Long-term outcome of renal transplantation in patients with familial Mediterranean fever amyloidosis: a single-center experience

Although recurrence of amyloid A deposition in the allograft can be seen in patients with secondary amyloidosis due to familial Mediterranean fever (FMF), renal transplantation remains to be a choice of treatment for end-stage renal disease. The aim of this study was to determine short- and long-term results of renal transplantation in patients with FMF amyloidosis. We compared the outcomes of 17 patients with FMF amyloidosis among 431 (3.9%) transplants with 209 control patients. We observed 93% and 94% graft and patient survivals at 1 year, and 89% and 90% at 5 years. Also, the mean serum creatinine levels at 1 and 5 years posttransplant were similar. Recurrence of amyloidosis was documented in two allograft recipients presenting with nephrotic range proteinuria (12%), one of whom lost the allograft due to recurrence. Eleven patients had FMF gene analysis. The results of MEFV mutation analyses were: M694V/M694V homozygote in six patients, M694V/EQ148 in one patient, M694V/V726A in one patient, 680M-I/E148Q in one patient. FMF gene analysis was negative in two patients. Recurrence was noticed in one patient with M694V/M694V, while the other did not have an FMF gene analysis. Colchicine was reduced in nine patients due to side effects. In conclusion, the long-term outcomes of transplantation in patients with amyloidosis secondary to FMF is similar to that in the general transplant population and maintenance colchicine, even at low dose, appears to effectively prevent recurrence of amyloidosis in the allograft.     

MEFV gene mutations in familial Mediterranean fever phenotype II patients with renal amyloidosis in childhood: a retrospective clinicopathological and molecular study.

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring attacks of fever and serositis. The definition of the mutated gene has allowed molecular diagnosis of the disease. The most important complication of FMF is the development of AA type secondary amyloidosis. In a group of patients clinically designated as phenotype II amyloidosis patients, renal amyloidosis develops without being preceded by typical attacks of the disease. In this study, the mutations of the MEFV gene were analysed in a group of patients clinically recognized as phenotype II. METHODS: DNA samples were obtained from tissue samples of the subjects. PCR-RFLP methods were used to analyse the M694V, M680I, V726A and E148Q mutations that have been previously defined by us to be the most common mutations in our Turkish cohort. RESULTS: The distribution of the four most common mutations among phenotype II patients was 38% for M694V, 8% for M680I, 4% for V726A and 4% for E148Q. CONCLUSIONS: In phenotype II amyloidosis patients, the distribution of the four common MEFV mutations was not significantly different from that found in all FMF patients with typical symptoms who do or do not develop amyloidosis. We therefore suggest that secondary genetic or environmental factors are operative in the development of secondary amyloidosis in patients with FMF.     

Two sisters with familial Mediterranean fever: lack of correlation between genotype and phenotype?

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever and serositis. The most important complication of FMF is renal amyloidosis, which determines the prognosis. The gene coding the disease (MEFV) is identified on the 16th chromosome. The most common MEFV mutations are M694V, M680I, V726A and M694I located on exon 10 and E148Q located on exon 2. Unfortunately, genotype-phenotype correlation is not well established and there are unexplained ethnic differences in amyloidosis rates. We report two sisters with a common genotype (M694V/M694V) presenting with different phenotypic characteristics: one complaining of intermittent abdominal pain, arthritis and fever, while the other was suffering from intermittent pleuritis and fever during attacks. The observation of different phenotypic presentations with a common genotype in two family members shows that different phenotypes cannot be explained by particular mutations. To understand the correlation between genotypic and phenotypic FMF variants the existence of complex alleles, modifier loci, genetic heterogeneity and possible epigenetic factors should be studied extensively.     

Mutational spectrum in the MEFV and TNFRSF1A genes in patients suffering from AA amyloidosis and recurrent inflammatory attacks.

