Background and Purpose The mechanism by which β3 receptor agonists (e.g. mirabegron) control bladder overactivity may involve adenosine release from human and rat detrusor smooth muscle. Retrograde activation of adenosine A1 receptors reduces ACh release from cholinergic bladder nerves. β3‐Adrenoceptors usually couple to adenylyl cyclase. Here we investigated, which of the cAMP targets, protein kinase A or the exchange protein directly activated by cAMP (EPAC) could be involved in this cholinergic inhibition of the bladder. Experimental Approach [3H]ACh and adenosine release from urothelium‐denuded detrusor strips of cadaveric human organ donors and rats were measured by liquid scintillation spectrometry and HPLC, respectively. In vivo cystometry was also performed in urethane‐anaesthetized rats. Key Results The exchange protein directly activated by cAMP (EPAC) inhibitor, ESI‐09, prevented mirabegron‐ and isoprenaline‐induced adenosine release from human and rat detrusor strips respectively. ESI‐09, but not the PKA inhibitor, H‐89, attenuated inhibition of [3H]ACh release from stimulated (10 Hz) detrusor strips caused by activating β3‐adrenoceptors, AC (forskolin) and EPAC1 (8‐CTP‐2Me‐cAMP). Isoprenaline‐induced inhibition of [3H]ACh release was also prevented by inhibitors of PKC (chelerythrine and Go6976) and of the equilibrative nucleoside transporter 1 (ENT1; dipyridamole and NBTI), but not by PLC inhibition with U73122. Pretreatment with ESI‐09, but not with H‐89, prevented the reduction of the voiding frequency caused by isoprenaline and forskolin in vivo. Conclusion and Implications Data suggest that β3‐adrenoceptor‐induced inhibition of cholinergic neurotransmission in human and rat urinary bladders involves activation of an EPAC1/PKC pathway downstream cAMP production resulting in adenosine outflow via ENT1.

Summary Kidney volume has been proven to be a surrogate marker of nephron mass and renal function. We studied 190 donor and recipient pairs undergoing living donor kidney transplantation at our institution during 9 years. Different metrics of donor kidney volume (DKV) were explored: alone or indexed to recipient’s anthropometry, as body surface area (BSA). DKV/BSA (min. 49.7; P33rd 77.7; P67th 95.3; max. 176 cm3/m2) was chosen given its higher correlation with eGFR at 1 year, and recipients were divided according to its tertiles (T). The eGFR at 1 year was lower in T1, when compared with T2 (P = 0.015) and T3 (P < 0.001). In a multivariable model, a regression spline revealed that a DKV/BSA lower than 80 was significantly associated with an eGFR at 1 year <60. In the first 6 years, the overall annual eGFR slope was −0.90 ml/min/year. Acute rejection occurred in 19%, 11%, and 0% of patients in T1, T2, and T3, respectively (P < 0.001). DKV/BSA increased stepwise from cellular‐ (n = 12) to antibody‐mediated (n = 7) AR cases and to those without AR (n = 171; P = 0.002; no AR versus cellular AR). Lower DKV/BSA ratio was associated with significantly worse graft function and higher incidence of AR. Hence, it can be a tool for better selection of donors in order to improve graft outcomes, particularly in the setting of multiple potential living donors or kidney paired exchange programs.

RESUMEN LEIOMIOMA DE VEJIGA. ANÁLISIS DE AGREGACIÓN DE 90 CASOS INTRODUCCIÓN:Los leiomiomas de vejiga (LV) son tumores raros. La mayoría de las publicaciones relativas a estos tumores describen casos aislados, no permitiendo evaluar estrategias diagnósticas y terapéuticas.MATERIAL Y MÉTODO: Realizamos un análisis de agregación de 90 casos de LV descritos en la literatura internacional.RESULTADOS: La edad media al diagnóstico fue de 45,3 años (19-85 años), 68 (75,6%) eran mujeres. Los síntomas más frecuentes eran de almacenamiento (50%) seguidos de los de vaciado (24,4%). Veinticuatro pacientes (26,7%) estaban asintomáticos. Cuarenta y seis tumores (51,1%) tenían crecimiento endoluminal, 27 (30%) eran intramurales y 15 (16,7%) extravesicales. A 56 pacientes (62,2%) se les realizó una laparotomía, con enucleación en 29 (32,2%), cistectomía parcial en 25 (27,8%) y cistectomía total en 2 (2,2%). Veintisiete (30%) fueron sometidos a resección transuretral y 5 pacientes (5,6%) a una enucleación transvaginal. Dos pacientes no fueron sometidos a ningún tratamiento. Fueron descritas 3 recidivas y una fístula vesicovaginal como única complicación.CONCLUSIONES: Aunque el LV sea un tumor raro, en el estudio de una neoformación vesical, los estudios de imagen, pueden hacer sospechar este diagnóstico. El tratamiento quirúrgico tiene una alta tasa de éxito. En la mayoría de los casos, la resección transuretral o la enucleación es suficiente, evitando así una cirugía más iatrogénica.PALABRAS CLAVE: Vejiga. Leiomioma. Diagnóstico. Tratamiento. Meta-analisis. ABSTRACT BLADDER LEIOMYOMA. A POOLED ANALYSIS OF 90 CASES INTRODUCTION:Bladder leiomyomas (BL) are rare. Most publications regarding these tumours are reports of isolated cases; therefore they don't allow an evaluation of diagnostic and treatment procedures. MATERIAL & METHODS:We preformed a pooled analysis of 90 cases of BL reported in the literature. RESULTS: Mean age was 45.3 (19 to 85 years), 68 (75.6%) were women. Filling symptoms were the most frequently reported (50%), followed by voiding symptoms (24.4%). Twenty four patients (26.7%) were asymptomatic. Tumours were endoluminal in 46 patients (51.1%), intramural in 27 (30%) and extravesical in 15 (16.7%). A laparotomy was preformed in 56 patients (62.2%), with enucleation in 29 (32.2%), partial cystectomy in 25 (27.8%) and total cystectomy in 2 (2.2%). A transurethral resection was preformed in 27 (30%) and a transvaginal resection in 5 (5.6%). Two patients underwent conservative treatment. In 3 cases there were reports of recurrence and one patient got a vesicovaginal fistula.CONCLUSIONS: Although BL are rare, when evaluating bladder tumours, imaging techniques can make suspect of this neoplasm. Surgical treatment of these tumours has a very high success rate. Usually an enucleation or a transurethral resection is sufficient to render the patient tumour free, avoiding a more iatrogenic surgery.

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