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.     

Acute renal failure after treatment with non-steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to have adverse effects on kidney function. Situations with a stimulated renin-angiotensin system such as volume depletion or pre-existing chronic renal failure predispose to acute renal failure (ARF) via inhibition of prostaglandin synthesis by NSAIDs. To date, NSAIDs are frequently used as antipyretic drugs even in situations predisposing to ARF. Within 20 months, seven children presenting with diarrhoea and/or vomiting and fever were treated with therapeutic doses (11.5–32 mg/kg per day) of ibuprofen for 1 to 3 days before developing ARF. Maximum plasma creatinine levels were 180–650 µmol/l. One patient required emergency dialysis for hyperkalaemia, uraemia, and hyperphosphataemia. After cessation of NSAID treatment and rehydration, all patients recovered completely with a normalised creatinine level after 3 to 9 days. Once the acute phase is controlled, long-term outcome is excellent. Interstitial nephritis, another possible adverse effect of NSAIDs, might require steroid treatment and is the major differential diagnosis. Only histological examination can confirm the exact pathomechanism of ARF after NSAID exposure. If immunological events are responsible for the ARF, the recovery period is usually longer. Conclusion: non-steroidal anti-inflammatory drugs are potentially dangerous in situations with even moderate volume depletion.Abbreviations AIN acute interstitial nephritis - ARF acute renal failure - COX cyclo-oxigenase - NSAIDs non-steroidal anti-inflammatory drugs - PG prostaglandin - RAS renin-angiotensin system     

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.     

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.     

药物性肾损害发病机制的研究进展

儿童药物性肾损害的发病机制是由儿童肾组织解剖学、生理学特征和药物结构与功能特征所决定的。肾脏微血管网络和肾小管-肾间质的分布面积占绝对优势,因此间质性肾损害非常多见。药物性肾损害发病机制包括细胞毒性（坏死或凋亡）、缺血性损伤和免疫性损伤,但由于各种药物之间化学结构和药理学差异,具体的单个药物所致肾损害的发生机制也有所不同,该文回顾了几种常见抗生素（头孢类、氨基甙类、万古霉素、碳青霉素类、两性霉素B）、非甾体类抗炎药物和环孢素A相关性肾损害发病机制的主要特征,以期提高儿科医师对药物性肾损害的意识。     

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.     

Plasma renin activity in acute poststreptococcal glomerulonephritis and the haemolytic-uraemic syndrome

Plasma renin activity (PRA) was determined in 10 children with acute glomerulonephritis and in 10 with the haemolytic-uraemic syndrome (HUS). Low renin levels were found in the hypertensive children with acute nephritis, all of whom had evidence of fluid overload. The amount of this overload correlated directly with the degree of hypertension and inversely with PRA. All the hypertensive children with HUS had high levels of plasma renin, and the highest levels were found in those cases who were subsequently shown to have the more severe degree of renal arteriolar occlusion. The findings emphasize the importance of measures designed to reduce salt and water overloading in the management of hypertension in acute nephritis, while drugs which suppress plasma renin are more likely to control blood pressure in HUS. Estimation of PRA may provide a guide to the management of hypertension in acute renal insufficiency.     

Non-steroidal anti-inflammatory drugs and slow-acting anti-rheumatic drugs in juvenile rheumatoid arthritis

The preferred drugs for the initial treatment of juvenile rheumatoid arthritis (JRA) are salicylates or other non-steroidal anti-inflammatory drugs (NSAID) such as tolmetin or naproxen. If the disease activity does not respond adequately to the treatment, slow-acting anti-rheumatic drugs (SAARD) such as oral gold agents, low-dose D-penicillamine, or sulfasalazine should be given in addition to NSAID. If the systemic manifestations are severe, corticosteroid therapy may be commenced. Furthermore, if the joint destruction is progressive, immunosuppressants such as methotrexate would be selected as the third-line drugs of choice. The safety and efficacy of SAARD and immunosuppressants for the treatment of children with JRA, however, have not yet been confirmed, as the adverse effects such as bone marrow suppression, oncogenicity and mutagenicity are sometimes intense. Consequently, the strict indications for use and new therapeutic concepts for the management of JRA based on its pathogenesis are required.     

Potential risk factors for the development of acute renal failure in preterm newborn infants: a case-control study

AIMS: To determine in a case-control study possible associations between the development of acute renal failure in preterm newborns and therapeutic interventions, particularly drug treatments. METHODS: The study population was 172 preterm infants of <38 weeks gestation; 71 had acute renal failure and 101 were controls closely matched for gestational age and birth weight. Maternal and neonatal information was collected for both groups through questionnaires and interviews. Routine data on renal variables were also collected. Univariate and multivariate logistic regression analyses were performed. RESULTS: Very low birthweight infants were at high risk of acute renal failure (79% of cases were <1500 g). However, the acute renal failure was transient. Mothers of infants with acute renal failure received more drugs during pregnancy and delivery (mainly antibiotics and non-steroidal anti-inflammatory drugs). Of the possible therapeutic interventions, intubation, catheterisation, and phototherapy were mainly applied to case subjects. A low Apgar score and patent ductus arteriosus were diagnosed in a greater percentage of neonates with acute renal failure. Moreover, in the first few days of life and before diagnosis of acute renal failure, case subjects received more drugs (antibiotics, non-steroidal anti-inflammatory drugs, and diuretics) and for a longer time. In the multivariate logistic analysis, medullary hyperechogenicity (odds ratio (OR) 4.491; 95% confidence interval (CI) 1.879 to 10.731) and ceftazidime administration (OR 5.082; 95% CI 1.493 to 17.297) were associated with a greater risk of acute renal failure. CONCLUSIONS: The results suggest the need for careful monitoring of very low birthweight infants and attention to drug treatments, as it is difficult to differentiate between normality and renal failure in the first few days of life.     

