Outcome of atypical hemolytic uremic syndrome: role of triggers and complement abnormalities in the response to C5 inhibition.

BACKGROUND: Atypical-hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy often due to uncontrolled complement activation, characterized by high risk of end-stage kidney disease (ESKD). Eculizumab has improved the outcome, however, its efficacy varies among patients and its discontinuation is debated. METHODS: To identify characteristics associated with treatment response, we analyzed 244 aHUS patients referred to our center. Patients were classified according to the presence/absence of complement abnormalities and/or triggers at onset in 4 categories: (1) primary (complement abnormality without trigger), (2) secondary (trigger without complement abnormality), (3) combined (trigger and complement abnormality), (4) idiopathic (no trigger, no complement abnormality). Response to treatment was evaluated by comparing the response to eculizumab with that of conventional therapy. Short- and long-term outcomes were evaluated with the relapse rate after discontinuation of C5-inhibition. RESULTS: Patients had a better outcome with eculizumab compared to conventional treatment, with a response rate of 81.9% vs 56.9%, p < 0.001 and a long-term cumulative incidence of ESKD of 5.8% vs 22.5% (hazard ratio 0.25, 95% confidence interval: 0.10-0.80). The excellent global response was driven by the primary and combined groups (89.8% vs 54.0% and 89.3% vs 54.2%, respectively). The relapse rate following discontinuation of the C5-inhibitor was as high as 66.7% in the primary group, 18.7% in the combined, and 0% in the secondary and idiopathic groups. CONCLUSIONS: Our data show a better outcome in aHUS patients treated with C5-inhibition, particularly in the primary and combined forms, which have a high risk of relapse after discontinuation that is not observed in the secondary and idiopathic forms.

Sleep-disordered breathing and heart failure: a vicious cycle of cardiovascular risk.

Sleep-disordered breathing (SDB) represents an important cardiovascular risk factor that is still often underestimated and not always optimally treated. Such breathing disorders can induce several harmful effects on the heart, also favoring the development of arrhythmias, ischemic heart disease, and left ventricular remodeling. Obstructive sleep apnea syndrome (OSA) is more frequent in heart failure patients than in the general population, promoting the worsening of left ventricular dysfunction. Both sleep apnea and heart failure have common clinical manifestations but also similar neurohormonal characteristics, both contributing to the development and progression of heart failure and resulting in increased mortality. The pathophysiological mechanisms underlying left ventricular dysfunction associated with SDB will be analyzed, and the potential therapeutic effects of gliflozins on OSA in heart failure patients will be discussed.

Rare Single Nucleotide and Copy Number Variants and the Etiology of Congenital Obstructive Uropathy: Implications for Genetic Diagnosis.

SIGNIFICANCE STATEMENT: Congenital obstructive uropathy (COU) is a prevalent human developmental defect with highly heterogeneous clinical presentations and outcomes. Genetics may refine diagnosis, prognosis, and treatment, but the genomic architecture of COU is largely unknown. Comprehensive genomic screening study of 733 cases with three distinct COU subphenotypes revealed disease etiology in 10.0% of them. We detected no significant differences in the overall diagnostic yield among COU subphenotypes, with characteristic variable expressivity of several mutant genes. Our findings therefore may legitimize a genetic first diagnostic approach for COU, especially when burdening clinical and imaging characterization is not complete or available. BACKGROUND: Congenital obstructive uropathy (COU) is a common cause of developmental defects of the urinary tract, with heterogeneous clinical presentation and outcome. Genetic analysis has the potential to elucidate the underlying diagnosis and help risk stratification. METHODS: We performed a comprehensive genomic screen of 733 independent COU cases, which consisted of individuals with ureteropelvic junction obstruction ( n =321), ureterovesical junction obstruction/congenital megaureter ( n =178), and COU not otherwise specified (COU-NOS; n =234). RESULTS: We identified pathogenic single nucleotide variants (SNVs) in 53 (7.2%) cases and genomic disorders (GDs) in 23 (3.1%) cases. We detected no significant differences in the overall diagnostic yield between COU sub-phenotypes, and pathogenic SNVs in several genes were associated to any of the three categories. Hence, although COU may appear phenotypically heterogeneous, COU phenotypes are likely to share common molecular bases. On the other hand, mutations in TNXB were more often identified in COU-NOS cases, demonstrating the diagnostic challenge in discriminating COU from hydronephrosis secondary to vesicoureteral reflux, particularly when diagnostic imaging is incomplete. Pathogenic SNVs in only six genes were found in more than one individual, supporting high genetic heterogeneity. Finally, convergence between data on SNVs and GDs suggest MYH11 as a dosage-sensitive gene possibly correlating with severity of COU. CONCLUSIONS: We established a genomic diagnosis in 10.0% of COU individuals. The findings underscore the urgent need to identify novel genetic susceptibility factors to COU to better define the natural history of the remaining 90% of cases without a molecular diagnosis.

