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In this retrospective registry analysis of kidney transplants, maintenance steroid dose shows a significant association with death due to infection or cardiovascular disease even in patients with good graft outcome in whom steroid treatment would appear to be unnecessary.

Death with a functioning graft remains a major challenge following kidney transplantation. Steroid dosing may be a modifiable risk factor. Collaborative Transplant Study (CTS) data were analyzed to assess the relationship between long-term steroid dose and death with function during years 2–5 posttransplant in 41 953 adult recipients of a deceased-donor kidney transplant during 1995–2010. Steroid dose at year 1 correlated significantly with death with function overall, and with death due to cardiovascular disease or infection (all p < 0.001). In patients with optimal graft function (serum creatinine <130 µmol/L) and no anti-rejection treatment during (a) year 1 (b) years 1 and 2, these significant associations remained (all p < 0.001). The center-specific incidence of steroid withdrawal during year 2 showed a significant inverse association with death due to cardiovascular disease (p < 0.001) or infection (p < 0.001) overall, and within the subpopulation with good graft function and no rejection during year 1 (p = 0.002 and p < 0.001, respectively). Maintenance steroid dose shows a highly significant association with death with a functioning graft caused by cardiovascular disease or infection during years 2–5 after kidney transplantation, even in patients with good graft outcomes in whom steroid treatment would appear to be unnecessary.

Natural killer (NK) cell function can be modulated by the killer cell immunoglobulin‐like receptors (KIR) which interact with human leukocyte antigen (HLA) class I molecules on target cells. KIR‐ligand mismatching has recently been shown by van Bergen et al. (American Journal of Transplantation 2011; 11(9): 1959–1964) to be a significant risk factor for long‐term graft loss in HLA‐A, ‐B and ‐DR compatible kidney transplants. To verify this potentially important finding, we performed genotyping of 608 deceased‐donor kidney graft recipients and their HLA‐A, ‐B and ‐DR compatible donors for KIR and HLA, using samples and clinical data provided by the Collaborative Transplant Study. Graft survival of KIR‐ligand‐matched and ‐mismatched transplants was compared. We found no impact of KIR‐ligand mismatching on 10‐year graft survival in HLA‐A, ‐B, ‐DR compatible kidney transplants. Further analysis did not reveal a significant effect of recipient activating/inhibitory KIR or KIR genotypes on graft survival. Our data do not support the concept that KIR‐HLA matching might serve as a tool to improve long‐term renal allograft survival.

Natural killer (NK) cell function can be modulated by the killer cell immunoglobulin-like receptors (KIR) which interact with human leukocyte antigen (HLA) class I molecules on target cells. KIR-ligand mismatching has recently been shown by van Bergen et al. (American Journal of Transplantation 2011; 11(9): 1959–1964) to be a significant risk factor for long-term graft loss in HLA-A, -B and -DR compatible kidney transplants. To verify this potentially important finding, we performed genotyping of 608 deceased-donor kidney graft recipients and their HLA-A, -B and -DR compatible donors for KIR and HLA, using samples and clinical data provided by the Collaborative Transplant Study. Graft survival of KIR-ligand-matched and -mismatched transplants was compared. We found no impact of KIR-ligand mismatching on 10-year graft survival in HLA-A, -B, -DR compatible kidney transplants. Further analysis did not reveal a significant effect of recipient activating/inhibitory KIR or KIR genotypes on graft survival. Our data do not support the concept that KIR-HLA matching might serve as a tool to improve long-term renal allograft survival.

HLA mismatches may correlate with risk of death with a functioning graft (DWFG) because of requirement for higher immunosuppression doses and more antirejection therapy. Deceased‐donor kidney transplants (n = 177 584) performed 1990–2009 and reported to the Collaborative Transplant Study were analyzed. The incidence of DWFG was found to be 4.8% during year 1 posttransplant and 7.7% during years 2–5 (Kaplan–Meier estimates). Most frequent causes of DWFG were infection, cardiovascular disease and malignancy (32.2%, 30.9% and 3.6% in year 1; 16.4%, 29.6% and 15.9% in years 2–5). HLA‐A + B + DR mismatches were significantly associated with DWFG during year 1 (p < 0.001), a correlation that diminished but persisted during years 2–5 (p < 0.001). HLA mismatch was associated with DWFG because of infection (p < 0.001 during year 1, p = 0.043 during years 2–5) or cardiovascular disease (p < 0.001 during year 1, p = 0.030 during years 2–5) but not malignancy. There was also a significant association between HLA mismatch and hospitalization for viral (p < 0.001) or bacterial (p = 0.002) infection. Multivariable analysis showed that mismatches for HLA class II were more strongly associated with both hospitalization and DWFG than mismatches for HLA class I.

HLA mismatches may correlate with risk of death with a functioning graft (DWFG) because of requirement for higher immunosuppression doses and more antirejection therapy. Deceased-donor kidney transplants (n = 177 584) performed 1990–2009 and reported to the Collaborative Transplant Study were analyzed. The incidence of DWFG was found to be 4.8% during year 1 posttransplant and 7.7% during years 2–5 (Kaplan–Meier estimates). Most frequent causes of DWFG were infection, cardiovascular disease and malignancy (32.2%, 30.9% and 3.6% in year 1; 16.4%, 29.6% and 15.9% in years 2–5). HLA-A + B + DR mismatches were significantly associated with DWFG during year 1 (p < 0.001), a correlation that diminished but persisted during years 2–5 (p < 0.001). HLA mismatch was associated with DWFG because of infection (p < 0.001 during year 1, p = 0.043 during years 2–5) or cardiovascular disease (p < 0.001 during year 1, p = 0.030 during years 2–5) but not malignancy. There was also a significant association between HLA mismatch and hospitalization for viral (p < 0.001) or bacterial (p = 0.002) infection. Multivariable analysis showed that mismatches for HLA class II were more strongly associated with both hospitalization and DWFG than mismatches for HLA class I.

