Outbreak of Escherichia coli O104:H4 haemolytic uraemic syndrome in France: outcome with eculizumab.

BACKGROUND: An outbreak of haemolytic uraemic syndrome (HUS) due to Shiga toxin-secreting Escherichia coli (STEC) O104:H4 from contaminated fenugreek sprouts occurred in June 2011 near Bordeaux, France. In the context of this outbreak, all patients were treated with the monoclonal anti-C5 antibody, eculizumab. METHODS: The diagnosis of HUS was made based on haemolytic anaemia, low platelet count and acute kidney injury. Data were obtained from initial gastrointestinal symptoms to the end of follow-up 10 weeks after the start of eculizumab. RESULTS: Among 24 cases of STEC gastroenteritis, HUS developed in nine patients (eight adults and one child), 6 (median; range 3-12) days after digestive symptoms begun. The median (range) highest or lowest biological values were platelet count 26 (range 14-93) G/L; haemoglobin 6.6 (range 5-10.7) g/dL; LDH 1520 (range 510-2568) IU/L; creatinine 152 (range 48-797) µmol/L. All patients had extra-renal complications (liver 9, pancreas 5, brain 3 and heart 3). Two patients were dialysed, and one was ventilated. After failure of plasma exchange to increase platelets in the first three patients, eculizumab was administered in all nine patients, 0-4 days after HUS diagnosis (median 1 day). One patient with very severe neurological HUS received immunoadsorption. Outcome was favourable in all patients, with rapid normalization of haemoglobin, platelets, LDH levels, renal function and neurological improvement. There were no deaths and no serious adverse events related to eculizumab. CONCLUSIONS: Early treatment of O104:H4 STEC-HUS by eculizumab was associated with a rapid and efficient recovery. Controlled prospective evaluation of eculizumab in STEC-HUS is warranted.

Rituximab for minimal-change nephrotic syndrome in adulthood: predictive factors for response, long-term outcomes and tolerance.

BACKGROUND: Minimal-change nephrotic syndrome (MCNS) is a common cause of steroid sensitive nephrotic syndrome (NS) with frequent relapse. Although steroids and calcineurin inhibitors (CNIs) are the cornerstone treatments, the use of rituximab (RTX), a monoclonal antibody targeting B cells, is an efficient and safe alternative in childhood. METHODS: Because data from adults remain sparse, we conducted a large retrospective and multicentric study that included 41 adults with MCNS and receiving RTX. RESULTS: Complete (NS remission and withdrawal of all immunosuppressants) and partial (NS remission and withdrawal of at least one immunosuppressants) clinical responses were obtained for 25 and 7 patients, respectively (overall response 78%), including 3 patients that only received RTX and had a complete clinical response. After a follow-up time of 39 months (6-71), relapses occurred in 18 responder patients [56%, median time 18 months (3-36)]. Seventeen of these received a second course of RTX and then had a complete (n = 13) or partial (n = 4) clinical response. From multivariate analysis, on-going mycophenolate mofetil (MMF) therapy at the time of RTX was the only predictive factor for RTX failure [HR = 0.07 95% CI (0.01-0.04), P = 0.003]. Interestingly, nine patients were still in remission at 14 months (3-36) after B-cell recovery. No significant early or late adverse event occurred after RTX therapy. CONCLUSIONS: RTX is safe and effective in adult patients with MCNS and could be an alternative to steroids or CNIs in patients with a long history of relapsing MCNS.

Impact of prior CKD management in a renal care network on early outcomes in incident dialysis patients: a prospective observational study.

BACKGROUND: Effective therapeutic strategies are available to prevent adverse outcomes in patients with chronic kidney disease (CKD) but their clinical results are hindered by unplanned implementation. Coordination of care emerges as a suitable way to improve patient outcomes. In this study, we evaluated the effect of planned and coordinated patient management within a dedicated renal care network comparatively to standard renal care delivered in nephrology departments of teaching hospitals. METHODS: This observational matched cohort study included 40 patients with CKD stage 4-5 in the network group as compared with a control group of 120 patients matched for age, sex and diabetic status. Main outcome was a composite endpoint of death from cardiovascular cause and cardiovascular events during the first year after dialysis initiation. RESULTS: There was no difference between the two groups neither for the primary outcome (40% vs 41%) nor for the occurrence of death from cardiovascular cause or cardiovascular events. Whereas the proportion of patients requiring at least one hospitalization was identical (83.3% vs 75%), network patients experienced less individual hospitalizations than control patients (2.3 ± 2.0 vs 1.6 ± 1.7) during the year before dialysis start. Patients of the network group had a slower renal function decline (7.7 ± 2.5 vs 4.9 ± 1.1 ml/min/1,73 m(2) per year; p=0.04). CONCLUSIONS: In this limited series of patients, we were unable to demonstrate a significant impact of the coordinated renal care provided in the network on early cardiovascular events in incident dialysis patients. However, during the predialysis period, there were less hospitalizations and a slower slope of renal function decrease.

