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Background and objectives: A genetic cause can be identified for an increasing number of pediatric and adult-onset kidney diseases. Preimplantation genetic testing (formerly known as preimplantation genetic diagnostics) is a reproductive technology that helps prospective parents to prevent passing on (a) disease-causing mutation(s) to their offspring. Here, we provide a clinical overview of 25 years of preimplantation genetic testing for monogenic kidney disease in The Netherlands.Design, setting, participants, & measurements: This is a retrospective cohort study of couples counseled on preimplantation genetic testing for monogenic kidney disease in the national preimplantation genetic testing expert center (Maastricht University Medical Center+) from January 1995 to June 2019. Statistical analysis was performed through chi-squared tests.Results: In total, 98 couples were counseled regarding preimplantation genetic testing, of whom 53% opted for preimplantation genetic testing. The most frequent indications for referral were autosomal dominant polycystic kidney disease (38%), Alport syndrome (26%), and autosomal recessive polycystic kidney disease (9%). Of couples with at least one preimplantation genetic testing cycle with oocyte retrieval, 65% experienced one or more live births of an unaffected child. Of couples counseled, 38% declined preimplantation genetic testing for various personal and technical reasons.Conclusions: Referrals, including for adult-onset disease, have increased steadily over the past decade. Though some couples decline preimplantation genetic testing, in the couples who proceed with at least one preimplantation genetic testing cycle, almost two thirds experienced at least one live birth rate.

Supplemental Digital Content is available in the text., Background. The incidence of pregnancy in kidney transplantation (KT) recipients is increasing. Studies report that the incidence of graft loss (GL) during pregnancy is low, but less data are available on long-term effects of pregnancy on the graft. Methods. Therefore, we performed a meta-analysis and systematic review on GL and graft function, measured by serum creatinine (SCr), after pregnancy in KT recipients, stratified in years postpartum. Furthermore, we included studies of nulliparous KT recipients. Results. Our search yielded 38 studies on GL and 18 studies on SCr. The pooled incidence of GL was 9.4% within 2 years after pregnancy, 9.2% within 2–5 years, 22.3% within 5–10 years, and 38.5% >10 years postpartum. In addition, our data show that, in case of graft survival, SCr remains stable over the years. Only within 2 years postpartum, Δ SCr was marginally higher (0.18 mg/dL, 95%CI [0.05-0.32], P = 0.01). Furthermore, no differences in GL were observed in 10 studies comparing GL after pregnancy with nulliparous controls. Systematic review of the literature showed that mainly prepregnancy proteinuria, hypertension, and high SCr are risk factors for GL. Conclusions. Overall, these data show that pregnancy after KT has no effect on long-term graft survival and only a possible effect on graft function within 2 years postpartum. This might be due to publication bias. No significant differences were observed between pre- and postpartum SCr at longer follow-up intervals.

Contains fulltext : 245148.pdf (Publisher’s version ) (Open Access) Kidney transplant candidates are blood group incompatible with roughly one out of three potential living donors. We compared outcomes after ABO-incompatible (ABOi) kidney transplantation with matched ABO-compatible (ABOc) living and deceased donor transplantation and analyzed different induction regimens. We performed a retrospective study with propensity matching and compared patient and death-censored graft survival after ABOi versus ABOc living donor and deceased donor kidney transplantation in a nationwide registry from 2006 till 2019. 296 ABOi were compared with 1184 center and propensity-matched ABOc living donor and 1184 deceased donor recipients (matching: recipient age, sex, blood group, and PRA). Patient survival was better compared with deceased donor [hazard ratio (HR) for death of HR 0.69 (0.49-0.96)] and non-significantly different from ABOc living donor recipients [HR 1.28 (0.90-1.81)]. Rate of graft failure was higher compared with ABOc living donor transplantation [HR 2.63 (1.72-4.01)]. Rejection occurred in 47% of 140 rituximab versus 22% of 50 rituximab/basiliximab, and 4% of 92 alemtuzumab-treated recipients (P

