Subsequent Kidney Transplantation Research Articles

La transplantation rénale et ses défis

To describe kidney transplantation surgical techniques and to propose strategies in high-risk recipients. Relevant publications were identified through Medline (http://www.ncbi.nlm.nih.gov/) and Embase (http://www.embase.com/) database using the following keywords, alone or in association, "renal transplantation; peripheral arterial disease; obesity; third and fourth transplantation; robotic-assisted kidney transplant; anticoagulant therapy; dual kidney transplant". Articles were selected according to methods, language of publication and relevance. The reference lists were used to identify additional historical studies of interest. Both prospective and retrospective series, in French and English, as well as review articles and case-reports were selected. A total of 1949articles were analyzed for arterial disease and anticoagulant therapy, 1083for obesity, 663for dual kidney transplants, 458for third and subsequent procedures and 84for robotic-assisted kidney transplantation. After careful selection, 304publications were eligible for our review. Surgical assessment of future recipients is a pivotal step to anticipate technical difficulties, to interrupt clopidogrel or direct oral anticoagulants and to propose a revascularization procedure when necessary. Lack of data regarding obese recipients does not allow us to conclude about best surgical care or optimal timing but suggest that an early global management of obesity in chronic kidney disease patients is mandatory to improve access to a successful transplantation. In neurologic bladder and congenital anomalies, urodynamics and bladder function must be assessed prior to the onset of oliguria to intend an early treatment. Urinary diversion may be performed prior to or after transplantation with similar survival outcome and comparable rates of infections. Because of a rigorous selection of donors, the French dual kidney transplant program provides satisfactory outcomes, but fails in convincing surgical teams nationwide. Third and subsequent transplant procedures remain a surgical and immunological challenge, with an increased morbidity and a moderate decline in transplant survival only when donors are extended criteria' with extensive duration of waiting time between procedures. Robotic-assisted kidney transplantation is a recent technique requiring methodical evaluation. Kidney transplantation in challenging recipients implies a global understanding of patients' prognosis and benefits versus dialysis, in the context of the attribution of a valuable resource awaited by other patients on waiting list.

Predicting renal recovery after liver transplant with severe pretransplant subacute kidney injury: The impact of warm ischemia time.

Identifying which liver transplantation (LT) candidates with severe kidney injury will have a full recovery of renal function after liver transplantation alone (LTA) is difficult. Avoiding unnecessary simultaneous liver-kidney transplantation (SLKT) can optimize the use of scarce kidney grafts. Incorrect predictions of spontaneous renal recovery after LTA can lead to increased morbidity and mortality. We retrospectively analyzed all LTA patients at our institution from February 2002 to February 2013 (n = 583) and identified a cohort with severe subacute renal injury (n = 40; creatinine <2 mg/dL in the 14-89 days prior to LTA and not on renal replacement therapy [RRT] yet, ≥2 mg/dL within 14 days of LTA and/or on RRT). Of 40 LTA recipients, 26 (65%) had renal recovery and 14 (35%) did not. The median (interquartile range) warm ischemia time (WIT) in recipients with and without renal recovery after LTA was 31 minutes (24-46 minutes) and 39 minutes (34-49 minutes; P = 0.02), respectively. Adjusting for the severity of the subacute kidney injury with either Acute Kidney Injury Network or Risk, Injury, Failure, Loss, and End-Stage Kidney Disease criteria, increasing WIT was associated with lack of renal recovery (serum creatinine <2 mg/dL after LTA, not on RRT), with an odds ratio (OR) of 1.08 (1.01-1.16; P = 0.03) and 1.09 (1.01-1.17; P = 0.02), respectively. For each minute of increased WIT, there was an 8%-9% increase in the risk of lack of renal recovery after LTA. In a separate cohort of 98 LTA recipients with subacute kidney injury, we confirmed the association of WIT and lack of renal recovery (OR, 1.04; P = 0.04). In LT candidates with severe subacute renal injury, operative measures to minimize WIT may improve renal recovery potentially avoiding RRT and the need for subsequent kidney transplant. Liver Transplantation 22 1085-1091 2016 AASLD.