Outbreak of Shiga toxin-producing Escherichia coli O104:H4 associated with organic fenugreek sprouts, France, June 2011.

BACKGROUND: On 22 June 2011, 8 patients with hemolytic uremic syndrome (HUS) or bloody diarrhea were reported in France. All 8 were attendees of a community center event on 8 June near Bordeaux. Three Escherichia coli cases were confirmed by isolation of Shiga toxin-producing E. coli O104:H4 stx2 aggR producing a cefotaximase (CTX-M) ß-lactamase (STEC O104:H4); the same rare serotype caused the outbreak in Germany in May-July 2011. An investigation was initiated to describe the outbreak, identify the vehicle for infection, and guide control measures. METHODS: We conducted a retrospective cohort study among all adults attending the event, including food handlers. A standardized questionnaire was administered to participants. A case was an attendee who developed HUS or diarrhea between 8 and 24 June. Cases were confirmed by isolation of STEC O104:H4 or O104 serology. Relative risks (RRs) and 95% confidence intervals (CIs) by exposure were calculated using a Poisson regression model. RESULTS: Twenty-four cases were identified (14% attack rate). Of these, 18 (75%) were women, 22 (92%) were adults, 7 (29%) developed HUS, 5 (21%) developed bloody diarrhea, and 12 (50%) developed diarrhea. Ten (42%) cases were confirmed. Fenugreek was the only sprout type with an independent association to illness (RR, 5.1; 95% CI, 2.3-11.1) in multivariable analysis. CONCLUSIONS: This investigation identified a point-source STEC O104:H4 outbreak associated with consumption of fenugreek sprouts. Comparison of results from French and German STEC O104:H4 outbreak investigations enabled identification of a common food vehicle, fenugreek sprouts, and resulted in implementation of Europe-wide control measures in July 2011.

[Psychological impact of lockdown and the COVID-19 epidemic on haemodialysis patients and carers in France]. / Répercussions psychologiques du confinement et de l'épidémie à COVID-19 chez les patients et soignants en hémodialyse en France.

INTRODUCTION: The health crisis linked to the COVID-19 epidemic has required lockdown measures in France and changes in practices in dialysis centers. The objective was to assess the depressive and anxiety symptoms during lockdown in hemodialysis patients and their caregivers. METHODS: We sent, during lockdown period, between April and May 2020, self-questionnaires to voluntary subjects (patients and caregivers), treated by hemodialysis or who worked in hemodialysis in one of the 14 participating centers in France. We analyzed their perception of dialysis sessions (beneficial or worrying), their stress level (VAS rated from 0 to 10), their anxiety and depressive symptoms (Hospital anxiety and depression scale). Factors associated with stress, anxiety and depression were analyzed with multiple linear regression models. RESULTS: 669 patients and 325 caregivers agreed to participate. 70 % of participants found it beneficial to come to dialysis during confinement. The proportions of subjects with a stress level ≥ 6 linked to the epidemic, confinement, fear of contracting COVID-19 and fear of infecting a loved one were respectively 23.9%, 26.2%, 33.4% and 42%. 39.2% presented with certain (13.7%) or doubtful (19.2%) anxious symptoms. 21.2% presented a certain (7.9%) or doubtful (13.3%) depressive symptomatology. Age, gender, history of psychological disorders and perception of dialysis sessions were associated with levels of stress, anxiety and depression. CONCLUSION: During the lockdown period, in France, the majority of hemodialysis patients and caregivers found it beneficial to come to dialysis. One in three subjects had anxiety symptoms and one in five subjects had depressive symptoms.

Large kidneys predict poor renal outcome in subjects with diabetes and chronic kidney disease.

