Patients Receiving Kidney Transplants Research Articles

Sirolimus and Non-melanoma Skin Cancer Prevention after Kidney Transplantation: A Meta-analysis

Whether sirolimus is useful in the prevention of non-melanoma skin cancer (NMSC) remains unclear and we therefore performed this meta-analysis of randomized controlled trials to test the hypothesis that Sirolimus-based immunosuppression is associated with a decrease in NMSC. The main outcomes were NMSC, squamous-cell carcinoma and basal-cell carcinoma. The pooled risk ratio (RR) with its 95% confidence interval (95%CI) were used to assess the effects. 5 randomized trials involving a total of 1499 patients receiving kidney transplantation were included. Patients undergoing Sirolimus-based immunosuppression had much lower risk of NMSC (RR = 0.49, 95%CI 0.32-0.76, P = 0.001). Subgroup analyses by tumor type showed that Sirolimus-based immunosuppression significantly decreased risk of both squamous-cell carcinoma (RR = 0.58, 95%CI 0.43-0.78, P < 0.001) and basal-cell carcinoma (RR = 0.56, 95%CI 0.37-0.85, P = 0.006). The quality of evidence was high for NMSC, and moderate for squamous-cell carcinoma and basal-cell carcinoma. No evidence of publication bias was observed. High quality evidence suggests that Sirolimus-based immunosuppression decreases risk of non-melanoma skin cancer, and Sirolimus has an antitumoral effect among kidney-transplant recipients.

Kidney Transplant Recipients with Cutaneous Squamous Cell Carcinoma Have an Increased Risk of Internal Malignancy

This study aimed to investigate whether the occurrence of cutaneous squamous cell carcinomas (SCCs) is associated with an increased risk of internal malignancies (IMs) in kidney transplant recipients (KTRs). In a cohort study, all patients receiving kidney transplantation in Leiden, the Netherlands, between 1966 and 2006 were followed up. All malignancies that had developed between 1966 and 2007 were recorded. Time-dependent Cox regression analyses were used to calculate the association between the development of cutaneous SCCs and IMs. The incidence of IMs in the KTRs after transplantation was also compared with the general Dutch population by calculating standardized morbidity ratios (SMRs) and was matched for age, sex, and time period in which the malignancy had occurred. Among 1,800 KTRs, 176 (9.8%) developed cutaneous SCCs and 142 (7.9%) developed IMs after transplantation. In patients with prior cutaneous SCCs, the adjusted risk to develop IMs was 3.0 (1.9; 4.7). In KTRs without cutaneous SCCs, the risk of IM compared with the general population was hardly increased. KTRs with cutaneous SCCs have an increased risk to develop IMs, and this information can be used to identify KTRs who are at an increased risk for IMs.

Renal Replacement Therapy in Patients With HIV Infection in a European Region: Outcomes Following Renal Transplantation

IntroductionThe prognosis of HIV infection has improved dramatically in patients with end-stage renal disease (ESRD). Thus, HIV infection is no longer an absolute contraindication for renal transplantation. MethodsA cross-sectional study was performed to analyze the characteristics of HIV patients receiving renal replacement therapy (RRT) in September 2011, using data from the Registry of Renal Patients in Andalusia. A retrospective cohort study was also carried out, analyzing patients receiving kidney transplants in the era of highly active antiretroviral therapy. ResultsIn Andalusia in September 2011, 8744 patients were on RRT; of these, 48 had HIV infection (prevalence 0.54%). The RRT modality was very different between HIV-negative and HIV-positive patients: renal transplantation 49.2% and 16.7%, hemodialysis 46.8% and 81.3%, and peritoneal dialysis 4% and 2%, respectively. The most frequent ESRD etiology was glomerulonephritis (37.5%). Twenty-seven (56.3%) had hepatitis C coinfection. Only three patients (7.5%) were on the waiting list for renal transplantation. From 2001 to September 2011, 10 HIV-infected patients received a renal transplantation (median follow-up 40.5 months). The initial immunosuppressive treatment included tacrolimus and mycophenolate without induction therapy. Only two patients presented acute rejection, both borderline and corticosensitive. All remain alive and the graft survival was 100% in the first and third years posttransplant. We compared demographic and comorbidity variables between patients transplanted or included on the waiting list (n = 12) and patients excluded and never transplanted (n = 36). We found differences only in the ESRD etiology (higher incidence of glomerulonephritis in excluded patients). ConclusionsRenal transplantation is safe in correctly selected HIV-infected patients. The number of patients on the waiting list is very small. This may reflect the high comorbidity but it is also possible that these patients are still not being assessed systematically for transplant in all centers.

