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Chronic Renal Failure - Five Flavors · PDF file Chronic Renal Failure Eric Yarnell, ND, RH(AHG) 2012 Abbreviations CCl = creatinine clearance CKD = chronic kidney disease CRF = chronic

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  • Chronic Renal Failure Eric Yarnell, ND, RH(AHG)

    2012

    Abbreviations

    CCl = creatinine clearance CKD = chronic kidney disease CRF = chronic renal failure eGFR = estimated GFR ESRD = end-stage renal disease GFR = glomerular filtration rate SCr = serum creatinine USRDS = United States Renal Data System

    Screening for Early CRF

    • Serum Creatinine (SCr): by the time it is abnormal, it is already too late

    • eGFR: same story as SCr

    • Urine protein- or albumin-to-creatinine ratio: positive much earlier, need to confirm single abnormals with repeat test in 1--2 months

    • Elevated urine protein or albumin is huge risk factor for CV disease anyway

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  • CRF and CV Disease

    • References showing urine albuminuria/proteinuria and early CRF are risks for CV disease mortality (more predictive than lipids):

    • N Engl J Med 2004;351:1296–305.

    • Circulation 2003;108:2154–69.

    • Circulation 2002;106:777–82

    When Kidneys Fail

    Major Causes

    • Diabetic nephropathy

    • Hypertensive nephropathy

    • Inflammatory/autoimmune diseases (glomerulonephritides)

    If at all possible, TREAT THE CAUSE!!!

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  • Epidemiology

    2011 USRDS Annual Data Report

    Condition US Deaths in 2006 Heart disease 629,191

    Influenza 56,247

    Kidney dz 44,791

    Liver dz 27,299

    NVSS 2008;56(16)

    Pathogenesis of CRF Nephron loss

    Uremic toxin

    buildup

    Electrolyte, water

    dysregulation

    Endocrine dysfunction

    Enzyme inhibition,

    cellular toxicity

    Erythropoietin Carnitine

    Vitamin D

    Neuropathy Fatigue

    Acidosis Dementia

    Dyslipidemia Homocys Nausea

    Hyperkalemia Hyponatremia

    Hyperaldosterone Edema

    Hypertension Isosthenuria

    Anemia Dyslipidemia Hypocalcemia

    High phos Osteodystrophy

    High PTH

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  • Importance of Protein Trafficking

    Renal injury with nephron loss

    Glomerular capillary hypertension

    Glomerular protein trafficking

    Inflammatory cascade activated

    Proteinuria

    Ann Rev Med 2000;51:315-27

    Definitions of CRF

    Stage GFR Symptoms

    I 60-99 ml/min* None II 60-99 ml/min** None

    IIIa 45-59 ml/min Mild/None IIIb 30-44 ml/min Mild/moderate IV 15-29 ml/min Moderate V

  • Limits and Possibilities

    Natural Medicine and CRF

    • Lack of understanding of renal physiology

    • Excessive focus on the liver

    • Mainstream medical ignorance of what we do

    • Failure to think outside the conventional box

    • We can help people with CRF, have to work cooperatively (esp. patients on dialysis)

    • What fear means

    Things Not to Do

    • Push lots of water

    • Give herbal diuretics

    • Give potassium-rich herbs/food without monitoring

    • Promise you can cure kidney failure

    • Tell people to go off dialysis

    • Give in to ignorance and fear

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  • Realistic Expectations

    • Early disease (stage I): stabilization, improvement IF causes are removed

    • Moderate disease (stages II, III): stabilization, mild improvement, difficulty removing causes thus frustration

    • Severe disease (stages IV, V): progressive but delayed decline, improvement in health while on dialysis

    Risk Factors for CRF

    • Identical to CV disease really

    • Standard American diet

    • Obesity

    • Smoking

    • Sedentariness

    • But also can be due to intrinsic kidney dz

    Basic Approach to Early CRF • Identify and treat the cause(s) above all else

    • Whole-food, plant-centered diet: very safe in stage I-III CRF (monitor labs stage IV); usually treats the cause.

    • Consider Paleolithic diet in patients with diabetic nephropathy

    • Regular exercise, stress reduction

    • Nonspecific nephroprotective herbs

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  • Low-Protein Diet • 0.6--0.8 g protein/kg body weight qd (most

    Americans eat double this amount)

    • Slows but doesn’t stop progression, which doesn’t seem all that useful as a result (Ann Intern Med 1996;124:627-32)

    • A more pescovegan, legume-based approach may be superior to standard high-carb low-protein diet (Lancet 1992;339:1131-4)

    • Unnecessary prior to stage IV

    • Better to treat the cause specifically if possible

    Renin-Angiotensin- Aldosterone System

    Renin

    Liver Angiotensinogen

    Angiotensin I (1-10)

    Angiotensin II (1-8)

