Low-Intensity Shockwave Therapy for Erectile Dysfunction: A Randomized Clinical Trial Comparing 2 Treatment Protocols and the Impact of Repeating Treatment.

BACKGROUND: There is lack of evidence-based optimization of the protocol for low-intensity shockwave therapy for erectile dysfunction. Furthermore, the safety and efficacy of repeating shockwave therapy have not been explored. AIM: To compare the efficacy and safety of 6 and 12 treatment sessions within a 6-week treatment period and investigate the effect of repeat treatment after a 6-month period in a 2-phase study. METHODS: Patients with vasculogenic erectile dysfunction that responded to phosphodiesterase type 5 inhibitors were randomized into 2 groups: low-intensity shockwave therapy sessions once (group A, n = 21) or twice (group B, n = 21) per week for 6 consecutive weeks (phase 1). Patients who completed 6-month follow-up were offered 6 additional sessions (phase 2); group A received 2 sessions per week and group B received 1 session per week. Patients were followed for 6 months. OUTCOMES: International Index for Erectile Function erectile function domain (IIEF-EF) score, minimally clinical important differences (MCIDs), Sexual Encounter Profile question 3 (SEP3) score, and triplex ultrasonographic parameters. RESULTS: In phase 1, groups A and B showed improvement in IIEF-EF score, MCID, SEP3 score, and mean peak systolic velocity compared with baseline. MCIDs were achieved in 62% of group A and 71% of group B, and the percentage of yes responses to SEP3 was 47% in group A and 65% in group B (P = .02). Mean peak systolic velocity at baseline and at 3-month follow-up were 29.5 and 33.4 cm/s for group A and 29.6 and 35.4 cm/s for group B (P = .06). In phase 2, group A showed a greater increase in the percentage of yes responses to SEP3 (group A = +14.9; group B = +0.3). When the impact of the total number of sessions received was examined, MCIDs in IIEF-EF score from baseline were achieved in 62%, 74%, and 83% of patients after 6, 12, and 18 sessions, respectively. No treatment-related side effects were reported. CLINICAL IMPLICATIONS: The total number of low-intensity shockwave therapy sessions affects the efficacy of erectile dysfunction treatment. Retreating patients after 6 months could further improve erectile function without side effects. 12 sessions can be delivered within 6 weeks without a 3-week break period. STRENGTHS AND LIMITATIONS: This study lacked a sham-controlled arm. However, all patients were randomized to different groups, and baseline characteristics were similar between groups. Also, all patients were confirmed by triplex ultrasonography to have arterial insufficiency. CONCLUSION: Patients can benefit more in sexual performance from 12 sessions twice per week compared with 6 sessions once a week. Shockwave therapy can be repeated up to a total of 18 sessions. Kalyvianakis D, Memmos E, Mykoniatis I, et al. Low-Intensity Shockwave Therapy for Erectile Dysfunction: A Randomized Clinical Trial Comparing 2 Treatment Protocols and the Impact of Repeating Treatment. J Sex Med 2018;15:334-345.

The Discovery of an S-shaped Kidney in a Patient With Prostate Cancer: A Rare Finding.

Crossed fused renal ectopia (CFRE) constitutes a rare congenital anomaly of the urinary tract, typically characterized by its predominantly asymptomatic nature and frequent incidental discovery. This case report delineates the clinical profile of a 56-year-old male admitted to our Prostate Cancer Outpatient Clinic due to elevated prostate-specific antigen (PSA) levels, ultimately leading to the diagnosis of prostate cancer. The patient was asymptomatic, with no family or surgical background. Notably, a fused ectopic kidney was incidentally identified during the staging process involving abdominal computed tomography (ACT) scanning. Remarkably, no additional abnormalities of the urinary tract or renal dysfunction manifested in this specific case. The significance of this report lies in the underscored emphasis on the importance of employing precise imaging techniques and tailored management strategies for patients harboring such anatomical variations.

Use of phosphate-binding agents is associated with a lower risk of mortality.