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.     

儿童紫癜性肾炎临床与病理相关性分析

目的：通过对95例紫癜性肾炎（HSPN）患儿临床表现及肾脏病理分析,阐明其临床及病理之间的联系。方法：对HSPN患儿进行临床分型及病理分级,对其进行综合分析。结果：①临床分型以肾病综合征型(27.4%)、蛋白尿＋血尿型(24.2%)多见,病理分级以Ⅲb(42.1%)最多见;②尿检正常者可见肾脏病理改变。尿检正常型、孤立性血尿或蛋白尿型以及血尿和蛋白尿型病理改变差异无显著性(P>0.05);③孤立性血尿或蛋白尿型以及血尿和蛋白尿型病例,病程越长病理分级也越重(P＜0.05);④免疫复合物沉积以IgA+IgG+IgM（58%)同时存在比例最高;病理分级越重,病程越短,IgA+IgG+IgM比例越高。结论：HSPN患儿临床表现为肾病综合征和肾炎型者病理改变相对较重,临床症状与病理不一定平行,尿检正常者病理改变也很明显,病程越长,病理改变呈加重趋势。免疫复合物沉积为IgA+IgG+IgM的病理改变相对较重。［中国当代儿科杂志,2007,9（2）：129-132］     

紫癜性肾炎患儿肾间质血管损害与临床的关系

目的探讨紫癜性肾炎患儿肾间质血管损害与肾脏病理及临床的关系。方法对肾穿刺活检确诊的39例紫癜性肾炎患儿进行肾间质血管损害、肾脏病理积分,并探讨其与临床的关系。结果1.肾脏病理检查中有不同程度肾间质血管损害者36例,占92.3%。其中轻度血管损害15例(38.4%);中度血管损害18例(46.2%);重度血管损害3例(7.7%)。2.肾间质血管中度与轻度损害组相比其血清清蛋白水平明显下降。3.肾间质血管病变积分与肾小球病变、肾间质纤维化、肾小管间质病变、肾脏总的病理损害积分均呈正相关。结论肾间质血管损害在绝大多数紫癜性肾炎患儿中存在,且与肾小球、肾小管间质病变呈正相关关系。     

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.     

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.     

Acute interstitial nephritis. A cause of inflammatory renal glycosuria

The discovery of glycosuria with normal glycemia is generally interpreted as a consequence of a congenital tubular defect. Nevertheless it may be also the result of an acute interstitial nephritis. This conclusion is supported by the clinical and biochemical picture observed in two children, presenting with apparently unexplained fever and significant increase of inflammatory blood indices, in whom euglycemic glycosuria represented the critical finding for diagnosis of acute interstitial nephritis.     

Acute and crescentic glomerulonephritis

Acute nephritic syndrome is clinically characterized by hematuria, proteinuria, oliguria, and volume overload with or without azotemia and histologically be acute proliferative glomerulonephritis. Acute post streptococcal glomerulonephritis is the commonest cause in children. There is a preceding infection prior to this condition in majority. This is one of the comonest causes of renal edema in children. Early recognition, prompt and aggressive therapy and adequate follow-up are mandatory. Prognosis is usually good unless associated with severe renal failure and crescentic glomerulonephritis where the outcome is relatively poor unless treatment is early and adequate. Pathologically acute proliferative nephritis is with diffuse proliferative glomerulonephritis with or without crescents. Immunosuppressive therapy is not needed in simple acute proliferative glomerulonephritis but is essential in modifying the outcome of crescentic glomerulonephritis. Delayed resolution, severe renal failure at onset, progressive renal failure and associated systemic features like skin rashes, joint pains, hepatosplenomegaly and persistent fever are the indications for biopsy. Overall the prognosis in classical post streptococcal acute proliferative glomerulonephritis is good.     

Acute and crescentic glomerulonephritis

Acute nephritic syndrome is clinically characterized by hematuria, proteinuria, oliguria, and volume overload with or without azotemia and histologically be acute proliferative glomerulonephritis. Acute post streptococcal glomerulonephritis is the commonest cause in children. There is a preceding infection prior to this condition in majority. This is one of the comonest causes of renal edema in children. Early recognition, prompt and aggressive therapy and adequate follow-up are mandatory. Prognosis is usually good unless associated with severe renal failure and crescentic glomerulonephritis where the outcome is relatively poor unless treatment is early and adequate. Pathologically acute proliferative nephritis is with diffuse proliferative glomerulonephritis with or without crescents. Immunosuppressive therapy is not needed in simple acute proliferative glomerulonephritis but is essential in modifying the outcome of crescentic glomerulonephritis. Delayed resolution, severe renal failure at onset, progressive renal failure and associated systemic features like skin rashes, joint pains, hepatosplenomegaly and persistent fever are the indications for biopsy. Overall the prognosis in classical post streptococcal acute proliferative glomerulonephritis is good.     

Colchicine for recurrent pericarditis in children

The incidence of recurrence of acute pericarditis in children varies from 15% to 30% and is accompanied by a high morbidity. Various treatment modalities have been used with variable success rates and side effects. La Serna et al. (Lancet 1987; 26: 1517) were the first to treat adults with recurrent pericarditis with colchicine, and were followed by other authors. To our knowledge no studies in children have been reported. In this paper, we present three children who suffered from viral or idiopathic recurrent pericarditis, despite multiple courses of non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids. They responded remarkably well to colchicine, which was administered for 6 months with no adverse reactions. They continue to do well 18, 11 and 12 months after cessation of treatment, respectively.