Cardiovascular Side Effects of Anthracyclines and HER2 Inhibitors among Patients with Breast Cancer: A Multidisciplinary Stepwise Approach for Prevention, Early Detection, and Treatment.

Cardiovascular (CV) diseases (CVD) are a major cause of long-term morbidity and mortality affecting life expectancy amongst cancer survivors. In recent years, because of the possibility of early diagnosis and the increased efficacy of neo-adjuvant and adjuvant systemic treatments (targeting specific molecular pathways), the high percentage of survival from breast cancer led CVD to become the first cause of death among survivors. Therefore, it is mandatory to adopt cardioprotective strategies to minimize CV side effects and CVD in general in breast cancer patients. Cancer therapeutics-related cardiac dysfunction (CTRCD) is a common group of side effects of chemotherapeutics widely employed in breast cancer (e.g., anthracycline and human epidermal growth factor receptor 2 inhibitors). The aim of the present manuscript is to propose a pragmatic multidisciplinary stepwise approach for prevention, early detection, and treatment of cardiotoxicity in patients with breast cancer.

Acute Heart Failure: Diagnostic-Therapeutic Pathways and Preventive Strategies-A Real-World Clinician's Guide.

Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical heterogeneity of the syndrome. Regardless of the underlying mechanism, peripheral and/or pulmonary congestion is present in the vast majority of cases. Furthermore, a marked reduction in cardiac output with peripheral hypoperfusion may occur in most severe cases. Diagnosis is made on the basis of signs and symptoms, laboratory, and non-invasive tests. After exclusion of reversible causes, AHF therapeutic interventions mainly consist of intravenous (IV) diuretics and/or vasodilators, tailored according to the initial hemodynamic status with the addition of inotropes/vasopressors and mechanical circulatory support if needed. The aim of this review is to discuss current concepts on the diagnosis and management of AHF in order to guide daily clinical practice and to underline the unmet needs. Preventive strategies are also discussed.

Exploring the Cardiotoxicity Spectrum of Anti-Cancer Treatments: Definition, Classification, and Diagnostic Pathways.

Early detection and treatment of cancer have led to a noticeable reduction in both mortality and morbidity. However, chemotherapy and radiotherapy could exert cardiovascular (CV) side effects, impacting survival and quality of life, independent of the oncologic prognosis. In this regard, a high clinical index of suspicion is required by the multidisciplinary care team in order to trigger specific laboratory tests (namely natriuretic peptides and high-sensitivity cardiac troponin) and appropriate imaging techniques (transthoracic echocardiography along with cardiac magnetic resonance, cardiac computed tomography, and nuclear testing (if clinically indicated)), leading to timely diagnosis. In the near future, we do expect a more tailored approach to patient care within the respective community along with the widespread implementation of digital health tools.

Severe Stenosis of Mitral Bioprosthetic Valve Thrombosis in a Patient with HCV-Related Cirrhosis and Duodenal Variceal Bleeding: The Deadly Triad.

