Herbs and kidney


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Herbs and kidney

  1. 1. Herbal Nephropathy Thitisak Kitthaweesin MD. Department of Medicine Phramongkutklao College of Medicine งานประชุมวิชาการประจำปี ราชวิทยาลัยอายุรแพทย์แห่งประเทศไทย ครั้งที่ 21
  2. 2. Short History of Medicine <ul><ul><li>“ I have an earache …” </li></ul></ul><ul><li>2000 BC – Here, eat this root </li></ul><ul><li>1000 AD – The root is heathen. Here say this prayer </li></ul><ul><li>1850 AD – The prayer is superstition. Here, drink this potion </li></ul><ul><li>1930 AD – This potion is snake oil. Here, swallow this pill </li></ul><ul><li>1960 AD – The pill is ineffective. Here, take this antibiotic </li></ul><ul><li>2000 AD – The antibiotic is artificial. Here eat this root </li></ul>
  3. 3. Definition of Herbal Medicine <ul><li>Herbal medicines are crude drugs of vegetable or plant origin, utilized for the treatment of disease states, often of chronic nature, or to attain or maintain a condition of improved health </li></ul>
  4. 4. Common Misconceptions on Herbal Medicine <ul><li>“ Herbals are … ” </li></ul><ul><li>Completely ineffective </li></ul><ul><li>Effective and completely safe </li></ul><ul><li>Approved by FDA </li></ul><ul><li>Recommended for use based on scientific studies </li></ul><ul><li>Similar to homeopathy </li></ul><ul><li>Have accurate information on product label </li></ul>
  5. 5. Renal Syndrome in Herbal Medicine
  6. 6. ATN AIN Interstitial Renal fibrosis Stone Cancer Hypertension Electrolyte disturbance Edema Urinary retention ???
  7. 7. Renal Failure <ul><li>Acute tubular necrosis </li></ul><ul><li>Acute interstitial nephritis </li></ul><ul><li>Papillary necrosis </li></ul><ul><li>Chronic interstitial renal fibrosis </li></ul>
  8. 8. Cape Aloes <ul><li>Laxatives </li></ul><ul><li>Contains aloesin (aloeresin B) and aloeresin A </li></ul><ul><li>Case report of acute oliguric renal failure in South Africa </li></ul>
  9. 9. Cape aloes <ul><li>A 47-year-old black man from Soweto, South Africa </li></ul><ul><li>Use herbal remedy to “clean the stomach” for month </li></ul><ul><li>Presented with acute oliguric renal failure </li></ul><ul><li>Dialysis dependent for 6 weeks </li></ul><ul><li>Herbal remedies analysis revealed the presence of Cape aloes </li></ul>Valerie et al. AJKD 2002;39:E13
  10. 10. Flavonoids <ul><li>Bioflavonoids </li></ul><ul><li>Water-soluble plant pigments </li></ul><ul><li>Categories : Isoflavones,anthocyanidins, flavans, flavonols, flavones and flavanones </li></ul><ul><li>Not essential nutrients </li></ul><ul><li>Deficiencies not been reported </li></ul>
  11. 11. Flavonoids <ul><li>Sources </li></ul><ul><ul><li>Soy products </li></ul></ul><ul><ul><li>Fruits: cranberry, citrus, apples </li></ul></ul><ul><ul><li>Wine, tea </li></ul></ul><ul><li>Health concerns </li></ul><ul><ul><li>Chronic venous insuff </li></ul></ul><ul><ul><li>Edema </li></ul></ul><ul><ul><li>Diabetes </li></ul></ul><ul><ul><li>Dysmenorrhea </li></ul></ul><ul><ul><li>Hemorrhoids </li></ul></ul>
  12. 12. Flavonoid-induced ARF <ul><li>8 cases </li></ul><ul><li>Extraction of Taxus celebica , used as Rx for DM </li></ul><ul><li>Initially presented with fever, gastrointestinal upset followed by cola - colored urine and jaundice </li></ul><ul><li>Acute oliguric renal failure </li></ul><ul><li>Elevation of BUN, Cr lasted for 2-9 weeks </li></ul>Lin J,Ho Y . AJKD 1994;23:433-440
