First, thank you so much for responding to my questions so thoroughly. You have no idea how much this support helps me and can’t appreciate it enough.
I asked you about this case 1.5 months ago. 32 YO Female with Lupus Nephritis that recently flared up. Dx originally about 6 yrs ago. Labs were WNL until 3 months ago after a few episodes of cold. She began to go downhill. Most recent labs –> DNA Ds Ab = 70. ACR = 360 (normal is < 2.5). UA –> lots of abnormals.
Increased urinary frequency; more fatigue. No joint symptoms.About 1.5 months ago after consultation with you, I started her on Redox Support (NAC, Vitamin C, E, D, B’s, minerals, curcumin).
Nephrologist last week prescribed Prednisone 50 mg for 1 month and then to taper. Increased Mycophenolate to 1000 mg BID. My question is: is Prednisone 50 mg for one month too excessive of a dose and how much Hydrocortisone should I prescribe once she start to taper down the prednisone. Would 20 mg BID of Hydrocortisone be appropriate?
Also, what else can I be doing to support the kidneys, besides the Redox protocol as you had suggested?
Dr. Paul S. Anderson:
I am going to give the scientific as well as an experiential basis for the therapy I am proposing in the first portion of this plan considering the significant medical consequences of this case. I want to underscore that although we have experience with these cases each is treated individually.
I include use of l-glutamine as mentioned in the plan section below. The use and safety of l-glutamine in kidney disease is well reported, extensively studied and considered both safe and effective [1-11]. Although some misguided reports relate concern regarding the use of glutamine in the case of CKD high parenteral doses (14 to 28 grams) have not only been tolerated but clinically helpful in kidney disease [4].
I also recommend specific dosing of both oral acetyl-l-carnitine as well as parenteral l-carnitine based on experience in this situation as well as significant data. Carnitine (as both l-carnitine and Ac-l-carnitine) metabolism id deranged in CKD and has been shown to be nephroprotective when administered in that patient setting [15-22]. Doses of parenteral l-carnitine have been given efficaciously in end stage renal disease (20 mg/kg) [17].
Pyridoxine and its active metabolite P-5-P are additionally deranged and necessary in the treatment of CKD due to long term renal transaminase dysfunction as well as many other factors [23-27].
Curcumin as renoprotective: Curcumin has been shown in many papers in human and animal studies to be renoprotective [30-35]. In our experience a liposomal oral preparation is an appropriate addition to therapeutic protocols in diminished renal function. The “Meriva” product at 2-3 PO BID or the “CuraPro” type product at 1-2 PO BID are commonly used. Intravenous curcumin is also in trials currently for human use in renal failure, but we have no data as of yet.
Chelation: Only in some cases and if physician experience and comfort allows. I employ the use of specific low dose chelators therapy in a very specific formulation and formula progression as listed below. I want to underscore my appreciation of the concern regarding these therapies and also reiterate that this therapy has safely and successfully been used in patients with eGFR as low as 15. The use of specifically designed doses of chelators such as EDTA have been shown to be safe in renal disease [12] and effective at low dose to remove metals [13]. In our clinical practice with renal failure patients we have had no adverse events using renally adjusted doses of IV chelators in renal disease spanning eGFR of 9 to 45 as well [14]. Former ACAM guidelines for the use of high dose EDTA contraindicated use over serum creatinine of 2.5, the use of eGFR calculations and specific renal adjustment of doses has yielded safe (when cautiously applied [14]) low dose chelation in patients with eGFR as low as 15 [28].
———————————————————–
Consider for oral regimen:
• l-glutamine powder dosed prior to a meal 3-4 grams in juice or cold to room temperature food TID
• Acetyl-l-carnitine dosed 400-600 mg BID prior to food.
