Disfunção autonômica cardiovascular e dano renal: papel da inflamação e do estresse oxidativo / Cardiovascular autonomic dysfunction e renal damage: role of inflammation and oxidative stress

Evidências demonstram que não só a elevação da pressão arterial, mas também o aumento da variabilidade da pressão arterial (VPA) pode contribuir para a piora no dano renal e redução da sobrevida em portadores doença renal crônica. Este artigo tem como objetivo revisar o impacto da disfunção autonômica cardiovascular (hiperatividade simpática, prejuízo nasensibilidade dos barorreceptores e/ou aumento da VPA) e sua associação com inflamação e estresse oxidativo no desenvolvimento e progressão do dano renal (AU).

Evidence shows that not only the increase in blood pressure, but also the increase in blood pressure variability (BPV) can contribute to worsening kidney damage and reduced survival in patients with chronic kidney disease. This article aims to review the impact of cardiovascular autonomic dysfunction (sympathetic hyperactivity, impaired baroreflex sensitivity and/or increased BPV) and its association with inflammation and oxidative stress on the development and progression of renal damage (AU).

HIV-related nephropathy: new aspects of an old paradigm

SUMMARY The scenario of infection by the human immunodeficiency virus (HIV) has been undergoing changes in recent years, both in relation to the understanding of HIV infection and regarding the treatments available. As a result, the disease, which before was associated with high morbidity and mortality, is now seen as a chronic disease that can be controlled, regarding both transmission and symptoms. However, even when the virus replication is well controlled, the infected patient remains at high risk of developing renal involvement, either by acute kidney injury not associated with HIV, nephrotoxicity due to antiretroviral drugs, chronic diseases associated with increased survival, or glomerular disease associated to HIV. This review will cover the main aspects of kidney failure associated with HIV.

RESUMO O panorama da infecção pelo vírus da imunodeficiência humana (HIV) vem sofrendo alterações nos últimos anos, tanto em relação ao entendimento da infecção pelo HIV quanto aos tratamentos disponíveis. Como resultado, a doença, que antes estava associada a alta morbimortalidade, é agora considerada uma doença crônica que pode ser controlada, tanto em relação à transmissão quanto aos sintomas. No entanto, mesmo quando a replicação viral é bem controlada, o paciente infectado tem um alto risco de desenvolver complicações renais, seja através de lesão renal aguda não relacionada ao HIV, por nefrotoxicidade causada por drogas antirretrovirais, por doenças crônicas associadas com o aumento da sobrevida ou por doença glomerular associada ao HIV. Esta revisão abordará os principais aspectos da insuficiência renal associada ao HIV.

Fabry disease: genetics, pathology, and treatment

SUMMARY Fabry disease (FD) is a recessive monogenic inheritance disease linked to chromosome X, secondary to mutations in the GLA gene. Its prevalence is estimated between 1:8,454 and 1:117,000 among males and is probably underdiagnosed. Mutations in the GLA gene lead to the progressive accumulation of globotriaosylceramide (Gb3). Gb3 accumulates in lysosomes of different types of cells of the heart, kidneys, skin, eyes, central nervous system, and gastrointestinal system, and may lead to different clinical scenarios. The onset of symptoms occurs during childhood, with acroparesthesia, heat intolerance, and gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, and neuropathic pain. Subsequently, symptoms related to progressive impairment appear, such as angiokeratomas, cornea verticillata, left ventricular hypertrophy, myocardial fibrosis, proteinuria, and renal insufficiency. The latter being the main cause of death in FD. The gold standard for diagnosis is the genetic analysis in search of mutation, in addition to family history. In homozygous patients, the enzyme activity can also be used. Once the diagnosis is confirmed, the patient and their family should receive genetic counseling. The treatment, in turn, currently focuses mainly on replacing the enzyme that is absent or deficient by means of enzyme replacement therapy, with the purpose of avoiding or removing deposits of Gb3. Chaperones can also be used for the treatment of some cases. It is considered that the specific treatment should be initiated as soon as a diagnosis is obtained, which can change the prognosis of the disease.

Trastornos glomerulares en la práctica médica / Glomerulopathies in the medical practice

RESUMEN Las glomerulopatías agrupan varias nefropatías con lesiones fundamentalmente del corpúsculo renal y que se expresan principalmente por proteinuria, hematuria, edemas e hipertensión arterial. La presentación clínica varía en dependencia del tipo de enfermedad de que se trate. Constituye la causa más frecuente de enfermedad renal crónica en adultos jóvenes, por lo que su estudio resulta imprescindible sobre todo para el nivel primario de salud. El propósito fue actualizar consideraciones pertinentes sobre la conducta diagnóstica y terapéutica integral ante una glomerulopatía y valorar emisión de recomendaciones al respecto. Se realizó una búsqueda, análisis y síntesis de información a través de Bases de datos ScieLO Cuba, ScieLO regional, Pubmed, Cumed, Clinical Key en el período 2012-2017 con las palabras clave: síndrome nefrótico, glomerulonefritis, diagnóstico, terapéutica, atención integral. El abordaje en las glomerulopatías es integral, multidisciplinario e individualizado. En Cuba constituyen la cuarta causa de enfermedad renal crónica y predomina el síndrome nefrítico agudo postinfeccioso. El método clínico juega en ello un papel trascendental a la hora de reconocer y registrar sus aspectos clínicos, su etiología, su fisiopatología, y los exámenes complementarios que confirman su presencia o sus complicaciones, así como un tratamiento oportuno que garanticen el perfeccionamiento asistencial. El arma más poderosa ante el reto de los trastornos glomerulares es la visión integradora y con enfoque individual y social protagonizado por el médico ante este grupo de nefropatías en adultos.