Hyperphosphatemia has been associated with higher mortality risk in CKD 5 patients receiving dialysis. Here, we determined the association between the use of single and combined phosphate-binding agents and survival in 6797 patients of the COSMOS study: a 3-year follow-up, multicenter, open-cohort, observational prospective study carried out in 227 dialysis centers from 20 European countries. Patient phosphate-binding agent prescriptions (time-varying) and the case-mix-adjusted facility percentage of phosphate-binding agent prescriptions (instrumental variable) were used as predictors of the relative all-cause and cardiovascular mortality using Cox proportional hazard regression models. Three different multivariate models that included up to 24 variables were used for adjustments. After multivariate analysis, patients prescribed phosphate-binding agents showed a 29 and 22% lower all-cause and cardiovascular mortality risk, respectively. The survival advantage of phosphate-binding agent prescription remained statistically significant after propensity score matching analysis. A decrease of 8% in the relative risk of mortality was found for every 10% increase in the case-mix-adjusted facility prescription of phosphate-binding agents. All single and combined therapies with phosphate-binding agents, except aluminum salts, showed a beneficial association with survival. The findings made in the present association study need to be confirmed by randomized controlled trials to prove the observed beneficial effect of phosphate-binding agents on mortality.

COSMOS: the dialysis scenario of CKD-MBD in Europe.

BACKGROUND: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are important complications of CKD5D patients that are associated with mortality. METHODS: COSMOS is a multicentre, open cohort, prospective, observational 3-year study carried out in haemodialysis patients from 20 European countries during 2005-07. The present article describes the main characteristics of the European dialysis population, the current practice for the prevention, diagnosis and treatment of secondary hyperparathyroidism and the differences across different European regions. RESULTS: The haemodialysis population in Europe is an aged population (mean age 64.8±14.2 years) with a high prevalence of diabetes (29.5%) and cardiovascular disease (76.0%), and 28.7% of patients have been on haemodialysis more than 5 years. Patients from the former Eastern countries are younger (59.3±14.3 versus 66.0±13.9), having a lower proportion of diabetics (24.1 versus 30.7%). There were relevant differences in the frequency of measurement of the main CKD-MBD biochemical parameters [Ca, P and parathyroid hormone (PTH)] and the Eastern countries showed a poorer control of these biochemical parameters (K/DOQI and K/DIGO targets). Overall, 48.0% of the haemodialysis patients received active vitamin D treatment. Calcitriol use doubled that of alfacalcidiol in the Mediterranean countries, whereas the opposite was found in the non-Mediterranean countries. The criteria followed to perform parathyroidectomy were different across Europe. In the Mediterranean countries, the level of serum PTH considered to perform parathyroidectomy was higher than in non-Mediterranean countries; as a result, in the latter, more parathyroidectomies were performed in the year previous to inclusion to COSMOS. CONCLUSIONS: The COSMOS baseline results show important differences across Europe in the management of CKD-MBD.

Up-regulation of urinary markers predict outcome in IgA nephropathy but their predictive value is influenced by treatment with steroids and azathioprine.

OBJECTIVE: Steroids and immunosuppressants can delay progression of renal function in IgAN, but their possible effect in local cytokines has not been studied. MATERIAL AND METHODS: Histology in 53 IgAN patients (M/F 35/18 age 40.5 years (17 - 65)) was evaluated using the Oxford classification system. IL-1ß, -2, -4, -5, -6, -10, -12 and -17, INF-γ and MCP-1 were measured subsequently by multiplex cytokine assay in first morning urine samples taken at the day of renal biopsy. After a 6-month course with RAASinhibitors + fish oils (FO), 35/53 patients, Group A, responded and continued on the same treatment, while in 18/53 who did not respond, Group B, steroids + azathiopine were added. RESULTS: The presence of endocapillary proliferation had significant correlation with the urinary excretion of pro-inflammatory and pro-fibrotic cytokines (IL-1ß, MCP-1, IL-17, INF-γ, IL-6 and IL-10). Serum creatinine at time of diagnosis had significant correlation with proteinuria (p = 0.02), urinary levels of IL-1ß (p = 0.03), IL-2 (p = 0.01) and MCP-1 (p = 0.03). GFR was reduced from 65 ± 29 to 57 ± 34 ml/min, p = 0.005 in Group A and remained stable in Group B patients (GFR from 63 ± 24 to 61 ± 30 ml/min, p = NS). Most of the measured cytokines in the urine predicted deterioration of renal function in Group A, but the urinary excretion of IL-6 seemed to predict renal function outcome in both groups of patients. CONCLUSION: Several cytokines are excreted in the urine of patients with IgAN, and their levels predict the outcome of the disease. Steroids + aza may exert their beneficial effect through suppression of the production or activation of most cytokines.

