Insuficiencia renal aguda

PROTOCOLOS TERAPEUTICOS. Insuficiéncia renal aguda. SOSPECHA Ausencia de diuresis espontánea en las prirneras 36 h. de vida. Existencia de factores de riesgo por la anamnesis (hipoxia, hemorragia, sepsis, etc.)...

Cytokine accumulation in osteitis fibrosa of renal osteodystrophy

Bone marrow fibrosis occurs in association with a number of pathological states. Despite the extensive fibrosis that sometimes characterizes renal osteodystrophy, little is known about the factors that contribute to marrow accumulation of fibrous tissue. Because circulating cytokines are elevated in uremia, possibly in response to elevated parathyroid hormone levels, we have examined bone biopsies from 21 patients with end-stage renal disease and secondary hyperparathyroidism. Bone sections were stained with antibodies to human interleukin-1alpha (IL-1alpha), IL-6, IL-11, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-ß (TGF-ß) using an undecalcified plastic embedding method. Intense staining for IL-1alpha, IL-6, TNF-alpha and TGF-ß was evident within the fibrotic tissue of the bone marrow while minimal IL-11 was detected. The extent of cytokine deposition corresponded to the severity of fibrosis, suggesting their possible involvement in the local regulation of the fibrotic response. Because immunoreactive TGF-ß and IL-6 were also detected in osteoblasts and osteocytes, we conclude that selective cytokine accumulation may have a role in modulating bone and marrow cell function in parathyroid-mediated uremic bone disease.

Early initiation of dialysis: mortality and renal function recovery in acute kidney injury patients

INTRODUCTION: The decision of when to start dialysis in Acute Kidney Injury (AKI) patients with overt uremia is strongly established, however, when blood urea nitrogen (BUN) levels is < 100 mg/dL the timing of initiation of dialysis remains uncertain. Purpose: The aim of this study was to assess mortality and renal function recovery AKI patients started on dialysis at different BUN levels. METHODS: This was a retrospective study performed at Medical School Hospital, São Paulo, Brazil, enrolling 86 patients underwent to dialysis. RESULTS: Dialysis was started when BUN < 75 mg/dl in 23 patients (Group I) and BUN > 75 mg/dl in 63 patients (Group II). Hypervolemia and mortality were higher in Group I than in Group II (65.2% vs. 14.3% - p < 0.05, 39.1% vs. 68.9%- p < 0.05, respectively). Among survivors, the rate of renal function recovery was higher in Group I (71.4% and 36.8%, respectively - p < 0.05). Multivariate analysis showed that sepsis, age > 60 years, peritoneal dialysis and BUN > 75 mg/dl at dialysis initiation were independently related with mortality. CONCLUSIONS: Lower mortality and higher renal function recovery rates were associated with early dialysis initiated at lower BUN leves in AKI patients.

Computerized Tomography Contrast Induced Nephropathy (CIN) among adult inpatients

Introduction: Contrast induced nephropathy (CIN) is one of the complications of the use of intravascular contrast agents, being defined as a reduction of the glomerular filtration rate caused by the iodinated contrast. Most CIN data derive from the cardiovascular literature, which identified as the most consistent risk factors pre-existing chronic renal insufficiency and diabetes mellitus. However, these studies limit their conclusions to a more specific patient population. Computerized tomography as a cause of CIN has been studied less often. Objective: To report on the incidence of computerized tomography contrast induced nephropathy (CIN) in an inpatient population of a tertiary general hospital, identifying potentially avoidable risk factors. Methods: We performed a prospective cohort study with inpatients admitted at a tertiary hospital requiring contrast-induced CT. The primary outcome was the development of CIN, measure by the alteration of serum creatinine or glomerular filtration rate in 48 or 72 hours. Through clinical interview, we verified possible risk factors and preventive measures instituted by the medical team and their association with development of CIN. Results: Of a total of 410 patients, 35 (8.5%) developed CIN. There was a positive correlation between CIN and the presence of diabetes mellitus (OR = 2.15; 95%CI 1.35-4.06; p = 0.02), heart failure (OR = 2.23; 95%CI 1.18-8.8; p = 0.022), and renal failure (OR = 3.36; 95%CI 1.57- 7.17; p = 0.002) Conclusion: Incidence of CIN varies according to the population. Diabetes mellitus, heart failure and renal failure were independent risk factors for the development of CT-associated CIN. Further studies are needed to better understand and treat CT-associated CIN.

