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The Role of GAG-replenishment Therapy in the Management of Chronic Cystitis
these are new infections. The symptoms of a urinary tract infection are patients were requested to keep a micturition diary and were
severe pain, especially on passing water, frequent urge to urinate, questioned about the course of their symptoms during the study. At the
greatly increased urinary frequency and haematuria. A damaged GAG end of the study the data of 32 patients in the chondroitin sulphate
layer can promote the adhesion of bacteria to the urothelium and their group and 35 patients in the tolterodine tartrate group were analysed.
dissemination. As a therapy option for chronically recurring cystitis, the In the chondroitin sulphate group, micturition frequency had decreased
guidelines of the European Association of Urology (EAU) recommend significantly from 14 to seven times daily and from four times to
either low-dose antibiotic therapy over about six months or a single once at night. In the subjective assessment of the therapy, 72% of
dose of antibiotic in risk. Guideline-compliant alternatives are drinking the patients treated with chondroitin sulphate documented an
cranberry juice, vaginal administration of lactobacilli or the use of improvement in symptoms, while in the anticholinergic group only 43%
immunostimulants. GAG-replenishment therapy with chrondroitin of the patients reported an improvement. No adverse events were
sulphate is also recommended as an innovative regimen for this observed on chondroitin sulphate. Twenty-four months after enrolment,
condition as an intact GAG layer offers resistance to the bacteria in the a follow-up investigation was performed.
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Eighteen of the 23 patients
bladder and prevents adherence to the urothelium. Out of 86 patients who benefited from the 12-month chondroitin sulphate treatment
with chronically recurring cystitis participating in the non-interventional continued to show a marked improvement in their symptoms after 24
study, more than 90% benefited from the instillation treatment with months. In the tolterodine tartrate group, after 24 months only five
0.2% chondroitin sulphate.
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patients from initially 15 patients were still responding to the therapy.
Overactive Bladder Syndrome Overall, the randomised, comparative study demonstrates the efficacy
Like IC, OAB is a diagnosis by exclusion. The first-line treatment is and tolerability of intravesically administered chondroitin sulphate in
behavioural therapy and anticholinergic medications; however, a range patients with overactive bladder syndrome. Additionally, it can be
of innovative options are available for the treatment of OAB and are concluded that intravesical treatment with sodium chondroitin
currently undergoing evaluation in clinical trials. In OAB there is also sulphate provides not only a short-term improvement in OAB but also
evidence that GAG-layer defects may be present and responsible for the an effect persisting after the end of therapy. This leads to the
symptoms and consequences mentioned above. suggestion that in a certain percentage of OAB patients – the real
percentage is not yet known, but OAB patients refractory to
If there is a conspicuous discrepancy between the diary entries and anticholinergics may belong to this group – this disease is in fact
the cystometry findings (which is usually performed with water or characterised by a GAG-layer defect, which can be treated causally
physiological sodium chloride [NaCl] solution), cystometry should be with chondroitin sulphate.
repeated with 0.2M potassium chloride solution. The reason for this is
that the discrepancy may be due to the fact that the urine of the Radiation Cystitis
patients has a completely different composition from the usually Radiation cystitis is a condition with similar symptoms to IC. The
employed filling medium, especially in terms of its potassium content. instillation of substances such as chondroitin sulphate for GAG-
If the maximum functional bladder capacity is conspicuously lower replenishment therapy is valuable, as radiation cystitis is typically
when using potassium chloride solution, an impairment of urothelial associated with a defect of the GAG layer. A replenishment of GAG
impermeability and thus a defect in the GAG layer may be assumed to should restore this protective barrier layer. In patients with radiation
be present. The potassium ions and aggressive components of the cystitis participating in the observational study, GAG replenishment
natural urine then diffuse into the bladder wall and may irritate the with chondroitin sulphate 0.2% was shown to be effective.
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bladder. In particular, the chemosensitive C-fibres are depolarised. If
this modified potassium test – which is not yet validated – suggests Summary
the presence of a GAG-layer defect, these patients frequently benefit Chronic forms of cystitis, such as IC, recurring cystitis, OAB and
from GAG-replenishment therapy. Causes of the damage to the GAG radiation cystitis, are characterised by high urinary frequency
layer may include recurrent urinary tract infections, radiotherapy/ and urinary urgency with or without pelvic pain. Depending on the
chemotherapy or vesical ischaemia due to overdistension, for clinical entity involved, the symptoms are of variable severity.
example. Repeated exposure to cold or excess consumption of coffee
are also considered to induce the defect. The range of oral and intravesical therapeutic options is limited. One
innovative treatment with highly rated efficacy and tolerability (also by
The efficacy of GAG replenishment with 0.2% chondroitin sulphate in the patients) is intravesical GAG-replenishment therapy. A large
OAB has been demonstrated by Gauruder-Burmester et al. in a surveillance study with chondroitin sulphate has demonstrated that
prospective, randomised, comparative study.
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Eighty-two patients who chronic forms of cystitis can be effectively treated and the therapy is
had been suffering for at least 12 months from the typical symptoms of well tolerated. Furthermore, in OAB the results of a randomised,
OAB and disease-related stress requiring treatment were enrolled in comparative study with a follow-up after 24 months clearly
this study and treated for 12 months. Patients were treated with either demonstrated that intravesical treatment with chondroitin sulphate
the anticholinergic tolterodine tartrate (4mg daily) or chondroitin provides an effect persisting after the end of therapy. The study data
sulphate; in the first month instillation was performed weekly and show that the concept of GAG-replenishment therapy works in
thereafter monthly. Before the start and at the end of the study the conditions with GAG-layer damage. ■
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2. Hurst RE, Eur Urol Suppl, 2003;2:10. edition, Wein Health Publication Ltd., 2009. Research), 2008;58:328.
3. Slobodov G, et al., J Urol, 2004;171:1554. 7. Perez-Marrero R, et al., J Urol, 1988;140:36. 11. Gauruder-Burmester A, et al., Zentralbl Gynakol, 2006;128:336.
4. Kyker KD, et al., BMC Urol, 2005;5:4. 8. Kuo HC, J Formos Med Assoc, 2001;100:309. 12. Gauruder-Burmester A, Popken G, Geburtsh Frauenheilk,
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EUROPEAN UROLOGICAL REVIEW 53
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