Associations of fetuin-A and osteoprotegerin with arterial stiffness and early atherosclerosis in chronic hemodialysis patients.

BACKGROUND: Cardiovascular morbidity and mortality remains excessive in patients with chronic kidney disease. The association of vascular changes with regulators of extraosseous calcification in this patient population is still under investigation. The aim of the present study was to investigate the associations of the calcification inhibitor fetuin-A, and the anti-osteoclastic factor osteoprotegerin (OPG) with vascular pathology in chronic hemodialysis patients. METHODS: In this cross-sectional study including 81 stable chronic hemodialysis patients, we measured carotid-to-femoral pulse wave velocity (cfPWV) with applanation tonometry, reflecting arterial stiffness, and common carotid intima-media thickness (ccIMT), a surrogate of early atherosclerosis, as well as serum levels of fetuin-A and OPG. Co-morbidities, traditional cardiovascular risk factors, inflammatory markers and mineral-bone disease serology parameters were also recorded. RESULTS: cfPWV correlated inversely with fetuin-A (r=-0.355, p=0.001) and positively with OPG (r=0.584, p<0.001). In multilinear regression analysis including age, gender, diabetes, cardiovascular disease, hypertension, pulse pressure, LDL, logCRP, both fetuin-A and OPG were independently associated with cfPWV (p=0.024 and p=0.041 respectively). ccIMT was negatively associated with fetuin-A (r=-0.312, p=0.005) and positively with OPG (r=0.521, p<0.0001); however these associations lost statistical significance after adjustment for age. CONCLUSION: In chronic hemodialysis patients both fetuin-A and OPG levels are independently associated with arterial stiffness but not with early atherosclerotic vascular changes.

Overview of current pharmacotherapeutic options in benign prostatic hyperplasia.

INTRODUCTION: Benign prostatic hyperplasia (BPH) represents the histological entity of prostate cell proliferation, which inflicts a gradually increasing obstruction of the bladder outlet and is accompanied by a progressing manifestation of lower urinary tract symptoms (LUTS). BPH management algorithm includes conservative measures, pharmaceutical agents, and surgical procedures. AREAS COVERED: A comprehensive literature review was performed using PubMed, Scopus, and Google Scholar databases to identify publications written in English, analyzing BPH pharmaceutical treatment. The search was conducted from January 2000 to January 2023. Six main drug classes can be administered, either as monotherapy or in combination. Furthermore, the authors provide current direction of research on future medications, which focuses on a more etiological interference to the BPH pathophysiological mechanism. EXPERT OPINION: The available medications represent an effective first-line step of BPH/LUTS therapy. Currently, the administration of BPH medications is tailored to patient/disease characteristics and entails long-time adherence to therapy. The emergence of new surgical modalities, which combine significantly lower morbidity compared to standard procedures and more durable effects than the available medications, seems to challenge the current treatment algorithm. More direct comparisons and the increasing experience with these surgical modalities will delineate the switch points between various therapy levels along the BPH management sequence.

The effect of standard percutaneous nephrolithotomy, miniaturized percutaneous nephrolithotomy and retrograde intrarenal surgery on biomarkers of renal injury: a randomized clinical trial.

