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OBJECTIVE: Aberrant subclavian arteries (aSCAs), with or without aortic pathology, are uncommon. The purpose of the present study was to review our experience with the surgical management of aSCA. METHODS: We performed a retrospective review of patients who had undergone surgery for an aSCA between 1996 and 2020. Symptomatic and asymptomatic patients were included. The primary end points were ≤30-day and late mortality. The secondary end points were ≤30-day complications, graft patency, and reinterventions. RESULTS: A total of 46 symptomatic and 3 asymptomatic patients with aSCA had undergone surgery (31 females [62%]; median age, 45 years). An aberrant right subclavian artery was present in 38 (78%) and an aberrant left subclavian artery in 11 patients (22%). Of the 49 patients, 41 (84%) had had a Kommerell diverticulum (KD) and 11 (22%) had had a concomitant distal arch or proximal descending thoracic aortic aneurysm. Symptoms included dysphagia (56%), dyspnea (27%), odynophagia (20%), and upper extremity exertional fatigue (16%). Five patients (10%) had required emergency surgery. The aSCA had been treated by transposition in 32, a carotid to subclavian bypass in 11, and an ascending aorta to subclavian bypass in 6. The KD was treated by resection and oversewing in 19 patients (39%). Fifteen patients (31%) had required distal arch or proximal descending thoracic aortic replacement for concomitant aortic disease and/or KD treatment. Thoracic endovascular aortic repair was used to exclude the KD in six patients (12%). Seven patients (14%) had undergone only bypass or transposition. The 30-day complications included one death from pulseless electrical activity arrest secondary to massive pulmonary embolism. The 30-day major complications (14%) included acute respiratory failure in three, early mortality in one, stroke in one, non-ST-elevation myocardial infarction in one, and temporary dialysis in one patient. The other complications included chylothorax/lymphocele (n = 5; 10%), acute kidney injury (n = 2; 4%), pneumonia (n = 2; 4%), wound infection (n = 2; 4%), atrial fibrillation (n = 2; 4%), Horner syndrome (n = 2; 4%), lower extremity acute limb ischemia (n = 1; 2%), and left recurrent laryngeal nerve injury (n = 1; 2%). At a median follow-up of 53 months (range, 1-230 months), 40 patients (82%) had had complete symptom relief and 9 (18%) had experienced improvement. Six patients had died at a median of 157 months; the deaths were not procedure or aortic related. The primary patency was 98%. Reintervention at ≤30 days had been required for two patients (4%) for ligation of lymphatic vessels and bilateral lower extremity fasciotomy after proximal descending thoracic aorta replacement. One patient had required late explantation of an infected and occluded carotid to subclavian bypass graft, which was treated by cryopreserved allograft replacement. CONCLUSIONS: Surgical treatment of the aSCA can be accomplished with low major morbidity and mortality with excellent primary patency and symptom relief.
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Aneurisma de la Aorta Torácica , Enfermedades de la Aorta , Implantación de Prótesis Vascular , Anomalías Cardiovasculares , Procedimientos Endovasculares , Femenino , Humanos , Persona de Mediana Edad , Aorta/cirugía , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/cirugía , Enfermedades de la Aorta/complicaciones , Implantación de Prótesis Vascular/efectos adversos , Anomalías Cardiovasculares/complicaciones , Anomalías Cardiovasculares/diagnóstico por imagen , Anomalías Cardiovasculares/cirugía , Procedimientos Endovasculares/efectos adversos , Estudios Retrospectivos , Arteria Subclavia/diagnóstico por imagen , Arteria Subclavia/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVE: Fenestrated/branched endovascular aortic repair (F/BEVAR) in patients with occluded iliac arteries is challenging owing to limited access for branch vessel catheterization and increased risk for leg and spinal ischemic complications. The aim of this study was to analyze technical strategies and outcomes of F/BEVAR in patients with unilateral iliofemoral occlusive disease. METHODS: We performed a retrospective review of all consecutive patients treated by F/BEVAR in two institutions (2003-2021). Patients with unilateral iliofemoral occlusive disease were included in the analysis. All patients had one patent iliac artery that was used for advancement of the