Nox1-derived oxidative stress as a common pathogenic link between obesity and hyperoxaluria-related kidney injury.

Specific relationships among reactive oxygen species, activation pathways, and inflammatory mechanisms involved in kidney injury were assessed in a combined model of obesity and hyperoxaluria. Male Wistar rats were divided into four groups: Control, HFD (high fat diet), OX (0.75% ethylene glycol), and HFD + OX (combined model) Changes in basal O2- levels were evaluated by chemiluminescence in renal interlobar arteries and renal cortex. Furthermore, the effect of different inhibitors on NADPH-stimulated O2- generation was assessed in renal cortex. Oxidative stress sources, and local inflammatory mediators, were also determined, in parallel, by RT-PCR, and correlated with measures of renal function, urinary biochemistry, and renal structure. Rats from the HFD group developed overweight without lipid profile alteration. Tubular deposits of crystals were seen in OX and severely enhanced in HFD + OX groups along with a significantly higher impairment of renal function. Basal oxidative stress was increased in renal cortex of OX rats and in renal arteries of HFD rats, while animals from the combined HFD + OX group exhibited the highest levels of oxidative stress in renal cortex, derived from xanthine oxidase and COX-2. NADPH oxidase-dependent O2- generation was elevated in renal cortex of the OX group and markedly enhanced in the HFD + OX rats, and associated to an up-regulation of Nox1 and a down-regulation of Nox4 expression. High levels of oxidative stress in the kidney, of OX and HFD + OX groups were also associated to an inflammatory response mediated by an elevation of TNFα, COX-2, NFκB1 MCP-1, and OPN. Oxidative stress is a key pathogenic factor in renal disease associated to hyperoxaluria and a common link underlying the exacerbated inflammatory response and kidney injury found under conditions of both obesity and hyperoxaluria. Nox1 pathway must be considered as a potential therapeutic target.

Review of the pathophysiological aspects involved in urological disease associated with metabolic syndrome. / Aspectos fisiopatológicos implicados en la patología urologica asociada al síndrome metabólico. Revisión bibliográfica.

INTRODUCTION: Metabolic syndrome is a constellation of disorders that includes insulin resistance, central obesity, arterial hypertension and hyperlipidaemia. These disorders can have implications for the genitourinary apparatus. OBJECTIVES: To conduct a review on the pathophysiological aspects that explain the relationship between metabolic syndrome and sexual dysfunction, lower urinary tract syndrome, prostate cancer and stone disease. METHODS: We performed a qualitative, narrative literature review through a literature search on PubMed of articles published between 1997 and 2015, using the terms pathophysiology, metabolic syndrome, endothelial dysfunction, lipotoxicity, mitochondrial dysfunction, kidney stones, hypogonadism, erectile dysfunction, lower urinary tract syndrome and prostate cancer. SYNTHESIS OF THE EVIDENCE: Metabolic syndrome constitutes an established complex of symptoms, defined as the presence of insulin resistance, central obesity, hypertension and hyperlipidaemia. Endothelial dysfunction secondary to lipotoxicity generates an inflammatory state, which involves renal cell metabolism, vascularisation of the pelvis and androgen production. These facts explain the relationship between metabolic syndrome, nephrolithiasis, lower urinary tract syndrome, hypogonadism and erectile dysfunction in men. CONCLUSIONS: Strategies such as proper diet, regular exercise, insulin treatment, testosterone-replacement therapy, therapy with antioxidants and free-radical inhibitors and urological treatments classically used for lower urinary tract syndrome have shown promising results in this syndrome.

[Prognostic factors of spontaneous expulsion in ureteral lithiasis]. / Factores predictivos para la expulsión de la litiasis ureteral.

UNLABELLED: Medical treatment, extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy are therapeutic options for ureteral stones. EWSL and endoscopic treatment of ureteral stones have a high success rate. However it has surgical as well as anaesthetic risks. For many patients, a medicinal treatment without invasive procedures is an option. Watchful waiting does not always result in stone clearance and may be associated with recurrent renal colic. The study of the prognostic factors for expulsion and the medical therapy will help us to select candidates for medical expulsive treatment. OBJECTIVES: To evaluate the characteristics of the stones and the medication administered (alpha blockers, NSAIDs or a combination of both) as predictors of spontaneous passage of the stone. MATERIAL AND METHODS: A retrospective observational study of 260 patients with 278 ureteral stones was conducted. Primary endpoint was stone expulsion. Univariate and multivariate analysis were conducted testing the effect of stone location, size and composition, and medication (alpha-blockers, NSAIDs, or combination) on stone clearance. RESULTS: 34,2% of the stones studied were spontaneously eliminated. Stone location (pelvic ureter, OR=1.823, p=0.013), size (>5 mm, OR=3.37, p>0.02), and medication (combination of alpha blockers and NSAIDs, OR=8.70, >0.001) were predictors of spontaneous clearance. Multivariate analysis confirmed size (p=0.006) and medication (p>0.001) as independent predictive factors.The use of the combination of NSAIDs and alpha-blockers versus observation multiplied times 8.21 (95%CI 3.37-20.01) the possibilities of spontaneous expulsion. CONCLUSIONS: Size of stone and medication were confirmed as independent factors for spontaneous expulsion of ureteral stones.

