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.     

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 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.     

Immunoallergic tubulo-interstitial nephritis following ingestion of carbamazepine

One month after taking carbamazepine for pain relief, a 13 year-old child with Friedrich's ataxia presented with an allergic rash and digestive and cardiac symptoms. Two weeks later, non-oliguric renal failure suggestive of interstitial nephritis was present. Acute renal failure resolved with pulse methyl prednisolone injections relayed with prednisone orally, for 2 months. Allergic manifestations with carbamazepine should lead to immediate withdrawal of treatment.     

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.     

Crohn's enteritis and chronic tubulo-interstitial nephropathy in an adolescent

We report for the first time a case of Crohn's enteritis associated with a chronic tubulo-interstitial nephritis in an adolescent. The illness started insidiously in an 11 year-old boy who had suffered from failure to thrive and protracted watery diarrhea. At presentation the patient had an inflammatory bowel disease located to the left colon but no renal dysfunction. Until the age of 15, the intestinal symptoms were stable but a progressive renal insufficiency developed. A percutaneous renal biopsy was then performed which showed a widespread chronic tubulo-interstitial nephritis. Following a 6 months corticosteroid treatment, renal dysfunction seemed to be stabilized. However, delayed growth and corticosteroid dependency led to total colectomy. Pathologic examination showed granulomatosis involvement of the entire colon and severe interstitial nephritis with neither linear nor granulous deposits along tubular basement membranes. After a 2 year-delay following the colectomy, renal function was stabilized and a catch up growth was achieved.     

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.     

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.     

Nephrotic syndrome associated with nonsteroidal anti-inflammatory drug use in two children

Two children with nephrotic syndrome in association with nonsteroidal anti-inflammatory drug (NSAID) use are described, and the literature concerning this association is reviewed. NSAIDs are drugs with the potential for causing significant renal toxicity including the nephrotic syndrome, interstitial nephritis, and renal failure even in children without obvious preceding renal disease. Children prescribed such drugs should be regularly monitored with urinalyses and plasma creatinine estimations. The possibility of toxicity to over-the-counter use of NSAIDs should be remembered.     

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.     

Interstitial nephritis in autoimmune hemolytic anemia

A case is reported of a 15-year-old boy with chronic autoimmune hemolytic anemia who developed renal insufficiency 3 years after splenectomy. An interstitial nephritis with striking lymphocytic infiltrates and sclerosed glomeruli could be demonstrated by percutaneous renal biopsy. Renal symptoms disappeared promptly after corticosteroid therapy. The renal lesions are thought to have arisen as part of the autoimmune disease.     

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.     

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.     

Type 4 Renal Tubular Acidosis (Sub-type 2) Associated with Idiopathic Interistitial Nephritis

ABSTRACT. An 18-month-old girl presenting with anorexia and failure to thrive, was referred for adenoidectomy. Arterial hypertension was discovered on physical examination. Laboratory results revealed hyperkalaemic, hyperchloraemic, metabolic acidosis, with slight azotemia. Urinary aldosterone excretion and plasma renin were decreased. Renal biopsy showed idiopathic interstitial nephritis. The diagnosis of type 4 renal tubular acidosis, sub-type 2, i.e. primary hyporeninaemic secondary hypoaldosteronism was proposed. According to our knowledge, this disease has not previously been reported in young children, but is well known in azotaemic adults. We therefore propose the inclusion of this uncommon renal disease in the differential diagnosis of failure to thrive in childhood.     

Type 4 renal tubular acidosis (sub-type 2) associated with idiopathic interstitial nephritis

An 18-month-old girl presenting with anorexia and failure to thrive, was referred for adenoidectomy. Arterial hypertension was discovered on physical examination. Laboratory results revealed hyperkalaemic, hyperchloraemic, metabolic acidosis, with slight azotemia. Urinary aldosterone excretion and plasma renin were decreased. Renal biopsy showed idiopathic interstitial nephritis. The diagnosis of type 4 renal tubular acidosis, sub-type 2, i.e. primary hyporeninaemic secondary hypoaldosteronism was proposed. According to our knowledge, this disease has not previously been reported in young children, but is well known in azotaemic adults. We therefore propose the inclusion of this uncommon renal disease in the differential diagnosis of failure to thrive in childhood.     

儿童慢性马兜铃酸肾病3例临床病理分析及文献复习

目的通过报告3例慢性马兜铃酸肾病,增加对其临床与病理特征的认识。方法对北京大学第一医院儿科收治的3例慢性马兜铃酸肾病患儿进行回顾性分析,总结其临床和病理特点,并复习相关文献。结果3例慢性马兜铃酸肾病患儿,男1例,女2例,年龄为10岁、14岁和16岁;分别因乙型肝炎、颅咽管瘤术后脑水肿和紫癜性肾炎服用含马兜铃酸成分的中草药或中成药4～8个月,于开始服用2个月至6年后发病;3例患儿均以不同程度的肾功能损害伴近-远端肾小管受损为主要表现,其中2例以贫血为首发症状,肾功能损害严重,均已达到肾衰竭尿毒症期,另1例以糖尿为首发表现,肾功能损害较轻,同时表现继发性Fanconi综合征。3例肾病理均以广泛性或多灶状寡细胞性间质纤维化和肾小管萎缩为特征,肾小球病变轻微,免疫荧光除2例因基础疾病见IgA(++～+++)外,均未见明显免疫复合物沉积。2例患儿停用含有马兜铃酸的药物后肾功能仍呈不同程度的进行性恶化,其中1例放弃治疗半年后死于消化道大出血,1例等待肾替代治疗;另1例肾功能损伤较轻者,停用含有马兜铃酸的药物后经小剂量糖皮质激素和营养肾小管治疗病情改善,肾功能及肾小管功能恢复,仍在临床随访中。结论儿童慢性马兜铃酸肾病临床特点是渐进性肾功能损害和肾小管功能受损,肾脏病理特征为广泛的寡细胞性间质纤维化和肾小管萎缩;在停服含马兜铃酸药物后肾功能恶化常不可逆转,最终导致终末期肾病;小剂量糖皮质激素对于缓解早期轻症者的病情可能有益。预防该病的关键在于提高对含马兜铃酸中药肾毒性的认识。     

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.     

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.     

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.