scholarly journals B-VITAMIN THERAPY FOR KIDNEY TRANSPLANT RECIPIENTS LOWERS HOMOCYSTEINE AND IMPROVES SELECTIVE COGNITIVE OUTCOMES IN THE RANDOMIZED FAVORIT ANCILLARY COGNITIVE TRIAL

Author(s):  
T.M. Scott ◽  
G. Rogers ◽  
D.E. Weiner ◽  
K. Livingston ◽  
J. Selhub ◽  
...  

Background: Objectives: Elevated plasma total homocysteine (tHcy) is associated with increased risk of cardiovascular disease, stroke and dementia. Results of clinical trials using B-vitamins to reduce the cognitive risks attributed to tHcy have been inconsistent. The high prevalence of both hyperhomocysteinemia and cognitive impairment among kidney transplant recipients makes them an important population in which to evaluate the effect of lowering homocysteine on cognitive function. We therefore evaluated whether B-vitamin therapy to lower tHcy would prevent cognitive-decline in a cohort of stable kidney transplant recipients. Design: The study was a longitudinal ancillary of the FAVORIT trial, a randomized, placebo-controlled multi-site trial of high-dose B vitamins to reduce cardiovascular and cerebrovascular events in clinically stable kidney transplant recipients with elevated tHcy. Participants: 584 participants from 18 sites across North America. Intervention: The intervention consisted of a daily multivitamin containing high-doses of folate (5.0 mg), vitamin B12 (1.0 mg) and vitamin B6 (50 mg). The placebo consisted of a daily multi-vitamin containing no folate and recommended daily allowances of vitamins B12 and B6 (0 mg folate; 2.0 µg vitamin B12; 1.4 mg vitamin B6). Measurements: Annual neuropsychological assessment for up to 5 years (mean 3.3 years) using a standardized test battery. Efficacy was analyzed on an intention-to-treat basis using end-of-trial data. Subgroup analyses included stratification for baseline plasma B-vitamin and tHcy concentrations. Results: At baseline, cognitive impairment was common with 61% of participants falling more than one standard deviation below published norms for at least one cognitive test. Fewer than 1% of participants had insufficient plasma folate < 5 ng/ml or vitamin B12 < 148 pmol/L. However, 44.6% had plasma B6 concentrations < 30 nmol/L. At follow-up, processing speed and memory scores were modestly but significantly better in the B-vitamin supplement group than in controls (p≤0.05). There was no interaction between baseline tHcy, B-vitamin status and treatment on the cognitive outcomes. Conclusions: High-dose B-vitamin supplementation provided modest cognitive benefit for kidney transplant recipients with elevated baseline tHcy. Since nearly all participants were folate and vitamin B12 sufficient at baseline, the potential cognitive benefits of folate and B12 supplementation in individuals with poor B-vitamin status remains to be determined.

2020 ◽  
Vol 26 (28) ◽  
pp. 3451-3459
Author(s):  
Tomáš Seeman

: Kidney transplantation is a preferable treatment of children with end-stage kidney disease. All kidney transplant recipients, including pediatric need immunosuppressive medications to prevent rejection episodes and graft loss. : Induction therapy is used temporarily only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. There is currently no consensus regarding the use of induction therapy in children; its use should be decided based on the immunological risk of the child. : The recent progress shows that the recommended strategy is to use as maintenance immunosuppressive therapy a combination of a calcineurin inhibitor (preferably tacrolimus) with an antiproliferative drug (preferably mycophenolate mofetil) with steroids that can be withdrawn early or late in low-risk children. The mTOR-inhibitors (sirolimus, everolimus) are used rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. The use of calcineurin inhibitors, mycophenolate, and mTOR-inhibitors should be followed by therapeutic drug monitoring. : Immunosuppressive therapy of acute rejection consists of high-dose steroids and/or anti-lymphocyte antibodies (T-cell mediated rejection) or plasma exchange, intravenous immunoglobulines and/or rituximab (antibodymediated rejection). : The future strategies for research are mainly precise characterisation of children needing induction therapy, more specific indications for mTOR-inhibitors and for the far future, the possibility to reach the immuno tolerance.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S930-S930
Author(s):  
Yanis Tamzali ◽  
Anne Scemla ◽  
Pierre Taupin ◽  
Sunny Randhawa ◽  
Valérie Moal ◽  
...  

