surgical complications and delayed graft function were also significant risk factors. Strategies to minimize these risk factors may help to prevent graft loss.

Risk Factors for Graft Loss in Kidney Transplant Recipients With Antibody Mediated Rejection and Three Consecutive Biopsies.

Risk factors for graft loss in patients with ABMR are not well established. We addressed this question in a cohort of 31 patients diagnosed with ABMR who received renal transplants between January 2009 and March 2011. Patients underwent 3 consecutive biopsies post-transplant which allowed for assessment of pathological change over time. Of the 31 patients, 58% were male, 19% were African American, and the mean age was 44.7 ±14.8 years. The mean age of donors was 42.8 ±13.4 years, 3% were African American and 23% were living donors. Mean wait time to transplant was 532 ±552 days. Thymoglobulin represented 26% of induction regimens, alemtuzumab accounted for 3% and the remaining patients received basiliximab. There were 14 graft failures and 4 patient deaths among the 31 recipients. The average time to graft failure or last follow-up was 907 ±372 days. Univariate cox regression analysis demonstrated that 6 month DSA >10,000 MFI and change in glomerulitis were associated with graft loss. Additionally, histologic characteristics on the second biopsy (tubulitis, intimal arteritis) and the third biopsy (interstitial inflammation, mesangial matrix increase, interstitial fibrosis, tubulitis, tubular atrophy) were also associated with graft loss. Multivariate stepwise cox regression analysis demonstrated that 6 month DSA >10,000 MFI after the first biopsy (HR 6.40, [1.43 to 28.6], P=0.01) and interstitial fibrosis on the third biopsy (HR 2.54, [1.37 to 4.71], P=0.003) were the variables most associated with graft loss.Table: No Caption available.Risk factors most associated with graft loss in renal transplant patients with ABMR that underwent 3 consecutive biopsies were interstitial fibrosis on the third biopsy and persistent DSA after the first biopsy. Further studies are needed to determine if specific therapies that reduce DSA after the first episode of rejection can improve long-term outcomes.

Outcomes in Kidney Transplant Recipients With Post-Transplant DSA in the Absence of Antibody Mediated Rejection.

There is limited information on the significance of HLA-DSA (human leukocyte antigen donor-specific antibody) on outcomes in kidney transplant recipients with no histopathological evidence of Antibody Mediated Rejection (ABMR). We addressed this question in patients who underwent a kidney allograft biopsy between 01/2009 and 06/2012(n=1470). There were 75 patients with DSA (+) ABMR (-) biopsies (5.1%). 489 patients (33.2%) were DSA (-) ABMR (-) [table 1]. We evaluated patient and allograft survival through 3 years post biopsy.Table: No Caption available.Patients with DSA (+) ABMR (-) were more sensitized as evidence by higher PRA and re-transplant rates. DSA in this group were directed against class II in 55%, class I - 36%, class I and II - 8.5, respectively. In 49% of cases DSA were found to be de novo DSA. Regression analysis demonstrated that anti-HLA DSA were significantly associated with graft loss (HR 2.7, 95% CI 1.67-4.42, p = 0.000) [figure 1], although they were not significantly associated with patient survival (HR 1.8, 95% CI 0.88-3.81, p = 0.14).Figure: No Caption available.Conclusion The observation that DSA is an independent risk factor for graft loss even in the absence of histological evidence of ABMR indicates that the pathologic effects of such DSA may be significant and warrant follow-up biopsies and/or therapeutic interventions.

Prevalence of Donor-Specific Anti-HLA Antibodies and C4 d Deposits in Pediatric Renal Transplant Recipients: Serological /histological Correlations and Impact On Graft Function and Survival.