[Relational database for urinary stone ambulatory consultation. Assessment of initial outcomes]. / Una base de datos relacional para consulta de litiasis urinaria. Evaluación inicial de resultados.

OBJECTIVES: To create a relational database for monitoring lithiasic patients. We describe the architectural details and the initial results of the statistical analysis. METHODS AND MATERIALS: Microsoft Access 2002 was used as template. Four different tables were constructed to gather demographic data (table 1), clinical and laboratory findings (table 2), stone features (table 3) and therapeutic approach (table 4). For a reliability analysis of the database the number of correctly stored data was gathered. To evaluate the performance of the database, a prospective analysis was conducted, from May 2004 to August 2009, on 171 stone free patients after treatment (EWSL, surgery or medical) from a total of 511 patients stored in the database. Lithiasic status (stone free or stone relapse) was used as primary end point, while demographic factors (age, gender), lithiasic history, upper urinary tract alterations and characteristics of the stone (side, location, composition and size) were considered as predictive factors. An univariate analysis was conducted initially by chi square test and supplemented by Kaplan Meier estimates for time to stone recurrence. A multiple Cox proportional hazards regression model was generated to jointly assess the prognostic value of the demographic factors and the predictive value of stones characteristics. RESULTS: For the reliability analysis 22,084 data were available corresponding to 702 consultations on 511 patients. Analysis of data showed a recurrence rate of 85.4% (146/171, median time to recurrence 608 days, range 70-1758). In the univariate and multivariate analysis, none of the factors under consideration had a significant effect on recurrence rate (p=ns). CONCLUSIONS: The relational database is useful for monitoring patients with urolithiasis. It allows easy control and update, as well as data storage for later use. The analysis conducted for its evaluation showed no influence of demographic factors and stone features on stone recurrence.

[Immune response during laparoscopic and open living donor nephrectomy. An experimental pig model]. / Respuesta inmunohumoral durante la nefrectomía abierta y laparoscópica de donante vivo. Modelo porcino experimental.

INTRODUCTION: It's been demonstrated laparoscopic access determines a lower surgical stress, by measurement of several markers as different interleuquines (IL) or C-reactive protein (CRP). Endothelin 1 (ET-1) is a powerful vasoconstrictor produced in renal endothelium scarcely studied in laparoscopy. The objective of this study is to analyze immune response during laparoscopic and open donor nephrectomy, in a porcine experimental model by means of measuring IL-2, 10, tumoral necrosis factor alpha (TNFalpha), CRP and ET-1. METHODS: Twenty pigs underwent left nephrectomy, 10 by laparoscopy and 10 by open approach in an experimental model. Both groups were monitorized IL-2, 10, TNF alpha, ET-1 at basal, immediately post surgery, first, third, fifth and seventh days after procedure. RESULTS: The comparative analysis between groups demonstrated a significant increase in levels of CRP (1.44+/-0.88 vs 1.32+/-0.14 mg/dl, p=0.046), TNF alpha (131.14+/-41.37 vs 57.19+/-23.71 pg/ml, p>0.001) and ET-1 (0.91+/-0.49 vs 0.56+/-0.5 fmol/ml, p=0.001) of open nephrectomy group, as a higher levels of IL-2 in laparoscopic group. CONCLUSIONS: Open donor nephrectomy determines a higher immune response than laparoscopic approach. The importance of this fact over the ischemia-reperfusion syndrome or the immediate function of graft is not clearly established.

[Experimental models for research and training in renal transplant]. / Modelos experimentales para la investigación y el entrenamiento en trasplante renal.

An update on aspects and use of different experimental models applied in kidney transplant research is presented . This paper includes qualities, as long as similarities between most frequently used animal models and human clinical standards. Contributions of those models based on microsurgical or laparoscopic techniques are revised. The physiological consequences (hemodynamic, immunologic) of surgical technique (laparoscopy), applied in experimental models as long as non-heart beating organ donor models and organ preservation methods are also reviewed. Finally, an update of those models applied in research in prothocols of either immunosupression or xenotransplant is done.

[Modification of the hemodynamic parameters and peripheral vascular flow in a porcine experimental of model of laparoscopic nephrectomy]. / Modificaciones de los parámetros hemodinámicos y de los distintos flujos vasculares periféricos en modelo experimental porcino de nefrectomía laparoscópica.