Body mass index and postoperative complications in kidney transplant recipients

There is a growing number of overweight and obese patients receiving kidney transplants, despite elevated body mass index (BMI) being associated with postoperative complications. Understanding associations between BMI and complications would allow more objectivity when recommending patients for transplantation or otherwise. We analysed a retrospective cohort of 508 adult patients who received primary kidney grafts at a single centre in South Australia, 2002-2009, using hospital records and Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data. Complications within 1 year of transplantation were classified into: surgical, wound, urological, delayed graft function, early nephrectomy and admission to intensive care unit (ICU). Overall, 62% of transplant recipients had a BMI above 25 kg/m(2) at transplant. Higher BMI was associated with an increased risk of wound complications (P < 0.001), early nephrectomy (P = 0.002) and delayed graft function (P = 0.03), but not associated with surgical or urological complications, or ICU admission. These associations were stronger for Indigenous Australians than other patients, especially for surgical complications. There was no BMI value above which risks of complications increase substantially. Delayed graft function is an important determinant of patient outcomes. Wound complications can be serious, and are more common in patients with higher BMI. This may justify the use of elevated BMI as a contraindication for transplantation, although no obvious cut-off value exists. Investigations into other measures of body fat composition and distribution are warranted.

Validation And Life-Cycle Management of A Quantitative Ligand-Binding Assay For The Measurement of Nulojix ® , A Ctla-4–Fc Fusion Protein, in Renal And Liver Transplant Patients

Nulojix(®) is a fusion protein composed of the Fc portion of a human IgG1 linked to the extracellular modified domain of CTLA-4. Nulojix differs from another Bristol Myers Squibb product, Orencia(®) by two amino acids and was approved by the FDA on 15 June 2011 for the prophylaxis of organ rejection in adult patients receiving kidney transplant. A sandwich ELISA utilizing two monoclonal antibodies against CTLA-4 was employed for Nulojix quantification and pharmacokinetic analysis. At least 17 analysts have qualified on the assay and contributed to reportable results over the last 7 years. In-study accuracy and precision demonstrate suitable performance: %bias within -4 to 4%, %CV ≤13% and total error within 6-15%. Incurred sample reanalysis was completed in applicable disease-state populations. The assay was automated and validated in additional clinical matrices (ascites and urine) and Nulojix quantification was validated in the presence of clinically relevant co-administered compounds. In 2011, the biotinylation procedure was modified meriting a regression change (quadratic to 4-parameter logistic) and associated partial validation. This long-term pharmacokinetic program provides a good example of the dynamic clinical environment and adaptation requirements of ligand-binding assays.