Introduction: Donor-specific anti-HLA antibodies (DSA) and C4d deposits in peritubular capillaries are associated with humoral rejection and graft loss. Aim: To assess in children with a renal transplant (RTX) who underwent a biopsy due to creeping creatinine ≥ 30% during 3 to 12 months previously: 1. Prevalence of DSA and C4d. 2. Graft survival according to histopathological diagnosis (Banff). 3. Risk factors of graft loss and DSA post RTX. Patients and Methods Between December 1998 and March 2013 700 RTX were performed. The clinical charts of children who underwent a kidney biopsy were retrospectively assessed. Results: Ninety-two children, 53 boys, were included in the study. Mean age at RTX was 9.6±3 years; 68 received a deceased donor (DD) organ; 90 had a first RTX, with a biopsy at a mean of 38 months post RTX (IQR: 20-66). Follow-up was 6.3± 3 years. Baseline immunosuppression was steroids, MMF/MPS and CsA (n=74), TAC (n=10), and SRL (n=8); DD RTX recipients received thymoglobulin induction. DSA (Luminex) were detected in 48%, diffuse C4d (IFI) in 48% and focal C4d in 27%. DSA were found in 93% of C4d-positive vs. 7% of C4d-negative biopsies (p<0.001) Histopathology: Chronic rejection (CR): n=53 with Transplant Glomerylopathy n=7, IFTA n=31, ACR n=4, others n=4. Graft survival at 12 years: IFTA 96%, CR: 53% (p: 0.02). Risk factors for graft loss (multivariate analysis): Acute tubular necrosis: (HR 7.3, 95%CI: 1.7-31), Chronic rejection with ACR: (HR 4.6, 95%CI:1.6-12.5), and age at RTX (HR 1.2: 95%CI: 1.2-1.5). Risk factors for post RTX DSA: No-adherence(OR: 6.9, 95CI%: 2.3-20), and peritubular capillaritis (HR: 2.4 IC95%, 1.5-19.9). Conclusion: Antibody-mediated damage was common in children with graft failure. Significant association was found between microvascular inflammation, no-adherence and the presence of DSA. Vascular rejection and concomitant ACR, acute tubular necrosis, and age at RTX were predictors of graft loss.

Long Term Outcomes of Renal Transplantation in Infants at a Single Center.

Objectives: Infants(age=<2 years) with end stage renal disease requiring dialysis experience high rates of morbidity and mortality. Yet, because of technical and management issues, there are still concerns about transplanting infants. We analyzed the Long term outcomes of renal transplants(tx) in infants. Methods: Between 1984-2012, n=132 infants underwent primary kidney tx(115 Living donor(LD); 17 deceased donor(DD). Outcomes were compared to those of children 2-18 yrs(n=381). Actuarial survival rates were estimated using Kaplan Meier methods. Cox regression analyses were performed to determine whether age had a significant impact on graft survival(with and without deaths censored) after adjusting for known risk factors for graft loss. Results: There was no statistical difference in actuarial outcomes(patient survival(PS),graft-survival(GS),& death censored GS) between infants and older children(HR=1.088(95%CI 0.8-1.5). In LDs, acute rejection free GS(71%[email protected] post-tx;p=0.05) and chronic rejection free GS(75%@5yrs post-txp; p=0.003) was higher in infants compared to 2-18 group. The LOS was longer-for-infants(18 vs.14days,p=<0.001). Those having tx in ≥>2002 (vs pre-2002) had improved PS and GS(p=<0.05). Since 2002, the 5-year patient survival of infants has been 100%. LD grafts had significantly improved outcomes. For those LDtx ≥ 2002, Graft half-life(starting @1yr post tx) for infants is 34years. Renal artery thrombosis was not different but incidence of urine leaks was higher in infants(p=0.02). CMV and BK virus infection were similar between age groups. By Cox regression analyses factors associated with decreased graft survival were DD donor graft(HR=1.47,p=0.025 compared to LD,<age 50), and transplant era 1984-2001(HR=1.64,p=0.047compared to 2002-2012). Successful TX in infants was associated rapid catch up growth(p=<0.05) and improved QoL. Conclusions: Infants with ESRD can achieve successful long term outcomes with renal TX. LD graft continues to provide the most benefit and should be the first option.Table: No Caption available.