BACKGROUND: Renal hypertrophy occurs early in diabetic nephropathy, its later value is unknown. Do large kidneys still predict poor outcome in patients with diabetes and Chronic Kidney Disease (CKD)? METHODS: Seventy-five patients with diabetes and CKD according to a Glomerular Filtration Rate (GFR, by 51Cr-EDTA clearance) below 60 mL/min/1.73 m2 or an Albumin Excretion Rate above 30 mg/24 H, had an ultrasound imaging of the kidneys and were cooperatively followed during five years by the Diabetology and Nephrology departments of the Centre Hospitalier Universitaire de Bordeaux. RESULTS: The patients were mainly men (44/75), aged 62 +/- 13 yrs, with long-standing diabetes (duration:17 +/- 9 yrs, 55/75 type 2), and CKD: initial GFR: 56.5 (8.5-209) mL/min/1.73 m2, AER: 196 (20-2358) mg/24 H. Their mean kidney lenght (108 +/- 13 mm, 67-147) was correlated to the GFR (r = 0.23, p < 0.05). During the follow-up, 9/11 of the patients who had to start dialysis came from the half with the largest kidneys (LogRank: p < 0.05), despite a 40% higher initial isotopic GFR. Serum creatinine were initially lower (Small kidneys: 125 (79-320) micromol/L, Large: 103 (50-371), p < 0.05), but significantly increased in the "large kidneys" group at the end of the follow-up (Small kidneys: 129 (69-283) micromol/L, Large: 140 (50-952), p < 0.005 vs initial). The difference persisted in the patients with severe renal failure (KDOQI stages 4,5). CONCLUSIONS: Large kidneys still predict progression in advanced CKD complicating diabetes. In these patients, ultrasound imaging not only excludes obstructive renal disease, but also provides information on the progression of the renal disease.

Restricted protein diet is associated with decrease in proteinuria: consequences on the progression of renal failure.

OBJECTIVE: Reduction of proteinuria is associated with a slower progression of renal failure. We questioned whether the change in proteinuria in response to a supplemented very low protein diet (SVLPD), which is known to reduce proteinuria, could function as a marker of the potential renoprotective effect of an SVLPD. DESIGN AND PATIENTS: In the 220 consecutive patients of our previously published cohort, the glomerular filtration rate (GFR) was assessed every 3 months using the (51)Cr-EDTA method. Seventy-eight patients (mean age 52 +/- 17 years, body mass index 23 +/- 3 kg/m(2), GFR 15 +/- 6 mL/min) exhibited a proteinuria more than 1 g per day at the start of the regimen. Mean protein intake assessed by urinary nitrogen appearance was 0.42 +/- 0.24 g/kg per day at 4 months. The median follow-up was 24 months. RESULTS: Proteinuria decreased significantly after patients were treated with an SVLPD. The maximum mean percent reduction was attained at 3 months (47% +/- 27%), was not influenced by the levels of baseline proteinuria, and was similar in patients receiving or not receiving angiotensin-converting enzyme inhibition at the start of the study. The percent reduction and the residual proteinuria at 3 months predicted the rate of the later GFR decline. GFR decline was significantly lower in patients whose reduction in proteinuria at 3 months was higher than 50% (0.42 +/- 0.37 mL/min/mo vs. 0.10 +/- 0.15 mL/min/mo and 1.0 +/- 0.6 mL/min/mo vs. 0.15 +/- 0.19 mL/min/mo, P < .001 in patients with proteinuria higher or lesser than 3 g/d at start, respectively). CONCLUSION: These results do not differ from those reported with therapies antagonizing angiotensin II formation and/or activity aiming at reducing proteinuria in chronic renal diseases.

[Strategies to slow the progression of chronic kidney disease]. / Stratégies pour ralentir la progression des maladies rénales chroniques.

High blood pressure and proteinuria are the major factors that drive progression of chronic kidney disease. Target levels for preserving renal function are blood pressure less than 130/80 mmHg and proteinuria less than 0.5 g/day. Angiotensin II converting enzyme inhibitors and sartans should be used as first-line therapy to reach these targets. Their use requires close monitoring of renal function and serum potassium levels. Moderate sodium restriction, possibly combined with diuretic therapy, helps to maximize the effect of renin-angiotensin inhibitors. Patients with chronic kidney disease have a high risk of acute kidney failure, especially due to drugs. All prescriptions must take into account the existence and extent of kidney disease. Patient adhesion and collaboration between health professionals are required if these measures are to be effective in the long term.

Early evolution of nutritional status and body composition after kidney transplantation.