Abstract Background The management of meningitis requires the prompt introduction of high-dose probabilistic anti-infectious therapy. The literature reporting on meningitis in kidney transplant recipients (KTR) is scarce and no recommendation exists for this specific population. Methods We retrospectively included all adult KTRs diagnosed with meningitis (cerebro-spinal fluid (CSF) cell count >10/mm3 or positive fungal antigen or direct examination) between 2007 and 2018 in 16 French hospitals. Clinical, biological, and therapeutic data, and 1-year kidney and patient survival were collected. Results Meningitis occurred in 134 KTRs (mean age 57+/11.8 years, 56% male), after a median time of 27 months (IQR 8–65); 25% of patients received an immunosuppressive treatment before kidney transplantation, induction treatment included lymphocyte-depleting antibodies in 63%, and 53% presented diabetes (34% before and 19% after the transplantation). The etiologies included Cryptococcus neoformans (30%), Herpesviridae (22%, including Varicella-Zoster Virus 15%), idiopathic forms (11%), Gram-negative bacilli (8% of which 20% produced an extended spectrum β-lactamase), %), infusion of intravenous immunoglobulins (6%), post-transplant lymphoproliferative disorders (5%), Aspergillus fumigatus (4%), Listeria monocytogenes (4%), Enterovirus (4%), and Mycobacterium tuberculosis (3%). The most common symptoms were fever (82.5%), headaches (75%), encephalitis (55%), and convulsion (22.5%). CSF hypercellularity (found in 92% of the cases) was lymphocytic in 65% of the cases and neutrophilic in 35%. Initial anti-infectious therapy was inappropriate in 27% of the cases. One-year patient, graft, and death-censored graft survival rates were 84%, 76%, and 89%, respectively. Conclusion Meningitis after kidney transplantation encompasses a wide range of causes, with C. neoformans and VZV explaining more than 50% of the cases. Gram-negative bacilli are the most represented bacteria with a high rate of antimicrobial resistance. Treatment guidelines should be reconsidered in the specific population of KTRs as the etiology greatly differs from what is observed in the general population. Disclosures All authors: No reported disclosures.


Author(s):  
QY Ho ◽  
R Sultana ◽  
TL Lee ◽  
S Thangaraju ◽  
T Kee ◽  
...  

Introduction: The clinical presentation and outcomes of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs) have not been well studied. Methods: We performed a meta-analysis to examine the presenting features, outcomes and the effect of treatment on outcomes of KTRs with COVID-19. Database search was performed up to 5 September 2020 through PubMed, EMBASE, Web of Science, SCOPUS, and CENTRAL. Results: Overall, 23 studies (1373 patients) were included in the review and meta-analysis. The most common presenting symptoms included fever (74.0%, 95% confidence interval [CI] 65.3–81.1), cough (63.3% 95% CI 56.5–69.6) and dyspnoea (47.5%, 95% CI 39.6–55.6). Pooled rates of mortality and critical illness were 21.1% (95% CI 15.3-28.4) and 27.7% (95% CI 21.5–34.8) respectively. Acute kidney injury occurred in 38.9% (95% CI 30.6–48.1) and dialysis was required in 12.4% (95% CI 8.3–18.0) of the cases. Discussion: KTRs with COVID-19 have a similar clinical presentation as the general population but have higher morbidity and mortality. It is uncertain whether high dose corticosteroid or hydroxychloroquine reduces the risks of mortality in KTRs with COVID-19.


Author(s):  
Bhuwania P ◽  

Background: Moderate-risk for Cytomegalovirus (CMV) infection includes patients with donor positive/recipient positive (D+/R+) or donor negative/ recipient positive antibody status (D-/R+). Guidelines recommend high-dose daily Valganciclovir (VGCV) as prophylaxis, which may be due to the paucity of data on the efficacy of every-other-day VGCV. Methods: Our experience of using every-other-day VGCV as a prophylactic strategy in moderate risk Kidney Transplant Recipients (KTR) has been described. We retrospectively reviewed 86 moderate-risk KTR in our institution between 2018 and 2020. CMV infection at 6 months post-transplant was the primary endpoint. Graft survival, biopsy-proven rejection, opportunistic infections, Haematological adverse events, and mortality were also evaluated. Results: CMV infection occurrence at 6 months was zero in our cohort. Incidence of leukopenia was 13%, BPAR-31%, OI-33%, and mortality being 3.5%. Conclusion: Every-Other-Day VGCV dosing can be an effective alternative in moderate risk KTR for CMV prevention.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1100-1100
Author(s):  
Brock Williams ◽  
Heather McCartney ◽  
Yvonne Lamers ◽  
Suzanne Vercauteren ◽  
John Wu ◽  
...  