fenestrated-branch component. Preloaded catheter/guidewire systems or steerable sheaths were used as adjuncts to facilitate catheterization. Primary endpoints were technical success, mortality, major adverse events (stroke, spinal cord injury, dialysis or decrease in the glomerular filtration rate of more than 50%, bowel ischemia, myocardial infarction, or respiratory failure), primary iliac patency, and freedom from reinterventions. RESULTS: There were 959 patients treated with F/BEVAR. Of these, 15 patients (1.56%; mean age, 74 years; 80% male) had occluded iliac arteries and 1 patent iliofemoral access and were treated for a thoracoabdominal aortic aneurysm (n = 8) or juxtarenal abdominal aortic aneurysm (n = 7). Brachial access was used in 14 of the 15 patients and preloaded systems in 7 of the 15 patients (47%). The remaining 53% had staggered deployment of stent grafts. There were seven physician-modified endovascular grafts, seven custom-made devices, and one off-the-shelf device used. Thirteen patients (87%) had distal seal using aortouni-iliac stent grafts and two (13%) had distal seal in the infrarenal aorta. Concomitant femoral crossover bypass (FCB) was performed in two patients and six patients had a prior FCB. Technical success was 100%. There were no intraoperative complications or early lower extremity ischemic complications, and all FCB were preserved. There was one mortality (7%) within 30 days owing to retrograde type A dissection. Major adverse events occurred in 20% of patients. The median follow-up was 12 months (range, 0-85 months). Two patients (13%) required three reinterventions. One patient required proximal stent graft extension for an acute type B dissection (3 months) and another required iliac extension for type Ib endoleak of an aortouni-iliac graft (21 months) and thrombolysis of that extension (50 months). At last follow-up, all patients had primary graft patency except one with secondary graft patency without new claudication. One patient had a single renal artery stent occlusion at follow-up with no r-intervention. The overall survival rate was 60%, without aortic-related deaths. CONCLUSIONS: Although challenging, F/BEVAR with unilateral femoral/brachial approach is feasible in patients with occluded iliac limbs, with an important rate of ischemic complications, but satisfactory outcomes.
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Aneurisma de la Aorta Torácica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Masculino , Anciano , Femenino , Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Reparación Endovascular de Aneurismas , Procedimientos Endovasculares/efectos adversos , Complicaciones Posoperatorias/etiología , Stents/efectos adversos , Aorta Abdominal/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Aneurisma de la Aorta Torácica/cirugía , Diseño de PrótesisRESUMEN
OBJECTIVE: Aberrant subclavian artery (ASA) and Kommerell's diverticulum (KD) are rare vascular anomalies that may be associated with lifestyle-limiting and life-threatening complications. The aim of this study is to report contemporary outcomes after invasive treatment of ASA/KD using a large international dataset. METHODS: Patients who underwent treatment for ASA/KD (2000-2020) were identified through the Vascular Low Frequency Disease Consortium, a multi-institutional collaboration to investigate uncommon vascular disorders. We report the early and mid-term clinical outcomes including stroke and mortality, technical success, and other operative outcomes including reintervention rates, patency, and endoleak. RESULTS: Overall, 285 patients were identified during the study period. The mean patient age was 57 years; 47% were female and 68% presented with symptoms. A right-sided arch was present in 23%. The mean KD diameter was 47.4 mm (range, 13.0-108.0 mm). The most common indication for treatment was symptoms (59%), followed by aneurysm size (38%). The most common symptom reported was dysphagia (44%). A ruptured KD was treated in 4.2% of cases, with a mean diameter of 43.9 mm (range, 18.0-100.0 mm). An open procedure was performed in 101 cases (36%); the most common approach was ASA ligation with subclavian transposition. An endovascular or hybrid approach was performed in 184 patients (64%); the most common approach was thoracic endograft and carotid-subclavian bypass. A staged operative strategy was employed more often than single setting repair (55% vs 45%). Compared with endovascular or hybrid approach, those in the open