Vitamins in renal transplantation

2. Vitamins in renal
transplantation
Dr Behnaz Bazargani
Pediatric nephrologist
TUMS. Children's medical center

3. Vitamin D Metabolism After Successful
Kidney Transplantation
Rapid reduction of FGF-23 level within the first 3
months
PTH levels rapidly decrease within the first 3
months, and remain stable and often elevated after
the first post-transplant year.

4. P↓ and Ca↑ are common in the early post-transplant
period and tend to normalise after the third month
of KT.
 It takes ≤18 months for VD status to improve
Despite the presence of a functioning graft, VD status
is usually suboptimal.

6. Recovery of graft function, inappropriately high PTH
levels and P↓ accelerate the conversion of 25(OH)D
into 1,25(OH).
 Conversely, high FGF23 levels during the first
months post-transplant could inhibit 1-α-hydroxylase
and enhance 24-α-hydroxylase, thereby reducing
1,25(OH) and 25(OH)D levels.

7. Immunosuppressive therapy and vitamin
D
 Glucocorticoids alter vitamin D metabolism, expressing
enzymes involved in vitamin D catabolism and increasing PTH
and FGF23 levels .
 The cumulative prednisone dose is inversely correlated with
1,25(OH)D levels 2 years after transplantation
 Low 1,25(OH)D levels could also be favored by higher FGF23
concentrations induced by steroid therapy.

8. Immunosuppressive therapy and vitamin
D
CNI is associated with lower 25(OH)D levels among
KTRs
 CNI-induced vitamin D resistance through VDR
downregulation .
Sirolimus has no effect on renal calcium excretion,
vitamin D metabolism, calcium channel expression
or calcium-binding proteins.

9. Importance of Vitamin D in the Post-Transplant
Period
The two major clinical issues concerning VD
after KT are mineral-bone disease and VD
pleiotropy.

10. Post-transplant mineral bone disease (PTr-
MBD)
Poor VD status is one of the factors for developing PTr-
MBD, together with immunosuppressive therapy,
persistent hyperparathyroidism, malnutrition, persistent
CKD, duration of CKD Stage 5, duration of dialysis,
obesity, and diabetes mellitus.

11. Biochemical abnormalities in post-
transplant mineral bone disease
Biochemical findings are highly dependent on
Pre-transplant CKD-MBD,
Immunosuppressive treatment,
Post-transplant graft function,
Concomitant diseases,
Medications.

12.  Mineral–bone indicators should be monitored closely
immediately after KT.
 The frequency of testing for ca , p , PTH, AlkP, and 25VD
should be determined according to graft function, duration of
transplantation, magnitude of abnormalities, and when
supplementation was initiated.

13. Post-transplant bone disease
A rapid reduction in bone density is widely
reported, with faster bone loss during the first
months after successful KT.
Major complication is increased fracture risk,
associated with increased morbidity and mortality.
 Pre-transplant bone health is crucial for post-
transplant outcomes.

14. A key factor in deteriorating bone health prior to
kidney transplantation are excessive VD doses, which
are associated with increased incidence of adynamic
bone disease before KT.
Therefore, adequate treatment of CKD-related MBD
should be performed in the pre and post-transplant
period.

15. Vitamin D and cardiovascular disease after
transplantation
The risk for CVD is increased after transplantation
compared to the general population, due to the
persistent CKD-associated vascular and cardiac
abnormalities, especially vascular calcifications.

16. Poor VD status is associated with arteriosclerosis and
endothelial dysfunction in ESRD patients.
VDR activation in cardiomyocytes suppresses their
proliferation.
Furthermore, higher doses of VD may be associated
with increased risk for vascular calcifications.

17. Vitamin D and rejection
 VDR is expressed in all immune cells, including those of the
innate immune dendritic cells and macrophages.
 Calcitriol suppresses T and B-lymphocyte proliferation;
inhibits dendritic cells and macrophages, suppresses IL and
Ig G production, and downregulates MHC class II expression.
 Better VD status is associated with lower incidence of acute
rejection.

18. Vitamin D and infection
 Infection represents a major cause of patient death and graft
loss after successful kidney transplantation.
 VD upregulates the synthesis of the lysosome protein
cathelicidin and the anti-microbial protein β–defensin.
 Better VD status was associated with lower incidence of viral,
bacterial, and fungal infections.

19. Vitamin D and malignancy
Neoplasia is one of the most common causes for
patient and graft loss in KTRs.
VD suppresses cellular proliferation and
angiogenesis, and stimulates cell differentiation and
apoptosis.