Background: Observational studies on the association of endourological procedures with renal parenchymal damage are lacking. This randomized trial examined the effect of standard percutaneous nephrolithotomy (sPCNL) in comparison with miniaturized-PCNL (mini-PCNL) and retrograde intrarenal surgery (RIRS) for nephrolithiasis treatment on novel biomarkers of renal injury. Methods: Seventy-five patients were randomized in a 1:1:1 ratio to receive sPCNL, mini-PCNL and RIRS for nephrolithiasis. The ratios of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) normalized for urinary creatinine (Cr) were calculated from urine samples collected at baseline (2-h preoperatively) and at 2-, 6-, 24- and 48-h postoperatively. Two-way mixed analysis of variance (ANOVA) for repeated measurements was used to evaluate the effects of type of procedure and time on studied biomarkers. Results: Between baseline and 2-h postoperatively, no significant differences were observed in NGAL/Cr changes between sPCNL [median (interquartile range) 9.46 (4.82-14.9)], mini-PCNL [12.78 (1.69-25.24)] and RIRS [6.42 (2.61-23.90)] (P = .902). Similarly, no between-group differences were observed for KIM-1/Cr (P = .853) and IL-18 (P = .980) at 2 h, and all biomarkers at any time-point postoperatively. Within-groups, significant increases from baseline were noted for NGAL/Cr (sPCNL, P < .001; mini-PCNL, P < .001; RIRS, P = .001), KIM-1/Cr and IL-18/Cr at 2 h; progressively lower increases from baseline were noted in all groups for KIM-1/Cr and IL-18/Cr at 6-, 24- and 48-h postoperatively. As such, a significant effect of time but not of type of procedure was evidenced with two-way mixed ANOVA. No significant between-group differences were observed in acute kidney injury incidence and complications. Conclusions: The endourological procedures under study are associated with similar patterns of early tubular injury, detected by novel biomarkers, which is largely reduced within 48 h and no changes in glomerular function.

En bloc resection, is this the future of non-muscle invasive bladder cancer management? Presentation of our technique and brief review of the literature.

INTRODUCTION: The quality of the initial transurethral resection of bladder tumors (TURBT) plays a key role in accurate local staging thus affecting treatment decision-making and disease prognosis. TURBT is still the gold standard for non-muscle invasive bladder cancer (NMIBC). However, en bloc resection of bladder tumors (ERBT) gradually expanded as a promising alternative to TURBT, aiming to overcome certain inherent limitations of conventional resection. We hereby describe a step-by-step bipolar ERBT technique and briefly review the current trends surrounding the role of various en bloc techniques in the field. CASE PRESENTATION: We present the case of a 65-year old patient undergoing bipolar ERBT for a single, approximately 2 cm, papillary bladder mass. An experienced urologist completed the procedure within 17 min and without any intra- or postoperative complications. No conversion to TURBT was needed, and an adequate specimen for histological assessment was obtained. The patient made an uneventful recovery, and no recurrence was noted at 12-months. CONCLUSION: Our initial experience demonstrates that ERBT via bipolar current is relatively quick, safe, and reliable. Prospective comparative clinical trials will examine its efficacy, and long-term oncological superiority in managing NMIBC.

Transforming urinary stone disease management by artificial intelligence-based methods: A comprehensive review.

Objective: To provide a comprehensive review on the existing research and evidence regarding artificial intelligence (AI) applications in the assessment and management of urinary stone disease. Methods: A comprehensive literature review was performed using PubMed, Scopus, and Google Scholar databases to identify publications about innovative concepts or supporting applications of AI in the improvement of every medical procedure relating to stone disease. The terms ''endourology'', ''artificial intelligence'', ''machine learning'', and ''urolithiasis'' were used for searching eligible reports, while review articles, articles referring to automated procedures without AI application, and editorial comments were excluded from the final set of publications. The search was conducted from January 2000 to September 2023 and included manuscripts in the English language. Results: A total of 69 studies were identified. The main subjects were related to the detection of urinary stones, the prediction of the outcome of conservative or operative management, the optimization of operative procedures, and the elucidation of the relation of urinary stone chemistry with various factors. Conclusion: AI represents a useful tool that provides urologists with numerous amenities, which explains the fact that it has gained ground in the pursuit of stone disease management perfection. The effectiveness of diagnosis and therapy can be increased by using it as an alternative or adjunct to the already existing data. However, little is known concerning the potential of this vast field. Electronic patient records, containing big data, offer AI the opportunity to develop and analyze more precise and efficient diagnostic and treatment algorithms. Nevertheless, the existing applications are not generalizable in real-life practice, and high-quality studies are needed to establish the integration of AI in the management of urinary stone disease.

