Patricia Van der Niepen

Intermittent versus continuous renal replacement therapy for acute kidney injury patients admitted to the intensive care unit: results of a randomized clinical trial

BACKGROUND There is uncertainty on the effect of different dialysis modalities for the treatment of patients with acute kidney injury (AKI), admitted to the intensive care unit (ICU). This controlled clinical trial performed in the framework of the multicentre SHARF 4 study (Stuivenberg Hospital Acute Renal Failure) aimed to investigate the outcome in patients with AKI, stratified according to severity of disease and randomized to different treatment options. METHODS This was a multicentre prospective randomized controlled trial with stratification according to severity of disease expressed by the SHARF score. ICU patients were eligible for inclusion when serum creatinine was >2 mg/dL, and RRT was initiated. The selected patients were randomized to intermittent (IRRT) or continuous renal replacement therapy (CRRT). RESULTS A total of 316 AKI patients were randomly assigned to IRRT (n = 144) or CRRT (n = 172). The mean age was 66 (range 18-96); 59% were male. Intention-to-treat analysis revealed a mortality of 62.5% in IRRT compared to 58.1% in CRRT (P = 0.430). No difference between IRRT and CRRT could be observed in the duration of ICU stay or hospital stay. In survivors, renal recovery at hospital discharge was comparable between both groups. Multivariate analysis, including the SHARF score, APACHE II and SOFA scores for correction of disease severity, showed no difference in mortality between both treatment modalities. This result was confirmed in pre-specified subgroup analysis (elderly, patients with sepsis, heart failure, ventilation) and after exclusion of possible confounders (early mortality, delayed ICU admission). CONCLUSIONS Modality of RRT, either CRRT or IRRT, had no impact on the outcome in ICU patients with AKI. Both modalities need to be considered as complementary in the treatment of AKI (Clinical Trial: SHARF 4, NCT00322933, http://ClinicalTrials.gov).

Renal replacement therapy is an independent risk factor for mortality in critically ill patients with acute kidney injury

IntroductionOutcome studies in patients with acute kidney injury (AKI) have focused on differences between modalities of renal replacement therapy (RRT). The outcome of conservative treatment, however, has never been compared with RRT.MethodsNine Belgian intensive care units (ICUs) included all adult patients consecutively admitted with serum creatinine >2 mg/dl. Included treatment options were conservative treatment and intermittent or continuous RRT. Disease severity was determined using the Stuivenberg Hospital Acute Renal Failure (SHARF) score. Outcome parameters studied were mortality, hospital length of stay and renal recovery at hospital discharge.ResultsOut of 1,303 included patients, 650 required RRT (58% intermittent, 42% continuous RRT). Overall results showed a higher mortality (43% versus 58%) as well as a longer ICU and hospital stay in RRT patients compared to conservative treatment. Using the SHARF score for adjustment of disease severity, an increased risk of death for RRT compared to conservative treatment of RR = 1.75 (95% CI: 1.4 to 2.3) was found. Additional correction for other severity parameters (Acute Physiology And Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA)), age, type of AKI and clinical conditions confirmed the higher mortality in the RRT group.ConclusionsThe SHARF study showed that the higher mortality expected in AKI patients receiving RRT versus conservative treatment can not only be explained by a higher disease severity in the RRT group, even after multiple corrections. A more critical approach to the need for RRT in AKI patients seems to be warranted.

Effect of carvedilol on ambulatory blood pressure, renal hemodynamics, and cardiac function in essential hypertension.

