Haemolytic uraemic syndrome associated with non shiga toxin-producing Escherichia coli bacteraemia: a case report.

BACKGROUND: Haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy (TMA) characterized by predominant renal involvement. Several types of HUS can be distinguished: the most frequent « typical ¼ HUS, due to shiga toxin producing Escherichia coli (STEC), "atypical" HUS due to complement alternative pathway dysregulation and "secondary" HUS associated with various diseases/conditions, the classification of which is still subject to debate. CASE PRESENTATION: We report a case of HUS following E.coli prostatitis and bacteraemia in an adult male. He presented with severe renal and neurological involvement. Initially considered as a "typical" HUS, the condition was treated by antibiotics. No other specific treatment for HUS was administered. The outcome was favorable. We eventually identified a non shiga toxin producing E.coli. Genetic testing of the complement alternative pathway revealed a rare - potentially pathogenic - variant of factor H. This constitutes a possible factor of susceptibility for atypical HUS, suggesting that E.coli infection may be the trigger. CONCLUSION: This case raises the question of complement exploration for HUS associated with infections, in order to classify such cases of HUS in accordance with their underlying pathophysiological mechanisms.

Evaluation of the efficacy of an interdialytic "ethanol 40% v/v - enoxaparin 1000 U/mL" lock solution to prevent tunnelled catheter infections in chronic hemodialysis patients: a multi-centre, randomized, single blind, parallel group study.

BACKGROUND: Tunnelled dialysis catheter (TC) infections are a major health complication and are associated with increased antibiotic consumption, hospital stays, health costs and mortality. Experimental data provide evidence that Ethenox, a mixture of enoxaparine 1000 U/mL in 40% v/v ethanol, could be a promising lock solution. The aim of the study is to compare an interdialytic lock solution of Ethenox with reference lock solutions, unfractionated heparin (UFH) or citrate 4% for the prevention of TCI in hemodialysis patients. METHOD: This study will monitor a multicentre, prospective, single blind, randomized, controlled, parallel group trial. The main inclusion criteria are patients > 18 years old with end-stage renal disease, treated with chronic hemodialysis/hemodiafiltration three times a week, with incident or prevalent non-impregnated internal jugular TCs inserted for at least 2 weeks and able to give informed consent. Exclusion criteria are TCI in the previous 4 weeks and anti-infective treatment for TCI in the previous 2 weeks. Patients will be randomized to receive either study treatment Ethenox in the intervention group or reference solutions in the control group, unfractionated heparin (UFH) or citrate 4% w/v according to usual practice. The primary outcome measure will be time to first TCIs assessed by an endpoint adjudication committee blinded to the study arm according to predefined criteria. Patients will receive the study treatment for up to 12 months. Intention-to-treat analysis of the primary endpoint will be performed with a marginal Cox proportional hazard model. Prospective power calculations indicate that the study will have 90% statistical power to detect a clinical significant two-fold increase in median infection-free survival if 200 patients are recruited into each arm over a period of 24 months. DISCUSSION: Firm evidence of the efficacy of the Ethenox lock in preventing TCI could be of major clinical benefit for patients. The results of this study will allow the development of new guidelines based on a high level of evidence. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03083184 , date of registration March 17 2017 and European Clinical Trials Database Identifier: EudraCT 2016-A00180-51), date of registration July 11 2016.

Mutation Update of the CLCN5 Gene Responsible for Dent Disease 1.

Dent disease is a rare X-linked tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis and/or nephrolithiasis, progressive renal failure, and variable manifestations of other proximal tubule dysfunctions. It often progresses over a few decades to chronic renal insufficiency, and therefore molecular characterization is important to allow appropriate genetic counseling. Two genetic subtypes have been described to date: Dent disease 1 is caused by mutations of the CLCN5 gene, coding for the chloride/proton exchanger ClC-5; and Dent disease 2 by mutations of the OCRL gene, coding for the inositol polyphosphate 5-phosphatase OCRL-1. Herein, we review previously reported mutations (n = 192) and their associated phenotype in 377 male patients with Dent disease 1 and describe phenotype and novel (n = 42) and recurrent mutations (n = 24) in a large cohort of 117 Dent disease 1 patients belonging to 90 families. The novel missense and in-frame mutations described were mapped onto a three-dimensional homology model of the ClC-5 protein. This analysis suggests that these mutations affect the dimerization process, helix stability, or transport. The phenotype of our cohort patients supports and extends the phenotype that has been reported in smaller studies.

[Amoxicillin induced crystal nephropathy : Monitoring of residual plasma levels]. / Cristalluries sous amoxicilline : intérêt du monitoring des concentrations plasmatiques résiduelles.