Pkd1 transgenic mice: Adult model of polycystic kidney disease with extrarenal and renal phenotypes

While high levels of Pkd1 expression are detected in tissues of patients with autosomal dominant polycystic kidney disease (ADPKD), it is unclear whether enhanced expression could be a pathogenetic mechanism for this systemic disorder. Three transgenic mouse lines were generated from a Pkd1-BAC modified by introducing a silent tag via homologous recombination to target a sustained wild type genomic Pkd1 expression within the native tissue and temporal regulation. These mice specifically overexpressed the Pkd1 transgene in extrarenal and renal tissues from approximately 2- to 15-fold over Pkd1 endogenous levels in a copy-dependent manner. All transgenic mice reproducibly developed tubular and glomerular cysts leading to renal insufficiency. Interestingly, Pkd1(TAG) mice also exhibited renal fibrosis and calcium deposits in papilla reminiscent of nephrolithiasis as frequently observed in ADPKD. Similar to human ADPKD, these mice consistently displayed hepatic fibrosis and approximately 15% intrahepatic cysts of the bile ducts affecting females preferentially. Moreover, a significant proportion of mice developed cardiac anomalies with severe left ventricular hypertrophy, marked aortic arch distention and/or valvular stenosis and calcification that had profound functional impact. Of significance, Pkd1(TAG) mice displayed occasional cerebral lesions with evidence of ruptured and unruptured cerebral aneurysms. This Pkd1(TAG) mouse model demonstrates that overexpression of wildtype Pkd1 can trigger the typical adult renal and extrarenal phenotypes resembling human ADPKD.

Identification de facteurs de risque d'insuffisance rénale en trauma

Contexte: la survenue d’IRA chez les patients ayant subi un traumatisme est une problématique qui a été peu étudiée jusqu’à ce jour. La présence de cette atteinte rénale a été démontrée comme étant associée à un risque accru de morbidités et de mortalité chez les sujets atteints. Objectifs: identifier les facteurs prédictifs d’insuffisance rénale ou plus récemment appelée atteinte rénale dans cette population particulière et tenter de trouver des facteurs qui peuvent être mesurés dans les premières heures de la prise en charge du patient. Aussi, nous avons cherché à savoir si l’injection de produit de contraste est associée à un risque accru d’insuffisance rénale aiguë dans cette population. Méthodes et résultats: la recherche a eu lieu à l’Hôpital du Sacré-Coeur de Montréal, un centre de traumatologie tertiaire en milieu urbain. Nous avons utilisé le registre des patients hospitalisés en traumatologie dans notre centre hospitalier entre 2002 et mars 2007 de même que les banques de données de laboratoire et de radiologie pour obtenir les données sur la créatinine et les examens avec produits de contraste. Finalement, une revue de dossiers structurée fut conduite pour recueillir le reste de l’information requise. L’incidence d’IRA dans la population étudiée est estimée à environ 5 %. Une analyse cas témoins fut conduite pour identifier les facteurs prédictifs d’IRA. Quarante-neuf cas d’IRA diagnostiqués par le médecin traitant et 101 témoins sélectionnés au hasard ont été analysés. Les facteurs prédictifs suivants ont été identifiés à l’analyse univariée : la première valeur de créatinine obtenue (p<0,001), l’instabilité hémodynamique (p<0,001), les antécédents d’insuffisance rénale chronique tels que notés dans le dossier par le médecin traitant (p=0,009), une maladie cardiaque (p=0,007), une chirurgie dans les 48 premières heures suivant le traumatisme (p=0,053), le niveau de gravité du traumatisme (Injury Severity Score) (p=0,046) et l’injection de produit de contraste au cours des 48 heures suivant le trauma (p=0,077). Parmi ces facteurs, deux ont été identifiés comme prédicteurs indépendants d’IRA à l’analyse multivariée. Une des valeurs était la première valeur de créatinine obtenue RC = 6,17 (p<0,001, IC95 % 2,81 – 13,53) pour chaque augmentation de 0.5mg/dL de créatinine. L’autre facteur était la présence d’instabilité hémodynamique RC 11,61 (p<0,001, IC95 % 3,71 – 36,29). Conclusion: des informations obtenues tôt dans la prise en charge du patient permettent de prédire le risque d’IRA chez ces patients. L’administration de contraste (intraveineuse ou intra-artérielle) ne s’est pas avérée un facteur indépendant de prédiction d’insuffisance rénale aiguë dans cette population dans le modèle multivarié.

