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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2016  |  Volume : 27  |  Issue : 3  |  Page : 590-594
Renal manifestations of human brucellosis: First report of minimal change disease

1 Department of Nephrology, General Hospital of Edessa, Edessa, Greece
2 Postgraduate Program, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Date of Web Publication13-May-2016


Human brucellosis is considered a great example of the complexity of clinical manifestations possibly affecting multiple organs or systems. Renal manifestations of human brucellosis have been documented in few case reports and one case series. Herein, we present a case of Nephrotic syndrome (NS) due to minimal change disease in the course of acute brucellosis. A 53-year-old male farmer was admitted to our department with acute brucellosis and NS. Renal biopsy revealed minimal change disease. Combined treatment with prednisone (1 mg/kg), rifampicin (600 mg/day), and doxycycline (200 mg/day) was initiated. Complete remission of NS was achieved at the end of the fourth week. One year later, the patient remained in complete remission of NS without any sign of relapse of brucellosis.

How to cite this article:
Sabanis N, Gavriilaki E, Paschou E, Tsotsiou E, Kalaitzoglou A, Kavlakoudis C, Vasileiou S. Renal manifestations of human brucellosis: First report of minimal change disease . Saudi J Kidney Dis Transpl 2016;27:590-4

How to cite this URL:
Sabanis N, Gavriilaki E, Paschou E, Tsotsiou E, Kalaitzoglou A, Kavlakoudis C, Vasileiou S. Renal manifestations of human brucellosis: First report of minimal change disease . Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2022 Jan 25];27:590-4. Available from: https://www.sjkdt.org/text.asp?2016/27/3/590/182413

   Introduction Top

Human brucellosis represents the most common bacterial zoonosis worldwide, which is mostly prevalent in developing countries. It is transmitted to humans through infected animals or raw dairy products. In the Balkan countries, human brucellosis has re-emerged as a major public health problem, in spite of prevention and control programs. In particular, Greece is included among the first 25 countries with the highest incidence of human brucellosis worldwide.[1]

Although novel species have been recognized in the modern Brucella taxonomy, the most common cause of human brucellosis remains Brucella melitensis, an intracellular Gram- negative bacterium.[2]Human brucellosis is considered an example of the complexity of clinical manifestations possibly affecting mul- tiple organs or systems. The diagnosis is often challenging due to the lack of typical signs or symptoms of the disease. Nevertheless, we should not forget that acute and chronic bru- cellosis may cause severe disability according to the World Health Organization's Global Burden of Disease Study.[3]

Herein, we present for a case of Nephrotic syndrome (NS) due to minimal change disease in the course of acute brucellosis.

   Case Report Top

A 53-year-old male farmer with a history of arterial hypertension and dyslipidemia under treatment with telmisartan and simvastatin for five years was admitted to our department due to acute onset peripheral edema. Three weeks prior to his admission, the patient reported progressively worsened fatigue, night sweat, low-grade fever, loss of appetite, low back pain without radiations, arthralgia in different joints, and diffuse myalgia.

Physical examination revealed the following vital signs: blood pressure 110/70 mm Hg, pulse rate 67/min, and temperature 37.8°C. On auscultation, the patient had normal heart sounds without any murmurs but fine crackles in the right lower lobe. The abdomen was soft with mildly tender hepatomegaly 3 cm below the right costal margin. Spleen and lymph nodes were not palpable but there was low back tenderness and marked edema on the legs and hips. Routine laboratory examinations are shown in [Table 1]. Massive proteinuria was found in 24 h urine. The microscopic urine examination revealed oval fat bodies and fatty casts, as well as indices of acute tubular nec- rosis. Overall, the patient presented with an infectious disease and NS (marked edema, pro- teinuria, hypoalbuminemia, and hyperlipidemia). Viral (HBV, HCV, and HIV) and immuno- logical (C3, C4, CH50, RF, ANA, anti- dsDNA, c-ANCA, p-ANCA, serum and urine protein electrophoresis, and immunoelectro- phoresis) tests were negative. The serum agglutination test (Wright) proved positive at titers greater than 1:320. In addition, IgM anti- Brucella antibodies were detected at high titers by ELISA.
Table 1. Basic laboratory findings

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Chest radiograph revealed blunting of the right costophrenic angle and bronchovascular prominence. The abdominal ultrasound repor- ted the presence of ascites, a marginally enlarged liver and a slight increase in renal echogenicity with corticomedullary differen- tiation. Thorax computed tomography showed bilateral cystic bronchiectasis in the lower lobes without pulmonary infiltrates. Echo- cardiography revealed no signs of endocar- ditis. Furthermore, other causes of NS were excluded by upper and lower gastrointestinal endoscopy.