  13. 13. Flavonoid-induced ARF <ul><li>Hemolysis ( 100% ) , cholestatic hepatitis ( 50% ) , and DIC ( 50% ) were also noted </li></ul><ul><li>All required HD and all but one who died completely recovered within 2-9 weeks </li></ul><ul><li>Renal biopsy showed acute interstitial nephritis with acute tubular necrosis </li></ul>Lin J,Ho Y . AJKD 1994;23:433-440
  14. 14. Kwao Krua <ul><li>Butea superba </li></ul><ul><li>Red Kwao Krua </li></ul><ul><li>Thailand’s endemic species </li></ul><ul><li>“ High flavonoids” </li></ul><ul><li>Claims to use in erectile dysfunction </li></ul><ul><li>Products:ingestion and topical form </li></ul>
  15. 15. White Kwao Krua <ul><li>Pueraria mirifica   </li></ul><ul><li>Underground tuber accumulate phytoestrogens comprising “isoflavone” </li></ul><ul><li>Miroestrol, Deoxymiroestrol.. estrogenic activity </li></ul><ul><li>Anti - breast cancer , anti - prostate hyperplasia, anti - colon cancer, anti - osteoporosis, reduction of blood cholesterol and anti - menopausal syndrome </li></ul>
  16. 16. Chinese Herbs Nephropathy <ul><li>Belgium, </li></ul><ul><li>Followed weight loss regimen in same clinic </li></ul><ul><li>Chinese herbs Stephania tetrandra in slimming pills </li></ul><ul><li>Extensive interstitial fibrosis </li></ul><ul><li>Rapid progression </li></ul>
  17. 17. Brussels, Belgium <ul><li>2 patients were seen in terminal renal failure and were started immediately on dialysis </li></ul><ul><li>7 other women, the nephropathy was characterised by a rapid deterioration in renal function, with initial serum creatinine doubling within 3 months </li></ul>Vanherweghem JL et al. Lancet . 1993 13;341(8842):387-91
  18. 18. <ul><li>Phytochemical analysis of 12 different samples of S tetranda in Belgium (1990-1992) </li></ul><ul><li>Only one corresponded to Stephania species </li></ul><ul><li>Others were Aristolochia species (Aristolochic Acid) </li></ul><ul><li>More than 100 patients recorded in Belgium </li></ul><ul><li>70% treated by maintenance dialysis </li></ul>
  19. 19. AAs Chinese herb 1 USA(2000) A.mollisemae Chinese herb 1 HK(2005) AAs Chinese herb 6,12,20 China(2000, 2001,2003) AAs Eczema Rx 2 UK(1999) A.pistolochia Herb mixture 1 Spain(1996) A.fangchi Slimming pills 2,2 France (1994,1998) AAs Slimming pills 9 Belgium (1993) Agents Treatment Number Country
  20. 20. Pathology Hypocellular interstitial fibrosis Tubular atrophy Predominant in superficial cortex Glomeruli relatively spared
  21. 21. Urothelial Malignancy <ul><li>First case of urinary tract cancer repoeted in 1994 </li></ul><ul><li>Schmeiser et al.(Cancer Res.1996) detect DNA adducts formed by metabolites of AA in kidney removed from AAN patients </li></ul><ul><li>Specific marker of AA exposure and involved in carcinogenesis </li></ul><ul><li>Regular cystoscope, prophylactic removal of native kidneys and ureters in all end-stage AAN with dialysis/KT </li></ul>
  22. 23. <ul><li>39 patients </li></ul><ul><li>18 cases of Urothelial carcinoma (46%) 95%CI,29-62% </li></ul><ul><li>21 cases without CA </li></ul><ul><ul><li>Mild-to-moderate Dysplasia 19 Cases </li></ul></ul>
  23. 24. Duration and Total Doses
  24. 25. Risk Factors
  25. 26. Zhu et al.