Since 2010, a lot of cases of amoxicillin induced crystal nephropathy have been reported to the French pharmacovigilance centers partly due to the high doses recommended by infectious disease guidelines. Typical clinical presentation and exclusion of others toxics or immuno-allergic causes are mandatory to assess the diagnostic. Amoxicillin crystals are rarely found or searched and renal biopsy is not frequently performed due to technical reasons and prompt renal recovery after antibiotics withdrawal. Monitoring of residual plasma concentration is rarely used in clinical practice for diagnostic or prognostic interest. We present 9 consecutive cases of acute kidney injury suspected to be due to amoxicillin crystals with residuals plasma levels to disclose a predictive threshold of tubulopathy. All patients had a high residual rate at diagnosis but we cannot find a threshold that would allow to adapt the antibiotic dose, enhance hydratation and alkalinizide urine to increase the medication solubility and limit renal toxicity.

Blood pressure control in patients with chronic kidney disease according to office and home blood pressures.

OBJECTIVES: The aim of this study was to assess blood pressure (BP) control in patients with chronic kidney disease (CKD) according to office and home BP and to assess the prevalence of normal BP, white-coat uncontrolled hypertension (WUCH), masked uncontrolled hypertension (MUCH) and elevated BP. METHODS: Patients with renal failure with or without proteinuria were included in this multicenter observational study. Office BP was first measured by the physician using a self-monitoring BP device (three automatic readings), then by the patient at home (morning and evening) over 3 consecutive days. WUCH was defined as a systolic BP (SBP)/diastolic BP (DBP) ≥140/90 mmHg in the clinic and SBP/DBP<135/85 mmHg at home. MUCH was defined as SBP/DBP <140/90 mmHg in the clinic and SBP/DBP ≥135/85 mmHg at home. RESULTS: Among the 243 included subjects, data of 225 patients were analyzed. Mean estimated glomerular filtration rate was 37.7 ± 15.7 mL/min/1.73 m and mean office SBP/DBP was 154 ± 19/83 ± 13 mmHg. Mean office SBP/DBP was significantly higher than home SBP/DBP (+9.0 ± 15.1/+7.0 ± 10.0 mmHg, P < 0.01). Normal BP (office and home BP), WUCH, MUCH and elevated BP (office and home BP) rates were 12.0, 14.2, 6.7 and 67.1%, respectively. The patients were taking, on average, 2.8 ± 1.5 antihypertensive drugs/day. CONCLUSION: BP control in patients with CKD was poor. Routine use of 'out-of-office' BP measurement, in addition to office BP by which we can identify patients with WUCH or MUCH, should be recommended based on the current findings.

[Polycystic kidney diseases: molecular genetics and counselling]. / La génétique des polykystoses rénales: mise au point et conseil génétique.

Autosomal dominant polycystic kidney disease (ADPKD) affects 1 newborn in 400 to 1000 making it the most common inherited form of genetic kidney disease and an important cause of medical morbidity and account for about 10% of end-stage renal disease. Autosomal recessive polycystic kidney disease (ARPKD) is a rare (1/20,000 to 1/40,000) inherited disease in children characterized by the association of dilation of collecting ducts and biliary dysgenesis. The clinical spectrum is variable but it represents an important cause of renal and liver-related morbidity and mortality in neonates and infancy. Symptoms of autosomal recessive PKD can begin before birth. ARPKD is genetically different from ADPKD. Parents who do not have the disease can have a child with the disease if both parents carry the abnormal gene and both pass the gene to their baby. Recently important advances in understanding the molecular basis of ADPKD (i.e. ADPKD1 and ADPKD2) and autosomal recessive PKD (i.e. PKHD1) have been done and are reported here. Genetic counselling is particularly advised in early onset disease families. It permits to determine the type of transmission, to describe the course and the major complications of the disease and to explain currents therapeutics possibilities.

Impact of miscuffing during home blood pressure measurement on the prevalence of masked hypertension.

BACKGROUND: Masked hypertension has been associated with obesity. However, because most studies do not mention the specific cuff size used for home measurements, masked hypertension prevalence may have been overestimated in obese patients because of undersized cuffs. In this prospective, observational study, the effect of miscuffing on hypertension status was evaluated in patients with large arms. METHODS: Fifty-three patients with an upper-arm circumference >33cm, undergoing treatment for mild-to-moderate hypertension, took 2 sets of home blood pressure (BP) measurements (standard vs. large cuff) using the validated Microlife BP A100 Plus automated device. RESULTS: Mean BP was 143/85mm Hg at the office using a large cuff, 141/84mm Hg at home using a standard cuff, and 134/80mm Hg at home using a large cuff. Standard vs. large cuff home BP mean differences were 6.9mm Hg (95% confidence interval (CI) = 4.7-9.2; P < 0.0001) for systolic BP and 4.0mm Hg (95% CI = 2.4-5.5; P < 0.0001) for diastolic BP. Hypertension status differed significantly between standard vs. large cuffs: sustained hypertension (56.6% vs. 41.5%, respectively; P = 0.002), controlled hypertension (20.8% vs. 28.3%, respectively; P = 0.04), white coat hypertension (7.5% vs. 22.6%, respectively; P = 0.002), masked hypertension (15.1% vs. 7.5%, respectively; P = 0.04). CONCLUSIONS: In patients with large arms, use of an appropriately sized large cuff for home BP measurements led to a 2-fold reduction in masked hypertension. Regarding clinical and epidemiological implications, future studies investigating masked hypertension should specify cuff size for home BP measurements. The low market availability and increased cost of large cuffs should also be addressed.

