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.

Impact of first dialysis modality on outcome of patients contraindicated for kidney transplant.

BACKGROUND: We compared, in patients contraindicated for kidney transplant, outcomes between those patients who were only on hemodialysis (HD) and those who were given peritoneal dialysis (PD) as first renal replacement therapy (RRT). DESIGN: Prospective, population-based cohort study of incident cases of end-stage renal disease between June 1997 and June 1999. SETTING: A network of dialysis care: NEPHROLOR, that is, all the renal units in Lorraine, one of the 22 French administrative regions (population over 2.3 million people). PARTICIPANTS: 387 patients were contraindicated for kidney transplant during the first 2 years of RRT: 284 were on HD, 103 on PD. Mean age was 67.6 +/- 11.3 years for HD patients and 70.8 +/- 11.4 years for PD patients (p = 0.015). MAIN OUTCOME MEASURES: Mortality until June 2003, hospitalization over the 2 first years of RRT, and Kidney Disease and Quality of Life Short Form (KDQOL-SF) 6 and 12 months after initiation of RRT. RESULTS: HD patients were more likely to die from cardiac or cerebrovascular causes, PD from cachexia or withdrawal from dialysis. Whatever mode of RRT, the unadjusted 2-year and 5-year survival rates were similar (p = 0.98). The rate of total duration of hospital stay per month of RRT was similarin HD and PD groups: 2.7 +/- 4.5 and 2.9 +/- 4.2 days respectively (p = 0.7). PD was associated with better quality of life than HD. The dimensions Role limitation due to emotional function, Burden of kidney disease, and Role limitation due to physical function ranked first, second, and third for PD. CONCLUSION: In Lorraine, end-stage renal disease patients who were given PD as first-line RRT had no excess of death risk or hospitalizations, and better quality of life the first year of RRT.

Impact of nephrology referral on early and midterm outcomes in ESRD: EPidémiologie de l'Insuffisance REnale chronique terminale en Lorraine (EPIREL): results of a 2-year, prospective, community-based study.

BACKGROUND: Most studies looking at how the outcome of end-stage renal disease (ESRD) is affected by the timing and quality of the care received before initiation of renal replacement therapy (RRT) are inconclusive. METHODS: Five hundred and two adult French patients (age, 62.8 +/- 16 years) receiving their first RRT were enrolled in a 2-year, community-based, prospective study. Subjects were assigned to 1 of 5 groups depending on the time between their first serum creatinine reading above 2 mg/dL (177 micromol/L): chronic renal failure (CRF) and nephrology referral (NR) and RRT. Multivariate logistic regression was used to analyze 90-day survival data, and data concerning long-term survival and inclusion on the waiting list for renal transplantation were analyzed using Cox proportional hazards regression. RESULTS: Overall survival rates were 88% at 90 days, 77.2% at 1 year, 65.2% at 2 years, and 54.2% at 3 years. The nephrology referral pattern was associated with age and systolic blood pressure, and independently predicted early death. Compared with group 1 (NR > 12 months), odds ratios (confidence interval 95%) were 2.7 (1.2 to 6.3) for group 2 (NR < or = 12 months or >4 months), 2.8 (1.0 to 8.0) for group 3 (NR < or = 4 months or >1 month), 4.9 (2.2 to 11.0) for group 4 (NR < or = 1 month; CRF > 1 month), and 5.2 (2.2 to 12.3) for group 5 (NR < or = 1 month; CRF < or = 1 month). Independent predictors of death in 90-day survivors were age, cardiac disease with previous episodes of heart failure, vascular disease, low diastolic blood pressure, and group 3 referral pattern. Not being entered on the waiting list for renal transplantation was predicted by age, diabetes, vascular disease, and nonelective first dialysis. CONCLUSION: Late nephrology referral is strongly associated with early death. Emergency first dialysis is an independent risk factor for not being placed on the waiting list for transplantation. Among 90-day survivors, referral pattern has little influence on mortality, which is mainly determined by cardiovascular complications at initiation of RRT.