Facteurs de risque d’insuffisance rénale chronique chez les greffés cardiaques : du phénotype aux tests pharmacogénomiques

L’insuffisance rénale chronique (IRC) est un problème majeur fréquemment rencontré chez les greffés cardiaques. Les inhibiteurs de la calcineurine, pierre angulaire de l’immunosuppression en transplantation d’organes solides, sont considérés comme une des principales causes de dysfonction rénale postgreffe. Plusieurs autres éléments tels que les caractéristiques démographiques, cliniques et génétiques du receveur contribuent également au phénomène, mais il demeure plutôt difficile de déterminer quels sont les patients les plus à risque de développer une IRC après la transplantation. Ainsi, la découverte de nouveaux marqueurs génétiques de dysfonction rénale pourrait un jour mener à l’individualisation de la thérapie immunosuppressive selon le profil génétique de chaque patient. Or, on ne connaît pas les opinions des greffés à l’égard des tests pharmacogénomiques et l’on ne sait pas si celles-ci diffèrent des opinions exprimées par les individus en bonne santé. Cette thèse de doctorat a donc pour objectifs : 1- De décrire l’évolution de la fonction rénale à très long terme après la transplantation et d’identifier les marqueurs démographiques et phénotypiques associés à l’IRC postgreffe cardiaque; 2- D’identifier les marqueurs génétiques associés à la néphrotoxicité induite par les inhibiteurs de la calcineurine; 3- D’évaluer et de comparer les attitudes des patients et des individus en bonne santé par rapport à l’intégration clinique potentielle des marqueurs pharmacogénomiques. Trois projets ont été réalisés pour répondre à ces questions. Le premier repose sur une analyse rétrospective de l’évolution de la fonction rénale chez les patients greffés au sein de notre établissement entre 1983 et 2008. Nous y avons découvert que le déclin de la fonction rénale se poursuit jusqu’à 20 ans après la transplantation cardiaque et que les facteurs de risque d’IRC incluent entre autres l’âge avancé, le sexe féminin, la dysfonction rénale prégreffe, l’hypertension, l’hyperglycémie et l’utilisation de la prednisone. Le deuxième projet est une étude pharmacogénomique s’intéressant aux déterminants génétiques de la néphrotoxicité induite par les inhibiteurs de la calcineurine. Elle nous a permis d’illustrer pour la première fois qu’un polymorphisme génétique lié à PRKCB (gène codant pour la protéine kinase C-β) est associé avec la fonction rénale des patients greffés cardiaques, alors que cela n’est probablement pas le cas pour les polymorphismes de TGFB1 (gène codant pour le transforming growth factor-β1). La troisième section de cette thèse rapporte les résultats d’un questionnaire dont le but était de comparer les attitudes envers les tests pharmacogénomiques parmi un groupe de personnes en bonne santé, de patients greffés cardiaques et de patients souffrant d’insuffisance cardiaque. Cette étude a démontré que, bien que l’enthousiasme pour la pharmacogénomique soit partagé par tous ces individus, les craintes liées à la confidentialité et aux répercussions potentielles sur l’emploi et les assurances sont plus prononcées chez les personnes en bonne santé. En résumé, les travaux issus de cette thèse ont révélé que l’identification précoce des patients greffés cardiaques les plus susceptibles de présenter une détérioration de la fonction rénale ainsi que l’adoption d’une approche thérapeutique individualisée reposant notamment sur les applications cliniques de la pharmacogénomique pourraient éventuellement permettre de freiner cette complication postgreffe.