BACKGROUND: Among hereditary fevers characterized by recurrent attacks of fever and organ localized inflammation, familial Mediterranean fever (FMF), and tumour necrosis factor receptor superfamily 1A (TNFRSF1A) receptor associated periodic syndrome (TRAPS) are diseases with identified genes that can be associated with renal amyloidosis of the AA type. In this study we have characterized FMF and TRAPS genotypes in 38 unrelated patients suffering from amyloidosis AA and recurrent inflammatory attacks. METHODS: Mutations of the MEFV and TNFRSF1A genes, responsible respectively for FMF and TRAPS, were searched for by amplifying, using polymerase chain reaction (PCR), genomic DNA, and direct sequencing. RESULTS: Twenty-seven patients (71%) carried mutations in MEFV (22 patients with two mutations, two patients with a single mutation) or TNFRSF1A genes (three patients). Patients with MEFV mutations belonged to the classical at-risk ethnic group for FMF: Sephardic Jews, Turks, Armenians, and Arabs from the Maghreb. The main genotype encountered was M694V/M694V (19/22), one Turkish patient was M680I/M680I, and two Arab patients from the Maghreb were M694I/M694I. We found three Caucasian patients with the C55S, C70Y, R92Q mutations in the TNFRSF1A gene. CONCLUSIONS: In this series we observed that FMF is the main cause of AA amyloidosis in Sephardic Jews and Turks. MEFV and TNFRSF1A mutations were found in only 6 of 14 Arab patients from the Maghreb. We found three families (one Caucasian and two from Maghreb) with AA amyloidosis without MEFV or TNFRSF1A mutations, suggesting that other genetic cause(s) exist(s). The characterization of mutations in MEFV and TNFRSF1A is important for the therapeutic behaviour of AA amyloidosis associated with inherited recurrent fever.     

Serum amyloid A1 -13 T/C alleles in Turkish familial Mediterranean fever patients with and without amyloidosis

Previously reported studies concerning the effect of homozygosity of the 1.1 allele of the SAA gene found a correlation between this haplotype and susceptibility to amyloidosis in FMF patients. Another report revealed a strong association between SAA1 -13T/C and secondary amyloidosis in the rheumatoid arthritis patient group. In this study, we aimed to determine the effect of SAA1 -13T/C in FMF patients with and without amyloidosis. The study cohort, consisting of 166 patients with FMF was divided into two groups, according to the presence (n=66) or absence (n=100) of renal amyloidosis at study entry. MEFV gene mutation analysis and allelic variant of SAA1 gene -13 T/C was analyzed according to the previously described techniques. SAA1 -13 T allele frequencies were 0.5816, 0.23 and 0.4242 in controls, FMF patients and FMF-amyloidosis patients respectively. The difference between controls vs. FMF patients and FMF-amyloidosis patients were 0.0002 and 0.1673 respectively. It was 0.0071 for FMF-patients vs. FMF-amyloidosis. When 694 M/V homozygous nonamyloid-FMF group was compared with 694 M/V carriers of the FMF-amyloidosis group, the difference was 0.049. When carrying TT allele was considered, the difference between controls vs. FMF patients and FMF-amyloidosis patients were 0.0001 and 0.58. It was 0.0003 for FMF patients vs. FMF-amyloidosis. When 694 M/V homozygous nonamyloid-FMF group was compared with 694 M/V carriers of the FMF-amyloidosis group, the difference was 0.03. Carrying SAA -13T in homozygote state revealed a 7.9 (95% CI 3.6 -17.5) fold risk for the occurrence of amyloidosis when compared with FMF patients without amyloidosis. This was 8.75 (95% CI 3.0 - 25.1) when 694 M/V homozygotes were taken into consideration. Our data revealed that the genotype SAA1 -13T has at least an effect on the development of amyloidosis. As more data on this polymorphism accumulate, we will understand its effect on the pathogenesis of amyloidosis in FMF.     