Liver Allograft Provides Immunoprotection for the Cardiac Allograft in Combined Heart-Liver Transplantation.

When transplanted simultaneously, the liver allograft has been thought to have an immunoprotective role on other organs; however, detailed analyses in simultaneous heart-liver transplantation (SHLT) have not been done to date. We analyzed patient outcomes and incidence of immune-mediated injury in 22 consecutive SHLT versus 223 isolated heart transplantation (IHT) recipients between January 2004 and December 2013, by reviewing 3912 protocol- and indication-specific cardiac allograft biopsy specimens. Overall survival was similar (86.4%, 86.4%, and 69.1% for SHLT and 93.3%, 84.7%, and 70.0% for IHT at 1, 5, and 10 years; p = 0.83). Despite similar immunosuppression, the incidence of T cell-mediated rejection (TCMR) was lower in SHLT (31.8%) than in IHT (84.8%) (p < 0.0001). Although more SHLT patients had preexisting donor-specific HLA antibody (22.7% versus 8.1%; p = 0.04), the incidence of antibody-mediated rejection was not different in SHLT compared with IHT (4.5% versus 14.8%, p = 0.33). While the left ventricular ejection fraction was comparable in both groups at 5 years, the incidence and severity of cardiac allograft vasculopathy were reduced in the SHLT recipients (42.9% versus 66.8%, p = 0.03). Simultaneously transplanted liver allograft was associated with reduced risk of TCMR (odds ratio [OR] 0.003, 95% confidence interval [CI] 0-0.02; p < 0.0001), antibody-mediated rejection (OR 0.04, 95% CI 0-0.46; p = 0.004), and cardiac allograft vasculopathy (OR 0.26, 95% CI 0.07-0.84; p = 0.02), after adjusting for other risk factors. These data suggest that the incidence of alloimmune injury in the heart allograft is reduced in SHLT recipients.

Post-Transplant Anemia Has Strong Influences on Renal and Patient Outcomes in Living Kidney Transplant Patients

BackgroundPost-transplant anemia (PTA) is a risk factor for mortality and graft loss in kidney transplant patients. MethodsIn all, 172 patients were included in this study. PTA was defined as hemoglobin <13.0 g/dL in men and 12.0 g/dL in women. The primary outcome of interest was the renal outcome, defined as a 50% increase in serum levels of creatinine, a return to chronic dialysis, and subsequent kidney transplantation (KTx). The secondary outcome was a composite of the primary outcome and death. ResultsAt baseline, 75 patients (43.6%) had PTA. During follow-up of a median of 7.3 years, 52 patients (30.2%) had 2-fold higher creatinine levels than at baseline, 24 patients (14.0%) had to return to chronic dialysis or subsequent KTx, and 11 patients (6.4%) died; 8 (4.7%) of the deceased patients had functioning allografts. Univariate regression analyses showed that a lower hemoglobin level and positive proteinuria were significantly associated with both outcomes. After adjusting for important clinical variables, a lower hemoglobin level remained a strong predictor for both outcomes. Restricted cubic splines showed an almost linear inverse association with a hemoglobin level ≥12 g/dL. The risk of the outcomes increased with decreasing tertiles of the baseline hemoglobin level for both men and women, but the associations in women were much weaker than those in men, suggesting a different prognostic value of the hemoglobin level between men and women. ConclusionsPTA strongly influenced the renal and patient outcomes in living kidney transplant patients.

Better HLA Matching Is Associated With First and Second Allograft Outcomes Among Pediatric Kidney Transplant Recipients.