Summary: A randomized, double‐blind, placebo‐controlled study was set up to study the effects of acute and chronic administration of carvedilol, a vasodilatory &bgr;‐blocker in essential hypertension. Acute administration of a single dose of 50 mg of carvedilol reduced systolic and diastolic blood pressure, without inducing reflex tachycardia. Renal blood flow was preserved: accordingly renal vascular resistance was significantly reduced. A significant reduction of glomerular filtration rate and filtration fraction was observed. Plasma renin activity (PRA) and plasma aldosterone were not changed. Chronic carvedilol treatment produced a significant fall in systolic and diastolic office and ambulatory blood pressure, heart rate, cardiac output, PRA and plasma aldosterone. Blood pressure variability was not changed. Renal blood flow, glomerular filtration rate and filtration fraction also remained unchanged; renal vascular resistance decreased significantly. It is concluded that carvedilol possesses definite antihypertensive and renal vasodilating properties, both acutely and after chronic treatment.

Prevalence of isolated uncontrolled systolic blood pressure among treated hypertensive patients in primary care in Belgium: results of the I-inSYST survey.

Objective To evaluate the prevalence of isolated uncontrolled systolic blood pressure (on-treatment isolated systolic hypertension) in treated hypertensive patients and identify the characteristics and treatment strategy in these patients. Methods Prospective cross-sectional survey in primary care. Participating physicians enrolled more than 13 consecutive treated hypertensive patients. Patients were considered to have isolated systolic hypertension when systolic blood pressure was at least 140 mmHg and diastolic blood pressure was less than 90 mmHg. Results On-treatment isolated systolic hypertension occurred in 28% of evaluable patients (n = 11562) and in 36% of uncontrolled patients (n = 9080). Among the isolated systolic hypertension and among other uncontrolled patients, 53% and 47%, respectively, used more than one antihypertensive drug class. β-Blockers were the most frequently prescribed antihypertensive drugs. Patients with isolated uncontrolled systolic blood pressure were more frequently treated with diuretics (43 vs. 39%) and angiotensin II receptor antagonists (23 vs. 17%). Despite blood pressure being under control in only 21% of the patients, hypertension treatment was not changed in 46% of patients with isolated uncontrolled systolic blood presssure vs. 14% of patients with both uncontrolled systolic and diastolic blood pressure. Conclusion In Belgium, the prevalence of on-treatment isolated systolic hypertension in treated hypertensive patients, was 28%. The goal blood pressure was likely not reached in most patients due to inadequate treatment. The overall control rate was worse for systolic than for diastolic blood pressure. Furthermore, antihypertensive treatment was less frequently adapted in patients with isolated uncontrolled systolic blood pressure than in those patients with both uncontrolled systolic and diastolic blood pressure.

Combined T1-based perfusion MRI and MR angiography in kidney: First experience in normals and pathology

OBJECTIVES To investigate the feasibility of implementing quantitative T1-perfusion in the routine MRA-protocol and to obtain a first experience in normals and pathology. MATERIALS AND METHODS For perfusion imaging, IR-prepared FLASH (one 4 mm slice at mid-renal level, TR 4.4 ms, TE 2.2 ms, TI 180 ms, FA 50 degrees , matrix 128 x 256, bandwidth per pixel 300, 400 dynamics, temporal resolution 0.3 s, total measurement time 2 min) was applied during the injection of 10 ml of standard 0.5 mmol/ml Gadolinium-DTPA solution at 2 ml/s, followed by 3DCE-MRA with bolus tracking (TR 5.4, TE 1.4, FA 40 degrees , matrix 192 x 512, NSA 1, slice thickness 1.5 mm), using a second dose of 0.1 mmol Gadolinium-DTPA per kg body weight with a maximum of 20 ml. The T1-weighted signals (perfusion data) were converted to tissue tracer concentrations and deconvolved with an inflow corrected AIF; blood flow, distribution volume, mean transit time and blood flow heterogeneity were derived. RESULTS MRA quality was uncompromised by the first bolus administered for perfusion purposes. In the normals, average cortical RBF, RVD and MTT were 1.2 ml/min/ml (S.D. 0.3 ml/min/ml), 0.4 ml/ml (S.D. 0.1 ml/ml) and 21s (S.D. 4s). These RBF values are lower than those found in the literature, probably due to residual AIF inflow effects. The sensitivity of the technique was sufficient to demonstrate altered perfusion in the examples of pathology. CONCLUSION Combined quantitative T1-perfusion and MRA have a potential for noninvasive renovascular screening and may provide an anatomical and physiological evaluation of renal status.

