KidneyVite is a state of the art multivitamin supplement specially designed for ALL patients: - with kidney disease - receiving hemodialysis and peritoneal dialysis - and kidney transplant recipients - with diabetes or hypertension, and therefore at risk for kidney disease.

1. Unmet Medical Needs for Vitamins with
Chronic Kidney Disease (CKD Stage 1-5)
and ESRD
KidneyViteTM
MyGen Labs Inc., Los Angeles, California

2. Vitamins Improve Survival in Dialysis Patients
DOPPS Data; Fissell et al, Am J Kidney Dis, 44:293-299, 2004

3. Comparison 1st Generation 2nd Generation 3rd Generation LATEST
Examples Nephrovite
Nephrocap Renavite
Dialyvite with Zinc
Prorenal Vital KidneyVite
Unique ingredient(s) added
for the first time
⎯ Zn Cu
5 methyl THF
Vitamin K
Lycopene
Lutein
Water Soluble Vitamins B
and C
✓
✓
✓
✓
Synthetic Folic acid ✓
✓
✓
⎯
Active Folate
(5-methyltetrahydrofolate)
⎯ ⎯ ⎯ ✓
Vitamin D ⎯ ✓
✓
✓
Vitamin K ⎯ ⎯ ⎯ ✓
Lycopene and Lutein ⎯ ⎯ ⎯ ✓
Zinc ⎯ ✓
✓
✓
Copper ⎯ ⎯ ✓
✓
Selenium ⎯ ⎯ ✓
✓

4. KidneyViteTM
A State of the Art Renal Vitamin
The First and Only Renal Vitamin with
1. 5-methyl tetrahydrofolate
(replaces synthetic folic acid)
2. Vitamin K
3. Lycopene
4. Lutein

5. B1 Thiamine; B2 Riboflavin; B3 Niacin; B5 Pantothenic Acid; B6 Pyridoxin; B7 Biotin; B12 Cobalamin
Non-Prescription Multivitamins for CKD

6. Why 5 methyl THF &
NOT synthetic folic acid?

7. Folate Metabolic Pathways

8. Effect of MTHFR Genotype on its Enzyme
Activity

9. Frequency of TT genotype for MTHFR C677T
South Chinese Han 8%
North Chinese Han 20-30%
US Caucasians 11%
US African Americans 2-3%
US Hispanics 18%
Mexico 32%
Israel 9%
Italy, Veneto 16%
Italy, Campania 27%
The dramatic frequency difference
reflects
the effect of dietary folate and
its selection pressure on
successful pregnancy and prenatal
survival
(Wilcken et al, 2003).
Between 5 and 10% of the population has a gene variant that reduces MTHFR
activity by 70%,while nearly 50% of people of European descent have a
genetic variation that decreases MTHFR activity by as much as 35%.

10. Hyperhomocystenemia
Independent risk factor for
cardiovascular diseases including
• atherosclerosis and its
consequences,
• heart attack, stroke, and
• peripheral vascular disease

11. Huo et al, JAMA. 2015;313(13):1325-1335

13. Incidence of First Stroke in HTN Subjects with Lowest Baseline Levels of Serum folate:
MTHFR Genotype Determines Benefit with Supplemental Folic Acid
CC CT TT
27% 49% 24%
Folic Acid is not effective in preventing stroke in the TT Genotype

14. Folic acid reduces rate of progression of CKD
In patients with CKD at baseline (n=1671), double-blind RCT (2008-2013)
0.8 mg folic acid+10 mg enalapril versus 10 mg enalapril
Median follow up: 4.4 years
Folic acid therapy resulted in a significant reduction in the risks for
• the primary event of ↓ eGFR (OR, 0.44; 95%CI, 0.26-0.75),
• Rapid decline ↓ eGFR (OR, 0.67; 95%CI, 0.47-0.96)
• Composite event (OR, 0.62; 95%CI, 0.43-0.90)
• 44% slower decline eGFR (0.96% vs 1.72% per year, P < .001).
• 2.9 (3.9 to 1.8) µM decrease in serum Hcy from baseline level of ~ 17 µM.
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• Primary event: 30% ↓ eGFR (if baseline eGFR> 60 mL/min) or
50% ↓ eGFR (if baseline eGFR < 60 mL/min) or ESRD
• Secondary event: composite of the primary outcome and all-cause death,
rapid decline in renal function, and rate of eGFR decline
China Stroke Primary Prevention Trial: The Renal Substudy. JAMA Intern Med. 2016;176(10):1443-1450

15. Renal Protection in MTHFR subtypes
Folic Acid supplementation fails to confer renal protection only in TT genotype

16. 5 Methyl THF and Survival in ESRD

18. Unmetabolized Folic Acid & Immune Dysfunction
• 400 µg Folic acid per day for about 4 months generates
unmetabolised folic acid in plasma
• ↓ natural killer cells in spleen,
• ↓ NK cell cytotoxic activity
• Effects on immune function worse in females > 60 yrs.
• Effects on immune function worse when > 400 µg/day
supplement
Sweene MR et al. Folic acid fortifiation and public health: report on threshold dose above which
unmetabolised folic acid appear in serum. BMC Public Health 2007
Sawaengsri et al., NK cell cytotoxicity is reduced in aged female mice fed a high folic acid diet. Faseb J 2013
Troen et al, Unmetabolized folic Acid in plasma and Reduced NK Cytotoxicity in postmenopausal women. J
Nutr 2006

