Low 25(OH) Vitamin-D levels are associated with inferior graft function in living related kidney transplant recipients

Introduction: Given the burden of posttransplant diabetes mellitus and the high prevalence of low vitamin D levels in kidney transplant recipients, it is reasonable to consider vitamin D as a novel and potentially modifiable risk factor in this patient population. Research question: To determine the association between 25- hydroxyvitamin D (25(OH)D) level and posttransplant diabetes among kidney transplant recipients. Design: In a multi-center cohort study of 442 patients who received a kidney transplant between January 1, 2005 and December 31, 2010, serum samples within one-year before transplant were analyzed for 25(OH)D levels. The association between 25(OH)D and posttransplant diabetes were examined in Cox proportional hazard models. Results: The median 25(OH)D level was 66 nmol/L. The cumulative probability of diabetes at 12-months by quartiles of 25(OH)D (< 42, 42 to 64.9, 65 to 94.9, and > 95 nmol/L) were 23.4%, 26.9%, 21.4%, and 15.6%, respectively. Compared to the highest 25(OH)D quartile, hazard ratios (95% CI) for the risk were 1.85 (1.03, 3.32), 2.01 (1.12, 3.60), 1.77 (0.96, 3.25) across the first to third quartiles, respectively. The associations were accentuated in a model restricted to patients on tacrolimus. When modeled as a continuous variable, 25(OH)D levels were significantly associated with a higher risk of diabetes (hazard ratio 1.06, 95% CI: 1.01, 1.13 per 10 nmol/L decrease). Discussion: Serum 25(OH)D was an independent predictor of posttransplant diabetes in kidney transplant recipients. These results may inform the design of trials using vitamin D to reduce the risk in kidney transplant recipients.

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Impact of pre and post transplant 25(OH) Vit-D levels on graft function in living related kidney transplant recipients

Indian Journal of Transplantation ◽

10.1016/j.ijt.2016.09.071 ◽

2016 ◽

Vol 10 (4) ◽

pp. 108-109

Author(s):

Sonia Mehrotra ◽

Raj Kumar Sharma ◽

Manas R. Patel ◽

Amit Gupta ◽

Narayan Prasad ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Function ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Post Transplant ◽

Living Related

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Low wintertime pre-diagnostic vitamin D status is associated with an increased risk of internal malignancies in kidney transplant recipients

Photochemical & Photobiological Sciences ◽

10.1039/c7pp00404d ◽

2018 ◽

Vol 17 (12) ◽

pp. 1946-1955 ◽

Cited By ~ 2

Author(s):

Frank R. de Gruijl ◽

Ron Wolterbeek ◽

Stan Pavel ◽

Johan W. de Fijter ◽

Neveen A. T. Hamdy ◽

...

Keyword(s):

Vitamin D ◽

Kidney Transplant ◽

Vitamin D Status ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Increased Risk ◽

Vitamin D Levels

Kidney transplant recipients with the lowest wintertime vitamin D levels appear to run the highest risk of internal malignancies. The effect was strongest in women.

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Prevalence and risk factors of post-kidney transplant hyperparathyroidism: a single-center study

Russian Journal of Transplantology and Artificial Organs ◽

10.15825/1995-1191-2020-2-63-71 ◽

2020 ◽

Vol 22 (2) ◽

pp. 63-71

Author(s):

O. N. Vetchinnikova ◽

M. Yu. Ivanova

Keyword(s):