Renal blood oxygenation level-dependent magnetic resonance imaging to measure renal tissue oxygenation: a statement paper and systematic review

Abstract Tissue hypoxia plays a key role in the development and progression of many kidney diseases. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is the most promising imaging technique to monitor renal tissue oxygenation in humans. BOLD-MRI measures renal tissue deoxyhaemoglobin levels voxel by voxel. Increases in its outcome measure R2* (transverse relaxation rate expressed as per second) correspond to higher deoxyhaemoglobin concentrations and suggest lower oxygenation, whereas decreases in R2* indicate higher oxygenation. BOLD-MRI has been validated against micropuncture techniques in animals. Its reproducibility has been demonstrated in humans, provided that physiological and technical conditions are standardized. BOLD-MRI has shown that patients suffering from chronic kidney disease (CKD) or kidneys with severe renal artery stenosis have lower tissue oxygenation than controls. Additionally, CKD patients with the lowest cortical oxygenation have the worst renal outcome. Finally, BOLD-MRI has been used to assess the influence of drugs on renal tissue oxygenation, and may offer the possibility to identify drugs with nephroprotective or nephrotoxic effects at an early stage. Unfortunately, different methods are used to prepare patients, acquire MRI data and analyse the BOLD images. International efforts such as the European Cooperation in Science and Technology (COST) action ‘Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease’ (PARENCHIMA) are aiming to harmonize this process, to facilitate the introduction of this technique in clinical practice in the near future. This article represents an extensive overview of the studies performed in this field, summarizes the strengths and weaknesses of the technique, provides recommendations about patient preparation, image acquisition and analysis, and suggests clinical applications and future developments.

Renal Artery Stenosis in Patients with Resistant Hypertension: Stent It or Not?

After three large neutral trials in which renal artery revascularization failed to reduce cardiovascular and renal morbidity and mortality, renal artery stenting became a therapeutic taboo. However, this is probably unjustified as these trials have important limitations and excluded patients most likely to benefit from revascularization. In particular, patients with severe hypertension were often excluded and resistant hypertension was either poorly described or not conform to the current definition. Effective pharmacological combination treatment can control blood pressure in most patients with renovascular hypertension. However, it may also induce further renal hypoperfusion and thus accelerate progressive loss of renal tissue. Furthermore, case reports of patients with resistant hypertension showing substantial blood pressure improvement after successful revascularization are published over again. To identify those patients who would definitely respond to renal artery stenting, properly designed randomized clinical trials are definitely needed.

Improved Blood Pressure Control in Elderly Hypertensive Patients: Results of the PAPY-65 Survey

