Severe reversible renal failure due to naproxen-associated acute interstitial nephritis

Acute interstitial nephritis is uncommon in children and has very rarely been described with naproxen treatment. We report the occurrence of severe acute renal failure in a 10-year-old girl with juvenile rheumatoid arthritis after 1 month of naproxen therapy. Renal biopsy showed severe acute interstitial nephritis. The patient recovered completely after discontinuation of naproxen and administration of methylprednisolone. A review of the literature regarding non-steroidal anti-inflammatory drug-associated acute interstitial nephritis is provided. CONCLUSION: In an era of increasing popularity of non-steroidal anti-inflammatory drugs for use in children, paediatricians should be aware of the potential renal complications of this class of drugs.     

Recurrent acute interstitial nephritis induced by azithromycin

A 14-year-old girl is reported with recurrent, azithromycin-induced, acute interstitial nephritis. The second episode was more severe than the first; and although both were treated with intensive corticosteroid therapy, renal function remained impaired. Although most cases of antibiotic induced acute interstitial nephritis are benign and self-limited, some patients are at risk for permanent renal injury.     

Acute interstitial nephritis of probable pharmacological origin

Acute interstitial nephritis in children is rare. We present a case of acute interstitial nephritis in a 10-year-old boy, which was probably drug-induced. Initial symptoms included fever, loss of appetite, weight loss, alterations in urine analysis and mild renal failure. Treatment with steroids produced a good clinical response and renal function returned to normal within a few months.     

Naproxen nephrotoxicity in a 2-year-old child

The development of acute renal failure and interstitial nephritis due to therapeutic doses of nonsteroidal anti-inflammatory drugs has been documented repeatedly in adult patients but is rare in children. We report the occurrence of this complication in a child. Acute renal failure and hyperkalemia developed in a 2-year-old boy with juvenile rheumatoid arthritis after one month of naproxen sodium therapy. The evidence of renal toxic effects became manifest after an episode of dehydration. A percutaneous renal biopsy specimen revealed interstitial nephritis. The patient recovered promptly after withdrawal of the drug.     

Interstitial nephritis of acute onset.

Interstitial nephritis was diagnosed at renal biopsy in 10 previously healthy children. All had identical clinical symptoms: anaemia, raised sedimentation rate, low glomerular filtration rate, protein and leucocytes in the urine, but no bacteria; nine also had glycosuria. Six of the children had a history of recent ingestion of drugs or a serologically proved infection, or both. One child later developed uveitis. After the acute phase all made at least partial recovery, but after a mean follow up of two years and eight months only four were without any signs of disease, three had equivocal findings, two definite renal disease, and one renal failure. Interstitial nephritis, therefore, seems to be a clinical entity often occurring without known cause or triggering factor, its prognosis is variable, and some patients may develop chronic renal failure.     

Terminal renal failure caused by interstitial nephritis following mushroom poisoning by Cortinarius speciocissimus

A 14 year old boy was admitted for vomiting, anorexia, flank pain and leukocyturia/hematuria. Shortly after admission, he developed anuria and acute renal failure so that hemodialysis had to be started. Pre- and post-renal causes were excluded. There were no signs of acute glomerulonephritis; liver enzymes were normal. The 123Iodine-Hippuran scan showed a shock kidney pattern lacking tubular clearance. Renal biopsy revealed an interstitial nephritis with edema and a mixed cellular infiltration. History was empty for nephrotoxic agents except for mushroom ingestion: Five days before admission the boy ate Cortinarius speciocissimus mushrooms, the toxine of which is known to be nephrotoxic, causing irreversible renal failure in severe cases (Orellanus Syndrome). Renal function did not improve much and renal transplantation was performed after 14 months on hemodialysis. In interstitial nephritis of unknown etiology the possibility of mushroom poisoning should be considered.     

Acute renal failure due to acute tubulointerstitial nephritis

Acute interstitial nephritis (AIN) should be ruled out in children with unexplained acute renal failure. We present a 4 1/2 year old girl who presented with oliguric acute renal failure preceded by a febrile illness. Renal histopathology revealed features of drug induced AIN. She recovered with dialysis, other supportive treatment and a course of steroids.     

Acute kidney injury in a girl with ulcerative colitis and cytomegalovirus-induced focal segmental glomerular sclerosis

Background

Mesalamine or 5-aminosalicylic acid (5-ASA) has proven efficacy in treating patients with ulcerative colitis (UC). Although mesalamine is considered safe, it has been associated with acute interstitial nephritis and renal failure.

Methods

Herein we present a case of a child with UC who developed acute renal failure on mesalamine therapy.

Results

A 15-year-old African-American girl with well-controlled UC presented to the Johns Hopkins Hospital with a four-day history of high fever, malaise, generalized body aches, and productive non-bloody cough. Over the next three days, she developed acute renal failure with fluid retention, and elevated serum creatinine and blood urea nitrogen. A kidney biopsy showed drug induced acute interstitial nephritis and focal segmental glomerulosclerosis with viral inclusion bodies likely secondary to cytomegalovirus.