  26. 27. Star Fruit <ul><li>Averrhoa carambola </li></ul><ul><li>Popular in tropical country </li></ul><ul><li>Types </li></ul><ul><ul><li>Sweet </li></ul></ul><ul><ul><li>Sour </li></ul></ul><ul><li>Oxalate …sour > sweet type </li></ul><ul><li>Vitamin C…26-53 mg/100 g of fruit </li></ul>
  27. 28. Star Fruit <ul><li>Sour type </li></ul><ul><ul><li>More oxalic acid </li></ul></ul><ul><ul><li>Smaller size </li></ul></ul><ul><ul><li>Rich flavored </li></ul></ul><ul><li>Sweet type </li></ul><ul><ul><li>Less oxalic acid </li></ul></ul><ul><ul><li>Larger size </li></ul></ul><ul><ul><li>Mild flavored </li></ul></ul>
  28. 29. Star Fruit Chang et al. AJKD 35:189-193,2000 114.3 3.31 191.9 Bottled 86.1 2.97 150.7 Canned 26 34.4 56 Fresh Cl K Na
  29. 30. Case Report Chen et al. AJKD 37:418-422, 2001 Abd/back pain N/V/backache Symptoms 4 hours hours Onset 3000 mL 1600 mL Amount Sour juice from vendor Pure fresh sour, juice Form Male Male Sex 38 77 Age
  30. 32. Dilatation of renal tubules Sloughing of renal tubular cells Interstitial edema Intraluminal and intraepithelial deposition of Oxalate Crystals Birefringence under polarized light
  31. 33. Oxalate <ul><li>Highly concentrated in urine </li></ul><ul><li>Freely filtered through glomeruli & active secretion from proximal tubule </li></ul><ul><li>Formation of calcium-oxalate crystal </li></ul><ul><li>Most crystals located at Papilla and Cortex (medullary rays were spared) </li></ul>
  32. 34. Conditions <ul><li>Ingestion of SOUR star fruit </li></ul><ul><li>Fasting </li></ul><ul><li>Dehydration </li></ul>
  33. 35. Star fruit in Uremic <ul><li>Level of intoxication </li></ul><ul><ul><li>Mild </li></ul></ul><ul><ul><ul><li>Hiccups, vomiting and insomnia </li></ul></ul></ul><ul><ul><li>Moderate </li></ul></ul><ul><ul><ul><li>Psychomotor agitation, numbness and paresthesias of the limbs, decreased muscle power, mild mental confusion </li></ul></ul></ul><ul><ul><li>Severe </li></ul></ul><ul><ul><ul><li>Severe mental confusion progressing to coma, seizures progressing to status epilepticus , hemodynamic instability progressing to hypotension and shock </li></ul></ul></ul>
  34. 36. Stone
  35. 37. Ma-Huang <ul><li>Ephedra sinica </li></ul><ul><li>E phedrine and pseudoephedrine </li></ul><ul><li>CNS stimulation, bronchodilation, and vasoconstriction </li></ul><ul><li>C ombination with caffeine, elicit weight loss </li></ul><ul><li>E fficacy in Rx of asthmatic bronchoconstriction and hypotension . </li></ul>
  36. 38. Renal Manifestation <ul><li>Hypertension </li></ul><ul><ul><li>1% ephedrine </li></ul></ul><ul><ul><li>Tea preparation containing 15-30 mg ephedrine </li></ul></ul><ul><ul><li>Maximum daily dose is 150 mg </li></ul></ul><ul><li>Kidney stones </li></ul><ul><ul><li>Ephedrine metabolites stone </li></ul></ul><ul><ul><li>Case of 27-year-old male with 6 episodes of renal colic in 6 months after ingestion of Ma-huang 4-12 tabs/day </li></ul></ul><ul><ul><li>(Powell T et al. AJKD 1998;32:153-159) </li></ul></ul>
  37. 39. Dietary supplements <ul><li>Promoted in US as means of losing weight & increasing energy </li></ul><ul><li>Stone analysis </li></ul><ul><ul><li>Orlando,FL…106 specimens of ephedrine stones among 166,466 stones (0.064%) (Powell T et al. AJKD 1998;32:153) </li></ul></ul><ul><li>Cardiovascular side effects </li></ul><ul><ul><li>HT, palpitation, tachycardia, stroke (Haller C et al. NEJM 2000;343:1833) </li></ul></ul>
