This document discusses vitamins and their roles and deficiencies in chronic kidney disease and hemodialysis patients. It covers several key water soluble vitamins (thiamine, riboflavin, niacin, B6, B9, B12, C) and fat soluble vitamins (A, D, E). It notes that CKD and dialysis patients are at higher risk for deficiencies due to reduced intake, restricted diets, losses during dialysis, and altered metabolism. Supplementation is generally recommended to prevent deficiencies, though levels of some vitamins like A may be elevated. The roles of vitamins in conditions like anemia, cardiovascular disease, and neuropathy are also covered.

1. Vitaminsinchronickidneydisease
and Hemodialysispatients
Azadeh Afshin MD, Assisstant Professor , Tehran univesity of medical science

2.  Vitamins are organic substances that cannot be synthesized by the
human body
 Their functions are essential for normal human metabolism
 In contrast to well-defined standards for healthy children/To date, there have
been no randomized controlled trials examining the intake and/or needs of
vitamins and trace elements in pediatric (CKD) or ESRD
 Natural dietary sources of water-soluble vitamins and key trace elements are
found in foods such as fruits, legumes, red meat, and dairy, all of which may
be limited in the ESRD population on dialysis because of high potassium and
phosphorus contents

3.  Frank scurvy, beriberi, and Wernicke’s encephalopathy have been
reported in dialysis patients.
 There is concern that subtle vitamin deficiencies, particularly in patients on
dialysis, may account for some of the general uremic symptomatology or for
more specific dialysis-associated syndromes such as anemia or peripheral
neuropathy
 The blood levels of fat-soluble vitamins A and E are normal or elevated in
pediatric patients receiving dialysis despite the lack of excessive dietary
intake or vitamin supplementation.
 The loss of clearance of vitamin A metabolites by the normal kidney places
dialysis patients at risk for symptoms of hypervitaminosis A

4.  There are five main reasons why CKD or dialysis patients may have
vitamin deficiencies:
1. reduced appetite
2. restricted diet
3. medications and co-morbidity / interfere with absorption
4. uremia / alter metabolic pathways
5.intradialytic losses
 Patients could have an impact on many complications linked to vitamin
and trace element disorders, including:
 high mortality, increased risk of atherosclerosis, inflammation, oxidative
stress, anemia, polyneuropathy, encephalopathy, weakness and fragility,
muscle cramps, bone disease, depression, or insomnia

5.  Thiamine deficiency
 Thiamine plays a pivotal role in carbohydrate metabolism as a coenzyme and
has functions independent of its coenzyme function in the initiation of nerve
impulse propagation
 It is absorbed in the upper small intestine, Most thiamine in the circulation is
within red blood cells and the remaining amount is albumin-bound.
 Thiamine and its metabolites are excreted principally in urine
 Thiamine is found in enriched, fortified, or whole grain products

6.  In acute thiamine deficiency, pyruvate accumulates and is metabolized to
lactate without accompanying acidosis(lactic acidosis)
 Early symptoms of mild thiamine deficiency :
irritability, fatigue, anorexia, peripheral neuropathy, sleep disturbance, and
depression
 Severe thiamine deficiency manifests as:
“dry Beriberi” with presentation of Wernicke encephalopathy as
characterized: the triad of confusion, ophthalmoplegia, and ataxia.
 The clinical syndrome is further expanded with presentation of
confabulation and amnesia, clinically termed Korsakoff syndrome

7.  It may also lead to diastolic cardiac dysfunction manifesting in edema and
peripheral vasodilation, known as wet Beriberi
 Diagnosis of thiamine deficiency can be made via clinical symptomatology
and laboratory evaluation using whole blood thiamine testing to quantitate the
active form of thiamine (thiamine diphosphate) as an indicator of total body
thiamine status
 Magnesium is a necessary component for the conversion of thiamine into
thiamine pyrophosphate [33]. Thus, thiamine replacement for suspected
severe thiamine deficiency should occur with replacement of magnesium as
indicated

8.  Thiamine blood concentrations in CKD patients are either within reference
range for healthy individuals or even increased.
 Nevertheless, the recent findings of high levels of thiamine antimetabolite
(oxythiamine) in ESRD shed new light on understanding thiamine deficiency,
which may not necessarily go in line with its low plasma values
 Current recommendations suggest a daily supplement of 1.1–1.2 mg thiamine
 A number of case reports, suggests that supplementary thiamine should be
particularly considered in dialysis patients with mental status changes

9. Vitamin B2 (Riboflavin)
 Riboflavin, or vitamin B2, plays a key role in energy metabolism
 Riboflavin is found in organ meats, milk, bread products and fortified cereal
 Riboflavin deficiency is characterized by angular stomatitis, cheilosis and
glossitis and typically occurs in association with other vitamin deficiencies
 No strong evidence exists for supplementation, but studies documenting
sufficiency were performed in patients receiving supplements
 There is no known riboflavin toxicity

10.  The dialyzability of riboflavin has been studied in a group of 30 dialysis
patients. There was a 7% reduction in total riboflavin postdialysis with no
differences between high- and low-flux membranes

