Publications by authors named "Andries J Hoitsma"

67 Publications

The Association Between Macroscopic Arteriosclerosis of the Renal Artery, Microscopic Arteriosclerosis, Organ Discard, and Kidney Transplant Outcome.

Transplantation 2020 12;104(12):2567-2574

Department of Surgery-Organ Donation and Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background: During organ retrieval, surgeons estimate the degree of arteriosclerosis and this plays an important role in decisions on organ acceptance. Our study aimed to elucidate the association between macroscopic renal artery arteriosclerosis, donor kidney discard, and transplant outcome.

Methods: We selected all transplanted and discarded kidneys in the Netherlands between January 1, 2000, and December 31, 2015, from deceased donors aged 50 y and older, for which data on renal artery arteriosclerosis were available (n = 2610). The association between arteriosclerosis and kidney discard, the relation between arteriosclerosis and outcome, and the correlation between macroscopic and microscopic arteriosclerosis were explored.

Results: Macroscopic arteriosclerosis was independently associated with kidney discard (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.02-1.80; P = 0.03). Arteriosclerosis (any degree) was not significantly associated with delayed graft function (OR, 1.16; 95% CI, 0.94-1.43; P = 0.16), estimated glomerular filtration rate 1-y posttransplant (B, 0.58; 95% CI, -2.07 to 3.22; P = 0.67), and long-term graft survival (hazard ratio, 1.07; 95% CI, 0.86-1.33; P = 0.55). There was a significant association between mild arteriosclerosis and primary nonfunction (OR, 2.14; 95% CI, 1.19-3.84; P = 0.01). We found no correlation between macroscopic and histological arteriosclerosis, nor between histological arteriosclerosis and transplant outcome.

Conclusions: Macroscopic arteriosclerosis of the renal artery was independently associated with kidney discard and somewhat associated with primary nonfunction posttransplant. However, there was no effect of arteriosclerosis on delayed graft function, estimated glomerular filtration rate at 1 y, or long-term graft survival. Our results are valid only after inevitable exclusion of discarded kidneys that had on average more arteriosclerosis. Hence, conclusions should be interpreted in the light of this potential bias.
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http://dx.doi.org/10.1097/TP.0000000000003189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668327PMC
December 2020

An Update on Early Urological Complications in Kidney Transplantation: A National Cohort Study.

Ann Transplant 2019 Dec 3;24:617-624. Epub 2019 Dec 3.

Department of Surgery, Radboud University Medical Center Nijmegen, Nijmegen, Netherlands.

BACKGROUND This study aimed to provide an update on the occurrence of early urological complications in living-donor and deceased-donor kidney transplantation (KTX). MATERIAL AND METHODS Data on all kidney transplant recipients in the Netherlands between January 2005 and December 2015 were retrieved from the prospectively collected Dutch National Organ Transplant Registry Database (NOTR). We assessed the incidence of major urological complications (MUCs) within 3 months after KTX, defined as urinary leakage and ureteral obstruction. Outcomes of living donor and deceased donor kidney transplants were compared. We performed regression analysis to identify predictive factors of urological complications and studied the influence of early urological complications on graft and patient survival. We performed an additional sub-study to explore the influence of preservation of the peri-ureteric connective tissue in living-donor KTX on the occurrence of urological complications. RESULTS Among 3329 kidney transplant recipients, urological complications occurred in 208 patients (6.2%) within 3 months after surgery. There were no significant differences in complication rates between recipients from living donors and deceased donors. Multiple regression analysis showed that older donor age and previous cardiac events of the recipient were predictors for the development of urological complications. Graft and patient survival were not affected by early MUCs. The additional sub-study showed that preservation of peri-ureteric tissue within living-donor KTX was not independently associated with urological complications. CONCLUSIONS Many living- and deceased-donor KTX recipients have early urological complications. MUCs did not affect long-term graft or patient survival.
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http://dx.doi.org/10.12659/AOT.920086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909919PMC
December 2019

Prolonged Duration of Brain Death was Associated with Better Kidney Allograft Function and Survival: A Prospective Cohort Analysis.

Ann Transplant 2019 Mar 15;24:147-154. Epub 2019 Mar 15.

Department of Surgery, Division of Vascular and Transplant Surgery, Radboud University Medical Center, Nijmegen, Netherlands.

BACKGROUND Brain death initiates hemodynamic, immunological, and hormonal changes that potentially compromise organ quality for transplantation. Therefore, it is generally believed that organs should be procured as soon as possible after the declaration of brain death. However, conflicting data exist regarding the impact of brain death duration on long-term graft function and survival. MATERIAL AND METHODS The effect of duration of brain death on graft survival and function of 1869 adult transplant recipients receiving kidneys from deceased donors after brain death was analyzed, using relevant donor and recipient characteristics and allograft related factors. RESULTS Duration of brain death was a significant predictor for long-term graft survival, whilst there was no significant effect of duration of brain death on the incidence of delayed graft function or acute graft rejection after kidney transplantation. After dividing the study population into a "short durBD" (<10.6 hours) group and a "long durBD" (>10.6 hours) group, the 15-year graft survival estimates were significantly higher and the serum creatinine at 3 months after transplantation was significantly lower in the "long durBD" group. CONCLUSIONS Duration of brain death does not affect the incidence of delayed graft function or acute rejection after kidney transplantation. However, longer duration of brain death is associated with better kidney allograft function and survival.
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http://dx.doi.org/10.12659/AOT.913869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434611PMC
March 2019

Psychosocial consequences of living kidney donation: a prospective multicentre study on health-related quality of life, donor-recipient relationships and regret.

Nephrol Dial Transplant 2019 06;34(6):1045-1055

Institute of Psychology, Health, Medical and Neuropsychology Unit, Leiden University, Leiden, The Netherlands.

Background: Previous studies have indicated decreased health-related quality of life (HRQoL) shortly after kidney donation, returning to baseline in the longer term. However, a subgroup of donors experiences persistent HRQoL problems. To identify which HRQoL aspects are impacted most by the donation and to identify at-risk donors, more specific insight into psychosocial donation consequences is needed.

Methods: The current study examined the HRQoL course, donor-perceived consequences of donation for donors, recipients and donor-recipient relationships, and regret up to 12 months post-donation in donors from seven Dutch transplantation centres. Kidney donor candidates (n = 588) completed self-report questionnaires early in the screening procedure, of which 361 (61%) donated their kidney.

