Endothelial Dysfunction: An Intermediate Clinical Feature between Urolithiasis and Cardiovascular Diseases.

An epidemiological relationship between urolithiasis and cardiovascular diseases has extensively been reported. Endothelial dysfunction is an early pathogenic event in cardiovascular diseases and has been associated with oxidative stress and low chronic inflammation in hypertension, coronary heart disease, stroke or the vascular complications of diabetes and obesity. The aim of this study is to summarize the current knowledge about the pathogenic mechanisms of urolithiasis in relation to the development of endothelial dysfunction and cardiovascular morbidities. METHODS: A non-systematic review has been performed mixing the terms "urolithiasis", "kidney stone" or "nephrolithiasis" with "cardiovascular disease", "myocardial infarction", "stroke", or "endothelial dysfunction". RESULTS: Patients with nephrolithiasis develop a higher incidence of cardiovascular disease with a relative risk estimated between 1.20 and 1.24 and also develop a higher vascular disease risk scores. Analyses of subgroups have rendered inconclusive results regarding gender or age. Endothelial dysfunction has also been strongly associated with urolithiasis in clinical studies, although no systemic serum markers of endothelial dysfunction, inflammation or oxidative stress could be clearly related. Analysis of urine composition of lithiasic patients also detected a higher expression of proteins related to cardiovascular disease. Experimental models of hyperoxaluria have also found elevation of serum endothelial dysfunction markers. CONCLUSIONS: Endothelial dysfunction has been strongly associated with urolithiasis and based on the experimental evidence, should be considered as an intermediate and changeable feature between urolithiasis and cardiovascular diseases. Oxidative stress, a key pathogenic factor in the development of endothelial dysfunction has been also pointed out as an important factor of lithogenesis. Special attention must be paid to cardiovascular morbidities associated with urolithiasis in order to take advantage of pleiotropic effects of statins, angiotensin receptor blockers and allopurinol.

Ureteroscopy for the treatment of urinary stones. Past, present and future.

OBJECTIVES: Ureteroscopy has been considered one of the most revolutionary techniques in modern urology for the treatment of urinary stones. The developments of new ureteroscopes, ancillary techniques or fragmentation devices have contributed to that evolution. To describe the evolution of imaging systems, auxiliary techniques and fragmentation methods for treatment of urinary stones from its beginnings to present time, with special emphasis on the different trends in the technique for the nearest future. METHODS: A bibliographic review is performed highlighting the development of technical details, and the impact on the results in terms of stone-free rate, and complications. CONCLUSIONS: Ureteroscopy has evolved into a first-line technique for the treatment of upper urinary tract stones. Technological advances in both imaging equipment and on different ancillary techniques and fragmentation methods have enabled improved stone free rates and decreased morbidity of the technique. Improvements in imaging systems, auxiliary instruments and fragmentation methods allow the treatment of stones progressively more complex.

Cardiovascular and Cerebrovascular Morbidity in Patients with Urolithiasis: An Epidemiological Approach Based on Hospitalization Burden Data from 1997 to 2021.

Background: Patients with kidney stones (KSFs) are known to have a heightened risk of coronary heart disease (CHD) or stroke. The objective of the present study was to describe the natural history of these complications through the longitudinal analysis of the hospitalizations due to kidney stones in Spain from 1997 to 2021. Methods: A retrospective longitudinal observational study was developed based on nationwide hospitalization data (minimum basic data base). Three different analyses were carried out. In the first step, the prevalence of coronary or cerebrovascular events in kidney stone hospitalizations was compared with the hospitalization burden of CHD or strokes related to the general population. In the second step, a survival analysis of the kidney stones-hospitalized patients using the Kaplan-Meier method was conducted. In the third step, a Cox regression was used to assess the influence of the classical comorbidities in the development of the lithiasic patients-cardiovascular disease. Results: Kidney stone-hospitalized patients exhibit a significantly higher risk of CHD (OR = 14.8 CI95%: 14.7-14.9) and stroke (OR = 6.7 CI95%: 6.6-6.8) compared to the general population across in all age groups, although they had less cardiovascular risk factors. A total of 9352 KSFs (1.5%) developed a coronary event within an average time of 78.8 months. A total of 2120 KSFs (0.33%) suffered a stroke in an average time of 71.1 months. Diabetes, hypertension, hyperlipidemia, and being overweight were identified as risk factors for developing CHD and stroke using a univariate and multivariate analysis. Conclusions: Our study confirms previous studies in which kidney stones must be considered as a risk factor for developing CHD or cerebrovascular disease. Preventive strategies should target patients with kidney stones and classical risk cardiovascular factors to mitigate modifiable conditions associated with cardiovascular diseases.

