Acute interstitial nephritis in a case of Ascaris lumbricoides infection

Oliver Jung1, Tilmann Ditting1, Hermann Josef Gröne2, Helmut Geiger1 and Ingeborg A. Hauser1

1Department of Nephrology, Johann Wolfgang Goethe-University, Frankfurt am Main and 2Department of Renal Pathology, Deutsches Krebsforschungszentrum, Heidelberg, Germany

Correspondence and offprint requests to: Dr I. A. Hauser, Klinikum der Johann Wolfgang Goethe-Universität, Medizinische Klinik IV, Funktionsbereich Nephrologie, D-60590 Frankfurt/Main, Germany. Email: i.hauser{at}em.uni-frankfurt.de

Keywords: acute interstitial nephritis; Ascaris lumbricoides; parasitosis



   Introduction
 Top
 Introduction
 Case
 Discussion
 References
 
Acute interstitial nephritis is an important cause of acute renal failure. The incidence of interstitial nephritis can only be estimated because of its minimal and non-specific symptoms except for the development of renal failure. Different studies focusing on apparently healthy individuals or unselected autopsy series estimate a prevalence of ~1% [1,2]. It is assumed that acute interstitial nephritis is the cause of acute renal failure in ~15% of cases [3].

Many causative factors leading to acute interstitial nephritis do exist, but may be categorized into distinctive groups: drug hypersensitivity reaction, infection, immune-mediated diseases, hereditary, metabolic and idiopathic forms. Within these broad categories, nowadays drugs are the predominant cause of interstitial nephritis, followed by infections and idiopathic lesions [4].

Acute pyelonephritis caused by renal invasion of virulent microorganisms has to be distinguished from acute interstitial nephritis, which can occasionally be seen in the setting of systemic bacterial and viral infection as a hypersensitivity reaction [3], whereas it is uncommon in human parasitosis.

Ascaris lumbricoides is the most prevalent of human helminths, affecting ~25% of the world's population. The highest carrier rates are observed in developing countries of the tropics and subtropics [5]. However, even in rural areas of industrialized western countries, infestation rates as high as 28% have been described, particularly in association with the use of sewerage for crop fertilization [6]. In adults, typical gastrointestinal symptoms, such as vomitus, can be seen only in a minority of cases of A.lumbricoides infection, as it usually causes only weak and unspecific clinical symptoms.

We report the case of a patient who, following a vacation in Russia, developed periodic nocturnal fever episodes accompanied by an impairment of renal function.



   Case
 Top
 Introduction
 Case
 Discussion
 References
 
A 48-year-old male developed nocturnal fever (maximum 38.6°C) 3 days after returning from a 2-week vacation in Russia. After 3 weeks of periodic nocturnal fever episodes accompanied by a growing feeling of sickness, weakness and a weight loss of 5 kg, he consulted his family physician. Because of an elevated serum creatinine (1.5 mg/dl), that had been in normal range (0.9 mg/dl) in a routine check 2 months before, he was admitted to hospital.

Physical examination revealed no abnormalities. The patient had never been ill nor taken any regular medications. X-ray investigation of the chest did not show any pathological findings. Ultrasound investigation showed normal sized kidneys with a slight increase in cortical echogenicity. No signs of renal artery stenosis could be found. Laboratory investigation revealed elevated C-reactive protein of 10 mg/dl (normal range <0.9 mg/dl) and elevated erythrocyte sedimentation rate of 85/115 mm. Blood, urine, sputum and stool culture were negative. Complete blood cell count revealed leukocytosis of 15/nl with eosinophilia of 1.8/nl (12% of white blood cells). Urinanalysis revealed a proteinuria of 0.6 g/day, glucosuria and leukocyturia of 20–30 per field with an eosinophiluria of >10% by Hansel's stain. Renal function was reduced (serum creatinine 2.1 mg/dl). Other blood parameters, e.g. electrolytes, were in the normal range. Testing for autoimmune antibodies, such as antinuclear antibodies, antiphospholipid antibodies, antineutrophil cytoplasmatic antibodies, antiglomerular basement membrane antibodies, as well as lues-serology (ELISA and VDRL), hepatitis B surface antigen and light chain proteinuria gave negative results. Complement C3 and C4 were in the normal range.

Because of marked eosinophilia and eosinophiluria suggestive of helminths, a screening for parasitosis was performed. In the faeces, eggs of A.lumbricoides were found, and therefore therapy with mebendazole (2 x 100 mg/day for 3 days) was administered.

At that time, serum creatinine had increased further to 2.7 mg/dl [blood urea nitrogen (BUN) 79 mg/dl]. Because of the unclear origin of the progressing renal impairment, a percutaneous renal biopsy was performed simultaneously with the initiation of mebendazole therapy.

Histological examination showed cortically accentuated interstitial nephritis with a dense peritubular infiltrate of lymphocytes, monocytes and granulocytes including eosinophils (Figure 1). No glomerular lesions were seen on light microscopy. Immunfluorescence staining was slightly positive for IgM and complement C3 in the mesangial area. Twenty percent of the cortical tubulointerstitium showed chronic alterations.