Risk Factors ◽

Vitamin D ◽

Kidney Transplant ◽

Graft Function ◽

Transplant Recipients ◽

Single Center ◽

Kidney Transplant Recipients ◽

Post Transplant ◽

Group 2 ◽

Group 1

Objective: to assess the prevalence of hyperparathyroidism (HPT) and the factors affecting its development in kidney transplant recipients. Materials and methods. The single-center observational cohort study included 97 kidney transplant recipients – 40 men, 57 women, age 50 ± 9 years. Inclusion criteria: more than 12 months of post-transplant period, 3 months of stable renal transplant function. Non-inclusion criterion: therapy with vitamin D, with its alternatives or with cinacalcet. Dialysis ranged from 0 to 132 months (median 18); 46% of patients had pre-operative secondary HPT. A comprehensive laboratory study included evaluation of serum concentrations of parathyroid hormone (PTH), 25-OH vitamin D, calcium, phosphorus, magnesium, total alkaline phosphatase (ALP) activity, albumin, creatinine and daily proteinuria. At the dialysis stage, the target PTH range of 130–585 pg/ ml was used, in the post-transplant period – ≤130 pg/ml. Glomerular filtration rate (eGFR) was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula. Results. Patients were divided into two groups based on PTH threshold level (130 pg/ml): the first with HPT (PTH >130 pg/ml, median 203), the second without HPT (PTH ≤130 pg/ml, median 101). Both groups were comparable in terms of gender, age, primary renal disease, dialysis modality, post-transplant follow-up, and immunosuppressive therapy regimen. In group 1 and group 2 recipients, dialysis therapy, pre-transplant median PTH level, incidence of reoperation and incidence of immediate renal graft function were 30 (14; 50) and 14 (6; 28) months (p = 0.004), 681 (538; 858) and 310 (182; 556) pg/ml (p < 0.001), 17% and 2% (p = 0.028), 51% and 80% (p = 0.005), respectively. At the time of the study, 72% of group 1 recipients had eGFR <60 ml/min, versus 36% of group 2 (p >< 0.001). Among HPT biochemical parameters, there were differences for ionized serum calcium (1.32 ± 0.07 versus 1.29 ± 0.04 mmol/l, p = 0.017) and ALP activity (113 ± 61 versus 75 ± 19 u/l, p = 0.021). Serum vitamin D in both groups reduced in equal measures – 14 ± 4 and 15 ± 6 ng/ml. Conclusion. Persistent HPT in the long-term post-transplant period reaches 48.5%. Risk factors for its development included dialysis for more than 18 months, pre-operative secondary HPT, repeated kidney transplantation, delayed graft function, and eGFR <60 ml/min.

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Associations of pre-transplant anemia management with post-transplant delayed graft function in kidney transplant recipients

Clinical Transplantation ◽

10.1111/j.1399-0012.2012.01598.x ◽

2012 ◽

Vol 26 (5) ◽

pp. 782-791 ◽

Cited By ~ 3

Author(s):

Miklos Z. Molnar ◽

Csaba P. Kovesdy ◽

Laszlo Rosivall ◽

Suphamai Bunnapradist ◽

Junichi Hoshino ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Function ◽

Delayed Graft Function ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Post Transplant ◽

Anemia Management

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Prevalence and risk factors for death with graft function among Egyptian kidney transplant recipients in Mansoura

Zagazig University Medical Journal ◽

10.21608/zumj.2021.55359.2074 ◽

2021 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

mostafa abu gharbia ◽

ahmed salah ◽

Yaser Elhendy ◽

Ayman refaie

Keyword(s):

Risk Factors ◽

Kidney Transplant ◽

Graft Function ◽

Transplant Recipients ◽

Kidney Transplant Recipients

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Association of Factor V Leiden Mutation with Delayed Graft Function, Acute Rejection Episodes and Long-term Graft Dysfunction in Kidney Transplant Recipients

Thrombosis and Haemostasis ◽

10.1055/s-0037-1612972 ◽

2002 ◽

Vol 87 (02) ◽

pp. 194-198 ◽

Cited By ~ 32

Author(s):

Torsten Slowinski ◽

Ingeborg Hauser ◽

Birgit Vetter ◽

Lutz Fritsche ◽

Daniela Bachert ◽

...