Activation of mitoKATP channels induces penile vasodilation and inhibits mitochondrial respiration and ROS production: Role of NO.

OBJECTIVE: Mitochondrial ATP-sensitive K+ (mitoKATP) channels are involved in neuronal and cardiac protection from ischemia and oxidative stress. Penile erection is a neurovascular event mediated by relaxation of the erectile tissue via nitric oxide (NO) released from nerves and endothelium. In the present study, we investigated whether mitoKATP channels play a role in the control of penile vascular tone and mitochondrial dynamics, and the involvement of NO. METHODS: The effect of the selective mitoKATP activator BMS191095 was examined on vascular tone, on mitochondrial bioenergetics by real-time measurements with Agilent Seahorse and on ROS production by MitoSOX fluorescence in freshly isolated microarteries. RESULTS: BMS191095 and diazoxide relaxed penile arteries, BMS191095 being one order of magnitude more potent. BMS191095-induced relaxations were reduced by mechanical endothelium removal and by inhibitors of the nitric oxide synthase (NOS) and PI3K enzymes. The NO-dependent component of the relaxation to BMS191095 was impaired in penile arteries from insulin resistant obese rats. The blockers of mitoKATP channel 5-HD, sarcolemma KATP (sarcKATP) channel glibenclamide, and large conductance Ca2+-activated K+ (BKCa) channel iberiotoxin, inhibited relaxations to BMS191095 and to the NO donor SNAP. BMS191095 reduced the mitochondrial bioenergetic profile of penile arteries and attenuated mitochondrial ROS production. Blockade of endogenous NO impaired and exogenous NO mimicked, respectively, the inhibitory effects of BMS191095 on basal respiration and oxygen consumed for ATP synthesis. Exogenous NO exhibited dual inhibitory/stimulatory effects on mitochondrial respiration. CONCLUSIONS: These results demonstrate that selective activation of mitoKATP channels causes penile vasodilation, attenuates ROS production and inhibits mitochondrial respiration in part by releasing endothelial NO. These mechanisms couple blood flow and metabolism in penile arterial wall and suggest that activation of vascular mitoKATP channels may protect erectile tissue against ischemic injury.

Hospitalization Burden of Patients with Kidney Stones and Metabolic Comorbidities in Spain during the Period 2017-2020.

Nephrolithiasis has become an increasing worldwide problem during the last decades. Metabolic syndrome, its components, and related dietary factors have been pointed out as responsible for the increasing incidence. The objective of this study was to evaluate the trends in the hospitalization rates of patients with nephrolithiasis, hospitalization features, costs, and how metabolic syndrome traits influence both the prevalence and complications of lithiasic patients. An observational retrospective study was conducted by analyzing hospitalization records from the minimum basic data set, including all patient hospitalizations in Spain in which nephrolithiasis has been coded as a main diagnosis or as a comorbidity during the period 2017-2020. A total of 106,407 patients were hospitalized and coded for kidney or ureteral lithiasis in this period. The mean age of the patients was 58.28 years (CI95%: 58.18-58.38); 56.8% were male, and the median length of stay was 5.23 days (CI95%: 5.06-5.39). In 56,884 (53.5%) patients, kidney or ureteral lithiasis were coded as the main diagnosis; the rest of the patients were coded mostly as direct complications of kidney or ureteral stones, such as "non-pecified renal colic", "acute pyelonephritis", or "tract urinary infection". The hospitalization rate was 56.7 (CI95%: 56.3-57.01) patients per 100,000 inhabitants, showing neither a significant increasing nor decreasing trend, although it was influenced by the COVID-19 pandemic. The mortality rate was 1.6% (CI95%: 1.5-1.7), which was higher, if lithiasis was coded as a comorbidity (3.4% CI95%: 3.2-3.6). Metabolic syndrome diagnosis component codes increased the association with kidney lithiasis when age was higher, reaching the highest in the eighth decade of life. Age, diabetes, and hypertension or lithiasis coded as a comorbidity were the most common causes associated with the mortality of lithiasic patients. In Spain, the hospitalization rate of kidney lithiasis has remained stable during the period of study. The mortality rate in lithiasic patients is higher in elderly patients, being associated with urinary tract infections. Comorbidity conditions such as diabetes mellitus and hypertension are mortality predictors.

