Managing chronic bladder diseases with the administration of exogenous glycosaminoglycans: an update on the evidence

Abstract

Although the pathophysiology of acute chronic cystitis and other ‘sensory’ disorders, i.e. painful bladder syndrome (PBS) or interstitial cystitis (IC), often remains multifactorial, there is a wide consensus that such clinical conditions may arise from a primary defective urothelium lining or from damaged glycosaminoglycans (GAGs). A ‘cascade’ of events starting from GAG injury, which fails to heal, may lead to chronic bladder epithelial damage and neurogenic inflammation. To restore the GAG layer is becoming the main aim of new therapies for the treatment of chronic cystitis and PBS/IC. Preliminary experiences with GAG replenishment for different pathological conditions involving the lower urinary tract have been reported. There is a range of commercially available intravesical formulations of these components, alone or in combination. Literature evidence shows that exogenous intravesical hyaluronic acid markedly reduces recurrences of urinary tract infections (UTIs). Patients treated with exogenous GAGs have fewer UTI recurrences, a longer time to recurrence and a greater improvement in quality of life. Exogenous intravesical GAGs have been used for the treatment of PBS/IC. Despite the limitations of most of the studies, findings confirmed the role of combination therapy with hyaluronic acid and chondroitin sulfate as a safe and effective option for the treatment of PBS/IC. To prevent and/or treat radiotherapy and chemotherapy induced cystitis, GAG replenishment therapy has been used showing preliminary encouraging results. The safety profile of exogenous GAGs has been reported to be very favourable, without adverse events of particular significance.

Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2–3 trial

“…143 Hyaluronic acid, a mucopolysaccharide, is believed to help restore the normal protective layer of polysaccharides that irradiation can damage. 146 Positive effects on bleeding as well as frequency, urgency, and pain have been reported. 147,148 Hyaluronic acid and hyperbaric oxygen had similar effects on hematuria in one study, with a response rate of 88-75%.…”

A Dutch Case Report of Successful Treatment of Chronic Relapsing Urinary Tract Infection with Bacteriophages in a Renal Transplant Patient

“…More episodes of UTI followed, and intravesical glycosaminoglycan (6) and intravesical amikacin (250 mg) adjunctive therapies were given by intermittent catheterization besides intravenous meropenem but failed (Fig. 1).…”

“…In our laboratory, we tested if the bacteriophage suspension our patient had received from Tbilisi was active against his causative ESBL-producing Klebsiella pneumoniae strain. To this end, we performed the bacteriophage spot test using the plaque assay for identification and enumeration of bacteriophages by the double-layer agar method (6). The spot test, which was performed in duplicates, showed lytic activity of the bacteriophage solution ( Fig.…”

Recurrent urinary tract infections: a critical review of the currently available treatment options

“…Pro‐inflammatory chemokines, such as interleukin‐8, guide neutrophil granulocytes to the area of urothelial damage. Chronic urothelial damage and neurogenic inflammation (the inflammatory response following chronic insult to the bladder nerve supply after depletion of the GAG layer) has been shown in bladder sections with deficient GAG layers . Histology has also shown that GAG supplements reduce neutrophil transmigration and halt the subsequent inflammatory process …”