Keyword(s):

Acute Rejection ◽

Kidney Transplant ◽

Graft Function ◽

Factor V Leiden ◽

Factor V ◽

Transplant Recipients ◽

Graft Dysfunction ◽

Kidney Transplant Recipients ◽

Factor V Leiden Mutation

SummaryWe analysed whether the factor V Leiden mutation – the most common hereditary predisposing factor for venous thrombosis – is associated with early and long-term graft dysfunction after kidney transplantation in 394 Caucasian kidney transplant recipients. The presence of factor V Leiden mutation was identified by allele specific PCR. The prevalence of the factor V Leiden mutation was compared to 32216 unselected neonates. The prevalence of the factor V Leiden mutation (GA genotype) was similar in 394 kidney transplant recipients and 32216 neonates. The frequency of known factors predicting long-term graft function were similar in patients with the GA genotype and with the normal factor V gene (GG genotype). The GA genotype was associated with the occurrence of no primary graft function (risk: 2.87; 95% confidence interval: 1.01-8.26; p < 0.05), the number of dialysis after transplantation in patients with no primary graft function until graft function (7.5 ± 2.06 dialysis in GA patients; 4.2 ± 0.36 dialyses in GG patients; p < 0.05), and the risk for at least one acute rejection episode (risk: 3.83; 95% confidence interval: 1.38-10.59; p < 0.02). The slope of 1/creatinine per year was significantly lower in patients with the GA genotype (GA patients: – 0.0204 ± 0.008 dl/mg per year; GG patients: 0.0104 ± 0.004 dl/mg per year; p < 0.02). The annual enhancement of the daily protein excretion rate was elevated in patients with the GA genotype (GA patients: 38.5 ± 16.6 mg/24 h per year; GG patients: 4.9 ± 4.4 mg/24 h per year; p < 0.02). Our study showed that the factor V Leiden mutation is associated with the occurrence of delayed graft function, acute rejection episodes and chronic graft dysfunction after kidney transplantation.

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A Prospective Controlled Trial to Evaluate Safety and Efficacy of in vitro Expanded Recipient Regulatory T Cell Therapy and Tocilizumab Together With Donor Bone Marrow Infusion in HLA-Mismatched Living Donor Kidney Transplant Recipients (Trex001)

Frontiers in Medicine ◽

10.3389/fmed.2020.634260 ◽

2021 ◽

Vol 7 ◽

Author(s):

Rainer Oberbauer ◽

Matthias Edinger ◽

Gabriela Berlakovich ◽

Peter Kalhs ◽

Nina Worel ◽

...

Keyword(s):

Bone Marrow ◽

Kidney Transplant ◽

Graft Function ◽

Control Group ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Post Transplant ◽

Donor Bone Marrow ◽

Living Donor Kidney Transplant

Background: The induction of donor-specific immunological tolerance could improve outcome after kidney transplantation. However, no tolerance protocol is available for routine clinical use. Chimerism-based regimens hold promise, but their widespread application is impeded in part by unresolved safety issues. This study tests the hypothesis that therapy with polyclonal recipient regulatory T cells (Tregs) and anti-IL6R (tocilizumab) leads to transient chimerism and achieves pro-tolerogenic immunomodulation in kidney transplant recipients also receiving donor bone marrow (BM) without myelosuppressive conditioning of the recipient.Methods/design: A prospective, open-label, controlled, single-center, phase I/IIa academic study is performed in HLA-mismatched living donor kidney transplant recipients.Study group: Recipients of the study group receive in vitro expanded recipient Tregs and a donor bone marrow cell infusion within 3 days after transplantation and tocilizumab for the first 3 weeks post-transplant. In addition they are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Starting 6 months post-transplant, sirolimus and steroids are withdrawn in a step-wise manner in stable patients.Control group: Recipients of the control group are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Co-primary endpoints of safety (impaired graft function [eGFR <35 mL/min/1.73 m2], graft-vs.-host disease or patient death by 12 months) and efficacy (total leukocyte donor chimerism within 28 days post-transplant) are assessed. Secondary endpoints include frequency of biopsy-proven acute rejection episodes and subclinical rejection episodes on surveillance biopsies, assessment of kidney graft function, and the evaluation whether the study protocol leads to detectable changes in the immune system indicative of pro-tolerogenic immune modulation.Discussion: The results of this trial will provide evidence whether treatment with recipient Tregs and donor BM is feasible, safe and efficacious in leading to transient chimerism. If successful, this combination cell therapy has the potential to become a novel treatment option for immunomodulation in organ transplantation without the toxicities associated with myelosuppressive recipient conditioning.Trial registration: European Clinical Trials Database EudraCT Nr 2018-003142-16 and clinicaltrials.gov NCT03867617.

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