19. Unmetabolized Plasma Folic Acid and Cancer
Ebbing et al, JAMA 2009

20. Why Prescribe Vitamin K to CKD Patients
• Vascular calcification (VC) in CKD → Asymmetric cardiac hypertrophy
↓
Sudden death ← Cardiac Arrhythmias
↑
Coronary artery calcification
• MGP (Matrix Gla protein) is a potent inhibitor of VC by bone morphogenetic protein-2 (BMP-2) antagonism & a
direct calcium-complexing effect
• MGP largely in vascular smooth muscle cells in the arterial media and chondrocytes
• Uncarboxylated MGP (ucMGP)) require Vitamin K to make active carboxylated MGP

21. MGP is a
critical anti-
calcific
molecule

22. Uncarboxylated MGP in CKD-HD & Effect of Vitamin K2
Supplementation
Baseline (compared with controls)
• 4.5-fold higher (also 8.4-fold higher uncarboxylated
osteocalcin)
After Rx with Vitamin K2 (menaquinone-7)
• 77% ↓ with 135 µg
• 93% ↓ with 360 µg
Westenfeld R. et al. Effect of vitamin K2 supplementation on functional vitamin K deficiency in
hemodialysis patients: A randomized trial. Am J Kidney Dis 2012; 59: 186–195.

23. Warfarin induced VC reversed by Vit K1 or vit K2
• a high intake of vitamin K2 (MK4) regresses
warfarin induced medial calcification in Wistar
rats^.
Schurgers LJ, Spronk HM, Soute BA et al. Regression of warfarin-induced medial
elastocalcinosis by high intake of vitamin K in rats. Blood 2007;109: 2823–2831.

24. Consequences of Zn Deficiency
• Oxidative stress
• Altered taste, anorexia
• Hair loss
• Delayed wound healing, skin lesions
• Growth retardation, delayed sexual maturation in children
• Immune dysfunction and Infections
• ↓T cell proliferation and function
• ↓ Macrophage phagocytic function

25. Cu Deficiency in CKD-HD
Group 1: AKI on HD; Group 2: CKD-HD
Exclusion criteria: DM, liver disease, alcoholics, smokers, respiratory diseases
Bhogade et al, Eur J General Med, 2013

27. Zn supplementation impairs Cu absorption

28. Zn and Cu ratio regulates Superoxide dismutase
1 (SOD-1)

29. Consequences of Cu Deficiency
• Oxidative stress
• Anemia: megaloblastic or
sideroblastic
• Leucopenia
• Growth retardation in children
• Decreased pigmentation
• Osteoporosis
• ↓Lipolysis, ↑fat in adipocytes, obesity
FOOD SOURCES: shell fish, legumes,
meat, nuts, cheese
Krishnamoorthy et al, Nature Chemical Biology 2016

30. Consequences of Se Deficiency
• Oxidant stress (Se dependent glutathione peroxidase activity
impaired)
• Cardiomyopathy
• Anemia
• Myopathy, myositis
FOOD SOURCES: seafood, meat, whole grains
• The Se content of plant or animal products depends on Se content of
soil in which plants grown or animals graze

31. Lycopene
Lycopene is a member
of the carotenoid
family, and it is the
naturally occurring
compound that gives
the characteristic red
color to the tomato,
watermelon, pink
grapefruit, and
orange.
• No β-ionone ring structure at
the end of the molecule,
cannot be converted to vitamin
A.
• Lycopene has a higher
antioxidant effect compared
to α-carotene and β-carotene

32. PBRC 2005
Lutein
Cell cultures, animal models, and human studies have
demonstrated the potential role of lutein in protecting
against several chronic diseases, particularly
• age-related macular degeneration (AMD)
• cataract,
• cancer at various sites, and
• heart disease and stroke

33. Lycopene and Lutein Deficiency in CKD-HD
Roehrs et al, BMC Nephrology, 2011

34. Composition of Current Renal Multivitamin
Formulations
B1 Thiamine; B2 Riboflavin; B3 Niacin; B5 Pantothenic Acid; B6 Pyridoxin; B7 Biotin; B12 Cobalamin

35. Composition of KidneyVite
Made in USA for
MyGen Labs, Inc.

36. Comparison 1st Generation 2nd Generation 3rd Generation LATEST
Examples Nephrovite
Nephrocap Renavite
Dialyvite with Zinc
Prorenal Vital KidneyVite
Unique ingredient(s) added
for the first time
⎯ Zn Cu
5 methyl THF
Vitamin K
Lycopene
Lutein
Water Soluble Vitamins B
and C
✓
✓
✓
✓
Synthetic Folic acid ✓
✓
✓
⎯
Active Folate
(5-methyltetrahydrofolate)
⎯ ⎯ ⎯ ✓
Vitamin D ⎯ ✓
✓
✓
Vitamin K ⎯ ⎯ ⎯ ✓
Lycopene and Lutein ⎯ ⎯ ⎯ ✓
Zinc ⎯ ✓
✓
✓
Copper ⎯ ⎯ ✓
✓
Selenium ⎯ ⎯ ✓
✓