Introduction: Kidney transplant(KT) graft survival is superior if received from ideal well-matched donors. Given the decline of living donor(LD) availability and the initiation of the Share35 kidney policy, we sought to determine the impact of Human Leukocyte Antigen(HLA) matching on allograft outcomes. Methods: A retrospective analysis of OPTN data(1988-2009) examining pediatric first and second KT allograft survival based on Share35 policy, HLA matching(0-2 vs 3+), and donor-type(LD vs Deceased Donor=DD) using Kaplan-Meier statistics and Cox regression analysis. Results:Of 13,489 first KT pediatric recipients, post-Share35 groups had poorer(0-2 antigen) matched grafts(64.88%) compared to the pre-Share35 cohort(39.69%; p<0.01), even when stratified by donor type. Additionally, there was a significant decline in LD availability post-Share35 initiation(-20.17%; p<0.01). Despite these findings, favorable graft outcomes exist for post-Share35 and LD recipients(p<0.01).Figure: No Caption available.Adjusting for all factors, better HLA-matching(HR=0.80; p<0.01), LD allografts(HR=0.65; p<0.01), and post-Share35 transplantation(HR=0.72;p<0.01) conferred better graft outcomes. In a secondary analysis, recipients with poorly matched(0-2 antigen) grafts at first transplant who underwent second kidney transplant, median wait-list time prior to second kidney transplant was longer(p<0.01), while second kidney graft survival was shorter(p=0.02). We also determined that better first HLA matching correlated with lower peak PRA level at second transplant(-0.14; p<0.01). Conclusion: Among pediatric kidney transplant recipients, improved allograft outcomes exist for better HLA-matched first and second transplants, despite Share35 policy initiation and decline of LD availability. HLA matching retains its prognostic value in graft outcomes for first and subsequent kidney transplants. This does not explain the improved early graft outcomes we see in the post-Share35 era. Finally, patients who are better matched for previous transplants are less sensitized, have shorter wait-list times, and overall longer subsequent allograft survival times.

Combined Liver Kidney Transplant (CLKT) and Subsequent Kidney Transplant in Liver Transplant Recipients (KALT) in a Single Center.

Background: The increasing survival in patients submitted to liver transplantation as well as the implementation of the MELD score has substantially increased the prevalence of chronic kidney disease (CKD) among these individuals. Aim: To evaluate the experience of a decade of CLKT and KALT in a Transplant Program with a large number of liver transplanted patients in São Paulo, Brazil. Methods: we performed a longitudinal and observational trial to evaluate the CLK and KAL transplants performed at the institution since the beginning of transplantation program at the institution, in 2002. The analyzed outcomes were: acute rejection (AR-k) and delayed graft function (DGF-k) in kidney graft, estimated glomerular filtration rate (GFR) and one year kidney graft survival. Results: In this period (2002 to May/2011), 56 transplants (CLKT and KALT) were performed: 39 were submitted to CLKT (69.6%) and 17 to KALT (30.4%). The main cause of liver failure in the study population was hepatitis C virus (HCV) infection, with no significant differences between CLKT (41%) and KALT (26%). The cause of CKD was undetermined in most patients (32.1%) of both subgroups, being the toxicity of calcineurin inhibitors the most important cause among KALT patients (0 vs. 29.4%). As expected, waiting time to transplant was longer in KALT than in CLKT (18.2 vs. 25.1 months p= 0.003). CIT was lower among KALT patients (13.0 vs. 21.2, p<0.001), and patients submitted to CLKT were inducted with Thymoglobulin more frequently: 8.1% vs. 80%, p<0.001. The prevalence of DGF-k was similar among both groups (66.7 vs. 70.6%, p=NS), despite of similar cold ischemia time. The prevalence of AR-k was 24.3% among KALT and 12.5% among CLKT (p=NS). It has been observed a trend towards higher 1-year-GFR in the KALT group (65.5 vs. 61.0 ml/min p = 0.63). Death was more frequent in CLKT (35.9% vs. 23.5%, p=0.26). Conclusion: acute rejection was more frequent in patients submitted to KALT, probably because of Thymoglobulin use. Graft function and death were similar among both groups.

Treatment with erythropoiesis-stimulating agents in chronic kidney disease patients with cancer

Treatment of anemia remains an important component in the care of patients with nondialysis chronic kidney disease (CKD) and end-stage renal disease (ESRD). Erythropoietin-stimulating agents (ESAs) remains a key anemia treatment strategy in this patient population. However, anemia management in this group can become more complicated by prior or current history of malignancy. There has been a great deal of work both scientifically and in clinical trials in oncology that have revealed certain concerns and risks of ESA use in patients with cancer. In this review, we will bring together knowledge from nephrology and oncology literature to help nephrologists understand the implications for ESA treatment when CKD/ESRD is complicated by cancer. We also suggest an approach to the management of anemia in this patient group with active or previous malignancy.