ABSTRACT Glomerulopathies encompass a group of several renal disorders with lesions, mainly in the renal corpuscle, expressed in proteinuria, hematuria, edemas and arterial hypertension. Their clinical manifestations change in dependence of the kind of disease. They are the most frequent cause of chronic renal disease in young adults; therefore their study is very important above all in the health care primary level. The aim was updating pertinent considerations on the diagnostic behavior and comprehensive therapy in the case of glomerulopathy, and evaluating the emission of recommendations regarding to them. A search, analysis and synthesis of information was carried out in the databases ScieLO Cuba, ScieLO regional, Pubmed, Cumed, and Clinical Key in the period 2012-2017, using the key words nephrotic syndrome, glomerulonephritis, diagnosis, therapeutics, comprehensive care. The approach to glomerulopathies is comprehensive, multidisciplinary and individualized. They are the fourth cause of chronic renal disease; the acute post-infectious nephritic syndrome predominates. The clinical method plays a transcendental role at the moment of recognizing and registering their clinical characteristics, etiology and physiopathology, while complementary tests confirm their presence or complications, and therefore an opportune treatment guarantying the healthcare improvement. The most powerful weapon against the challenge of the glomerular disorders is the integrated vision with an individual and social approach led by the physician in the case of these nephropathies in adults.

ANCA associated vasculitis: experience of a tertiary care referral center / Vasculite associada a ANCA: experiência de um centro de referência de atendimento terciário

ABSTRACT Background and objectives: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a small vessel vasculitis with insufficient epidemiologic estimates in the United States. We aimed to determine demographic and clinical features of ANCA associated vasculitis patients presenting to a large tertiary care referral center in Upstate New York. Design, setting, participants, and measurements: A retrospective analysis of cases with pauci-immune GN on renal biopsy and clinical diagnosis of ANCA vasculitis presenting over 11 years was conducted. Outcomes of interest were: demographics, ANCA antibody positivity, patient and renal survival, and regional trends. Results: 986 biopsies were reviewed, 41 cases met the criteria for inclusion: 18 GPA, 19 MPA, and 4 double positive (anti-GBM disease plus ANCA vasculitis). Mean age at presentation was 52.4 years (SD 23.7), 23 (56%) were male and median creatinine was 2.6 mg/dL. The median patient follow up was 77 weeks (IQR 10 - 263 weeks), with a 3-month mortality rate of 5.7% and a 1-year estimated mortality rate of 12%. Thirteen patients required hemodialysis at the time of diagnosis; 7 patients came off dialysis, with median time to renal recovery of 4.86 weeks (IQR 1.57 - 23.85 weeks). C-ANCA positivity (p < 0.001) and C-ANCA plus PR3 antibody pairing (p = 0.005) was statistically significant in GPA versus MPA. P-ANCA positivity was observed in MPA versus GPA (p = 0.02) and double positive versus GPA (p = 0.002), with P-ANCA and MPO antibody pairing in MPA versus GPA (p = 0.044). Thirty-seven of the 41 cases were referred locally, 16 cases were from within a 15-mile radius of Albany, Schenectady, and Saratoga counties. Conclusions: ANCA vasculitis is associated with end stage renal disease and increased mortality. Our study suggests the possibility of higher regional incidence of pauci-immune GN in Upstate New York. Further studies should investigate the causes of clustering of cases to specific regions.

RESUMO Introdução e objetivos: A vasculite associada a anticorpos anticitoplasma de neutrófilo (ANCA) é uma vasculite de pequenos vasos com estimativas epidemiológicas insuficientes nos Estados Unidos. Nosso objetivo foi determinar características demográficas e clínicas de pacientes com vasculite associada à ANCA, apresentando-se a um grande centro de referência de atendimento terciário em Upstate New York. Formato, cenário, participantes e medidas: Foi realizada uma análise retrospectiva dos casos de GN pauci-imune em biópsias renais e diagnóstico clínico de vasculite ANCA por mais de 11 anos. Os resultados de interesse foram: dados demográficos, positividade de anticorpos ANCA, sobrevidas renal e de pacientes e tendências regionais. Resultados: 986 biópsias foram revisadas, 41 casos preencheram os critérios de inclusão: 18 GPA, 19 PAM, e 4 duplo-positivos (doença anti-MBG com vasculite ANCA). A média de idade na apresentação foi de 52,4 anos (DP 23,7), 23 (56%) eram do sexo masculino e mediana de creatinina de 2,6 mg/dL. O acompanhamento mediano dos pacientes foi de 77 semanas (IQR 10 - 263 semanas), com uma taxa de mortalidade de 3 meses de 5,7% e uma taxa de mortalidade estimada em 1 ano de 12%. Treze pacientes necessitaram de hemodiálise no momento do diagnóstico; 7 pacientes saíram da diálise, com tempo médio para recuperação renal de 4,86 semanas (IQR 1,57 - 23,85 semanas). A positividade para C-ANCA (p < 0,001) e o pareamento de anticorpos C-ANCA mais PR3 (p = 0,005) foram estatisticamente significantes em GPA versus PAM. A positividade de P-ANCA foi observada em PAM versus GPA (p = 0,02) e duplo positivo versus GPA (p = 0,002), com pareamento de anticorpos P-ANCA e MPO em PAM versus GPA (p = 0,044). Trinta e sete dos 41 casos foram encaminhados localmente, 16 casos foram de dentro de um raio de 15 milhas dos condados de Albany, Schenectady e Saratoga. Conclusões: A vasculite por ANCA está associada à doença renal terminal e aumento da mortalidade. Nosso estudo sugere a possibilidade de maior incidência regional de GN pauci-imune no norte do estado de Nova York. Novos estudos devem investigar as causas do acúmulo de casos em regiões específicas.