Risk of Acute Myeloid Leukemia Among Solid Organ Transplant Recipients

Abstract 2559 Background.Patients receiving solid organ transplants experience increased risk of subsequent hematologic malignancies, particularly post-transplant lymphoproliferative disorder and non-Hodgkin lymphoma, likely in relation to infection with oncogenic viruses and pharmacologic immunosuppression to prevent graft rejection. However, less is known about the risks for myeloid neoplasms such as acute myeloid leukemia (AML). Methods.We linked data from the US Scientific Registry of Transplant Recipients, a national database of solid organ transplantation, with 13 state and regional cancer registries to obtain cancer occurrence among 175,732 solid organ transplants during 1987–2008. The observed number of patients developing AML was compared to that expected in the general population of the 13 registry areas using standardized incidence ratios (SIRs). Results.AML was identified in 107 solid organ transplant recipients (13.8 cases/100,000 person-years), a rate that was nearly three times higher than expected in the general population [SIR=2.9, 95% confidence interval (CI) 2.4–3.5]. Excess risks were highest among children and young adults but remained significantly elevated among individuals receiving a solid organ transplant prior to age 65 years (SIR, 95%CI: <20 years=9.3, 3.4–20.2; 20–34 years=6.3, 3.2–11.3; 35–49 years=3.9, 2.6–5.6; 50–64 years=2.5, 1.9–3.3; 65+years=1.7, 0.9–2.9). Patients receiving liver or heart and/or lung transplants had higher risks than patients receiving kidney transplants (liver=4.1, 2.9–5.7; heart and/or lung=4.0, 2.7–5.7; kidney=2.0, 1.4–2.7). Risks also were higher among individuals receiving a second solid organ transplant than those receiving their first (second=6.8, 3.5–11.9; first=2.7, 2.2–3.3). Excess risks persisted throughout the 22-year period and showed no trend over time. Conclusions.In the largest population-based study of transplant-related malignancies conducted to date, we demonstrate that patients receiving solid organ transplants have substantially elevated risk for subsequent AML. Future investigations should evaluate the possible role of specific immunosuppressive medications in the etiology of post-transplant AML. Disclosures:No relevant conflicts of interest to declare.

Prediction tacrolimus blood levels based on the Bayesian method in adult kidney transplant patients

The use of tacrolimus is complicated by its narrow therapeutic index and wide intra- and interpatient variability. We have previously described a tacrolimus population pharmacokinetics model obtained in an adult kidney transplant cohort. The aims of the present study were (1) to validate that model using an external dataset and (2) to evaluate the prediction using a Bayesian method. Data were retrospectively collected from 34 adult patients receiving kidney transplantation. Trough blood concentrations of tacrolimus were predicted using the empirical Bayesian method with sparse samples obtained during the previous week. The system performance was evaluated by the mean prediction error (ME), mean absolute prediction error (MAE). and root mean square error (RMSE). Patients were administrated oral or intravenous tacrolimus as part of a triple immunosuppressive regimen with mycophenolate mofetil and corticosteroids. Subsequent doses were adjusted on the basis of clinical evidence of efficacy and toxicity and by routine therapeutic drug monitoring. In our previous model, clearance increased with post transplantation days and with prednisone dosage. Concentrations predicted by the population mean pharmacokinetic parameter values match well with observed concentrations during oral therapy. Bayesian prediction using trough concentrations obtained after 21days of treatment significantly decreased ME, MAE, and RMSE compared with predictions from data including this period. After 21days of treatment, there was an insignificant bias ME (0.22±2.59ng/ml), a reasonable precision MAE (1.97±1.69ng/ml) and RMSE (1.28±0.58ng/ml). The present study demonstrates the suitability of the Bayesian method for the prediction of trough blood concentrations of tacrolimus using only few samples in adult kidney transplantation recipients.

Comparison of Clinical Outcomes by Different Renal Replacement Therapy in Patients with End-Stage Renal Disease Secondary to Lupus Nephritis

Background/AimsMany studies have compared patients with systemic lupus erythematosus (SLE) on renal replacement therapy (RRT) with non-lupus patients. However, few data are available on the long-term outcome of patients with end-stage renal disease (ESRD) secondary to SLE who are managed by different types of RRTs.MethodsWe conducted a retrospective multicenter study on 59 patients with ESRD who underwent maintenance RRT between 1990 and 2007 for SLE. Of these patients, 28 underwent hemodialysis (HD), 14 underwent peritoneal dialysis (PD), and 17 patients received kidney transplantation (KT). We analyzed the clinical outcomes in these patients to determine the best treatment modality.ResultsThe mean follow-up period was 5 ± 3 years in the HD group, 5 ± 3 years in the PD group, and 10 ± 5 years in the KT group (p = 0.005). Disease flare-up was more common in the HD group than in the KT group (p = 0.012). Infection was more common in the PD and HD groups than in the KT group (HD vs. KT, p = 0.027; PD vs. KT, p = 0.033). Cardiovascular complications were more common in the HD group than in the other groups (p = 0.049). Orthopedic complications were more common in the PD group than in the other groups (p = 0.028). Bleeding was more common in the HD group than in the other groups (p = 0.026). Patient survival was greater in the KT group than in the HD group (p = 0.029). Technique survival was lower in the PD group than in the HD group (p = 0.019).ConclusionsAmong patients with ESRD secondary to SLE, KT had better patient survival and lower complication rates than HD and lower complication rates than PD. The prognosis between the HD and PD groups was similar. We conclude that if KT is not a viable treatment option, any alternative treatment should take into account the patient's general condition and preference.