What should be the correct indications for laparoscopic inguinal hernia repair?

We read with great interest the article entitled ‘‘A modified laparoscopic hernioplasty (TAPP) is the standard procedure for inguinal and femoral hernias: a retrospective 17-year analysis with 1,123 hernia repairs’’ by Peitsch [1]. Peitsch analyzed retrospectively 5,764 patients who had undergone hernia repair surgery 2–17 years earlier at one large center. His report discussed the transabdominal preperitoneal (TAPP) approach for treating incarcerated hernias, scrotal hernias, and hernias after radical prostatectomy, as well as recurrent hernias after TAPP and totally extraperitoneal (TEP) procedures (complex hernias). He concluded that a modified TAPP procedure with suturing of hernia defects larger than 1 9 1 cm can be used as the standard procedure without recurrences for femoral hernias, incarcerated hernias, and hernias after radical prostatectomy, and for scrotal hernias with low recurrence rates [1]. Several studies have shown that laparoscopic hernia repair is a safe, efficient method and offers the advantages of minimally invasive surgery such as less postoperative pain, faster return to normal activities, and less long-term complications like chronic pain and numbness. Despite these advantages, the recurrence rate was similar to those of classic open tension-free mesh techniques [2]. However, the mesh that is used in laparoscopic hernia repair can cause an intense fibrotic reaction that makes the dissection to expose the endopelvic fascia difficult, causes difficulties in the surgery of pelvic organs (e.g., prostate, bladder) and is a potential complicating factor in subsequent kidney transplantation [3–5]. Based on clinical experience and the literature, we believe that the patients scheduled for laparoscopic inguinal herniorrhaphy with mesh should be screened for prostate and bladder cancer and also for chronic renal failure. This procedure should be considered in a comprehensive manner and the indications should be determined correctly. In his study, Peitsch did not discuss in detail whether the patients who had undergone laparoscopic inguinal hernia repair had risk factors for pelvic surgery or renal transplantation. We believe that our opinion will contribute to this valuable article.

Pancreas Transplant Alone

The goal of this review is to highlight the significant improvements, over the past four decades, in outcomes after a pancreas transplant alone (PTA) in patients with brittle diabetes and recurrent episodes of hypoglycemia and/or hypoglycemic unawareness. A successful PTA—in contrast to intensive insulin regimens and insulin pumps—restores normoglycemia without the risk of hypoglycemia and prevents, halts, or reverses the development or progression of secondary diabetes complications. In this International Pancreas Transplant Registry (IPTR) analysis, we reviewed the records of 1,929 PTA recipients from December 1966 to December 2011. We computed graft survival rates according to the Kaplan-Meier method and used uni- and multivariate analyses. In the most recent era (January 2007–December 2011), patient survival rates were >95% at 1 year posttransplant and >90% at 5 years. Graft survival rates with tacrolimus-based maintenance therapy were 86% at 1 year and 69% at 3 years and with sirolimus, 94 and 84%. Graft survival rates have significantly improved owing to marked decreases in technical and immunologic graft failure rates (P < 0.05). As a result, the need for a subsequent kidney transplant has significantly decreased, over time, to only 6% at 5 years. With patient survival rates of almost 100% and graft survival rates of up to 94% at 1 year, a PTA is now a highly successful long-term option. It should be considered in nonuremic patients with brittle diabetes in order to achieve normoglycemia, to avoid hypoglycemia, and to prevent the development or progression of secondary diabetes complications.