The preoperative stratification of patients based on renal scan data is unable to predict the functional outcome after partial nephrectomy

ABSTRACT Introduction: eGFR-categories are used to predict functional outcome after partial nephrectomy (PN); no study categorized patients according to preoperative renal scan (RS) data. Aim of the study was to evaluate if stratification of patients according to RS is a reliable method to predict minor/major loss of renal function after PN. Materials and Methods: We considered patients who underwent PN and RS pre-/post-PN for T1 tumor in our Institution (2007-2017). Demographics, perioperative and specifically functional data were analysed. On the basis of the baseline Split Renal Function (SRF), patients were stratified into risk-categories: 1) baseline operated-kidney SRF range 45-55%; 2) baseline operated-kidney SRF <45%. Risk categories were analysed with postoperative functional outcome: postoperative operated-kidney SRF decrease below 90% of baseline was considered significant loss of function. Contingency tables and univariate/multivariate regression were analysed looking for independent factors of postoperative functional impairment. Results: 224 patients were analysed, 125 (55.8%) maintained >90% of their baseline function. Worse probability of maintaining ≥90 baseline renal function was found in patients with Charlson's Comorbidity Index (CCI≥3) (p=0.004) and patients with PADUA score ≥8 (p=0.023). After stratification by baseline renal function, ischemia was the only independent factor: no effect on patients with poorer baseline renal function. Patients with baseline SRF 45-55% who did not experience ischemia had the highest probability to maintain ≥90% baseline SRF (p=0.028). Ischemia >25 minutes was detrimental (p=0.017). Conclusions: Stratification of patients by SRF before PN is not a reliable predictor of renal functional outcome. Ischemia seems to scarcely influence patients with poorer renal function.

Predicting outcomes in partial nephrectomy: is the renal score useful?

ABSTRACT Introduction and Objective The R.E.N.A.L. nephrometry system (RNS) has been validated in multiple open, laparoscopic and robotic partial nephrectomy series. The aim of this study was to test the accuracy of R.E.N.A.L. nephrometry system in predicting perioperative outcomes in surgical treatment of kidney tumors <7.0cm in a prospective model. Materials and Methods Seventy-one patients were selected and included in this prospective study. We evaluate the accuracy of RNS in predicting perioperative outcomes (WIT, OT, EBL, LOS, conversion, complications and surgical margins) in partial nephrectomy using ROC curves, univariate and multivariate analyses. R.E.N.A.L. was divided in 3 groups: low complexity (LC), medium complexity (MC) and high complexity (HC). Results No patients in LC group had WIT >20 min, versus 41.4% and 64.3% MC and HC groups respectively (p=0.03); AUC=0.643 (p=0.07). RNS was associated with convertion rate (LC:28.6% ; MC:47.6%; HC:77.3%, p=0.02). Patients with RNS <8 were most often subjected to partial nephrectomy (93% x 72%, p=0.03) and laparoscopic partial nephrectomy (56.8% x 28%, p=0.02), AUC=0.715 (p=0.002). The RNS was also associated with operative time. Patients with a score >8 had 6.06 times greater chance of having a surgery duration >180 min. (p=0.017), AUC=0.63 (p=0.059). R.E.N.A.L. score did not correlate with EBL, complications (Clavien >3), LOS or positive surgical margin. Conclusion R.E.N.A.L. score was a good method in predicting surgical access route and type of nephrectomy. Also was associated with OT and WIT, but with weak accuracy. Although, RNS was not associated with Clavien >3, EBL, LOS or positive surgical margin.

Relación entre gravedad de arteriosclerosis y progresión de enfermedad renal en pacientes nefrectomizados / Relation between severity of atherosclerosis and progression of renal disease in nephrectomized patients

Nefrectomía radical se asocia a disminución progresiva de función renal. Los parámetros en insuficiencia renal post-nefrectomía están identificados, no así la importancia de la histopatología vascular en la pieza de nefrectomía. Nuestro objetivo fue evaluar si la gravedad de la aterosclerosis en tejido renal no neoplásico puede predecir la evolución del filtrado glomerular en pacientes con nefrectomía total. Se incluyeron 31 pacientes con nefrectomía radical unilateral, no donantes. Edad promedio 68.5 ± 11.8 años, 80% tenían antecedentes de hipertensión, 64% sobrepeso, 51% fumadores. Se estimó tasa de filtración glomerular preoperatoria, postoperatoria y a 6, 12 y 24 meses de cirugía. Se determinó grado de arteriolosclerosis según porcentaje de estrechamiento de luz vascular (grado 0: sin estrechamiento vascular; grado 1: menos del 25%; grado 2: 25-50%; grado 3: más del 50%). Los 10 pacientes con arteriolosclerosis grado 0 tuvieron mayor tasa de filtración glomerular basal (75 ± 13 ml/min/1.73 m²) que los 8 con grado 2 y 3 (55 ± 22 ml/min/1.73 m2) (p 0.0886). En la última evaluación, la tasa de filtrado glomerular fue 60 ± 13 ml/min/1.73 m² (grado 0) y 39 ± 11 ml/min/1.73 m² (grados 2 y 3) (p = 0.05). La disminución del filtrado glomerular fue mayor en grados más graves de ateroesclerosis (sin significación estadística). El análisis histológico de piezas quirúrgicas de nefrectomía permitiría identificar aquellos con mayor riesgo de progresión de enfermedad renal según gravedad de las lesiones vasculares ateroscleróticas.