Agregação familiar e resultados maternos e perinatais da pré-eclâmpsia severa em população do Rio Grande do Norte

To determine whether there is familiar aggregation of severe preeclampsia in a Brazilian population from Rio Grande do Norte and to characterize the maternal and perinatal outcomes in the studied population. Methods: A case control study was performed with 412 participants who were admitted at Maternidade Escola Januário Cicco (MEJC) for medical care. Of these, 264 subjects presented normal blood pressure and 148 were cases. Cases were composed of eclampsia (n=47), HELLP Syndrome (n=85) and Eclampsia associated with HELLP syndrome (n=16). The diagnosis of these illness were based on the citeria developed by National High Blood Pressure Education Program Working (2000). An interview was performed with each subject and questions related to personal and familiar history of hypertension, preeclampsia, HELLP syndrome and eclampsia. Statistical analysis was performed and comparison of median and mean between cases and controls were performed, with the level of significance of 5%. The Odds-Ratio was determined to estimate the risk of preeclampsia within the families. Results: There were no difference in the demographic data between cases and controls. Previous history of chronic hypertension and preeclampsia was more frequent in the case group. Headaches were more frequent in eclampsia and epigastric pain in the HELLP syndrome cases. Bleeding and oliguria were more frequently found in the eclampsia associated with HELLP syndrome cases. Acute Renal insufficiency was a common complication in the case group, but these cases did not evolve to chronic renal insufficiency. The maternal mortality was 0.4% and the perinatal mortality was high, 223 per 1,000 live births. The 111 risk of a woman to develop preeclampsia whose mother has hypertension or had preeclampsia was respectively 2.5 and 3.5. This risk was increased 5 times, when a sibling has hypertension and 6 times when both sibling and mother had previous history of preeclampsia. Conclusions: This study confirms that there is familiar aggregation of preeclampsia in this Brazilian population. The potential for cardiovascular complications due to development of chronic hypertension indicates the need of closely follow up of women who develop preeclampsia

Redução da morbi-mortalidade na síndrome de hellp completa com o uso de altas doses de dexametasona

Objective: To determine the clinical maternal and neonatal outcomes in HELLP syndrome patients treated with dexamethasone who either developed renal injury or renal insufficiency and to identify predictive values of urea and creatinine for the identification of subjects with HELLP syndrome at risk of developing renal insufficiency. Methods: Non-radomized intervention study of dexamethasone use in HELLP syndrome. A total of 62 patients were enrolled at Maternidade Escola Januário Cicco (MEJC). Patients received a total of 30 mg of dexamethasone IV, in three doses of 10 mg every 12 hours. A clinical and laboratory follow up were performed at 24, 48 and 72 hours. Patients were followed up to 6 months after delivery. Patients were grouped in accordance to renal function, i.e, normal and some type of renal lesion. Renal lesion was considered when creatinine was equal or greater than 1.3 mg/dl and diuresis less than 100 ml in 4 hours period and renal insufficiency was defined when dialysis was needed. Results: A total of 1230 patients with preeclampsia were admitted at MEJC. Of those 62 (5%) developed HELLP syndrome. There was no statistical difference in the groups with renal involvement or normal renal function with respect to the demographics, type of anesthesia used and delivery, and weight of the newborn. An improvement in the AST, ALT, LDH, haptoglobine, antithrombine, fibrinogenen and platelets was observed within 72 hours after dexamethosone use. There was a significant increase in the diuresis within the interval of 6 hours before the delivery and 24 hours after it. Of the 62 patients, 46 (74. 2%) had normal renal function and 16 (25.8%) evolved with renal lesion, with 5 (8.1%) needing dialysis. These 5 patients who received dialysis recovered the xi renal function. The delay in administering dexamethasone increased in 4.6% the risk of development of renal insufficiency. Patients with renal insufficiency had received significantly more blood products than subjects without renal lesion (p=0.03). Diuresis, leukocytes, uric acid, urea, creatinine were significantly different between the groups with normal renal function, renal lesion and renal insufficiency. The levels of creatinine 1.2mg/dl and uric acid 51mg/dl, at admission are predictive of subjects who will evolve with renal lesion (p<0.001). Maternal mortality was 3.2%. None of the subjects with renal insufficiency evolved with chronic renal disease. Conclusions: Dexamethasone in patients with HELLP syndrome seems to reduce significantly the hepatic microthrombosis and normalize hemostasis as seen by improvement of liver function. Renal injury can be considered, in HELLP syndrome, when creatinine levels are greater than 1.3 mg/dl and diuresis less than 100 ml/h in interval of 4 hours. The level of creatinine greater than 1.2 mg/dl and urea greater than 51mg/dl are predictive of subjects with HELLP syndrome who will develop renal injury. Patients who receive more red cell packs develop renal insufficiency. Finally, the delay in administering dexamethasone increases the risk of developing renal insufficiency

