Triplex Doppler da artéria renal e a relação entre a ecobiometria dos rins com distância atlanto-coccígea e altura em Canis familiaris

O objetivo do trabalho foi estabelecer a relação entre a ecobiometria renal com medidas de conformação corporal como a distância atlanto-coccígea (DAC) e a altura (H) de cães adultos saudáveis, obtendo-se parâmetros de normalidade para avaliar o tamanho e volume renal, bem como estabelecer valores de referência para avaliar a perfusão sanguínea dos rins por meio do índice de resistividade (IR) e do índice de pulsatilidade (IP) do ramo principal da artéria renal. No estudo foram utilizados 22 cães adultos sem raça definida, sendo 11 machos e 11 fêmeas. Os animais foram previamente aferidos quanto a DAC e a H. Os exames ultra-sonográficos foram realizados com um aparelho HDI 4000 PHILIPS munido de um transdutor microconvexo multifreqüêncial (5-8 MHz), dispositivos Doppler Colorido e Doppler de Fluxo. Os animais foram posicionados em decúbito lateral direito ou esquerdo, de acordo com o rim a ser avaliado. Os diâmetros longitudinal (DL) e dorsoventral (DDV) dos rins foram mensurados na secção longitudinal e, o diâmetro transversal (DT) foi aferido no plano transversal. O volume (V) foi calculado automaticamente pelo software do ultra-som. Com o uso do Triplex Doppler, o IR e o IP das artérias renais direita e esquerda foram obtidos. Todos os dados foram apresentados em média ± EPM. Análises de regressão linear foram realizadas tendo o DL, DDV, DT e V como variáveis dependentes e a DAC e H como variáveis independentes. Os IR e IP dos rins direito e esquerdo foram comparados pelo teste t de Student. A DAC variou de 54-78cm para machos e 37-71cm para fêmeas e a altura variou entre 34-64 cm para os machos e 24-57cm para as fêmeas. As médias obtidas para DL, DDV, DT e V dos rins esquerdo e direito foram: 5,24±0,27cm, 3,07±0,15cm, 3,07±0,9cm, 28,01±3,4mL e 4,50±0,19cm, 2,88±0,14cm, 2,71±0,15cm, 21,27±2,6mL, respectivamente. As análises de regressão linear entre as medidas lineares e volume renal com a DAC e a H foram significativas para os interceptos e coeficientes de regressão (P<0,01). Houve diferenças estatísticas quando comparado os IR e IP entre os rins direito e esquerdo (P=0,001), sendo que as médias para IR e IP dos rins esquerdo e direito foram 0,62±0,08; 1,34±0,18 e 0,70±0,06; 1,62±0,13; respectivamente. Os dados obtidos no presente trabalho podem auxiliar na avaliação do tamanho, volume e perfusão dos rins de cães adultos.

Estudo da proteção renal com antioxidante durante isquemia e reperfusão e hiperglicemia transitória

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeitos da ciclosporina na lesão renal por isquemia-reperfusão em ratos: estudo em modelo experimental

Pós-graduação em Anestesiologia - FMB

Late evaluation of the relationship between morphological and functional renal changes and hypertension after non-operative treatment of high-grade renal injuries