Radical nephrectomy is associated with a progressive decline in renal function. Clinical parameters in post-nephrectomy insufficiency were described but the impact of histopathologic vascular findings in the non-neoplastic kidney of nephrectomy specimen, has been poorly studied. Our aim was to evaluate whether the severity of atherosclerosis in non-neoplastic renal tissue predicts the evolution of glomerular filtration rate in patients undergoing total nephrectomy. Thirty-one non-donor patients with unilateral radical nephrectomy were included. Average age was 68.5 ± 11.8 years, 80% had a history of hypertension, 64% overweight and 51% were smokers. The glomerular filtration rate was estimated preoperatively, postoperatively and at 6, 12 and 24 months after surgery. Arteriolosclerosis was scored based on degree of narrowing of the vascular lumen (stage 0: no vascular narrowing; stage 1: less than 25%; stage 2: 25-50%; stage 3: more than 50%). Ten patients in stage 0 had higher basal glomerular filtration rate (75 ± 13 ml/min/1.73 m²) than eight patients in stage 2 or 3 (55 ± 22 ml/min/1.73 m²) (p 0.0886). At the last postoperative evaluation, the glomerular filtration rate was 60 ± 13 ml/min/1.73 m² (stage 0) and 39 ± 11 ml/min/1.73 m² (stage 2 or 3) (p = 0.05). The decrease in glomerular filtration rate was higher in patients with more severe degrees of atherosclerosis but the difference was not statistically significant. The histological evaluation of the severity of arteriosclerosis in the whole kidney allows the identification of patients with a greater risk of decreased glomerular filtration rate after a post radical nephrectomy.

Comparative analysis of primary and secondary glomerulopathies in the northeast of Brazil: data from the Pernambuco Registry of Glomerulopathies - REPEG / Análise comparativa de glomerulopatias primária e secundária no nordeste do Brasil: dados do Registro Pernambucano de Glomerulopatias - REPEG

Abstract Introduction: In Brazil, glomerulopathies are the third leading cause of chronic renal disease, accounting for 11% of dialysis patients. Studies on the prevalence of this disease in Northeastern Brazil are scarce. Objective: The aim was to describe the findings of biopsies and to conduct a comparative analysis on the clinical laboratory presentation of primary glomerulopathies (PG) and secondary glomerulopathies (SG). Methods: This was a retrospective study conducted at two public teaching hospitals in the state of Pernambuco, Northeastern Brazil. Results: A total of 1151 biopsies performed between 1998 and 2016 were analyzed. The sample consisted of 670 biopsies of native kidneys, after excluding extra glomerular diseases and unsuitable material. PG were more frequent than SG (58% vs. 42%). There was a prevalence among PG of focal segmental glomerulosclerosis (43%). Membranoproliferative glomerulonephritis and collapsing glomerulopathy, accounted for 9% and 3% of the PG, respectively. For SG, the main etiologies were lupus nephritis (67%) and infections (10%). Female sex, hematuria and an elevated level of creatinine were related to a greater chance of SG, at multivariate analysis. An increase of proteinuria reduced this chance. Nephrotic syndrome was more common among the PG, while urinary abnormalities and nephritic syndrome prevailed in patients with SG. Conclusion: This is the first registry of glomerulopathies in Northeastern Brazil. It also presents a comparative analysis of the main clinical laboratory abnormalities of PG and SG, and includes the current classifications of glomerular diseases.

Resumo Introdução: No Brasil, glomerulopatias são a terceira causa de doença renal crônica terminal, responsáveis por 11% dos pacientes em diálise. Entretanto, estudos sobre a prevalência desta patologia no nordeste do Brasil são escassos. Objetivo: O objetivo foi descrever os achados das biópsias e analisar comparativamente a apresentação clínico laboratorial entre as glomerulopatias primárias (GP) e as glomerulopatias secundárias (GS). Métodos: Estudo retrospectivo, realizado em dois hospitais públicos de ensino do estado de Pernambuco, nordeste do Brasil. Resultados: Foram avaliadas 1.151 biópsias, de 1998 a 2016. A amostra foi composta por 670 biópsias de rins nativos, após exclusão de patologias extra glomerulares e materiais inadequados. GP foram mais frequentes do que GS (58% × 42%). Dentre as GP, houve predomínio de glomeruloesclerose segmentar e focal (GESF). Glomerulonefrite membranoproliferativa e glomerulopatia colapsante foram responsáveis por 9% e 3% das GP, respectivamente. Das GS, as etiologias principais foram nefrite lúpica (67%) e infecciosas (10%). Sexo feminino, hematúria e nível elevado de creatinina estiveram relacionadas a uma maior chance de GS na análise multivariada. Síndrome nefrótica foi mais comum dentre as GP, já anormalidades urinárias e síndrome nefrítica prevaleceram nos pacientes com GS. Conclusões: Este é o primeiro registro de glomerulopatias do nordeste do Brasil. Demonstrou-se também uma análise comparativa das principais alterações clínico laboratoriais das GP e GS, com classificações atualizadas das doenças glomerulares.

Upregulation of microRNA 142-3p in the peripheral blood and urinary cells of kidney transplant recipients with post-transplant graft dysfunction

We analyzed microRNA (miR)-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23), acute tubular necrosis group (n=18) and stable patients group used as a control for gene expression (n=8). Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (P<0.05) and urine (P<0.001) compared to the stable patients group. Also, in the peripheral blood, miR-142-3p expression was significantly higher in the acute tubular necrosis group compared to the acute rejection group (P<0.05). Urine samples of the acute rejection group presented higher expression compared to the stable patients group (P<0.001) but the difference between acute tubular necrosis and acute rejection groups was not significant in the urinary analyzes (P=0.079). miR-142-3p expression has a distinct pattern of expression in the setting of post-operative acute tubular necrosis after kidney transplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.