Long-term outcome of pediatric renal transplantation: a single center study in Japan.

Little is known about the risk factors for long-term poor outcome in pediatric renal transplantation. Between 1973 and 2010, 111 renal transplants (92 living donations) were performed in 104 children (56 males, mean age, 12.5yr) at the Social Insurance Chukyo Hospital, and followed-up for a mean period of 13.6yr. The patient survival at 1, 5, 10, 15, 20 (living- and deceased-donor transplants), and 30yr (living-donor transplants only) was 98.1%, 92.8%, 87.8%, 84.9%, 82.6%, and 79.3%. The graft survival at 1, 5, 10, 15, 20, and 30yr was 92.0%, 77.3%, 58.4%, 50.8%, 38.5%, and 33.3%. The most common cause of graft loss was CAI, AR, death with functioning, recurrent primary disease, ATN, and malignancy. Donor gender, ATN, malignancy/cardiovascular events, and eras affected patient survival. AR and CAI were the risk factors for graft loss. The evolved immunosuppression protocols improved the outcome by reducing AR episodes and ATN but not CAI, suggesting CAI as the major risk factor for graft loss. CAI was correlated with AR episodes, CMV infection, and post-transplant hypertension. Strategies for preventing the risk factors for malignancy/cardiovascular events and CAI, including hypertension/infection, are crucial for better outcomes.

Expanding the use of expanded criteria donors in kidney transplantation

Although the use of kidney allografts from expanded criteria donors (ECD) has increased in recent years, the reported discard rates are also growing. The influence of ECD characteristics on transplant outcomes is still underevaluated. This retrospective study investigated the influence of preimplantation biopsy findings and delayed graft function (DGF) on patient and graft survivals and renal function at 36 months in a cohort of 372 ECD kidney transplant recipients. Patient and graft survivals were 91.6 and 68.9 %. The incidence of biopsy-proven acute rejection was 31 %. There were no differences in patient (88.6 vs. 91.1 vs. 94.7 vs. 78.6 %, p = 0.10) or graft (78.1 vs. 72.2 vs. 60.5 vs. 62.6 %, p = 0.14) survivals and renal function (41.7 ± 25.6 vs. 39.9 ± 29.9 vs. 38.1 ± 30.6 vs. 37.4 ± 29.2 mL/min, p = 0.79) comparing ECD kidneys with mild, moderate, and severe histological changes or with no preimplantation biopsy, respectively. However, severe scored transplants had the worst death-censored graft survival (OR 3.1, 95 % CI 1.4-6.9, p = 0.007). No significant differences in patient (86.2 vs. 83.4 %, p = 0.17) or graft (73.7 vs. 65.9 %, p = 0.06) survivals and renal function (38.9 ± 28.6 vs. 39.9 ± 28.4 mL/min, p = 0.72) were observed comparing patients with or without DGF. Multivariable analysis found diabetes history as the only independent risk factor for graft loss (OR 2.1, 95 % CI 1.3-3.3, p = 0.003) or patient death (OR 3.1, 95 % CI 1.5-5.8, p < 0.001). Within the limitations of sample size and short follow-up time, in this cohort of ECD kidney transplant recipients the severity of histological changes observed in preimplantation biopsies was independently associated with graft loss.

Vascular anastomosis for paediatric renal transplantation and new strategy in low‐weight children

The technical aspects of RT in low-weight children should be specific, particularly with regard to VA. This retrospective study assesses the main VA options in paediatric RTs and proposes a new strategy for renal artery trajectory when using the Ao and the right iVC. The sample included 81 patients and was categorized into a group of children weighing <16kg and the other group of children weighing 16kg or more. The smaller children received the graft predominantly on the Ao and iVC (63%); however, the VA options varied in children weighing more than 16kg, with anastomoses predominantly to the common iliac vessels (46%). In the first group, when the Ao was the selected vessel for anastomosis on the right side, the trajectory adopted for the transplanted kidney artery was posterior to the iVC. This strategy may reduce the risk of compression of the iVC by the renal artery of the donor kidney and may reconstitute the normal anatomy of the renal artery. Moreover, it did not represent a risk factor for graft loss in this sample.