Genetic risk factors of amyloidogenesis in familial Mediterranean fever

BACKGROUND/AIMS: Evaluation of the risk factors, and phenotype-genotype correlation of familial Mediterranean fever (FMF) gene (MEFV) and serum amyloid A1 (SAA1) gene polymorphisms in renal amyloidosis. METHODS: We investigated MEFV and SAA1 genotypes (alpha, beta, and gamma isoforms) in 50 FMF patients and 50 healthy children. Tel-Hashomer criteria were used for the diagnosis and severity scoring of FMF. RESULTS: The most common MEFV mutation and SAA1 genotype were M694V/M694V (n = 26/50) and SAA1 alpha/alpha (n = 26/50), respectively. Positive family history for amyloidosis was significantly higher (p < 0.001) with more severe clinical course (p = 0.006) in the amyloidosis group than the non-amyloid group. In M694V/M694V mutation, erysipelas-like skin erythema (p = 0.029), arthritis (p = 0.004), arthralgia (p < 0.001) were significantly more frequent with higher severity scores (p = 0.008) than the patients with other mutations. Comparison of the SAA1 alpha/alpha genotype with other genotypes revealed more frequent arthritis (p = 0.003) in the SAA1 alpha/alpha genotype. In amyloidosis group patients having both M694V/M694V and SAA1 alpha/alpha genotypes were the largest subgroup (n = 14, p < 0.001). Logistic regression analysis for amyloidosis corrected risk revealed a 1.2 times increase in M694V/M694V, a 2.4 times increase in SAA1 alpha/alpha genotypes and a 2.5 times increase when both are together. CONCLUSION: Positive family history for amyloidosis and presence of SAA1 alpha/alpha genotype in M694V/M694V mutation may predispose to amyloidosis by increasing the clinical severity. Therefore, in such children early colchicine treatment might be recommended even if they are asymptomatic.     

Phenotype 2 Familial Mediterranean Fever: Evaluation of 22 Case Series and Review of the Literature on Phenotype 2 FMF

Familial Mediterranean fever (FMF) is an autosomal recessive autoimmune disorder characterized by recurrent bouts of fever and serosal inflammation. FMF may be complicated by AA-type amyloidosis, worsening the prognosis, with associated renal failure in some patients. Complication rate varies with race, being as high as 60% in Turks and as low as 2% in Armenians. In a few cases of patients with FMF (phenotype 2), amyloid nephropathy may be the presenting manifestation. This study included 420 patients who were admitted to the Nephrology and Rheumatology Departments of Atatürk Education and Research Hospital with unexplained proteinuria/nephrotic syndrome. The initial screening test for amyloidosis was the presence of significant proteinuria (300 mg/24 h). All MEFV gene exons were screened for causative mutations by direct DNA sequencing to check for any mutations. There were 22 phenotype 2 FMF patients with 27 allelic variants. The most prevalent allelic variants were M694V (10/27, 37%) and E148Q (7/27, 26%). Phenotype 2 FMF is not as rare as it was thought before; this should be kept in mind for all patients with unexplained proteinuria and/or acute phase response in high-risk ethnic groups for FMF.     

The Relationship between the MEFV Genotype,Clinical Features,and Cytokine-Inflammatory Activities in Patients with Familial Mediterranean Fever

Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by periodic attacks of fever and polyserositis. The effects of the MEFV genotype differences on clinical picture and inflammatory activity have not been well documented. The aim of this study was to investigate levels of conventional inflammation markers, procalcitonin, interleukin levels, TNF-alpha, and C5a levels in patients with FMF who had different MEFV genotypes and compare them with those of healthy subjects. The study consisted of 41 patients with FMF (F/M: 23/18), and 31 healthy subjects (F/M: 18/13). Tests were performed during the attack-free period.

White-blood cell count, CRP and IL-8 levels were higher in patients with FMF than in healthy subjects (p < 0.05) and also higher in M680I carriers than in the patients with M694V allele carriers. However, ESR, fibrinogen, procalcitonin, IL-6, C5a, TNF-alpha, and IgD levels were not significantly different between patients and healthy subjects (p > 0.05). Arthralgia or arthritis was significantly higher in M694V carriers than in non-M694V carriers (p < 0.05). It is concluded that the clinical features and inflammatory-cytokine activities were higher in patients with FMF during the attack-free period than in healthy subjects, and the different genotype might be related to different clinical pictures.     