Three-dimensional reconstructive kidney volume analyses according to the endophytic degree of tumors during open partial or radical nephrectomy

ABSTRACT Objectives To investigate the renal function outcomes and contralateral kidney volume change measured by using a 3-dimensional reconstructive method after open partial nephrectomy (PN) or open radical nephrectomy (RN) according to the endophytic degree of tumors. Materials and Methods We included 214 PN and 220 RN patients. According to the endophytic degree of the tumors, we divided patients into 3 groups. Patients were assessed for renal function and kidney volume change both preoperatively and postoperatively at 6 months. Kidney volume was calculated by using personal computer-based software. Subgroup analyses was performed for tumor >4cm. Results Larger and complex tumors were more frequent in the RN group than PN group. Among patients with exophytic and mild endophytic tumors, the mean postoperative renal function was well preserved in PN group and the mean contralateral kidney volume significantly increased in the RN compared to the PN group (PN, 145.55 to 149.98mL; 3.0% versus RN, 143.93 to 169.64mL;17.9% p=0.006). However, in fully endophytic tumors, compensatory hypertrophy of the contralateral kidney was similar between PN and RN (PN, 138.16 to 159.64mL; 15.5 % versus RN, 138.65 to 168.04mL; 21.2% p=0.416) and renal functional outcomes were similar between both groups. These results were also confirmed in tumors >4cm in size. Conclusions In fully endophytic tumors, especially large tumors, the postoperative renal function and contralateral kidney volume were similar; therefore, we should consider RN preferentially as surgical option for these tumors.

Superoxide overproduction and kidney fibrosis: a new animal model / Produção aumentada de superóxido e fibrose renal: novo modelo animal

Objective To establish whether the mutation in the Immp2L gene induces renal fibrosis and whether aging exacerbates renal morphology in mice. Methods Female mutant mice with mutation in the inner mitochondrial membrane peptidase 2-like protein at 3 and 18 months of age were used. Renal fibrosis was analyzed using classic fibrosis score, Masson’s trichrome staining, and analysis of profibrotic markers using real time polymerase chain reaction (superoxide dismutase 1, metalloproteinase-9, erythropoietin, transforming growth factor beta), and immunostaining (fibroblasts and Type IV collagen). Oxidative stress markers were determined by immunohistochemistry. The number of renal apoptotic cells was determined. Renal function was estimated by serum creatinine. Results Young mutant mice had significantly more glomerulosclerosis than age-matched mice (p=0.034). Mutant mice had more tubular casts (p=0.025), collagen deposition (p=0.019), and collagen type IV expression (p<0.001). Superoxide dismutase 1 expression was significantly higher in young mutants (p=0.038). Old mutants exhibited significantly higher expression of the fibroblast marker and macrophage marker (p=0.007 and p=0.012, respectively). The real time polymerase chain reaction of metalloproteinase-9 and erythropoietin were enhanced 2.5- and 6-fold, respectively, in old mutants. Serum creatinine was significantly higher in old mutants (p<0.001). Conclusion This mutation altered renal architecture by increasing the deposition of extracellular matrix, oxidative stress, and inflammation, suggesting a protective role of Immp2L against renal fibrosis. .

Objetivo Estabelecer se a mutação no gene Immp2L induz à fibrose renal e se o envelhecimento exacerba a morfologia renal em camundongos. Métodos Foram usadas fêmeas de camundongos mutantes para proteína semelhante à peptidase 2 da camada interna da mitocôndria, com 3 e 18 meses de idade. Para analisar a fibrose renal, foram usados o escore clássico de fibrose, a coloração com tricrômio de Masson, e a análise de marcadores profibróticos, por meio da reação em cadeia de polimerase em tempo real (superóxido dismutase 1, metalonoproteinase-9, eritropoietina e fator transformador de crescimento beta), e a imunocoloração (fibroblastos e colágeno IV). Marcadores de estresse oxidativo foram determinados por imuno-histoquímica. O número de células apoptóticas renais foi analisado. A função renal foi estimada por creatinina sérica. Resultados Camundongos mutantes jovens apresentaram glomeruloesclerose em quantidade significativamente maior que animais da mesma idade (p=0,034). Os mutantes mostraram maior formação de cilindros tubulares (p=0,025), deposição de colágeno (p=0,019) e maior expressão de colágeno do tipo IV (p<0,001). A expressão de superóxido dismutase 1 foi maior em mutantes jovens (p=0,038). Mutantes idosas exibiram maior expressão dos marcadores de fibroblastos e macrófagos (p=0,007 e p=0,012, respectivamente). As reações da cadeia de polimerase em tempo real da metalanoproteinase-9 e da eritropoietina estavam aumentadas em 2,5 e 6 vezes, respectivamente, em mutantes idosas. A creatinina sérica foi significantemente maior em animais idosos mutantes (p<0,001). Conclusão Essa mutação alterou a arquitetura renal pelo aumento da deposição de matriz extracelular, estresse oxidativo e inflamação, sugerindo papel de proteção de Immp2L contra a fibrose renal. .

