Eric Yarnell, ND, RH(AHG)
2013
VESICOURETERAL REFLUX
Figure 1 Diagram of the bladder submucosal tunnel
Reference: Cooper 2009Normal Short
Figure 2 International Reflux Grading System
Reference: Cooper 2009
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Figure 7. Grading of vesicoureteral reflux with the International Reflux System.
Reference: Fernbach 2000
©2000 by Radiological Society of North America
EVALUATION
To diagnose VUR:
VCUG: urethral/bladder function assessed, requires catheter
Nuclear cystograph: to assess kidney function and structure
Other assessments:
Kidney/bladder US: to see gross defects
IVP: visualizes entire urinary tract
DMSA scintigraphy: to assess renal scarring
MONITORING
UTI incidence
Blood pressure
Urine creatinine
Urine microalbumin
Renal ultrasound (if no scarring and no UTI x 5 yr, stop monitoring)
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ANTIBIOTIC PROPHYLAXIS?
Increases resistance without decreasing UTI incidence in huge study, n = 74,974 (Conway 2007).
That includes VUR kids (stage 4-5 most likely to get recurrent UTI)
Trial showing no prevention of pyelonephritis or renal scarring in 100 Italian kids with VUR II-V vs. no tx, 4 yr follow-up (Pennesi 2008)
SURGERY?
Indication for referral: VUR III+ with multiple recurrent UTIs, pyelonephritis, or signs of kidney damage
Not superior to medical tx in randomized trial (Smellie 2001)
“It is uncertain whether the treatment of children with VUR confers clinically important benefit. The additional benefit of surgery over antibiotics alone is small at best. Assuming a UTI rate of 20% for children with VUR on antibiotics for five years, nine re-implantations would be required to prevent one febrile UTI, with no reduction in the number of children developing any UTI or renal damage.” (Hodson 2007)
NATURAL TREATMENT PRINCIPLES
Bacterial adhesion inhibitors; probiotics
Immunostimulants, immunomodulators
Urinary tract tonics
Antifibrotics
Treat acute UTIs; if not much better in 24-48 h resort to antibiotics
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Vacciniummacrocarpon
V. ovatum © 2012 G. Maroney, used with permissionV. macrocarpon © 2013 E. Yarnell
CLINICAL TRIAL 1
Japanese children (n=7 boys, 5 girls) with VUR I-IV given 100 ml juice concentrate (“50%”) qd
Controls: 11 boys, 8 girls given cefaclor 5--10 mg/kg
3--27 mon follow-up
UTI (defined as fever, elev CRP, 106 CFU/ml) occurred in 2 pt in each group (not significantly different)
Reference: Nishizaki 2009
CLINICAL TRIAL 2
Italian children n=186, double-blind trial, 1 yr follow-up
Randomized to cranberry juice (“2.8% extract”) or trimethoprim syrup
No difference in UTI rates between groups
Subgroup with high ferulic acid levels in urine did have higher UTI rate. Difference in grain intake, or gut flora?
Ref: Uberos 2012
HO
H3COOH
O
ferulic acid
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CRANBERRY INTERACTIONS
No interaction with cefaclor or amoxicillin in humans (Li 2009)
Sulfamethoxazole-trimethoprim: unknown, unlikely
Nitrofurantoin: unknown, unlikely
Confusing data on warfarin interactions
Safe in pregnancy (Wing 2008)
MISC ADHESION INHIBITORS
Vaccinium vitis-idaea (lingonberry)
Equisetum arvense (horsetail)
Betula pendula (birch)
Galium odoratum (sweet woodruff)
Urtica dioica (nettle) leaf
Herniaria glabra (rupturewort)
Zea mays (corn) stigmata
Elymus repens (couch grass)
Reference: Rafsanjany 2013;
Wojnicz 2012
Betula papyrifera © 2013 E. Yarnell
Mahonia aquifolium
N+
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O
O
OCH3
OCH3
M. aquifolium © 2013 E. Yarnell
M. aquifolium © 2013 Heron Botanicals,used with permission
O
OH
HO
O
O
OOH
O
OH
O
berberine
5’-methoxyhydnocarpin
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BERBERINE
In vitro, assembly of fibrimiae by uropathogenic E. coli inhibited by berberine (Sun 1988).
In vitro, blocks biofilm formation by Strep. epidermidis (Wang 2009).