Prevalence and significance of MEFV gene mutations in a cohort of patients with rheumatoid arthritis

ObjectivesPyrin/marenostrin, an inhibitory regulator of inflammation, is encoded by MEditerranean FeVer (MEFV) gene. Mutations of this gene are the cause of familial Mediterranean fever (FMF). A connection between MEFV gene mutations and rheumatic diseases has been suggested. The aim of this study was to explore the frequency and clinical significance of MEFV gene mutations in a cohort of Turkish patients with rheumatoid arthritis (RA).MethodsThe study included 103 patients with RA and 103 age-, sex- and origin-matched healthy controls (HC). In all participants, genomic DNA was isolated and genotyped using amplification refractory mutation system or restriction fragment length polymorphism for the eight MEFV gene mutations (E148Q, M694V, M694I, M680I, V726A, A744S, R761H, and P369S). In the RA group, disease activity was determined using the disease activity score-28 (DAS-28), and radiological damage was evaluated by the modified Larsen scoring method.ResultsCarrier rates of MEFV gene mutations were 26/103 (25.2%) and 24/103 (23.3%) in the RA and HC groups, respectively (p > 0.05, OR: 0.9, 95% CI: 0.48–1.71). In the RA group, while deformed joint count was significantly higher in the mutation carrier group than those of the non-carrier group (p < 0.05), the level of C-reactive protein, DAS-28 and modified-Larsen scores were slightly but not significantly higher in the carrier group.ConclusionThe results of this study suggest that MEFV gene mutations appear to be an aggravating factor for the severity of RA, and consequently, patients with RA might be screened for MEFV gene mutations in countries where FMF is frequent. Whether the searching of MEFV gene mutations in RA patients is cost-effective deserves further investigations.     

Higher thrombin activatable fibrinolysis inhibitor levels are associated with inflammation in attack-free familial Mediterranean fever patients

Background: Coagulation abnormalities have been reported in familial Mediterranean fever (FMF) patients with amyloidosis and nephrotic syndrome; but there is not enough data about the continuity of the thrombogenic activity in FMF patients in clinical remission. The purpose of this study was to assess thrombin activatable fibrinolysis inhibitor (TAFI) levels and its relationship with fibrinolytic activity and also evaluate relationships between mutations and clinical signs in attack-free patients without amyloidosis. Methods: Seventy-nine FMF patients and 40 healthy adults were included. The study group was divided into five groups as follows: first group, homozygote M694V; second group, homozygote M680I; third group, M694V in one allele, the other allele have other mutations or not; fourth group, other mutations; and fifth group, no mutation. Results: Serum TAFI levels were significantly increased in patients compared with healthy individuals (116.64?±?21.8 vs. 78.48?±?19.7?μg/mL, p?r?=?0.247, p?=?0.029 and r?=?0.252, p?=?0.032, respectively). Mean fibrinogen and TAFI levels were significantly higher in Group 1 than the other groups (p?=?0.04 and p?=?0.001, respectively) and in Group 3 it was higher than Groups 2, 4 and 5 (p?=?0.04 and p?=?0.001, respectively). Conclusions: High level of TAFI antigen in attack-free period of FMF disease shows ongoing subclinical inflammation and hypercoagulability. Clinicians should be careful about thrombosis even in patients at clinical remission. Also, genetic tests must be considered to predict clinical outcome and to reduce complications of FMF disease.     

The relationship between the MEFV genotype, clinical features, and cytokine-inflammatory activities in patients with familial mediterranean fever

Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by periodic attacks of fever and polyserositis. The effects of the MEFV genotype differences on clinical picture and inflammatory activity have not been well documented. The aim of this study was to investigate levels of conventional inflammation markers, procalcitonin, interleukin levels, TNF-alpha, and C5a levels in patients with FMF who had different MEFV genotypes and compare them with those of healthy subjects. The study consisted of 41 patients with FMF (F/M: 23/18), and 31 healthy subjects (F/M: 18/13). Tests were performed during the attack-free period. White-blood cell count, CRP and IL-8 levels were higher in patients with FMF than in healthy subjects (p < 0.05) and also higher in M680I carriers than in the patients with M694V allele carriers. However, ESR, fibrinogen, procalcitonin, IL-6, C5a, TNF-alpha, and IgD levels were not significantly different between patients and healthy subjects (p > 0.05). Arthralgia or arthritis was significantly higher in M694V carriers than in non-M694V carriers (p < 0.05). It is concluded that the clinical features and inflammatory-cytokine activities were higher in patients with FMF during the attack-free period than in healthy subjects, and the different genotype might be related to different clinical pictures.     