Conclusion

When treating UC patients with a history of underlying renal disease, it is advised to carefully monitor renal function while on mesalamine therapy.     

The role of mast cells in acute tubulo-interstitial nephritis with uveitis

We describe the clinicopathological characteristics of two patients with acute tubulo-interstitial nephritis with uveitis (TINU) with mast cells infiltrating the interstitium. The pathogenesis of TINU remains unknown, but a T-cell-mediated immune response was suggested to be involved. Recent studies have shown that infiltrating mast cells are closely associated with the development of renal interstitial fibrosis in glomerulonephritis. To address the role of mast cells in the renal interstitial injury in TINU, immunohistochemical studies were performed in renal biopsy sections using anti-human mast cell tryptase antibody specific for mast cells. In addition, we tried to detect CD68-positive macrophages to compare with the localisation of mast cells within the renal interstitium. Mast cells and macrophages could be detected in renal interstitial lesions of both patients. Massive infiltration of macrophages into interstitial lesions was observed, whereas mast cells were detected in a sporadic rather than a clustered manner, and associated with fibrotic lesions. Repeat renal biopsy findings suggested the involvement of these cells in the renal interstitial injury because the number of infiltrating mast cells and macrophages in the interstitium decreased with the improvements in clinical symptoms and pathological lesions. CONCLUSION: The present study showed that mast cells might play an important role in the development of renal interstitial injury in tubulo-interstitial nephritis with uveitis.     

Chronic inflammatory intestinal disease and nephritis]

An 11 year old CD-patient developed an interstitial nephritis and acute kidney failure following treatment with Mesalazine (5-ASA) and Salazosulfapyridine (SASP). After removal of the medication and treatment with hemofiltration and prednisone there was only an incomplete recovery of the renal function (creatinine-clearance 34 ml/1,73 m2/min). It is thought that an hyperergic-allergic reaction due to SASP and 5-ASA causes interstitial nephritis in inflammatory bowel disease (IBD). This reaction can be induced by re-exposition too. On the other hand IBD can be associated with glomerulonephritis. This could be a not very well known extraintestinal manifestation in IBD caused by immune-complexes in serum and glomerula. A rapid histological verification of the renal disease is necessary for successful treatment. In both renal manifestations chronic courses are possible. These observations should not lead to avoid SASP/5-ASA in treatment of IBD, but renal function should be routinely investigated.     

Structure of interstitial nephritis in children]

The authors provide the data on 24 cases of interstitial nephritis in children treated at the Nephrological Center of the city of Kuibyshev in 1986-1990. Describe the etiological structure of interstitial nephritis using the classification developed by N. A. Korovina and coworkers (1982), randomization according to the age, sex, and the disease course. Demonstrate the predominance of the postviral and toxicoallergic disease patterns in children of the early, preschool and junior school age. Estimate the importance of the types of urine proteinograms in the diagnosis of interstitial nephritis.     

关注儿童用药后的肾损伤

药物性肾损伤是儿童急性肾损伤的主要原因之一。药物经由肾脏代谢排泄时导致肾小管上皮细胞损伤、肾脏免疫炎症,或导致肾内血流动力学改变,或形成结晶堵塞肾小管。临床主要表现为急性肾损伤、急性肾小管坏死、急慢性间质性肾炎、结晶性肾病、肾病综合征、肾小管功能障碍等。应用生物标志物可以早期监测药物性肾损伤。临床工作中应及时纠正药物性肾损伤的高危因素,及时停用相关药物和监测肾功能,力求早期诊断,早期干预,改善预后。     

��ע��ͯ��ҩ���������

??Drug-induced kidney injury is one of the main causes of acute kidney injury in children. Certain drugs can lead to tubular epithelial injury??kidney immune inflammation??or alter the intraglomerular hemodynamics??or cause intrarenal obstruction??which contribute to clinical manifestations including acute kidney injury??acute tubular necrosis??acute or chronic interstitial nephritis??nephrolithiasis/crystal nephropathy??nephrotic syndrome??tubular dysfunction??et al. The setting of several biomarkers are used for prediction and detection of early drug-induced kidney injury. In clinical practice the risk factors of drug-induced kidney injury should be corrected in time and the related drugs be stopped and kidney function be monitored in order to achieve early diagnosis and early intervention??which can improve the prognosis.     

Kidney involvement in infectious diseases

Involvement of the kidneys without direct invasion of them by the pathogenic agents has been recognized in a variety of infections with bacteria, viruses, fungi, and protozoa. Pathogenetic importance attaches to immune mechanisms with formation and glomerular deposition of immune complexes, or direct damage caused to the renal parenchyma by microbial toxins. Signs and symptoms may range from minimal proteinuria and/or microhematuria, through nephritic or nephrotic syndrome, to acute or chronic renal failure. Accordingly, all kinds of glomerulonephritis or interstitial nephritis may be found on histological examination. With rapid elimination of the causative agent the prognosis is generally good.     