• Rentone 1 tablet TID prior to a meal (http://www.ayush.com/RENTONE_p_288.html) [12]
• Chinese Kidney Formula 3 BID prior to or with a meal http://www.americandragon.com/Herb%20Formulas%20copy/ShenQiWan.html [12,29]
• “Meriva” product at 2-3 PO BID or the “CuraPro” type product at 1-2 PO BID [30-35]
———————————————————–
References:
1. Ann Surg. 1998 Feb;227(2):302-8
2. European Journal of Clinical Nutrition (2008) 62, 575–583; doi:10.1038/sj.ejcn.1602754;
3. Hübl W1, Druml W, Roth E, Lochs H. Importance of liver and kidney for the utilization of glutamine-containing dipeptides in man. Metabolism. 1994 Sep;43(9):1104-7. PMID: 8084285
4. Weingartmann G1, Fridrich P, Mauritz W, Götzinger P, Mittlböck M, Germann P, Karner J, Roth E. Safety and efficacy of increasing dosages of glycyl-glutamine for total parenteral nutrition in polytrauma patients. Wien Klin Wochenschr. 1996;108(21):683-8. PMID: 8956477
5. Fürst P1, Albers S, Stehle P. Availability of glutamine supplied intravenously as alanylglutamine. Metabolism. 1989 Aug;38(8 Suppl 1):67-72. PMID: 2668705
6. Fürst P1, Albers S, Stehle P. Stress-induced intracellular glutamine depletion. The potential use of glutamine-containing peptides in parenteral nutrition. Beitr Infusionther Klin Ernahr. 1987;17:117-36. PMID: 3120690
7. Fürst P1, Albers S, Stehle P. Evidence for a nutritional need for glutamine in catabolic patients. Kidney Int Suppl. 1989 Nov;27:S287-92. PMID: 2517677
8. Fürst P1, Albers S, Stehle. Glutamine-containing dipeptides in parenteral nutrition. JPEN J Parenter Enteral Nutr. 1990 Jul-Aug;14(4 Suppl):118S-124S. PMID: 2119457
9. Lin MT1, Kung SP, Yeh SL, Lin C, Lin TH, Chen KH, Liaw KY, Lee PH, Chang KJ, Chen WJ. The effect of glutamine-supplemented total parenteral nutrition on nitrogen economy depends on severity of diseases in surgical patients. Clin Nutr. 2002 Jun;21(3):213-8. PMID: 12127929
10. Tamarappoo BK1, Joshi S, Welbourne TC. Interorgan glutamine flow regulation in metabolic acidosis. Miner Electrolyte Metab. 1990;16(5):322-30. PMID: 2283995
11. Guder WG1, Häussinger D, Gerok W. Renal and hepatic nitrogen metabolism in systemic acid base regulation. J Clin Chem Clin Biochem. 1987 Aug;25(8):457-66. PMID: 3320262
12. Lamson DW, Wright JV. A Case of EarlyRenal Functional Impairment Resolved with Nutrients and Botanicals. Alternative Medicine Review. Page 55 Volume 8, Number 1. 2003
13. Mikirova N, Casciari J, Hunninghake R, Riordan N. EDTA chelation therapy in the treatment of toxic metals exposure. Spatula DD. 2011; 1(2):81-89. DOI 10.5455/spatula.20110504045803
14. Anderson PS. Unpublished clinical experience using ultra low dose chelation and other nephroprotective parenteral substances in low eGFR – n=5. Personal communication.
15. Matera M, Bellinghieri G, Costantino G, Santoro D, Calvani M, Savica V. History of L-carnitine: implications for renal disease. J Ren Nutr. 2003 Jan;13(1):2-14. PMID: 12563618
16. Calvani M1, Benatti P, Mancinelli A, D’Iddio S, Giordano V, Koverech A, Amato A, Brass EP. Carnitine replacement in end-stage renal disease and hemodialysis. Ann N Y Acad Sci. 2004 Nov;1033:52-66. PMID: 15591003
17. Evans AM, Faull R, Fornasini G, Lemanowicz EF, Longo A, Pace S, Nation RL. Pharmacokinetics of L-carnitine in patients with end-stage renal disease undergoing long-term hemodialysis. Clin Pharmacol Ther. 2000 Sep;68(3):238-49. PMID: 11014405
18. Guarnieri G, Biolo G, Vinci P, Massolino B, Barazzoni R. Advances in carnitine in chronic uremia. J Ren Nutr. 2007 Jan;17(1):23-9. PMID: 17198928
