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Chronic Renal FailureEric Yarnell, ND, RH(AHG)
2012
Abbreviations
CCl = creatinine clearanceCKD = chronic kidney diseaseCRF = chronic renal failureeGFR = estimated GFRESRD = end-stage renal diseaseGFR = glomerular filtration rateSCr = serum creatinineUSRDS = 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 CRFNephron loss
Uremic toxin
buildup
Electrolyte, water
dysregulation
Endocrine dysfunction
Enzyme inhibition,
cellular toxicity
ErythropoietinCarnitine
Vitamin D
NeuropathyFatigue
AcidosisDementia
DyslipidemiaHomocysNausea
HyperkalemiaHyponatremia
HyperaldosteroneEdema
HypertensionIsosthenuria
AnemiaDyslipidemiaHypocalcemia
High phosOsteodystrophy
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* NoneII 60-99 ml/min** None
IIIa 45-59 ml/min Mild/NoneIIIb 30-44 ml/min Mild/moderate IV 15-29 ml/min ModerateV <15 ml/min Severe or on dialysis
* = SCr nl; ** = SCr elevated
Nomenclatural Morass
Pathological Syndrome
Clinical Syndrome
Hypertensive nephropathyGlomerulonephritis
Diabetic nephropathy
Asymptomatic proteinuriaChronic renal failure
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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
LiverAngiotensinogen
Angiotensin I(1-10)
Angiotensin II(1-8)
Lungs
Angiotensin-convertingenzyme (ACE)
Aldosterone
stimulates
High-molecular weightKininogen
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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Lespedezacapitata
Planta Med 1992;58:297.
Lespedeza capitata Range
Crataegus laevigataPhytomedicine 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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Urticadioicaseed
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
HOCH3
OH
O
CH2OH
O
CH3
CH3OH
O
CH2OH
O
11B-HSD2
Cortisol Cortisone
Glycyrrhetinic acidPotassiumwasting
Kidney Int 2009;76:877-84n=10 on hemodialysis, DBPC3 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% placeboNo 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 Yi Jie He Za Zhi 1992;12(8):461-4, 451-2.)
• Astragalus membranaceus
• Panax ginseng
Symptom Management
• Anorexia: Swertia radiata, Mahonia aquifolium, Gentiana lutea, other bitters
• Dysgeusia: bitters
• Nausea: Zingiber officinale, Mentha x piperita, Matricaria recutita
• Dyslipidemia: Allium sativum, plant or fish essential fatty acids (esp. Perilla frutescens)
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Case Examples
Base FormulaHerb Extract Amount
Urtica dioica seed Tincture 20-25%
Lespedeza capitata herb Tincture 20-25%
Parietaria judaica herb Tincture 15-20%
Codonopsis pilosula root Tincture 15-20%
Ceanothus gre)ii root Tincture 5-10%
Glycyrrhiza glabra root Glycerite 5-10%
Diabetic Nephropathy Case 1
0
2.5
5.0
7.5
10.0
11/1
3/02
7/30
/03
9/9/
03
4/22
/04
8/26
/04
9/23
/04
10/1
9/04
11/2
3/04
1/18
/05
2/15
/05
4/12
/05
5/15
/05
5/17
/05
6/30
/05
8/9/
05
Serum creatinine (mg/dL)Serum potassium (mmol /L)
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0
45
90
135
180
7/30
/03
9/9/
03
4/22
/03
10/1
9/04
1/18
/05
2/15
/05
4/12
/05
6/30
/05
8/9/
05
Serum glucose (mg/dL)
Diabetic Nephropathy Case 1
Lespedeza capitata herb Tincture 23%
Parietaria judaica herb Tincture 22%
Urtica dioica seed Tincture 12%
Panax ginseng root Tincture 12%
Astragalus membr. root Tincture 10%
Rheum palmatum root Tincture 10%
Foeniculum vulgare fruit Tincture 5%
Diabetic Nephropathy Case 1
Diabetic Nephropathy Case 2
1.30
1.45
1.60
1.75
1.90
2.05
2.20
6/10 8/10 10/10 2/11
Creatinine, serum
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Herbal FormulaCrataegus monogyna herb Glycerite 30%Fumaria officinalis herb Tincture 20%Piper methysticum root Tincture 20%
Urtica dioica seed Tincture 10%Glycyrrhiza glabra root Fluid extract 5%
Rauvolfia serpentina root Fluid extract 5%Ceanothus gre)ii root Tincture 5%
Zingiber officinale rhizome Tincture 5%
Polycystic Kidney Case
8.000
9.167
10.333
11.500
12.667
13.833
15.000
12/06 3/07 7/07 9/07
Creatinine, serum
On formula On formula
Off formula
Polycystic Kidney CaseUrtica dioica seed Tincture 25%
Lespedeza capitata herb Tincture 25%
Astragalus membr. root Glycerite 15%
Phytolacca americana root Tincture 15%
Salvia miltiorrhiza root Tincture 10%
Rheum palmatum root Tincture 10%
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Hypertensive Nephropathy Case
0
0.475
0.950
1.425
1.900
2/26/10 3/2/10 4/22/10 5/13/10 8/10/10 3/26/11 6/6/11 8/8/11 3/26/12
SCr
Hypertensive Nephropathy CaseWithania somnifera root Tincture 20%
Ammi visnaga fruit Tincture 15%Catharanthus roseus herb Tincture 15%Crataegus monogyna herb Glycerite 12.5%
Urtica dioica seed Tincture 10%Piscidia piscipula bark Tincture 10%
Cephalotaxus fortunei seed Tincture 5%Phytolacca americana root Tincture 5%
Taxus brevifolia leaf Tincture 5%Rauvolfia serpentina root Fluid extract 2.5%
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