Results: Data for 230 donors (64%) with complete assessments before donation and 6 and 12 months post-donation were analysed. Results indicated that donor physical HRQoL was comparable at all time points, except for an increase in fatigue that lasted up to 12 months post-donation. Mental HRQoL decreased at 6 months post-donation, but returned to baseline at 12 months. Donors reported large improvements in recipient's functioning and a smaller influence of the recipient's kidney disease or transplantation on the donor's life over time. A subgroup experienced negative donation consequences with 14% experiencing regret 12 months post-donation. Predictors of regret were more negative health perceptions and worse social functioning 6 months post-donation. The strongest baseline predictors of higher fatigue levels after donation were more pre-donation fatigue, worse general physical functioning and a younger age.

Conclusions: Future research should examine predictors of HRQoL after donation to improve screening and to provide potential interventions in at-risk donors.
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http://dx.doi.org/10.1093/ndt/gfy307DOI Listing
June 2019

Toward a Sensible Single-antigen Bead Cutoff Based on Kidney Graft Survival.

Transplantation 2019 04;103(4):789-797

Department of Immunogenetics, Sanquin Diagnostic Services, Amsterdam, The Netherlands.

Background: There is no consensus in the literature on the interpretation of single-antigen bead positive for a specific HLA antibody.

Methods: To inform the debate, we studied the relationship between various single-antigen bead positivity algorithms and the impact of resulting donor-specific HLA antibody (DSA) positivity on long-term kidney graft survival in 3237 deceased-donor transplants.

Results: First, we showed that the interassay variability can be greatly reduced when working with signal-to-background ratios instead of absolute median fluorescence intensities (MFIs). Next, we determined pretransplant DSA using various MFI cutoffs, signal-to-background ratios, and combinations thereof. The impact of the various cutoffs was studied by comparing the graft survival between the DSA-positive and DSA-negative groups. We did not observe a strong impact of various cutoff levels on 10-year graft survival. A stronger relationship between the cutoff level and 1-year graft survival for DSA-positive transplants was found when using signal-to-background ratios, most pronounced for the bead of the same HLA locus with lowest MFI taken as background.

Conclusions: With respect to pretransplant risk stratification, we propose a signal-to-background ratio-6 (using the bead of the same HLA-locus with lowest MFI as background) cutoff of 15 combined with an MFI cutoff of 500, resulting in 8% and 21% lower 1- and 10-year graft survivals, respectively, for 8% DSA-positive transplants.
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http://dx.doi.org/10.1097/TP.0000000000002357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430591PMC
April 2019

Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure.

J Am Soc Nephrol 2018 09 26;29(9):2279-2285. Epub 2018 Jul 26.

Department of Immunogenetics, Sanquin, Amsterdam, The Netherlands.

Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients. Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay. Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non-C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non-C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non-C3d-fixing DSA; =0.93). Patients without DSA had a 10-year graft survival of 78%. The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.
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http://dx.doi.org/10.1681/ASN.2018020205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115667PMC
September 2018

Development and feasibility of a guided and tailored internet-based cognitive-behavioural intervention for kidney donors and kidney donor candidates.

BMJ Open 2018 06 30;8(6):e020906. Epub 2018 Jun 30.

Institute of Psychology, Health, Medical and Neuropsychology Unit, Leiden University, Leiden, The Netherlands.

Objectives: Living donor kidney transplantation is currently the preferred treatment for patients with end-stage renal disease. A subgroup of the kidney donor population experiences adjustment problems during or after the donation procedure (eg, anxiety or fatigue). There is a need for evidence-based interventions that decrease donation-related difficulties before or after donation. In the current study, a guided and tailored internet-based cognitive-behavioural therapy (ICBT) intervention for donors and donor candidates was developed and the feasibility and perceived effectiveness were evaluated.

Design: Pilot study including qualitative and quantitative research methods for intervention development and evaluation.

Setting: Living kidney donor population of two Dutch transplantation centres.

Participants: Donors and healthcare professionals participated in focus group interviews conducted to identify intervention themes and to map attitudes towards internet-based interventions. In a pilot feasibility study, 99 donors and donor candidates participated, of whom 38 completed the screening. Eight donors or donor candidates with a risk profile (ie, impaired mental health-related quality of life (HRQoL)) received and evaluated the intervention.

Interventions: A guided and tailored ICBT intervention for donors and donor candidates was developed. Donation-related treatment modules, assignments and psychoeducation were integrated within an existing disease-generic ICBT intervention.

Outcome Measures: HRQoL, anxiety and depression were assessed before and after the ICBT intervention. Additional questionnaires were included to identify specific problem areas of donor functioning to tailor the ICBT intervention to the donor's needs.

Results: Different intervention themes were derived from the focus group interviews (eg, physical limitations, and donation-specific emotional and social-relational problems). Participants were satisfied about the intervention content (7.7±0.8 on a 0-10 scale) and the therapeutic relationship (4.4±0.6 on a 1-5 scale), and indicated an improvement on domains of their treatment goals (3.2±0.7 on a 1-4 scale).

Conclusion: This study showed positive evaluations concerning both feasibility and perceived effectiveness of the tailored ICBT intervention in kidney donors and donor candidates, in line with previous studies using comparable ICBT treatment protocols in other populations. Future research should examine the possibilities of integrating the intervention into psychosocial care for kidney donors.
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http://dx.doi.org/10.1136/bmjopen-2017-020906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042571PMC
June 2018

Performance of an easy-to-use prediction model for renal patient survival: an external validation study using data from the ERA-EDTA Registry.

Nephrol Dial Transplant 2018 10;33(10):1786-1793

Dutch Transplant Foundation, Organ Centre, Leiden, The Netherlands.

Background: An easy-to-use prediction model for long-term renal patient survival based on only four predictors [age, primary renal disease, sex and therapy at 90 days after the start of renal replacement therapy (RRT)] has been developed in The Netherlands. To assess the usability of this model for use in Europe, we externally validated the model in 10 European countries.

Methods: Data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry were used. Ten countries that reported individual patient data to the registry on patients starting RRT in the period 1995-2005 were included. Patients <16  years of age and/or with missing predictor variable data were excluded. The external validation of the prediction model was evaluated for the 10- (primary endpoint), 5- and 3-year survival predictions by assessing the calibration and discrimination outcomes.