Background Orthodontic treatment can successfully align pathologically migrated teeth and lead to improvement of periodontal stability in patients with periodontitis. Periodontic-orthodontic approaches have gained increasing attention in the past years. Here, we investigated the interest of adults affected by chronic periodontitis in undergoing orthodontic treatment as well as patient-related and tooth-related influence factors. Methods Periodontal and orthodontic measurements/indices were taken from 115 adult patients with moderate-to-severe periodontitis. The study participants answered a questionnaire investigating patient demographics, quality of life aspects, and their interest in undergoing orthodontic treatment. Correlations between clinical data, questionnaire responses, and this interest were analyzed by means of an age- and sex-adjusted multiple regression model. Results Two-thirds of the participants were interested in orthodontic therapy and indicated long-term healthy and esthetically appealing teeth as their main motives. A significant correlation was found between subjectively felt impaired dental esthetics and an interest in orthodontic treatment. However, there were no correlations with the severity of periodontitis, tooth alignment, or patient demographics, including sex. Older patients were significantly more often interested in orthodontic treatment. Most participants had never been provided with information about orthodontic treatment options for adults. Conclusions A considerable number of adult patients with periodontitis were interested in orthodontics to improve tooth alignment. However, severity of periodontitis and tooth misalignment or demographic factors may not be indicative thereof. Therefore, dental practitioners need to be aware of patients wishing to align their teeth and to provide them with the relevant information and, if appropriate, enable interdisciplinary treatment planning.

Item does not contain fulltext BACKGROUND: Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs. METHODS: To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples. Anti-HLA antibodies were detected with a Luminex single-antigen bead assay. RESULTS: Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pre-transplant DSAs had a significantly lower 10-year death-censored graft survival (55% versus 82%, P=0.0001). We identified 192 pairs with one recipient as nDSA positive (against Class I and/or II) and the other without anti-HLA antibodies. For the patients with nDSAs against either Class I or II, graft survival did not significantly differ compared with patients without anti-HLA antibodies (74% versus 77%, P = 0.79). Only in patients with both nDSAs Class I and II was there a trend towards a lower graft survival (58%, P = 0.06). Lastly, in a small group of 42 recipient pairs, 10-year graft survival in recipients with DSAs was 49% compared with 68% in recipients with nDSAs (P=0.11). CONCLUSION: This paired kidney analysis confirms that the presence of pre-transplant DSAs in deceased donor transplantations is a risk marker for graft loss, whereas nDSAs in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSAs against Class I and II, nDSAs may be a risk marker for graft loss in the long term.

Background and Aims Genetic testing in patients with suspected hereditary kidney disease does not always reveal the genetic cause for the patient's disorder. Potentially pathogenic variants can reside in genes that are not known to be involved in kidney disease, which makes it difficult to prioritize and interpret the relevance of these variants. As such, there is a clear need for methods that predict the phenotypic consequences of gene expression in a way that is as unbiased as possible. To help identify candidate genes we have developed KidneyNetwork, in which tissue-specific expression is utilized to predict kidney-specific gene functions. Method We combined gene co-expression in 878 publicly available kidney RNA-sequencing samples with the co-expression of a multi-tissue RNA-sequencing dataset of 31,499 samples to build KidneyNetwork. The expression patterns were used to predict which genes have a kidney-related function, and which (disease) phenotypes might be caused when these genes are mutated. By integrating the information from the HPO database, in which known phenotypic consequences of disease genes are annotated, with the gene co-expression network we obtained prediction scores for each gene per HPO term. As proof of principle, we applied KidneyNetwork to prioritize variants in exome-sequencing data from 13 kidney disease patients without a genetic diagnosis. Results We assessed the prediction performance of KidneyNetwork by comparing it to GeneNetwork, a multi-tissue co-expression network we previously developed. In KidneyNetwork, we observe a significantly improved prediction accuracy of kidney-related HPO-terms, as well as an increase in the total number of significantly predicted kidney-related HPO-terms (figure 1). To examine its clinical utility, we applied KidneyNetwork to 13 patients with a suspected hereditary kidney disease without a genetic diagnosis. Based on the HPO terms “Renal cyst” and “Hepatic cysts”, combined with a list of potentially damaging variants in one of the undiagnosed patients with mild ADPKD/PCLD, we identified ALG6 as a new candidate gene. ALG6 bears a high resemblance to other genes implicated in this phenotype in recent years. Through the 100,000 Genomes Project and collaborators we identified three additional patients with kidney and/or liver cysts carrying a suspected deleterious variant in ALG6. Conclusion We present KidneyNetwork, a kidney specific co-expression network that accurately predicts what genes have kidney-specific functions and may result in kidney disease. Gene-phenotype associations of genes unknown for kidney-related phenotypes can be predicted by KidneyNetwork. We show the added value of KidneyNetwork by applying it to exome sequencing data of kidney disease patients without a molecular diagnosis and consequently we propose ALG6 as a promising candidate gene. KidneyNetwork can be applied to clinically unsolved kidney disease cases, but it can also be used by researchers to gain insight into individual genes to better understand kidney physiology and pathophysiology. Acknowledgments This research was made possible through access to the data and findings generated by the 100,000 Genomes Project; http://www.genomicsengland.co.uk.