Mesangial proliferative glomerulonephritis in familial Mediterranean fever patient with E148Q mutation: the first case report

Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease characterized by recurrent attacks of fever, usually accompanied by sterile polyserositis. Although amyloidosis is the most common renal involvement, non-amyloid renal lesions, such as glomerulonephritis, have been described in patients with FMF. In this report, we present the first case of an FMF patient with heterozygous mutation of E148Q, mesangial proliferative glomerulonephritis, and no amyloidosis. While the association of mutation E148Q with renal involvement is still obscure, colchicine treatment is useful in mesangial proliferative glomerulonephritis with FMF.     

The Effect of Dialytic Modalities on Clinical Outcomes in ESRD Patients with Familial Mediterranean Fever

Background. Familial Mediterranean fever (FMF) is an autosomal recessive disease seen primarily in Sephardic Jews, Turks, and Armenians. The disease manifests as recurrent attacks of fever and serositis. The most important complication of FMF is the development of renal failure due to AA type amyloidosis. There has not been extensive experience with renal replacement therapy in FMF amyloidosis. Nevertheless, there may be a concern about the possibility of higher rates of morbidity and mortality in amyloidotic patients maintained on chronic hemodialysis. Moreover, there is not enough experience regarding patients on chronic peritoneal dialysis. As a result, the best treatment modality of end-stage renal disease (ESRD) in these circumstances still remains unclear. This study aimed to compare the effect of hemodialysis and peritoneal dialysis modalities on clinical outcomes in ESRD patients associated with FMF amyloidosis. Methods. Forty FMF patients with ESRD due to amyloidosis were retrospectively analyzed. All 40 patients were on renal replacement therapy, 20 on hemodialysis (HD), 20 on peritoneal dialysis (PD). Peritoneal solute transport rates, weekly mean creatinine clearance, and daily mean ultrafiltration (UF) of the patients on chronic peritoneal dialysis were evaluated. Weekly dialysis durations, dialysis membrane properties, Kt/V values, interdialytic weight gains, and frequency of hypotension during dialysis were evaluated on hemodialysis patients. All of the patients were examined according to their demographic characteristics, laboratory results, duration time on dialysis, erythropoietin requirements, frequencies of infectious complications requiring hospitalization, and the two renal replacement modalities mentioned above were compared in terms of these parameters. Results. Serum albumin levels of the patients with FMF amyloidosis who were maintained on peritoneal dialysis treatment were lower (2.87 vs 3.45) and the frequency of infections of the same group was higher (4.2 vs 0.5) than the patients with ESRD secondary to other diseases in the CAPD group. Conclusions. This retrospective analysis showed that peritoneal dialysis may have some disadvantages in amyloidotic patients. Due to the high frequency of hypoalbuminemia and infectious complications seen in this group, peritoneal dialysis is widely accepted as an alternative choice of treatment when hemodialysis is not appropriate.     

Familial Mediterranean fever (FMF) and renal AA amyloidosis--phenotype-genotype correlation,treatment and prognosis

Familial Mediterranean fever (FMF) is an autosomal recessive disease, which primarily affects the population surrounding the Mediterranean basin. It is characterized by recurrent attacks of fever and peritonitis, pleuritis, arthritis or erysipelas-like erythema. Amyloidosis, causing renal failure, is one of the most severe complications of the disease. The gene associated with FMF (MEFV) has been recently isolated. Phenotype-genotype correlation studies revealed that amyloidosis was more common in FMF patients originating from North-Africa who were homozygous for the M694V mutation. Such a correlation was not found in Turkish patients. The risk of amyloidosis is increased in male FMF patients and in patients bearing polymorphism a/a in the SAA1 gene. Colchicine is the chosen drug for the treatment of FMF and can prevent amyloidosis.     

