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
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
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