    Lungs

    Angiotensin- converting enzyme (ACE)

    Aldosterone

    stimulates

    High-molecular weight Kininogen

    Bradykinin

    Inactive

    ACE

    Kallikrein

    Angiotensin (1-9)

    Angiotensin (1-7)

    ACE

    ACE2

    ACE2

    Kidneys

    Kidneys

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  • ACE Inhibitors

    • Reduce progression of CRF in some populations independent of lowering BP

    • Most helpful in diabetic nephropathy and glomerulonephritis

    • Five best studied for CRF patients: benazepril, captopril, enalapril, quinapril, ramipril

    • All available generic (ramipril most expensive)

    ACEi Adverse Effects

    • Irritating cough (bradykinin excess; common)

    • Hypotension (rare)

    • Hyperkalemia (uncommon)

    • Mild elevated SCr (common)

    • Angioedema (rare but dangerous)

    • CI in pregnancy; don’t combine with NSAIDs

    Natural ACEIs • Lespedeza capitata (round-headed lespedeza)

    • Crataegus spp (hawthorn)

    • A$ium sativum (garlic)

    • Ganoderma lucidum (reishi, ling zhi)

    • Hibiscus spp (roselle)

    • Do so much more than drug ACEi, milder ACEi, safer, also cheap

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  • Lespedeza capitata

    Planta Med 1992;58:297.

    Lespedeza capitata Range

    Crataegus laevigata Phytomedicine 2001;8(1):47-52.

    © 2012 Yarnell

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  • Ganoderma lucidum (reishi)

    J Biosci Bioeng 2004;97:24-8; Chem Pharm Bull 1986;34:3025-8

    © 2012 Yarnell

    Hibiscus waimeae

    © 2012 Yarnell

    Apigenin

    Kaempferol Quercetin

    O

    OH

    OH

    OOH

    HO

    Luteolin

    O

    OH O

    HO

    OH

    OH

    OH

    O

    OH O

    HO

    OH

    OH

    ACEi Flavonols and Flavones

    Phytother Res 2007;21:32--36

    O

    OH O

    HO

    OH

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  • Angiotensin Receptor Blockers

    • Antagonize angiotensin II AT1 receptors

    • Vasodilatory, decrease ADH & aldosterone

    • Newer, more expensive

    • “Me too” syndrome like ACEi (puts the lie to drug companies as innovative, see Angell Truth About the Drug Companies)

    • Losartan, irbesartan, candesartan, valsartan

    ARB Toxicity

    • Adverse effects: orthostatic hypotension, HA, hyperkalemia, incr SCr

    • Rare: neutropenia, angioedema

    • May increase risk of getting cancer, without increasing mortality (Lancet Oncol 2010;11:627-36).

    • Valsartan at least is a vit D blocker

    • Drug interactions: NSAIDs, lithium, diuretics

    Nephroprotective Herbs

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  • Urtica dioica seed

    Slide courtesy of Jonathan Treasure MNIMH.

    Urtica seed for CRF

    Slide courtesy of Jonathan Treasure MNIMH.

    Urtica seed for CRF

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  • Rheum palmatum

    © 2012 Yarnell

    © 2012 Heron Botanicals, used with permission

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    2.5

    5.0

    7.5

    10.0

    Pre-Tx Post-Tx

    Daio group Control group

    Creatinine Clearance with Rheum

    Am J Chin Med 2003;31:267-75

    SCr

    Parietaria officinalis © 2012 Heron Botanicals, used with permission

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  • Orthosiphon spp

    © 2012 Yarnell

    Hyperkalemia

    Glycyrrhiza glabra

    © 2012 Yarnell

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  • O

    CH3

    HO CH3

    OH

    O

    CH2OH

    O

    CH3

    CH3 OH

    O

    CH2OH

    O

    11B-HSD2

    Cortisol Cortisone

    Glycyrrhetinic acid Potassium wasting

    Kidney Int 2009;76:877-84 n=10 on hemodialysis, DBPC 3 mon on each tx (500 mg GA bid vs. dextrose in cookies) 9 of 10 had lowered K+ on GA; 70% nl during GA vs. 24% placebo No htn or weight gain on GA

    Erythropoietin

    Epoetin

    • If Hgb incr. above 13 g/dl, incr. CV mortality (>50% of dialysis patients were over limit)

    • Amgen and Johnson and Johnson were pushing unsafe prescribing, paying doctors to use (dose tripled from introduction in 1991 to 2001)

    • Single largest drug expense for Medicare

    • Synthetic alternative: darbepoietin (no better)

    New York Times 9 May 2007

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  • Adaptogens and Bone

    • Guishao Sijunzi Tang (Four Nobles with Danggui and Paeonia) (J Tradit Chin Med 1999;19:3-9)

    • Baoyuan Tang (Zhon)uo Zhong Xi