A sepse como causa de lesão renal aguda: modelo experimental

A sepse associada à falência de múltiplos órgãos como a lesão renal aguda (LRA) demonstra alta taxa de mortalidade no paciente crítico. Este estudo investigou a LRA induzida pela sepse em modelo experimental. Foram utilizados ratos da raça Wistar, adultos e machos divididos nos seguintes grupos: Controle - controle cirúrgico e Sepse - indução da sepse pela ligadura e punção do cécon (LPC). Foram avaliados os parâmetros fisiológicos (temperatura retal, pressão arterial média - PAM, glicemia sérica e fluxo urinário); a função renal (clearance de creatinina); o estresse oxidativo (peróxidos urinários e substâncias reativas com ácido tiobarbitúrico - TBARS) e realizada a análise histológica renal. O estudo conclui que a LRA induzida pela sepse caracteriza-se por lesão endotelial com disfunção hemodinâmica, liberação de mediadores inflamatórios e geração de espécies reativas de oxigênio (EROs) por células tubulares, caracterizando-se como uma associação de vasoconstrição renal de origem hemodinâmica e inflamatória.

La dénervation rénale unilatérale et le système kallikréine-bradykinine rénal chez le rat [Unilateral renal denervation and the renal kallikrein-bradykinin system in the rat].

AIM: The antihypertensive effect of renal denervation in hypertensive patients is partially explained by increased tubular natriuresis. To study the possible contribution of the kallikrein-kinin system (KKS) to this natriuretic effect in rats, we measured kallikrein activity (KA) and bradykinin concentrations (BK) in plasma and tissues. METHODS: To measure KA, we adapted and validated an enzymatic assay that cleaves para-nitroaniline (pNA) from the tripeptide H-D-Pro-Phe-Arg-pNA. The coefficients of variation (CV) within- and between-assays were less than 8% for plasma and tissue KA (plasma n=6 and 13; tissue n=4). Linear results for serially diluted samples confirmed the assay specificity. Tissue BK determinations were based on an established assay for plasma BK: tissue was homogenized and kinins extracted in ethanol, and BK was isolated by high-performance (HPLC) liquid chromatography and quantitated by radioimmunassay. Within- and between-assay CV for plasma BK were 18% (n=8 and n=35, respectively) and for BK in various tissues less than 16% (n=5-8). RESULTS: In male Wistar rats (n=3), plasma BK was 8.2±6.6 fmol/mL (mean±SD), and tissue BK (fmol/g) in 14 tested organs varied between brain (14±3) and submaxillary gland (521±315). Six days after left-sided unilateral renal denervation, left renal tissue BK (89±9) was not different from right renal BK (75±23). Similarly, KA was comparable in the two kidneys (left 18.0±1.5, right 15.8±1.4μkat/g). CONCLUSION: Any possible effect of unilateral renal denervation on the kidney's KKS would have to be bilateral.

Prediction of clinical response after renal angioplasty: respective value of renal Doppler sonography and scintigraphy.

OBJECTIVE: The goal of our study was to compare Doppler sonography and renal scintigraphy as tools for predicting the therapeutic response in patients after undergoing renal angioplasty. SUBJECTS AND METHODS. Seventy-four hypertensive patients underwent clinical examination, Doppler sonography, and renal scintigraphy before and after receiving captopril in preparation for renal revascularization. The patients were evaluated for the status of hypertension 3 months after the procedure. The predictive values of the findings of clinical examination, Doppler sonography, renal scintigraphy, and angiography were assessed. RESULTS: For prediction of a favorable therapeutic outcome, abnormal results from renal scintigraphy before and after captopril administration had a sensitivity of 58% and specificity of 57%. Findings of Doppler sonography had a sensitivity of 68% and specificity of 50% before captopril administration and a sensitivity of 81% and specificity of 32% after captopril administration. Significant predictors of a cure or reduction of hypertension after revascularization were low unilateral (p = 0.014) and bilateral resistive (p = 0.016) indexes on Doppler sonography before (p = 0.009) and after (p = 0.028) captopril administration. On multivariate analysis, the best predictors were a unilateral resistive index of less than 0.65 (odds ratio [OR] = 3.7) after captopril administration and a kidney longer than 93 mm (OR = 7.8). The two best combined criteria to predict the favorable therapeutic outcome were a bilateral resistive index of less than 0.75 before captopril administration combined with a unilateral resistive index of less than 0.70 after captopril administration (sensitivity, 76%; specificity, 58%) or a bilateral resistive index of less than 0.75 before captopril administration and a kidney measuring longer than 90 mm (sensitivity, 81%; specificity, 50%). CONCLUSION: Measurements of kidney length and unilateral and bilateral resistive indexes before and after captopril administration were useful in predicting the outcome after renal angioplasty. Renal scintigraphy had no significant predictive value.