19. Bellinghieri G1, Santoro D, Calvani M, Savica V.Role of carnitine in modulating acute-phase protein synthesis in hemodialysis patients. J Ren Nutr. 2005 Jan;15(1):13-7. PMID: 15648000
20. Savica V, Santoro D, Mazzaglia G, Ciolino F, Monardo P, Calvani M, Bellinghieri G, Kopple JD. L-carnitine infusions may suppress serum C-reactive protein and improve nutritional status in maintenance hemodialysis patients. J Ren Nutr. 2005 Apr;15(2):225-30. PMID: 15827896
21. Kalantar-Zadeh K1, Braglia A, Chow J, Kwon O, Kuwae N, Colman S, Cockram DB, Kopple JD.An anti-inflammatory and antioxidant nutritional supplement for hypoalbuminemic hemodialysis patients: a pilot/feasibility study. J Ren Nutr. 2005 Jul;15(3):318-31. PMID: 16007562
22. Duranay M1, Akay H, Yilmaz FM, Senes M, Tekeli N, Yücel D. Effects of L-carnitine infusions on inflammatory and nutritional markers in haemodialysis patients. Nephrol Dial Transplant. 2006 Nov;21(11):3211-4. Epub 2006 Jul 22. PMID: 16861734
23. A. Mitwalli, A. Ayiomamitis, L. Grass, D. G. Oreopoulos. Control of hyperoxaluria with large doses of pyridoxine in patients with kidney stones. International Urology and Nephrology. 1988, Volume 20, Issue 4, pp 353-359
24. Clayton PT. B6-responsive disorders: a model of vitamin dependency. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):317-26. PMID: 16763894
25. Laso Guzmán FJ1, González-Buitrago JM, Vela R, Cava F, de Castro S. Vitamin B6 status in uremia. Klin Wochenschr. 1990 Feb 1;68(3):183-6. PMID: 2314006
26. Ono K1, Ono T, Matsumata T. The pathogenesis of decreased aspartate aminotransferase and alanine aminotransferase activity in the plasma of hemodialysis patients: the role of vitamin B6 deficiency. Clin Nephrol. 1995 Jun;43(6):405-8. PMID: 7554526
27. Kopple JD, Mercurio K, Blumenkrantz MJ, Jones MR, Tallos J, Roberts C, Card B, Saltzman R, Casciato DA, Swendseid ME. Daily requirement for pyridoxine supplements in chronic renal failure. Kidney Int. 1981 May;19(5):694-704. PMID: 7289398
28. Osborne V, Anderson P. EDTA Chelation and Intravenous Detoxification Therapies – Certification Course for Physicians. Slide 60 and 215. IIVNTP Publications, 09-2007 (updated 01-2014).
29. Yifei Zhong1. Therapeutic use of traditional Chinese herbal medications for chronic kidney diseases. Kidney International (2013) 84, 1108–1118; doi:10.1038/ki.2013.276; published online 17 July 2013
30. NM Rogers, MD Stephenson, AR Kitching, JD Horowitz, and PTH Coates. Amelioration of renal ischaemia–reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells. British Journal of Pharmacology (2012) 166 194–209
31. S. S. Ghosh, et.al. Curcumin and enalapril ameliorate renal failure by antagonizing inflammation in 5⁄6 nephrectomized rats: role of phospholipase and cyclooxygenase. Am J Physiol Renal Physiol 302: F439–F454, 2012.
32. JoyceTrujillo, et.al. Renoprotectiveeffectoftheantioxidantcurcumin: Recent findings. RedoxBiology1(2013)448–456
33. Fang ZHONG, Hui CHEN, Lin HAN, Yuanmeng JIN, and Weiming WANG. Curcumin Attenuates Lipopolysaccharide-Induced Renal Inflammation. Biol. Pharm. Bull. 34(2) 226—232 (2011)
34. Prabhleen Singh, Aihua Deng, Roland C. Blantz, and Scott C. Thomson. Unexpected effect of angiotensin AT1 receptor blockade on tubuloglomerular feedback in early subtotal nephrectomy. Am J Physiol Renal Physiol 296: F1158–F1165, 2009.
35. Soetikno V, Sari FR, Lakshmanan AP, Arumugam S, Harima M, Suzuki K, Kawachi H, Watanabe K. Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2-keap1 pathway. Mol Nutr Food Res. 2013 Sep;57(9):1649-59. doi: 10.1002/mnfr.201200540. Epub 2012 Nov 23. PMID: 23174956