Different Etiologies of Graft Loss and Death in Asian Kidney Transplant Recipients: A Report From Thai Transplant Registry

Background Kidney transplantation is the most performed solid organ transplantation in Thailand. Over 4000 patients have received kidney transplantation from 23 centers within the kingdom. This study sought to demonstrate the causes of graft loss and death in Thai patients receiving kidney transplant during the past decade. Patients and Methods The Thai Transplant Registry database was used to evaluate the causes of graft loss and death. This database was established since 1997, a total of 2298 kidney transplants were available for analysis. Graft loss was defined as return to dialysis, graft removal, retransplantation, or death of the recipients. Patient survival was analyzed by all deaths. Results Among 2298 recipients, 59% received organs from deceased donors. The mean age at transplantation was 42 years (SD 12) and 61% were male. The most common identified causes of the end-stage renal disease were chronic glomerulonephritis (25.3%) and hypertensive nephropathy (11.3%); half of those were unknown. Actuarial graft survival rates at 1 and 5 years were 89% and 73%, respectively. The common causes of graft loss were chronic allograft nephropathy (53%), acute rejection (15%), death with a functioning graft (15%), and transplant renal artery diseases (7%). The greatest proportion (64%) of deaths was infection owing to septicemia and/or pulmonary infection. The others were from cardiovascular deaths (12%), liver disease (6%), and malignancy (4%). Conclusion Graft survival rates were comparable with previous reports. However, the proportion of death with functioning graft and cardiovascular death as a cause of graft and patient loss is lower than that of Caucasian populations.

Polymorphisms of Superoxide Dismutase, Glutathione Peroxidase and Catalase Genes in Patients with Post-transplant Diabetes Mellitus

Post-transplant diabetes mellitus (PTDM) is a metabolic disorder that develops in response to a relative insulin deficiency in patients after organ transplantation treated with immunosuppressive drugs. Several studies have suggested that oxidative stress may be associated with diabetes and its complications. The aim of this study was to examine the association of polymorphisms in superoxide dismutase, catalase and glutathione peroxidase genes with PTDM in patients after kidney transplantation. The study included 159 patients receiving kidney transplants. PTDM was diagnosed in 21 patients. Analyzing the C599T (Pro200Leu) polymorphism in the GPX1 gene PTDM was diagnosed in 8.45% of patients with CC genotype, 13.43% with CT and in 28.57% with TT. Allele T was significantly more frequent among patients with PTDM compared to patients without PTDM (OR = 2.14, 95% CI = 1.11-4.12, p = 0.024). There were no associations between SOD1, SOD2 and CAT polymorphisms and PTDM. The present results suggest that Pro200Leu polymorphism of the GPX1 gene may be associated with the risk of PTDM development in renal graft recipients.

Posttransplant Lymphoproliferative Disorders of the Central Nervous System After Kidney Transplantation: Single Center Experience Over 40 Years -Two Case Reports-

Posttransplant lymphoproliferative disorder (PTLD) is one of the life-threatening complications of organ transplantation. PTLD sometimes involves the central nervous system (CNS), but the clinical characteristics are not well recognized. A total of 631 patients received kidney transplantation at Osaka University Hospital between March 1965 and December 2008. Two of the 631 patients (0.32%) developed CNS PTLD. A 40-year-old Japanese woman suffered onset of CNS PTLD 5 years after renal transplantation. After diagnosis based on histological examination by open biopsy, she obtained remission with dose increase of steroid and dose reduction of mycophenolate mofetil. She experienced relapse 20 months after first remission. She underwent second biopsy and the diagnosis was recurrent CNS PTLD. Further reduction of mycophenolate mofetil and increase of steroid led to second remission. The disease remained in complete remission at 60 months after first onset. A 61-year-old woman suffered onset of CNS PTLD 19 years after renal transplantation. After tumor removal, whole brain irradiation was performed. The disease remained in remission at 54 months after onset. Histological examination showed polymorphic-type PTLD in both cases. The first case of polymorphic CNS PTLD was successfully treated by modulation of immunosuppressants without radiation therapy even at recurrence. PTLD should be included in the differential diagnosis of brain tumors in recipients of solid organ transplantation, and histological subtype should be carefully identified to establish the correct treatment strategy.

