| Abstract|| |
Acute renal failure (ARF) is a rare but severe complication of active idiopathic nephrotic syndrome (INS) in children. It may be due to several causes with different outcomes. Both the clinical picture of the patient as well as laboratory, imaging and histopathological findings may help in the diagnosis. We present a case of drug-induced acute interstitial nephritis (AIN), complicated with ARF, in a 2 1/2 -year-old girl with active INS. The child was referred to the Hippokration General Hospital, Thessaloniki, Greece hospital with steroid-resistant NS; renal biopsy was performed, which did not show any remarkable findings and cyclosporine was administered in addition to steroid therapy. The first day after biopsy, the child developed gross hematuria and abdominal pain and an antibiotic was added to her treatment. In the following days, fever, vomiting, hypertension and ARF occurred. Ultrasound study revealed enlarged kidneys with increased echogenity and loss of corticomedullary differentiation. The antibiotic and cyclosporine were stopped and the child was managed with furosemide, nifedipine and steroids. A second renal biopsy was performed, which confirmed the diagnosis of acute interstitial nephritis. The child did not require dialysis therapy. Her urine output improved gradually and the serum creatinine normalized one month after the initial episode. Our case re-emphasizes the need for investigation of factors precipitating ARF in children with idiopathic NS.
|How to cite this article:|
Printza N, Koukourgianni F, Saleh T, Goga C, Papachristou F. Drug-induced interstitial nephritis in a child with idiopathic nephrotic syndrome. Saudi J Kidney Dis Transpl 2009;20:1072-5
|How to cite this URL:|
Printza N, Koukourgianni F, Saleh T, Goga C, Papachristou F. Drug-induced interstitial nephritis in a child with idiopathic nephrotic syndrome. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2020 Jun 6];20:1072-5. Available from: http://www.sjkdt.org/text.asp?2009/20/6/1072/57267
| Introduction|| |
Acute renal failure (ARF) is a rare complication of idiopathic nephrotic syndrome (INS) in children, accounting for up to 0.8% of cases. It may be a consequence of severe intravascular volume depletion, acute tubular necrosis, bilateral renal vein thrombosis, acute pyelonephritis, rapid progression of the original glomerular disease or acute interstitial nephritis (AIN). , Drug-induced AIN may occur as an adverse reaction to many different drugs. Establishing a clear link between a medication and AIN may be difficult because in many cases, several medications are administered simultaneously. We present a case of drug-induced AIN complicated with ARF, in a child with active INS. We mainly highlight the causative factors, the laboratory, imaging and histopathological findings and the outcome of ARF in this child. We would like also to re-emphasize the need for investigation of factors precipitating ARF in nephrotic children.
| Case Report|| |
A two and a half-year-old girl was referred to our hospital for management of a relapse of the nephrotic syndrome. At admission, she had peri-orbital edema, edema in her lower extremities and Cushingoid face. Her blood pressure was normal. The patient's past medical history was unremarkable while the family history was positive for proteinuria of unknown origin in her grandfather.
The child was already on steroid therapy (60 mg/m 2 /day) and we continued and completed five weeks of steroid treatment. The patient did not go into remission and three courses of methylprednisone pulse therapy (1 gr/1.73 m 2 on alternate day), were given. She was also treated with intravenous albumin and furosemide. Due to the steroid-resistant nephrotic syndrome, a renal biopsy was performed, which did not show any remarkable findings and, cyclosporine therapy was started in a dose of 6 mg/kg/day. The first day after biopsy, she developed gross hematuria and abdominal pain. A urine culture was obtained and child was treated with amoxicillin/clauvulinic acid. The following days, fever went up to 40°C, and oliguria, hypertension and vomiting occurred, in addition. Laboratory findings revealed leukocytosis, eosinophilia, elevated erythrocyte sedimentation rate and C-reactive protein levels, increased serum creatinine levels up to 2 mg/ dL, blood urea nitrogen up to 170 mg/dL, metabolic acidosis and normal serum electrolytes. Urinalysis revealed proteinuria, microscopic hematuria and glycosuria in the absence of hyperglycemia. Urine culture was negative. The tubular reabsorption of phosphorus was 46% and the glomerular filtration rate (GFR) was estimated at 22 mL/min/1.73 m2.
Ultrasound study revealed increase in dimension and echogenicity of the cortex of both kidneys with loss of corticomedullary differrentiation, indicating parenchymal damage. Doppler study showed normal blood flow.