Hyperoxaluria Induces Endothelial Dysfunction in Preglomerular Arteries: Involvement of Oxidative Stress.

Urolithiasis is a worldwide problem and a risk factor for kidney injury. Oxidative stress-associated renal endothelial dysfunction secondary to urolithiasis could be a key pathogenic factor, similar to obesity and diabetes-related nephropathy. The aim of the present study was to characterize urolithiasis-related endothelial dysfunction in a hyperoxaluria rat model of renal lithiasis. EXPERIMENTAL APPROACH: Endothelial dysfunction was assessed in preglomerular arteries isolated from control rats and in which 0.75% ethylene glycol was administered in drinking water. Renal interlobar arteries were mounted in microvascular myographs for functional studies; superoxide generation was measured by chemiluminescence and mRNA and protein expression by RT-PCR and immunofluorescence, respectively. Selective inhibitors were used to study the influence of the different ROS sources, xanthine oxidase, COX-2, Nox1, Nox2 and Nox4. Inflammatory vascular response was also studied by measuring the RNAm expression of NF-κB, MCP-1 and TNFα by RT-PCR. RESULTS: Endothelium-dependent vasodilator responses were impaired in the preglomerular arteries of the hyperoxaluric group along with higher superoxide generation in the renal cortex and vascular inflammation developed by MCP-1 and promoted by NF-κB. The xanthine oxidase inhibitor allopurinol restored the endothelial relaxations and returned superoxide generation to basal values. Nox1 and Nox2 mRNA were up-regulated in arteries from the hyperoxaluric group, and Nox1 and Nox2 selective inhibitors also restored the impaired vasodilator responses and normalized NADPH oxidase-dependent higher superoxide values of renal cortex from the hyperoxaluric group. CONCLUSIONS: The current data support that hyperoxaluria induces oxidative stress-mediated endothelial dysfunction and inflammatory response in renal preglomerular arteries which is promoted by the xanthine oxidase, Nox1 and Nox2 pathways.

Differential contribution of renal cytochrome P450 enzymes to kidney endothelial dysfunction and vascular oxidative stress in obesity.

Arachidonic acid (AA)-derived cytochrome P450 (CYP) derivatives, epoxyeicosatrienoic acids (EETs) and 20-hidroxyeicosatetranoic acid (20-HETE), play a key role in kidney tubular and vascular functions and blood pressure. Altered metabolism of CYP epoxygenases and CYP hydroxylases has differentially been involved in the pathogenesis of metabolic disease-associated vascular complications, although the mechanisms responsible for the vascular injury are unclear. The present study aimed to assess whether obesity-induced changes in CYP enzymes may contribute to oxidative stress and endothelial dysfunction in kidney preglomerular arteries. Endothelial function and reactive oxygen species (ROS) production were assessed in interlobar arteries of obese Zucker rats (OZR) and their lean counterparts lean Zucker rats (LZR) and the effects of CYP2C and CYP4A inhibitors sulfaphenazole and HET0016, respectively, were examined on the endothelium-dependent relaxations and O2- and H2O2 levels of preglomerular arteries. Non-nitric oxide (NO) non-prostanoid endothelium-derived hyperpolarization (EDH)-type responses were preserved but resistant to the CYP epoxygenase blocker sulfaphenazole in OZR in contrast to those in LZR. Sulfaphenazole did not further inhibit reduced arterial H2O2 levels, and CYP2C11/CYP2C23 enzymes were downregulated in intrarenal arteries from OZR. Renal EDH-mediated relaxations were preserved in obese rats by the enhanced activity and expression of endothelial calcium-activated potassium channels (KCa). CYP4A blockade restored impaired NO-mediated dilatation and inhibited augmented O2- production in kidney arteries from OZR. The current data demonstrate that both decreased endothelial CYP2C11/ CYP2C23-derived vasodilator H2O2 and augmented CYP4A-derived 20-HETE contribute to endothelial dysfunction and vascular oxidative stress in obesity. CYP4A inhibitors ameliorate arterial oxidative stress and restore endothelial function which suggests its therapeutic potential for the vascular complications of obesity-associated kidney injury.