Animal model of chronic kidney disease using a unilateral technique of renal ischemia and reperfusion in White New Zealand rabbits

PURPOSE: To establish a model of chronic kidney disease in White New Zealand rabbits, using an exclusive unilateral technique of renal ischemia and reperfusion. METHODS: Twenty males White New Zealand rabbits were used. All animals were subjected to the following: pre-surgical blood collection (1st collection) for creatinine and urea serum analysis, left renal ischemia and reperfusion surgery technique, another blood sample was collected after 6 weeks post surgery (2nd collection), the last blood sample (3rd collection) blood sample was taken 11 weeks post surgery (pre-euthanasia), euthanasia and withdrawal of right and left kidney for histopathological analysis. RESULTS: The creatinine levels after surgery was statistically significant higher in the 3rd collection, regarding the 1st and 2nd collection (p<0.05). A significant statistic increase for urea was showed only in the 2nd collection (p<0.05) when compared to the 1st and 3rd collections. Histopathological analysis showed bilateral lesions in the renal tissue, consistent to the process of ischemia and reperfusion. CONCLUSION: This exclusive unilateral technique of renal ischemia and reperfusion without nephrectomy in White New Zealand rabbits, showed effectiveness in getting an animal model of chronic kidney disease .

Active surveillance of renal masses: an analysis of growth kinetics and clinical outcomes stratified by radiological characteristics at diagnosis

AIMS To determine the growth rate of renal masses (RMs) under active surveillance (AS), and to describe the clinical outcome of AS patients. Materials and Methods We conducted a retrospective review of an AS database to obtain demographics, radiological and pathologic characteristics and RM size of patients. RMs were followed at 6-12 month intervals for ≥1 year with computed tomography (CT), magnetic resonance imaging (MRI), or renal ultrasound. Kaplan-Meier analysis determined the annual likelihood of intervention. RMs were divided into 3 radiographic subcategories (solid, cystic, and angiomyolipoma). A linear regression model determined RM growth rates. Results 131 RMs in 114 patients were included. Median age, Charlson Comorbidity Index score and mean follow-up were 69.1 years, 4.0 and 4.2±2.6 years, respectively. Maximal tumor diameter (MTD) at diagnosis was 2.1±1.3 cm. 49 RMs exhibited negative or zero net growth. Mean MTD growth rate for all RMs was 0.72±3.2 (95% CI: 0.16-1.28) mm/year. When stratified by MTD at diagnosis, mean RM growth rates were 0.84, 0.84, 0.44, 0.74 and 0.71 mm/year for RMs <1 cm, 1-<2cm, 2-<3cm, 3-<4cm and ≥4cm, respectively (p<0.01). The 5 and 10-year freedom from intervention rates were 93.1% and 88.5%, respectively. There was a single case of suspected metastases, but no deaths related to kidney cancer. Conclusions RMs under AS grew slowly, and had a low incidence of requiring surgical intervention and progression. Solid enhancing masses grew slowly, and were more likely to trigger intervention. AS should be considered for selected patients with small RMs. .

Uso de sirolimus en pacientes pediátricos con poliquistosis renal autosómica dominante / Use of sirolimus in pediatric patients with autosomal dominant polycystic kidney disease

La poliquistosis renal autosómica dominante (PQRAD) se caracteriza por la aparición de quistes renales. Objetivos: Evaluar el crecimiento del volumen renal y de los quistes en los pacientes tratados con sirolimus, en comparación con aquellos que reciben el tratamiento habitual para la PQRAD; evaluar la aparición de efectos adversos relacionados con el uso de sirolimus; evaluar los cambios en la presión arterial, la proteinuria y el filtrado glomerular (FG) estimado. Materiales y métodos: Durante 24 meses se asignaron al azar 12 pacientes con PQRAD a un grupo de tratamiento con sirolimus (6 pacientes recibieron sirolimus 2 a 3 mg/m2/día, con un máximo de 5 mg/día) o a un grupo control (bajo tratamiento habitual). Resultados: De los 12 pacientes, los 6 pertenecientes al grupo de tratamiento con sirolimus tuvieron, al final del estudio, un aumento del volumen renal total y del volumen quístico del 13% y el 32%, respectivamente. En el grupo control, los 6 pacientes restantes tuvieron aumentos del 11% y el 23%, respectivamente. El FG fue normal para ambos grupos. La proteinuria para los grupos de sirolimus y control fue inicialmente 7.3 mg/m2/h y 6 mg/m2/h, respectivamente. Al finalizar el estudio era normal para ambos grupos. Tres pacientes tenían hipertensión arterial, pero a los 24 meses la presión arterial fue normal. Los efectos adversos observados fueron: anemia, diarrea y úlceras bucales. Conclusiones: El sirolimus no disminuyó el volumen renal ni el quístico. No hubo un aumento significativo en la proteinuria o una disminución en el FG. La media de la presión arterial se mantuvo normal.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by the develop-ment of kidney cysts. Objectives: To assess the growth of kidney and cystic volume in patients treated with rapamycin compared with patients receiving the usual treatment for ADPKD; assess the occurrence of adverse effects associated with the use of sirolimus; evaluate changes in blood pressure, proteinuria and estimated glomerular filtration rate (eGFR). Materials and methods: For a 24-month period, 12 patients with ADPKD were randomly allocated to a sirolimus group (6 patients, received rapamycin, 2-3 mg/m2/day, max. 5 mg/day) and the other 6 patients were allocated to a control group (receiving conventional treatment). Results: Out of the 12 patients, the 6 patients in the sirolimus group had a total increase in kidney and cystic volume of 13% and 32%, respectively, by the end of the study. In the control group, the other 6 patients had increases of 11% and 23%, respectively. eGFR was normal in both groups. Baseline proteinuria was 7.3 mg/m2/hour and 6 mg/m2/hour in the sirolimus- and control groups, respectively. By the end of the study, it was normal in both groups. Three patients had high blood pressure at baseline, but it was normalized at 24 months. Adverse effects were: anemia, diarr-hea, and mouth sores. Conclusions: Sirolimus did not reduce kidney and cystic volume. No significant increase in proteinuria or decrease in eGFR were observed. Mean blood pressure remained normal.