Bioprosthetic valve thrombosis (BPVT) is considered a relatively rare but life-threatening clinical entity. Thus, there is the need of high clinical suspicion in order to make a timely diagnosis and related appropriate therapeutic interventions. In this regard, the management of BPVT is high risk, whatever the option taken (surgery and/or systemic fibrinolysis). The presence of severe comorbidities-as decompensated cirrhosis-further complicates the clinical decision-making process, calling for a patient-tailored integrated multidisciplinary approach. We report a challenging case of a 45-year-old patient with mitral bioprosthetic valve thrombosis and hepatitis C virus (HCV)-related cirrhosis complicated by active duodenal variceal bleeding.

Effects of Exercise on Heart Failure with Preserved Ejection Fraction: An Updated Review of Literature.

Heart failure with preserved ejection fraction (HFpEF) represents the most common HF phenotype of patients aged > 65 years, with an incidence and a prevalence that are constantly growing. The HFpEF cardinal symptom is exercise intolerance (EI), defined as the impaired ability to perform physical activity and to reach the predicted age-related level of exercise duration in the absence of symptoms­such as fatigue or dyspnea­and is associated with a poor quality of life, a higher number of hospitalizations, and poor outcomes. The evidence of the protective effect between exercise and adverse cardiovascular outcomes is numerous and long-established. Regular exercise is known to reduce cardiovascular events and overall mortality both in apparently healthy individuals and in patients with established cardiovascular disease, representing a cornerstone in the prevention and treatment of many cardio-metabolic conditions. Several studies have investigated the role of exercise in HFpEF patients. The present review aims to dwell upon the effects of exercise on HFpEF. For this purpose, the relevant data from a literature search (PubMed, EMBASE, and Medline) were reviewed. The analysis of these studies underlines the fact that exercise training programs improve the cardiorespiratory performance of HFpEF patients in terms of the increase in peak oxygen uptake, the 6 min walk test distance, and the ventilatory threshold; on the other hand, diastolic or systolic functions are generally unchanged or only partially modified by exercise, suggesting that multiple mechanisms contribute to the improvement of exercise tolerance in HFpEF patients. In conclusion, considering that exercise training programs are able to improve the cardiorespiratory performance of HFpEF patients, the prescription of exercise training programs should be encouraged in stable HFpEF patients, and further research is needed to better elucidate the pathophysiological mechanisms underpinning the beneficial effects described.

Complement System as a New Target for Hematopoietic Stem Cell Transplantation-Related Thrombotic Microangiopathy.

Thrombotic microangiopathy (TMA) is a complication that may occur after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) and is conventionally called transplant-associated thrombotic microangiopathy (TA-TMA). Despite the many efforts made to understand the mechanisms of TA-TMA, its pathogenesis is largely unknown, its diagnosis is challenging and the case-fatality rate remains high. The hallmarks of TA-TMA, as for any TMA, are platelet consumption, hemolysis, and organ dysfunction, particularly the kidney, leading also to hypertension. However, coexisting complications, such as infections and/or immune-mediated injury and/or drug toxicity, together with the heterogeneity of diagnostic criteria, render the diagnosis difficult. During the last 10 years, evidence has been provided on the involvement of the complement system in the pathophysiology of TA-TMA, supported by functional, genetic, and therapeutic data. Complement dysregulation is believed to collaborate with other proinflammatory and procoagulant factors to cause endothelial injury and consequent microvascular thrombosis and tissue damage. However, data on complement activation in TA-TMA are not sufficient to support a systematic use of complement inhibition therapy in all patients. Thus, it seems reasonable to propose complement inhibition therapy only to those patients exhibiting a clear complement activation according to the available biomarkers. Several agents are now available to inhibit complement activity: two drugs have been successfully used in TA-TMA, particularly in pediatric cases (eculizumab and narsoplimab) and others are at different stages of development (ravulizumab, coversin, pegcetacoplan, crovalimab, avacopan, iptacopan, danicopan, BCX9930, and AMY-101).