Urolithiasis Develops Endothelial Dysfunction as a Clinical Feature.

An increased risk of cardiovascular morbidity has been reported in lithiasic patients. In this context, endothelial dysfunction (ED), an earlier status of atherogenesis, has been identified in hyperoxaluria rat models of urolithiasis. OBJECTIVE: The purpose of this study was to determine the endothelial vascular function in patients with urolithiasis in relation to systemic inflammatory, oxidative stress, and vascular function serum markers. METHODS: A cross-sectional study was performed between 27 urolithiasic patients, matched for age and sex, with 27 healthy patients. Endothelial function was assessed by measuring flow-mediated dilation (Celermajer method). Fasting blood was collected to determine metabolic parameters (glucose and lipid profile), along with serum CRP, IL-6, MDA, ADMA, and VCAM-1. RESULTS: Both the control and urolithiasis groups were homogenous in anthropometric, exploration, and general laboratory measures. Flow-mediated dilation (%FMD) was 11.85% (SE: 2.78) lower in the lithiasis group (p < 0.001). No significant differences were achieved between groups when CRP, IL-6, MDA, ADMA, and VCAM-1 were compared, although slightly higher values of CRP, ADMA, and VCAM-1 were detected in the lithiasic group. A correlation was not reached in any of the serum markers when they were related to flow-mediated values, although a slight negative correlation trend was observed in MDA, VCAM-1, and IL-6 values. CONCLUSIONS: Endothelial dysfunction constitutes an important disorder related to urolithiasis patients. It must be considered as an early feature responsible for future cardiovascular events. Our study did not find a significant association between inflammatory, oxidative stress, endothelial serum markers, and flow-mediated dilation.

Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity.

BACKGROUND AND PURPOSE: Obesity is a risk factor for the development of chronic kidney disease independent of diabetes, hypertension and other co-morbidities. Obesity-associated nephropathy is linked to dysregulation of the cell energy sensor AMP-activated protein kinase (AMPK). We aimed here to assess whether impairment of AMPK activity may cause renal arterial dysfunction in obesity and to evaluate the therapeutic potential of activating renal AMPK. EXPERIMENTAL APPROACH: Effects of the AMPK activator A769662 were assessed on intrarenal arteries isolated from ob/ob mice and obese Zucker rats and then mounted in microvascular myographs. Superoxide and hydrogen peroxide production were measured by chemiluminescence and fluorescence, respectively, and protein expression was analysed by western blotting. KEY RESULTS: Endothelium-dependent vasodilation and PI3K/Akt/eNOS pathway were impaired in preglomerular arteries from genetically obese rats and mice, along with impaired arterial AMPK activity and blunted relaxations induced by the AMPK activator A769662. Acute ex vivo exposure to A769662 restored endothelial function and enhanced activity of PI3K/Akt/eNOS pathway in obese rats, whereas in vivo treatment with A769662 improved metabolic state and ameliorated endothelial dysfunction, reduced inflammatory markers and vascular oxidative stress in renal arteries and restored redox balance in renal cortex of obese mice. CONCLUSION AND IMPLICATIONS: These results demonstrate that AMPK dysregulation underlies obesity-associated kidney vascular dysfunction and activation of AMPK improves metabolic state, protects renal endothelial function and exerts potent vascular antioxidant and anti-inflammatory effects. The beneficial effects of vascular AMPK activation might represent a promising therapeutic approach to the treatment of obesity-related kidney injury.

Renocolic fistula as a complication of radiofrequency in the treatment of renal cell carcinoma.