Alterações salivares na disfunção renal crônica em ratos induzida por 5/6 de nefrectomia / Salivary alterations in chronic renal dysfunction in rats induced by 5/6 nephrectomy

A saliva é um fluído produzido e secretado pelas glândulas salivares. Ela desempenha um importante papel na homeostase dos indivíduos. Diversas doenças afetam a produção ou a composição da saliva secretada, dentre elas a doença renal crônica (DRC). A DRC é definida como um dano renal ou diminuição da função renal por um período igual ou superior a três meses. É classificada em estágios, sendo que em seu grau mais avançado existe a necessidade de terapias de hemodiálise ou transplante renal. Muitos são os estudos que buscaram manifestações orais, alterações de fluxo e composição salivares nestes pacientes, contudo quando buscamos na literatura, não encontramos trabalhos que utilizaram um modelo animal para o estudo de parâmetros de composição salivar na doença renal crônica. O objetivo deste estudo foi analisar alterações em alguns componentes na saliva de ratos estimulada por pilocarpina (1mg/Kg) ou isoproterenol (5mg/Kg), em um modelo de 5/6 de nefrectomia (IRC), comparando com um grupo controle positivo (Sham) e outro controle negativo (C) em dois tempos experimentais de 8 e 12 semanas. A nefropatia crônica foi obtida com 5/6 de nefrectomia pela ligadura de dois ramos da artéria renal esquerda e nefrectomia total direita e os grupos Sham foram submetidos à simulação do procedimento cirúrgico. Ao final dos tempos experimentais, amostras de sangue e saliva foram coletadas de todos os grupos e foram analisados: fluxo salivar, concentração de proteína total, atividades das enzimas amilase e peroxidase, ácido siálico livre e total, bem como as dos íons: cálcio, fósforo, sódio, potássio e concentração de ureia salivar. Foram analisadas também as concentrações séricas de ureia e creatinina.

Observamos aumento significativo das concentrações séricas de ureia e creatinina e das concentrações salivares de ureia nos grupos IRC em ambos os tempos experimentais; Com estímulo de pilocarpina, observamos que com 8 semanas ocorreu diminuição significativa da atividade da enzima amilase e com 12 semanas ocorrem aumentos significativos da concentração de proteínas totais e atividade da enzima peroxidase. No estímulo com isoproterenol, observamos que com 8 semanas ocorrem diminuições significativas das atividades das enzimas amilase e peroxidase, com 12 semanas ocorreu diminuição significativa do fluxo salivar do grupo IRC em relação ao grupo Sham, aumento significativo da atividade da enzima amilase e diminuição significativa da atividade da enzima peroxidase no grupo IRC em relação aos grupos controle e sham. Concluímos que o período de 12 semanas pós-cirurgia apresentou maiores alterações da saliva coletada tanto pelo estímulo simpático quanto pelo estímulo parassimpático, devendo este período ser utilizado nas futuras análises em glândulas salivares.

Saliva is a fluid produced and secreted by the salivary glands. It plays an important role in the homeostasis of individuals. Several diseases affect the production or composition of saliva secreted, among them chronic kidney disease (CKD). CKD is defined as a kidney damage or decreased kidney function for a three months exceeding period. It is classified in stages, and in its most advanced level there is a need for hemodialysis therapies or kidney transplantation. Many studies have sought oral manifestations, changes in salivary flow and composition in these patients, however when we look at the literature, we did not found studies that used an animal model for the study of salivary composition in chronic kidney disease. The aim of this study was to analyze changes in some components in the saliva of rats stimulated by pilocarpine (1mg/Kg) or isoproterenol (5mg/kg) in a model of 5/6 nephrectomy (CRF), compared with a positive control group (Sham) and a negative control (C) at two time period of 8 and 12 weeks. The chronic nephropathy was obtained with 5/6 nephrectomy by ligation of two branches of the left renal artery and right radical nephrectomy and Sham groups underwent surgery simulation. At the end of the experimental period, blood and saliva samples were collected from all groups and were analyzed: salivary flow rate, total protein concentration, activities of amylase and peroxidase, free and total sialic acid, as well as the ions calcium, phosphorus, sodium, potassium and urea concentration in saliva

We also evaluate the serum concentrations of urea and creatinine. We observed a significant increase in serum urea and creatinine concentrations and salivary urea in IRC groups in both experimental times; Under pilocarpine stimulation, we found a significant decrease in the activity of the enzyme amylase 8 weeks after the surgery. 12 weeks after the surgery increase in the total protein concentration and peroxidase activity were observed; Under stimulation with isoproterenol, we observed decreases in the activities of amylase and peroxidase after 8 weeks; 12 weeks after the surgery we found decrease in salivary flow compared to the sham group, increase in the activity of the enzyme amylase and decrease of the peroxidase activity in CRF group when compared to control and sham groups. We conclude that the period of 12 weeks after surgery showed greater changes in saliva collected both by sympathetic stimulation and by parasympathetic stimulation, and this period should be used in future analyzes in salivary glands.