Detection of multiple cytokines in the urine of patients with focal necrotising glomerulonephritis may predict short and long term outcome of renal function.

BACKGROUND: Detection of urinary cytokines in pauci-immune focal segmental necrotizing glomerulonephritis (FSNGN) may provide valuable information about disease pathogenesis and prognosis. METHODS: Epidermal growth factor (EGF), transforming growth factor (TGF-ß1) and vascular endothelial growth factor (VEGF) were measured by ELISA, and Interleukins, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP1ß) by a multiplex cytokine assay, in 38 patients with FSNGN. Their levels were correlated with severity of histological findings and renal function outcome in short and long term. RESULTS: The percentage of crescents in renal biopsy had positive correlation with TGF-ß1 (p=0.004) and IL-15 urinary excretion (p=0.01), and negative correlation with EGF (p=0.01). Increased urinary excretion of IL-6, IL-15, VEGF and MIP-1ß was associated with poor renal function outcome, but increased levels of EGF, IL-2 and IL-9 predicted a favourable prognosis. In multiple regression analysis IL-6 and VEGF urinary levels were independent predictors of no-response at the acute phase (p=0.001 and p<0.0001, respectively), while, IL-6 was the only factor (p=0.03) predicted worse outcome at the end of follow-up (39.4±45 months). CONCLUSION: Increased urinary excretion of IL-6, IL-15, VEGF, TGF-ß1, MCP-1 and MIP-1ß and reduced EGF, IL-2, IL-9 may be associated with histological damage and influence response to treatment in pauci-immune FSNGN.

Impact of long-term cinacalcet, ibandronate or teriparatide therapy on bone mineral density of hemodialysis patients: a pilot study.

BACKGROUND: Insufficient evidenced-based information is available for the treatment of osteoporosis in hemodialysis (HD) patients. METHODS: In 102 HD patients, bone mineral density (BMD) was measured twice 16 ± 3 months apart. In the second BMD measurement 66 of them had a femoral neck (FN) T-score <-2.5. Of these 66 patients, 38 consented to a bone biopsy. Depending on both the bone biopsy findings and parathyroid hormone levels, patients were assigned to treatment groups. Eleven patients with osteitis fibrosa and iPTH >300 pg/ml received cinacalcet, 11 with osteitis fibrosa and iPTH <300 pg/ml received ibandronate, 9 with adynamic bone disease received teriparatide, and 7 with mild abnormalities received no treatment. A third BMD measurement was done after an average treatment period of 13-16 months. We compared the annual percent change of FN and lumbar spine (LS) BMD before and during treatment. RESULTS: FN and LS BMD decreased significantly in the cinacalcet group, with an annual change of 3.6 and 3.4% before treatment to -4.2% (p = 0.04) and -7.7% (p = 0.02) during treatment, respectively. In the teriparatide group, FN and LS BMD increased, although not significantly, with an annual change of -5.4 and -2.6% before treatment to 2.7 and 4.9% during treatment, respectively. In both the ibandronate and the no treatment groups, BMD change rate remained negative during the whole study. CONCLUSIONS: Teriparatide administration improved BMD in HD patients with adynamic bone disease, although these results did not reach statistical significance. In HD patients with osteitis fibrosa, ibandronate did not improve BMD while cinacalcet reduced BMD.

The effects of vitamin E-coated membrane dialyzer compared to simvastatin in patients on chronic hemodialysis.