Whether treatment with angiotensin‐converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) increases the risk of cancer is controversial. Collaborative transplant study data were analyzed according to whether kidney transplant recipients were treated with ACEi/ARB at year 1. Twenty‐four thousand and ninety patients were studied of whom 9079 (38%) patients received ACEi/ARB. There were 872 nonskin malignancies during years 2–8 posttransplant, including 107 respiratory/intrathoracic tumors. The standardized incidence ratio (SIR) for all nonskin malignancies was similar between the ACEi/ARB (1.91) and no ACEi/ARB (1.81) groups (p = 0.42). For respiratory/intrathoracic tumors, however, SIR was significantly higher with ACEi/ARB (1.65 vs. 1.09 for no ACEi/ARB, p = 0.033). Multivariate Cox regression analysis showed that ACEi/ARB treatment was not associated with an increased risk of respiratory/intrathoracic tumors in nonsmokers. In patients with a history of smoking, however, the risk of respiratory/intrathoracic tumors was 2.77 (95% CI 1.19–6.43, p = 0.018) in patients without ACEi/ARB treatment as compared to 7.10 (95% CI 3.27–15.4, p < 0.001) in patients treated with ACEi/ARB. Our data indicate that in kidney transplant recipients, ACEi/ARB treatment is associated with a significant increase in the rate of respiratory/intrathoracic tumors in the subpopulation of patients with a history of smoking.

Whether treatment with angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) increases the risk of cancer is controversial. Collaborative transplant study data were analyzed according to whether kidney transplant recipients were treated with ACEi/ARB at year 1. Twenty-four thousand and ninety patients were studied of whom 9079 (38%) patients received ACEi/ARB. There were 872 nonskin malignancies during years 2–8 posttransplant, including 107 respiratory/intrathoracic tumors. The standardized incidence ratio (SIR) for all nonskin malignancies was similar between the ACEi/ARB (1.91) and no ACEi/ARB (1.81) groups (p = 0.42). For respiratory/intrathoracic tumors, however, SIR was significantly higher with ACEi/ARB (1.65 vs. 1.09 for no ACEi/ARB, p = 0.033). Multivariate Cox regression analysis showed that ACEi/ARB treatment was not associated with an increased risk of respiratory/intrathoracic tumors in nonsmokers. In patients with a history of smoking, however, the risk of respiratory/intrathoracic tumors was 2.77 (95% CI 1.19–6.43, p = 0.018) in patients without ACEi/ARB treatment as compared to 7.10 (95% CI 3.27–15.4, p < 0.001) in patients treated with ACEi/ARB. Our data indicate that in kidney transplant recipients, ACEi/ARB treatment is associated with a significant increase in the rate of respiratory/intrathoracic tumors in the subpopulation of patients with a history of smoking.

HLA-C is the major inhibitory ligand for killer immunoglobulin-like receptors (KIRs) that are expressed on natural killer (NK) cells. Based on their KIR specificity, HLA-C alleles can be divided into two groups, termed HLA-C1 and HLA-C2. Donor HLA-C group has recently been identified by Hanvesakul et al. (Am J Transplant 2008) as a critical determinant of clinical outcome following liver transplantation: Possession of at least one HLA-C group 2 allele by the donor was associated with significantly improved long-term graft and patient survival, presumably due to an inhibition of host NK cell function. To verify this study, we performed genotyping of 913 deceased liver donors for the relevant KIR epitopes of HLA-C and correlated the presence or absence of donor HLA-C2 genotype with graft and patient survival. In our study, donor HLA- C2 genotype had no impact on 10-year graft or patient survival. We cannot confirm a major role of donor HLA-C2 genotype on long-term allograft survival after liver transplantation.

HLA-C is the major inhibitory ligand for killer immunoglobulin-like receptors (KIRs) that are expressed on natural killer (NK) cells. Based on their KIR specificity, HLA-C alleles can be divided into two groups, termed HLA-C1 and HLA-C2. Donor HLA-C group has recently been identified by Hanvesakul et al. (Am J Transplant 2008) as a critical determinant of clinical outcome following liver transplantation: Possession of at least one HLA-C group 2 allele by the donor was associated with significantly improved long-term graft and patient survival, presumably due to an inhibition of host NK cell function. To verify this study, we performed genotyping of 913 deceased liver donors for the relevant KIR epitopes of HLA-C and correlated the presence or absence of donor HLA-C2 genotype with graft and patient survival. In our study, donor HLA-C2 genotype had no impact on 10-year graft or patient survival. We cannot confirm a major role of donor HLA-C2 genotype on long-term allograft survival after liver transplantation.

Summary In this paper the eigenvalue problemAx=?Bx is considered, whereA andB are symmetric matrices so large that they cannot be stored in the high speed storage of a computer. A general theory of the conjugate gradient method for minimizing the Rayleigh quotient is described and extended to a more general functional for computing simultaneously a few of the largest or smallest eigenvalues and the corresponding eigenvectors. Abandoning the advantage of the basic algorithm, which does not require the inversion or the factorization of one of the given matrices, the procedure can be used to solve the problem more effectively than by simultaneous iteration, especically in the case of clustered eigenvalues in the end of the spectrum.