Progression of coronary artery calcification in conventional hemodialysis, nocturnal hemodialysis, and kidney transplantation

Introduction Cardiovascular 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. Methods We 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 (Delta CAC SQRV) using linear mixed models. Reference category was conventional hemodialysis. Results The 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. Conclusions Nocturnal 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

Coronary Artery Calcification in Hemodialysis and Peritoneal Dialysis

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 (CAC SQRV) and with Tobit mixed models. We adjusted for potential confounders. Results: In the cross-sectional cohort, CAC volume scores were 92 mm(3) in hemodialysis and 492 mm(3) in peritoneal dialysis (adjusted difference 436 mm(3); 95% CI -47 to 919; p = 0.08). In the longitudinal cohort, peritoneal dialysis was associated with significantly more CAC progression defined as CAC 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 mm(3); 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

Preimplantation Genetic Testing for Monogenic Kidney Disease

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

ABO-incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies:a propensity-matched analysis

BACKGROUND: 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. METHODS: 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. RESULTS: 296 ABOi were compared to 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 to deceased donor (hazard ratio (HR) for death of HR 0.69 [0.49-0.96], and not-significantly different from ABOc living donor recipients (HR 1.28 [0.90-1.81]). Rate of graft failure was higher compared to 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 <0.001). CONCLUSIONS: ABOi kidney transplantation is superior to deceased donor transplantation. Rejection rate and graft failure are higher compared to matched ABOc living donor transplantation, underscoring the need for further studies into risk stratification and induction therapy

Eigenvalue asymptotics for weighted Laplace equations on rough Riemannian manifolds with boundary

Our topological setting is a smooth compact manifold of dimension two or higher with smooth boundary. Although this underlying topological structure is smooth, the Riemannian metric tensor is only assumed to be bounded and measurable. This is known as a rough Riemannian manifold. For a large class of boundary conditions we demonstrate a Weyl law for the asymptotics of the eigenvalues of the Laplacian associated to a rough metric. Moreover, we obtain eigenvalue asymptotics for weighted Laplace equations associated to a rough metric. Of particular novelty is that the weight function is not assumed to be of fixed sign, and thus the eigenvalues may be both positive and negative. Key ingredients in the proofs were demonstrated by Birman and Solomjak nearly fifty years ago in their seminal work on eigenvalue asymptotics. In addition to determining the eigenvalue asymptotics in the rough Riemannian manifold setting for weighted Laplace equations, we also wish to promote their achievements which may have further applications to modern problems

PIRCHE-II Is Related to Graft Failure after Kidney Transplantation

Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor–recipient couples that were transplanted between 1995 and 2005. For these donors–recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04–1.23, p = 0.003]. When analyzing a subgroup of patients who had their first transplantation, the HR of graft failure for ln(PIRCHE-II) was higher compared with the overall cohort (HR: 1.22, 95% CI: 1.10–1.34, p &lt; 0.001). PIRCHE-II demonstrated both early and late effects on graft failure in this subgroup. These data suggest that the PIRCHE-II may impact graft survival after kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival

T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation

CD4(+) T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4(+) memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4(+) memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4(+) memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4(+) memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation

Health-related quality of life compared between kidney transplantation and nocturnal hemodialysis

Background Health-related quality of life (HRQOL) is an important outcome measure in patients with end-stage renal disease. HRQOL is assumed to improve with kidney transplantation and also with nocturnal hemodialysis compared to conventional hemodialysis. However, there is no evidence regarding HRQOL to support the optimal treatment choice for patients on nocturnal hemodialysis who hesitate opting for transplantation. We therefore compared HRQOL between patients who were treated with kidney transplantation or nocturnal hemodialysis for one year. Methods We assessed HQROL using the Kidney Disease Quality of Life–Short Form questionnaire in a cross-sectional sample of patients who were treated with kidney transplantation (n = 41) or nocturnal hemodialysis (n = 31) for one year. All patients on nocturnal hemodialysis were transplantation candidates. Using linear regression, we compared HRQOL between kidney transplantation and nocturnal hemodialysis, and adjusted for age, sex, dialysis duration, cardiovascular disease, and presence of residual urine production. Results At one year follow-up, mean age of the study population was 54 ±13 years, and median dialysis duration was 3.2 (IQR 2.1–5.0) years. Kidney transplantation was associated with significantly higher HRQOL on the domain “effects” compared to nocturnal hemodialysis (adjusted difference 12.0 points, 95% CI 3.9; 20.1). There were potentially clinically relevant differences between kidney transplantation and nocturnal hemodialysis on the domains “burden” (adjusted difference 11.1 points, 95% CI -2.6; 24.8), “social support” (adjusted difference 6.2, 95% CI -6.6; 19.1), and the physical composite score (adjusted difference 3.0, 95% CI -2.0; 8.1), but these were not significant. Conclusions After kidney transplantation, HRQOL is especially higher on the domain “effects of kidney disease” compared to nocturnal hemodialysis. This can be useful when counseling patients on nocturnal hemodialysis who may opt for transplantation

Progression of coronary artery calcification in conventional hemodialysis, nocturnal hemodialysis, and kidney transplantation

Introduction Cardiovascular 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. Methods We 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. Results The 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. Conclusions Nocturnal 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