  38. 40. Cranberry <ul><li>Vaccinium macrocarpon </li></ul><ul><li>Main claim of benefit is Prevention and treatment of UTI </li></ul><ul><li>Benefits </li></ul><ul><ul><li>Acidify urine </li></ul></ul><ul><ul><li>Excretion of Hippuric acid (bacteriostatic) </li></ul></ul><ul><ul><li>May cause loss of fimbriae and elongation of E.coli </li></ul></ul><ul><ul><li>In vitro evidence not associated with clinical benefits </li></ul></ul>
  39. 41. Cranberry Tablet <ul><li>Ingestion of cranberry concentrate tablets </li></ul><ul><li>Increased urinary oxalate excretion </li></ul><ul><li>Promote calcium oxalate nephrolithiasis </li></ul>
  40. 42. Oxalate Food
  41. 43. Pumpkin seeds <ul><li>Effect on oxalocrystalluria and urinary composition in 20 boys age 2-7 yr from a hyperendemic area of Ubol province </li></ul><ul><li>Experiment had 4 periods : </li></ul><ul><ul><li>control ( before treatment ) </li></ul></ul><ul><ul><li>oxalate supplementation 5mg/kg/day </li></ul></ul><ul><ul><li>pumpkin - seed or orthophosphate supplementation 60 mg/kg/day </li></ul></ul><ul><ul><li>post-treatment </li></ul></ul><ul><li>Morning and 24-h urines were collected analyzed for crystalluria, pH, Ca, P, oxalate, Cr, Na, K, citrate glycosaminoglycans, and pyrophosphate </li></ul>Supakarn et al. Am J Clin Nutr . 1987;45(1):115-21
  42. 44. Pumpkin seeds <ul><li>Pumpkin seeds lowered calcium - oxalate crystal occurrence and calcium level </li></ul><ul><li>But increased phosphorus, pyrophosphate, glycosaminoglycans, and potassium in urine </li></ul><ul><li>Pumpkin seeds provide high phosphorus levels and can be used as a potential agent in lowering the risk of bladder - stone disease . </li></ul>Supakarn et al. Am J Clin Nutr . 1987;45(1):115-21
  43. 45. Hypertension <ul><li>Glycyrrhiza species (Licorice) </li></ul><ul><li>Ephedra species (Ma-Huang) </li></ul><ul><li>Ya Hom </li></ul>
  44. 46. Licorice ( Glycyrrhiza glabra) Glycyrrhizic acid Glycyrrhetenic acid Renal 11 β -hydroxy-steroid dehydrogenase Hydrolyzed Inhibit
  45. 47. Apparent Mineralocorticoid Excess
  46. 48. AME <ul><li>Mineralocorticoid receptor in CCD 100:1 greater affinity to Aldosterone than cortisol </li></ul><ul><li>But circulating cortisol level are 10,000:1 relative to aldosterone </li></ul><ul><li>11 β -hydroxy-steroid dehydrogenase convert cortisol to inactive cortisone </li></ul><ul><li>Glycyrrhizic acid inhibit 11 β -OHSD retard local cortisol inactivation, leaving MN receptor vulnerable to cortisol activation </li></ul>
  47. 49. Manifestations <ul><li>Headache </li></ul><ul><li>Lethargy </li></ul><ul><li>Hypertension </li></ul><ul><li>Hypokalemia </li></ul><ul><li>Metabolic alkalosis </li></ul><ul><li>Heart failure </li></ul><ul><li>Cardiac arrest </li></ul>
  48. 50. Licorice <ul><li>Licorice bar </li></ul><ul><li>Candy </li></ul><ul><li>Chewing gum </li></ul><ul><li>Herbal cough mixture </li></ul><ul><li>Licorice tea </li></ul><ul><li>Licorice root </li></ul>De Klerk et al. BMJ 1997;314:731-735