Physiologic Range of Myocardial Mechano-Energetic Efficiency among Healthy Subjects: Impact of Gender and Age.

BACKGROUND: Myocardial mechano-energetic efficiency (MEE) is the capability of the left ventricle (LV) to convert the chemical energy obtained from the cardiac oxidative metabolism into mechanical work. The aim of present study was to establish normal non-invasive MEE and MEEi reference values. METHODS: In total, 1168 healthy subjects underwent physical examinations, clinical assessment, and standardized transthoracic echocardiographic (TTE) examination. MEE was obtained by TTE as the ratio between stroke volume (SV) and heart rate (HR): MEE = SV/HR [HR expressed in seconds (HR/60)]. Because MEE is highly related to left ventricular mass (LVM), MEE was then divided by LVM with the purpose of obtaining an estimate of energetic expenditure per unit of myocardial mass (i.e., indexed MEE, MEEi, mL/s/g). RESULTS: The mean values of MEE and MEEi in the overall population were 61.09 ± 18.19 mL/s; 0.45 ± 0.14, respectively. In a multivariable analysis, gender, body surface area (BSA), diastolic blood pressure, left atrial volume indexed to BSA, E/e' and tricuspid annular plane systolic excursion (TAPSE) were the independent variables associated with MEE, while age, gender, BSA and TAPSE were the independent variables associated with MEEi. CONCLUSIONS: The knowledge of age- and gender-based MEE and MEEi normal values may improve the global assessment of LV cardiac mechanics and serve as a reference to identify phenotypes at high risk of cardiovascular events.

Definition, diagnosis and clinical management of non-obstructive kidney dysplasia: a consensus statement by the ERKNet Working Group on Kidney Malformations.

Kidney dysplasia is one of the most frequent causes of chronic kidney failure in children. While dysplasia is a histological diagnosis, the term 'kidney dysplasia' is frequently used in daily clinical life without histopathological confirmation. Clinical parameters of kidney dysplasia have not been clearly defined, leading to imprecise communication amongst healthcare professionals and patients. This lack of consensus hampers precise disease understanding and the development of specific therapies. Based on a structured literature search, we here suggest a common basis for clinical, imaging, genetic, pathological and basic science aspects of non-obstructive kidney dysplasia associated with functional kidney impairment. We propose to accept hallmark sonographic findings as surrogate parameters defining a clinical diagnosis of dysplastic kidneys. We suggest differentiated clinical follow-up plans for children with kidney dysplasia and summarize established monogenic causes for non-obstructive kidney dysplasia. Finally, we point out and discuss research gaps in the field.

Management of the congenital solitary kidney: consensus recommendations of the Italian Society of Pediatric Nephrology.

BACKGROUND: In recent years, several studies have been published on the prognosis of children with congenital solitary kidney (CSK), with controversial results, and a worldwide consensus on management and follow-up is lacking. In this consensus statement, the Italian Society of Pediatric Nephrology summarizes the current knowledge on CSK and presents recommendations for its management, including diagnostic approach, nutritional and lifestyle habits, and follow-up. We recommend that any antenatal suspicion/diagnosis of CSK be confirmed by neonatal ultrasound (US), avoiding the routine use of further imaging if no other anomalies of kidney/urinary tract are detected. A CSK without additional abnormalities is expected to undergo compensatory enlargement, which should be assessed by US. We recommend that urinalysis, but not blood tests or genetic analysis, be routinely performed at diagnosis in infants and children showing compensatory enlargement of the CSK. Extrarenal malformations should be searched for, particularly genital tract malformations in females. An excessive protein and salt intake should be avoided, while sport participation should not be restricted. We recommend a lifelong follow-up, which should be tailored on risk stratification, as follows: low risk: CSK with compensatory enlargement, medium risk: CSK without compensatory enlargement and/or additional CAKUT, and high risk: decreased GFR and/or proteinuria, and/or hypertension. We recommend that in children at low-risk periodic US, urinalysis and BP measurement be performed; in those at medium risk, we recommend that serum creatinine also be measured; in high-risk children, the schedule has to be tailored according to kidney function and clinical data.