11. Vitamin B3 (Niacin = nicotinic acid; niacinamide = nicotinamide)
 Vitamin B3 is crucial in the synthesis of carbohydrates, proteins, and fatty
acids and therefore plays key role in energy metabolism
 Niacin is readily found in meat, fish, poultry, and enriched whole grain
products
 Niacin is an accepted treatment for the reduction of total and LDL-cholesterol
in the general population
 The main side effect of supplementation with niacin is the flushing reaction
associated with nicotinic acid, a symptom that can be reduced with sustained
released prepration

12.  Deficiency of niacin results in a photosensitive pigmented dermatitis called
pellagra
 In the general population, niacin toxicity has included GI symptoms as well
as elevated transaminases and myopathy
 Niacin levels do not change pre- and post a single hemodialysis treatment
 The available evidence suggests that niacin could potentially accumulate in
dialysis patients, and long-term safety in this population is unclear
 There is no recommendation for niacin prescription for individuals with
low GFR or ESRD

13.  .

14. Vitamin B6 (pyridoxine, pyridoxal)
 Pyridoxine (B6) is one of three derivatives of the pyridine ring: pyridoxine,
pyridoxal, and pyridoxamine.
 Pyridoxine is a critical coenzyme for erythrocyte transaminase activity,
influencing the stability and affinity of oxygen to hemoglobin polymers
 Dietary sources of B6 include fortified cereals, organ meats, fortified soy-
based meat substitutes, yeast, nuts, beans, avocados, and bananas
 B6 is a component of two enzymes that metabolize homocysteine, deficiency
of B6 leads to hyperhomocysteinemia, which is associated with thrombosis
and atherosclerosis

15.  There has been a reported 35% drop in pyridoxine concentration after a
single dialysis session , especialy in high flux HD but it was seen in low-flux
HD and PD patients.
 Most reports of toxicity, in the form of peripheral neuropathy, have occurred
in the context of intakes of >600 mg daily
 Vitamin B6 supplementation lowered oxalate levels in a small study of
patients on peritoneal dialysis who were receiving ascorbate
supplementation

16.  In a blinded randomized trial of 26 patients on high-flux HD who had
peripheral neuropathy, B6 50 mg/day compared with B12 500 mg/day resulted
in improvement in peripheral neuropathy scores
 10 mg of B6 per day seems to be sufficient for CKD and ESRD patients.
 It would be better if started earlier in the course of kidney disease or at the
initiation of dialysis.

17. Vitamin B7 (biotin)
 Dietary sources include yeast, liver, egg yolk, tomato, soybeans, rice, and
bran
 B7 is a cofactor responsible for carbon transfer in several carboxylase
Reactions
 Egg white contains a glycoprotein, avidin, that tenaciously binds B7;
excessive consumption of egg white (more than 20 a day) can lead to frank
clinical deficiency, called egg-white disease, and characterized by scaly
dermatitis and skin dryness, atrophy of lingual papillae, graying of mucous
membranes, depression, lassitude, and muscle pain

18.  B7 deficiency in humans have identified seborrhoeic dermatitis as the
cardinal manifestation
 B7 and its metabolite was excrete from urine , Patients on HD for longer
than 5 years had levels that were higher than those on of more recent
vintage

19. Vitamin B9 (folic acid, folate)
 Folic acid (B9) functions as a necessary enzymatic cofactor in the synthesis
of purine and thymidine nucleotides critical for red blood cell formation
 Weak binding of folic acid (FA) to plasma proteins results in significant
losses during each dialysis session
 Green leafy vegetables, whole grains, yeast, and liver are particularly rich in
Folate, particularly when raw or not heavily processed, Intestinal bacteria
also synthesize Folate.
 In many countries, flour and bread are fortified with Folate as a public health
measure, and many breakfast cereals are also fortified with 25–100% of the
RDA per serving

20.  Folate stores are low, so deficiency can occur 21– 28 days of severe dietary
deficiency
 The cardinal clinical manifestation of frank deficiency is megaloblastic
anemia
 Patients on HD consistently have lower RBC folate that those on CAPD
 In one small pre–post study, sevelamer use was associated with a decrease
in serum folate levels (5.5 vs. 4.79 ng/ml, p < 0.05) and an increase in
homocysteine levels (51 vs. 68 nmol/ml)
 Folate deficiency may manifest as erythropoietin resistance in pediatric
hemodialysis patients; improvement in serum hemoglobin and reduction in
erythropoietin requirement occurs following folate provision

21.  Concern for erythropoietin resistance, in conjunction with megaloblastic
anemia, should prompt evaluation for folate deficiency.
 Severe deficiencies of folate and pyridoxine may lead to seizures, mental
status changes, chronic abdominal cramping/discomfort, nausea, and/or
diarrhea
 According to the available evidence, folate supplementation in a dose of 1
mg/day should prevent deficiencies in hemodialysis patients
 folate supplementation in a dose of 2 mg/day results in a five-fold increase in
plasma concentration, were used to limit cardiovascular complications in
ESRD patients, due to its effect on homocysteine methylation