Poststreptococcal nephritis--a rare disease?.

Forty-three children presenting with acute nephritis were studied for evidence of preceeding steptococcal infection. They were compared with a group of control children of similar age. Two-thirds of those with nephritis gave a history of a preceeding respiratory infection (compared with one-third of the controls). A significant rise of antistreptolysin O tire occurred in only 16 children with nephritis and within this minority several did not show a fall of serum C3 level. It is probable that only one-third of the children with acute nephritis had poststreptoccoccal glomerulonephritis. Poststreptococcal glomerulo-nephritis is no longer the main cause of childhood acute nephritis in the Leeds area. There may be many different aetiological factors and this diversity calls for more rigorous investigations and a more guarded prognosis.     

A case of tubulo-interstitial nephritis with exfoliative dermatitis and hepatitis due to phenobarbital hypersensitivity

Severe exfoliative dermatitis and liver dysfunction developed in a 5-year-old girl 3 weeks after initiation of phenobarbital therapy. Liver function improved gradually after discontinuation of phenobarbital. During the convalescent stage an initially mild renal dysfunction was exacerbated by episodes of post-transfusion haemolysis. Liver biopsy revealed moderate parenchymal damage with subacute cellular infiltration. Renal biopsy demonstrated the cardinal findings of interstitial nephritis, excluding the possibility of acute tubular necrosis caused by haemolysis. Serial lymphocyte transformation studies and skin patch tests gave positive results for phenobarbital, supporting the view that these were unusual complications of phenobarbital hypersensitivity.     

Fatal mumps nephritis and myocarditis

The case of a 14-year-old girl with fatal interstitial nephritis and myocarditis as complications of mumps is reported. The illness began with parotitis; renal symptoms developed within a week. The patient's renal and cardiac status and clinical course rapidly deteriorated and the outcome was fatal. The post-mortem renal biopsy sample showed interstitial mononuclear cell infiltration, oedema, and focal tubular epithelial damage in biopsy material of kidney, confirming the clinical diagnosis. Myocarditis was determined by electrocardiographic and echocardiographic findings. Since it has been reported that fatal complications such as myocarditis, dilated cardiomyopathy, and nephritis may develop in the course of mumps, the patients with mumps, especially in complicated cases, should be followed closely because of the severe clinical conditions which may progress.     

Acute tubulointerstitial nephritis and uveitis (TINU syndrome) in childhood

During the last two years we have observed three children, aged 12-15 years, who developed acute non-oliguric renal failure with concomitant uveitis. Acute interstitial nephritis with lympho-monocytic infiltrates was diagnosed in all cases by renal biopsy. While two patients went into spontaneous remission, renal function in the remaining child improved only after treatment with oral prednisone. Withdrawal of steroid medication was promptly followed by a relapse, necessitating steroid therapy for a total of 4 months. The clinical and histological findings were consonant with the so-called TINU syndrome. While the pathogenesis of this syndrome is unclear, the prognosis seems to be favorable and most cases resolve spontaneously. However, in some cases, prolonged therapy with corticosteroids may be required.     

Management of acute renal failure in children

The term acute kidney injury (AKI) has replaced acute renal failure, recognizing that an acute decline in renal function is often secondary to an injury or insult. The incidence of AKI was 8 per million total population in a UK retrospective study. AKI is classified into three groups: pre-renal, intrinsic renal and obstructive post-renal AKI. Haemolytic uraemic syndrome and acute tubular necrosis (ATN) are the most common causes in children. This review discusses the clinical evaluation, investigation and management of AKI and its associated complications. The prognosis for AKI depends upon the underlying cause. It is good for ATN and interstitial nephritis but AKI following cardiac surgery has the worst outcome. Other poor prognostic factors include multiorgan failure, inotropic support, ventilation and need for dialysis therapy. AKI due to primary renal disease is not common but is the cause for the majority of children who need chronic dialysis therapy. All children with AKI who require renal replacement therapy need long-term follow-up to monitor blood pressure, proteinuria and renal function.     

Rapid onset of co-trimoxazole induced interstitial nephritis

An infant developed anuric renal failure within 18 hours of starting therapy with Co-trimoxazole for otitis media. There was no prior exposure to Co-trimoxazole, sulfonamides or trimethoprim. A renal biopsy revealed acute interstitial nephritis with eosinophilic infiltration (AIN). The lymphocyte blast transformation test revealed increased proliferation of the patient's lymphocytes on exposure to Co-trimoxazole (Bactrim). Both parents have clinically demonstrated hypersensitivity to sulfonamides. The extremely short latent period between ingestion of the offending drug and the onset of AIN in the absence of prior exposure to the drug has been reported previously. It suggests that drug induced AIN may develop more rapidly in patients with a strong genetic hypersensitivity to the drug.