Abstract Objectives Canadian children with sickle cell disease (SCD) are routinely supplemented with high-dose folic acid (1 mg/d), synthetic folate, due to increased erythrocyte production and turn-over in the disease. Folate also plays a vital role in one-carbon metabolism. Impairments in this folate-dependent mechanism can also occur due to secondary B-vitamin (vitamin B2, B6 and B12) deficiencies. The study objective was to determine B-vitamin status in Canadian children with SCD. Methods Serum and plasma samples from children diagnosed with SCD were obtained from BC Children's Hospital BioBank (Vancouver, Canada). Samples were analyzed for folate, vitamin B6, and related metabolites using electrospray ionization-liquid chromatography-tandem mass spectrometry. Vitamin B12 concentrations were analyzed using chemiluminescent immunoassay. World Health Organization cut-offs were used to determine deficiencies of folate (&lt;10 nmol/L) and vitamin B12 (&lt;150 pmol/L), and European Food Safety Authority Panel cut-offs were used for vitamin B6 (&lt;30 nmol/L pyridoxal 5’-phosphate; PLP). Medians with interquartile ranges (IQR) are presented. Results Six individuals (50% male; SCD type: Hgb SS n = 3, Hgb SC n = 2, HbSβ,0-Thal n = 1) were included. Median age of participants was 15 (9, 18) years. Half (50%) of participants were prescribed hydroxyurea (median dose: 21(14, 30) mg/kg/d), and all participants were prescribed 1 mg/d folic acid (adherence data not available). Median serum folate was 55.4 (43.1, 71.9) nmol/L, with levels 3 to 15 times above the cut-off for deficiency. Unmetabolized folic acid (UMFA), unused folic acid in circulation, was detected in all six participants. All participants were vitamin B12 sufficient, with median plasma vitamin B12 of 325 (288, 411) nmol/L. The majority (n = 5; 83%) had sufficient B6 status, with median serum PLP of 39 (36.9, 44.2) nmol/L. Conclusions In this pilot project, there was limited evidence of B-vitamin deficiencies among Canadian children with SCD. Serum folate levels exceeded the cut-off for deficiency by 3 to 15 times, with all participants having detectable levels of UMFA. A randomized clinical trial re-assessing the routine practice of high-dose folic acid supplementation in children with SCD is warranted. Funding Sources Thrasher Research Fund and Rare Disease Foundation.


2012 ◽  
Vol 12 (7) ◽  
pp. 1793-1800 ◽  
Author(s):  
Z. Aydin ◽  
M. J. K. Mallat ◽  
A. F. M. Schaapherder ◽  
A. J. van Zonneveld ◽  
C. van Kooten ◽  
...  

2007 ◽  
Vol 92 (4) ◽  
pp. 1535-1541 ◽  
Author(s):  
Pål I. Holm ◽  
Steinar Hustad ◽  
Per Magne Ueland ◽  
Stein Emil Vollset ◽  
Tom Grotmol ◽  
...  

Abstract Context: Betaine is formed from the essential nutrient choline or is supplied from the diet. It serves as a substrate in the betaine-homocysteine methyltransferase reaction and thereby provides methyl groups for the homocysteine-methionine cycle, which is regulated by enzymes dependent on folate, vitamin B12, riboflavin (vitamin B2), or vitamin B6. Objective: We investigated how betaine affected total homocysteine (tHcy) concentration within the frame of variable B-vitamin status and according to the methylenetetrahydrofolate reductase (MTHFR) 677C-&gt;T genotype. Design/Setting/Patients: This is a population-based study with a cross-sectional design. It includes 10,601 healthy men and women aged 50–64 yr. Outcome Measures: Plasma samples were analyzed for tHcy, betaine, choline, dimethylglycine, riboflavin, and vitamin B6, whereas folate and vitamin B12 were analyzed in serum. Results: Betaine was a strong determinant of plasma tHcy in subjects with low serum folate and the MTHFR TT genotype. The association was further strengthened at low levels in the circulation of the other B-vitamins (B2, B6, and B12). Thus, in subjects with the combination of serum folate in the lowest quartile, low vitamin B2, B6, and B12 status, and the MTHFR TT genotype, the difference in tHcy (mean, 95% confidence interval) across extreme plasma betaine quartiles was 8.8 (1.3–16.2) μmol/liter. Conclusion: Betaine may thus be an important one-carbon source, particularly in MTHFR 677 TT subjects with inadequate B-vitamin status.


2010 ◽  
Vol 12 (2) ◽  
pp. 127-131 ◽  
Author(s):  
S.P. Watcharananan ◽  
T. Suwatanapongched ◽  
P. Wacharawanichkul ◽  
W. Chantratitaya ◽  
V. Mavichak ◽  
...  

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