Organ Transplantation in Hereditary Fibrinogen A α-Chain Amyloidosis: A Case Series of French Patients.

RATIONALE & OBJECTIVE: Fibrinogen A α-chain amyloidosis (AFib amyloidosis) is a form of amyloidosis resulting from mutations in the fibrinogen A α-chain gene (FGA), causing progressive kidney disease leading to kidney failure. Treatment may include kidney transplantation (KT) or liver-kidney transplantation (LKT), but it is not clear what factors should guide this decision. The aim of this study was to characterize the natural history and long-term outcomes of this disease, with and without organ transplantation, among patients with AFib amyloidosis and various FGA variants. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 32 patients with AFib amyloidosis diagnosed by genetic testing in France between 1983 and 2014, with a median follow-up of 93 (range, 4-192) months, were included. RESULTS: Median age at diagnosis was 51.5 (range, 12-77) years. Clinical presentation consisted of proteinuria (93%), hypertension (83%), and kidney failure (68%). Manifestations of kidney disease appeared on average at age 57 (range, 36-77) years in patients with the E526V variant, at age 45 (range, 12-59) years in those with the R554L variant (P<0.001), and at age 24.5 (range, 12-31) years in those with frameshift variants (P<0.001). KT was performed in 15 patients and LKT was performed in 4. In KT patients with the E526V variant, recurrence of AFib amyloidosis in the kidney graft was less common than with a non-E526V (R554L or frameshift) variant (22% vs 83%; P=0.03) and led to graft loss less frequently (33% vs 100%). Amyloid recurrence was not observed in patients after LKT. LIMITATIONS: Analyses were based on clinically available historical data. Small number of patients with non-E526V and frameshift variants. CONCLUSIONS: Our study suggests phenotypic variability in the natural history of AFib amyloidosis, depending on the FGA mutation type. KT appears to be a viable option for patients with the most common E526V variant, whereas LKT may be a preferred option for patients with frameshift variants.

[Patterns of nephrology referral and predialysis management of patients with chronic kidney disease]. / Suivi néphrologique et niveau de prise en charge des patients en insuffisance rénale terminale.

INTRODUCTION: Numerous studies showed that late referral (LR) to a nephrologist of patients with chronic kidney disease stated by a simple quantitative criterium (initiation of renal replacement therapy (RRT) within 3 or 4 months of referral to a nephrologist, independantly from the quality of care) is associated with worse survival rate, limited to the first 3 months following the initiation of RRT. We wanted to test a criterium of LR definition supposing a more important "dose of nephrological care", to try to understand the reasons of this early death. METHODS: One hundred and thirty-eight patients receiving their first RRT in 1999 and 2000 in Valenciennes (France) were enrolled in this study. Two LR definitions were used: a qualitative criterium C1 (whether the patient was under an uninterrumpted nephrological pre-dialysis care - independantly from the date of the nephrological referral - or not) and a more simple quantitative criterium C2 (initiation of RRT within 3 months of referral to a nephrologist). Comorbidity was assessed by Charlson's score. The analysis concerned the respective influence of C1 and C2 on the clinical and biological effects of chronical azotemia, on the circumstances at first RRT (emergency first dialysis, pulmonary edema, type of vascular access), and on survival rates (Kaplan-Meier's analysis). RESULTS: LR rates are 23% according to C1 and 20% according to C2. Comorbidity is similar in the different groups. Whatever the definition criterium, LR is associated to a lower hemoglobin and albumin, a more severe acidosis, a longer duration of first hospitalization, and higher rate of emergency first dialysis and use of central temporary catheter. The survival rates at 2 years following the first RRT of lately referred patients are 53% according to C1 (vs 86% for early referred patients, P<0,001) and 56% according to C2 (vs 84%, P<0,05). For both, early death (within the first 3 months) explained the observed differences of survival rates. CONCLUSION: In this study, early death of lately referred patients seems to be independant from the criterium of definition of LR. Elements of explanation are suggested, and can lead to further prospective studies.