BackgroundGenetic testing in patients with suspected hereditary kidney disease may not reveal the genetic cause for the disorder as potentially pathogenic variants can reside in genes that are not yet known to be involved in kidney disease. To help identify these genes, we have developed KidneyNetwork, that utilizes tissue-specific expression to predict kidney-specific gene functions.MethodsKidneyNetwork is a co-expression network built upon a combination of 878 kidney RNA-sequencing samples and a multi-tissue dataset of 31,499 samples. It uses expression patterns to predict which genes have a kidney-related function and which (disease) phenotypes might result from variants in these genes. We applied KidneyNetwork to prioritize rare variants in exome sequencing data from 13 kidney disease patients without a genetic diagnosis.ResultsKidneyNetwork can accurately predict kidney-specific gene functions and (kidney disease) phenotypes for disease-associated genes. Applying it to exome sequencing data of kidney disease patients allowed us to identify a promising candidate gene for kidney and liver cysts: ALG6.ConclusionWe present KidneyNetwork, a kidney-specific co-expression network that accurately predicts which genes have kidney-specific functions and can result in kidney disease. We show the added value of KidneyNetwork by applying it to kidney disease patients without a molecular diagnosis and consequently, we propose ALG6 as candidate gene in one of these patients. KidneyNetwork can be applied to clinically unsolved kidney disease cases, but it can also be used by researchers to gain insight into individual genes in order to better understand kidney physiology and pathophysiology.Significance statementGenetic testing in patients with suspected hereditary kidney disease may not reveal the genetic cause for the patient’s disorder. Potentially pathogenic variants can reside in genes not yet known to be involved in kidney disease, making it difficult to interpret the relevance of these variants. This reveals a clear need for methods to predict the phenotypic consequences of genetic variation in an unbiased manner. Here we describe KidneyNetwork, a tool that utilizes tissue-specific expression to predict kidney-specific gene functions. Applying KidneyNetwork to a group of undiagnosed cases identified ALG6 as a candidate gene in cystic kidney and liver disease. In summary, KidneyNetwork can aid the interpretation of genetic variants and can therefore be of value in translational nephrogenetics and help improve the diagnostic yield in kidney disease patients.

IntroductionCardiovascular disease is the leading cause of death in end-stage renal disease (ESRD) and is strongly associated with vascular calcification. An important driver of vascular calcification is high phosphate levels, but these become lower when patients initiate nocturnal hemodialysis or receive a kidney transplant. However, it is unknown whether nocturnal hemodialysis or kidney transplantation mitigate vascular calcification. Therefore, we compared progression of coronary artery calcification (CAC) between patients treated with conventional hemodialysis, nocturnal hemodialysis, and kidney transplant recipients.MethodsWe measured CAC annually up to 3 years in 114 patients with ESRD that were transplantation candidates: 32 that continued conventional hemodialysis, 34 that initiated nocturnal hemodialysis (≥4x 8 hours/week), and 48 that received a kidney transplant. We compared CAC progression between groups as the difference in square root transformed volume scores per year (ΔCAC SQRV) using linear mixed models. Reference category was conventional hemodialysis.ResultsThe mean age of the study population was 53 ±13 years, 75 (66%) were male, and median dialysis duration was 28 (IQR 12–56) months. Median CAC score at enrollment was 171 (IQR 10–647), which did not differ significantly between treatment groups (P = 0.83). Compared to conventional hemodialysis, CAC progression was non-significantly different in nocturnal hemodialysis -0.10 (95% CI -0.77 to 0.57) and kidney transplantation -0.33 (95% CI -0.96 to 0.29) in adjusted models.ConclusionsNocturnal hemodialysis and kidney transplantation are not associated with significantly less CAC progression compared to conventional hemodialysis during up to 3 years follow-up. Further studies are needed to confirm these findings, to determine which type of calcification is measured with CAC in end-stage renal disease, and whether that reflects cardiovascular risk.