Results: We used a data set of 136 304 patients from 10 countries. The calibration in the large and calibration plots for 10 deciles of predicted survival probabilities showed average differences of 1.5, 3.2 and 3.4% in observed versus predicted 10-, 5- and 3-year survival, with some small variation on the country level. The concordance index, indicating the discriminatory power of the model, was 0.71 in the complete ERA-EDTA Registry cohort and varied according to country level between 0.70 and 0.75.

Conclusions: A prediction model for long-term renal patient survival developed in a single country, based on only four easily available variables, has a comparably adequate performance in a wide range of other European countries.
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http://dx.doi.org/10.1093/ndt/gfx348DOI Listing
October 2018

Pre-donation cognitions of potential living organ donors: the development of the Donation Cognition Instrument in potential kidney donors.

Nephrol Dial Transplant 2017 03;32(3):573-580

Leiden University, Institute of Psychology, Health, Medical and Neuropsychology Unit, Leiden, The Netherlands.

Background: Cognitions surrounding living organ donation, including the motivation to donate, expectations of donation and worries about donation, are relevant themes during living donor evaluation. However, there is no reliable psychometric instrument assessing all these different cognitions. This study developed and validated a questionnaire to assess pre-donation motivations, expectations and worries regarding donation, entitled the Donation Cognition Instrument (DCI).

Methods: Psychometric properties of the DCI were examined using exploratory factor analysis for scale structure and associations with validated questionnaires for construct validity assessment.

Results: From seven Dutch transplantation centres, 719 potential living kidney donors were included. The DCI distinguishes cognitions about donor benefits, recipient benefits, idealistic incentives, gratitude and worries about donation (Cronbach's alpha 0.76-0.81). Scores on pre-donation cognitions differed with regard to gender, age, marital status, religion and donation type. With regard to construct validity, the DCI was moderately correlated with expectations regarding donor's personal well-being and slightly to moderately to health-related quality of life.

Conclusions: The DCI is found to be a reliable instrument assessing cognitions surrounding living organ donation, which might add to pre-donation quality of life measures in facilitating psychosocial donor evaluation by healthcare professionals.
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http://dx.doi.org/10.1093/ndt/gfw421DOI Listing
March 2017

Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands.

Nephrol Dial Transplant 2016 11 10;31(11):1947-1956. Epub 2016 Jun 10.

Department of Pediatric Nephrology, Emma Children's Hospital, Academic Medical Center at the University of Amsterdam, Room H7-232 Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

Introduction: Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether 'transition' (the transfer from paediatric to adult care) influences control of hypertension. We assessed the prevalence of hypertension and uHT among Dutch paediatric and young adult KTRs and analysed the effects of transition. Additionally, we made an inventory of variations in treatment policies in Dutch transplant centres.

Methods: Cross-sectional and longitudinal national data from living KTRs ≤30 years of age (≥1-year post-transplant, eGFR >20 mL/min) were extracted from the 'RICH Q' database, which comprises information about all Dutch KTRs <19 years of age, and the Netherlands Organ Transplant Registry database for adult KTRs (≥18-30 years of age). We used both upper-limit blood pressure (BP) thresholds for treatment according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. uHT was defined as a BP above the threshold. A questionnaire on treatment policies was sent to paediatric and adult nephrologists at eight Dutch transplant centres.

Results: Hypertension and uHT were more prevalent in young adult KTRs (86.4 and 75.8%) than in paediatric KTRs (62.7 and 38.3%) according to the KDIGO definition. Time after transplantation was comparable between these groups. Longitudinal analysis showed no evidence of effect of transition on systolic BP or prevalence of uHT. Policies vary considerably between and within centres on the definition of hypertension, BP measurement and antihypertensive treatment.

Conclusion: Average BP in KTRs increases continuously with age between 6 and 30 years. Young adult KTRs have significantly more uHT than paediatric KTRs according to KDIGO guidelines. Transition does not influence the prevalence of uHT.
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http://dx.doi.org/10.1093/ndt/gfw225DOI Listing
November 2016

Increased risk of graft failure and mortality in Dutch recipients receiving an expanded criteria donor kidney transplant.

Transpl Int 2017 Jan;30(1):14-28

Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.

Survival of expanded criteria donor (ECD) kidneys and their recipients has not been thoroughly evaluated in Europe. Therefore, we compared the outcome of ECD and non-ECD kidney transplantations in a Dutch cohort, stratifying by age and diabetes. In all first Dutch kidney transplants in recipients ≥18 years between 1995 and 2005, both relative risks (hazard ratios, HR) and adjusted absolute risk differences (RD) for ECD kidney transplantation were analysed. In 3062 transplantations [recipient age 49.0 (12.8) years; 20% ECD], ECD kidney transplantation was associated with graft failure including death [HR 1.62 (1.44-1.82)]. The adjusted HR was lower in recipients ≥60 years of age [1.32 (1.07-1.63)] than in recipients 40-59 years [1.71 (1.44-2.02) P = 0.12 for comparison with ≥60 years] and recipients 18-39 years [1.92 (1.42-2.62) P = 0.03 for comparison with ≥60 years]. RDs showed a similar pattern. In diabetics, the risks for graft failure and death were higher than in the nondiabetics. ECD kidney grafts have a poorer prognosis than non-ECD grafts, especially in younger recipients (<60 years), and diabetic recipients. Further studies and ethical discussions should reveal whether ECD kidneys should preferentially be allocated to specific subgroups, such as elderly and nondiabetic individuals.
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http://dx.doi.org/10.1111/tri.12863DOI Listing
January 2017

Improved Mortality Prediction in Dialysis Patients Using Specific Clinical and Laboratory Data.

Am J Nephrol 2015 26;42(2):158-67. Epub 2015 Sep 26.

Dutch Transplant Foundation, Organ Centre, Leiden, The Netherlands.

Background: Risk prediction models can be used to inform patients undergoing renal replacement therapy about their survival chances. Easily available predictors such as registry data are most convenient, but their predictive value may be limited. We aimed to improve a simple prediction model based on registry data by incrementally adding sets of clinical and laboratory variables.

