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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2020  |  Volume : 31  |  Issue : 2  |  Page : 537-541
Familial mediterranean fever and immunoglobulin A nephropathy: A case report and review of the literature

1 Department of Nephrology, Antalya Atatürk State Hospital, Antalya, Turkey
2 Department of Nephrology, Ankara Numune Education and Research Hospital, Ankara, Turkey

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Date of Submission30-Mar-2019
Date of Decision24-May-2019
Date of Acceptance27-May-2019
Date of Web Publication09-May-2020


Familial Mediterranean fever (FMF) is an autosomal recessive disease charac-terized by recurrent fever episodes and polyserositis. The most important complication is amyloidosis. Nonamyloidotic nephropathy in FMF is poorly documented. Besides amyloidosis, different types of glomerulonephritis may rarely be seen in FMF patients. A 24-year-old male patient followed up due to FMF was evaluated for macroscopic hematuria and acute kidney injury. The patient was diagnosed as immunoglobulin A nephropathy with renal biopsy. The patient gave a good response to colchicine and steroid treatment. The case reports in the literature about the treatment of the patients with association of FMF and glomerulonephritis are insufficient, and there are no satisfactory epidemiological and treatment outcome reports.

How to cite this article:
Yilmaz F, Keleş M. Familial mediterranean fever and immunoglobulin A nephropathy: A case report and review of the literature. Saudi J Kidney Dis Transpl 2020;31:537-41

How to cite this URL:
Yilmaz F, Keleş M. Familial mediterranean fever and immunoglobulin A nephropathy: A case report and review of the literature. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2021 Sep 27];31:537-41. Available from: https://www.sjkdt.org/text.asp?2020/31/2/537/284033

   Introduction Top

Familial Mediterranean fever (FMF) is an autosomal recessive, autoinflammatory disease characterized by recurrent and self-limited episodes of fever and sterile serosal inflammation. The disease is caused by mutations in the MEFV gene. Although AA-type amyloi- dosis is the most common renal complication, nonamyloid renal diseases, such as some type of glomerulonephritis [particularly immuno- globulin A nephropathy (IgAN), membrano- proliferative glomerulonephritis, membranous nephropathy, and focal segmental glomerulo- sclerosis) and vasculitis (Henoch-Schonlein purpura (HSP) and polyarteritis nodosa (PAN)], have been cases reported in patients with FMF.[1],[2],[3] IgAN is the most common type of primary glomerulonephritis.[4]

In this case report, here, we describe a patient with FMF presenting with macroscopic hema- turia and acute kidney injury during attack-free period, in whom renal biopsy diagnosed the IgAN.

   Case Report Top

Informed consent was obtained from the patient before publishing the case.

A 24-year-old male was admitted in our clinic because of macroscopic hematuria and acute kidney injury which were detected by routine blood and urine analysis in July 2015. The patient had been diagnosed with FMF nine years previously as a result of recurrent fever and painful attacks of sterile polysero- sitis. Analysis of MEFV gene, heterozygous for M694V mutation, was detected. With 1.5 mg/day of colchicine, the disease was followed without attack. There was nothing remarkable other than FMF in the medical history. The family history was negative for AA amyloidosis and FMF.

On physical examination, blood pressure was 155/93 mm Hg, pulse was 88/min, and fever was 36.9°C. Lung, heart, gastrointestinal system, and locomotor system examinations were within normal limits. The results of laboratory tests are listed in [Table 1].
Table 1: Laboratory results of the patient.

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In urine dipstick test, proteinuria 3+, 47 red blood cells, 12 white blood cells, and 24-h urinary total protein of 2370 mg/day were detected. Urine, blood, and throat cultures were negative. The antistreptolysin O titer was 60 Todd unit (normal: 0-200 Todd unit). Dysmorphic erythrocytes were seen on microscopic examination of urine. Three months before admission the routine laboratory tests revealed a urea 27 mg/dL, crea- tinine 0.9 mg/dL, protein 7.1 g/dL, albumin 4.1 g/dL, 24 h urinary total protein of 245 mg/day and without edema.

Renal ultrasonography showed normal-sized kidneys. Serologic tests for antinuclear antibodies, anti-dsDNA, cytoplasmic and peri- nuclear antineutrophil cytoplasmic antibodies, and anti-glomerular basement membrane antibody were negative, and rheumatoid factor and complement (C3: 98 mg/dL; C4: 39 mg/dL) were normal.