procedure group were more likely to be younger (49 years vs 61 years; P < .0001), female (64% vs 36%; P < .0001), and symptomatic (85% vs 59%; P < .0001). Complete or partial symptomatic relief at 1 year after intervention was 82.6%. There was no association between modality of treatment and symptom relief (open 87.2% vs endovascular or hybrid approach 78.9%; P = .13). After the intervention, 11 subclavian occlusions (4.5%) occurred; 3 were successfully thrombectomized resulting in a primary and secondary patency of 95% and 96%, respectively, at a median follow-up of 39 months. Among the 33 reinterventions (12%), the majority were performed for endoleak (36%), and more reinterventions occurred in the endovascular or hybrid approach than open procedure group (15% vs 6%; P = .02). The overall survival rate was 87.3% at a median follow-up of 41 months. The 30-day stroke and death rates were 4.2% and 4.9%, respectively. Urgent or emergent presentation was independently associated with increased risk of 30-day mortality (odds ratio [OR], 19.8; 95% confidence interval [CI], 3.3-116.6), overall mortality (OR, 3.6; 95% CI, 1.2-11.2) and intraoperative complications (OR, 8.3; 95% CI, 2.8-25.1). Females had a higher risk of reintervention (OR, 2.6; 95% CI, 1.0-6.5). At an aneurysm size of 44.4 mm, receiver operator characteristic curve analysis suggested that 60% of patients would have symptoms. CONCLUSIONS: Treatment of ASA/KD can be performed safely with low rates of mortality, stroke and reintervention and high rates of symptomatic relief, regardless of the repair strategy. Symptomatic and urgent operations were associated with worse outcomes in general, and female gender was associated with a higher likelihood of reintervention. Given the worse overall outcomes when symptomatic and the inherent risk of rupture, consideration of repair at 40 mm is reasonable in most patients. ASA/KD can be repaired in asymptomatic patients with excellent outcomes and young healthy patients may be considered better candidates for open approaches versus endovascular or hybrid modalities, given the lower likelihood of reintervention and lower early mortality rate.
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Aneurisma , Implantación de Prótesis Vascular , Divertículo , Procedimientos Endovasculares , Accidente Cerebrovascular , Humanos , Femenino , Persona de Mediana Edad , Masculino , Endofuga/etiología , Aneurisma/diagnóstico por imagen , Aneurisma/cirugía , Aneurisma/complicaciones , Arteria Subclavia/diagnóstico por imagen , Arteria Subclavia/cirugía , Arteria Subclavia/anomalías , Procedimientos Endovasculares/efectos adversos , Accidente Cerebrovascular/etiología , Divertículo/diagnóstico por imagen , Divertículo/cirugía , Aorta Torácica/cirugía , Resultado del Tratamiento , Implantación de Prótesis Vascular/efectos adversosRESUMEN
BACKGROUND: Aberrant subclavian artery (ASA) with or without Kommerell's diverticulum (KD) is a rare anatomic aortic arch anomaly that can cause dysphagia and/or life-threatening rupture. The objective of this study is to compare outcomes of ASA/KD repair in patients with a left versus right aortic arch. METHODS: Using the Vascular Low Frequency Disease Consortium methodology, a retrospective review was performed of patients ≥18 years old with surgical treatment of ASA/KD from 2000 to 2020 at 20 institutions. RESULTS: 288 patients with ASA with or without KD were identified; 222 left-sided aortic arch (LAA), and 66 right-sided aortic arch (RAA). Mean age at repair was younger in LAA 54 vs. 58 years (P = 0.06). Patients in RAA were more likely to undergo repair due to symptoms (72.7% vs. 55.9%, P = 0.01), and more likely to present with dysphagia (57.6% vs. 39.1%, P < 0.01). The hybrid open/endovascular approach was the most common repair type in both groups. Rates of intraoperative complications, death within 30 days, return to the operating room, symptom relief and endoleaks were not significantly different. For patients with symptom status follow-up data, in LAA, 61.7% had complete relief, 34.0% had partial relief and 4.3% had no change. In RAA, 60.7% had complete relief, 34.4% had partial relief and 4.9% had no change. CONCLUSIONS: In patients with ASA/KD, RAA patients were less common than LAA, presented more frequently with dysphagia, had symptoms as an indication for intervention, and underwent treatment at a younger age. Open, endovascular and hybrid repair approaches appear equally effective, regardless of arch laterality.