Objective: To evaluate the anatomical and functional renal alterations and the association with post-traumatic arterial hypertension. Methods: The studied population included patients who sustained high grades renal injury (grades III to V) successfully non-operative management after staging by computed tomography over a 16-year period. Beyond the review of medical records, these patients were invited to the following protocol: clinical and laboratory evaluation, abdominal computed tomography, magnetic resonance angiography, DMSA renal scintigraphy, and ambulatory blood pressure monitoring. The hypertensive patients also were submitted to dynamic renal scintigraphy (Tc-99m EC), using captopril stimulation to verify renal vascular etiology. Results: Of the 31 patients, there were thirteen grade III, sixteen grade IV (nine lacerations, and seven vascular lesions), and two grade V injuries. All the patients were asymptomatic and an average follow up post-injury of 6.4 years. None had abnormal BUN or seric creatinine. The percentage of renal volume reduction correlates with the severity as defined by OIS. There was no evidence of renal artery stenosis in Magnetic Resonance angiography (MRA). DMSA scanning demonstrated a decline in percentage of total renal function corresponding to injury severity (42.2 +/- 5.5% for grade III, 35.3 +/- 12.8% for grade IV, 13.5 +/- 19.1 for grade V). Six patients (19.4%) had severe compromised function (< 30%). There was statistically significant difference in the decrease in renal function between parenchymal and vascular causes for grade IV injuries (p < 0.001). The 24-hour ambulatory blood pressure monitoring detected nine patients (29%) with post-traumatic hypertension. All the patients were male, mean 35.6 years, 77.8 % had a familial history of arterial hypertension, 66.7% had grade III renal injury, and average post-injury time was 7.8 years. Seven patients had negative captopril renography. Conclusions: Late results of renal function after conservative treatment of high grades renal injuries are favorable, except for patients with grades IV with vascular injuries and grade V renal injuries. Moreover, arterial hypertension does not correlate with the grade of renal injury or reduction of renal function.

Mesenchymal stem cells (MSC) prevented the progression of renovascular hypertension, improved renal function and architecture

Renovascular hypertension induced by 2 Kidney-1 Clip (2K-1C) is a renin-angiotensin-system (RAS)-dependent model, leading to renal vascular rarefaction and renal failure. RAS inhibitors are not able to reduce arterial pressure (AP) and/or preserve the renal function, and thus, alternative therapies are needed. Three weeks after left renal artery occlusion, fluorescently tagged mesenchymal stem cells (MSC) (2×10(5) cells/animal) were injected weekly into the tail vein in 2K-1C hypertensive rats. Flow cytometry showed labeled MSC in the cortex and medulla of the clipped kidney. MSC prevented a further increase in the AP, significantly reduced proteinuria and decreased sympathetic hyperactivity in 2K-1C rats. Renal function parameters were unchanged, except for an increase in urinary volume observed in 2K-1C rats, which was not corrected by MSC. The treatment improved the morphology and decreased the fibrotic areas in the clipped kidney and also significantly reduced renal vascular rarefaction typical of 2K-1C model. Expression levels of IL-1β, TNF-α angiotensinogen, ACE, and Ang II receptor AT1 were elevated, whereas AT2 levels were decreased in the medulla of the clipped kidney. MSC normalized these expression levels. In conclusion, MSC therapy in the 2K-1C model (i) prevented the progressive increase of AP, (ii) improved renal morphology and microvascular rarefaction, (iii) reduced fibrosis, proteinuria and inflammatory cytokines, (iv) suppressed the intrarenal RAS, iv) decreased sympathetic hyperactivity in anesthetized animals and v) MSC were detected at the CNS suggesting that the cells crossed the blood-brain barrier. This therapy may be a promising strategy to treat renovascular hypertension and its renal consequences in the near future.

[Endovascular therapy of an abdominal aortic aneurysm in a renal transplant recipient]

INTRODUCTION: The indications for endovascular aortic aneurysm repair (EVAR) are mainly established in hostile abdomen, in patients with significant comorbidities which affect the general operability of the patient and, given the necessary infrastructure, also in ruptured aneurysm. Along to those, we present another possible indication in the presence of a kidney allograft in patients with aortic aneurysm. METHODS: Based on a case report of aorto-biiliac stent-graft repair of an infrarenal aortic aneurysm in a patient with renal allograft, a systematic review of the literature was performed of all similar cases concerning surgical therapy in this constellation. RESULTS: EVAR was performed using an aorto-biiliac system (Zenith) Trifab, COOK) in a 61-year-old male patient 11 years after heterotopic renal allotransplantation in the right iliac fossa. Preoperative renal function was normal. Because the donor renal artery was anastomosed to the recipient's external iliac artery the stent-graft was implanted from the left common femoral artery to minimize temporary allograft ischemia. The intra- and postoperative course was uneventful with a follow-up of presently 12 months. A primary type-II endoleak (retroleak from a lumbar artery) is being treated conservatively so far with embolization being a future option. At present there are 15 cases of EVAR in renal allograft patients that have been reported, all of them being successful. DISCUSSION: All data existing in the literature reported to date as well as our own experience justify the first choice of EVAR in morphologically suitable cases. One major advantage of EVAR in this constellation is the avoidance of aortic cross clamping which poses the graft at risk of ischemia. Long-term results will be most important for definite assessment of EVAR. However, contrast media application during the operation and for CT surveillance should be considered as a major disadvantage.