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Fig. 1. (A) Glomerulus with regular peripheral basement membranes, typical mesangium and normal cell number. A periglomerular mononuclear interstitial infiltrate is apparent (arrows). (B) Focally dense inflammatory interstitial infiltrate, consisting of eosinophilic granulates (arrowheads), monocytes and lymphocytes. Tubules show focal acute damage with flat epithelia (arrow).

 
After successful treatment of the underlying Ascaris infection, clinical symptoms persisted and renal insufficiency had progressed further (serum creatinine 3.2 mg/dl, creatine clearance 41 ml/min x 1.73 m2, BUN 79 mg/dl).

As a consequence of this observation, suggesting ongoing interstitial nephritis even after elimination of the pathological agent, oral corticosteroid therapy consisting of 1 mg/kg/day prednisone was introduced, maintained for 2 weeks and reduced stepwise according to the scheme shown in Figure 2.



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Fig. 2. Graph showing the time course of serum creatinine levels in a patient with biopsy-proven acute interstitial nephritis due to Ascaris lumbricoides infection. The treatment periods and doses of mebendazole and prednisone are indicated on the graph.

 
Within 3 days, the body temperature dropped and renal function started to improve. After 2 months, renal function had completely recovered (Figure 2).



   Discussion
 Top
 Introduction
 Case
 Discussion
 References
 
Renal involvement in parasitic infections is polymorphic, ranging from direct invasion to various types of glomerulonephritis. Acute interstitial nephritis as a form of hypersensitivity reaction is an uncommon manifestation in the setting of human parasitosis [7].

Acute interstitial nephritis is a heterogeneous disorder not only in aetiology, but also in presentation, laboratory findings and outcome.

We present a case of acute interstitial nephritis in association with A.lumbricoides infection of a 48-year-old patient. A combination of antibiotic and steroid therapy led to eradication of the helminths and to full recovery of renal function.

The aetiology of interstitial nephritis remains unclear in many patients, particularly in those taking potentially offending drugs. In our case, the patient was not taking any medication and denied taking any drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), prior to the current hospital stay. In vivo as well as in vitro bleeding time assessed prior to percutaneous renal biopsy had been in the normal range, supporting the notion that at least NSAIDs had not been taken by our patient.

Besides invasive ascariasis of the kidney [8] and acute renal failure in the setting of A.lumbricoides-induced acute pancreatitis [9], to date only three cases of acute interstitial nephritis in A.lumbricoides infection have been described in the literature [10,11]. In one patient, acute interstitial nephritis was accompanied by pulmonary and hepatic involvement, and in one case by pulmonary infiltrates and generalized lymph node swelling. In the third case reported, no organ manifestation apart from acute interstitial nephritis was observed, as in the case presented here. We excluded pulmonary involvement by X-ray and sputum examination which showed no eosinophils or Charcot–Leyden crystals.

In none of the described patients did eradication of A.lumbricoides alone lead to recovery of renal function. In the first two cases described, acute interstitial nephritis progressed to acute renal failure leading to death in the pre-haemodialysis era.

In the third case dating from 1995, acute interstitial nephritis progressed and haemodialysis was required as a supportive treatment because of transient uraemia. Similar to the clinical course of our patient, in the latter case introduction of steroid therapy led to full recovery of renal function.

Infection with A.lumbricoides and presentation of its antigens has been demonstrated to activate granulocytes and lymphocytes and leads to an induction of various cytokines, such as interleukin-4 and interleukin-5 [12]. These mechanisms also play a major role in the pathogenesis of antigen-mediated acute interstitial nephritis and may therefore present a common pathway in these cases [4]. Moreover, it has been described that eosinophils and eosinophil granule proteins are elevated in the urine of A.lumbricoides-infected patients even in the absence of renal involvement [13].

Ascaris lumbricoides affects ~25% of the world's population, but acute interstitial nephritis is rarely seen and seems to be a quite uncommon complication in the course of infection, even when it is taken into account that most infections occur in developing countries, where medical standards are low and intermittent impairment of renal function might be underdiagnosed, as patients only have limited access to medical care.

It has been shown recently that host genetics is an important determinant of the intensity and time course of A.lumbricoides infection [14]. A special genetic or allergic predisposition could therefore have been the reason for the renal involvement in these patients. Moreover, it is well described that concurrent helminth infections, such as A.lumbricoides, alter the immune response to non-parasite antigens through bystander effects, e.g. in the post-vaccination immune response and in the setting of asthma [12]. Therefore, it is also possible that Ascaris-derived antigens themselves did not lead to acute interstitial nephritis but had a permissive effect on other inflammatory stimuli in susceptible patients.

Most infections with parasites cause only weak and unspecific clinical symptoms leading to difficulties in diagnosis. Gastrointestinal or pulmonary symptoms are rarely observed in the course of A. lumbricoides infection, and severe complications, such as intestinal obstruction and perforation or pneumonia, are less frequent than 0.2% of all cases. In cases of an unexplained decrement in renal function, especially in patients living in conditions of lower hygienic standards and with symptoms indicating microbial infections, parasitosis should therefore be considered in the differential diagnosis.

Conflict of interest statement. None declared.



   References
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 Introduction
 Case
 Discussion
 References
 

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Received for publication: 2.10.03
Accepted in revised form: 4. 2.04





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