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Trastornos de Deglución , Divertículo , Cardiopatías Congénitas , Enfermedades Vasculares , Adolescente , Humanos , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Aorta Torácica/anomalías , Trastornos de Deglución/etiología , Trastornos de Deglución/cirugía , Divertículo/diagnóstico por imagen , Divertículo/cirugía , Divertículo/complicaciones , Cardiopatías Congénitas/complicaciones , Arteria Subclavia/diagnóstico por imagen , Arteria Subclavia/cirugía , Arteria Subclavia/anomalías , Resultado del Tratamiento , Enfermedades Vasculares/complicaciones , Adulto , Persona de Mediana EdadRESUMEN
Although the role of urea in urine concentration is known, the effect of urea handling by the urea transporters (UTs), UT-A1 and UT-A3, on sodium balance remains elusive. Serum and urinary sodium concentration is similar between wild-type mice (WT) and UT-A3 null (UT-A3 KO) mice; however, mice lacking both UT-A1 and UT-A3 (UT-A1/A3 KO) have significantly lower serum sodium and higher urinary sodium. Protein expression of renal sodium transporters is unchanged among all three genotypes. WT, UT-A3 KO, and UT-A1/A3 KO acutely respond to hydrochlorothiazide and furosemide; however, UT-A1/A3 KO fail to show a diuretic or natriuretic response following amiloride administration, indicating that baseline epithelial Na+ channel (ENaC) activity is impaired. UT-A1/A3 KO have more ENaC at the apical membrane than WT mice, and single-channel analysis of ENaC in split-open inner medullary collecting duct (IMCD) isolated in saline shows that ENaC channel density and open probability is higher in UT-A1/A3 KO than WT. UT-A1/A3 KO excrete more urinary nitric oxide (NO), a paracrine inhibitor of ENaC, and inner medullary nitric oxide synthase 1 mRNA expression is ~40-fold higher than WT. Because endogenous NO is unstable, ENaC activity was reassessed in split-open IMCD with the NO donor PAPA NONOate [1-propanamine-3-(2-hydroxy-2-nitroso-1-propylhydrazine)], and ENaC activity was almost abolished in UT-A1/A3 KO. In summary, loss of both UT-A1 and UT-A3 (but not UT-A3 alone) causes elevated medullary NO production and salt wasting. NO inhibition of ENaC, despite elevated apical accumulation of ENaC in UT-A1/A3 KO IMCD, appears to be the main contributor to natriuresis in UT-A1/A3 KO mice.
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Canales Epiteliales de Sodio/metabolismo , Médula Renal/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Óxido Nítrico/metabolismo , Sodio/metabolismo , Animales , Transporte Iónico/fisiología , Capacidad de Concentración Renal/fisiología , Proteínas de Transporte de Membrana/genética , Ratones , Ratones Noqueados , Transportadores de UreaRESUMEN
Urea has a critical role in urinary concentration. Mice lacking the inner medullary collecting duct (IMCD) urea transporter A1 (UT-A1) and urea transporter A3 (UT-A3) have very low levels of urea permeability and are unable to concentrate urine. To investigate the role of UT-A1 in the concentration of urine, we transgenically expressed UT-A1 in knockout mice lacking UT-A1 and UT-A3 using a construct with a UT-A1 gene that cannot be spliced to produce UT-A3. This construct was inserted behind the original UT-A promoter to yield a mouse expressing only UT-A1 (UT-A1(+/+)/UT-A3(-/-)). Western blot analysis demonstrated UT-A1 in the inner medulla of UT-A1(+/+)/UT-A3(-/-) and wild-type mice, but not in UT-A1/UT-A3 knockout mice, and an absence of UT-A3 in UT-A1(+/+)/UT-A3(-/-) and UT-A1/UT-A3 knockout mice. Immunohistochemistry in UT-A1(+/+)/UT-A3(-/-) mice also showed negative UT-A3 staining in kidney and other tissues and positive UT-A1 staining only in the IMCD. Urea permeability in isolated perfused IMCDs showed basal permeability in the UT-A1(+/+)/UT-A3(-/-) mice was similar to levels in wild-type mice, but vasopressin stimulation of urea permeability in wild-type mice was significantly greater (100% increase) than in UT-A1(+/+)/UT-A3(-/-) mice (8% increase). Notably, basal urine osmolalities in both wild-type and UT-A1(+/+)/UT-A3(-/-) mice increased upon overnight water restriction. We conclude that transgenic expression of UT-A1 restores basal urea permeability to the level in wild-type mice but does not restore vasopressin-stimulated levels of urea permeability. This information suggests that transgenic expression of UT-A1 alone in mice lacking UT-A1 and UT-A3 is sufficient to restore urine-concentrating ability.
