Acute Renal Failure Associated with Rhabdomyolysis in Acute Q Fever

Abstract

The clinical presentation of Q fever is polymorphic and non-specific, and it may be presented as an acute or chronic disease. Renal complications of acute Q fever such as acute glomerulonephritis are not uncommon. Acute renal failure induced by rhabdomyolysis in acute Q fever has until now never been reported in the literature. We presented a case of acute Q fever associated by extreme rhabdomyolysis and consecutive acute renal failure. A male patient was treated with doxycycline and continuous venovenous hemodiafiltration. After two weeks of treatment, the patient completely recovered kidney function, and there were no clinical abnormalities. Acute Q fever must be considered as a possible cause of rhabdomyolysis and acute renal failure. The continuous venovenous hemodiafiltration may be effective, and it seems to be the treatment of choice in severe rhabdomyolysis and consecutive acute renal failure.

Keywords:

• Q fever
• rhabdomyolysis
• continuous venovenous hemodiafiltration

INTRODUCTION

Q fever is a zoonosis caused by Coxiella burnetti. The most common reservoirs are domesticated animals, primarily cattle, sheep, and goats. This bacterium is very resistant and may survive for a long period of time in the environment. Humans, who are very susceptible to the disease, are infected by inhalation aerosols or contaminated dusts derived from infected animal products, mainly during parturitation.[1] The incubation period of the disease is 2–3 weeks after exposure; one-half of those who are infected show signs of clinical illness.[2] The clinical presentation of Q fever is polymorphic and non-specific. It may be presented as an acute or chronic disease. Acute Q fever most commonly manifests as a self-limited febrile illness, atypical pneumonia, and hepatitis[2]; a rare complication can be glomerulonephritis [3–5] and in some cases rhabdomyolysis.[6–8] The clinical manifestations of Q fever may be so variable that disease is often diagnosed only if it has been systematically considered. However, when evoked, a definite diagnosis of the disease is easy and remains based upon serology.[2]

Because there are no data dealing with Q fever complicated by rhabdomyolysis and subsequently acute renal failure, a new case is presented here.

CASE REPORT

A 41-year-old man, locksmith by profession, was admitted to the Department of Pulmonology with a high fever (38°C), headache, extreme fatigue, generalized arthromyagias, as well as strong muscle tenderness. He had a history of contact with parturient of goats during recent Q fever outbreak. His illness commenced five days before hospitalization. The patient had no significant medical history. He did not smoke, drink, or take any drugs. He did not have any trauma, either.

On admission, physical examination revealed a body temperature of 38°C, blood pressure of 120/80 mmHg, regular pulse rate of 84 bpm, and respiratory rate of 14 bpm. There was diffuse muscle tenderness in the extremities. The remainder of the examination was unremarkable. Laboratory investigations showed the following significant data: white cell count of 6,800/mm³, differential cell count and red blood cell within normal range, platelet count of 397,000 /mm³, a C-reactive protein (CRP) value of 283,6 mg/L, BUN 5,2 mmol/L, creatinine 95 μmol/L, SGOT 810 U/L, SGPT 240 U/L, LDH 4450 U/L, CK 64340 U/L, CKMb 872 U/L. His serum electrolytes were normal. The urinary output was 400 ml per day. A urinalysis revealed proteinuria, the sediment contained 10 RBC/hpf, 15 WBC/hpf, and haem-pigmented granular casts. Serology testing was negative for acute infection with Chlamydia psittaci, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila. Serology for Coxiella burnetti was detected by indirect immunofluorescence assay (IFA): serum samples on second day of hospitalization showed anti-IgM 1:160 (positive) and anti- IgG 1:80 (positive), and on the 17th day of hospitalization, anti-IgM 1:640, and anti-IgG 1:1280. The other laboratory findings during hospitalization were as follow: a hepatitis B virus and a hepatitis C virus tests negative, the immunological tests within normal limits (anti-Ro, anti-La, anti-Jo, ANA, anti-ds DNA, C3, C4, Latex CIC, anti-GBM, ANCA-MPO, ANCA-PR3), as well as TSH. A chest x-ray on the first day of hospitalization showed left paracardial lung infiltration. An electrocardiogram was normal. Echocardiogram revealed normal systolic and diastolic function, with slightly altered myocardial echogenicity. Abdominal sonography was also normal.

Doxycycline treatment, 200 mg bid, was started on the first day, and continued for a total of three weeks.

On the third day, the patient's condition worsened: he developed anuria and was transferred to the Renal Unit. The laboratory tests disclosed the following significant data: BUN 21,1 mmol/L, creatinine 386 μmol/L, CK 239000 U/L, SGOT 2370 U/L, SGPT 730 U/L, LDH 13480 U/L, and electrolytes within normal range. Because of anuria, which continued over next 12 hours, the indication for dialysis was made,[9] and the central venous catheter was placed. The continuous venovenous hemodiafiltration (CVVHD) was started with daily monitoring of diuresis and laboratory tests (see Figure 1).