OBJECTIVES: It has been demonstrated that abdominal high-pressure and the use of CO2 pneumoperitoneum induce changes of the cardiovascular and respiratory systems, attributable to two factors: changes of the cardiac output (CO) and hypercarbia. Other modifications derived from these facts include changes of the systemic vascular resistances (SVR), blood pressure (BP), central venous pressure (CVP), vascular changes like modifications of the renal blood flow (RBF), carotid flow (CF), portal flow, and hepatic artery flow (HAF). Our objective is to analyze the hemodynamic modifications induced by pneumoperitoneum on renal blood flow, carotid flow, portal flow and hepatic artery flow in a porcine experimental model. METHODS: We compared two groups of pigs: CONTROL group (n = 10) and LAPAROSCOPIC group (n = 10), undergoing open or laparoscopic nephrectomy respectively. In every case, catheters were inserted into the right external jugular vein and femoral artery and cardiac output, CVP, blood pressure and systemic vascular resistances (calculated as RVS = (BP/CVP)x 80/CO); these measurements were taken at the following times: baseline, 5, 30, 60 min. and postoperatively. Renal blood flow, carotid flow, portal flow and hepatic artery flow were registered by means of an electromagnetic probe around the vessel 30 minutes after the start of surgery. RESULTS: Comparative analysis shows: an increase of cardiac output in the laparoscopic group, the difference which was maximal at 30 minutes (4.33 + 0.73 vs. 8 .54 + 1.26 l/min., p < 0.,001); a descent of the systemic vascular resistances (1118.81 + 302.52 vs. 663.37 + 81.45 dynes .s.cm5, p < 0.001) and an increase of blood pressure (66.5 + 11.52 vs. 80.25 + 2.49 mm Hg in the laparoscopic group. Flow analysis showed an increase of the carotid artery flow (125.73 + 41.69 vs. 291.7 + 51.52 ml/min., p < 0.001) and a decrease of portal flow (973.67 + 131.70 vs. 546.83 + 217.53 ml/min., p = 0.001) and hepatic artery flow (278.00 + 94.71 vs. 133.33 + 112.32 ml/min., p = 0.03) in the laparoscopic group. There were no significant differences in renal blood flow with the volume expansion used. CONCLUSIONS: Laparoscopic nephrectomy conditions an increase of carotid flow, probably secondary to the increase of cardiac output, and also a diminishment of hepatic perfusion, both arterial and portal. Nevertheless, volume expansion and the limitation of intra-abdominal pressure to 12 mm Hg enable to maintain similar renal blood flow in both groups.

[Adequacy of referral from primary care to a Department of Urology]. / Adecuación de las derivaciones desde Atención Primaria a un Servicio de Urología.

OBJECTIVE: [corrected] To indirectly address the adequacy of referrals from general practitioners (GP) to specialized care taking into account a previously agreed protocol on ten urological topics. MATERIALS & METHODS: The study analyzed all referrals to the Urology department originated in 10 primary care centres (135 GPs involved) throughout a 19-month period. Adequacy of 2841 referrals was checked. The urologist judged the referral as compliant (adequate) or not compliant (inadequate) with the terms of the protocol. Compliance per primary care centres was compared. Also referral adequacy corrected per centre and clinical topic was compared. The relationship between "absolute number of referrals" and "adequate referrals" was tested using a linear regression model. RESULTS: 57.2% of the referrals were inadequate. Overall, no significant differences were detected between primary care centres. Nevertheless significant differences between centres were evident in terms of referrals due to renal colic and female urinary incontinence. 70% (94/135) of the GPs complied with the protocol in, at least, 50% of the cases. A strong association between "absolute number of referrals" and "adequate referrals" was evident (r2=0.86). CONCLUSIONS: Overall compliance with the protocol was modest. While no significant differences between centres were detected in terms of adequacy of referrals certain conditions have to be locally revisited; most of the topics (particularly microhematuria) have to be revisited in every center.

[Adrenal pseudocyst. Report of a new case and review of the literature]. / Pseudoquiste adrenal. Aportación de un nuevo caso y revisión de la literatura.

Adrenal pseudocyst is the commonest type of benign lesions of adrenal gland althought is a very rare entity. Most of them are found as "incidentalomas" during imaging studies. A case of a patient with a left non-functioning and asymptomatic adrenal pseudocyst is reported. The diagnostic and therapeutic options are discussed and the literature is reviewed.

[Renal metastasis of hepatocellular carcinoma]. / Metástasis renal de hepatocarcinoma.

OBJECTIVE: To report the case of a solitary renal metastasis secondary to hepatocellular carcinoma. METHODS: We report the case of a 51 year old patient who on abdominal ultrasonography was revealed a left renal tumour and a hepatic mass incidentally. A TAC showed the left renal tumor measuring 17 cm in size, possible involvement of left renal vein and a tumour mass in the right lobe of the liver. A TAC guided fine needle punction aspiration biopsy demonstrated a malignant hepatic lesion compatible with hepatocarcinoma, and malignant renal cells compatible with renal or adrenal carcinoma. Left radical nephrectomy and right hepatectomy was performed. RESULTS: Histopathologic study confirmed the diagnosis of moderately differentiated trabecular hepatocarcinoma with lymph node and left renal metastasis.