Anatomical eligibility of the renal vasculature for catheter-based renal denervation in hypertensive patients.

OBJECTIVES This study sought to determine the vascular anatomical eligibility for catheter-based renal artery denervation (RDN) in hypertensive patients. BACKGROUND Arterial hypertension is the leading cardiovascular risk factor for stroke and mortality globally. Despite substantial advances in drug-based treatment, many patients do not achieve target blood pressure levels. To improve the number of controlled patients, novel procedure- and device-based strategies have been developed. RDN is among the most promising novel techniques. However, there are few data on the vascular anatomical eligibility. METHODS We retrospectively analyzed 941 consecutive hypertensive patients undergoing coronary angiography and selective renal artery angiography between January 1, 2010, and May 31, 2012. Additional renal arteries were divided into 2 groups: hilar (accessory) and polar (aberrant) arteries. Anatomical eligibility for RDN was defined according to the current guidelines: absence of renal artery stenosis, renal artery diameter ≥4 mm, renal artery length ≥20 mm, and only 1 principal renal artery. RESULTS A total of 934 hypertensive patients were evaluable. The prevalence of renal artery stenosis was 10% (n = 90). Of the remaining 844 patients without renal artery stenosis, 727 (86%) had nonresistant hypertension and 117 (14%) had resistant hypertension; 62 (53%) of the resistant hypertensive and 381 (52%) of the nonresistant hypertensive patients were anatomically eligible for sympathetic RDN. CONCLUSIONS The vascular anatomical eligibility criteria of the current guidelines are a major limiting factor for the utilization of RDN as a therapeutic option. Development of new devices and/or techniques may significantly increase the number of candidates for these promising therapeutic options.

Creation of a reversible on/off system for site-specific in vivo control of exogenous gene activity in the renal glomerulus.

Using genetically engineered glomerular mesangial cells, an in vivo gene transfer approach was developed that specifically targets the renal glomerulus. By combining this system with a tetracycline (Tc)-responsive promoter, the present study aimed to create a reversible on/off system for site-specific in vivo control of exogenous gene activity within the glomerulus. In the Tc regulatory system, a Tc-controlled transactivator (tTA) encoded by a regulator plasmid induces target gene transcription by binding to a tTA-responsive promoter located in a response plasmid. Tc inhibits this tTA-dependent transactivation via its affinity for tTA. In double-transfected cells, therefore, the activity of a transgene can be controlled by Tc. Cultured rat mesangial cells were cotransfected with a regulator plasmid and a response plasmid that introduces a beta-galactosidase gene. In vitro, stable double-transfectant MtTAG cells exhibited no beta-galactosidase activity in the presence of Tc. However, following withdrawal of Tc from culture media, expression of beta-galactosidase was induced within 24 h. When Tc was again added, the expression was rapidly resuppressed. Low concentrations of Tc were sufficient to maintain the silent state of tTA-dependent promoter. MtTAG cells were then transferred into the rat glomeruli via renal artery injection. In the isolated chimeric glomeruli, expression of beta-galactosidase was induced ex vivo in the absence of Tc, whereas it was repressed in its presence. When Tc-pretreated MtTAG cells were transferred into the glomeruli of untreated rats, beta-galactosidase expression was induced in vivo within 3 days. Oral administration of Tc dramatically suppressed this induction. These data demonstrate the feasibility of using mesangial cell vectors combined with the Tc regulatory system for site-specific in vivo control of exogenous gene expression in the glomerulus.