Transcatheter Aortic-Valve Endocarditis Confirmed by Transesophageal Echocardiography

70-year-old white man was admitted to the Department of Vascular Surgery with a critical right forearm ischemia caused by acute thromboembolic occlusion and underwent operative embolectomy. Microbiological testing revealed colonization of the embolus with Staphylococcus lugdunensis and S. epidermidis. Because of pain in the lower thoracic spine, elevated C-reactive protein, and a recent history of spondylodiscitis with evidence of coagulase-negative Staphylococcus spp., the patient was transferred to the Department of Neurosurgery 16 days after vascular surgery. S. epidermidis was then isolated from blood cultures. The patient had a history of coronary heart disease with reduced left ventricular function, atrial fibrillation, diabetes mellitus, and hemodialysis resulting from diabetic nephropathy, as well as kidney transplantation and subsequent kidney transplant failure in 2000. The patient was taking no immunosuppressive medication at admission. He had had a transcatheter aortic valve (CoreValve, Medtronic) implanted 12 months before as a result of severe native valve stenosis (logistic EuroSCORE, 33.11% at the time of implantation). He was transferred to our echocardiography laboratory with persistently elevated levels of C-reactive protein. Three months before transthoracic and transesophageal echocardiography (Movies I and II in the online-only Data Supplement), he was negative for signs of prosthetic valve endocarditis (PVE). Two- and 3-dimensional transesophageal echocardiography now showed an elongated mass 3 cm in length floating around a longitudinal axis within the stent lumen of the prosthetic valve. Apparently, the mass was attached to the stent struts. In addition, there were signs of a paravalvular abscess at the noncoronary sinus (Figure 1 and Movies III through V in the online-only Data Supplement). Minor paravalvular regurgitation was present at the left coronary sinus. The native valves did not show any signs of endocarditic lesions. The peak velocity across the valve had increased by ≈140 cm/s (Figure 2). After echocardiographic diagnosis of PVE and initiation of calculated antibiotic therapy with vancomycin, gentamicin, and rifampicin, the patient was transferred to the Department of Cardiac Surgery. The infected valve was replaced by a porcine valve (Hancock II, Medtronic; diameter 25 mm) under extracorporeal circulation. Intraoperative findings confirmed massive lesions on the biological parts of the transcatheter valve consistent with PVE (Figure 3). Surprisingly, 3 to 4 stent struts had penetrated the aortic sinotubular junction close to the noncoronary sinus. The valve was

Glomerular disease recurrence in second and subsequent kidney transplants

Primary glomerular diseases such as primary focal segmental glomerular sclerosis (FSGS), IgA Nephropathy and membrano-proliferative glomerulonephritis (MPGN) may recur in renal transplants, and can potentially lead to graft failure. The rate of recurrence in second and subsequent renal transplants, following failure of the first graft due to recurrence, is unclear. A retrospective review of the Irish transplant database from 1982 to 2009 was performed. Patients were included for analysis if their first graft failed due to biopsy-confirmed recurrent glomerular disease (primary FSGS, IgA nephropathy or MPGN) and they underwent subsequent re-transplantation. 3,330 deceased and living renal transplants were performed during the time period in question. 33 patients had a deceased donor renal transplant following recurrence of primary FSGS, IgA nephropathy or MPGN causing first graft failure. Clinically significant disease recurrence was seen in 44% of re-transplants at 10 years. Median second graft survival in this group was 9.1 years. The median graft survival was 10.5 years for all other re-transplants performed in Ireland during the same time period. Clinically significant disease recurrence does not necessarily affect re-transplants following loss of the first graft to disease recurrence. Selected patients who experience first graft failure due to recurrent glomerular disease should not be precluded from receiving a second transplant.

The role of initial hemodialysis vascular access in the outcome of subsequent kidney transplantation

The role of initial hemodialysis vascular access in the subsequent kidney transplant outcome is unclear. Study population was derived from the United States Renal Data System and included adult patients with end-stage renal disease who started HD 1/1/2005-9/1/2009 and subsequently received at least one kidney transplant. Primary outcome variables were death-censored graft loss and all-cause recipient mortality. Among the study population (n = 17 157), 12 428 (72.4%) patients were initiated on HD with a catheter, 4090 (23.8%) patients with an arterio-venous fistula (AVF), and 639 (13.7%) patients with an arterio-venous graft (AVG). The rate of death-censored kidney allograft loss in AVF and AVG groups was not significantly different from the catheter group (HR, 0.82; p = 0.07 and HR, 0.68; p = 0.13, respectively). All-cause mortality of patients initiated on HD with AVG (HR, 0.761; p = 0.21) was not significantly different compared to those with catheters. However, all-cause mortality in the AVF group was lower compared to patients initiated on HD with catheters (HR, 0.65; p = 0.001). AVF used at the initiation of HD was associated with lower rate of all-cause mortality after kidney transplantation compared to the catheter. The type of initial vascular access for hemodialysis was not associated with kidney allograft survival.