Methods: Our data set includes 1,835 Dutch patients from the Netherlands Cooperative Study on the Adequacy of Dialysis. The potential survival predictors were categorized on availability. The first category includes easily available clinical data. The second set includes laboratory values like albumin. The most laborious category contains glomerular filtration rate (GFR) and Kt/V. Missing values were substituted using multiple imputation. Within 1,225 patients, we recalibrated the registry model and subsequently added parameter sets using multivariate Cox regression analyses with backward selection. On the other 610 patients, calibration and discrimination (C-index, integrated discrimination improvement (IDI) index and net reclassification improvement (NRI) index) were assessed for all models.

Results: The recalibrated registry model showed adequate calibration and discrimination (C-index=0.724). Adding easily available parameters resulted in a model with 10 predictors, with similar calibration and improved discrimination (C-index=0.784). The IDI and NRI indices confirmed this, especially for short-term survival. Adding laboratory values resulted in an alternative model with similar discrimination (C-index=0.788), and only the NRI index showed minor improvement. Adding GFR and Kt/V as candidate predictors did not result in a different model.

Conclusion: A simple model based on registry data was enhanced by adding easily available clinical parameters.
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http://dx.doi.org/10.1159/000439181DOI Listing
July 2016

Nighttime kidney transplantation is associated with less pure technical graft failure.

World J Urol 2016 Jul 14;34(7):955-61. Epub 2015 Sep 14.

Division of Vascular and Transplant Surgery, Department of Surgery, Radboud University Medical Center Nijmegen, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, The Netherlands.

Purpose: To minimize cold ischemia time, transplantations with kidneys from deceased donors are frequently performed during the night. However, sleep deprivation of those who perform the transplantation may have adverse effects on cognitive and psychomotor performance and may cause reduced cognitive flexibility. We hypothesize that renal transplantations performed during the night are associated with an increased incidence of pure technical graft failure.

Methods: A retrospective analysis of data of the Dutch Organ Transplant Registry concerning all transplants from deceased donors between 2000 and 2013 was performed. Nighttime surgery was defined as the start of the procedure between 8 p.m. and 8 a.m. The primary outcome measure was technical graft failure, defined as graft loss within 10 days after surgery without signs of (hyper)acute rejection.

Results: Of 4.519 renal transplantations in adult recipients, 1.480 were performed during the night. The incidence of pure technical graft failure was 1.0 % for procedures started during the night versus 2.6 % for daytime surgery (p = .001). In a multivariable model, correcting for relevant donor, recipient and graft factors, daytime surgery was an independent predictor of pure technical graft failure (p < .001).

Conclusions: Limitation of this study is mainly to its retrospective design, and the influence of some relevant variables, such as the experience level of the surgeon, could not be assessed. We conclude that nighttime surgery is associated with less pure technical graft failures. Further research is required to explore factors that may positively influence the performance of the surgical team during the night.
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http://dx.doi.org/10.1007/s00345-015-1679-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921110PMC
July 2016

Is the Reluctance for the Implantation of Right Donor Kidneys Justified?

World J Surg 2016 Feb;40(2):471-8

Division of Vascular and Transplant Surgery, Department of Surgery, Radboud University Nijmegen Medical Center, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, The Netherlands.

Background: The lengths of right renal veins are shorter when compared to their left counterparts. Since the implantation of kidneys with short renal veins is considered more challenging, many surgeons prefer left kidneys for transplantation. Therefore, our hypothesis is that the implantation of right kidneys from living and deceased donors is associated with more technical graft failures as compared to left kidneys.

Methods: Two consecutive cohorts of adult renal allograft recipients of living (n = 4.372) and deceased (n = 5.346) donor kidneys between January 1, 2000 and January 1, 2013 were analyzed. Data were obtained from the prospectively maintained electronic database of the Dutch Organ Transplant Registry. Technical graft failure was defined as failure of the renal allograft within 10 days after renal transplantation without signs of acute rejection.

Results: In the living donor kidney transplantation cohort, the implantation of right donor kidneys was associated with a higher incidence of technical graft failure (multivariate analysis p = 0.03). For recipients of deceased donor kidneys, the implantation of right kidneys was not significantly associated with technique-related graft failure (multivariate analysis p = 0.16).

Conclusions: Our data show that the implantation of right kidneys from living donors is associated with a higher incidence of technique-related graft failure as compared to left kidneys.
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http://dx.doi.org/10.1007/s00268-015-3232-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709383PMC
February 2016

Calculating the Rate of Senescence From Mortality Data: An Analysis of Data From the ERA-EDTA Registry.

J Gerontol A Biol Sci Med Sci 2016 Apr 16;71(4):468-74. Epub 2015 Apr 16.

Department of Gerontology and Geriatrics, Leiden University Medical Center, the Netherlands. Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

The rate of senescence can be inferred from the acceleration by which mortality rates increase over age. Such a senescence rate is generally estimated from parameters of a mathematical model fitted to these mortality rates. However, such models have limitations and underlying assumptions. Notably, they do not fit mortality rates at young and old ages. Therefore, we developed a method to calculate senescence rates from the acceleration of mortality directly without modeling the mortality rates. We applied the different methods to age group-specific mortality data from the European Renal Association-European Dialysis and Transplant Association Registry, including patients with end-stage renal disease on dialysis, who are known to suffer from increased senescence rates (n = 302,455), and patients with a functioning kidney transplant (n = 74,490). From age 20 to 70, senescence rates were comparable when calculated with or without a model. However, when using non-modeled mortality rates, senescence rates were yielded at young and old ages that remained concealed when using modeled mortality rates. At young ages senescence rates were negative, while senescence rates declined at old ages. In conclusion, the rate of senescence can be calculated directly from non-modeled mortality rates, overcoming the disadvantages of an indirect estimation based on modeled mortality rates.
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http://dx.doi.org/10.1093/gerona/glv042DOI Listing
April 2016

Incidence of renal replacement therapy for diabetic nephropathy in the Netherlands: Dutch diabetes estimates (DUDE)-3.

BMJ Open 2015 Jan 30;5(1):e005624. Epub 2015 Jan 30.

Diabetes Centre, Isala, Zwolle, The Netherlands Department of Internal Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands Department of Internal Medicine, Isala, Zwolle, The Netherlands.

Objectives: Describe the incidence, prevalence and survival of patients needing renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to diabetes mellitus (DM)-related glomerulosclerosis or nephropathy (diabetic nephropathy, DN) in the Netherlands.