The antibiotic and cyclosporine were stopped and the child was managed with intravenous albumin, furosemide, oral steroids and nifedipine due to the mild hypertension. There was no clinical or laboratory evidence of infection. The immunological findings noticed included decreased IgG and IgM immunoglobulins due to the active nephrotic syndrome and elevated C3 complement as a marker of inflammation. A second percutaneous renal biopsy was performed. The main findings were interstitial infiltration predominantly of mononuclear cells, with invasion of tubular epithelium (tubulitis) and cystic dilatation of tubules with hyaline cast [Figure 1], findings consistent with a diagnosis of AIN. She did not require dialysis therapy. Her urine output improved gradually and serum creatinine normalized one month after the episode. Thereafter, she was treated with steroids on alternate days and tacrolimus, as proteinuria was still present at nephrotic levels. On follow-up three months later, she went into remission of the nephrotic syndrome with a serum creatinine of 0.45 mg/dL.
| Discussion|| |
Acute renal failure is an uncommon but severe complication of INS in children. , Pstrusinska et al noticed ARF in eight of 1006 children (0.8%) with INS aged between six and 17.5 years.  Protracted ARF necessitating dialysis and followed by delayed recovery also occurs rarely in children. Most patients (85%) with ARF and nephrotic syndrome have minimal change disease.  Amongst the causes of ARF, in 60% of the patients, tubulointerstitial changes compatible with acute tubular necrosis are present. In 40%, no tubular damage is found, although there is considerable interstitial edema. 
AIN must be considered in the differential diagnosis of ARF because it accounts for 10-25% of reported cases of ARF in adults and up to 7% in children. Drugs, which are associated with AIN are antibiotics, non-steroidal antiinflammatory drugs (NSAIDs), anticonvulsants and diuretics.  The most common drugs in children are penicillin and NSAIDs. AIN is a hypersensitivity reaction mediated through both humoral and cell-mediated mechanisms.  Symptoms of the disease occur within hours to months after drug administration; earlier presentation is observed, if the patient had been earlier sensitized to the same or a chemically similar agent.  In our case, antibiotic therapy with amoxicillin/clavulanic acid was implicated as the offending factor and not cyclosporine. On the other hand, the parents reported that their child had been previously treated with amoxicillin/clavulanic acid.
Drug-induced AIN is suspected as the cause of ARF in a child with fever, anorexia, emesis, weight loss, and sore throat, which are the most common findings. Urticarial rash and arthralgia are rare. Renal manifestations include ARF, eosinophiluria, proteinuria, glycosuria, hematuria and decreased tubular reabsorption of phosphorus.  Other laboratory findings include leukocytosis, non-hemolytic anemia and elevated erythrocyte sedimentation rate and C-reactive protein levels. , Our patient had majority of the above mentioned findings. Renal ultrasound examination in AIN demonstrates either normal or enlarged kidneys with increased echogenity of the cortex, as in our case, depending on the extent of tubulointerstitial inflammation and edema. Doppler study was performed in order to exclude renal vein thrombosis, as the patient was in active nephrotic syndrome. Significant hypoalbuminemia and infection are reported by Nagamani et al to be risk factors for the development of ARF in nephrotic patients.  Unlike this report, in our patient there were no other risk factors, except for the drug administration.
Because of variable non-specific clinical manifestations and laboratory findings, the importance of renal biopsy for diagnosis of AIN has to be emphasized.  In our case, we performed two biopsies in a period of two weeks. The first was performed due to the steroidresistant characteristics of the nephrotic syndrome and the second was aimed at establishing the cause of ARF in this child with active steroid-resistant nephrotic syndrome. The definitive diagnosis of AIN by renal biopsy was very helpful to our therapeutic strategy.
The initial treatment of antibiotic-induced AIN is primarily supportive care, including withdrawal of possible offending medications and dialysis therapy when necessary.  The use of corticosteroid therapy remains controversial.  Our patient continued with her steroid treatment as this was prescribed for the nephrotic syndrome.
Prognosis for recovery of renal function in children with drug induced AIN is excellent.  Most affected patients recover renal function completely within weeks or months of onset. Our patient did not require dialysis therapy and her renal functions normalized one month from onset.
In conclusion, ARF is a serious but rare complication in children with INS. Drug-induced AIN may cause ARF in these children and it is important to consider the same in the differrential diagnosis. An observation which should be emphasized in our study is that ARF due to drug-induced AIN is reversible even in children with active INS.
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1st Pediatric Department, Aristotles University of Thessaloniki, Hippokration General Hospital, Konstantinoupoleos 49, 54642 Thessaloniki