In vitro, inhibits MRSA adhesion, also synergistic with ampicillin and oxacillin, even restoring their efficacy (Yu 2005)
Equisetumarvense
E. arvense © 2013 E. Yarnell
Galiumaparine
Galium spp © 2013 E. Yarnell
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Parietariajudaica
P. judaica © 2013 Heron Botanicals,used with permission
Parietariafloridiana
P. floridiana © 2013 E. Yarnell
Echinaceaangustifolia
E. pa$ida © 2013 E. Yarnell
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Codonopsispilosula(dǎngshēn)党参
C. pilosula © 2013 E. Yarnell
Astragalusmembranaceus(huángqí)黃芪
C. pilosula © 2013 E. Yarnell
Anti-kidney scarring(Lu 1997)
Centellaasiatica
C. asiatica © 2013 Heron Botanicals,used with permission
C. asiatica © 2013 E. Yarnell
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ACUTE UTI TREATMENT
Definition: fever, pyuria, >106 CFU/ml bacteriuria
Rest, no sweets, pungent foods, avoid sugar
Juniperus communis aril tincture 3-10 gtt q2h
Echinacea angustifolia fresh root tincture 2.5 ml (0.5 tsp) q2h
Urtica dioica leaf tea, 0.5-1 cup 4-5 times a day
Reminder: if not significantly better in 24-48 h, antibiotics
CASE STUDY
2-yo white girl, grade I (left), II (right) VUR, good diet/lifestyle, no other health issues
Two confirmed UTIs to date, recovered quickly from both with antibx
Parents prefer no antibx, ND rx cranberry powder and D-mannose
One-year follow-up: one instance of culture-negative UTI-like sx (with pyuria), no need for antibx
REFERENCES
Conway PH, Cnaan A, Zaoutis T, et al. Recurrent urinary tract infections in children: risk factors and association with prophylactic antimicrobials. JAMA 2007;298(2):179-86.
Cooper CS. Diagnosis and management of vesicoureteral reflux in children. Nat Rev Urol 2009;6(9):481-9.
Fernbach SK, Feinstein KA, Schmidt MB. Pediatric voiding cystourethrography: a pictorial guide. Radiographics 2000;20(1):155-68; discussion 168-71.
Hodson EM, Wheeler DM, Vimalchandra D, et al. Interventions for primary vesicoureteric reflux. Cochrane Database Syst Rev 2007;(3):CD001532.
Li M, Andrew MA, Wang J, et al. Effects of cranberry juice on pharmacokinetics of beta-lactam antibiotics following oral administration. Antimicrob Agents Chemother 2009;53(7):2725-32.
Lu Y, Li JZ, Zheng X. Effect of Astragalus Angelica mixture on serum lipids and glomerulosclerosis in rats with nephrotic syndrome. Zhongguo Zhong Xi Yi Jie He Za Zhi 1997;17(8):478-80 [in Chinese].
Nishizaki N, Someya T, Hirano D, et al. Can cranberry juice be a substitute for cefaclor prophylaxis in children with vesicoureteral reflux? Pediatr Int 2009;51(3):433-4.
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Pennesi M, Travan L, Peratoner L, et al. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial. Pediatrics 2008;121(6):e1489-94.
Rafsanjany N, Lechtenberg M, Petereit F, Hensel A. Antiadhesion as a functional concept for protection against uropathogenic Escherichia coli: in vitro studies with traditionally used plants with antiadhesive activity against uropathognic Escherichia coli. J Ethnopharmacol 2013;145(2):591-7.
Smellie JM, Barratt TM, Chantler C, et al. Medical versus surgical treatment in children with severe bilateral vesicoureteral reflux and bilateral nephropathy: A randomised trial. Lancet 2001;357:1329-33.
Sun D, Abraham SN, Beachey EH. Influence of berberine sulfate on synthesis and expression of Pap fimbrial adhesin in uropathogenic Escherichia coli. Antimicrob Agents Chemother 1988;32(8):1274-7.
Uberos J, Fernández-Puentes V, Molina-Oya M, et al. Urinary excretion of phenolic acids by infants and children: a randomised double-blind clinical assay. Clin Med Insights Pediatr 2012;6:67-74.
Wang X, Yao X, Zhu Z, et al. Effect of berberine on Staphylococcus epidermidis biofilm formation. Int J Antimicrob Agents 2009;34(1):60-6.
Wing DA, Rumney PG, Preslicka CW, et al. Daily cranberry juice for the prevention of asymptomatic batteriuria in pregnancy: a randomized, controlled pilot study. J Urol 2008;180:1367–1372.
Wojnicz D, Kucharska AZ, Sokół-Łętowska A, et al. Medicinal plants extracts affect virulence factors expression and biofilm formation by the uropathogenic Escherichia coli. Urol Res 2012;40(6):683-97.
Yu HH, Kim KJ, Cha JD, et al.Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. J Med Food 2005;8(4):454-61.
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