Immortal Time Bias in Cohort Studies of Kidney Transplant Recipients

To the Editor: I read with interest the paper by Jones et al. (1Jones DG Taylor AM Enkiri SA et al.Extent and severity of coronary disease and mortality in patients with end‐stage renal failure evaluated for renal transplantation.Am J Transplant. 2009; 9: 1846-1852Crossref PubMed Scopus (17) Google Scholar) in the August 2009 issue of the American Journal of Transplantation. One of their main conclusions is that kidney transplantation affords a dramatic survival benefit for dialysis patients on the waiting list regardless of the extent of their coronary artery disease. I found the paper unclear about two important methodologic issues that may significantly impact on the validity of the authors’ inferences. First, there is no mention in the Methods section that kidney transplantation was handled as a time‐dependent covariate in the multivariable Cox proportional hazards model. Assuming this was not done, the marked reduction in the relative hazard of death for patients receiving kidney transplants shown in Table 3 (i.e. HR 0.191, p < 0.001) is likely a substantial overestimate of the protective effect of transplantation. By definition, patients who ultimately received a kidney transplant had to survive the waitlisting period (i.e. they were ‘immortal’ during this time). Therefore, attributing this waiting time to the transplanted group (instead of the group remaining on the waiting list) will exaggerate the survival benefit of transplantation. This ‘immortal time bias’ in observational studies has been previously recognized and described in the medical literature (2Suissa S Effectiveness of inhaled corticosteroids in chronic obstructive pulmonary disease: Immortal time bias in observational studies.Am J Respir Crit Care Med. 2003; 168: 49-53Crossref PubMed Scopus (217) Google Scholar, 3Sylvestre MP Huszti E Hanley JA Do OSCAR winners live longer than less successful peers? A reanalysis of the evidence.Ann Intern Med. 2006; 145: 361-363Crossref PubMed Scopus (114) Google Scholar, 4Shariff SZ Cuerden MS Jain AK Garg AX The secret of immortal time bias in epidemiologic studies.J Am Soc Nephrol. 2008; 19: 841-843Crossref PubMed Scopus (134) Google Scholar). A time‐dependent Cox regression model would ensure that the person‐time experience on the waiting list for those patients who eventually received a kidney transplant is properly attributed to the wait‐listed state. This methodology can also be extended to the construction of Kaplan–Meier survival curves (5Snapinn SM Jiang Q Iglewicz B Illustrating the impact of a time‐varying covariate with an extended Kaplan‐Meier estimator.Am Stat. 2005; 59: 301-307Crossref Scopus (165) Google Scholar). Second, the etiologic question of the reduction in mortality associated with kidney transplantation in dialysis patients possessing various degrees of coronary artery disease is one of effect modification or interaction. In this case, an interaction term for the extent of coronary artery disease and kidney transplantation should have been incorporated into the Cox regression model so that the relative hazard of death for those receiving (vs. not receiving) a kidney transplant can be compared across coronary artery disease burden groups. From what can be discerned in the Methods and Results sections, this was not done and thus the authors’ assertion is not supported by their data.

Long-term survival of living donor renal transplants: A single center study

Kidney transplantation is the treatment of choice for end-stage renal disease. The aim of this study was to determine the ten-year graft survival rate of renal transplantation in patients who have been transplanted from live donors. This is a historical cohort study designed to determine the organ survival rate after kidney transplantation from live donor during a 10-year period (from March 1999 to March 2009) on 843 patients receiving kidney transplant in the transplantation center of Namazi hospital in Shiraz, Iran. Kaplan-Meier method was used to determine the survival rate, log-rank test was used to compare survival curves, and Cox proportional hazard model was used to multivariate analysis. Mean follow-up was 53.07 ± 34.61 months. Allograft survival rates at 1, 3, 5, 7, and 10 years were 98.3, 96.4, 92.5, 90.8, and 89.2%, respectively. Using Cox proportional hazard model, the age and gender of the donors along with the creatinine level of the patients at discharge were shown to have a significant influence on survival. The 10-year graft survival rate of renal transplantation from living donor in this center is 89.2%, and graft survival rate in our cohort is satisfactory and comparable with reports from large centers in the world.