Hypertension in post-renal transplant patients: Pilot study

Post-transplant hypertension is a major risk factor for graft loss and patient survival; therefore, hypertension following renal transplantation must be treated strictly. There seems to be a strong association between hypertension, total body water (TBW) and dry weight. In this study, we report the relationship of body water and body composition with hypertension in post-renal transplant patients. Forty-five post-transplant patients were enrolled in the study. Blood pressure (BP) was labeled as controlled if BP was 120/80 mm Hg and not under good control if BP was above 120/80 mm Hg. Based on the number of antihypertensive medications a patient was taking, patients were divided into two groups: Group 1 patients on one antihypertensive drug and Group 2 patients on more than one antihypertensive drug. Nutritional status of the patients was assessed. Body composition (water compartments, body fat and lean mass) was assessed using bioelectrical impedance analysis (BIA). Patient data were compared with 30 healthy volunteers. In patients, systolic BP was associated with TBW (P = 0.016), extracellular water (ECW Lt; r = 0.99), ECW% (r = 0.78) and diastolic BP with TBW% (P = 0.003), dry weight (r = 0.76) ECW% (r = 0.95) and percent intracellular water (ICW%) (r = 0.79). Compared with controls, ECW and ECW% was higher in patients, and the ICW% was less in patients. There was significant difference in the actual weight of the patients and BIA-derived dry weight, although patients were clinically not edematous. The study showed a significant increase in diastolic BP with increase in dry weight. Significant difference in TBW was observed when the patients were grouped on the basis of the antihypertensive medication a patient was taking (one antihypertensive drug versus more than one antihypertensive drug). This study also showed an association between hypertension and overhydration. BIA may be a useful tool for the clinical assessment of overhydration in non-edematous patients.

Alemtuzumab and Minimization Immunotherapy in Kidney Transplantation: Long-Term Results of Comparison With Rabbit Anti-Thymocyte Globulin and Standard Triple Maintenance Therapy

BackgroundEfforts to improve long-term patient and allograft survival have included use of induction therapies as well as steroid and/or calcineurin inhibitor (CNI) avoidance/minimization. MethodsThis is a retrospective review of kidney transplant recipients between September 2004 and July 2009. Immune minimization (group 1; n = 182) received alemtuzumab induction, low-dose CNI, and mycophenolic acid (MPA). Conventional immunosuppression (group 2; n = 232) received rabbit anti-thymocyte globulin, standard-dose CNI, MPA, and prednisone. ResultsBoth groups were followed up for same length of time (49.4 ± 21.7 months; P = .12). Patient survival was also similar (90% vs 94%; P = .14). Death-censored graft survival was inferior in group 1 compared with group 2 (86% vs 96%, respectively; P = .003). On multivariate analysis, group 1 was an independent risk factor for graft loss (aHR = 2.63; 95% confidence interval [CI], 1.32–5.26; P = .006). Biopsy-proven acute rejection occurred more in group 1, due to late rejections compared with group 2 (7% vs 2%; P < .01 respectively). Graft function was lower in group 1 compared with group 2 at 3 months (49.5 mL/mt vs 70.7 mL/mt, respectively; P < .001) to 48 months (48.6 mL/mt vs 69.4 mL/mt, respectively; P = .04). ConclusionMinimization of maintenance immunosuppression after alemtuzumab correlated with higher acute rejection and inferior graft survival compared with thymoglobulin and conventional triple immunotherapy.