Aldosterone-to-renin ratio for diagnosing aldosterone-producing adenoma: a multicentre study.

BACKGROUND: Biological diagnostic criteria for diagnosing aldosterone-producing adenoma (APA) are not well-established. AIM: The aim of the study was to establish the best biological predictors of APA. METHODS: A prospective register was implemented in 17 secondary or tertiary hypertension centres. The inclusion criterion was one of the following: onset of hypertension before 40 years of age; history of hypokalaemia; drug-resistant hypertension (resistant to three drugs); or spironolactone efficiency on BP. RESULTS: Among the 338 collected cases, 192 patients had two aldosterone-to-renin ratio (ARR) determinations (after 1 hour supine and at least 1 hour upright) on the same occasion. Twenty-five patients (8.2%) had biological hyperaldosteronism and an adrenal adenoma identified by computed tomography. APA was histologically confirmed in all 12 patients who underwent surgery. Histologically proven APAs were used as the 'gold standard' in receiver operating characteristic (ROC) curve analysis. ARRs were computed with a minimum renin value set at 5 ng/L to avoid misclassification of so-called 'low-renin hypertension'. To predict an APA, the ARR area under the ROC curve was 0.93. A supine ARR cut-off value of 32ng/ng provided the highest sum of sensitivity (92%) plus specificity (92%). On the basis of an ARR≥32 ng/ng in the supine and/or upright position, sensitivity reached 100%. CONCLUSION: The proposed cut-off value of 32 ng/ng for ARR (minimum renin value set at 5 ng/L) in one of two determinations had 100% sensitivity and 72% specificity with 20% positive and 100% negative predictive values for diagnosing APA.

[Tunnelled internal jugular vein catheters with taurolidine lock: an acceptable challenge to arterio-venous fistula in 70 years old haemodialyzed patients: a prospective pilot study]. / Les cathéters jugulaires internes tunnellisés avec verrou antiseptique par taurolidine : une alternative acceptable aux fistules artérioveineuses chez les hémodialysés de plus de 70ans : résultats d'une étude pilote prospective.

Arteriovenous fistula (AVF) is still in 2010 the gold standard of vascular(2) access in haemodialysis (HD) patients. Nevertheless it may be difficult to obtain and/or to use AVF in elderly. With this prospective randomised pilot study, we compare two strategies of vascular access in 70 years old or more new HD patients. AVF were compared to tunnelled jugular vein catheters (TIJC) with taurolidine as bacterial lock solution. Results were as follow: [table: see text] The responses with the visual analogic scale of comfort was 8/10 for TIJC and 5/10 with AVF * P<0.05. In five TIJC patients, heparin was added with success to taurolidine because of partial clotting of catheters. Albuminemia was significantly lower in AVF failure patients compared to AVF success patients (24.8g/L vs 31.1g/L). This pilot study allows to conclude that TIJC is an acceptable challenge to AVF in haemodialysed patients of 70 years or more in a two years long use.

Systolic blood pressure is depending on the arm position when home blood pressure is measured with a wrist or an arm validated monitor.

OBJECTIVES: To compare home blood pressure (BP) values obtained with two validated OMRON (wrist or arm) monitors used in the same individual sequentially, but with two different hand positions. METHODS: In 200 hypertensive individuals referred to hypertension specialists, a self-measurement of BP was performed sequentially with an OMRON M4-I (arm cuff, A/A, British Hypertention Society validation) and an OMRON RX-I (wrist cuff, B/B, BHS validation). Each patient recorded home BP during two periods of 4 days with three measures in the morning and three in the evening. Order for use of each monitor was randomized. For the first 100 patients, the hand was positioned on the opposite shoulder whereas for the next 100 patients, the hand was positioned on the opposite elbow. BP values were reported on a standardized document. RESULTS: In this population, aged 60+/-10 years, with 54% of men, BP values were 136+/-/80+/- mmHg with the wrist monitor (WM) when the hand is positioned on the opposite shoulder as compared with 144+/-16/81+/-9 mmHg obtained with the arm monitor taken as the gold standard. On the contrary, BP values were 142+/-/82+/- mmHg with the WM when the hand is positioned on the opposite elbow as compared with 144+/-16/81+/-9 mmHg obtained with the arm monitor. The lower value of systolic blood pressure observed with WM positioned on the shoulder is independent of age, initial BP level and order of use (multivariate analysis). CONCLUSION: When advising home BP monitoring with a WM, the instruction to be given to patients is to position the hand on the opposite elbow.