MEFV E148Q polymorphism is associated with Henoch–Schönlein purpura in Chinese children

Henoch–Schönlein purpura (HSP) is a multifactorial inflammatory disease whose pathogenesis remains unknown. Pyrin encoded by the MEFV gene (NM_000243; OMIM 608107) is an important active member of the inflammasome and has been shown to affect the expression of many of the genes involved in immune and inflammatory responses. The aim of our study was to elucidate the possible roles of MEFV genetic variants on the susceptibility to HSP and its clinical outcomes in 78 patients with HSP and 189 controls in China. A significant association was found between the E148Q polymorphism (G->C) and HSP susceptibility (odds ratio 2.76, 95% confidence interval 1.76-4.34, P=0.0001). The C allele of E148Q was associated with joint involvement (P?=?0.014) but not with HSP nephritis (P?=?0.1). The clinical score was higher in subjects with the CC genotype than in those with the CG or GG genotype (4.13?±?3.53 vs. 1.94?±?1.70, respectively; P?=?0.011). P369S was not associated with HSP or other phenotypes. M694V and M680I were absent in our patients. Our results suggest that MEFV E148Q could be a contributory genetic factor to HSP and HSP-related joint syndromes.     

Long-term Results of Kidney Transplantation in Patients With Familial Mediterranean Fever and Amyloidosis

IntroductionAmyloid A amyloidosis is most commonly caused by familial Mediterranean fever (FMF) in Turkey. Amyloidosis secondary to FMF is an important cause of end-stage renal failure, and kidney transplantation (KT) in these cases can be complicated, with long-term results oftentimes inferior compared with organ transplant in patients without FMF. The present study aims to show the long-term results of patients with secondary amyloidosis caused by FMF undergoing KT .MethodsWe enrolled 27 patients with a history of FMF amyloidosis undergoing KT and a control group of 614 patients undergoing KT between 2005 and 2018 at Ankara University Medical School. All data were recorded retrospectively from patients files.ResultsTwenty-two patients (81.5%) were treated with triple immunosuppressive therapy consisting of mycophenolate mofetil, tacrolimus, and a steroid; 5 patients (18.5%) were treated with tacrolimus, azathioprine, and prednisolone. Acute cellular rejection was seen in 3 patients (11.1%), and acute cellular- and antibody-mediated rejection occurred in 1 patient (3.7%). During the follow-up period, graft loss due to acute cellular rejection was observed in only 1 patient. One patient was lost to follow-up.     

Kidney transplantation for end‐stage renal disease secondary to familial Mediterranean fever

Although kidney transplantation (KT) is widely used for treating renal amyloidosis secondary to familial Mediterranean fever (FMF), data concerning transplant outcome are limited and inconsistent. The aim of this study was to determine the long‐term outcome of KT in patients with amyloidosis secondary to FMF. Kidney transplantation outcome in 24 patients with FMF was compared to that in 72 controls matched for age, gender of recipient, and type of the donor that underwent KT due to end‐stage renal disease (ESRD) not caused by FMF. Mean follow‐up time was 80.3 ± 55.1 months in the FMF group, vs. 86.5 ± 47.6 months in the control group. Death‐censored graft survival at five and 10 yr in the FMF group was 95.8% and 78.4%, respectively, and was comparable to that in the control group. In the FMF group, five‐ and 10‐yr patient survival (87.5 and 65.6%) was shorter than in the control group, but the difference was not statistically significant. The findings show that long‐term outcome of KT in the patients with amyloidosis secondary to FMF was comparable to that in patients with ESRD not caused by FMF. Recurrence of amyloidosis in the allograft, gastrointestinal intolerance, and fatal infections remain as major complications during the post‐transplant period.     