BACKGROUND: We investigated the effects of the use of vitamin E-coated membrane (VEM) dialyzer in comparison to simvastatin on markers of chronic inflammation, oxidative stress, and endothelial cell apoptosis in ten patients on chronic hemodialysis (HD), aiming at distinguishing the different treatment effects and their time sequence on these pathogenetic routes. METHODS: Ten HD patients were sequentially submitted to a 6-month treatment with the use of VEM and 10 mg of simvastatin daily, interrupted by a 3-month washout period. At baseline, at 3, and 6 months of each trial, serum C-reactive protein (CRP), apolipoprotein (Apo) A1 and B, lipoprotein-a [Lp(a)], high-sensitivity interleukin-6 (hsIL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble Fas (sFas), soluble Fas ligand (sFasL), and plasma oxidized low-density lipoproteins (oxLDL) levels were determined. RESULTS: VEM treatment resulted in a significant decrease in CRP, IL-6, sICAM-1 at 3 months, and oxLDL at 6 months, compared to baseline. Simvastatin resulted in a significant decrease in CRP, which correlated with decreases in both total (r = 0.87, p < 0.05) and low-density lipoprotein cholesterol, IL-6, sICAM-1, sVCAM-1, oxLDL, and sFas at 6 months, compared to baseline. Simvastatin effects on sVCAM-1 (mean difference = 652 ng/mL; 95% CI = 294 to 2686; p < 0.05) and sFas (mean difference = 1284 pg/mL; 95% CI = 510 to 1910; p < 0.05) differed significantly from the corresponding VEM effects. CONCLUSIONS: The 6-month use of VEM resulted in more direct and immediate anti-inflammatory effects compared with those caused by the 6-month treatment with simvastatin. Simvastatin caused a more intense decrease in the markers of inflammation, which was in part correlated with its lipid-lowering effects.

Incidental discovery of endourethral clip migration 10 years after radical prostatectomy: A case report and review of the literature.

INTRODUCTION: Surgical clips (SCs) have been widely used for a variety of surgical procedures over the years. Despite their advantages and proven effectiveness, several clip-related complications have been reported, creating dilemmas as to their optimal use. CASE DESCRIPTION: Herein, we present a rare delayed and incidental discovery of two endourethral metallic SCs in a 77-year-old male seeking treatment for acute renal colic. The patient had undergone open radical retropubic prostatectomy 10 years ago, and had an uneventful postoperative recovery. Computed tomography scan revealed left-sided hydronephrosis secondary to proximal ureteral calculus, as well as SCs at the level of vesico-urethral (VUR) anastomosis. Flexible cystoscopy confirmed the imaging findings, showing two endourethral clips, partly obstructing the VUR. Firstly, a serial wire-guided dilation took place, followed by left ureteral double-J stent placement. Unfortunately, the clips could not be concurrently removed due to their firm attachment to the bladder neck. Hence, our patient was scheduled for transurethral resection of the bladder neck and simultaneous endoscopic clip removal. CONCLUSIONS: To the best of our knowledge, this is the first report to highlight such a delayed incidental finding, 10 years after open retropubic radical prostatectomy (RRP), during a JJ stent insertion for obstructive uropathy without previous clip-induced lower urinary tract symptoms. Although rare, physicians should be aware of the potential clip-related complications arising either in the short- or long-term postprostatectomy setting.

Jackstone: A Calculus "Toy" in the Bladder. A Case Report of Rare Entity and Comprehensive Review of the Literature.

Background: An uncommon type of urinary calculus, Jackstone was named after its distinct resemblance to the children's game "Jacks." It typically involves the bladder and, to a lesser extent, the upper urinary tract. Case Presentation: Herein, we report a case of Jackstone vesical calculus in a 75-year-old male undergoing elective open prostate surgery for benign prostate hyperplasia refractory to medical treatment. Preoperative clinical examination revealed intermittent gross hematuria and symptoms suggestive of bladder outlet obstruction, while radiological investigation confirmed the presence of a solitary star-shaped spike-like bladder stone along with an overly enlarged prostate. Following open simple prostatectomy and concomitant intact stone removal, our patient made an uneventful postoperative recovery. Conclusion: This case highlights an infrequent subtype of bladder lithiasis and further expands upon the importance of promptly treating the underlying cause once this rare entity is detected. A comprehensive review of the literature on Jackstone calculi is further presented.

