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

0

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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