Vitamin D2 versus vitamin D3 supplementation in hemodialysis patients: a comparative pilot study.

BACKGROUND: In patients with chronic kidney disease, vitamin D insufficiency is highly prevalent. It can be corrected by supplementation with either vitamin D(2) or vitamin D3. Recent studies in patients without impaired kidney function suggest that vitamin D(3) is more efficient than vitamin D(2) in correcting vitamin D insufficiency. However, no direct comparison has been made in hemodialysis (HD) patients. METHODS: Thirty-nine HD patients with serum 25-hydroxyvitamin D (25(OH)D) levels =20 ng/mL were enrolled in this comparative, prospective pilot study. They were divided into 3 groups and treated over a 3-month period. Each patient received oral doses of 200,000 international units (IU) vitamin D per month according to the following treatment schedule: (i) vitamin D(2) in small fractionated doses at each HD session, 3 times per week (group D2S); (ii) vitamin D(2) once a month (group D2M); or (iii) vitamin D(3) once a month (group D3M). Changes in serum 25(OH)D levels were measured at the end of the study. RESULTS: Posttreatment serum 25(OH)D levels increased significantly in all groups. The mean ± SD serum 25(OH)D value for group D3M patients (40 ± 13 ng/mL) was significantly higher than that for groups D2M (25 ± 9 ng/mL, p<0.01) and D2S patients (25 ± 9 ng/mL, p<0.01). Serum 25(OH)D increased to levels >30 ng/mL in 84% of group D3M patients, but in only 15% and 27% of group D2M and D2S subjects, respectively. CONCLUSION: Vitamin D(3) is more effective than vitamin D(2) in providing adequate 25(OH)D serum levels in HD patients.

Higher parathyroid hormone (PTH) concentrations with the Architect PTH assay than with the Elecsys assay in hemodialysis patients, and a simple way to standardize these two methods.

BACKGROUND: The Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend maintaining serum parathyroid hormone (PTH) concentration between 150 and 300 pg/mL in patients with chronic kidney disease (CKD) stage 5. However, a marked inter-method variability in PTH measurement has been reported recently. The aim of this study was to evaluate whether harmonization of the results measured with two commercial kits known to produce significantly different serum PTH concentrations could be reasonably achieved by a simple procedure. METHODS: The study comprised a total of 216 hemodialyzed patients in whom blood was collected immediately before a dialysis session. The patients were from three dialysis centers, which defined three groups (119, 34, and 63 patients for groups 1, 2, and 3, respectively). PTH was measured by two automated assays, the Elecsys (Roche Diagnostics) and Architect (Abbott Diagnostics) assays, in three different laboratories and with different lots of reagents. We arbitrarily chose the Roche assay as the reference method, because several studies had previously shown that the concentrations measured with this assay were very close to the Allegro assay used in the studies that defined the K/DOQI thresholds. Data are median (interquartile range). RESULTS: The median PTH concentrations were higher (p<0.001) in the Architect assay [238 (140-434) pg/mL] when compared to the Elecsys assay [182 (109-338) pg/mL]. Bland-Altman plots in the three groups showed a similar proportional bias between both kits. The Architect PTH/Elecsys PTH ratios were similar in the three groups [1.30 (1.25-1.35), 1.30 (1.19-1.39), and 1.31 (1.25-1.35)], and the ratio was 1.30 (1.25-1.35) in the cohort (pooling the three groups). In the whole population, 53 patients (24.5%) were classified differently by the two kits according to the K/DOQI cut-off values. We divided the Architect values by 1.3 to obtain "corrected" values. These corrected Architect values were not different to the measured Elecsys values, and the Bland-Altman plot comparing the Elecsys and the corrected Artchitect values did not show any systematic proportional bias. Only six patients (2.8%) were still classified differently by the Elecsys and the corrected Architect concentrations. CONCLUSIONS: We propose to divide the PTH values measured with the Architect PTH assay by 1.3 so that the corrected values are almost identical to those measured with the Elecsys assay.