MICROBIOLOGICAL CONTAMINATION of A HEMODIALYSIS CENTER WATER DISTRIBUTION SYSTEM

The microbiological monitoring of the water used for hemodialysis is extremely important, especially because of the debilitated immune system of patients suffering from chronic renal insufficiency. To investigate the occurrence and species diversity of bacteria in waters, water samples were collected monthly from a hemodialysis center in upstate São Paulo and tap water samples at the terminal sites of the distribution system was sampled repeatedly (22 times) at each of five points in the distribution system; a further 36 samples were taken from cannulae in 19 hemodialysis machines that were ready for the next patient, four samples from the reuse system and 13 from the water storage system. To identify bacteria, samples were filtered through 0.22 mu m-pore membranes; for mycobacteria, 0.45 mu m pores were used. Conventional microbiological and molecular methods were used in the analysis. Bacteria were isolated from the distribution system (128 isolates), kidney machine water (43) and reuse system (3). Among these isolates, 32 were Gram-positive rods, 120 Gram-negative rods, 20 Gram-positive cocci and 11 mycobacteria. We propose the continual monitoring of the water supplies in hemodialysis centers and the adoption of effective prophylactic measures that minimize the exposure of these immunodeficient patients to contaminated sources of water.

Tratamento da síndrome do roubo devido a fístula arteriovenosa para hemodiálise em membro inferior por meio da técnica de ligadura arterial e revascularização distal (técnica de DRIL)

RESUMO A fístula arteriovenosa com bom fluxo sangüíneo é de fundamental importância para os pacientes portadores de insuficiência renal crônica em tratamento hemodialítico. Uma das complicações da fístula arteriovenosa é a síndrome do roubo, mas esta é de ocorrência incomum, e o seu tratamento está diretamente indicado quando há sintomas manifestos. Vários métodos foram propostos para sua correção nos membros superiores, sendo considerada a revascularização distal com ligadura arterial o procedimento de escolha. Neste relato de caso inédito, descreve-se o tratamento da síndrome do roubo de uma fístula arteriovenosa realizada em membro inferior, tratada com sucesso por meio da mesma técnica indicada para os membros superiores.

Fatores de risco pré-operatórios para o desenvolvimento de Insuficiência Renal Aguda em cirurgia cardíaca

OBJETIVO:Avaliar os fatores de risco clínicos pré-cirurgicos para o desenvolvimento de Insuficiência Renal Aguda (IRA) em pacientes submetidos à cirurgia cardíaca. MÉTODO: Foram estudados, de modo prospectivo, 150 pacientes submetidos à cirurgia cardíaca, durante 21 meses consecutivos, havendo um leve predomínio de homens (57%), idade média de 56 ± 15 anos, sendo que 66% apresentavam insuficiência coronariana como principal diagnóstico e 34% valvulopatias. A mediana da creatinina sérica no período pré-operatório foi de 1,1 mg/dl. IRA foi definida como elevação de 30% da creatinina sérica basal. O protocolo de variáveis clínicas teve seu preenchimento iniciado 48 horas antes do procedimento cirúrgico e encerrado 48 horas após o mesmo, incluindo variáveis cardiológicas e não-cardiológicas, além de resultados laboratoriais. RESULTADOS: A IRA esteve presente em 34% dos casos. Após análise multivariada, presença de doença vascular periférica foi fator pré-operatório identificado. CONCLUSÃO: Os resultados obtidos nesse estudo permitiram sinalizar alguns fatores contributivos para o desenvolvimento de IRA em cirurgia cardíaca, o que pode possibilitar condutas clínicas simples para evitar a disfunção renal nestas situações e, conseqüentemente, redução da taxa de mortalidade. No presente trabalho, o tamanho da amostra talvez tenha impedido a identificação de outros fatores de risco significativos.