Embolization of a Failed Renal Allograft Is Associated with Higher Allosensitization and Worse Graft Outcome in Subsequent Kidney Transplants

Embolization of a Failed Renal Allograft Is Associated with Higher Allosensitization and Worse Graft Outcome in Subsequent Kidney Transplants

Embolization of a Failed Renal Allograft Is Associated with Higher Allosensitization and Worse Graft Outcome in Subsequent Kidney Transplants

Introduction: Despite the significant improvement achieved in patient and kidney allograft survival nowadays, an important number of patients return to dialysis showing increased allosensitization and worse graft and patient outcome after receiving a second kidney allograft as compared to the first transplant. Whether removal of the failed allograft by selective embolization or transplant nephrectomy directly influences on allosensitization and subsequent graft outcome is still poorly known. Methods: Herein, in a case control study, we evaluated 62 kidney transplant patients from 2000 to 2010; 31 patients undergoing selective embolization for cause of the failed first allograft (group 1) were compared to 31 patients preserving the first failed organ (group 2). We compared the percentages of panel reactive antibody (PRA) between both groups at baseline (before any transplant), after failure of the first transplant as well as after allograft embolization. Moreover, main clinical outcome when receiving a subsequent second kidney allograft between both groups was also analyzed in a 5-year of mean follow-up. Results: Baseline allosensitization was comparable between both groups (PRA>25%: 6.5%± and 4.8%± for groups 1 and 2, respectively). After failure of the first transplant, patients maintaining the failed organ showed significantly higher allosensitization than patients before undergoing selective embolization (PRA>25%: 25.4%± and 8.5%±, respectively; p=0.029). After allograft embolization, patients showed a significant increased in % of PRA levels than before(19.2% to 46.2%, p=0.09). No differences were found between groups regarding incidence of acute tubular necrosis (ATN), acute rejection (AR) or other main clinical variables. Noteworthy, patients maintaining the failed renal allograft displayed a significantly better graft function evolution at 5 years than patients undergoing selective transplant embolization (eGFR=51,91ml/min and 41.5 ml/min, respectively; p=0.09) Conclusion: Preservation of previous renal failed allografts seems to prevent enhance peripheral allosensitization thus, favouring a better allograft outcome in a subsequent renal transplantation. Our data emphasizes the importance of an accurate immunosuppression management after a failed kidney transplant in order to prevent transplant embolization for cause.

Long-term control of parathyroid hormone and calcium-phosphate metabolism after parathyroidectomy in children with chronic kidney disease

Hyperparathyroidism (HPT) is an essential contributor to bone disease and cardiovascular calcifications in children with chronic kidney disease (CKD). Pharmacological and dietary interventions are of limited efficacy; calcimimetics are not yet recommended in children. Parathyroidectomy (PTX) is ultimately performed if HPT becomes refractory to conservative measures; the long-term results and the impact of subsequent kidney transplantation (NTX), however, have not yet been evaluated. We analyzed the postsurgical course of 18 paediatric CKD patients with refractory HPT who underwent PTX and autotransplantation of tissue fragments. PTX was successful in all but one patient with an ectopic fifth gland; median follow-up time was 8.3 (range 2.8-19) years. Parathyroid hormone (PTH) dropped within 1 year after PTX from 1030 +/- 108 to 98 +/- 18 pg/ml, Ca*P from 59.5 +/- 3 to 49 +/- 2 mg(2)/dl(2). Oral calcium supply transiently increased from 18.7 +/- 4.2 to 24.1 +/- 4.8 mg/kg/day within the first 6 months (all P < 0.05). Haemoglobin increased from 10.7 +/- 0.4 to 11.5 +/- 0.3 g/dl (P < 0.01), despite similar erythropoietin dose and ferritin levels. In patients on long-term dialysis, Ca*P increased again after 18 months; three patients required a second PTX after 3.8, 12 and 12.3 years. Twelve patients underwent NTX 1.8 (0.3-3.8) years after PTX, which decreased mean PTH and Ca*P into the target range throughout the entire post-NTX observation period. Postoperative complications included one transient recurrent nerve palsy, one hypocalcaemic seizure and a case of haemopericardium. At present, no patient has clinical signs of bone disease. PTX accomplishes long-term control of HPT and calcium-phosphate metabolism in children with CKD and following PTX and may thus mitigate uraemic bone and cardiovascular disease. This has to be taken into account if alternative long-term therapy with calcimimetics (with as yet unknown effects on longitudinal growth and pubertal development) is considered.