Blood pressure changes after renal denervation at 10 European expert centers.

We did a subject-level meta-analysis of the changes (Δ) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P0.08). Normalization was a systolic BP of <140 mm Hg on office measurement or <130 mm Hg on 24-h monitoring and improvement was a fall of 10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20-μmol l(-1) increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment.

Volume of Traffic on the Primary Road System, 2002

The Office of Transportation Data, in cooperation with the Federal Highway Administration, prepares this biennial traffic report. This report is used by federal, state, and local governmental agencies in determining highway needs, construction priorities, route location and environmental impact studies, and the application of appropriate design standards. The general public uses this information in determining the amount of traffic that passes a given area as they make their development plans and propose land use changes. The above reflects only a few of the many technical uses for this data.

Body surface area and body weight predict total liver volume in Western adults.

Computed tomography (CT) is used increasingly to measure liver volume in patients undergoing evaluation for transplantation or resection. This study is designed to determine a formula predicting total liver volume (TLV) based on body surface area (BSA) or body weight in Western adults. TLV was measured in 292 patients from four Western centers. Liver volumes were calculated from helical computed tomographic scans obtained for conditions unrelated to the hepatobiliary system. BSA was calculated based on height and weight. Each center used a different established method of three-dimensional volume reconstruction. Using regression analysis, measurements were compared, and formulas correlating BSA or body weight to TLV were established. A linear regression formula to estimate TLV based on BSA was obtained: TLV = -794.41 + 1,267.28 x BSA (square meters; r(2) = 0.46; P &lt;.0001). A formula based on patient weight also was derived: TLV = 191.80 + 18.51 x weight (kilograms; r(2) = 0.49; P &lt;.0001). The newly derived TLV formula based on BSA was compared with previously reported formulas. The application of a formula obtained from healthy Japanese individuals underestimated TLV. Two formulas derived from autopsy data for Western populations were similar to the newly derived BSA formula, with a slight overestimation of TLV. In conclusion, hepatic three-dimensional volume reconstruction based on helical CT predicts TLV based on BSA or body weight. The new formulas derived from this correlation should contribute to the estimation of TLV before liver transplantation or major hepatic resection.

Effect of sodium loading/depletion on renal oxygenation in young normotensive and hypertensive men.

