Lucile Mercadal

Presentation and Outcome of Patients with Systemic Amyloidosis Undergoing Dialysis

BACKGROUND AND OBJECTIVES Light chain (AL) and secondary (AA) amyloidosis usually present as a systemic disease frequently involving the kidney and leading to ESRD. Data regarding patients with AA or AL amyloidosis undergoing dialysis remain scarce. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We retrospectively studied patients with AA or AL amyloidosis who started dialysis in five French centers between January 1, 1995 and December 31, 2005. RESULTS We identified 19 patients with AL and 20 patients with AA amyloidosis undergoing dialysis. Patients with AL amyloidosis had shorter time from diagnosis to dialysis (25.2 versus 69.3 mo, P < 0.05) and more extrarenal amyloidosis, especially cardiac (63.2 versus 5%, P < 0.0001). Mean duration of follow-up was 37.4 and 31.8 mo for patients with AL and AA amyloidosis, respectively. Fifteen patients (78.9%) with AL and three patients (15%) with AA amyloidosis died on dialysis. Median survival was shorter in patients with AL (26 mo) than AA amyloidosis [not definable (ND)] (P < 0.02). Sepsis and cardiac deaths were the main causes of mortality. Prognosis factors for death at 1 yr were AL type (P < 0.01), cardiac amyloidosis [odds ratio (OR) = 18, P < 0.01], heart failure (OR = 8, P < 0.04), and shorter time from diagnosis to dialysis (6.1 versus 56 mo, P < 0.03). Multivariate analysis indicated that AL type (P = 0.02), but not cardiac amyloidosis was independently associated with global mortality. CONCLUSIONS Survival of patients with amyloidosis undergoing dialysis, especially AL type, is probably better than previously reported. However, mortality is higher in AL than AA type, especially in the setting of cardiac involvement.

Timing and Determinants of Erythropoietin Deficiency in Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Anemia in patients with CKD is highly related to impaired erythropoietin (EPO) response, the timing and determinants of which remain unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study measured EPO levels and studied their relation to GFR measured by 51Cr-EDTA renal clearance (mGFR) in 336 all-stage CKD patients not receiving any erythropoiesis-stimulating agent. RESULTS In patients with anemia defined by World Health Organization criteria (hemoglobin [Hb] <13 g/dl in men and 12 g/dl in women), EPO response to Hb level varied by mGFR level. EPO and Hb levels were negatively correlated (r=-0.22, P=0.04) when mGFR was >30 ml/min per 1.73 m(2), whereas they were not correlated when mGFR was <30 (r=0.09, P=0.3; P for interaction=0.01). In patients with anemia, the ratio of observed EPO to the level predicted by the equation for their Hb level decreased from 0.72 (interquartile range, 0.57-0.95) for mGFR ≥60 ml/min per 1.73 m(2) to 0.36 (interquartile range, 0.16-0.69) for mGFR <15. Obesity, diabetes with nephropathy other than diabetic glomerulopathy, absolute iron deficiency, and high C-reactive protein concentrations were associated with increased EPO levels, independent of Hb and mGFR. CONCLUSIONS Anemia in CKD is marked by an early relative EPO deficiency, but several factors besides Hb may persistently stimulate EPO synthesis. Although EPO deficiency is likely the main determinant of anemia in patients with advanced CKD, the presence of anemia in those with mGFR >30 ml/min per 1.73 m(2) calls for other explanatory factors.

Electrophysiological response to dialysis: the role of dialysate potassium content and profiling.