Background and Aims Due to the fast-paced developments in human genetics, a genetic cause can now be identified for an increasing number of pediatric and adult-onset kidney diseases. A monogenic kidney disease (MKD) can impact prognostication and therapy decisions. It also provides patients with options regarding family planning such as preimplantation genetic testing (PGT), a reproductive technology that helps prospective parents prevent passing on a disease-causing mutation to their offspring. There are limited reports on PGT for MKD and most are focused on severe pediatric-onset diseases. The Dutch system of insurance reimbursement and nationwide regulation is unique, and it has allowed the Netherlands to be one of a handful of countries where couples have the option to choose PGT for MKD, including adult-onset forms of kidney disease. Here we provide the 25-year Dutch experience with PGT for MKD. Method We performed a retrospective cohort study of all couples counselled on PGT for MKD in the Maastricht University Medical Center+, the expert centre where all Dutch single cell genetic testing on embryos is performed, from January 1995 until June 2019. Results 99 couples were counseled for PGT, of which currently 15% is waiting for the genetic test to be validated. In the early years of PGT for MKD, referrals were incidental and only for couples at risk for offspring with paediatric-onset disease. From 2009 onwards, the number of referrals has steadily increased as has the number of couples referred for adult-onset MKD. Overall, the most frequent indications for referral for PGT were ADPKD (37%), X-linked Alport syndrome (25%) and ARPKD (9%). After counselling, 36% of n=99 couples started PGT treatment. In total n=80 cycles with oocyte retrieval were performed (median 2 cycles [range 1-4]). These cycles led to a median of n=10 embryos (range 2-31) suitable for biopsy and a median of n=3 embryos (range 1-14) being genetically unaffected. Seventy-five percent (n=) of couples achieved at least one live birth. Of n=99, 48% did not proceed with PGT, for various personal and technical reasons. Major reasons for opting out of PGT were that prospective parents did not want to wait for the lengthy PGT procedure (9%) or had a wish for natural conception with prenatal genetic testing (11%). Live birth rate was 40% (n=19) in the non-PGT group, with notably a similar duration to a live birth as the PGT group (2 years, range 0-5 years). Conclusion We provide the largest overview to date of the indications, uptake and results of PGT for MKD. Referrals for PGT, including adult-onset disease, have increased steadily over the past decade. PGT has favorable outcomes, with 75% of couples having at least one live birth, though this is likely due to our small sample size. Genetic and reproductive counseling, including information on PGT, should be provided to all patients and prospective parents from families with MKD to enable informed decision making.

Background:Thanks to the advances in care, pregnancy is now attainable for the majority of young female CKD patients, although it is still a high-risk endeavor. Clinical decision-making in these cases is impacted by a myriad of factors, making (pre)pregnancy counseling a complex process. The complexities, further impacted by limited data and unknown risks regarding outcome, can cause discussions when deciding on the best care for a specific patient. Objectives:In this article, we provide an overview of the considerations and dilemmas we encounter in preconception counseling and offer our perspective on how to deal with them in daily clinical practice. Methods:The main topics we discuss in our counseling are (1) the high risk of pregnancy complications, (2) the risk of permanent CKD deterioration due to pregnancy and subsequent decreased life expectancy, (3) appropriate changes in renal medication, and (4) assisted reproduction, genetic testing, and prenatal or preimplantation genetic diagnostics. Results and Conclusions:In our clinic, we openly address moral dilemmas arising in clinical practice in pregnancy and CKD, both within the physician team and with the patient. We do this by ensuring an interpretive physician-patient interaction and shared decision-making, deliberating in a multidisciplinary setting and, if needed, with input from an expert committee.

The clinical significance of non‐HLA antibodies on renal allograft survival is a matter of debate, due to differences in reported results and lack of large‐scale studies incorporating analysis of multiple non‐HLA antibodies simultaneously. We developed a multiplex non‐HLA antibody assay against 14 proteins highly expressed in the kidney. In this study, the presence of pretransplant non‐HLA antibodies was correlated to renal allograft survival in a nationwide cohort of 4770 recipients transplanted between 1995 and 2006. Autoantibodies against Rho GDP‐dissociation inhibitor 2 (ARHGDIB) were significantly associated with graft loss in recipients transplanted with a deceased‐donor kidney (N = 3276) but not in recipients of a living‐donor kidney (N = 1496). At 10 years after deceased‐donor transplantation, recipients with anti‐ARHGDIB antibodies (94/3276 = 2.9%) had a 13% lower death‐censored covariate‐adjusted graft survival compared to the anti‐ARHGDIB‐negative (3182/3276 = 97.1%) population (hazard ratio 1.82; 95% confidence interval, 1.32‐2.53; P = .0003). These antibodies occur independently from donor‐specific anti‐HLA antibodies (DSA) or other non‐HLA antibodies investigated. No significant relations with graft loss were found for the other 13 non‐HLA antibodies. We suggest that pretransplant risk assessment can be improved by measuring anti‐ARHGDIB antibodies in all patients awaiting deceased‐donor transplantation., From a multicenter evaluation of kidney transplants, the authors report that the pretransplant presence of autoantibodies against ARHGDIB are associated with long‐term graft loss in recipients transplanted with a deceased donor kidney, independent from donor‐specific HLA antibodies.