Influence of fluid volume variations on the calculated value of the left ventricular mass measured by echocardiogram in patients submitted to hemodialysis

The left ventricular mass (LVM) measurement is of major importance for renal patients, as ventricular hypertrophy is an important prognostic index. The echo-cardiogram of the ventricular mass is larger before than it is after hemodialysis, which can confuse data interpretation. The aim of this work is to study the influence of alterations in fluid volume on the variations in measurements of ventricular mass observed during the course of a hemodialysis. Sixteen patients with chronic renal insufficiency in hemodialysis were evaluated at the Dialysis Unit of the University Hospital-UNESP, Botucatu, São Paulo State. The left ventricular mass was calculated from echocardiograms taken before and after hemodialysis and simultaneous ultra-filtration (12 patients: UF GROUP) and before and after hemodialysis isovolemic phase with sequential ultra-filtration (10 patients: ISO GROUP). Six of these patients were submitted to measurements of left ventricular mass before and after hemodialysis in both isovolemic and simultaneous ultra-filtration procedures. In the UF group, there was significant reduction in the following parameters before and after dialysis: diastolic diameter from 54.0 +/- 6.0 mm to 45.6 +/- 7.6 mm; left ventricular mass from 342 +/- 114 g to 265 +/- 117 g; and its respective index (IMVE) from 214 +/- 68 g/m(2) to 168 +/- 71 g/m(2). The ISO group showed no statistically significant variation. The behavior of the variables of six patients submitted to both observations confirm these results. In conclusion, the variations in echocardiogram measurements of the left ventricular mass relating to hemodialysis appear to be induced by alterations of the volemic condition.

Early initiation of dialysis: mortality and renal function recovery in acute kidney injury patients

INTRODUÇÃO: A decisão de quando iniciar a diálise em pacientes com lesão renal aguda (LRA) que apresentam síndrome urêmica está bem estabelecida, entretanto, com ureia < 200 mg/dl o melhor momento para iniciar a diálise torna-se incerto. OBJETIVO: Este estudo teve como objetivo avaliar a mortalidade e a recuperação da função renal em pacientes com LRA, cujo início da diálise ocorreu em diferentes níveis de ureia. MÉTODOS: Estudo retrospectivo desenvolvido em hospital escola, no estado de São Paulo, Brasil, envolvendo 86 pacientes submetidos à diálise. RESULTADOS: A diálise foi iniciada com uréia > 150 mg/dl em 23 pacientes (grupo I) e uréia > 150 mg/dl em 63 pacientes (grupo II). Hipervolemia e mortalidade foram mais frequentes no grupo I que no grupo II (65,2 x 14,2% - p < 0,05; 39,1 x 68,9% - p < 0,05, respectivamente). Entre os sobreviventes, a recuperação renal foi maior no grupo I (71,4 e 36,8%, respectivamente, p < 0,05). A análise multivariada mostrou risco independente de mortalidade relacionado à sepse, idade > 60 anos, diálise peritoneal e uréia > 150 mg/dl no início da diálise. CONCLUSÃO: Menor mortalidade e maior recuperação renal estão associadas com o diálise iniciada precocemente, conforme baixos níveis de ureia, em pacientes com LRA.

Tempo de circulação extracorpórea como fator risco para insuficiência renal aguda

OBJETIVO: A insuficiência renal aguda (IRA) no pósoperatório (PO) de cirurgia cardíaca é complicação grave. O objetivo deste trabalho é avaliar o tempo de circulação extracorpórea (CEC) como fator de risco para IRA. MÉTODO: Foram avaliados 116 pacientes de um único centro, submetidos a cirurgia cardíaca com CEC. Foram avaliados os dados demográficos, características clínicas, variáveis intra e pós-operatórias. A creatinina sérica e o clearance de creatinina foram avaliados até o 5ºPO. IRA foi definida como necessidade de diálise. Os pacientes foram estratificados em dois grupos: grupo CEC< 70 min e grupo CEC> 90min. RESULTADOS: O aumento médio da creatinina sérica no PO foi 0,18+0,41 no grupo CEC<70min e 0,42+0,44 no grupo CEC>90min (p=0,005). Diálise foi necessária em 1,3% dos pacientes do grupo CEC<70min, e em 12,5% do grupo CEC> 90min (p=0,018). O risco relativo para diálise foi 1,12 (IC 95%, 1,00-1,20) para CEC>90min. Não houve diferença para mortalidade (5,2 versus 7,5%, p=0,631). CONSLUSÃO: O desenvolvimento de IRA no pós-operatório de cirurgia cardíaca foi observado em pacientes com tempo de CEC superior a 90 minutos, embora o clearance de creatinina não tenha demonstrado alteração entre os grupos.