20. Vitamin D and mortality
All-cause mortality is increased in KTRs, due to
persistent CKD, persistent cardio-vascular disease,
post-transplant mineral bone disease, and increased
neoplastic incidence and infection rate.
Sub-optimal VD is associated with higher all-cause
mortality in KTRs.

21. Vitamin D Treatment in Kidney Transplant
Recipients
 Treatment should be tailored to the initial VD status after KT,
post-transplant ca–ph metabolism, due to the increased
incidence of Ca↑ and P↓ after successful KT.
 The values for Ca , Ph , ALKP, and PTH should be evaluated
regularly.
 The frequency of laboratory testing should be based on
graft function, degree of biochemical abnormalities, and
supplementation initiated.

22.  The 2017 KDIGO CKD-MBD Guideline recommended BMD
testing in the first 3 months following transplantation in
patients with an GFR greater than 30 if they receive
corticosteroids or have risk factors for osteoporosis.
 In patients in the first 12 months after kidney transplant with
an GFR greater than approximately 30 and low BMD,
treatment with vitamin D, calcitriol be considered .

23. Magnesium Status after Kidney
Transplantation
 Hypomagnesemia is frequently observed after kidney
transplantation, in part to
 Immunosuppressive regimens including CNI that induce Mg
urinary waste.
 Sirolimus might induce hypomagnesemia through inhibition
of Na-K-Cl co-transporter 2 expression in the thick
ascending loop of Henle .

24. Many other factors influence Mg levels after kidney
transplantation, such as post-transplantation volume
expansion, metabolic acidosis, insulin resistance,
decreased gastro-intestinal absorption due to
diarrhea, low Mg intake and medication such as
diuretics or proton pump inhibitors.

26. Serum Magnesium and New-Onset
Diabetes Mellitus after Transplantation
In a retrospective cohort of 173 young recipients
with a median age of 7 years, 20 patients developed
PTDM at 9 days post transplantation on average.
Hypomagnesemia and high tacrolimus levels were
significant and independent risk factors for PTDM

27. Magnesium Status and Cardiovascular
Risk after Kidney Transplantation
Hypomagnesemia has been shown to play a role in
the pathogenesis of arterial hypertension,
endothelial dysfunction, dyslipidemia and
inflammation, with all these factors contributing to
coronary heart disease (CHD).

29. Antioxidant Supplementation
Dysfunction of the renal graft may not only be due
to rejection but also other causes such as ischemia
and reperfusion injury and CNI nephrotoxicity.
Antioxidant free radical scavengers may decrease
oxidative stress and lipid peroxidation.
Antioxidant supplementation with vitamin C or E
may improve renal transplant function

30. Antioxidant supplementation reduces CsA trough-
levels in renal transplant recipients. Injudicious use of
vitamin C and E supplementation should therefore be
avoided.
 Decreased CsA levels associated with their use pose
no risk for transplant rejection.
 Transplant nephrologists should be aware of the CsA
trough level lowering effect of anti-oxidants.

31. KTRs may be at increased risk of B12 deficiency due to :
The recommendation to decrease the intake of animal protein before
KT (during non-dialysis treatment);
The excessive weight gain that is common in KTR;
The use of MMF.

32.  Including KTR with a minimum of 6 months of transplantation,
B12 deficiency prevalence was 14 %.
The intake of B12 was significantly lower in participants with
B12 deficiency . the intake of protein presented a tendency to
be lower in the B12-deficient group .
 B12 dietary intake needs to be carefully monitored in KTR,
especially in those with lower protein intake.

33. B12 deficiency was associated with increased central body
adiposity .
In KTR with adequate B12 intake, the frequency of B12 deficiency
was higher in patients using MMF than in those using AZA. This
finding suggests that KTR using MMF may be at increased risk of
B12 deficiency even if they present adequate B12 intake.

34. Higher prevalence of vitamin B-6 deficiency in RTRs
Vitamin B-6 intake in RTRs is similar to that in controls and yet plasma PLP
concentrations are lower
Poor vitamin B-6 status in RTRs is the consequence of altered vitamin B-6
handling rather than inadequate intake.

35.  Gradual increase in all-cause and cardiovascular mortality
across groups with worse vitamin B-6 status
 No associations between plasma PLP concentrations and graft
failure were observed .
 A diet based on foods rich in this vitamin, in particular fruits
and legumes, in RTRs with a low vitamin B-6 status.

36.  Treatment of stable kidney transplant recipients with a
multivitamin containing high-dose folic acid, B6, and B12
lowers tHcy levels relative to standard multivitamin
supplementation and in many cases to normal levels but does
not reduce CVD outcomes or total mortality .