Renal endothelial dysfunction and impaired autoregulation after ischemia-reperfusion injury result from excess nitric oxide

Endothelial dysfunction in ischemic acute renal failure (IARF) has been attributed to both direct endothelial injury and to altered endothelial nitric oxide synthase ( eNOS) activity, with either maximal upregulation of eNOS or inhibition of eNOS by excess nitric oxide ( NO) derived from iNOS. We investigated renal endothelial dysfunction in kidneys from Sprague-Dawley rats by assessing autoregulation and endothelium-dependent vasorelaxation 24 h after unilateral ( U) or bilateral ( B) renal artery occlusion for 30 (U30, B30) or 60 min (U60, B60) and in sham-operated controls. Although renal failure was induced in all degrees of ischemia, neither endothelial dysfunction nor altered facilitation of autoregulation by 75 pM angiotensin II was detected in U30, U60, or B30 kidneys. Baseline and angiotensin II-facilitated autoregulation were impaired, methacholine EC50 was increased, and endothelium-derived hyperpolarizing factor ( EDHF) activity was preserved in B60 kidneys. Increasing angiotensin II concentration restored autoregulation and increased renal vascular resistance ( RVR) in B60 kidneys; this facilitated autoregulation, and the increase in RVR was abolished by 100 mu M furosemide. Autoregulation was enhanced by N-omega-nitro-L-arginine methyl ester. Peri-ischemic inhibition of inducible NOS ameliorated renal failure but did not prevent endothelial dysfunction or impaired autoregulation. There was no significant structural injury to the afferent arterioles with ischemia. These results suggest that tubuloglomerular feedback is preserved in IARF but that excess NO and probably EDHF produce endothelial dysfunction and antagonize autoregulation. The threshold for injury-producing, detectable endothelial dysfunction was higher than for the loss of glomerular filtration rate. Arteriolar endothelial dysfunction after prolonged IARF is predominantly functional rather than structural.

Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure

Administration of human recombinant erythropoietin ( EPO) at time of acute ischemic renal injury ( IRI) inhibits apoptosis, enhances tubular epithelial regeneration, and promotes renal functional recovery. The present study aimed to determine whether darbepoetin-alfa ( DPO) exhibits comparable renoprotection to that afforded by EPO, whether pro or antiapoptotic Bcl-2 proteins are involved, and whether delayed administration of EPO or DPO 6 h following IRI ameliorates renal dysfunction. The model of IRI involved bilateral renal artery occlusion for 45 min in rats ( N = 4 per group), followed by reperfusion for 1-7 days. Controls were sham-operated. Rats were treated at time of ischemia or sham operation ( T0), or post-treated ( 6 h after the onset of reperfusion, T6) with EPO ( 5000 IU/kg), DPO ( 25 mu g/kg), or appropriate vehicle by intraperitoneal injection. Renal function, structure, and immunohistochemistry for Bcl-2, Bcl-XL, and Bax were analyzed. DPO or EPO at T0 significantly abrogated renal dysfunction in IRI animals ( serum creatinine for IRI 0.17 +/- 0.05mmol/l vs DPO-IRI 0.08 +/- 0.03mmol/l vs EPO-IRI 0.04 +/- 0.01mmol/l, P = 0.01). Delayed administration of DPO or EPO ( T6) also significantly abrogated subsequent renal dysfunction ( serum creatinine for IRI 0.17 +/- 0.05mmol/l vs DPO-IRI 0.06 +/- 0.01mmol/l vs EPO-IRI 0.03 +/- 0.03mmol/l, P = 0.01). There was also significantly decreased tissue injury ( apoptosis, P < 0.05), decreased proapoptotic Bax, and increased regenerative capacity, especially in the outer stripe of the outer medulla, with DPO or EPO at T0 or T6. These results reaffirm the potential clinical application of DPO and EPO as novel renoprotective agents for patients at risk of ischemic acute renal failure or after having sustained an ischemic renal insult.