Acute kidney injury due to osmotic nephrosis following intraoperative placement of an intraperitoneal antiadhesive barrier.

In recent years, a common strategy for the prevention of postsurgical intra-abdominal adhesions has been intrasurgical placement of adhesion barriers into the peritoneal cavity. Osmotic agents, such as various polysaccharides, frequently are used as antiadhesive materials. The effects of these materials on kidney function have not yet been studied. We report a case of an individual with pre-existing chronic kidney disease who developed acute kidney injury after surgical placement of an antiadhesive barrier of macromolecular polysaccharides. A kidney biopsy, performed because of persistent kidney failure, showed tubular cell lesions compatible with osmotic nephrosis lesions. This case suggests that use of polysaccharide-containing antiadhesive barriers can induce severe kidney damage. Such barriers should be used with caution in patients with abnormal kidney function to prevent irreversible damage.

Effects of vitamin E-coated membrane dialyser on markers of oxidative stress and inflammation in patients on chronic haemodialysis.

BACKGROUND: In the present prospective, controlled, observational cohort study, we investigated the effects of the use of a vitamin E-coated membrane dialyser (VEM) on markers of chronic inflammation, oxidative stress and endothelial cell apoptosis in end-stage renal disease (ESRD) patients on chronic haemodialysis (HD), as long as evidence of their effects on these pathogenetic routes are inconclusive as yet, despite their use for the last several years. METHODS: Thirty-five stable ESRD patients underwent HD with the use of VEM for 6 months. Another 25 age- and sex-matched ESRD patients, being dialysed with conventional dialysers, served as controls. In both patient groups, beyond complete haematology and biochemistry work-up, serum CRP, apolipoproteins A1 and B, lipoprotein (a) (Lp(a)), hsIL-6, MCP-1, sICAM-1, sVCAM-1, sE-selectin, sFas and sFasL as well as plasma oxLDL, TBARS and TAS levels were determined at baseline and at 6 months of the study. RESULTS: In the VEM group at 6 months, a significant reduction in CRP (P = 0.004), IL-6 (P = 0.004) and sICAM-1 (P = 0.04) levels was observed compared with baseline, along with a remarkable change in all markers of oxidative stress, i.e. increase in TAS (P = 0.005) and decrease in TBARS (P = 0.04) and oxLDL (P < 0.001). No significant changes were noted in the other parameters studied in the VEM group or in any parameter studied in the controls. Between the groups, significant differences were found in the change of CRP (P = 0.001), sICAM-1 (P = 0.03) and oxLDL (P = 0.04) compared with baseline. CONCLUSIONS: HD with the use of VEM resulted in a significant reduction in inflammation and oxidative stress markers. Larger prospective randomized studies will need to confirm the findings of the present observational study.

Osmotic nephrosis due to the use of anti-adhesive membrane intraperitoneally.

BACKGROUND: A common strategy for the prevention of intra-abdominal adhesions post-operatively has been the application of adhesion barriers into the peritoneal cavity. Side effects of these barriers are infection, abscesses and inadequate wound healing. There is no information about such a side effect of these materials on renal function. The aim of this study was to evaluate the effect of two different, commercially available polysaccharide-based anti-adhesive materials on renal function. METHODS: In 24 adult Wistar rats, an abdominal midline incision was performed, and an anti-adhesion membrane was placed in the peritoneal cavity so as to cover its whole surface. Four rats were used as the control group. In 12 rats, a membrane of macromolecular polysaccharides, weighing 40 mg/cm2, was placed intra-abdominally and in 8 rats, a hyaluronic acid-hydroacidmethylcellulose membrane weighing 0.4 mg/cm2 was placed. At 24 or 70 h, the rats were sacrificed, and we evaluated changes in serum creatinine, urea, uric acid, K and Na, and histologic examination of the kidney was performed. RESULTS: The use of the thicker macromolecular membrane was associated with a rise in serum creatinine and urea levels, vacuolization of all the tubular epithelial cells and mild interstitial infiltration. Rats in which the hyaluronic acid-hydroacidmethylcellulose membrane was used did not show any creatinine elevation, and they presented milder histologic lesions. CONCLUSION: Polysaccharide and cellulose anti-adhesive membrane cause renal damage with tubular cell vacuolization. The severity of kidney damage is relative to the quantity of the membrane material used.