Design: Using the national registry for RRT (RENINE-registry), data of all Dutch individuals initiating RRT for ESRD and having DN as primary diagnosis in the period 2000-2012 were obtained.

Setting: Observational study in the Netherlands.

Patients: Patients with ESRD needing RRT for DN.

Outcome Measurements: Age and gender adjusted incidence and prevalence of RRT for DN in the period 2000-2012. In addition, trends in time and patient's survival were examined.

Results: The prevalence of DM in the general population increased from approximately 466 000 in 2000 to 815 000 in 2011. The number of individuals who started RRT with DN as primary diagnosis was 17.4 per million population (pmp) in 2000 and 19.1 pmp in 2012, with an annual percentage change (APC) of 0.8% (95% CI -0.4 to 2.0). For RRT due to type 1 DN, the incidence decreased from 7.3 to 3.5 pmp (APC -4.8%, 95% CI -6.5 to -3.1) while it increased for type 2 DN from 10.1 to 15.6 pmp (APC 3.1%, 95% CI 1.3 to 4.8). After 2009, the prevalence of RRT for DN remained stable (APC 1.0%, 95% CI -0.4 to 2.5). Compared to the period 2000-2004, patients initiating RRT and dialysis in 2005-2009 had better survival, HRs 0.8 (95% CI 0.7 to 0.8) and 0.8 (95% CI 0.7 to 0.9), respectively, while survival after kidney transplantation remained stable, HR 0.8, 95% CI 0.5 to 1.1).

Conclusions: Over the last decade, the incidence of RRT for DN was stable, with a decrease in RRT due to type 1 DN and an increase due to type 2 DN, while survival increased.
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http://dx.doi.org/10.1136/bmjopen-2014-005624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316478PMC
January 2015

Urinary biomarkers after donor nephrectomy.

Transpl Int 2015 May 2;28(5):544-52. Epub 2015 Feb 2.

Department of Nephrology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands; Department of Nephrology, Isala Zwolle, Zwolle, The Netherlands.

As the beginning of living-donor kidney transplantation, physicians have expressed concern about the possibility that unilateral nephrectomy can be harmful to a healthy individual. To investigate whether the elevated intra-abdominal pressure (IAP) during laparoscopic donor nephrectomy causes early damage to the remaining kidney, we evaluated urine biomarkers after laparoscopic donor nephrectomy. We measured albumin and alpha-1-microglobulin (α-1-MGB) in urine samples collected during and after open and laparoscopic donor nephrectomy and laparoscopic cholecystectomy and colectomy. Additionally, kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were measured in urine samples collected during and after laparoscopic donor nephrectomy and colectomy. The same biomarkers were studied in patients randomly assigned to standard or low IAP during laparoscopic donor nephrectomy. We observed a peak in urinary albumin excretion during all procedures. Urine α-1-MGB rose in the postoperative period with a peak on the third postoperative day after donor nephrectomy. Urine α-1-MGB did not increase after laparoscopic cholecystectomy and colectomy. After laparoscopic nephrectomy, we observed slight increases in urine KIM-1 during surgery and in urine NGAL at day 2-3 after the procedure. After laparoscopic colectomy, both KIM-1 and NGAL were increased in the postoperative period. There were no differences between the high- and low-pressure procedure. Elevated urinary α-1-MGB suggests kidney damage after donor nephrectomy, occurring irrespective of IAP during the laparoscopic procedure.
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http://dx.doi.org/10.1111/tri.12523DOI Listing
May 2015

Renal replacement therapy for rare diseases affecting the kidney: an analysis of the ERA-EDTA Registry.

Nephrol Dial Transplant 2014 Sep;29 Suppl 4:iv1-8

ERA-EDTA Registry and ESPN/ERA-EDTA Registry, Department of Medical Informatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Background: In recent years, increased efforts have been undertaken to address the needs of patients with rare diseases by international initiatives and consortia devoted to rare disease research and management. However, information on the overall prevalence of rare diseases within the end-stage renal disease (ESRD) population is limited. The aims of this study were (i) to identify those rare diseases within the ERA-EDTA Registry for which renal replacement therapy (RRT) is being provided and (ii) to determine the prevalence and incidence of RRT for ESRD due to rare diseases, both overall and separately for children and adults.

Methods: The Orphanet classification of rare disease was searched for rare diseases potentially causing ESRD, and these diagnosis codes were mapped to the corresponding ERA-EDTA primary renal disease codes. Thirty-one diagnoses were defined as rare diseases causing ESRD.

Results: From 1 January 2007 to 31 December 2011, 7194 patients started RRT for a rare disease (10.6% children). While some diseases were exclusively found in adults (e.g. Fabry disease), primary oxalosis, cystinosis, congenital anomalies of the kidney and urinary tract (CAKUT) and medullary cystic kidney disease affected young patients in up to 46%. On 31 December 2011, 20 595 patients (12.4% of the total RRT population) were on RRT for ESRD caused by a rare disease. The point prevalence was 32.5 per million age-related population in children and 152.0 in adults. Only 5.8% of these patients were younger than 20 years; however, 57.7% of all children on RRT had a rare disease, compared with only 11.9% in adults. CAKUT and focal segmental glomerulosclerosis were the most prevalent rare disease entities among patients on RRT.

Conclusions: More than half of all children and one of nine adults on RRT in the ERA-EDTA Registry suffer from kidney failure due to a rare disease, potentially with a large number of additional undiagnosed or miscoded cases. Comprehensive diagnostic assessment and the application of accurate disease classification systems are essential for improving the identification and management of patients with rare kidney diseases.
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http://dx.doi.org/10.1093/ndt/gfu030DOI Listing
September 2014

15-year follow-up of a multicenter, randomized, calcineurin inhibitor withdrawal study in kidney transplantation.

Transplantation 2014 Jul;98(1):47-53

1 Department of Internal Medicine, Erasmus Medical Centre Rotterdam, The Netherlands. 2 Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands. 3 Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands. 4 Dutch Transplantation Foundation, Leiden, The Netherlands. 5 Department of Nephrology University Medical Centre, Utrecht, The Netherlands. 6 Address correspondence to: J. I. Roodnat, M.D., Ph.D., Erasmus Medical Centre, Room D427, PO box 2040, 3000CA Rotterdam, The Netherlands.