Modulation of Human Peripheral Blood Mononuclear Cell Proliferative Response by Diltiazem

The gradual aging of population has increased the number of elderly patients receiving kidney transplants. In elderly transplant recipients, careful immunosuppression has to be maintained to avoid both rejection and adverse effects. Clinical protocols after kidney transplantation include use of the calcium channel antagonist diltiazem to ameliorate the hypertensive effect and nephrotoxicity of the immunosuppressant agent ciclosporin (cyclosporine). Since immune response can be impaired by senescence, we evaluated the influence of diltiazem on lymphocyte proliferation both alone and in the presence of ciclosporin in younger versus older subjects. Peripheral blood mononuclear cells (PBMC) from younger healthy donors (aged 19-24 years) and older subjects (aged 59-65 years) were isolated and stimulated with mitogens, recombinant human interleukin-2 (IL-2), purified protein derivative (PPD) antigen from Mycobacteriumtuberculosis, and anti-CD3 monoclonal antibody (alphaCD3 moAb) in the presence or absence of 10(-4), 10(-5), 10(-6), 10(-7) mol/L concentrations of diltiazem. In some experiments, lymphocytes from younger and older subjects were used as responder cells in an allogeneic mixed lymphocyte reaction (MLR) in the presence of different concentrations of diltiazem and 10 ng/mL of ciclosporin. We found that PBMC from older subjects were more susceptible to immunosuppression induced by low concentrations of diltiazem when mitogens were used to stimulate cells. In particular, when pokeweed mitogen was used, diltiazem 10(-7) mol/L was associated with statistically significant immunosuppression in older subjects compared with younger subjects. This effect was not observed when IL-2, PPD antigen and alphaCD3 moAb were used as stimulators. Moreover, in the allogeneic MLR, we found no differences between younger and older subjects when the 10(-)(5), 10(-)(6) and 10(-7) mol/L concentrations of diltiazem were used alone or in the presence of ciclosporin. Only addition of the supratherapeutic 10(-4) mol/L concentration of diltiazem to ciclosporin was associated with statistically significant immunosuppression in older versus younger subjects. Our results show that PBMC from older subjects are no more susceptible than PBMC from younger subjects to therapeutic doses of diltiazem when T-cell receptors are directly or indirectly involved. On the contrary, when PBMC activation was not mediated by T-cell receptor involvement, as in the case of pokeweed mitogen, susceptibility to a therapeutic concentration of diltiazem in older subjects was enhanced. Moreover, co-administration of therapeutic doses of diltiazem and ciclosporin in an MLR showed no significant differences between younger and older subjects in an in vitro model of lymphocyte response to allogeneic transplantation. Since we found no variations in immunosuppression between older and younger subjects when therapeutic doses of diltiazem were added to ciclosporin, our data do not discourage the use of diltiazem in older kidney transplant recipients receiving ciclosporin therapy.

Improving Preemptive Transplant Education to Increase Living Donation Rates: Reaching Patients Earlier in Their Disease Adjustment Process

Patients who receive a preemptive kidney transplant before starting dialysis avoid the medical complications related to dialysis and have the highest graft success and lowest mortality rates. Because only 2.5% of incident patients receive kidney transplants preemptively, improved psychosocial education may assist more patients in accessing preemptive transplant. This article outlines (1) unique psychosocial issues affecting patients with chronic kidney disease stage 4 (glomerular filtration rates > 20 mL/min per 1.73 m2) and (2) how an educational program about preemptive living donor transplant should be designed and administered to increase access to this treatment option. Early referral patients may be overwhelmed in coping with and learning about their disease and, therefore, not ready to make a treatment decision, or they may be highly motivated to obtain a transplant to avoid dialysis and return to a normal life. An education program that defines the quality-of-life and health benefits possible with early transplant is outlined. The program is focused on minimizing the disruption of starting 2 treatment techniques and maximizing early transplant health, graft survival, employability, and retention of insurance coverage. Once the benefits of preemptive living donor transplant are outlined, educators can focus on demystifying the living donor evaluation process and assisting interested patients in planning how to find a living donor. To reach all patients, especially racial minorities, education about preemptive transplant should be available in primary-care physicians' and community nephrologists' offices, at dialysis centers, and through other kidney organizations.