Effect of sildenafil in renal ischemia/reperfusion injury in rats

To evaluate the effect of sildenafil, administered prior to renal ischemia/reperfusion (I/R), by scintigraphy and histopathological evaluation in rats. Methods: Twenty-four rats were divided randomly into two groups. They received 0.1 ml of 99mTechnetium-etilenodicisteine intravenous, and a baseline (initial) renal scintigraphy was performed. The rats underwent 60 minutes of ischemia by left renal artery clamping. The right kidney was not manipulated. The sildenafil group (n=12) received orally 1 mg/kg of sildenafil suspension 60 minutes before ischemia. Treatment with saline 0.9% in the control group (n=12). Half of the rats was assessed after 24 hours and half after seven days I/R, with new renal scintigraphy to study differential function. After euthanasia, kidneys were removed and subjected to histopathological examination. For statistical evaluation, Student t and Mann-Whitney tests were used. Results: In the control group rats, the left kidneys had significant functional deficit, seven days after I/R, whose scintigraphic pattern was consistent with acute tubular necrosis, compared with the initial scintigraphy (p<0.05). Sildenafil treatment resulted in better differential function of the left kidneys 24h after reperfusion, compared with controls. Histopathologically, the left kidney of control rats (24 hours after I/R) showed a higher degree of cellular necrosis when compared with the sildenafil treated rats (p<0.05). Conclusion: Sildenafil had a protective effect in rat kidneys subjected to normothermic I/R, demonstrated by scintigraphy and histomorphometry

Squamous cell carcinoma of the renal pelvis with stones and inferior vena cava infiltration. Case report

We report a rare case of a 50 year old man with renal squamous cell carcinoma (SCC) who first came to our attention with renal colic and fever not responding to antibiotic or analgesic treatment. He had a long history of kidney stones, but had not undergone any imaging in the last 5 years. Physical examination revealed tenderness and a palpable mass in the right flank and lumbar region. A whole body CT scan was performed, revealing an 11 cm mass in the right kidney infiltrating the inferior vena cava. There were areas of calcification within the mass and multiple stones within the renal pelvis. The tumor was considered unsuitable for resection according to radiological and clinical criteria. The mass was biopsied percutaneously under CT guidance and histological examination revealed squamous cell carcinoma of the renal pelvis. The patient was treated with neoadjuvant chemotherapy and embolization of the renal artery. He died one month after diagnosis. To our knowledge this is the second reported case in the world of renal SCC infiltrating the inferior vena cava and with kidney stones.

Effect of sildenafil in renal ischemia/reperfusion injury in rats

To evaluate the effect of sildenafil, administered prior to renal ischemia/reperfusion (I/R), by scintigraphy and histopathological evaluation in rats. Methods: Twenty-four rats were divided randomly into two groups. They received 0.1 ml of 99mTechnetium-etilenodicisteine intravenous, and a baseline (initial) renal scintigraphy was performed. The rats underwent 60 minutes of ischemia by left renal artery clamping. The right kidney was not manipulated. The sildenafil group (n=12) received orally 1 mg/kg of sildenafil suspension 60 minutes before ischemia. Treatment with saline 0.9% in the control group (n=12). Half of the rats was assessed after 24 hours and half after seven days I/R, with new renal scintigraphy to study differential function. After euthanasia, kidneys were removed and subjected to histopathological examination. For statistical evaluation, Student t and Mann-Whitney tests were used. Results: In the control group rats, the left kidneys had significant functional deficit, seven days after I/R, whose scintigraphic pattern was consistent with acute tubular necrosis, compared with the initial scintigraphy (p<0.05). Sildenafil treatment resulted in better differential function of the left kidneys 24h after reperfusion, compared with controls. Histopathologically, the left kidney of control rats (24 hours after I/R) showed a higher degree of cellular necrosis when compared with the sildenafil treated rats (p<0.05). Conclusion: Sildenafil had a protective effect in rat kidneys subjected to normothermic I/R, demonstrated by scintigraphy and histomorphometry