The patient was subsequently subjected to renal biopsy that revealed minimal change di- sease. The patient initially received treatment with human albumin and diuretics, as well as low molecular weight heparin due to severe hypoalbuminemia and then, combined treatment with prednisone (1 mg/kg) for eight weeks and rifampicin (600 mg/day) and doxycycline (200 mg/day) for six weeks. Clinical improvement was evident from the 6th day since the initia- tion of prednisone treatment. Complete remis- sion of the NS was achieved at the end of the 4th week. Prednisone tapering began at the 8th week and prednisone treatment was discon- tinued at 12 months. One year later, the patient is in complete remission of the NS without any sign of relapse of brucellosis.

   Discussion Top

Human brucellosis is characterized by the complexity of clinical manifestations. Renal manifestations were firstly described by Bruce et al in 1889 and have been since documented in a few case reports and one case series of 15 patients.[4]They are summarized in [Table 2] and are mainly categorized into acute or chronic kidney injury.
Table 2. Summary of renal manifestations during brucellosis

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First, prerenal azotemia during brucellosis is mainly attributed to reduced renal blood flow in patients with dehydration due to prolonged fever or vomiting[5]or rarely to acute aortic insufficiency, myocarditis, rhabdomyolysis,[3],[6]or NS leading to reduced blood volume and increased interstitial fluid which was observed in our case report.

Second, acute tubular necrosis results from prolonged ischemia or could be a side effect of brucellosis treatment (such as rifampicin and aminoglycosides). In other cases, it could be attributed to nonsteroidal anti-inflammatory drugs (NSAID) administration which is com- mon in patients with musculoskeletal mani- festations or fever. Acute tubular necrosis has been also reported as a consequence of rhab- domyolysis that causes myoglobinuria.

In addition, acute interstitial nephritis in bru- cellosis[7],[8]is either caused by direct tubulo- interstitial invasion of Brucella spp. or by an immunological process related to nephrotoxic drug administration, such as NSAIDs or rifam- picin. Although brucellosis affects more com- monly the genitourinary system,[9]it has been reported as a cause of acute pyelonephritis with or without renal abscess[10]either directly or due to concomitant endocarditis. More re- cently, Öncü et al[11]described the first case of renal cyst infection in a patient with polycystic kidney disease.

Fourth, chronic brucellosis has been described to result in granulomatous tubulointerstitial nephritis.[12]This represents a very rare renal manifestation of brucellosis that mimics renal tuberculosis, since Brucella spp. is characterized by a tropism for the splenic and hepatic reticuloendothelial system.

Furthermore, glomerular nephritis and acute interstitial nephritis in brucellosis can occur with or without endocarditis, which represents the most common cardiovascular complication. of brucellosis, reported in <2% of patients with brucellosis.[13],[14]Glomerular injury related to endocarditis is caused by the formation of immunocomplexes in the circulation or in situ.[15]Case reports have documented the pre- sence of mesangioproliferative,[16],[17]membrano- proliferative,[16],[18]postinfectious,[19]and p-ANCA positive rapidly progressive glomeruloneph- ritis[20]in the course of brucellosis. On the other hand, reported nephritis without endocarditis can be divided into immune-complex glome- rulonephritis and pauci-immune nephritis. Immune-complex nephritis described in pa- tients with brucellosis are IgA nephropathy,[21],[22],[23]membranous glomerulonephritis,[24]membra- noproliferative glomerulonephritis,[25],[26]and hemolytic uremic syndrome.[27]On the other hand, pauci-immune nephritis not related to endocarditis has been described in one case report of focal segmental glomerulosclerosis[7]besides the our index case.

To our knowledge, there is no previous report of minimal change disease during acute brucellosis. Minimal change disease represents a podocyte immune disorder characterized by the absence of abnormalities by light micros- copy. Brucellosis-induced cell-mediated immu- nity that results in excessive cytokine produc- tion (tumor necrosis factor-a, interferon-γ, and interleukin-12)[28],[29]may provide a pathophysio- logical link to cytokine-induced abnormal per- meability function observed in the glomerular capillary of minimal change disease.[30]

   Conclusion Top

We report for the first time a case of NS due to minimal change disease in a patient with acute brucellosis. The possible immunological link between the two entities remains to be further investigated. Physicians, especially in endemic areas, should always bear in mind the diagnosis of brucellosis in patients with renal manifestations and general symptoms.