Impact of Double-J Ureteric Stent in Kidney Transplantation: Single-Center Experience

We retrospectively evaluated the use of double-j stent and the incidence of urological complications in 2 groups of patients who received a kidney transplant. From January 2005 to September 2007 we studied 172 patients receiving kidney transplants, 65 and 107 from living and cadaver donors, respectively. From the 172 patients, a total of 34 were excluded due to ureterostomy or Politano-Leadbetter ureterovesical anastomosis. Another 21 patients were excluded from the study due to graft loss due to acute or hyperacute rejection, cytomegalovirus (CMV) infection, or vascular complication. The remaining patients were divided into 2 groups: group A (44 patients) and B (73 patients) with versus without the use of a double-j-stent, respectively. The 2 groups were comparable in terms of donor and recipient gender, ischemia time, and delayed graft function. We failed to observes significant differences between the 2 groups in mean hospital stay (23 ± 9 and 19 ± 9), urinary leak (2.3% and 4.1%), and urinary tract infection (20.4% and 19.2%), among groups A and B, respectively. The only difference observed concerned the gravity of the urinary leak; no surgical intervention was needed among the double-j stent group versus 2 patients demanding ureterovesical reconstruction in the nonstent group. In conclusion, our data suggested that the routine use of a double-j stent for ureterovesical anastomosis neither significantly increased urinary tract infection rates, nor decreased the incidence of urinary leaks, but may decrease the gravity of the latter as evidenced by the need for surgical intervention.

Pediatric Kidney Transplantation in Thailand: Experience in a Developing Country

From July 1996 to November 2006, 46 patients received kidney transplants at five pediatric centers in Thailand. The male-female ratio was 1.9:1. The primary causes of end-stage renal disease (ESRD) included hypoplastic or dysplastic kidney, chronic glomerulonephritis, reflux nephropathy, pyelo nephritis or interstitial nephritis, focal segmental glomerulosclerosis, and rapidly progressive glomerulonephritis. Mean (SD) age at onset of ESRD was 10.1 (3.1) years, and at transplantation was 11.1 (2.9) years. Preemptive transplantation was performed in 2 patients. Cadaveric donors were used in 67.4% of procedures. Induction of immunosuppression with interleukin (IL)–2 monoclonal antibody was used in 41.3% of the patients. At 1 year posttransplantation, maintenance therapy included corticosteroids in 100% of patients, cyclosporine in 81.6%, tacrolimus in 15.8%, azathioprine in 31.6%, and mycophenolate mofetil in 57.9%. Standardized height z scores at transplantation and last follow-up (mean [SD], 40.0 [28.3] months) remained the same at −1.9. Mean (SD) serum creatinine level at the last follow-up was 1.3 (0.8) mg/dL. Patient survival at 1 and 5 years was 96% and 88%, respectively. Graft survival at 1 and 5 years was 98% and 84%, respectively. The medical expenses at 1, 6, and 12 months were US$601, US$464, and US$384 per month, respectively. The Thai per gross domestic product per capita was US$758 per month. Medical expenses were paid by the government in 44.2% of cases, charity foundations in 39.5%, and the patients' parents in 16.3%. Although the causes, management, and outcomes of ESRD were not different from those in other countries, access to treatment and medical expenses may be substantial barriers in developing countries.