Definition, diagnosis and management of fetal lower urinary tract obstruction: consensus of the ERKNet CAKUT-Obstructive Uropathy Work Group.

Fetal lower urinary tract obstruction (LUTO) is associated with high mortality and postnatal morbidity caused by lung hypoplasia and impaired kidney function. Specific diagnostic features that can guide clinical approach and decisions are lacking; thus, the European Reference Network for Rare Kidney Diseases established a work group to develop recommendations regarding the clinical definition, diagnosis and management of prenatally detected LUTO. The work group recommends the use of antero-posterior diameter of renal pelvis as the most reliable parameter for suspecting obstructive uropathies and for suspecting prenatal LUTO in the presence of fetal megacystis. Regarding prenatal and postnatal prognosis of fetuses with LUTO, the risk of fetal and neonatal death depends on the presence of oligohydramnios or anhydramnios before 20 weeks' gestation, whereas the risk of kidney replacement therapy cannot be reliably foreseen before birth. Parents of fetuses with LUTO must be referred to a tertiary obstetric centre with multidisciplinary expertise in prenatal and postnatal management of obstructive uropathies, and vesico-amniotic shunt placement should be offered in selected instances, as it increases perinatal survival of fetuses with LUTO.

Right Heart Pulmonary Circulation Unit Response to Exercise in Patients with Controlled Systemic Arterial Hypertension: Insights from the RIGHT Heart International NETwork (RIGHT-NET).

BACKGROUND: Systemic arterial hypertension (HTN) is the main risk factor for the development of heart failure with preserved ejection fraction (HFpEF). The aim of the study was was to assess the trends in PASP, E/E' and TAPSE during exercise Doppler echocardiography (EDE) in hypertensive (HTN) patients vs. healthy subjects stratified by age. METHODS: EDE was performed in 155 hypertensive patients and in 145 healthy subjects (mean age 62 ± 12.0 vs. 54 ± 14.9 years respectively, p < 0.0001). EDE was undertaken on a semi-recumbent cycle ergometer with load increasing by 25 watts every 2 min. Left ventricular (LV) and right ventricular (RV) dimensions, function and hemodynamics were evaluated. RESULTS: Echo-Doppler parameters of LV and RV function were lower, both at rest and at peak exercise in hypertensives, while pulmonary hemodynamics were higher as compared to healthy subjects. The entire cohort was then divided into tertiles of age: at rest, no significant differences were recorded for each age group between hypertensives and normotensives except for E/E' that was higher in hypertensives. At peak exercise, hypertensives had higher pulmonary artery systolic pressure (PASP) and E/E' but lower tricuspid annular plane systolic excursion (TAPSE) as age increased, compared to normotensives. Differences in E/E' and TAPSE between the 2 groups at peak exercise were explained by the interaction between HTN and age even after adjustment for baseline values (p < 0.001 for E/E', p = 0.011 for TAPSE). At peak exercise, the oldest group of hypertensive patients had a mean E/E' of 13.0, suggesting a significant increase in LV diastolic pressure combined with increased PASP. CONCLUSION: Age and HTN have a synergic negative effect on E/E' and TAPSE at peak exercise in hypertensive subjects.