UNLABELLED The task of dialysis therapy is, amongst other things, to remove excess potassium (K+) from the body. The need to achieve an adequate K+ removal with the risk of cardiac arrhythmias due to sudden intra-extracellular K+ gradient advises the distribution of the removal throughout the dialysis session instead of just in the first half. The aim of the study was to investigate the electrical behavior of two different K+ removal rates on myocardial cells (risk of arrhythmia and ECG alterations). Constant acetate-free biofiltration (AFB) and profiled K+ (decreasing during the treatment) AFB (AFBK) were used in a patient sample to understand, first of all, the effect on premature ventricular contraction (PVC) and on repolarization indices [QT dispersion (QTd) and principal component analysis (PCA)]. The study was divided into two phases: phase 1 was a pilot study to evaluate K+ kinetics and to test the effect on the electrophysiological response of the two procedures. The second phase was set up as an extended cross-over multicenter trial in patient subsets prone to arrhythmias during dialysis. Phase 1: PVC increased during both AFB and AFBK but less in the latter in the middle of dialysis (298 in AFB vs. 200 in AFBK). The PVC/h in a subset of arrhythmic patients was 404 +/- 145 in AFB and 309 +/- 116 in AFBK (p = 0.0028). QT interval (QTc) prolongation was less pronounced in AFBK than in AFB. Phase 2: The PVC again increased in both AFB and AFBK but less in the latter mid-way through dialysis (79 +/- 19 AFB vs. 53 +/- 13 AFBK). Moreover, in the most arrhythmic patients the benefit accruing from the smooth K+ removal rate was more pronounced (103 +/- 19 in AFB vs. 78 +/- 13 in AFBK). CONCLUSION It is not the K+ dialysis removal alone that can be destabilizing from an electrophysiological standpoint, but rather its removal dynamics. This is all the more evident in patients with arrhythmias who benefit from the K+ profiling during their dialysis treatment.

Neurotoxicity of Valacyclovir in Peritoneal Dialysis: A Pharmacokinetic Study

Valacyclovir is an effective oral agent for the treatment of herpes virus infection, however, the pharmacokinetics of the drug are altered in renal failure. It is increasingly recognized that dose adjustment of oral valacyclovir in renal failure is necessary to avoid neurotoxicity. We studied this drug in a continuous ambulatory peritoneal dialysis (CAPD) and immunocompromised patient. She developed neurotoxicity with an adjustment dosage of valacyclovir for a cutaneous zoster infection. The elimination half-time (15 h) was similar to that reported for end-stage renal disease patients, while the steady-state volume of distribution (85 l) and the area under the curve concentration (127 mg/l·h) were greater. The mean CAPD dialysance was only 5.27 ml/min with less than 1% of an administered dose being recovered in the 24-hour dialysate. 48 h after interrupting treatment, she recovered normal neurological status and 500 mg of valacyclovir every 2 days was effective and well tolerated.

Improved survival associated with acetate-free haemodialysis in elderly: a registry-based study

BACKGROUND Acetate-free dialysis (AFD) improves haemodynamic stability during dialysis, compared with standard haemodialysis (HD) with a small amount of acetic acid. Using the national REIN registry, we classified 15 160 incident patients who started HD from 2008 to 2010 into three exposure categories according to the type of dialysate used in their dialysis unit: standard dialysate only (reference), both standard and AFD (mixed unit) or HCl dialysate only (100% HCl unit). METHODS Cox survival analysis was adjusted for 15 baseline comorbidities, laboratory data and haemodiafiltration (HDF). We took patient clustering within units into account, used age as the time scale and treated patient exposure to AFD and to HDF as time-dependent variables. RESULTS Median age (interquartile range) was 70.5 years (58.1-78.8). Over a median follow-up of 1.8 years (1.2-2.6), 658 patients were dialysed in a 100% HCl unit, 3021 in a mixed unit and 11 481 were never exposed to AFD. The relation between AFD and mortality was not constant with age (Schoenfeld residuals test P = 0.01 for mixed group and P = 0.03 for 100%HCl group). Patients older than 70 years had a significantly lower mortality risk associated with AFD [hazard ratio (HR) = 0.79, 95% confidence interval (CI) = 0.67 to 0.94 for patients exposed in a 100% HCl unit; HR = 0.83, 95% CI = 0.74 to 0.94 for patients exposed in a mixed unit], but no association was found in younger patients. CONCLUSIONS AFD was associated with improved survival independent of comorbidities and HDF in patients aged 70 years and older but not in patient younger than 70 years.