BACKGROUND: Previous series have dealt with nutritional status after kidney transplantation. However, few studies have described the outcome of body composition after kidney transplantation. METHODS: A total of 44 cadaver kidney transplant recipients (28 men and 16 women) were followed prospectively during the first post-transplant year. Biochemical nutritional markers, dietary records, anthropometric measurements, and body composition were assessed at kidney transplantation and 3, 6, and 12 months later. RESULTS: By the end of the first year, serum albumin level was not significantly different from initial values. Prealbumin and retinol binding protein decreased from 42.3 +/- 10.2 mg/dL to 30.4 +/- 6.3 mg/dL and from 1.96 +/- 0.61 g/dL to 0.65 +/- 0.2 g/dL (P < 0.0001). Separating patients by gender showed that dietary caloric and protein intake increased in women only. At the end of the follow-up period, mean weight change was +5.4 kg in women (P = 0.009) and -0.9 kg in men (not significant). Body composition analyses showed that in women total fat and lean masses increased (+2.1 kg, P = 0.05, and +2.4 kg, P = 0.006), whereas in men total fat mass decreased (-1.4 kg, P = 0.04), and total lean mass tended to increase (+0.5 kg, not significant). Percentage change in total bone mass was +1.4% in women (not significant) and -2.1% in men (P = 0.05). In multivariate analyses, an independent impact of female gender on weight gain was observed, although increased fat mass was related only to energy intake. Increased total lean mass was related to low steroid doses and the absence of acute rejection and delayed graft function. Bone loss was related to male gender and high steroid doses. CONCLUSION: Changes in body composition during the first year after kidney transplantation are modulated by gender, energy intake, steroid doses, the occurrence of acute rejection, and delayed graft function.

[Renal involvement in cancer and renal paraneoplastic syndromes]. / Syndromes paranéoplasiques à expression rénale et atteintes rénales des cancers.

BACKGROUND: Renal alterations in the context of neoplastic disease are relatively frequent manifestations but are overall poorly reported. MATERIAL AND METHODS: A search in the English and French literature was performed using the following key words: "cancer", "renal", "paraneoplastic syndrome", "glomerulopathy" and "kidney failure". RESULTS: The various renal manifestations can be divided into specific and paraneoplastic. They include paraneoplastic glomerulopathies (membranous glomerulonephristis being the most frequent), direct involvement of the renal parenchyma, hydroelectrolytic abnormalities (hypercalcemia, inappropriate antidiuretic hormone secretion…), retroperitoneal fibrosis, micro-angiothrombotic disease and tumor lysis syndrome. Anticancer and symptomatic treatments do not guaranty complete recovery in all cases. CONCLUSION: The frequency and the severity of some renal manifestations associated with malignant hemopathies and carcinomas indicates a need for initial renal-oriented work-up and follow-up.

Long-term outcome on renal replacement therapy in patients who previously received a keto acid-supplemented very-low-protein diet.

BACKGROUND: The consequences of a supplemented very-low-protein diet remain a matter of debate with regard to patient outcome before or after the onset of renal replacement therapy. OBJECTIVE: We evaluated the long-term clinical outcome during maintenance dialysis and/or transplantation in patients who previously received a supplemented very-low-protein diet. DESIGN: We assessed the outcome of 203 patients who received a supplemented very-low-protein diet for >3 mo (inclusion period: 1985-2000) and started dialysis after a mean diet duration of 33.1 mo (4-230 mo). RESULTS: The survival rate in the whole cohort was 79% and 63% at 5 and 10 y, respectively. One hundred two patients continued with chronic dialysis during the entire follow-up, and 101 patients were grafted at least once. Patient outcomes were similar to those of the French Dialysis Registry patients for the dialysis group and similar to the 865 patients who were transplanted in Bordeaux during the same period for the transplant group. There was no correlation between death rate and duration of diet. CONCLUSIONS: The lack of correlation between death rate and duration of diet and the moderate mortality rate observed during the first 10 y of renal replacement therapy confirm that a supplemented very-low-protein diet has no detrimental effect on the outcome of patients with chronic kidney disease who receive renal replacement therapy.

Nutrition in hemodialysis patients previously on a supplemented very low protein diet.

BACKGROUND: Nutritional safety of protein-restricted diets in patients with chronic renal failure is controversial. In the present study, we have assessed the evolution of nutritional status after initiation of hemodialysis in patients previously treated by a supplemented very low protein diet (SVLPD). METHODS: Nutritional data were prospectively collected during the first year of hemodialysis from 15 consecutive patients treated with a SVLPD (0.3 g protein/kg/day supplemented with essential amino acids, calcium, iron, and vitamins) and compared to 15 age- and gender-matched end-stage renal disease (ESRD) patients previously on a less-restricted diet (0.90 +/- 0.21 g protein/kg/day) who started hemodialysis during the same period. Dual-energy x-ray absorptiometry (DEXA) was used to assess body composition at 0, 6, and 12 months. Hemodialysis prescriptions, biologic data and 3-day food records were collected every 3 months. RESULTS: Protein intake was higher than 1.2 g/kg/day in both groups as soon as 3 months after the start of hemodialysis. Albumin and prealbumin increased significantly during the first 6 months in all patients. Body mass index (BMI) increased in all patients (+0.97 +/- 1.31 kg/m2; P < 0.001) reflecting a gain in fat mass in the overall population (+2.36 +/- 2.94 kg/m2; P < 0.001) while lean body mass remained stable overall. CONCLUSION: Once on hemodialysis, SVLPD patients rapidly increased protein intake. Nutritional status improved in all patients, with a gain in fat mass in all, and a gain in lean body mass in SVLPD men only. These data indicate that treatment with a SVLPD prior to hemodialysis initiation is nutritionally safe.