Hallazgos bucales en niños con enfermedad bucal / Buccal finding in children with renal disease

La frecuencia e incidencia de enfermedades renales en niños ha sido documentada, destacándose las disfunciones tubulares, acidosis tubular, insuficiencia renal crónica, litiasis renal, entre otras. El objetivo de la investigación fue caracterizar los hallazgos bucales en niños de 1 a 13 años con enfermedad renal. Se realizó una investigación de tipo descriptiva con diseño transversal durante enero-abril de 2010, en el Servicio de Nefrología Pediátrica de la Ciudad Hospitalaria "Dr. Enrique Tejera", en Valencia-Estado Carabobo, Venezuela, se evaluaron 50 pacientes con edad promedio 6.85 años, con diversas enfermedades renales, la mayoría con hipercalciuria (58%) y sin otro compromiso sistémico. Los hallazgos bucales encontrados fueron hipoplasias de esmalte 30%, caries dental 36%, retardo en la erupción 16%, maloclusiones 10% y lengua geográfica 6%; ningún paciente presentó cálculo dental. Un dato importante fue que 44% de los pacientes nunca habían asistido a consulta odontológica. Se concluye que los hallazgos bucales con mayor frecuencia encontrados en niños con enfermedad renal fueron hipoplasias del esmalte, caries dental y retardo en la erupción dentaria, destacándose el desinterés por parte de los pacientes a la consulta odontológica

The frequency and incidence of renal disease in children had been documented, highlighting tubular dysfunctions, tubular acidosis, renal insufficiency, renal lithiasis, among others. The aim of this investigation was to characterize the buccal findings in children of 1 to 13 years old with renal disease. The investigation was a descriptive type, in a transversal design during january-april of 2010, in the Pediatric Nephrologic Service of the Hospital City "Dr. Enrique Tejera", in Valencia, Carabobo State, Venezuela, there were 50 patients with a mean age 6.85 years old, with hypercalciuria in 56% with no other systemic disease. The buccal findings were enamel hypoplasia 30%, dental caries 36%, delay eruption 16%, maloclussion 10% and geographic tongue 6%; none of the patients presented dental calculus. An important data was that 44% of the patients never had assisted to a dental appointment. The conclusions of this study are that the buccal findings more seen in children with renal disease are enamel hypoplasias, dental caries and delay eruption, underlying the lack of interest of the patients to the dental consult

Displasia renal em cão da raça Rotweiller / Renal dysplasia in a dog breed Rotweiller

Descreveram-se os achados clínicos e patológicos de um caso de displasia renal em um cão da raça Rotweiller com oito meses de idade. O animal apresentou vômitos, emagrecimento, polidpsia e poliúria. Houve elevação sanguínea de creatinina, cálcio e da fosfatase alcalina. À necropsia, notaram-se os rins diminuídos de tamanho, com estruturas císticas proeminentes sobre a superfície natural do órgão e, ao corte, firmes e com estruturas císticas distribuídas pelo parênquima. Na avaliação histológica, havia glomérulos imaturos, fibroplasia intersticial e dilatação cística tubular.

In this study we describe the clinical and pathological findings of a case of renal dysplasia in a dog from the Rottweiler breed at 8 months of age. The animal presented vomiting, weight loss, polydipsia and polyuria. There was an increase of blood creatinine, calcium, and alkaline phosphatase. At necropsy it was noted that the kidneys were reduced in size, with prominent cystic structures on the natural surface of the body and the cutting and firm with cystic structures distributed throughout the parenchyma. The histological evaluation was immature glomeruli, interstitial fibroplasia and tubular cystic dilation.

A case of late-onset oligomeganephronia / Um caso de oligomeganefronia de início tardio

A 33-year old caucasian man was investigated for pain in the right flank, proteinuria, hemathuria and an elevated serum creatinine level. He also presented an abnormal ultrasonography, which revealed asymmetric kidneys. Through renal biopsy, the diagnosis of oligomeganephronia (OMN) was confirmed. OMN is a very rare form of renal hypoplasia, and late-onset in adulthood is even rarer. In the pediatric population, OMN leads to end-stage-renal-failure(ESRF) in a few years. This is the sixth case related in the literature of a late-onset OMN who have not yet developed ESRF.

Paciente do sexo masculino, 33 anos de idade, foi investigado por apresentar um quadro de dor abdominal em flanco direito, proteinúria, hematúria e níveis elevados de creatinina sérica. A ultrassonografia evidenciou rins de tamanhos assimétricos, e a biópsia renal confirmou o diagnóstico de oligomeganefronia (OMN). OMN é uma forma muito rara de hipoplasia renal, e ainda mais infrequente na faixa etária adulta. Na população pediátrica, OMN culmina com insuficiência renal terminal em poucos anos. Este é o sexto caso de oligomeganefronia de início tardio relatado na literatura, que ainda não teve evolução para insuficiência renal crônica.

Factores de riesgo de enfermedad renal crónica / Chronic renal disease risk factors / Fatores de risco de doença renal crônica

La enfermedad renal crónica es una patología muy frecuente asociado con múltiples coomorbilidades. La fisiopatología del daño endotelial es diferente en los pacientes con enfermedad renal crónica y en este es un campo de investigación en la actualidad. El propósito de esta revisión es analizar la evidencia actual alrededor de los diferentes factores de riesgo asociados con la aparición de enfermedad renal crónica...

The chronic renal disease is a very frequent pathology associated with multiple comorbidities. The pathophysiology of the endothelial damage is different in chronic renal disease patients and this is presently a research domain. The aim of this review is to analyze the current evidence around the different risk factors associated with the appearing of chronic renal disease...

A doença renal crônica é uma patologia muito frequente associada com múltiplas coomorbilidades. A fisiopatologia do dano endotelial é diferente nos pacientes com doença renal crônica e este é um campo de pesquisa na atualidade. O propósito desta revisão é analisar a evidência atual ao redor dos diferentes fatores de risco associados com a aparição de doença renal crônica...