METHOD: Beyond postoperative suspicion, retrograde pyelogram was performed, the images of which are displayed, and demonstrated the fistula. RESULTS: Treatment has been definitive nephrectomy after failed attempt to seal the fistula with suture and TachoSil. CONCLUSIONS: Although radiofrequency ablation can be a valid technique for treating small renal tumors in patients with high morbidity, it is not without significant complications as described in this case, despite the precautions taken.

Activation of the AMP-related kinase (AMPK) induces renal vasodilatation and downregulates Nox-derived reactive oxygen species (ROS) generation.

AMP-activated protein kinase (AMPK) is a cellular energy sensor activated during energy stress to stimulate ATP production pathways and restore homeostasis. AMPK is widely expressed in the kidney and involved in mitochondrial protection and biogenesis upon acute renal ischemia, AMPK activity being blunted in metabolic disease-associated kidney disease. Since little is known about AMPK in the regulation of renal blood flow, the present study aimed to assess the role of AMPK in renal vascular function. Functional responses to the selective AMPK activator A769662 were assessed in intrarenal small arteries isolated from the kidney of renal tumour patients and Wistar rats and mounted in microvascular myographs to perform simultaneous measurements of intracellular calcium [Ca2+]i and tension. Superoxide (O2.-) and hydrogen peroxide (H2O2) production were measured by chemiluminescence and fluorescence and protein expression by Western blot. Activation of AMPK with A769662 increased AMPKα phosphorylation at Thr-172 and induced potent relaxations compared to AICAR in isolated human and rat intrarenal arteries, through both endothelium-dependent mechanisms involving nitric oxide (NO) and intermediate-conductance calcium-activated potassium (IKCa) channels, as well as activation of ATP-sensitive (KATP) channels and sarcoplasmic reticulum Ca2+-ATPase (SERCA) in vascular smooth muscle (VSM). Furthermore, AMPK activator reduced NADPH oxidase 4 (Nox4) and Nox2-derived reactive oxygen species (ROS) production. These results demonstrate that A769662 has potent vasodilator and antioxidant effects in intrarenal arteries. The benefits of AMPK activation in rat kidney are reproduced in human arteries and therefore vascular AMPK activation might be a therapeutic target in the treatment of metabolic disease-associated kidney injury.

Differential contribution of Nox1, Nox2 and Nox4 to kidney vascular oxidative stress and endothelial dysfunction in obesity.

Oxidative stress-associated endothelial dysfunction is a key pathogenic factor underlying the microvascular complications of metabolic disease. NADPH oxidase (Nox) is a major source of oxidative stress in diabetic nephropathy and chronic kidney disease, despite Nox4 and Nox2 have been identified as relevant sources of vasodilator endothelial H2O2.The present study was sought to investigate the role of Nox enzymes in renal vascular oxidative stress and endothelial dysfunction in a rat model of genetic obesity. Endothelial function was assessed in intrarenal arteries of obese Zucker rats (OZR) and their counterparts lean Zucker rats (LZR) mounted in microvascular myographs, and superoxide (O2.-) and H2O2 production were measured. Impaired endothelium-dependent relaxations to acetylcholine (ACh) were associated to augmented O2.- generation, but neither ROS scavengers nor the Nox inhibitor apocynin significantly improved these relaxant responses in renal arteries of OZR. Whereas NO contribution to endothelial relaxations was blunted, catalase-sensitive non-NO non-prostanoid relaxations were enhanced in obese rats. Interestingly, NADPH-dependent O2.- production was augmented while NADPH-dependent H2O2 generation was reduced, and cytosolic and mitochondrial SOD were up-regulated in kidney of obese rats. Nox4 was down-regulated in renal arteries and Nox4-dependent H2O2 generation and endothelial relaxation were reduced in OZR. Up-regulation of both Nox2 and Nox1 was associated with augmented O2.- production but reduced H2O2 generation and blunted endothelial Nox2-derived H2O2-mediated in obese rats. Moreover, increased Nox1-derived O2.- contributed to renal endothelial dysfunction in OZR. In summary, the current data support a main role for Nox1-derived O2.- in kidney vascular oxidative stress and renal endothelial dysfunction in obesity, while reduced endothelial Nox4 expression associated to decreased H2O2 generation and H2O2-mediated vasodilatation might hinder Nox4 protective renal effects thus contributing to kidney injury. This suggests that effective therapies to counteract oxidative stress and prevent microvascular complications must identify the specific Nox subunits involved in metabolic disease.