C-reactive protein and procalcitonin as markers of mortality in hemodialysis patients: a 2-year prospective study.

OBJECTIVE: We have previously shown in a transversal study that PCT combined to CRP is associated to an altered nutritional status in hemodialysis patients. In a 2-year prospective study, we have assessed the relationship between markers of inflammation or nutrition and mortality. DESIGN: Two-year prospective study, in 61 patients dialyzed in our unit (29 M/32 F, age 63 +/- 15 years, on dialysis for 76 +/- 94 months, 12 hrs/wk, on high-flux (HF) membrane for 25 patients and low-flux (LF) for 36 patients, without reuse). Kt/V was 1.53 +/- 0.30. SETTING: Hospital-based dialysis unit. MAIN OUTCOME MEASURE: CRP, PCT, ferritin, albumin, and prealbumin, were measured in 04/99 (T0) and every 6 months thereafter. Interleukin-6 (IL6) and fibrinogen were measured at the start of study. The outcome and the causes of death of patients were noted in 58 patients, 3 patients were lost of follow-up. RESULTS: The mortality (24 deaths) was 42% at 2 years in this hospital based unit. The main causes of mortality were cardiovascular diseases (71%) and infection (17%). Patients were classified according to their CRP (CRP+ if CRP > or = 5 mg/L; n = 40), and PCT values (PCT + if PCT > or = 0.5 ng/mL; n = 25). IL6 level was > or = 10 pg/mL for 95% of the patients. Mortality was higher in the CRP+ group (Kaplan-Meier test P < .01) but not in the PCT or IL6 positive patients. All patients of the CRP+ group at T0 remained CRP+. Only 56% of patients of PCT+ remained positive at 6 months. When patients were grouped according to CRP quartile the difference on survival remained significant (P = .03), patients who were classified in the third and fourth quartile (upper than 9.9 mg/L), exhibited a higher rate of mortality than the lower quartile. The concomitant presence of a high level of PCT and CRP was associated with a worsened nutritional status at T0 but PCT level had no influence on 2-year mortality. CONCLUSION: In this 2-year prospective study in a hospital-based cohort of high-risk hemodialysis patients, elevated CRP, but not raised PCT, was associated with increased mortality. Inflammation remained present throughout a 2-year follow-up in patients with an initial CRP higher than 5 mg/L. An upper value of CRP above 9.9 mg/L is independly predictive of mortality, mainly from cardiovascular causes. The association of high PCT and CRP was no more predictive of mortality than high CRP.

Mycophenolic acid antagonizes the activation of cultured human mesangial cells.

BACKGROUND: Activation of mesangial cells is observed in several forms of chronic renal disease, and in culture conditions upon stimulation by fetal calf serum (FCS), or agonists such as transforming growth factor beta (TGF-beta). Mycophenolate mofetil (MMF), the precursor of mycophenolic acid (MPA), is currently used in organ transplantation and has been shown to be protective in clinical and experimental glomerulonephritis. This study assessed the effects of MPA on markers of human mesangial cells (HMC) activation. METHODS: Primary cultures of HMC and of an immortalized HMC clone (IP15 cells characterized in this report) were stimulated either by FCS or by TGF-beta, and treated by MPA at clinically relevant concentrations (1 to 10 micromol/L) for 24 hours to 14 days. HMC proliferation, smooth muscle alpha-actin (SMA), collagen type I alpha-1 chain (coll I) and fibronectin synthesis were used as markers of HMC phenotypic activation. RESULTS: Exposure of HMC to MPA inhibited proliferation induced by FCS without cytotoxicity. MPA counteracted the stimulatory effects of FCS and TGF-beta on coll I mRNA and protein and fibronectin protein. SMA expression was increased upon exposure to MPA, without cell hypertrophy. CONCLUSION: Treatment of cultured HMC with MPA inhibited mesangial cell proliferation and matrix production induced by stimulation with either FCS or TGF-beta. Such mechanisms may contribute to the favorable effects of treatment using mycophenolate mofetil in chronic fibrotic kidney diseases, including chronic allograft rejection.