A case of familial Mediterranean fever with amyloidosis as the first manifestation

We describe a 22-year-old Turkish woman with nephrotic syndrome who had a history of acute myelocytic leukemia. After careful clinical evaluation, the patient underwent a renal biopsy. Light microscopic examination showed deposition of Congo-positive material both in the mesangium and around the small vessels. By histochemical analyses, the deposited material was proved to be amyloid A (AA). Because the patient's history did not reveal any event that might explain the development of secondary amyloidosis, she was screened for mutations causing familial Mediterranean fever (FMF) and was found to be homozygous for the M694V mutation by denaturing gradient gel electrophoresis. We recommend that FMF-Phenotype II and the development of amyloid nephropathy, before or without other symptoms of FMF, should be kept in mind in the face of unexplained proteinuria/amyloidosis, especially in high-risk ethnic groups. © 2001 by the National Kidney Foundation, Inc.     

The effect of dialytic modalities on clinical outcomes in ESRD patients with familial Mediterranean fever

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease seen primarily in Sephardic Jews, Turks, and Armenians. The disease manifests as recurrent attacks of fever and serositis. The most important complication of FMF is the development of renal failure due to AA type amyloidosis. There has not been extensive experience with renal replacement therapy in FMF amyloidosis. Nevertheless, there may be a concern about the possibility of higher rates of morbidity and mortality in amyloidotic patients maintained on chronic hemodialysis. Moreover, there is not enough experience regarding patients on chronic peritoneal dialysis. As a result, the best treatment modality of end-stage renal disease (ESRD) in these circumstances still remains unclear. This study aimed to compare the effect of hemodialysis and peritoneal dialysis modalities on clinical outcomes in ESRD patients associated with FMF amyloidosis. METHODS: Forty FMF patients with ESRD due to amyloidosis were retrospectively analyzed. All 40 patients were on renal replacement therapy, 20 on hemodialysis (HD), 20 on peritoneal dialysis (PD). Peritoneal solute transport rates, weekly mean creatinine clearance, and daily mean ultrafiltration (UF) of the patients on chronic peritoneal dialysis were evaluated. Weekly dialysis durations, dialysis membrane properties, Kt/V values, interdialytic weight gains, and frequency of hypotension during dialysis were evaluated on hemodialysis patients. All of the patients were examined according to their demographic characteristics, laboratory results, duration time on dialysis, erythropoietin requirements, frequencies of infectious complications requiring hospitalization, and the two renal replacement modalities mentioned above were compared in terms of these parameters. RESULTS: Serum albumin levels of the patients with FMF amyloidosis who were maintained on peritoneal dialysis treatment were lower (2.87 vs 3.45) and the frequency of infections of the same group was higher (4.2 vs 0.5) than the patients with ESRD secondary to other diseases in the CAPD group. CONCLUSIONS: This retrospective analysis showed that peritoneal dialysis may have some disadvantages in amyloidotic patients. Due to the high frequency of hypoalbuminemia and infectious complications seen in this group, peritoneal dialysis is widely accepted as an alternative choice of treatment when hemodialysis is not appropriate.     

Myositis in a patient with familial Mediterranean fever and spondyloarthritis successfully treated with anakinra

Familial Mediterranean fever is an autosomal-recessive autoinflammatory disorder more commonly observed in Mediterranean populations and characterized by recurrent episodes of fever, serositis, myalgia and arthritis. There is rarely any association with spondyloarthritis. The most important long-term complication is progressive systemic type AA amyloidosis. Treatment with colchicine is effective in reducing the frequency of attacks and prevents the development of amyloidosis. However, 5% of cases are considered resistant to colchicine. We here describe the case of a 39-year-old man, with a history of arthritis, arthralgias, and sacroiliitis in the course of a familial Mediterranean fever. He is homozygous for the M694I mutation in the MEFV gene. He subsequently developed myositis of the right quadriceps muscle confirmed by magnetic resonance imaging, electromyography and histology. He had frequent and severe arthralgias, despite colchicine, then etanercept and adalimumab, impairing his quality of life. The patient was successfully treated with the IL-1 receptor antagonist anakinra with a dramatic improvement of muscular and articular symptoms. To our knowledge, our patient is the first patient with coexisting FMF, spondyloarthritis and myositis responding to anakinra treatment. Moreover this is the second case in the literature of myositis associated with familial Mediterranean fever.