Background 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.Methods 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.Results 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; P=0.93). Patients without DSA had a 10-year graft survival of 78%.Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.

Background: Vascular calcification is seen in most patients on dialysis and is strongly associated with cardiovascular mortality. Vascular calcification is promoted by phosphate, which generally reaches higher levels in hemodialysis than in peritoneal dialysis. However, whether vascular calcification develops less in peritoneal dialysis than in hemodialysis is currently unknown. Therefore, we compared coronary artery calcification (CAC), its progression, and calcification biomarkers between patients on hemodialysis and peritoneal dialysis. Methods: We measured CAC in 134 patients who had been treated exclusively with hemodialysis (n = 94) or peritoneal dialysis (n = 40) and were transplantation candidates. In 57 of them (34 on hemodialysis and 23 on peritoneal dialysis), we also measured CAC progression annually up to 3 years and the inactive species of desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), fetuin-A, osteoprotegerin. We compared CAC cross-sectionally with Tobit regression. CAC progression was compared in 2 ways: with linear mixed models as the difference in square root transformed volume score per year (ΔCAC SQRV) and with Tobit mixed models. We adjusted for potential confounders. Results: In the cross-sectional cohort, CAC volume scores were 92 mm3 in hemodialysis and 492 mm3 in peritoneal dialysis (adjusted difference 436 mm3; 95% CI –47 to 919; p = 0.08). In the longitudinal cohort, peritoneal dialysis was associated with significantly more CAC progression defined as ΔCAC SQRV (adjusted difference 1.20; 95% CI 0.09 to 2.31; p = 0.03), but not with Tobit mixed models (adjusted difference in CAC score increase per year 106 mm3; 95% CI –140 to 352; p = 0.40). Peritoneal dialysis was associated with higher osteoprotegerin (adjusted p = 0.02) but not with dp-ucMGP or fetuin-A. Conclusions: Peritoneal dialysis is not associated with less CAC or CAC progression than hemodialysis, and perhaps with even more progression. This indicates that vascular calcification does not develop less in peritoneal dialysis than in hemodialysis.

Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long‐term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995‐2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6‐month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA‐B plus 1 HLA‐DR, or 2 HLA‐DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low‐risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals., The authors show that kidney allocation to highly sensitized patients based on proven acceptable HLA antigens results in a significantly lower incidence of rejection episodes when compared to allocation based on the avoidance of unacceptable HLA antigens only.

Supplemental Digital Content is available in the text., 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.

Background Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based on historical data, it was not possible to account for the presence of pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker for impaired graft survival. The aim of this study was to evaluate to what extent frequently used initial immunosuppressive therapies increase graft survival in immunological low-risk patients. Methods We performed an analysis on the PROCARE cohort, a Dutch multicentre study including all transplantations performed in the Netherlands between 1995 and 2005 with available pretransplant serum (n = 4724). All sera were assessed for the presence of DSA by a luminex single-antigen bead assay. Patients with a previous kidney transplantation, pretransplant DSA or receiving induction therapy were excluded from the analysis. Results Three regimes were used in over 200 patients: cyclosporine (CsA)/prednisolone (Pred) (n = 542), CsA/mycophenolate mofetil (MMF)/Pred (n = 857) and tacrolimus (TAC)/MMF/Pred (n = 811). Covariate-adjusted analysis revealed no significant differences in 10-year death-censored graft survival between patients on TAC/MMF/Pred therapy (79%) compared with patients on CsA/MMF/Pred (82%, P = 0.88) or CsA/Pred (79%, P = 0.21). However, 1-year rejection-free survival censored for death and failure unrelated to rejection was significantly higher for TAC/MMF/Pred (81%) when compared with CsA/MMF/Pred (67%, P Conclusion These results suggest that in immunological low-risk patients excellent long-term kidney graft survival can be achieved irrespective of the type of initial immunosuppressive therapy (CsA or TAC; with or without MMF), despite differences in 1-year rejection-free survival.