AbstractBackground Blood pressure (BP) control is far from optimal. Studies on factors influencing BP control in the elderly are limited, yet identification of factors contributing to the low rate of BP control is a prerequisite to improvement of clinical management. Objective To evaluate the rate of BP control and the relationship between different clinical characteristics and BP control in treated hypertensive outpatients aged ≥65 years. Methods The PAPY-65 Survey was a prospective cross-sectional survey conducted in primary care in Belgium in 2007. Participating primary-care physicians were required to include consecutive hypertensive patients aged ≥65 years and treated with antihypertensive drugs. Demographic and anthropometric data as well as data on cardiovascular risk factors and history were obtained. BP was measured in accordance with the European Society of Hypertension/European Society of Cardiology guidelines. Results The mean±standard deviation (SD) age of the 1272 patients enrolled in the survey was 75±7 years; 702 (55%) patients were women. The mean±SD systolic/diastolic BP was 134/79±13/8 mmHg. BP was normalized (reduced to <140/90mmHg, or <130/80 mmHg in patients with diabetes mellitus) in 617 (48.5%) patients overall and in 88 (24%) patients with diabetes (n= 371). The majority of patients (921; 72%) were treated with two or more antihypertensive drugs. Both general obesity (body mass index ≥30 vs <25 kg/m2) and abdominal obesity were associated with lack of BP control (unadjusted odds ratio [OR] 2.988, 95% CI 2.200, 4.057 and OR 2.066, 95% CI 1.649, 2.588, respectively). Abdominal obesity was no longer related to BP control when adjusted for the presence of diabetes. Diabetes was strongly associated with lack of BP control only when a stringent definition of BP control (<130/80 mmHg) was used. The combined presence of subclinical organ damage and a history of cardiovascular disease was associated with less uncontrolled BP (OR 0.62, 95% CI 0.48, 0.80). Conclusion Compared with previous data in the elderly in Belgium, a clear improvement in BP control was observed, probably related to the use of more antihypertensive agents. The presence of diabetes, excess bodyweight and abdominal obesity were all associated with poor BP control.

Diabetic Microangiopathic Hemolytic Anemia: Beneficial Effect of an Antiplatelet Agent?

A 66-yr-old man with non-insulin-dependent diabetes mellitus complicated by retinopathy and nephropathy presented with shortened red cell survival associated with prominent fragmentation of erythrocytes and leading to severe hemolytic anemia. Neither abnormal carbohydrate tolerance per se nor renal failure was related to the red cell fragmentation syndrome. Also, a marked platelet hyperaggregability, which disappeared under treatment with ticlopidine, was demonstrated. Furthermore, during treatment with this potent platelet inhibitor, red cell survival normalized and all signs of hemolysis, as well as the schistocytes present in the peripheral blood smears, disappeared. Two weeks after stopping ticlopidine administration, microangiopathic hemolytic anemia relapsed. We suggest that the fragmentation hemolysis in this patient was related to diabetic microangiopathy, and that the beneficial effects of ticlopidine are related to its platelet-inhibiting activities. This case further reaffirms that antiplatelet agents may have a beneficial effect on the vascular disease of diabetes mellitus.

Belgian global implementation of cardiovascular and stroke risk assessment study: methods and baseline data of the BELGICA-STROKE STUDY.

Objectives: BELGICA-STROKE is a longitudinal study to enhance the use of online cardiovascular risk prediction scores based on the SCORE 10-year risk estimates for fatal cardiovascular disease (adapted for Belgium) and the Framingham 10-year stroke risk and to evaluate their impact on the cardiovascular risk profile of hypertensive patients. Methods and baseline characteristics are described here. Design: Prospective, multicenter study in primary care. Methods: General practitioners (N = 810) recruited consecutive hypertensive patients aged >40 years who were not at blood pressure goal and assessed them every 4 months. The estimated 10-year risks for fatal cardiovascular disease and stroke were available on a secured, specially designed study website. The calculated risk profile of a patient was modifiable by adding treatment goals in order to increase awareness and motivation of both physician and patient. An automated feedback on goal-level attainment and both cardiovascular risk scores was provided. Results: Mean age of the 15,744 patients was 66.3 years: 51.9% were men, 77.8% had excess weight, 19.4% were smokers, and 25.9% had diabetes. Left ventricle hypertrophy was present in 20.0%, atrial fibrillation in 5.8%. Mean blood pressure was 153.8/88.2 mmHg, mean cholesterol 211.5 mg/dl. Most patients (89.2%) received antihypertensive medication, of which 36.9% was monotherapy. Mean estimated 10-year stroke risk was 19.1%, and mean estimated 10-year fatal cardiovascular disease risk 5.9%. Conclusions: The 10-year estimated stroke and fatal cardiovascular disease risks were moderate to high in hypertensive patients not at goal blood pressure, emphasizing the importance of global cardiovascular risk factor assessment.