Hydrogen peroxide derived from NADPH oxidase 4- and 2 contributes to the endothelium-dependent vasodilatation of intrarenal arteries.

The role of NADPH oxidase (Nox)-derived reactive oxygen species in kidney vascular function has extensively been investigated in the harmful context of oxidative stress in diabetes and obesity-associated kidney disease. Since hydrogen peroxide (H2O2) has recently been involved in the non-nitric oxide (NO) non-prostanoid relaxations of intrarenal arteries, the present study was sought to investigate whether NADPH oxidases may be functional sources of vasodilator H2O2 in the kidney and to assess their role in the endothelium-dependent relaxations of human and rat intrarenal arteries. Renal interlobar arteries isolated from the kidney of renal tumor patients who underwent nephrectomy, and from the kidney of Wistar rats, were mounted in microvascular myographs to assess function. Superoxide (O2.-) and H2O2 production was measured by chemiluminescence and Amplex Red fluorescence, and Nox2 and Nox4 enzymes were detected by Western blotting and by double inmunolabeling along with eNOS. Nox2 and Nox4 proteins were expressed in the endothelium of renal arterioles and glomeruli co-localized with eNOS, levels of expression of both enzymes being higher in the cortex than in isolated arteries. Pharmacological inhibition of Nox with apocynin and of CYP 2C epoxygenases with sulfaphenazol, but not of the NO synthase (NOS), reduced renal NADPH-stimulated O2.- and H2O2 production. Under conditions of cyclooxygenase and NOS blockade, acetylcholine induced endothelium-dependent relaxations that were blunted by the non-selective Nox inhibitor apocynin and by the Nox2 or the Nox1/4 inhibitors gp91ds-tat and GKT136901, respectively. Acetylcholine stimulated H2O2 production that was reduced by gp91ds-tat and by GKT136901. These results suggest the specific involvement of Nox4 and Nox2 subunits as physiologically relevant endothelial sources of H2O2 generation that contribute to the endothelium-dependent vasodilatation of renal arteries and therefore have a protective role in kidney vasculature.

Metabolic syndrome contributes to renal injury mediated by hyperoxaluria in a murine model of nephrolithiasis.

Metabolic syndrome (MS) individuals have a higher risk of developing chronic kidney disease through unclear pathogenic mechanisms. MS has been also related with higher nephrolithiasis prevalence. To establish the influence of MS on renal function, we designed a murine model of combined metabolic syndrome and hyperoxaluria. Four groups of male Sprague-Dawley rats were established: (1) control group (n = 10) fed with standard chow; (2) stone former group (SF) (n = 10) fed with standard chow plus 0.75% ethylene glycol administered in the drinking water; (3) metabolic syndrome group (MS) (n = 10), fed with 60% fructose diet; (4) metabolic syndrome + stone former group (MS + SF) (n = 10), 60% fructose diet and 0.75% EG in the drinking water. MS group showed a significant injury to renal function when hyperoxaluria was induced. It was demonstrated by a significant decrease of creatinine clearance (p < 0.001), with higher tubular damage (34.3%, CI 95% 23.9-44.7, p < 0.001), produced by deposition of crystals, and increased tubular synthesis of osteopontin as a response to tubular damage. Induction of hyperoxaluria in rats with MS causes severe morphological alterations with a significant impairment of renal function. This impairment is not produced in rats without MS. Therefore, this model can be useful for the study of the influence of MS in stone formation.

[Laparoscopic Boari Flap ureteral reimplantation.] / Reimplante ureteral laparoscópico con Flap de Boari.

