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Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder included in ciliopathies, representing the fourth cause of end stage renal disease (ESRD), with an estimated prevalence between 1:1000 and 1:2500. It is mainly caused by mutations in the PKD1 and PKD2 genes encoding for polycystin 1 (PC1) and polycystin 2 (PC2), which regulate differentiation, proliferation, survival, apoptosis, and autophagy. The advances in the knowledge of multiple molecular pathways involved in the pathophysiology of ADPKD led to the development of several treatments which are currently under investigation. Recently, the widespread approval of tolvaptan and, in Italy, of long-acting release octreotide (octreotide-LAR), represents but the beginning of the new therapeutic management of ADPKD patients. Encouraging results are expected from ongoing randomized controlled trials (RCTs), which are investigating not only drugs acting on the calcium/cyclic adenosin monoposphate (cAMP) pathway, the most studied target so far, but also molecules targeting specific pathophysiological pathways (e.g. epidermal growth factor (EGF) receptor, AMP-activated protein kinase (AMPK) and KEAP1-Nrf2) and sphingolipids. Moreover, studies on animal models and cultured cells have also provided further promising therapeutic strategies based on the role of intracellular calcium, cell cycle regulation, MAPK pathway, epigenetic DNA, interstitial inflammation, and cell therapy. Thus, in a near future, tailored therapy could be the key to changing the natural history of ADPKD thanks to the vigorous efforts that are being made to implement clinical and preclinical studies in this field. Our review aimed to summarize the spectrum of drugs that are available in the clinical practice and the most promising molecules undergoing clinical, animal, and cultured cell studies. Graphical abstract: [Figure not available: see fulltext.]

Laparoscopic ventral mesh rectopexy (LVR) is gaining wider acceptance as the preferred procedure to correct internal as well as external rectal prolapse associated with obstructed defaecation syndrome and/or faecal incontinence. Very few reports exist on the use of biologic mesh for LVR. The aim of our study was to report the complication and recurrence rate of our first 100 cases of LVR for symptomatic internal rectal prolapse and/or rectocele using a porcine dermal collagen mesh. Prospectively collected data on LVR for internal rectal prolapse were analysed. Surgical complications and functional results in terms of faecal incontinence (measured with the Faecal Incontinence Severity Index = FISI) and constipation (measured with the Wexner Constipation Score = WCS) at 3, 6 and 12 months were analysed. It was considered an improvement if FISI or WCS scores were reduced by at least 25 % and a cure if the FISI score decreased to < 10 and the WCS decreased to < 5. Between April 2009 and April 2013, 100 consecutive female patients (mean age 63 years, range 24-88 years) underwent LVR. All patients had internal rectal prolapse (grade III [n = 25] and grade IV [n = 75] according to the Oxford classification) and rectocele. Mean operative time was 85 +/- A 40 min. Conversion rate to open technique was 1 %. There was no post-operative mortality. Overall 16 patients (16 %) experienced 18 complications, including rectal perforation (n = 1), small bowel obstruction (n = 2), urinary tract infection (n = 8), subcutaneous emphysema (n = 3), wound haematoma (n = 2), long lasting sacral pain (n = 1) and incisional hernia (1). Median post-operative length of stay was 2 days. Ninety-eight out of 100 patients completed follow-up. At the end of follow-up, the mean FISI score improved from 8.4 (+/- 4.0 standard deviation (SD) p = 0.003) to 3.3 +/- 2.3 SD (p = 0.04). Incontinence improved in 37 out of 43 patients (86 %), and 31 patients (72 %) were cured. Similarly, the mean WCS score improved from 18.4 +/- 11.6 SD to 5.4 +/- 4.1 SD (p = 0.04). Constipation improved in 82 out of 89 patients (92 %), and 70 patients (79 %) were cured. No worsening of continence status, constipation or sexual function was observed. Fourteen patients (14 %) experienced persistence or recurrence of prolapse. LVR using biologic mesh is a safe and effective procedure for improving symptoms of obstructed defaecation and faecal incontinence in patients with internal rectal prolapse associated with rectocele.