A 3-Marker Index Improves the Identification of Iron Disorders in CKD Anaemia

Background Iron disorders are common and complex in chronic kidney disease (CKD). We sought to determine whether a 3-marker index would improve the classification of iron disorders in CKD anaemia. Methods We studied the association between Hb level and iron indexes combining 2 or 3 of the following markers: serum ferritin (<40 ng/mL), transferrin saturation (TSAT<20%) and total iron binding capacity (TIBC<50 µmol/L) in 1011 outpatients with non-dialysis CKD participating in the Nephrotest study. All had glomerular filtration rates measured (mGFR) by 51Cr-EDTA renal clearance; 199 also had hepcidin measures. Results The TSAT-TIBC-ferritin index explained Hb variation better than indexes combining TSAT-TIBC or ferritin-TSAT. It showed hypotransferrinaemia and non-inflammatory functional iron deficiency (ID) to be more common than either absolute or inflammatory ID: 20%, 19%, 6%, and 2%, respectively. Hb was lower in all abnormal, compared with normal, iron profiles, and decreased more when mGFR was below 30 mL/min/1.73 m2 (interaction p<0.0001). In patients with mGFR<30 mL/min/1.73 m2, the Hb decreases associated with hypotransferrinaemia, non-inflammatory functional ID, and absolute ID were 0.83±0.16 g/dL, 0.51±0.18 and 0.89±0.29, respectively. Compared with normal iron profiles, hepcidin was severely depressed in absolute ID but higher in hypotransferrinaemia. Conclusions The combined TSAT-TIBC-ferritin index identifies hypotransferrinaemia and non-inflammatory functional ID as the major mechanisms of iron disorders in CKD anaemia. Both disorders were associated with a greater decrease in Hb when mGFR was <30 mL/min/1.73 m2. Taking these iron profiles into account may be useful in stratifying patients in clinical trials of CKD anaemia and might improve the management of iron therapy.

Rituximab alone as induction therapy for membranous lupus nephritis: A multicenter retrospective study

Abstract The optimal treatment for pure membranous lupus nephritis (MLN) remains undetermined. Rituximab constitutes a promising therapeutic option for lupus nephritis and is currently being evaluated for use in idiopathic membranous nephritis. We retrospectively analysed the efficacy and tolerance of rituximab as a monotherapy in the induction treatment of pure MLN. We retrospectively investigated SLE patients with biopsy-proven pure class V lupus nephritis presenting with a protein-to-creatinine ratio of at least 2 g/g and treated with rituximab as monotherapy. A background low dose of corticosteroids (⩽20 mg/day) was allowed, as was hydroxychloroquine; higher doses of steroids and/or immunosuppressive drugs fell under the exclusion criteria. Remission status was evaluated at baseline and 6, 12, and 24 months after rituximab. The study included 15 patients (13 women, median age 37 years, 27% with extra-renal manifestations, median SLE duration 1.5 years). The median protein-to-creatinine ratio was 4.9 g/g, 80% of the patients had nephrotic-range proteinuria, the median serum albumin was 24 g/L, the median serum creatinine was 0.7 mg/dL, and the median eGFR was 122 mL/min/1.73 m2. The median follow-up was 29 months (6–112 months). Treatment failure occurred in 2 patients. However, remission was recorded in the remaining 13 (87%, complete remission in 8 patients) with a median time to remission of 5 months. Median proteinuria decreased from 4.9 g/g to 0.16 g/g at month 12 and to 0.11 g/g at month 24. Median serum albumin increased to 36.5 g/L at month 24, and all patients had serum albumin levels greater than 30 g/L at month 12. Renal function remained stable in all patients. Relapse of proteinuria was recorded in 3 patients (at 12, 29, and 34 months). No patients experienced serious adverse events. Rituximab as monotherapy may represent an effective treatment for pure MLN with an excellent tolerance profile.