Report of the first international liver transplantation society expert panel consensus conference on renal insufficiency in liver transplantation

Michael R. Charlton, William J. Wall, Akinlolu O. Ojo, Pere Gines, Stephen Textor, Fuad S. Shihab, Paul Marotta, Marcelo Cantarovich, James D. Eason, Russell H. Wiesner, Michael A. Ramsay, Juan C. Garcia-Valdecasas, James M. Neuberger, Sandy Feng, Connie L. Davis, Thomas A. Gonwa, and the International Liver Transplantation Society Expert Panel Mayo Clinic, Rochester MN; Department of General Surgery, London Health Science Center, London, Ontario, Canada; Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI; Liver Unit, Hospital Clinic, University of Barcelona School of Medicine, Barcelona, Spain; Department of Nephrology, University of Utah School of Medicine, Salt Lake City, UT; Medical School, University of Western Ontario, London, Ontario, Canada; Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada; Transplant Institute, University of Tennessee, Memphis, TN; Baylor University Medical Center, Dallas, TX; Hospital Clinic I Provincial, Barcelona, Spain; Queen Elizabeth Hospital, Birmingham, England; Department of Transplant Surgery, University of California San Francisco Medical Center, San Francisco, CA; Department of Medicine, University of Washington Medical Center, Seattle, WA; and Mayo Clinic, Jacksonville, FL

Optimizing outcomes for neonatal ARPKD

A retrospective analysis was conducted on 10 consecutive cases of neonatal ARPKD, 9 of whom received kidney transplants (KT). All were diagnosed antenatally (n = 6) or at birth. In the first month of life 70% required ventilatory support. Pre-emptive bilateral nephrectomy and peritoneal dialysis (PD) catheter placement were performed in 9 at a mean age of 7.8 +/- 11.9 months. The indications for nephrectomy were massive kidneys, resulting in suboptimal nutrition and respiratory compromise. All patients received assisted enteral nutrition, with significant increase in mean tolerated feeds following nephrectomy (p < 0.05), with increase in mean normalized weight and height (0.92 and 1.2 delta SDS respectively), by one year post-transplantation. KT was performed at a mean age and weight of 2.5 +/- 1.4 years and 13.3 +/- 6.1 kg. The mean creatinine clearance at one year post-KT was 91.3 +/- 38.1 mls/min/1.73 m(2), with a projected graft life expectancy of 18.4 years. Patient survival was 89% and death censored graft survival was 100%, at a mean follow-up of 6.1 +/- 4.5 years post-transplant. Six patients demonstrated evidence of hepatic fibrosis, one of which required liver transplantation. In patients with massive kidneys from ARPKD, pre-emptive bilateral nephrectomy, supportive PD and early aggressive nutrition, can minimize early infant mortality, so that subsequent KT can be performed with excellent patient and graft survival.

Impact of Surgical Procedures and Complications on Outcomes of Third and Subsequent Kidney Transplants