Eculizumab treatment in atypical hemolytic uremic syndrome: correlation between functional complement tests and drug levels.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is characterized by platelet consumption, hemolysis, and renal injury. Eculizumab, a humanized antibody that blocks complement activity, has been successfully used in aHUS, but the best treatment schedule has not yet been clearly defined. METHODS: Herein we report our experience with eculizumab maintenance treatment, in which the interval between subsequent doses was adjusted based on classical complement pathway (CCP) activity, targeted to < 30% for the prevention of relapses. Trough circulating levels of free eculizumab were determined by an immunoenzymatic method. Genetic and serologic characteristics of the patients were also assessed. RESULTS: We report on 38 patients with aHUS with a median age of 25.0 years (range 0.5-60.0 years) treated with eculizumab. Once stable disease remission was obtained, the interval between eculizumab doses was extended based on target CCP activity. With this approach, presently, 22 patients regularly receive eculizumab infusion every 28 days and 16 receive it every 21. During a median observation period of 32.3 months (range 4.0-92.4 months) and a cumulative period of 1295 months, no patient relapsed. An inverse correlation between CCP activity and eculizumab circulating levels was present (r = - 0.690, p = 0.0001), with CCP activity being inhibited as long as free eculizumab was measurable in serum. CONCLUSIONS: In patients with aHUS on eculizumab maintenance treatment, complement activity measurement can be used as a proxy for circulating levels of the drug. Monitoring complement activity allows for safe tailoring of the frequency of eculizumab administration, thus avoiding excessive drug exposure while keeping the disease in remission.

Multiple, random spot urine sampling for estimating urinary sodium excretion.

The measurement of sodium intake may be important for the management of hypertension. Dietary surveys and 24-h urinary collection are often unreliable and/or impractical. We hypothesized that urinary sodium excretion can be accurately estimated through multiple spot urine samples from different days. All enrolled subjects were children of the coauthors of the study. Fifty-two 24-h urinary collections (4 per subject) for measuring sodium excretion and the 297 related urinary samples (1 per voiding) were collected for calculating the urinary sodium/urinary creatinine ratio in 13 children. The mean of 4 measured sodium excretions served as the individual "gold standard". Twenty-four urinary collections were used to generate the equation predicting the mean measured sodium excretion from the mean of 4 urinary sodium/urinary creatinine [= 0.016 × urinary sodium (mmol/L) / urinary creatinine (mmol/L) ratio + 3.3)]; the remaining 28 urinary collections and 153 urinary samples were used for the external validation. All subjects underwent an additional validation procedure involving 12 urinary samples randomly collected on different days 6 months apart. The performance of sodium excretion calculated from a total of over 22,000 possible means of 4 out of all the available urinary samples, randomly taken on different days, was analyzed as to precision (by means of the coefficient of variation) and as to accuracy (by means of the P30). The coefficients of variations of measured vs. calculated sodium excretion were 25.3% vs. 25.8%, and the P30 of calculated sodium excretion was 100%. The excellent performance of calculated sodium excretion was confirmed both by external validation and by samples collected 6 months apart with mean P30s, all between 86 and 100%.Conclusion: In the described experimental conditions, urinary sodium excretion was estimated with equal precision and more accurately (and practically) by the mean of 4 urinary sodium/urinary creatinine ratios from random samples from different days than by a single urinary collection. In real life, with several errors systematically affecting urinary collection, the superiority of calculated sodium excretion is likely to be even greater. What is Known: • The measurement of sodium intake with the current standards of care (dietary survey or 24-h urinary collection) is laborious and can be inaccurate. What is New: • The study provides evidence that sodium intake can be estimated equally precisely, more accurately and more practically with the urinary sodium-to-urinary creatinine ratio from 4 urine samples taken on different days than with a single urinary collection.

Calcium carbonate-enriched cheese to improve nutrition, compliance and phosphorus control in patients on kidney replacement therapy.