Figure 1. Changes of clinical parameters of the patient.

A clinical improvement occurred gradually. On the sixth day of hospitalization, the patient started to pass the urine (100 mL/day), with notifiable daily urinary output augmentation. Control chest x-ray on 10th day of hospitalization showed a complete resolution of the pulmonary finding. The high CK value persisted up to the eighth day of hospitalization, but a compartment syndrome was not detected. Subsequently, CK level decreased progressively until normalization on day 17. CVVHD was performed for the 14 days (up to the seventeenth day of hospitalization), after which it was replaced by short duration hemodialysis (two hours) for the next three consecutive days. Hemodialysis was stopped on day 20. His condition and renal function continuously improved, and he required no further dialysis. The patient was discharged on day 37, completely recovered with serum biochemical parameters within normal range.

DISCUSSION

In this article, for the first time, the case of acute Q fever associated by extreme rhabdomyolysis and consecutive acute renal failure was presented. Although there are several reported cases of acute renal failure in Q fever,[3–5] none of them was due to rhabdomyolysis. Betrosian and coworkers observed that patients with infectious rhabdomyolysis had acute renal failure more frequently than those who had infection but not rhabdomyolysis.[10] The clinical course of the patient presented here supports this statement. Suggested mechanisms for an acute renal failure induced by rhabdomyolysis include: precipitation of myoglobin and uric acid crystals within renal tubules, decreased glomerular perfusion, and the nephrotoxic effect of ferrihemate (formed upon dissociation of myoglobin in acid environment of renal parenchyme).[11] Indeed, the highest level of serum CK (239 000 IU/L; the intensity of rhabdomyolysis was close to that found in the crush-syndrome[12]) observed in presented patient has not been reported so far. The highest CK level described during Q fever actually was 47659 IU/L.[6] Unusually high levels of CK might explain the development of ARF in the patient reported here, as CK levels are known to correlate with the development of ARF.[13]

The pathogenesis of rhabdomyolysis in patient with acute C. burnetii infection is unclear. It seems that, like in Legionella species (a phylogenetically the closest microorganism to C. burnetti), some endotoxin or exotoxin caused rhabdomyolysis.[14] This hypothesis is supported by fact that biopsy muscle specimens are negative for the organism examined by immunofluorescence.[15] Because the role of toxins and inflammatory mediators, especially tumor necrosis factor-α (TNF-α) was important (namely, in animal model, elevated levels of TNF induced skeletal muscle breakdown[14]), the usage of CVVHD was chosen. It is well known that CVVHD is the best method for the removal of inflammatory mediators from the blood of patients with systemic inflammatory response syndrome and acute renal failure.[16],[17]

C. burnetii is acquired most often via inhalation of aerosols. C. burnetii as an intracellular pathogen lives in an acidic vacuole in akaryocytic cells. A virulence is correlated with lipopolysaccharide content of the organism. In the lungs, it proliferates in macrophages, in an acid phagolysosome vacuole, and then gains access to blood, producing a transient bacteriemia that invades distant organs (first the liver), targeting Kuppfer cells, and initiating local inflammation and the formation of granulomas.[18] A patient presented here had also very high level of liver function tests during initial phase of disease. Unexpectedly, it was not accompanied with the presence of antinuclear antibodies, which is described as an almost classical pattern of hepatitis caused by Coxiella burnetii.[2] A rhabdomyolysis in this case was also not accompanied by a significant presence of antibodies to the extranuclear antigens, as well as antiphospholipidic antibodies.[2] Previous examinations of biopsy specimens obtained during acute C. Burnetii infections showed major inflammatory response, but few organisms.[2] Following that report, a serological confirmation of the disease, as was done in presented patient, seems to be enough to establish the diagnosis.

The patient reported here followed a favorable course, requiring antibiotic treatment and hemodialysis. He finally recovered full renal function. Patient was advised for a monthly checkup and IFA C. Burnetti control in a few months hence, as phase I antigen level greater than 1:800 is a courier of possible chronic infection [2].

In summary, acute Q fever must be considered as a possible cause of rhabdomyolysis and acute renal failure. Further, it is obvious that the determination of CK and creatinine levels have to be added to the regular panel of laboratory tests in acute Q fever (especially during outbreaks of the disease). Namely, the change virulence and mutations of the bacteria and consecutive clinical presentation cannot be anticipated. In addition, the use of CVVHD in the successful treatment of severe rhabdomyolysis and consecutive acute renal failure is documented here.