Background: Calcineurin inhibitors (CNIs) are essential immunosuppressive drugs after renal transplantation. Because of nephrotoxicity, withdrawal has been a challenge since their introduction.

Methods: A randomized multicenter trial included 212 kidney patients transplanted between 1997 and 1999. All patients were initially treated with mycophenolate mofetil (MMF), cyclosporine A (CsA), and prednisone (pred). At 6 months after transplantation, 63 patients were randomized for MMF/pred, 76 for MMF/CsA, and 73 for MMF/CsA/pred. Within 18 months after randomization 23 patients experienced a rejection episode: MMF/pred (27.0%), MMF/CsA (6.8%) and MMF/CsA/pred (1.4%) (P<0.001).

Results: During 15 years of follow-up, 73 patients died with a functioning graft, and 43 patients lost their graft. Ninety-six were alive with a functioning graft. Intention-to-treat analysis did not show a significant difference in patient and graft survival. In multivariate analysis, death-censored graft survival was significantly associated with serum creatinine at 6 months after transplantation and maximum PRA but not with the randomization group. CNI withdrawal did not result in a reduced incidence of or death by malignancy or cardiovascular disease. Death-censored graft survival was significantly worse in those patients randomized for CNI withdrawal that had to be reverted to CNI. Independent of randomization group, compared with no rejection, death-censored graft survival was significantly worse in 23 patients with acute rejection after randomization.

Conclusion: Fifteen years after conversion to a CNI free regimen, there was no benefit regarding graft and patient survival or regarding prevalence of or death by comorbidities. However, rejection shortly after CNI withdrawal was associated with decreased graft survival.
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http://dx.doi.org/10.1097/01.TP.0000442774.46133.71DOI Listing
July 2014

Survival prognosis after the start of a renal replacement therapy in the Netherlands: a retrospective cohort study.

BMC Nephrol 2013 Nov 20;14:258. Epub 2013 Nov 20.

Organ Centre, Dutch Transplant Foundation, Leiden, the Netherlands.

Background: There is no single model available to predict the long term survival for patients starting renal replacement therapy (RRT). The available models either predict survival on dialysis until transplantation, survival on the transplant waiting list, or survival after transplantation. The aim of this study was to develop a model that includes dialysis survival and survival after an eventual transplantation.

Methods: From the Dutch renal replacement registry, patients of 16 years of age or older were included if they started RRT between 1995 and 2005, still underwent RRT at baseline (90 days after the start of RRT) and were not registered at a non-renal organ transplant waiting list (N = 13868). A prediction model of 10-year patient survival after baseline was developed through multivariate Cox regression analysis, in one half of the research group. Age at start, sex, primary renal disease (PRD) and therapy at baseline were included as possible predictors. A sensitivity analysis has been performed to determine whether listing on the transplant waiting list should be added. The predictive performance of the model was internally validated. Calibration and discrimination were computed in the other half of the research group. Another sensitivity analysis was to assess whether the outcomes differed if the model was developed and tested in two geographical regions, which were less similar than the original development and validation group. No external validation has been performed.

Results: Survival probabilities were influenced by age, sex, PRD and therapy at baseline (p < 0.001). The calibration and discrimination both showed very reasonable results for the prediction model (C-index = 0.720 and calibration slope for the prognostic index = 1.025, for the 10 year survival). Adding registration on the waiting list for renal transplantation as a predictor did not improve the discriminative power of the model and was therefore not included in the model.

Conclusions: With the presented prediction model, it is possible to give a reasonably accurate estimation on the survival chances of patients who start with RRT, using a limited set of easily available data.
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http://dx.doi.org/10.1186/1471-2369-14-258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225578PMC
November 2013

Severe fatigue after kidney transplantation: a highly prevalent, disabling and multifactorial symptom.

Transpl Int 2013 Oct 17;26(10):1007-15. Epub 2013 Aug 17.

Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Department of Health Sciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Fatigue is a common symptom of patients with chronic kidney disease, but seldom investigated after transplantation. We determined the prevalence, impact and related factors of severe fatigue in kidney transplant recipients (KTRs). Medical records and questionnaires were used to assess kidney function, donor characteristics, fatigue (Checklist Individual Strength), functional impairments (Sickness Impact Profile), work status, body mass index (BMI), pain, depressive symptoms, social support and sleeping problems in 180 participating KTRs. KTRs were compared with sex- and age-matched population-based controls. KTRs were significantly more often severely fatigued (39%) compared to matched controls (22%; P = 0.001). Severely fatigued KTRs had significantly more functional impairments than nonseverely fatigued recipients (effect size ≥ 0.7) P < 0.001, and less often a paid job (27% vs. 48%, P = 0.005). Univariate analysis showed that severely fatigued KTRs received more often a kidney from a deceased donor, had a higher BMI, more pain, discrepancy in social support, depressive symptoms and sleeping problems. In a multivariate analysis (n = 151) the latter two associations remained significant. Severe fatigue is a highly prevalent and disabling symptom in KTRs. Moreover, severe fatigue after kidney transplantation is more strongly related to behavioural and psychosocial factors than specific transplantation-related factors. Findings have implications for fatigue management.
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http://dx.doi.org/10.1111/tri.12166DOI Listing
October 2013

Effect of a single intraoperative high-dose ATG-Fresenius on delayed graft function in donation after cardiac-death donor renal allograft recipients: a randomized study.

Exp Clin Transplant 2013 Apr 22;11(2):134-41. Epub 2013 Feb 22.

Department of Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Objectives: Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess.

Patients And Methods: We performed a randomized study to evaluate the effect of a single intraoperative high-dose of anti-T-lymphocyte immunoglobulin (ATG)-Fresenius (9 mg/kg body weight) on the incidence of delayed graft function. Eligible adult recipients of a first donation after cardiac death donor renal allograft were randomly assigned to ATG-Fresenius or no induction therapy. Maintenance immunosuppression consisted of tacrolimus, in an unadjusted dose, mycophenolate mofetil, and steroids.

Results: The study was prematurely terminated because of a lower-than-anticipated inclusion rate. Baseline characteristics were comparable in the ATG-Fresenius group (n=28) and the control group (n=24). Twenty-two patients in the ATG-Fresenius group (79%) had delayed graft function, compared with 13 in the control group (54%; P = .06). Allograft and patient survival were comparable in both groups. Serious adverse events occurred more frequently in the ATG-Fresenius group than they did in the control group (57% vs 29%; P < .05).