OBJECTIVES: To report our initial experience with laparoscopic Boari flap ureteral reimplantation and to review the main technical elements in ureteral reconstructive surgery. METHODS: In a 10-year period we performed 23 laparoscopic ureteral reimplantations. Three cases required a Boari flap. Two patients presented ureteral stenosis above the iliac vessels and the third one a urothelial tumor of the pelvic ureter. RESULTS: Two cases were completed laparoscopically; the third one was electively converted to open surgery to avoid prolonged OR time. Mean operative time was 276 minutes (270-290 min). There were no intraoperative complications. Mean hospital stay was 6.6 days. One patient presented postoperative UTI (Clavien 2). One patient developed with history of sever arteriopathy and aortorenal by pass developed ureteral stenosis proximal to the ureteral reimplantation eight months after the operation. CONCLUSIONS: Laparoscopic Boari flap ureteral reimplantation is an affective technique for ureteral reconstruction, safe and reproducible, reserved for cases of ureteral pathology in which the distance to bridge between the bladder and the ureteral stump is long.

An intervention to improve the adequacy of referrals from primary care to a department of urology.

INTRODUCTION: This study analyses the effect of two interventions implemented in order to improve adherence to the terms of a protocol for referring patients from primary care to a urology department. MATERIAL AND METHOD: A telephone counselling line for professionals was implemented, and joint training sessions were held (twice, at six-month intervals). The terms "appropriate" and "inappropriate" were used to identify referrals complying with the locally developed protocol and those that did not, respectively. Referral appropriateness at baseline (T0) was compared with that six months after the first (T1) and second (T2) meeting. Linear trend analysis was used to test for trends in adequacy across the study. RESULTS: Appropriateness of 6,088 consecutive referrals was analysed. At T0, 58% of the referrals (2810/4841) were judged to be "appropriate". Adequacy improved significantly at T1 (70.6% vs. 58% at T0; chi2 < 0.001). At T2, 75.4% of the referrals met the terms of the protocol; the difference between results at T1 and T2 was not statistically significant (chi2 = 0.06). Overall (T0 vs. T2), a 17.4% improvement was confirmed (chi2 < 0.001). A trend toward more appropriate referrals was detected over time (Mantel-Haenszel test for linear trend, z = 9.62; p < 0.001). As the use of communication resources was anecdotal, mathematical analysis of its effect on adequacy could not be performed. CONCLUSIONS: Training activities are worthwhile for improving referral adequacy. Stable rates over time are possible. Using communication resources may be unnecessary if accessibility is guaranteed.

[Usefulness of cytokines as surgical aggression markers in the ischemia-reperfusion syndrome and post transplant renal function in an experimental model of laparoscopic vs. open renal autotransplantation]. / Utilidad de las citocinas como marcadores de agresión quirúrgica, en el síndrome de isquemia-reperfusión y en la función postrasplante renal, en un modelo experimental de autotraplante renal laparoscópico versus abierto.

OBJECTIVES: To analyze the modifications induced by laparoscopic and open nephrectomies in living donor transplantation on cytokines, to evaluate operative trauma of different surgical techniques and the influence on ischemia/reperfusion syndrome and renal function. METHODS: Thirty pigs underwent left nephrectomy, 15 by laparoscopy and 15 by open approach in an experimental autotransplantation model. RESULTS: Serum level of IL-2, IL-6, IL-10 and tumor necrosis factor (TNF) were lower during laparoscopic than open nephrectomy: 6.8 +/- 0.6 vs 13.9 +/- 1.1 pg/ml for IL-2, 46.2 +/- 2.3 vs 84.4 +/- 2.5 pg/ml for IL-6, 26.1 +/- 2.4 vs 92.8 +/- 12.6 pg/ml for IL-10, and 17.6 +/- 2.1 vs 38.5 +/- 4.8 pg/ml for TNF. There was no association between renal blood flow (RBF) and cytokines levels during nephrectomy: IL-2 (p = 0.498), IL-6 (p = 0.117), IL-10 (p = 0.081) y TNF (p = 0.644). However, there was correlation between IL-10 and the decrease of RBF after transplantation: (R2 0.48; p = 0.02). Initial serum creatinine levels were correlated with RBF and IL-2 levels during nephrectomy (R = 0.831, R2 = 0.691, p = 0.025), and postransplantation RBF (R = 0.784, R2 = 0.614, p < 0.0001). Seventh day creatinine levels were correlated with postransplantation RBF (R = 0.537, R2 = 0.289, p = 0.002) and IL-2 levels during nephrectomy (R = 0.685, R2 = 0.469, p = 0.015). CONCLUSIONS: Cytokine levels were higher during the open approach than laparoscopic procedure. High levels of RBF during nephrectomy and transplantation improve early graft function while low levels of RBF and high levels ol IL-2 during nephrectomy induce delayed graft function.