Steroids and azathioprine in the treatment of IgA nephropathy.

AIM: IgA nephropathy (IgAN) is a very common glomerulonephritis among young adults, but the best therapeutic approach has not been fully elucidated. This study evaluated the effect of two different treatment regimes in IgAN, steroids alone or in combination with azathioprine. METHODS: Among 122 patients with primary IgA nephropathy diagnosed in the 2000-2007 period, 22 fulfilled the inclusion criteria for the study: estimated glomerular filtration rate (eGRF) ≥30 ml/min/1.73 m(2), urine protein (Upr) ≥1 g/24 h, blood pressure (BP) <130/80 mmHg, and previous treatment with renin-angiotensin system inhibitors (RAASi) and polyunsaturated fatty acids (PFA) for at least 6 months. Patients were randomized to receive either methylprednisolone alone (MP group) or MP in combination with azathioprine (MP + Aza group) for 12 months, while treatment with RAASi + PFA continued unchanged in both groups. RESULTS: At the completion of the trial, renal function in the MP group remained stable, eGFR from 52 ± 26.7 to 53.6 ± 27.3 ml/min/1.73 m(2), p = NS, and Upr decreased from 2.4 ± 0.9 to 0.8 ± 0.5 g/24 h, p < 0.001. In the MP + Aza group, eGFR slightly increased from 57.4 ± 28.7 to 66 ± 31 ml/min/1.73 m(2), p = NS, and Upr decreased from 2.4 ± 1 to 0.7 ± 0.7 g/24 h, p < 0.001. Four patients from the MP group with partial remission at the end of the trial had a complete response when converted to Aza. Eleven patients (5 from the MP and 6 from the MP + Aza group) relapsed after stopping treatment and were restarted on lower doses. CONCLUSIONS: Both, steroid treatment alone and steroids in combination with azathioprine seem to be effective in reducing the severity of proteinuria and stabilizing renal function in IgAN. Patients who do not respond to steroids may have a better response with the combination of steroids and azathioprine.

Influence of aldosterone synthase gene C-344T polymorphism on focal segmental glomerulosclerosis.

AIM: We evaluated the influence of C-344T polymorphism of the aldosterone synthase gene, associated with aldosterone levels and the development of arterial hypertension, on focal segmental glomerulosclerosis (FSGS). METHODS: We studied 81 patients with primary FSGS followed up for 8.0 ± 12 years. Patients were classified according to their slope of reciprocal serum creatinine into group A (slow progressors, n = 57) and B (fast progressors, n = 24). One hundred healthy volunteers were analysed as controls. The biopsies of n = 50 patients were reviewed and analysed by the same pathologist. C-344T polymorphism was determined by polymerase chain reaction. RESULTS: The allele frequencies differed significantly between patients (C-allele: 0.55, T-allele: 0.45) and controls (C-allele: 0.45, T-allele: 0.55; P < 0.05). Patients carrying the C-allele tended to have a higher percentage of sclerosed glomeruli (41.8 ± 30% vs 31. 2 ± 19% in TT genotype, ns) and tubulointerstitial fibrosis (22.8 ± 18% vs 16.0 ± 5%, ns). The rate of deterioration of renal function was higher in the CC/CT genotypes (-0.216 ± 0.449 dL/mg per year) compared to the TT genotype (-0.030 ± 0.041 dL/mg per year, P = 0.002). Furthermore, 36.4% of the C-allele carriers and none of the patients with the TT genotype belonged to group B (P = 0.005). C-allele carriers also had a worse kidney survival in the Kaplan-Meier analysis (P = 0.027). CONCLUSION: Our results indicate that aldosterone synthase gene C-344T polymorphism not only acts as a risk factor for the development of FSGS, but also may influence its pathologic appearance and could serve as a marker of disease progression.