ADPKD:Beyond Growth and Decline

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and is characterized by progressive cyst formation in both kidneys and renal function loss. It is the fourth most common cause of end-stage renal disease for which renal replacement therapy has to be started. Beyond decline of renal function and renal cyst growth, patients may experience other symptoms such as pain, gastrointestinal discomfort and polyuria (large production of urine). In the first part of this thesis a comprehensive overview of pain in ADPKD is given, and several novel pharmacological approaches and minimally invasive therapeutic options are investigated as potential new therapies for ADPKD-related pain. In the second part, the symptom polyuria caused by an impaired urinary concentrating capacity is evaluated and discussed, with special attention for its possible consequence for disease progression. Results of this thesis show that although these symptoms are common in ADPKD patients, they attain little attention and their consequences may be underestimated by physicians. The diagnosis of this inherited kidney disease may be an emotional burden, because of the consequences for family and career planning. For these reasons sometimes customized care by physicians or nurses with specific experience in ADPKD is indicated. Also for regular clinicians it is important to recognize and adequately respond to the emotional, social and symptom burden that ADPKD patients can experience, because they can have a negative impact on a patient’s quality of life

Argus-T adjustable male sling:A follow-up study on urinary incontinence and patient's satisfaction

Aims: The use of Argus-T adjustable sling may be a promising alternative option for the treatment of urinary incontinence after radical prostatectomy, however long-term data is lacking. The aim of this study is to evaluate the long-term results of the Argus-T sling on incontinence rates, patient's quality of life and tape-related complications. Methods: Patients were eligible if persistent stress incontinence was present >= 12 months after radical prostatectomy. Measurements included 24 h frequency volume micturition list, 24 h pad test, 24 h pad count and quality of life questionnaires. Argus-T adjustable sling was placed with a single perineal route incision approach. Results: Seventy-eight patients were included, 69 +/- 6 years, pre-intervention 24 h urinary loss 212 (75-385) g. Directly after surgery, 63.6% of the patients was completely dry, 79.2% of the patients reported greater than 90% improvement of their urinary loss and 92.2% > 50% improvement. Median follow-up time was 3.2 (2.5-6.1) years. After 5 years of follow-up, 53.3% of the patients were completely dry, 71.5% reported an improvement greater than 90% and 79.6% reported an improvement of greater than 50%. Patients with preoperative urinary loss less than 250 g reported significantly higher improvement of their urinary loss compared to patients with urinary loss >= 250 g (p = .02). Patients satisfaction was still increased after 5 years follow-up (70 +/- 21 vs.16 +/- 9, p < .001) and patients quality of life remained high (85 +/- 20 vs. 88 +/- 13, p = .1). Complications were mainly observed directly after surgery. Two patients (2.6%) needed reimplantation of the sling. Conclusion: These data indicate that Argus-T sling is an effective treatment option in obtaining substantial long-term incontinence relief in patients with invalidating moderate stress urinary incontinence after radical prostatectomy

Somatostatin in renal physiology and autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation, leading to growth in kidney volume and renal function decline. Although therapies have emerged, there is still an important unmet need for slowing the rate of disease progression in ADPKD. High intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) are involved in cell proliferation and fluid secretion, resulting in cyst formation. Somatostatin (SST), a hormone that is involved in many cell processes, has the ability to inhibit intracellular cAMP production. However, SST itself has limited therapeutic potential since it is rapidly eliminated in vivo. Therefore analogues have been synthesized, which have a longer half-life and may be promising agents in the treatment of ADPKD. This review provides an overview of the complex physiological effects of SST, in particular renal, and the potential therapeutic role of SST analogues in ADPKD

The effect of office based flexible and rigid cystoscopy on pain experience in female patients

Purpose: Rigid and flexible cystoscopies are both routinely used in female patients. Literature is conflicting whether flexible cystoscopy is less painful compared to rigid cystoscopy. The aim of this study was therefore to investigate whether using flexible cystoscopy leads to less discomfort and pain compared to rigid cystoscopy in female patients who underwent first time cystoscopy. Materials and Methods: One hundred eighty-nine female patients, who never had undergone cystoscopy, were randomized into 2 groups: 92 patients underwent rigid cystoscopy and 97 patients flexible cystoscopy. Directly after the cystoscopy procedure all patients were asked to fill out their pain experience on a 100-mm visual analogue pain scale (VAS). Results: Median VAS score was significantly lower for women undergoing flexible cystoscopy (0 [0–20]) compared to rigid cystoscopy (15 [0–38], p<0.001). In addition, age was inversely associated with VAS score, indicating that younger females experienced more pain (R=−0.30, p=0.001). The use of flexible cystoscopy was associated with a decrease in VAS score and remained significant after adjustment for age, sex of urologist, performing urologist and indication (standardized β =−0.17, p=0.048). Conclusions: The use of flexible cystoscopy resulted in a significantly lower pain experience compared to rigid cystoscopy. Based on patient’s pain experience during cystoscopy, this study implicates to use flexible cystoscopy in female patients who undergo first time cystoscopy

Proton gradient formation in early endosomes from proximal tubules

AbstractHeavy endosomes were isolated from proximal tubules using a combination of magnesium precipitation and wheat-germ agglutinin negative selection techniques. Two small GTPases (Rab4 and Rab5) known to be specifically present in early endosomes were identified in our preparations. Endosomal acidification was followed fluorimetrically using acridine orange. In presence of chloride ions and ATP, the formation of a proton gradient (ΔpH) was observed. This process is due to the activity of an electrogenic V-type ATPase present in the endosomal membrane since specific inhibitors bafilomycin and folimycin effectively prevented or eliminated endosomal acidification. In presence of chloride ions (Km = 30 mM) the formation of the proton gradient was optimal. Inhibitors of chloride channel activity such as DIDS and NPPB reduced acidification. The presence of sodium ions stimulated the dissipation of the proton gradient. This effect of sodium was abolished by amiloride derivative (MIA) but only when loaded into endosomes, indicating the presence of a physiologically oriented Na+/H+-exchanger in the endosomal membrane. Monensin restored the gradient dissipation. Thus three proteins (V-type ATPase, Cl−-channel, Na+/H+-exchanger) present in early endosomas isolated from proximal tubules may regulate the formation, maintenance and dissipation of the proton gradient