[Renal autotransplantation: a valid option in the resolution of complex cases]. / Autotrasplante renal: una alternativa valida en la resolucion de casos complejos.

OBJECTIVES: To analyze the current indications for renal autotransplantation, as well as the technical features, complications and long-term follow-up of the technique. METHODS: From 1990 to 2005 we have performed autotransplantation in 10 patients, 7 adults and 3 children. The indication was established due to vascular pedicle pathology in 8 cases and ureteral lesion in 2. The cause of vascular pathology was: atherosclerotic stenosis (4), dysplastic stenosis (2), Takayasu's disease stenosis (1), and renal artery aneurysm (1). The patients with ureteral lesion had ureteral stenosis secondary to Crohn's disease in one case, initially solved by ureteral stent and subsequently obstructed by lithiasic encrustation, and ureteral avulsion in the other case. The vascular grafts employed in the 8 cases with vascular reconstruction were: hypogastric artery 7 cases, and sophena vein in one case. Ureteral reimplantation was necessary in 5 cases after bench surgery; in other five cases vascular reconstruction was performed without ureteral division. All grafts were perfused with 4 degrees C lactate ringer or Wisconsin solution and protected with surface cold ischemia. Ischemia times ranged from 42 to 89 minutes. RESULTS: Nine kidneys (90%) functioned after autotransplantation, 8 of them had immediate function, and one had delayed graft function after a six-day period of acute tubular necrosis. The kidney with arterial stenosis secondary to Takayasu's disease never functioned. The cause of graft loss was renal vein thrombosis. Postoperative mortality was zero. After a mean follow-up of 72+/- 13 months mean serum creatinine is 1.6+- 0.4 mg/dl (1.1-2.4) and 70% (7/10) of the patients have normal blood pressure without antihypertensive medication. CONCLUSIONS: Currently, renal autotransplantation, with or without extracorporeal vascular reconstruction, is a complex technique with exceptional indications, but it allows recovering renal units with vascular pathology not amenable to angioplasty or in situ revascularization. It is also a valid alternative to ileal ureteral substitution in cases of extensive ureteral lesion.

[Outpatient female stress urinary incontinence surgery: budget impact study]. / Cirugia de la incontinencia urinaria femenina en regimen de cirugia mayor ambulatoria: estudio de impacto presupuestario.

OBJECTIVES: The surgical procedures for the insertion of tension free vaginal tapes in the treatment of female stress urinary incontinence (SUI) are simple and can be done as outpatient operations. The aim of this study was to perform a budget study comparing TVT in an outpatient basis with transobturator tape (TOT) with hospital admission. METHODS: Retrospective analysis of the medical records of 23 patients undergoing surgery for SUI between October 2004 and October 2005. 13 patients were treated by TVT in an outpatient basis (group 1, Department of Urology), 10 patients were treated by TOT with hospital admission (Group 2, Department of Gynaecology). Cost analysis was carried out by the construction of a Marcov model, incorporating the time sequence of the treatment, including adverse events and results. Variables considered for the analysis: number of visits, preoperative tests, operative time, tape cost, hospital stay, unpredicted visits in the first postoperative month at the outpatient clinics or emergency room, and hospital readmissions. Statistical analysis was performed with the G-Stat software. Student's t test was used to compare quantitative variables. RESULTS: 11/13 patients (84.6%) in group 1 completed the day-surgery protocol. Mean surgical time was 61.7 min. (SD 16.2; 35-100) and 61.6 min. (SD 8.3; 50-73) for groups I and 2 respectively. Two cases in group 1 had perioperative complications (15.4%); no patient in group 2 had perioperative complications. Mean hospital stay was 1.3 days for group 1 (SD 0.85; 1-4) and 2.9 days for group 2 (SD 0.31; 2-3). Three patients in group 1 (23%) and 2 in group 2 (20%) presented postoperative complications. Mean cost per process was 4740 EUR for group 1 and 7099 EUR for group 2. CONCLUSIONS: SUI correction by tension free tapes as day surgery is a valid option which saves a substantial amount of resources.