[Posterior sacral root neuromodulation in the treatment of chronic urinary dysfunction]. / Neuromodulación de raíces sacras posteriores en el tratamiento de la disfunción miccional crónica.

OBJECTIVES: To describe the effectiveness of sacral root neuromodulation in ameliorating symptoms of refractory voiding disfunction in our center. MATERIAL AND METHODS: During the period from december 1998 throught december 2001, 31 Percutaneous Nerve Evaluation (PNE) was performed to 20 patients with refractory voiding dysfunction; a sacral nerve stimulation device was implanted in 10 patients (8 female, 2 male). The median age was 49 years. Refractory voiding dysfunction included: mixed disorders (30%), idiopathic nonobstructive chronic urinary retention (20%), urgency/frequency (20%), faecal and urinary incontinence with absence of sphincter defect (20%) and frequency (10%). RESULTS: The 2 patients with frequency/urgency decreased their symptoms more than 50%, bladders were emptied without post-void residual urine in 2 patients with urinary retention, faecal and urinary incontinence in 2 patients and mixed disorders in other 3, reduced their symptoms more than 90% without residual urine. The frequency improved more than 50% in 1 patient. CONCLUSIONS: Sacral Root Neuromodulation is a successful treatment in some cases of idiopathic chronic micturition dysfunction which don't respond to pharmacotheraphy or bladder retraining. The effects of neuromodulation are long-lasting and associated morbidity is low.

[Urethro-vesical foreign bodies]. / Cuerpos extraños uretro-vesicales.

We report the case of a squizoid 45 year old man who presented an acute urinary retention and had several foreign bodies in the urethra and bladder.

[Metachronous solitary contralateral adrenal metastasis of primary renal carcinoma: report of a new case]. / Metástasis adrenal metacrónica solitaria contralateral de un carcinoma renal primario: aportación de un nuevo caso.

OBJECTIVE: To report a case of solitary metachronous contralateral metastasis of a renal carcinoma that had been previously resected. METHODS: A 63-year-old male that had previously undergone a right radical nephrectomy due to renal carcinoma is presented. The patient's left breast was found to be slightly larger at the control evaluation 24-months postoperatively. Analytical and hormonal studies showed no significant findings except for a serum creatinine value of 1.75 mg/dl. However, a CT scan showed a left adrenal nodule of 3 cm. After 6 months of watchful waiting, the nodule had increased to 4.3 cm. A CT-guided fine needle punction aspiration biopsy demonstrated a malignant lesion and a left adrenalectomy was performed. RESULTS: Histopathological analysis of the surgical specimen showed adrenal metastasis of clear cell renal carcinoma. At 21 months' follow-up after adrenalectomy, there is no evidence of recurrence of the metastasis. CONCLUSIONS: This type of lesion is uncommon. We emphasize the importance of the analytical and hormonal studies, as well as CT and FNPA, in the diagnosis of this adrenal pathology. Like other authors, we advocate performing adrenalectomy in these cases.

[Partial nephrectomy in lithiasis]. / Nefrectomía parcial en la patología litiásica.

OBJECTIVE: To analyze our series of patients with renal lithiasis who underwent partial nephrectomy from 1980-1999. METHODS: 28 patients who underwent partial nephrectomy were analyzed (22 females; mean age 48.09 years, and 6 males; mean age 60 years). Surgery for lithiasis had been previously performed in 5 renal units. Nine patients had previously undergone ESWL (more than 3 sessions), all of whom subsequently developed multiple residual calculi. Twelve patients had a microbiologically confirmed positive urine culture. The renal lithiasis amenable to treatment by partial nephrectomy was frequently localized in the lower calyces (17 cases). RESULTS: Histopathological analysis of the nephrectomy specimen showed a prevalence of signs of chronic parenchymal atrophy (25 cases). Three cases showed segmental renal dysplasia (those in whom a superior heminephrectomy was performed for duplex excretory system). Fifty percent of the stone fragments analyzed showed calcium phosphocarbonate. Eight patients had postoperative complications; the most important were two cases of renal cutaneous fistula and one subphrenic abscess. At 9 1/2 years' mean follow-up, renal function is normal in 25 patients. Lithiasis developed in the contralateral unit in 6 cases and in the same renal unit in one case. CONCLUSIONS: Partial nephrectomy continues to be a therapeutic option for lithiasis. Its indication depends on the morphological and functional characteristics of the compromised renal unit, especially in those cases in whom renal preservation can be obviated due to its scanty significance.