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.     

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.     

The evaluation of renal hemodynamics changes in Familial Mediterranean fever with color Doppler sonography

Background: Renal resistive index (RRI) scanned through renal Doppler is a practical marker employed in measuring blood flow in renal and intrarenal arteries and in noninvasive evaluation of renal vascular resistance. We aimed to investigate the renal hemodynamic variations in patients with Familial Mediterranean Fever (FMF).

Material and methods: Seventy-nine FMF patients and 51 healthy subjects suitable for age and sex were included. Patients were divided into two groups according to their urinary albumin excretion. Fifty-two patients with 0–29?mg/day albuminuria were included in the normoalbuminuric group while 27 patients with 30–299?mg/day albuminuria were included in the microalbuminuric group.

Results: RRI values were higher in patients with FMF compared to the healthy subjects (p?p?=?0.002, p?p?=?0.013.

Conclusion: RRI may be a marker that may be used in assessing resistance to renal blood flow, early renal damage, and progression of renal damage in FMF patients.     

Spontaneous regression of bilateral surrenal haematoma and subclinical hypoaldosteronism in a patient with renal amyloidosis secondary to Familial Mediterranean Fever

This report describes a patient with Familial Mediterranean Fever (FMF) associated with renal amyloidosis, bilaretal surrenal haematomas andhypoaldosteronism which was clinically asymptomatic. The deposition of AAamyloide was found on the renal and bone marrow biopsies. Bilateralsurrenal haematoma regressed after six month from the first events.Colchicine therapy controlled the attacks of the disease. This revised version was published online in August 2006 with corrections to the Cover Date.     

Long-Term Outcome of Renal Transplantation in Patients With Familial Mediterranean Fever Amyloidosis: A Single-Center Experience

IntroductionFamilial Mediterranean fever (FMF) is an autosomal-recessive disorder, affecting multiple organs. The AA type of amyloidosis is most common and serious complication cause nephropathy and end-stage renal disease (ESRD). Renal transplantation (RTX) remains treatment of choice for ESRD. We aimed to investigate long-term results of RTX in patients with FMF amyloidosis.Patients and MethodsWe compared the outcomes of 18 patients (12 men and 6 women) with FMF amyloidosis among 601 (2.9%) transplants with 200 control patients. Demographic data and gene analysis were evaluated.ResultsIn our study the 1-year graft and patient survivals were 94.44% and 100%, respectively. At 5 years after RTX, they were 94.73% and 88.88%, respectively, in the FMF group without difference from controls. Mean creatinine level at 1 and 5 years were 1.43 ± 0.54 and 1.73 ± 0.89, respectively. The results of MEFV mutation analyses were: M694V/M694V homozygote in 1 patient, M694V/EQ148 in 3, M694V/V726A in 2, 680M-I/E148Q in 3, M694V/M680I in 5, R202Q/M680I in 2, and M694V/R202Q in 2. Recurrence was noticed in 1 patient with M694V/M680I. One patient died because of graft loss and cardiac complications with M694V/M680I gene analysis. Colchicine was reduced in 4 patients owing to side effects.ConclusionLong-term outcomes of transplantation in patients with amyloidosis secondary to FMF is similar to that in the general transplant population and maintenance colchicine, even after decreasing its dose, effectively prevents recurrence of amyloidosis in the allograft.     

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.     

The Effects of Long-term Colchicine Therapy on Male Fertility in Patients with Familial Mediterranean Fever

Four out of 19 male patients suffering from familial Mediterranean fever (FMF) had fertility problems while on colchicine therapy (0.5-2.0 mg daily for as long as 11 years). Three of the patients had had children while off therapy but their wives could not conceive while they were on therapy. In one patient primary sterility remained one year after cessation of colchicine. In this and two other patients the spermiogram was normal but the sperm penetration test was pathological. The fourth patient had azoospermia. Patients should be informed about this possible risk of colchicine therapy. The need for continued follow-up and the value of the sperm penetration test in the detection of fertility problems in male patients on long-term colchicine therapy are stressed. It is concluded however, that overall the benefits outweigh the danger of long-term colchicine treatment in male patients with FMF.     

Cyclosporin: Poorly Tolerated in Familial Mediterranean Fever

Cyclosporin is poorly tolerated in patients with amyloidosisdue to familial mediterranean fever who are receiving colchicine.There is a high incidence of gastro-intestinal side-effectsand muscle weakness, both of which are reversible on stoppingcyclosporin. Thus in patients with amyloidosis secondary tofamilial mediterranean fever treated with colchicine, the useof cyclosporin as an immunosuppressive agent may be restricted.     

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.     

Familial Mediterranean fever and mesangial proliferative glomerulonephritis: report of a case and review of the literature

In familial Mediterranean fever (FMF), a genetically inherited disease characterized by fever and serositis, renal involvement is mainly AA amyloidosis. We report a patient with FMF who developed mesangial proliferative glomerulonephritis; presumably in response to colchicine treatment, the activity of the disease decreased and renal function tests and urinary findings normalized. This report emphasizes the concurrent existence of mesangial proliferative glomerulonephritis with FMF in the absence of renal amyloidosis. Due to increased inflammatory response observed in FMF, immunologic glomerular injury, a common cause of glomerulonephritis, may occur more frequently in patients with FMF.     