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Proteínas de Transporte de Membrana/genética , Urea/orina , Animales , Proteínas de Transporte de Membrana/fisiología , Ratones , Ratones Noqueados , Fenómenos Fisiológicos del Sistema Urinario , Transportadores de UreaRESUMEN
We present a case of a 42-year-old man with DiGeorge syndrome and congenital cardiac anomalies including a type B interrupted aortic arch who had previously undergone two bypasses between the ascending and descending thoracic aorta in childhood. He was found to have a 7.4-cm pseudoaneurysm of the descending thoracic aorta with the left subclavian artery arising from the aneurysm. The patient was treated with a single stage hybrid repair including left common carotid to subclavian bypass followed by thoracic endovascular aortic aneurysm repair.
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Introduction Individuals using cocaine, methamphetamines, cannabis, and other mood-altering drugs (MADs) have been reported to have greater stroke risk when compared to individuals who do not use these drugs. Yet, the impact that MAD use has on stroke outcomes has not been adequately explored, with existing research not agreeing on the extent to which the use of these drugs influences stroke outcomes. This study aimed to determine the impact that the use of common MADs has on stroke outcome factors such as length of stay (LOS), discharge modified Rankin Scale (mRS), and discharge disposition. Methods A retrospective case-matched study was conducted with two adult cohorts treated for cerebrovascular accidents: those who use MADs and those who do not use MADs prior to their stroke. Subjects identified for the users of MADs cohort were matched at a 1:1 ratio to those who do not use MADs (control cohort) by age, sex, and stroke type (e.g., hemorrhagic or ischemic). Logistic regression was used to calculate odds ratios for functional outcomes for stroke patients with and without prior MAD use. Results Active users of MADs had an increased overall risk of poor stroke outcome, i.e., increased length of stay, discharge disposition other than to home or to rehabilitation, discharge modified Rankin scale (mRS) 3-6 after controlling for stroke severity from initial National Institutes of Health Stroke Scale (NIHSS) (X2{9}=21.68, p<0.01, Cox adjusted R2=0.31). This finding was driven predominately by increased hospital LOS (p=0.006) among the MAD cohort, whereas discharge mRS 3-6 (p=0.24) and discharge disposition to care facility (p=0.27) and expired (p=0.26) did not vary significantly between groups. Conclusion Our study suggests that patients who had actively used MADs prior to their stroke may be at risk of poorer stroke outcomes, namely an increased LOS. Future research should be conducted to further elucidate which factors, such as individual drugs, amount of drug, acute or recreational use versus chronic or long-term use, and route of administration, for instance, specifically contribute to a longer LOS so that they may be targeted for mitigation.
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BACKGROUND: Medullary thyroid cancer is a neuroendocrine malignancy that can occur sporadically or as the result of genomic rearranged during transfection mutations. Medullary thyroid cancer has a higher rate of metastasis than well-differentiated thyroid cancer. Lateral neck dissection is often performed, and its prophylactic use is controversial. METHODS: Single-center, retrospective review (2000-2017) of patients undergoing primary surgical treatment for medullary thyroid cancer who had negative lateral neck imaging preoperatively. Demographics, genetic associations, clinical, and imaging findings were analyzed. Locoregional recurrence, overall recurrence, and overall survival were examined. RESULTS: A total of 110 patients were identified, of which 18 underwent prophylactic lateral neck dissection and 92 did not. Age, sex distribution, preoperative calcitonin levels, and follow-up were similar among groups. Overall recurrence was 20% for no prophylactic lateral neck dissection and 39% for prophylactic lateral neck dissection (P = .46). Most recurrences were locoregional recurrence, 7.6% for no prophylactic lateral neck dissection versus 22% for prophylactic lateral neck dissection (P = .08), half of it being to the lateral neck in both groups. A total of 7 patients from the no prophylactic lateral neck dissection group required treatment for recurrences versus 4 patients in prophylactic lateral neck dissection group (P = .57). Overall survival at 5 years was similar, 43% the no prophylactic lateral neck dissection group and 31% for prophylactic lateral neck dissection group (P = .52). CONCLUSION: Lateral neck dissection has no effect in decreasing locoregional or overall recurrences in medullary thyroid cancer and has no effect in overall survival when performed prophylactically at index surgical intervention.