Conflicts of Interest: None declared.

   References Top

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Pappas G. The changing Brucella ecology: Novel reservoirs, new threats. Int J Antimicrob Agents 2010;36 Suppl 1:S8-11.  Back to cited text no. 2
Dean AS, Crump L, Greter H, Hattendorf J, Schelling E, Zinsstag J. Clinical manifestations of human brucellosis: A systematic review and meta-analysis. PLoS Negl Trop Dis 2012;6: e1929.  Back to cited text no. 3
Ceylan K, Karahocagil MK, Soyoral Y, et al. Renal involvement in Brucella infection. Urology 2009;73:1179-83.  Back to cited text no. 4
Dagli O, Dokur M, Guzeldag G, Ozmen Y. Acute renal failure due to Brucella melitensis. J Infect Dev Ctries 2011;5:893-5.  Back to cited text no. 5
Khorvash F, Keshteli AH, Behjati M, Salehi M, Naeini AE. An unusual presentation of brucellosis, involving multiple organ systems, with low agglutinating titers: A case report. J Med Case Rep 2007;1:53.  Back to cited text no. 6
Dunea G, Kark RM, Lannigan R, D'Alessio D, Muehrcke RC. Brucella nephritis. Ann Intern Med 1969;70:783-90.  Back to cited text no. 7
Ghanei E, Miladipour A, Nasrollahi A, Homayuni M. Brucellosis with kidney failure. Iran J Kidney Dis 2009;3:109-11.  Back to cited text no. 8
Colmenero JD, Munoz-Roca NL, Bermudez P, Plata A, Villalobos A, Reguera JM. Clinical findings, diagnostic approach, and outcome of Brucella melitensis epididymo-orchitis. Diagn Microbiol Infect Dis 2007;57:367-72.  Back to cited text no. 9
Onaran M, Sen I, Polat F, Irkilata L, Tunc L, Biri H. Renal brucelloma: A rare infection of the kidney. Int J Urol 2005;12:1058-60.  Back to cited text no. 10
Öncü S, Saylak Ö, Köseoglu K, et al. Renal cyst infection caused by Brucella abortus. Ren Fail 2013;35:302-4.  Back to cited text no. 11
Petereit MF. Chronic renal brucellosis: A simulator of tuberculosis. Case report. Radiology 1970;96:85-6.  Back to cited text no. 12
Memish Z, Mah MW, Al Mahmoud S, Al Shaalan M, Khan MY. Brucella bacteraemia: Clinical and laboratory observations in 160 patients. J Infect 2000;40:59-63.   Back to cited text no. 13
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Elzouki AY, Akthar M, Mirza K. Brucella endocarditis associated with glomeruloneph- ritis and renal vasculitis. Pediatr Nephrol 1996; 10:748-51.  Back to cited text no. 15
Abu Romeh SH, Kozma GN, Johny KV, Sabha M. Brucella endocarditis causing acute renal failure. Nephron 1987;46:388-9.  Back to cited text no. 16
Oguzhan N, Akgun H, Unal A, et al. Brucella glomerulonephritis and prosthetic valve endo- carditis: A case report. Int Urol Nephrol 2012; 44:643-6.  Back to cited text no. 17
Altiparmak MR, Pamuk GE, Pamuk ON, Tabak F. Brucella glomerulonephritis: Review of the literature and report on the first patient with brucellosis and mesangiocapillary glomerulo- nephritis. Scand J Infect Dis 2002;34:477-80.  Back to cited text no. 18
Kocyigit I, Celik A, Tokgoz B, et al. Acute postinfectious glomerulonephritis with native aorta valve endocarditis and myopericarditis due to brucellosis. Ren Fail 2011;33:367-70.  Back to cited text no. 19
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Nunan TO, Eykyn SJ, Jones NF. Brucellosis with mesangial IgA nephropathy: Successful treatment with doxycycline and rifampicin. Br Med J (Clin Res Ed) 1984;288:1802.  Back to cited text no. 21
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Kusztal M, Dorobisz A, Kuzniar J, et al. Dissecting aneurysm of the thoracic aorta in a patient with nephrotic syndrome and brucel- losis. Int Urol Nephrol 2007;39:641-5.  Back to cited text no. 25
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Correspondence Address:
Eleni Gavriilaki
Department of Nephrology, General Hospital of Edessa, Edessa
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DOI: 10.4103/1319-2442.182413

PMID: 27215256

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