CMV Infection in the Donor and Increased Kidney Graft Loss: Impact of Full HLA-I Mismatch and Posttransplantation CD8+ Cell Reduction

Despite a large body of literature, the impact of chronic cytomegalovirus (CMV) infection in donor on long-term graft survival remains unclear, and factors modulating the effect of CMV infection on graft survival are presently unknown. In this retrospective study of 1279 kidney transplant patients, we analyzed long-term graft survival and evolution of CD8+ cell population in donors and recipients by CMV serology and antigenemia status. A positive CMV serology in the donor was an independent risk factor for graft loss, especially among CMV-positive recipients (R+). Antigenemia was not a risk factor for graft loss and kidneys from CMV-positive donors remained associated with poor graft survival among antigenemia-free recipients. Detrimental impact of donor’s CMV seropositivity on graft survival was restricted to patients with full HLA-I mismatch, suggesting a role of CD8+ cells. In R+ patients with positive CMV antigenemia during the first year, CD8+ cell count did not increase at 2 years posttransplantation, in contrast to R− recipients. In addition, marked CD8+-cell decrease was a risk factor of graft failure in these patients. This study identifies HLA-I full mismatch and a decrease of CD8+ cell count at 2 years as important determinants of CMV-associated graft loss.

Metabolic syndrome in children with chronic kidney disease and after renal transplantation

Visceral obesity and metabolic abnormalities typical for metabolic syndrome (MS) are the new epidemic in adolescence. MS is not only the risk factor for cardiovascular disease but also for chronic kidney disease (CKD). Thus, there are some reasons to recognize MS as a new challenge for pediatric nephrologists. First, hypertensive and diabetic nephropathy, the main causes of CKD in adults, both share the same pathophysiological abnormalities associated with visceral obesity and insulin resistance and have their origins in childhood. Secondly, as the obesity epidemic also affects children with CKD, MS emerges as the risk factor for progression of CKD. Thirdly, metabolic abnormalities typical for MS may pose additional risk for cardiovascular morbidity and mortality in children with CKD. Finally, although the renal transplantation reverses uremic abnormalities it is associated with an exposure to new metabolic risk factors typical for MS and MS has been found to be the risk factor for graft loss and cardiovascular morbidity after renal transplantation. MS is the result of imbalance between dietary energy intake and expenditure inducing disproportionate fat accumulation. Thus, the best prevention and treatment of MS is physical activity and maintenance of proper relationship between lean and fat mass.

Rejection Is a Strong Graft Survival Predictor in Live Donor Pediatric Renal Transplantation Using Cyclosporine, Mycophenolate Mofetil, and Steroids: 5-Year Outcomes in a Single Mexican Center

Long-term graft function and survival are of particular importance in children assuming that they have a longer transplantation life span than most adults. Because acute rejection episodes (ARE) continue to have a serious impact on graft loss, we analyzed the effects of ARE on 5-year survival and function in our population. Fifty-seven living donor kidney transplant recipients (34 males) younger than 18 years of age (13.5 ± 2.6 years; range, 5–17) were follow up for at feast 12 months using cyclosporine, mycophenolate mofetil, and steroid therapy with or without induction treatment between February 2003 and December 2010. ARE incidence during the first 12 months following transplantation was 14%. One-, 3- and 5-year serum creatinine values were 1.24 ± 0.39, 2.16 ± 2.39, and 1.76 ± 0.9 mg/dL, respectively. Mean calculated creatinine clearances (Schwartz) at 1, 3, and 5 years were 82.5 ± 24.8, 64.7 ± 24.1, and 67 ± 27.5 mL/min*1.73 m2, respectively. Patient/graft survival rates were 96/85%, 90/72%, and 88/65% at 1, 3, and 5 years, respectively. Patients who experienced an ARE within 12 months following transplantation displayed a reduced 5-year graft survival rate (37.5%) versus those who did not (78%; P = .005). Patients who did not have an ARE during 60 months had a higher graft survival rate (76%) than those who had ARE (33%; P = .001). Patient without basiliximab induction showed a lower 5-year graft survival rate (61% vs 100%; P = not significant [NS]). ARE is an important risk factor for graft loss in the pediatric kidney transplant population.