Impedancias basales registradas durante la denervación renal por radiofrecuencia en pacientes con hipertensión arterial resistente

Objetivo: Determinar diferencias en las impedancias basales registradas durante los procedimientos de denervación renal por radiofrecuencia de los pacientes sometidos a este procedimiento en la Fundación Cardioinfantil de Bogotá durante los años 2012 a 2015. Materiales y métodos: Estudio observacional, analítico de corte retrospectivo, donde se analizaron todas las impedancias basales medidas durante los procedimientos de denervación renal, buscando diferencias significativas entre los segmentos de las arterias intervenidas, estratificados en proximal, medio distal y superior, lateral, inferior u ostial. Con seguimiento a los pacientes a tres, seis y doce meses en cuanto a presión arterial de consultorio. Resultados: Se evaluaron 150 puntos de denervación renal exitosos, correspondientes a 23 arterias renales de 11 procedimientos. La mediana de edad fue 56 años. Al realizar un modelo de regresión lineal no se encontró ninguna diferencia estadísticamente significativa entre las impedancias de ninguno de los segmentos de las arterias ni sitios anatómicos. Se documentó disminución de presión arterial sistólica a tres meses, seis meses y doce meses de 14 mmHg (RIQ 10-33mmHg), 21 mmHg (RIQ 12-42mmHg) y 19 mmHg (RIQ 11-42 mmHg) respectivamente

Avaliação estereológica glomerular em rins de ratos após isquemia-reperfusão por clampeamento arteriovenoso e arterial

A técnica de isquemia-reperfusão tem sido utilizada em cirurgias conservadoras do rim como a nefrectomia parcial e em transplantes renais. Para se realizar a isquemia pode-se fazer o bloqueio do fluxo sanguíneo da artéria renal ou o bloqueio simultâneo da artéria e da veia renal. O evento isquêmico acarreta em dano celular ao rim principalmente pelo estresse oxidativo local e a liberação de radicais livres assim como o aumento da resposta inflamatória. Diversos autores verificaram lesão renal após a isquemia-reperfusão, porém, apenas testes funcionais foram realizados até o momento. Os autores que tentaram avaliar a lesão morfológica do rim apenas fizeram a quantificação de escores subjetivos. O nosso objetivo é avaliar por quantificação estereológica o dano causado pela isquemia-reperfusão comparando o clampeamento somente arterial com o clampeamento arteriovenoso. Utilizamos 24 ratos wistar, machos, de quatro meses de idade. Os animais foram divididos em três grupos: o grupo Sham (n=8), o grupo de clampeamento somente da artéria renal (n=8) e o grupo de clampeamento simultâneo da artéria e da veia renal (n=8). Os animais foram submetidos a laparotomia mediana. Os animais do grupo Sham permaneceram os 60 minutos anestesiados mas sem obstrução do fluxo sanguíneo de seus vasos renais. Os animais do grupo de clampeamento arterial foram submetidos à clampeamento de sua arterial renal esquerda por 60 minutos e os animais do grupo de clampeamento arterial e venoso tiveram seus vasos renais esquerdos clampeados simultaneamente e em bloco pelo mesmo tempo. Após os 60 minutos os animais foram suturados e mantidos por 30 dias em caixas próprias sendo mortos por sobredose anestésica após decorrido esse tempo. Os rins foram coletados e mantidos em solução de formalina tamponada e posteriormente processados para análise histológica e estereológica. Foram analisados a densidade volumétrica (Vv) dos glomérulos, o número de glomérulos/mm3(Nv) e o volume glomerular médio (VGM). A Vv e Nv se encontrou reduzida nos rins esquerdos submetidos à isquemia mas foi somente significativa nos animais do grupo de clampeamento arterial e venoso. Mesmo usando o rato como modelo animal experimental, a partir de nossos resultados recomendamos o uso do clampeamento somente arterial nos casos em que mínina lesão ao rim é imperiosa.