Massive renal and adrenal calcifications in a young dialysis patient with familial Mediterranean fever

A 34-year-old patient was hospitalized for progressive developmentof asthenia, muscle weakness and weight loss. This Greek manhad familial Mediterranean     

Renal Transplantation in Patients With AA Amyloidosis Nephropathy: Results From a French Multicenter Study

Although end‐stage renal disease related to AA amyloidosis nephropathy is well characterized, there are limited data concerning patient and graft outcome after renal transplantation. We performed a multicentric retrospective survey to assess the graft and patient survival in 59 renal recipients with AA amyloidosis. The recurrence rate of AA amyloidosis nephropathy was estimated at 14%. The overall, 5‐ and 10‐year patient survival was significantly lower for the AA amyloidosis patients than for a control group of 177 renal transplant recipients (p = 0.0001, 0.028 and 0.013, respectively). In contrast, we did not observe any statistical differences in the 5‐ and 10‐ year graft survival censored for death between two groups. AA amyloidosis‐transplanted patients exhibited a high proportion of infectious complications after transplantation (73.2%). Causes of death included both acute cardiovascular events and fatal septic complications. Multivariate analysis demonstrated that the recurrence of AA amyloidosis on the graft (adjusted OR = 14.4, p = 0.01) and older recipient age (adjusted OR for a 1‐year increase = 1.06, p = 0.03) were significantly associated with risk of death. Finally, patients with AA amyloidosis nephropathy are eligible for renal transplantation but require careful management of both cardiovascular and infectious complications to reduce the high risk of mortality.     

Concomitance of Gitelman Syndrome and Familial Mediterranean Fever: A Rare Case Presentation

We report a case that has Gitelman syndrome (GS) and familial Mediterranean fever (FMF) presenting with recurrent arthritis of right knee and heel pain. Investigations showed hypokalemia and hypomagnesemia with urinary magnesium wasting. Genetic analysis revealed the presence of heterozygous E148Q mutation in the MEFV gene. Management with potassium, magnesium supplements, spironolactone for GS, and colchicine for FMF resulted in a signi?cant improvement in symptoms. To the best of our knowledge, this is the first report of association between GS and FMF. Further studies are needed to identify if there is an association between these two diseases and the genes responsible for these diseases.     

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.     

Renal Amyloidosis with Nephrotic Syndrome in a Spanish Subcutaneous Heroin Abuser

A 25-year-old drug addict who practiced subcutaneous injectionof heroin and crushed narcotic tablets, a practice known as‘skin popping’, developed nephrotic syndrome secondaryto renal amyloidosis. The patient had chronic inflammation ofthe skin in the form of abscesses and ulcerations. She had practicedsubcutaneous drug administration for only 2 years. Amyloidosishad the staining characteristics and tissue distribution ofthe secondary type, and was directly related to chronic skinsuppuration. To our knowledge, this represents the first reportedcase of renal amyloidosis in a subcutaneous drug abuser residingin Europe.     

IgA nephropathy in an Italian child with familial Mediterranean fever

Familial Mediterranean fever is an autosomal recessive disorder characterized by transient attacks of fever and polyserositis with substantial risk of developing amyloidotic nephropathy over time. We report an Italian child with familial Mediterranean fever presenting with hematuria during attacks in whom kidney biopsy documented the presence of mesangial IgA deposits and the absence of amyloidosis. Kidney biopsy should be performed in patients showing microscopic or gross hematuria during attacks of familial Mediterranean fever in order to gain additional epidemiological data about specific features of renal involvement and to allow adequate treatment.     

Urinary Reconstruction Using Appendix as a Urinary and Catheterizable Conduit in 12 Patients

Background The appendix vermiformis can. provide an excellent urinary conduit or a catheterizable outlet in continent urinary reservoirs in selected cases. We report our clinical experience using the appendix in urinary reconstruction in adult patients.
Methods A total of 12 patients underwent urinary reconstruction using the appendix. The indications were pelvic malignancies except for 1 patient with neurogenic bladder and difficulty in self-catheterization via urethra. The appendix was used as a catheterizable conduit in 8 patients, and as a urinary conduit in 4 patients. The in situ submucosally embedded method was used in 6 patients and the Mitrofanoff method was used in 2 patients. Follow-up ranged from 3 to 41 months (mean, 22).
Results Early complications occurred in 3 patients (wound infection, false passage and intestinal anasotomotic leak). Late complications occurred in 3 (slight hydronephrosis, ileus, stomal stenosis). Emergent colostomy and pouchstomy with resection of the appendix was performed in the patient with anastomotic leak. The isoperistaltic Kock nipple valve was reconstructed for continence in this case. Prolonged ileus in 1 patient was treated by open surgery. Other complications were managed conservatively. End results were excellent in 8 patients, good in 3, and poor in 1.
Conclusions The appendix can be used advantageously as an outlet of continent urinary reservoirs or for a urinary conduit when the ureter is too short to reach the skin. Complete continence and easy catheterization can be obtained, and the appendix construction can be used as a urinary conduit instead of the ileal conduit in poor risk patients.