Non-invasive diagnosis of acute rejection in kidney transplants with delayed graft function

Delayed graft function (DGF) often occurs in kidney transplants from deceased donors. We wanted to provide studies giving more accurate non-invasive tests for acute rejection (AR). Using real-time PCR, we examined the expression of cytolytic molecules such as perforin, granzyme B, and fas-ligand along with serpin proteinase inhibitor-9. We also measured the expression of FOXP3, a characteristic gene of T-regulatory cells known to be involved in AR. These studies were conducted on peripheral blood monocytes, urinary cells, and 48 surveillance kidney biopsies taken from a total of 35 patients with DGF. Of these patients, 20 had a histopathological diagnosis of AR, whereas other 28 had characteristics of acute tubular necrosis (ATN). Expression of cytolytic and apoptotic-associated genes in the biopsy tissue, peripheral blood leukocytes, and urinary cells was significantly higher in patients with AR than that in patients with ATN. Diagnostic parameters associated with FOXP3 gene expression were most accurate in peripheral blood leukocytes and urine cells with sensitivity, specificity, positive and negative predictive values, and accuracy between 94 and 100%. Our study shows that quantification of selected genes in peripheral blood leukocytes and urinary cells from renal transplant patients with DGF may provide a useful and accurate non-invasive diagnosis of AR.

Cyclosporine A: A Review of Current Oral and Intravenous Delivery Systems

ABSTRACTAs early as 1978, the immunosuppressive effect of cyclosporine A (CsA), a metabolite of the fungus Tolypocladium inflatum (), was reported to be effective in inhibiting organ rejection in patients receiving kidney transplants from mismatched cadaver donors () and in the treatment of graft-versus-host disease in patients with acute leukemia following bone marrow transplants (). Today, CsA is still indicated to prevent rejection following solid organ transplantations, prevent and treat graft-vs-host disease following bone marrow transplants, and has also been used in the treatment of autoimmune disease such as psoriasis, rheumatoid arthritis, and nephrotic syndrome (). The effectiveness of CsA is derived from its ability to specifically and reversibly inhibit immunocompetent lymphocytes in the G0 and G1 phase of the cell cycle. The T-helper cells are the main target, but suppression of the T‐suppressor cells also occurs. The production and release of lymphokines, including interleukin-2 are also inhibited (). CsA can be administered intravenously as well as orally in the form of a solution or a soft gelatin capsule. The following review will focus on the evolution of the emulsion-based oral formulations from the first generation as Sandimmune® to the second generation Neoral®, both products of Novartis Pharmaceutical, as well as on the Sandimmune® commercial intravenous formulation. The potential of alternative delivery systems, including micelles, micro- and nanoparticles, and liposomes, will also be discussed.

Serum concentrations of adiponectin and serum amyloid A in patients with end-stage renal disease and following successful kidney transplantation

Objective Adiponectin (ADPN), a collagen-like protein of the collectin family produced by adipocytes, may play a crucial role in the association between inflammation, atherosclerosis, and IR. Plasma ADPN is also down-regulated in association with obesity-linked diseases including coronary artery diseases. Although reports have shown that ADPN increases during maintenance hemodialysis (HD) and decreases following successful renal transplantation, there is no evidence about whether ADPN causes the deterioration of vasculitis. Methods To determine if ADPN causes inflammation and insulin resistance, we examined the differences in serum concentrations of serum amyloid A (SAA), homeostasis model assessment value for insulin resistance (HOMA-R), and ADPN in patients who had undergone both maintenance HD and who had later received a renal transplant. Results The mean SAA (27.7 ± 8.3 g/mL) and ADPN (20.8 ± 11 g/mL) levels in the patients while they underwent HD were high. ADPN increased after an HD session (30.2 ± 10.5 g/mL). Patients with diabetes mellitus (DM) who had low ADPN concentrations of at least 20 g/mL had higher body mass index (BMI), HOMA-R, and SAA values. One month after the patients received kidney transplantation, plasma ADPN decreased to 15.2 ± 1.3 g/mL, and mean SAA increased (14.6 ± 4.8 vs. 89.5 ± 23.5 g/mL before and after treatment, respectively). Conclusions Both the serum ADPN and SAA levels of the patients while they underwent were high, and their ADPN levels decreased after successful kidney transplantation. Conversely, their SAA levels increased after kidney transplantation. These results suggest a correlation between ADPN level and vasculitis. Also, this is the first time it has been shown that ADPN and SAA increase simultaneously.