Renal biopsy was performed. A total of 16 glomeruli were detected in light microscopy. Four glomeruli exhibited global sclerosis, two glomerulus exhibited segmental sclerosis, and eight glomeruli presented with a cellular seg- mental crescent. Renal biopsy was showed an increase of mesangial matrix and cells (mesangial hypercellularity), and immunofluo- rescence microscopic examination revealed dominant IgA (3+) and C3 (2+) depositions in the mesangial area. There were no tubular atrophy and interstitial fibrosis. No amyloid accumulation was detected by the Congo red stain. In addition, there were no vascular lesions. The diagnosis was reported as IgAN.

The patient received three days of methyl- prednisolone pulse treatment, 500 mg/day, followed by a tapering dose of prednisolone 1

mg/kg/day for four weeks and continuing dose of colchicine 1.5 mg/day. Steroid treatment was reduced to maintenance dose in three months (methylprednisolone 4 mg/day). The follow-up showed that 24-h urine total protein was 459 mg/day and serum creatinine 1.1 mg/dL after three months of treatment.

   Discussion Top

FMF is an autosomal recessive disease characterized by recurrent fever episodes and polyserositis with the most important complication, amyloidosis. The most commonly affected societies are Turks, Arabs, Armenians, and Sephardic Jews. AA-type amyloidosis is resulting in nephrotic syndrome, chronic kidney disease, and end-stage renal disease.

Nonamyloid kidney disease should be considered in the differential diagnosis of renal involvements in patients with FMF.[5] Non- amyloidotic nephropathy in FMF is poorly documented.[6] In the Turkish FMF working group study evaluating 2436 FMF patients, amyloidosis was seen by 12.9% and non- amyloid glomerular disease, PAN, and HSP by 4.4%.[7] In a study by Kukuy et al, amyloidosis was observed in 15 (60%) and nonamyloid nephropathy in 10 of 25 patients FMF patients who underwent biopsy due to proteinuria.[8] Our patient was biopsied due to glomerular- induced hematuria and kidney damage.

IgAN in patients with FMF has been previously reported.[1],[9],[10] It has been reported that MEFV gene mutations (M694V, V726A, and E148Q) are not associated with the phenotype, severe-ness, and biopsy findings of glomerulo- nephritis and do not cause susceptibility to the disease in patients with primary glomerulo- nephritis without FMF.[11] Our patients had M694V mutation.

IgAN is associated with minimal urine findings and normal range of renal function, and it shows good long-term prognosis.[12] Acute kidney injury is known as an uncommon presentation in IgAN. Experience regarding the treatment of FMF-related GN (particularly IgAN) is limited, and colchicine is the most common agent used.[1],[9],[13],[14] There is not much evidence, which shows that colchicine alone would be sufficient to treat FMF-related glomerulonephritis.[9] There are cases in the literature in which steroids, azathioprine, and cyclophosphamide therapies were used in combination with colchicine in patients with glomerulonephritis.[10],[15] In a study by Akpolat et al, the use of colchicine and immunosuppres- sive drugs (steroids, azathioprine, and cyclo- phosphamide) was evaluated in 21 patients diagnosed as glomerulonephritis with biopsy, and the patients receiving immunosuppressive drugs were those with crescentic glomerulo- nephritis, diffuse proliferative glomerulo- nephritis, and membranous nephropathy.[10] In the same study, colchicine alone was used in three patients diagnosed with IgAN, and a good clinical outcome was obtained.[10] Colchi- cine alone was used in two patients with IgAN by Huzmeli et al,[16] one patient by Gullu et al,[9] one patient by Rigante et al,[13] and three patients by Said et al[14],[17] and a good result was obtained. In the study by Huzmeli et al, patients receiving immunosuppressive therapy were those with membranous nephropathy and mesangioproliferative and immunocomplex glomerulonephritis.[16] Koukoui et al reported a case heterozygous for a MEFV mutation who suffered from IgAN and responded good colchicine treatment over 22 years.[18] Methyl- prednisolone plus colchicine treatment was successful for complete remission in our patient after three months of therapy. Demographic and clinical findings of reported FMF-related IgAN cases (1984-2016) in [Table 2] have been summarized.
Table 2: Summary of reported familial Mediterranean fever-related immunoglobulin A nephropathy cases.

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   Conclusion Top

Several types of primary glomerulonephritis, particularly IgAN, can be seen in FMF. Kidney diseases other than amyloidosis should be kept in mind in proteinuria, hematuria, and acute kidney damage in each FMF patient. There are no recommendations on the treatment of these patients because of the limited number of patients.