Conclusions: Intraoperative administration of a single high-dose of ATG-Fresenius in donation after cardiac death donor renal allograft recipients, followed by triple immunosuppression with an unadjusted tacrolimus dose, seems ineffective to reduce the incidence of delayed graft function. Moreover, this was associated with a higher rate of serious adverse events (EudraCT-number, 2007-000210-36.).
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http://dx.doi.org/10.6002/ect.2012.0220DOI Listing
April 2013

Two-year randomized controlled prospective trial converting treatment of stable renal transplant recipients with cutaneous invasive squamous cell carcinomas to sirolimus.

J Clin Oncol 2013 Apr 28;31(10):1317-23. Epub 2013 Jan 28.

Nijmegen Medical Center, Radboud University, Nijmegen, the Netherlands.

Purpose: In light of the significant morbidity and mortality of cutaneous invasive squamous cell carcinomas (SCCs) in renal transplant recipients, we investigated whether conversion to sirolimus-based immunosuppression from standard immunosuppression could diminish the recurrence rate of these skin cancers.

Patients And Methods: In a 2-year randomized controlled trial, 155 renal transplant recipients with at least one biopsy-confirmed SCC were stratified according to age (< 55 v ≥ 55 years) and number of previous SCCs (one to nine v ≥ 10) and randomly assigned to conversion to sirolimus (n = 74) or continuation of their original immunosuppression (n = 81). Development of a new SCC within 2 years after random assignment was the primary end point.

Results: After 2 years of follow-up, the risk reduction of new SCCs in the multivariable analysis was not significant, with a hazard ratio (HR) of 0.76 (95% CI, 0.48 to 1.2; P = .255), compared with a non-sirolimus-based regimen. After the first year, there was a significant 50% risk reduction, with an HR of 0.50 (95% CI, 0.28 to 0.90; P = .021) for all patients together and an HR of 0.11 (95% CI, 0.01 to 0.94; P = .044) for patients with only one previous SCC. The tumor burden of SCC was reduced during the 2-year follow-up period in those receiving sirolimus (0.82 v 1.38 per year; HR, 0.51; 95% CI, 0.32 to 0.82; P = .006) if adjusted for the number of previous SCCs and age. Twenty-nine patients stopped taking sirolimus because of various adverse events.

Conclusion: Conversion to sirolimus-based immunosuppression failed to show a benefit in terms of SCC-free survival at 2 years.
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http://dx.doi.org/10.1200/JCO.2012.45.6376DOI Listing
April 2013

Outcomes of male patients with Alport syndrome undergoing renal replacement therapy.

Clin J Am Soc Nephrol 2012 Dec 20;7(12):1969-76. Epub 2012 Sep 20.

Dept Nephrology&Rheumatology, University Medical Center Göttingen, Göttingen, Germany.

Background And Objectives: Patients with the hereditary disease Alport syndrome commonly require renal replacement therapy (RRT) in the second or third decade of life. This study compared age at onset of RRT, renal allograft, and patient survival in men with Alport syndrome receiving various forms of RRT (peritoneal dialysis, hemodialysis, or transplantation) with those of men with other renal diseases.

Design, Setting, Participants, & Measurements: Patients with Alport syndrome receiving RRT identified from 14 registries in Europe were matched to patients with other renal diseases. A linear spline model was used to detect changes in the age at start of RRT over time. Kaplan-Meier method and Cox regression analysis were used to examine patient and graft survival.

Results: Age at start of RRT among patients with Alport syndrome remained stable during the 1990s but increased by 6 years between 2000-2004 and 2005-2009. Survival of patients with Alport syndrome requiring dialysis or transplantation did not change between 1990 and 2009. However, patients with Alport syndrome had better renal graft and patient survival than matched controls. Numbers of living-donor transplantations were lower in patients with Alport syndrome than in matched controls.

Conclusions: These data suggest that kidney failure in patients with Alport syndrome is now being delayed compared with previous decades. These patients appear to have superior patient survival while undergoing dialysis and superior patient and graft survival after deceased-donor kidney transplantation compared with patients receiving RRT because of other causes of kidney failure.
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http://dx.doi.org/10.2215/CJN.02190312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513741PMC
December 2012

Imprecise definitions of starting points in retrospectively reviewing potential organ donors causes confusion: call for a reproducible method like 'imminent brain death'.

Transpl Int 2012 Aug 30;25(8):830-7. Epub 2012 May 30.

Dutch Transplant Foundation, Leiden, The Netherlands.

Low donor supply and the high demand for transplantable organs is an international problem. The efficiency of organ procurement is often expressed by donor conversion rates (DCRs). These rates differ among countries, but a uniform starting point for defining a potential heart-beating donor is lacking. Imprecise definitions cause confusion; therefore, we call for a reproducible method like imminent brain death (IBD), which contains criteria in detail to determine potential heart-beating donors. Medical charts of 4814 patients who died on an ICU in Dutch university hospitals between January 2007 and December 2009 were reviewed for potential heart-beating donors. We compared two starting points: 'Severe Brain Damage' (SBD) (old definition) and IBD (new definition), which differ in the number of absent brainstem reflexes. Of the potential donors defined by IBD 45.6% fulfilled the formal brain death criteria, compared with 33.6% in the larger SBD group. This results in a higher DCR in the IBD group (40% vs. 29.5%). We illustrated important differences in DCRs when using two different definitions, even within one country. To allow comparison among countries and hospitals, one universal definition of a potential heart-beating donor should be used. Therefore, we propose the use of IBD.
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http://dx.doi.org/10.1111/j.1432-2277.2012.01505.xDOI Listing
August 2012

[Causes of decreased use of peritoneal dialysis as a kidney replacement therapy in the Netherlands].

Ned Tijdschr Geneeskd 2012 ;156(21):A3871

Nederlandse Transplantatie Stichting, afd. Orgaancentrum, Leiden.

Objective: To study the extent and causes of the declining use of peritoneal dialysis (PD) as kidney replacement therapy in patients with end-stage renal disease in the Netherlands.

Design: Retrospective cohort study.

Method: The prevalence and incidence of various kidney replacement therapies in the Netherlands from 1995 to 2010 were analysed. Also the 5-year outflow of patients on PD or haemodialysis (HD) from 1995 to 2006 was analysed using the cumulative incidence competing risks method and Cox regression analysis.