  49. 51. Licorice <ul><li>Chinese herbal tea </li></ul><ul><ul><li>74% contain Glycyrrhiza glabra and Glycyrrhiza radix (Winslow et al.Arch Intern Med 1998;158:2192-2199) </li></ul></ul><ul><li>To minimize the risk </li></ul><ul><ul><li>Licorice not be ingested for longer than 4-6 weeks (Walker et al. Endocrinol Metab Clin North Am 1994;23:359-377 ) </li></ul></ul>
  50. 52. Ya-Hom <ul><li>Ya - hom , a traditional Thai herbal formulation </li></ul><ul><li>Use for fainting treatment </li></ul><ul><li>To determine the effect on the blood pressure in rats </li></ul><ul><li>The water extract of Ya - hom at 0.2, 0.4, 0.6 and 0.8g / kg initially transiently decreased BP and over time, increased BP </li></ul><ul><li>The duration and time to maximal effect was dose dependent </li></ul>Suvitayavat et al. J Ethnopharmacol 2005 ;97(3):503-8
  51. 53. Herb-drug Interactions
  52. 54. St John’s wort <ul><li>Extracts of Hypericum perforatum L . </li></ul><ul><li>Most common use is Rx depression </li></ul><ul><li>Numerous studies report to be more effective than placebo and equally effective as TCA in the short - term treatment of mild - to - moderate major depression ( 1-3 months ) </li></ul>
  53. 55. St John’s wort <ul><li>Potent inducer of cytochrome P450 isoenzymes (Ernst EE. Lancet 1999;354:2014-2016) </li></ul><ul><li>Decreased plasma levels of various drugs </li></ul><ul><ul><li>Johne A, Clin Pharmacol Ther 1999;66: 338-345 </li></ul></ul><ul><ul><li>Piscitelli SC . Lancet 2000;355:547-548 </li></ul></ul><ul><ul><li>Yue QY . Lancet 2000;355: 576-577 </li></ul></ul>
  54. 56. St John’s wort Decreased concentrations in serum Cyclosporine Breakthrough bleeding Oral pills Reduced total absorption Indinavir Increased INR Warfarin Decreased AUC, decreased peak and trough of concentrations Digoxin Decreased concentrations Theophylline
  55. 57. Barone GW et al. Transplant 2001;71:239-241
  56. 58. <ul><li>In renal transplant recipients </li></ul><ul><li>Concomitant use of St John’s wort with Cyclosporine or Tacrolimus could favor graft rejection </li></ul><ul><li>B y induction of the CYP3A4 system with St John's wort </li></ul>Bolley R et al . Transplantation 2002;73:1009
  57. 59. Ginkgo <ul><li>Ginkgo biloba </li></ul><ul><li>I ntermittent claudication, Alzheimer's , multi-infarct dementia, and &quot;cerebral insufficiency&quot; </li></ul><ul><li>E arly evidence favoring use of ginkgo for memory enhancement in healthy subjects, mountain sickness, premenstrual syndrome, and reduction of chemotherapy-induced end-organ vascular damage </li></ul>
  58. 60. Ginkgo Intracerebral haemorrhage Warfarin Subarachnoid haemorrhage and subdural haematoma have been reported with the use of ginkgo alone Bilateral subdural haematoma . Paracetamol and ergotamine / caffeine Ginkgolides are potent inhibitors of PAF . Spontaneous hyphema Aspirin
  59. 61. Hyperkalemia <ul><li>Noni juice </li></ul><ul><li>Alfalfa </li></ul><ul><li>Dandelion </li></ul>
  60. 62. Contaminated Herb <ul><li>Heavy metals : cadmium, lead </li></ul><ul><li>Drugs : analgesics, NSAIDS, steroid </li></ul>
  61. 63. Conclusion <ul><li>Herbal medicine is worldwide </li></ul><ul><li>Variety of renal syndromes </li></ul><ul><li>Under-reported therapy and adverse health effects </li></ul><ul><li>Physicians be aware of the potential risks and carefully question their patients about use of herbal medicine </li></ul>