Conflict of interest: None declared.

   References Top

Gok F, Sari E, Erdogan O, Altun D, Babacan O. Familial mediterranean fever and IgA nephropathy: Case report and review of the literature. Clin Nephrol 2008;70:62-4  Back to cited text no. 1
Ceri M, Unverdi S, Altay M, Unverdi H, Ensari A, Duranay M. Familial Mediterranean fever and membranous glomerulonephritis: Report of a case. Ren Fail 2010;32:401-3  Back to cited text no. 2
Huzmeli C, Candan F, Bagci G, et al. Frequency of familial Mediterranean fever (MEFV) gene mutations in patients with biopsy-proven primary glomerulonephritis. Clin Rheumatol 2017;36:2589-94  Back to cited text no. 3
Donadio JV, Grande JP. IgA nephropathy. N Engl J Med 2002;347:738-48  Back to cited text no. 4
Ardalan M, Nasri H. Massive proteinuria and acute glomerulonephritis picture in a patient with Familial Mediterranean fever and E148Q mutation. Iran J Kidney Dis 2014;8:486-8  Back to cited text no. 5
Peru H, Elmaci AM, Akin F, Akcoren Z, Orhan D. An unusual association between familial mediterranean fever and IgM nephropathy. Med Princ Pract 2008;17:255-7  Back to cited text no. 6
Tunca M, Akar S, Onen F, et al. Turkish FMF study group. Turkish FMF study group. Familial Mediterranean Fever (FMF) in Turkey: Results of a nationwide multicenter study. Medicine (Baltimore) 2005;84:1-11  Back to cited text no. 7
Kukuy O, Livneh A, Ben-David A, et al. Familial Mediterranean fever (FMF) with proteinuria: Clinical features, histology, predictors, and- prognosis in a cohort of 25 patients. J Rheumatol 2013;40:2083-7  Back to cited text no. 8
Gullu BE, Celik S, Dagel T, et al. IgA Nephritis in a Patient with Familial Mediterranean Fever: 5 Years-Follow-up. Turk Neph Dial Transp 2010;19:224-7  Back to cited text no. 9
Akpolat T, Akpolat I, Karagoz F, Yilmaz E, Kandemir B, Ozen S. Familial Mediterranean fever and glomerulonephritis and review of the literature. Rheumatol Int 2004;24:43-5  Back to cited text no. 10
Kukuy OL, Kopolovic J, Blau A, et al. Mutations in the familial Mediterranean fever gene of patients with IgA nephropathy and other forms of glomerulonephritis. Clin Genet 2008;73:146-51  Back to cited text no. 11
Gutierrez E, Zamora I, Ballarin JA, et al; Grupo de Estudio de Enfermedades Glomerulares de la Sociedad Espanola de Nefrologia (GLOSEN). Long-termout comes of IgA nephropathy presenting with minimal or no proteinuria. J Am Soc Nephrol 2012; 23:1753-60  Back to cited text no. 12
Rigante D, Federico G, Ferrara P, et al. IgA nephropathy in an Italian child with familial Mediterranean fever. Pediatr Nephrol 2005; 20:1642-4  Back to cited text no. 13
Said R, Hamzeh Y, Said S, Tarawneh M, al- Khateeb M. Spectrum of renal involvement in familial Mediterranean fever. Kidney Int 1992;41:414-9  Back to cited text no. 14
Cagdas DN, Gucer S, Kale G, Duzova A, Ozen S. Familial Mediterranean fever and mesangial proliferative glomerulonephritis: Report of a case and review of the literature. Pediatr Nephrol 2005;20:1352-4  Back to cited text no. 15
Huzmeli C, Kogkara AS, Candan F, Kayata? M. Biopsy proven non-amyloid glomerular diseases in patients with familial mediterranean fever. J Nephrology Res 2015; 1:34-9  Back to cited text no. 16
Said R, Nasrallah N, Hamzah Y, Tarawneh M, al-Khatib M. IgA nephropathy in patients with familial Mediterranean fever. Am J Nephrol 1988;8:417-20  Back to cited text no. 17
Koukoui L, Blau A, Kopolovic J, Pras M, Livneh A. A possible favorable effect of colchi cine in IgA nephropathy in a carrier of a MEFV mutation. Clin Nephrol 2004;62:226-8.  Back to cited text no. 18

Correspondence Address:
Fatih Yilmaz
Department of Nephrology, Antalya Atatürk State Hospital, Antalya
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DOI: 10.4103/1319-2442.284033

PMID: 32394931

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