Results: The absolute number of patients starting PD between 1995 and 2008 was stable at about 400 per year. There was a relative decline in the use of PD in the total dialysis population from 15% in 1995 to 8% in 2010. This decrease was seen in both large and small centres and was related to a relative increase in the numbers undergoing HD (67% before 2001, 74% in 2009), and kidney transplantation before dialysis (3% before 2002, 9% in 2009), as well as a decrease in change of therapy from HD to PD. The increased number starting on HD was associated with the growth of the incident patient group aged 65 years or older, most of whom (80-85%) underwent HD. Within the younger group (0-65 years) there was an increase in numbers on HD and in the number of pre-emptive transplantations.

Conclusion: The decline in the prevalence of PD was partly explained by the relative increase in numbers starting HD, associated with an ageing patient population, fewer people changing from HD to PD therapy, and the increased number of kidney transplantations before dialysis in younger patients. The increasing prevalence of HD has been made possible by growth of the HD capacity.
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July 2012

Anti-T-cell antibodies for the treatment of acute rejection after renal transplantation.

Expert Opin Biol Ther 2012 Aug 15;12(8):1031-42. Epub 2012 May 15.

Radboud University Nijmegen Medical Centre, Department of Nephrology, Nijmegen, The Netherlands.

Introduction: Given the central role of T cells in the alloimmune response, anti-T-cell antibodies retain a prominent place in the treatment of renal allograft rejection. During the past decades, many anti-T-cell antibodies have emerged and subsequently left the field of solid organ transplantation, but rabbit-antithymocyte globulin (ATG) and the humanized anti-CD52 monoclonal rat antibody alemtuzumab have remained.

Areas Covered: This article reviews the literature about the use of ATG and alemtuzumab for the treatment of acute rejection after renal transplantation. Furthermore, it discusses possible side effects, including infusion reactions. A literature search using PubMed and Embase databases was undertaken using search words alemtuzumab, antithymocyte globulin, rejection, kidney and renal transplantation.

Expert Opinion: Treatment of severe or steroid-resistant renal allograft rejections with ATG is very effective, but is also associated with frequent infusion reactions and an increased incidence of infections and posttransplant lymphoproliferative disease. Alemtuzumab may prove to be an attractive alternative. It can be administered easily, is relatively cheap and nearly devoid of acute side effects, but the long-term efficacy and safety as anti-rejection treatment are currently difficult to judge. The increasing knowledge about lymphocyte subsets and their plasticity will drive the development of new, specific immunosuppression that lacks side effects of ATG and alemtuzumab. TOL101, a monoclonal antibody specifically directed against the human αβ T cell receptor, might be of potential value.
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http://dx.doi.org/10.1517/14712598.2012.689278DOI Listing
August 2012

Time trend in access to the waiting list and renal transplantation: a comparison of four European countries.

Nephrol Dial Transplant 2012 Sep 3;27(9):3621-31. Epub 2012 May 3.

ERA–EDTA Registry, Department of Medical Informatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Background: To examine the time trend and international differences in access to the waiting list and renal transplantation of patients with end-stage kidney disease.

Methods: We included all patients (n = 30 961) from Austria, Norway, the Netherlands and Scotland who started renal replacement therapy (RRT) between 1995 and 2003 with their kidney transplant waiting list data (until 31 December 2005) and follow-up data on RRT and mortality (until 31 December 2007). The outcome measure was access to the waiting list within 2 years and to a first renal transplant within 4 years from the start of RRT, expressed as incidence per million age-related population (p.m.a.r.p.) per year. To estimate trends over time, mean percentage annual change (MPAC) and 95% confidence interval (CI) were calculated.

Results: In each country, the number of patients starting RRT > 65 years increased significantly over time, whereas the number of renal transplants did not increase to the same extent. Only in Norway were almost all patients on the waiting list transplanted within 4 years of RRT start if they were < 65 years. In patients who started RRT > 65 years, the access to renal transplantation was high in Norway (49 p.m.a.r.p.) and low in Austria ( < 26 p.m.a.r.p.), the Netherlands and Scotland (both < 10 p.m.a.r.p.) but increased significantly in Austria (MPAC = 9.8%; 95% CI = 3.9-16.9) and the Netherlands (MPAC = 9.0%; 95% CI = 3.2-15.0).

Conclusion: Only in Norway, virtually all patients on the waiting list < 65 years received a transplant within 4 years after the start of RRT and, remarkably, also most of those > 65 years of age.
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http://dx.doi.org/10.1093/ndt/gfs089DOI Listing
September 2012

Anogenital malignancies in women after renal transplantation over 40 years in a single center.

Transplantation 2012 May;93(9):914-22

Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Background: Renal transplant recipients have an increased risk to develop human papillomavirus (HPV)-related anogenital malignancies. A clinical overview of female anogenital posttransplantation malignancies and possible multifocal premalignancies over a period of 40 years renal transplantation is presented. Additionally, the genotype-specific prevalence of HPV in these (pre)malignancies was investigated.

Methods: Data of 1023 women, who underwent a renal transplantation between 1968 and 2008, were collected. Clinical data of all female renal transplant recipients who developed anogenital malignancies were retrospectively analyzed. The histology, cytology, and distribution of genotype-specific HPV infections were analyzed in all primary anogenital tumors and possible (multifocal) premalignancies.

Results: Sixteen anogenital malignancies (1.6%) were found: vulva (n=6), cervix (n=5), and anus (n=5). Twelve of 16 patients never had a cervical smear before transplantation. The median interval between transplantation and diagnosis of malignancy was 136 months (range, 16-288 months). High-risk HPV was detected in 91.7% of investigated lesions, HPV subtype 16 predominated (54.5%). Four of seven patients with two distinct anogenital lesions had different HPV types in the lesions.

Conclusions: A high number of anogenital malignancies developed in our cohort, which are nearly all caused by HPV. Multifocal lesions within one patient frequently contained different high-risk HPV genotypes in both lesions. Our results underline the importance of anogenital screening and monitoring before and periodically after renal transplantation to prevent morbidity and mortality from anogenital malignancies.
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http://dx.doi.org/10.1097/TP.0b013e318249b13dDOI Listing
May 2012
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