22. Vitamin B12
 The main source of cobalamin is from dietary intake of animal and dairy
products
 Patients with frank deficiency can present with hematologic or
neuropsychiatric syndromes
 Megaloblastic Anemia( Macrocytic anemia )is the most common
manifestation of vitamin B12 deficiency
 Vitamin B12 deficiency is the major cause of elevated plasma total
homocysteine in folate-fortified populations

23.  Long-standing vitamin B12 deficiency can lead to various neurologic
sequelae including peripheral neuropathy, cognitive impairments, and
subacute combined degeneration of the spinal cord
 Vitamin B12 status in the renal population is dependent on the extent of
uremia and the impact on nutrition
 Uremia may also reduce the activity of methionine synthase

24.  As folic acid, vitamin B6, and vitamin B12 have a role in the generation of
homocysteine , many cardiovascular studies examining the effects of
vitamin supplements employed all three vitamins
 Adequate folate and pyridoxine and vit B12 stores are required for the
conversion of homocysteine to methionine
 Hyperhomocysteinemia is a well-known complication of ESRD with
associated adverse cardiovascular outcomes
 current pediatric dialysis literature provides support for supplementation
with 2.5–5.0 milligrams per day of folic acid in the setting of
hyperhomocysteinemia

26. Vitamin C
 (Ascorbic acid) is a water-soluble vitamin produced from metabolism of
glucose, It is required as a critical co-factor for synthesis of collagen
 It is an abundant plasma and intracellular antioxidant vitamin
 This antioxidant vitamin also plays a key role in prevention of chronic-
disease related anemia in the ESRD population through increased
absorption and utilization of dietary non-heme iron facilitation of
erythropoiesis, and enhanced red blood cell stability
 The clinical manifestations of vitamin C deficiency may initially be subtle
and confused with complaints of chronic uremia – weakness, malaise,
fatigue, and minor bleeding

27.  Recent clinical case report describes clinical diagnosis of scurvy in a
pediatric peritoneal dialysis patient – including :
 long-bone changes, gingival hyperplasia and bleeding, perifollicular
hemorrhage, and bloody dialysate – with full clinical resolution of
symptoms following appropriate oral vitamin C supplementation
 Aggressive enteral and/or parenteral iron repletion should be provided in
cases of suspected vitamin C deficiency in the dialysis patient given the
high likelihood of coexisting, profound iron deficiency anemia
 Functional Iron Deficiency and Erythropoietin Hyporesponsiveness
 vitamin C levels were positively associated with GFR, Many vitamin-C-rich
foods are also high in potassium, which may lead to their restriction in
patients with advanced renal failure and in those on dialysis

28.  Oxalate is a product of metabolism of vitamin C and though dialyzable,
accumulates in patients on dialysis
 The levels of oxalate in dialysis patients are twofold higher than normal, and
after vitamin C supplementation might be even seven-fold higher
 It seems reasonable to administer low-dose vitamin C supplementation,
perhaps 60–100 mg daily, to patients on hemodialysis, and to consider the
diagnosis of vitamin C deficiency in patients whose anemia or fatigue is
disproportionate to their known comorbidities

29. Vitamin E
 A combined vitamin E and selenium or glutathione deficiency leads to
pronounced and progressive oxidative damage to renal structure and
function
 The membrane antioxidant vitamin E (α‐tocopherol) is examined as a
potential therapeutic intervention that may help to slow the rate of decline of
kidney function in such conditions
 Vitamin E therapy is also considered as a means of correcting plasma
antioxidant status and attenuating the cardiovascular disease that
accompanies kidney failure
 In healthy individuals, the recommended daily intake for vitamin E is 8 mg
(12 IU) for women and 10 mg (15 IU) for men (1 mg = 1.5 IU), based on
minimum levels required to prevent deficiency symptoms
 The optimal dose for vitamin E that may be helpful in slowing renal failure in
humans may lie between 300 to 700 IU/day

31.  References:
 Lyndsay A. Harshman, Kathy Lee-Son. Vitamin and trace element deficiencies in the
pediatric dialysis patient. Pediatr Nephrol. 2018 July ; 33(7): 1133–1143.
doi:10.1007/s00467-017-3751-z
 Magdalena Jankowska *, Bolesław Rutkowski. Vitamins and Microelement
Bioavailability in Different Stages of Chronic Kidney Disease. Nutrients 2017, 9, 282;
doi:10.3390/nu9030282
 Irene Capelli, Giuseppe Cianciolo. Folic Acid and Vitamin B12 Administration in CKD,
Why Not? Nutrients 2019, 11, 383; doi:10.3390/nu11020383
 ERIC DESCOMBES, ALFRED B. HANCK. Water soluble vitamins in chronic
hemodialysis patients and need for supplementation. Kidney International, Vol. 43
(1993), PP. 1319—1328
 Catherine M. Clase,*† Vincent Ki. Water-Soluble Vitamins in People with Low
Glomerular Filtration Rate or On Dialysis: A Review. Seminars in Dialysis—Vol 26, No 5
(September–October)
2013 pp. 546–567 DOI: 10.1111/sdi.12099 published by Wiley Periodicals, Inc.
 KDOQI Clinical Practice Guideline for Nutrition in Children with CKD: 2008 Update