The goal of this study was to investigate the effect of sodium intake on renal tissue oxygenation in humans. To this purpose, we measured renal hemodynamics, renal sodium handling, and renal oxygenation in normotensive (NT) and hypertensive (HT) subjects after 1 week of a high-sodium and 1 week of a low-sodium diet. Renal oxygenation was measured using blood oxygen level-dependent magnetic resonance. Tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* values in the medulla and cortex were calculated, with a low R2* indicating a high tissue oxygenation. Ten male NT (mean age: 26.5+/-7.4 years) and 8 matched HT subjects (mean age: 28.8+/-5.7 years) were studied. Cortical R2* was not different under the 2 conditions of salt intake. Medullary R2* was significantly lower under low sodium than high sodium in both NT and HT subjects (28.1+/-0.8 versus 31.3+/-0.6 s(-1); P<0.05 in NT; and 27.9+/-1.5 versus 30.3+/-0.8 s(-1); P<0.05, in HT), indicating higher medullary oxygenation under low-sodium conditions. In NT subjects, medullary oxygenation was positively correlated with proximal reabsorption of sodium and negatively with absolute distal sodium reabsorption, but not with renal plasma flow. In HT subjects, medullary oxygenation correlated with the 24-hour sodium excretion but not with proximal or with the distal handling of sodium. These data demonstrate that dietary sodium intake influences renal tissue oxygenation, low sodium intake leading to an increased renal medullary oxygenation both in normotensive and young hypertensive subjects.

Population pharmacokinetics of ganciclovir in solid-organ transplant recipients receiving oral valganciclovir.

Valganciclovir (VGC) is an oral prodrug of ganciclovir (GCV) recently introduced for prophylaxis and treatment of cytomegalovirus infection. Optimal concentration exposure for effective and safe VGC therapy would require either reproducible VGC absorption and GCV disposition or dosage adjustment based on therapeutic drug monitoring (TDM). We examined GCV population pharmacokinetics in solid organ transplant recipients receiving oral VGC, including the influence of clinical factors, the magnitude of variability, and its impact on efficacy and tolerability. Nonlinear mixed effect model (NONMEM) analysis was performed on plasma samples from 65 transplant recipients under VGC prophylaxis or treatment. A two-compartment model with first-order absorption appropriately described the data. Systemic clearance was markedly influenced by the glomerular filtration rate (GFR), patient gender, and graft type (clearance/GFR = 1.7 in kidney, 0.9 in heart, and 1.2 in lung and liver recipients) with interpatient and interoccasion variabilities of 26 and 12%, respectively. Body weight and sex influenced central volume of distribution (V(1) = 0.34 liter/kg in males and 0.27 liter/kg in females [20% interpatient variability]). No significant drug interaction was detected. The good prophylactic efficacy and tolerability of VGC precluded the demonstration of any relationship with GCV concentrations. In conclusion, this analysis highlights the importance of thorough adjustment of VGC dosage to renal function and body weight. Considering the good predictability and reproducibility of the GCV profile after treatment with oral VGC, routine TDM does not appear to be clinically indicated in solid-organ transplant recipients. However, GCV plasma measurement may still be helpful in specific clinical situations.

La néphropathie ischémique par athérosclérose aortorénale : diagnostic [Atherosclerotic renal artery disease diagnosis update].

Atherosclerotic renal artery disease represents a cause of which little is known but not a cause to be neglected for hypertension and renal insufficiency. Even though its occurrence remains badly defined, atherosclerotic renal artery disease is constantly on the rise due to the aging population, the never prevailing hypertension and diabetes mellitus. This review aims to give a clinical profile of patients presenting with atherosclerotic renal artery disease and to discuss, in the light of study results, which diagnostic evaluation should be used considering the sequence and the benefit and risk of each in order to initiate a personalized treatment. Patients affected by atherosclerotic renal artery disease are likely to have more complications and more extensive target-organ damage than patients without renal artery stenosis. The evolution of the atherosclerotic renal artery disease is in general slow and progressive. Nevertheless, certain clinical cases manifest themselves with the onset of acute renal failure bought upon by the administration of blockers of the rennin-angiotensin-aldosterone system, or by some other causes responsible for a sudden drop in renal plasma flow (e.g., thrombosis of the renal artery). The relationship between atherosclerotic renal artery disease and atherosclerosis is complex, and mediators implicated in the pathophysiology of renovascular disease may also contribute to the progression of cardiovascular damage. An early assumption of the atherosclerotic renal artery stenosis is warranted to determine the adapted treatment (i.e., medical treatment, revascularisation...) just as the assumption and the correction of the more general cardiovascular risk factors.