Abbreviations & Acronyms 5-ASA = 5-aminosalicylic bwk = biweekly CS = chondroitin sulphate GAG = glycosaminoglycans HA = hyaluronic acid IL-6 = interleukin-6 LE = evidence level LPS = lipopolysaccharide NGF = nerve growth factor PS = protamine sulfate PSP = pentosanpolysulphate RCT = randomized controlled trial rUTI = recurrent urinary tract infections SAGE = semi-synthetic glycosaminoglycans ethers sNOCC = N-sulphonato-N,O -carboxymethylchitosan UTI = urinary tract infections Abstract: Restoring the bladder glycosaminoglycans layer has recently been introduced as prophylactic treatment for recurrent urinary tract infections. Herein, we analyze the latest main clinical and experimental studies to support this therapeutic option. An electronic research was carried out in the most common databases in order to identify any published studies. Retrieved studies were categorized as experimental or clinical according to their setting. For the clinical studies, the evidence level was assigned. A total of 13 laboratory studies showed how bladder glycosaminoglycans instillations act: attenuation of the inflammation process, reduction of bladder contraction amplitude and frequency, reduction of epithelium damage, and lower bacterial growth in urine and tissue samples. Likewise, two randomized clinical trials with grade 2 evidence level and two case series with grade 4 evidence level reported glycosaminoglycans as an alternative to reduce episodes and to prolong recurrence time in patients with recurrent urinary tract infections. At least 12 months of follow up was completed. No serious adverse events were reported. Compared with a placebo, in one randomized study a significantly higher maximum cystometric capacity was obtained, whereas in the other study a significant increase in quality of life scores was reported too. An improvement in the urinary symptoms score was reported by the two randomized trials. Although the clinical use of glycosaminoglycans replacement therapy for recurrent urinary tract infections is supported by a small number of clinical studies with different evidence levels, the laboratory studies show that glycosaminoglycans could have a protective role against inflammatory factors, supporting the idea "to restore the glycosaminoglycans bladder layer to prevent chronic disease course".
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