Surgical procedures and complications have rarely been described in patients receiving a third or subsequent renal transplant. Data from 61 consecutive third (n=56), fourth (n=4), and fifth (n=1) renal transplants performed during 1974 to 2005 were analyzed retrospectively. Actuarial graft survival was 91%, 74%, and 57% at one, five, and 10 years, respectively. Technical failure accounted for the loss of three grafts (5%). A transperitoneal approach was necessary in 41% of patients. Technical difficulties occurred in half of the procedures, mainly due to atheroma or vascular calcifications. Overall, there were 45 surgical complications in 30 patients, of urological (n=11), vascular (n=6), infectious (n=9), hemorrhagic (n=12), digestive (n=3), or wound origin (n=4). The rate of surgical revision was 16%. Univariate analysis showed that among surgical complications, only vascular complications were associated with a poor graft outcome (P=0.02). Urological complications did not influence long-term graft outcome. Multivariate analysis of all surgical procedures and complications that might have influenced graft survival showed that only vascular complications were associated with a poorer graft outcome (relative risk=6.13, P=0.015). Despite a high rate of surgical complications and revisions, third and subsequent kidney transplantations may be performed safely by experienced surgeons without surgical complications influencing long-term graft outcome.

Lung Calcifications and Chronic Kidney Failure

Pulmonary calcification is relatively uncommon and typically asymptomatic. A number of diseases are associated with this disorder, including chronic kidney failure, infections, and lung amyloidosis. There are, moreover, a number of conditions, such as hypercalcemia, hyperphosphatemia, alkalosis, and alveolar damage, which predispose a patient to calcification. We describe a case of pulmonary calcifications associated with chronic kidney failure which had required hemodialysis and a subsequent kidney transplant.

Detection and analysis of HLA class I and class II specific alloantibodies in the sera of dialysis recipients waiting for a renal retransplantation

The objective of this study was to evaluate the specificities of HLA class I (-A,-B) and class II (-DR,-DQ) antibodies (Ab) detected in the sera of alloimmunized patients waiting for a subsequent renal transplantation. The study group consisted of 62 dialysis patients (42 men and 20 women, mean age: 43 +/- 18 yr) on waiting list for a subsequent kidney transplant (52 for a second and 10 for a third transplant) at S. Martino Hospital Transplant Centre in Genoa/Italy, who were enrolled from 2002 to 2004 for HLA antibody screening. Complement dependent cytotoxicity (CDC) technique was used firstly to select anti-HLA class I sensitized patients; indeed sera from 50 individuals out of 62 (80.6%) were found to display persistent HLA class I PRA (panel reactive antibody) values >4% (range: 20-100). ELISA technique was subsequently adopted to analyze HLA class I Ab positive sera for the presence also of HLA class II Ab and to characterize class I and class II Ab specificities. Anti-class I immunized patients were divided in three groups according to the type of class I Ab specificities, that were classified as private, public, and multispecific. The first group included 35 patients (70% of the total number of positive patients) showing only antibodies directed against private HLA class I specificities, represented in 33 cases by those expressed by graft donors (first or second transplant). In this group anti-class I PRA% values ranged from 20% to 60%. HLA class II Ab, with an heterogeneous specificity pattern (private, public or multispecific), were present in 25 (78.1%) out of the 32 patients, whose sera were also available for this analysis. The second group comprised 12 patients (24%) who displayed antibodies directed against class I public epitopes belonging to CREGs (Cross reactive Groups) or an association of anti-private and anti-public antibodies. In this group PRA values ranged from 25% to 90%. Five patients (46.7%) were positive for HLA class II Ab, whose specificity pattern appeared also heterogeneous (private or multispecific). The third group was represented by three patients (6%) displaying multispecific antibodies with PRA values > or = 90%. No multispecific class II Ab were found in this group, where only two patients had class II Ab showing anti-private or anti-private plus public specificities. Globally, 74% of anti-class I Ab positive patients, having at least one HLA class II antigen mismatch, appeared also positive for class II Ab. These results indicate that: (i) a large proportion of patients, waiting for a kidney retransplantation, display in their sera alloantibodies specific for graft mismatched HLA class I (80.6%) and class II antigens (54.2); (ii) the immunogenic determinants, mainly involved in HLA class I and II specific Ab production, were, in a significant rate, private specificities of mismatched HLA antigens (70% for class I and 59.4% for class II), and in a lesser percentage by public (CREG) epitopes (24% for class I and 34.3% for class II). In a few patients only no HLA class I and class II Ab specificities could be determined, as they displayed multispecific antibodies (6% for class I and 6.2% for class II). These findings may have important implications to improve donor-recipient matching in dialysis recipients waiting for a subsequent renal transplantation.