BACKGROUND: Patients on renal replacement therapy face many dietary limitations, and cheese is often limited because of its high phosphate content; we have developed cheese with added calcium carbonate (CaCO3) to provide patients with a nutritional opportunity while improving their phosphate control. METHODS: The present double-blind crossover study was aimed to compare the new modified cheese with an equivalent standard product in 16 patients. The increase in inter-dialysis phosphorus (ΔP) and pre-dialysis calcium were used as the primary endpoints for efficacy and safety. RESULTS: The median ΔP (and IQR) was significantly lower with the modified cheese compared with the standard product: 2.5 (1.9-2.9) mg/dL vs. 2.7 (2.2-3.4) mg/dL, respectively (p < 0.02). No difference was observed in pre-dialysis serum calcium levels. CONCLUSIONS: The described modified cheese may represent an interesting means of overcoming some of the dietary limitations in patients on dialysis to help them achieve better nutrition and quality of life.

Haemoglobinuria for the early identification of aHUS relapse: data from the ItalKId-HUS Network.

BACKGROUND: Atypical haemolytic uremic syndrome (aHUS) is at high risk of relapse at any time, therefore patients require lifelong monitoring. The most appropriate way to monitor patients is not yet clear. Patients could be monitored for relapse by urine dipstick testing for haemoglobinuria based on the hypothesis that thrombotic microangiopathy involving the glomerulus and associated with renal damage (like aHUS) cannot occur without haematuria. METHODS: The aim of this retrospective study is to analyse our experience with this approach in aHUS patients who have never previously been treated, who are currently on treatment or who have discontinued C5 inhibition. The records of all aHUS patients (children and adults) managed by or referred to our Centre from January 2009 to March 2020 were included and the analysis for the presence of haemoglobinuria was restricted to the period following primary remission. A positive test was defined as haemoglobin ≥ 1 + . Patients reporting positive urine dipstick tests underwent laboratory investigations to rule in or out the diagnosis of aHUS relapse. RESULTS: Eighty-four patients were included with 1517 determinations of haemoglobinuria during a cumulative observation period of 8904 patient-months. Haemoglobinuria for the early diagnosis of ongoing aHUS relapse shows a sensitivity of 100% and a specificity of 87.4% with a positive predictive value (PPV) of 10.5% and a negative predictive value (NPV) of 100%. The accuracy of the test was 87.6%. CONCLUSION: Haemoglobinuria is a very sensitive and acceptably specific marker of aHUS relapse. This finding and its validation may have a positive impact on patients' quality of life and on the outcome of this life threatening disease via early diagnosis of relapse.

Fluid intake and blood pressure in children: the Salus per Aquam project.

BACKGROUND: Sodium intake is known to contribute to the development of hypertension, thus intake reduction is a cornerstone in the prevention and management of hypertension. The increase in renal sodium excretion might represent a further potential preventive and/or therapeutic opportunity. OBJECTIVE: To explore the working hypothesis that an increased fluid intake can improve renal sodium handling towards a decrease in blood pressure. METHODS: The SPA Project is a multicenter, observational, cross-sectional, cohort study investigating healthy children, aged 5-8 years as to sodium and fluid intake by means of urinary sodium and creatinine from multiple samples taken in different days in order to characterize them in lower/higher sodium and lower/higher fluid intake. Both SBP and DBP (by multiple office blood pressure measurements) were used as outcome measures. RESULTS: Three hundred and thirty-nine healthy, nonoverweight children (51.6% boys) with a median age of 5.7 years old (IQR: 5.3-6.2) participated in the study but only 223 could be analyzed. Among children with higher sodium intake, those introducing more fluids, showed a significantly lower blood pressure (both systolic and diastolic) compared with those with lower fluid intake: systolic 86.0 ±â€Š8.5 vs. 90.0 ±â€Š8.1 mmHg; P = 0.014 and diastolic: 53.8 ±â€Š4.9 vs. 58.6 ±â€Š6.6 mmHg; P < 0.0001. CONCLUSION: An increased fluid intake is associated with a reduced blood pressure possibly by increasing renal sodium excretion. We speculate that this simple, highly acceptable, inexpensive, and harmless measure might have a role in preventing and/or minimizing the epidemics of hypertension and of its related morbidities both in children and in adults.