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Carcinoma Neuroendocrino/cirugía , Metástasis Linfática/prevención & control , Disección del Cuello/estadística & datos numéricos , Recurrencia Local de Neoplasia/epidemiología , Neoplasias de la Tiroides/cirugía , Adulto , Anciano , Carcinoma Neuroendocrino/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Estudios Retrospectivos , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Tiroidectomía/métodos , Tiroidectomía/estadística & datos numéricosRESUMEN
OBJECTIVE: To study the complications of hand-assisted laparoscopic living donor nephrectomy (HALLDN) with an emphasis on complications occurring early after hospital discharge up to 120 days after surgery. PATIENTS AND METHODS: We retrospectively categorized complications using the Clavien-Dindo classification in 3002 HALLDNs performed at 1 center from January 1, 2000, through December 31, 2019. In addition to overall summaries, modeling was used to identify correlates of complications before and after living donation. RESULTS: Of these donors, 87% were White, 59% were female, the mean age was 45 years (range, 18-77 years), 30.3% had a body mass index of at least 30, and 36.3% had previous abdominopelvic surgery. There were no deaths related to the surgery. The incidence of major complications (intraoperative complications plus Clavien-Dindo grade ≥III postoperatively) was 2.5% (n=74). The overall complication rate was 12.4% (n=371), including 15 intraoperative, 76 postoperative before discharge, and 280 after discharge to 120 days. Reoperation was required in 1.8% of patients (n=54), and all but 1 of these were incision-related problems. Seventy-six percent of all complications occurred after discharge, including 85% of the reoperations. For major complications, no risk factor was found. Risk factors for any complication included paramedian incision (hazard ratio [HR], 2.54; 95% CI, 1.49 to 4.34; P<.001); a history of abdominopelvic surgery (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), male sex (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), non-White race (HR, 1.40; 95% CI, 1.05 to 1.88; P=.02), and early era of the experience. CONCLUSION: Most major complications of HALLDN occur after discharge, suggesting that close follow-up is warranted and that the current literature may underestimate the true incidence.
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Laparoscópía Mano-Asistida , Trasplante de Riñón , Femenino , Laparoscópía Mano-Asistida/efectos adversos , Humanos , Trasplante de Riñón/efectos adversos , Donadores Vivos , Masculino , Persona de Mediana Edad , Nefrectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
ATP is an important paracrine regulator of renal tubular water and urea transport. The activity of P2Y2 , the predominant P2Y receptor of the medullary collecting duct, is mediated by ATP, and modulates urinary concentration. To investigate the role of purinergic signaling in the absence of urea transport in the collecting duct, we studied wild-type (WT) and UT-A1/A3 null (UT-A1/A3 KO) mice in metabolic cages to monitor urine output, and collected tissue samples for analysis. We confirmed that UT-A1/A3 KO mice are polyuric, and concurrently observed lower levels of urinary cAMP as compared to WT, despite elevated serum vasopressin (AVP) levels. Because P2Y2 inhibits AVP-stimulated transport by dampening cAMP synthesis, we suspected that, similar to other models of AVP-resistant polyuria, purinergic signaling is increased in UT-A1/A3 KO mice. In fact, we observed that both urinary ATP and purinergic-mediated prostanoid (PGE2 ) levels were elevated. Collectively, our data suggest that the reduction of medullary osmolality due to the lack of UT-A1 and UT-A3 induces an AVP-resistant polyuria that is possibly exacerbated by, or at least correlated with, enhanced purinergic signaling.
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Médula Renal/metabolismo , Túbulos Renales Colectores/metabolismo , Proteínas de Transporte de Membrana/genética , Receptores Purinérgicos P2Y2/metabolismo , Urea/metabolismo , Animales , Modelos Animales de Enfermedad , Masculino , Proteínas de Transporte de Membrana/deficiencia , Proteínas de Transporte de Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Concentración Osmolar , Transducción de Señal , Transportadores de UreaAsunto(s)
Carcinoma Neuroendocrino/cirugía , Ablación por Catéter/métodos , Etanol , Recurrencia Local de Neoplasia/cirugía , Neoplasias de la Tiroides/cirugía , Ultrasonografía Intervencional , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Ultrasonografía Intervencional/métodos , Adulto JovenRESUMEN
Lithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in â¼40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCα KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCα KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCα KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCα KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCα KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCα KO mice. Our data show that ablation of PKCα preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy.