Evaluation of renal function in sickle cell disease patients in Brazil

The objective of this study was to investigate renal function in a cohort of 98 patients with sickle cell disease (SCD) followed up at a tertiary hospital in Brazil. Clinical and laboratory characteristics at the time of the most recent medical examination were analyzed. Renal function was evaluated by the estimation of glomerular filtration rate (GFR) by the criteria of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). We compared patients with normal GFR to patients with decreased GFR (<60 mL·min-1·(1.73 m²)-1) and hyperfiltration (>120 mL·min-1·(1.73 m²)-1). Comparison between patients according to the use of hydroxyurea and comparison of clinical and laboratory parameters according to GFR were also carried out. Average patient age was 33.8 ± 13.3 years (range 19-67 years), and 57 (58.1%) patients were females. The comparison of patients according to GFR showed that patients with decreased GFR (<60 mL·min-1·(1.73 m²)-1) were older, had lower levels of hematocrit, hemoglobin and platelets and higher levels of urea and creatinine. Independent risk factors for decreased GFR were advanced age (OR = 21.6, P < 0.0001) and anemia (OR = 39.6, P < 0.0001). Patients with glomerular hyperfiltration tended to be younger, had higher levels of hematocrit, hemoglobin and platelets and lower levels of urea and creatinine, with less frequent urinary abnormalities. Hydroxyurea, at the dosage of 500-1000 mg/day, was being administered to 28.5% of the patients, and there was no significant difference regarding renal function between the two groups. Further studies are required to establish the best therapeutic approach to renal abnormalities in SCD.

Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease

Circulating microRNAs (miRNAs) may represent a potential noninvasive molecular biomarker for various pathological conditions. Moreover, the detection of circulating miRNAs can provide important novel disease-related information. In particular, inflammation-associated miR-155 and endothelial-enriched miR-126 are reported to be associated with vascular homeostasis. Vascular damage is a common event described in end-stage renal disease (ESRD). We hypothesized that miR-155 and miR-126 may be detectable in the circulation and serve as potential biomarkers for risk stratification. In this study, we assessed miR-155 and miR-126 in the plasma of 30 ESRD patients and 20 healthy controls using real-time quantification RT-PCR. The circulating levels of miR-155 and miR-126 were significantly reduced in patients with ESRD compared to healthy controls. However, there was no significant difference of circulating miR-155 and miR-126 levels between prehemodialysis and posthemodialysis patients. Furthermore, both circulating miR-126 and miR-155 correlated positively with estimated glomerular filtration rate (miR-126: r = 0.383, P = 0.037; miR-155: r = 0.494, P = 0.006) and hemoglobin (miR-126: r = 0.515, P = 0.004; miR-155: r = 0.598, P < 0.001) and correlated inversely with phosphate level (miR-126: r = -0.675, P < 0.001; miR-155: r = -0.399, P = 0.029). Pearson’s correlation was used to compare circulating levels of miRNAs with clinical parameters. These results suggested that circulating miR-155 and miR-126 might be involved in the development of ESRD. Further studies are needed to demonstrate the role of circulating miR-155 and miR-126 as candidate biomarkers for risk estimation.

Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg-1·day-1, sc) and progesterone (OVP, 1.7 mg·kg-1·day-1,sc). We assessed Na+ and Cl-fractional excretion (FENa+ and FECl-, respectively) and renal and plasma catecholamine release concentrations. FENa+, FECl-, water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+, FECl-, water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function.

Effect of castration on renal glycosaminoglycans and their urinary excretion in male and female rats with chronic renal failure

Glycosaminoglycans (GAGs) participate in a variety of processes in the kidney, and evidence suggests that gender-related hormones participate in renal function. The aim of this study was to analyze the relationship of GAGs, gender, and proteinuria in male and female rats with chronic renal failure (CRF). GAGs were analyzed in total kidney tissue and 24-h urine of castrated (c), male (M), and female (F) Wistar control (C) rats (CM, CMc, CF, CFc) and after 30 days of CRF induced by 5/6 nephrectomy (CRFM, CRFMc, CRFF, CRFFc). Total GAG quantification and composition were determined using agarose and polyacrylamide gel electrophoresis, respectively. Renal GAGs were higher in CF compared to CM. CRFM presented an increase in renal GAGs, heparan sulfate (HS), and proteinuria, while castration reduced these parameters. However, CRFF and CRFFc groups showed a decrease in renal GAGs concomitant with an increase in proteinuria. Our results suggest that, in CRFM, sex hormones quantitatively alter GAGs, mainly HS, and possibly the glomerular filtration barrier, leading to proteinuria. The lack of this response in CRFMc, where HS did not increase, corroborates this theory. This pattern was not observed in females. Further studies of CRF are needed to clarify gender-dependent differences in HS synthesis.

Extracellular vesicles: structure, function, and potential clinical uses in renal diseases

Interest in the role of extracellular vesicles in various diseases including cancer has been increasing. Extracellular vesicles include microvesicles, exosomes, apoptotic bodies, and argosomes, and are classified by size, content, synthesis, and function. Currently, the best characterized are exosomes and microvesicles. Exosomes are small vesicles (40-100 nm) involved in intercellular communication regardless of the distance between them. They are found in various biological fluids such as plasma, serum, and breast milk, and are formed from multivesicular bodies through the inward budding of the endosome membrane. Microvesicles are 100-1000 nm vesicles released from the cell by the outward budding of the plasma membrane. The therapeutic potential of extracellular vesicles is very broad, with applications including a route of drug delivery and as biomarkers for diagnosis. Extracellular vesicles extracted from stem cells may be used for treatment of many diseases including kidney diseases. This review highlights mechanisms of synthesis and function, and the potential uses of well-characterized extracellular vesicles, mainly exosomes, with a special focus on renal functions and diseases.

More than 10 years survival with sequential therapy in a patient with advanced renal cell carcinoma: a case report

Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.

Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats

Exercise training (Ex) has been recommended for its beneficial effects in hypertensive states. The present study evaluated the time-course effects of Ex without workload on mean arterial pressure (MAP), reflex bradycardia, cardiac and renal histology, and oxidative stress in two-kidney, one-clip (2K1C) hypertensive rats. Male Fischer rats (10 weeks old; 150–180 g) underwent surgery (2K1C or SHAM) and were subsequently divided into a sedentary (SED) group and Ex group (swimming 1 h/day, 5 days/week for 2, 4, 6, 8, or 10 weeks). Until week 4, Ex decreased MAP, increased reflex bradycardia, prevented concentric hypertrophy, reduced collagen deposition in the myocardium and kidneys, decreased the level of thiobarbituric acid-reactive substances (TBARS) in the left ventricle, and increased the catalase (CAT) activity in the left ventricle and both kidneys. From week 6 to week 10, however, MAP and reflex bradycardia in 2K1C Ex rats became similar to those in 2K1C SED rats. Ex effectively reduced heart rate and prevented collagen deposition in the heart and both kidneys up to week 10, and restored the level of TBARS in the left ventricle and clipped kidney and the CAT activity in both kidneys until week 8. Ex without workload for 10 weeks in 2K1C rats provided distinct beneficial effects. The early effects of Ex on cardiovascular function included reversing MAP and reflex bradycardia. The later effects of Ex included preventing structural alterations in the heart and kidney by decreasing oxidative stress and reducing injuries in these organs during hypertension.

Multiple facets of HIV-associated renal disease

HIV infection has a broad spectrum of renal manifestations. This study examined the clinical and histological manifestations of HIV-associated renal disease, and predictors of renal outcomes. Sixty-one (64% male, mean age 45 years) HIV patients were retrospectively evaluated. Clinical presentation and renal histopathology were assessed, as well as CD4 T-cell count and viral load. The predictive value of histological lesion, baseline CD4 cell count and viral load for end-stage renal disease (ESRD) or death were determined using the Cox regression model. The outcomes of chronic kidney disease (CKD) and ESRD or death were evaluated by baseline CD4 cell count. The percent distribution at initial clinical presentation was non-nephrotic proteinuria (54%), acute kidney injury (28%), nephrotic syndrome (23%), and chronic kidney disease (22%). Focal segmental glomerulosclerosis (28%), mainly the collapsing form (HIVAN), acute interstitial nephritis (AIN) (26%), and immune complex-mediated glomerulonephritis (ICGN) (25%) were the predominant renal histology. Baseline CD4 cell count ≥200 cells/mm3 was a protective factor against CKD (hazard ratio=0.997; 95%CI=0.994-0.999; P=0.012). At last follow-up, 64% of patients with baseline CD4 ≥200 cells/mm3 had eGFR >60 mL·min-1·(1.73 m2)-1 compared to the other 35% of patients who presented with CD4 <200 cells/mm3 (log rank=9.043, P=0.003). In conclusion, the main histological lesion of HIV-associated renal disease was HIVAN, followed by AIN and ICGN. These findings reinforce the need to biopsy HIV patients with kidney impairment and/or proteinuria. Baseline CD4 cell count ≥200 cells/mm3 was associated with better renal function after 2 years of follow-up.

Impact of specimen adequacy on the assessment of renal allograft biopsy specimens

The Banff classification was introduced to achieve uniformity in the assessment of renal allograft biopsies. The primary aim of this study was to evaluate the impact of specimen adequacy on the Banff classification. All renal allograft biopsies obtained between July 2010 and June 2012 for suspicion of acute rejection were included. Pre-biopsy clinical data on suspected diagnosis and time from renal transplantation were provided to a nephropathologist who was blinded to the original pathological report. Second pathological readings were compared with the original to assess agreement stratified by specimen adequacy. Cohen's kappa test and Fisher's exact test were used for statistical analyses. Forty-nine specimens were reviewed. Among these specimens, 81.6% were classified as adequate, 6.12% as minimal, and 12.24% as unsatisfactory. The agreement analysis among the first and second readings revealed a kappa value of 0.97. Full agreement between readings was found in 75% of the adequate specimens, 66.7 and 50% for minimal and unsatisfactory specimens, respectively. There was no agreement between readings in 5% of the adequate specimens and 16.7% of the unsatisfactory specimens. For the entire sample full agreement was found in 71.4%, partial agreement in 20.4% and no agreement in 8.2% of the specimens. Statistical analysis using Fisher's exact test yielded a P value above 0.25 showing that - probably due to small sample size - the results were not statistically significant. Specimen adequacy may be a determinant of a diagnostic agreement in renal allograft specimen assessment. While additional studies including larger case numbers are required to further delineate the impact of specimen adequacy on the reliability of histopathological assessments, specimen quality must be considered during clinical decision making while dealing with biopsy reports based on minimal or unsatisfactory specimens.

Urine beta2-microglobulin is an early marker of renal involvement in LPI. (Virtsan beta2-mikroglobuliini on varhaisen vaiheen markkeri LPI-taudin munuaiskomplikaatioiden havaitsemisessa.)

Lysinurinen proteiini-intoleranssi (LPI) on suomalaiseen tautiperintöön kuuluva kationisten aminohappojen, arginiinin, ornitiinin ja lysiinin, kuljetushäiriö suolen ja munuaistubulusten basolateraalisilla kalvoilla. Arginiinin ja ornitiinin puute aiheuttaa häiriöitä ureasyklin toiminnassa, aterian jälkeistä hyperammonemiaa ja proteiiniaversiota. Lysiinin puute vaikuttaa mm. kasvuun ja puolustusmekanismeihin. Hoidossa keskeistä on vähäproteiininen ruokavalio ja L-sitrulliinilisä, joka parantaa ureasyklin toimintaa. Koska LPI-tauti on kuvattu vasta 1960-luvulla, sen luonnollinen kulku tunnetaan vielä huonosti. Tautiin liittyvistä komplikaatioista vakavimmat ovat toistaiseksi tuntemattomalla mekanismilla kehittyvä keuhkojen alveolaarinen proteinoosi ja munuaisongelmat. Suomalaisista LPI-potilaista noin kolmanneksella on havaittu merkkejä munuaisten vajaatoiminnasta, ja muutamilla potilailla munuaisongelmat ovat edenneet loppuvaiheen munuaistautiin (ESRD) saakka. Potilaiden munuaisongelmia tutkittiin viimeksi vuonna 2007. Tämän tutkimuksen tarkoitus oli selvittää, onko LPI-potilaiden munuaisfunktio olennaisesti muuttunut seuranta-aikana 2007-2013. LPI-potilaiden seuranta on valtakunnallisesti keskitetty Turun yliopistollisen keskussairaalan (Tyks) lastenklinikan aineenvaihduntapoliklinikalle. Seurannassa on 41 potilasta, jotka käyvät Tyks:ssä 1—2 kertaa vuodessa. Tässä tutkimuksessa analysoitiin näiden LPI-potilaiden sairaskertomuksia ja laboratoriotutkimuksia. Kiinnostuksen kohteena olivat erityisesti verenpaine, munuaisten toimintatestit, virtsan proteiini- ja aminohappopitoisuudet ja plasman sitrulliinipituisuus. Munuaisten vajaatoiminnan kehitystä arvioitiin seuraamalla seerumin kystatiini C:n, kreatiniinipitoisuuksien ja virtsan beta2-mikroglobuliinipitoisuuksien muutoksia ajan funktiona. Tutkimuksessa havaittiin, että seuranta-ajan loppuun mennessä suurimmalla osalla potilaista oli merkkejä munuaisten vajaatoiminnasta ja osalle potilaista oli kehittynyt vakava munuaisvaurio, joka vaati dialyysihoitoa tai munuaissiirron. Munuaisongelmien määrä oli lisääntynyt seuranta-aikana, vaikka potilaiden munuaisfunktiota oli seurattu säännöllisesti ja riskitekijöitä hoidettu. Sitrulliiniannostuksella ei näyttänyt olevan yhteyttä munuaisten vajaatoiminnan kehittymiseen. Munuaissiirtopotilaista yksi potilas menetti siirrännäisen, muutoin elinsiirtopotilaiden munuaisfunktio on säilynyt tyydyttävänä. Lisäksi havaittiin, että virtsan beeta-2-mikroglobuliinimäärityksellä pystytään havaitsemaan munuaisten vajaatoiminta varhaisessa vaiheessa tässä potilasryhmässä.

Insuficiência renal aguda nefrotóxica: prevalência, evolução clínica e desfecho

INTRODUÇÃO: A insuficiência renal aguda (IRA) nefrotóxica é frequente e importante causa de morbimortalidade. OBJETIVO: Avaliar a prevalência, o curso clínico e o desfecho da IRA nefrotóxica. PACIENTES e MÉTODOS: Coorte histórica realizada em um hospital de ensino terciário, no período de fevereiro a novembro de 1997. Foram incluídos pacientes acima de 12 anos, com diagnóstico de IRA, acompanhados pela equipe de Interconsulta de Nefrologia. Foram excluídos transplantados renais, portadores de insuficiência renal crônica, dialisados por intoxicação exógena e aqueles transferidos de hospital durante o tratamento. RESULTADOS: Dos 234 pacientes acompanhados, 12% apresentaram IRA nefrotóxica e 24%, IRA multifatorial associada ao uso de drogas nefrotóxica. Entre as comorbidades mais prevalentes, estão hipertensão arterial, hepatopatias, neoplasias, insuficiência cardíaca congestiva e diabetes mellitus. Quinze por cento necessitaram de diálise, e o tipo mais frequentemente usado foi hemodiálise venovenosa contínua; 42% eram oligúricos, 44,7% evoluíram para óbito e 33% recuperaram a função renal. Antibióticos, AINH e contraste radiológico foram as drogas nefrotóxicas mais prevalentes.Os medicamentos nefrotóxicos implicados foram, em ordem de frequência, vancomicina, aminoglicosídeos, aciclovir, quimioterápicos e contraste radiológico. Hepatopatia foi a única variável com significância estatística (p = 0,03, IC = 1,08 a 6,49) em análise multivariada. Na comparação entre IRA nefrotóxica e não nefrotóxica, houve aumento da mortalidade proporcionalmente aos dias de internação. CONCLUSÃO: IRA nefrotóxica é frequente, grave e deve ser continuamente monitorada, tanto ambulatorialmente quanto no ambiente intra-hospitalar.

A dimensão educativa da equipe de nefrologia na promoção de saúde bucal de crianças e adolescentes portadores de doença renal crônica

INTRODUÇÃO: Objetivou-se avaliar a dimensão educativa das percepções e atitudes de médicos, enfermeiros e auxiliares de enfermagem na saúde bucal de crianças e adolescentes portadores de insuficiência renal crônica (IRC) em três hospitais do Rio de Janeiro. MÉTODOS Realizou-se uma entrevista com perguntas abertas e fechadas com 43 profissionais de saúde. Os dados foram coletados e tabulados no programa SPSS 13.0. Empregou-se o teste Qui-quadrado, com nível de significância estatística p < 0,05. RESULTADOS: A média de idade foi 36,5 anos (± 11,3), com 80% do sexo feminino. A maioria dos médicos (71,4%, n = 10) e enfermeiros (72,4%, n = 21) acredita que esses pacientes podem ter alguma alteração bucal decorrente da doença, sendo perda de esmalte e descalcificação as mais citadas. Em relação à orientação sobre higiene bucal, pouco mais da metade da amostra respondeu que orienta seus pacientes no sentido de realizar escovação (72,7%, n = 16), usar fio dental (9%, n = 2), fazer bochecho (18,1%, n=4) e limpar a língua (9%, n = 2). Apenas 9% (n = 2) orientam a higiene após o uso de medicamentos. Quanto à necessidade de cuidados diferenciados para esses pacientes, 65,5% dos enfermeiros e auxiliares de enfermagem acreditam que estes devam ocorrer. Para a maioria dos médicos (57,1%, n = 8), não há necessidade de tais cuidados. Apesar disso, 78,6% (n = 11) dos médicos têm o hábito de encaminhar os pacientes a serviços odontológicos. CONCLUSÕES: Diante da metodologia empregada, concluiuse que a maioria dos profissionais de saúde têm algum conhecimento sobre saúde bucal, porém suas atitudes não refletem esse fato.

Estudo prospectivo observacional sobre a incidência de injúria renal aguda em unidade de terapia intensiva de um hospital universitário

OBJETIVO: Analisar comparativamente características clínicas e evolução de pacientes com e sem IRA adquirida em UTI geral de um hospital universitário terciário. MÉTODO: Estudo prospectivo observacional com 263 pacientes acompanhados diariamente durante a internação em UTI Geral do Hospital das Clínicas da Faculdade de Medicina de Botucatu no período de julho de 2007 a abril de 2008. RESULTADOS: A incidência de IRA foi de 31,2%. Os grupos foram semelhantes quanto ao sexo e diferiram quanto à etiologia da admissão em UTI (sepse: 31,7% x 13,1%, p < 0,0001, pós-operatório: 11% x 43%, p < 0,0001), idade (59,6 ± 18,1 x 50,2 ± 18,6 anos, p < 0,0001), APACHE II: (21 ± 11,1 x 11 ± 4,8, p = 0,002), oligúria (67,7% x 4,5%, p < 0,0001), presença de ventilação mecânica (81,7 x 57,7%, p = 0,0014), uso de drogas vasoativas (62,2 x 32,6%, p < 0,0001) e enfermaria de procedência (PS: 22 x 14,5%, p = 0,02 e centro cirúrgico: 42,7 x 62,6%, p = 0,03). Quanto às comorbidades, os grupos foram diferentes quanto à presença de HAS e IRC (42,6 x 35,9%, p = 0,005 e 15,8 x 2,1%, p = 0,04, respectivamente) e semelhantes quanto à presença de diabetes e ICC (19,5 x 11%, ns e 6 x 1,1%, ns, respectivamente). A mortalidade foi superior nos pacientes que contraíram IRA (62,1 x 16,5%, p < 0,0001). CONCLUSÃO: A incidência de IRA é elevada em UTI e presente em pacientes com parâmetros clínicos e índices prognósticos de maior gravidade, o que justifica a maior mortalidade observada neles.

Diálise peritoneal (DP) como tratamento da insuficiência cardíaca congestiva (ICC) em pacientes com doença renal crônica estágio IV

A Insuficiência Cardíaca Congestiva (ICC) é uma patologia com incidência crescente e que representa uma condição de grande impacto na saúde pública, com alta morbidade e mortalidade. O excesso de volume é uma complicação prevalente, presente em 80% dos pacientes atendidos com o diagnóstico de ICC. Estratégias farmacológicas e não farmacológicas no manejo terapêutico da ICC visam ao melhor manejo do volume e à redução no uso de diuréticos. A ultrafiltração extracorpórea tem evidenciado melhor controle de peso, redução nos dias de hospitalização e re-hospitalização dos pacientes com ICC. Neste artigo, relatamos dois casos atendidos no Hospital de Clínicas de Porto Alegre, relativos a pacientes com diagnóstico de ICC tratados com diálise peritoneal.

Trombólise tardia e espontânea de artéria renal sem comprometimento funcional

A aterosclerose em artérias renais é um importante fator desencadeante de tromboses com subsequente comprometimento da função e da viabilidade renal. A oclusão aguda das artérias renais por trombo ou êmbolo é causa incomum e potencialmente reversível de falência renal. Todavia, a duração e o grau de oclusão arterial compatível com a manutenção da viabilidade do parênquima renal ainda não estão bem estabelecidos, razão pela qual o diagnóstico precoce e a intervenção são importantes. O objetivo deste artigo é descrever um caso de trombose de artéria renal de rim funcional único, com lise espontânea e tardia do trombo seguida de recuperação funcional inesperada.