Sulfasalazine and renal tubular function: lack of an effect

Sulfasalazine (SASP) is frequently used in the treatment of chronic inflammatory bowel disease (IBD), particularly colitis. Because the drug poses a theoretical risk for renal tubular damage, 26 patients, 8-18 years of age, with Crohn's ileocolitis were studied. Thirteen children were receiving SASP while 13 served as disease controls. Renal tubular function was assessed by measurement of urinary beta 2-microglobulin and n-acetylglucosaminidase activity. No abnormalities were found on routine measurement of renal function. Similarly, urinary beta 2-microglobulin and n-acetylglucosaminidase activities were within normal limits for patients receiving SASP, as well as for disease controls. Although there is a theoretical risk for renal tubular damage from the prolonged use of SASP, this study would suggest that IBD patients receiving the drug are at no greater risk for renal injury than their counterparts not receiving the medication.     

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.     

Pediatric case of mesalazine‐induced interstitial nephritis with literature review

We present the case of a 14‐year‐old boy with ulcerative colitis who was diagnosed with mesalazine‐induced interstitial nephritis (M‐IIN). Improvement in renal function occurred with discontinuation of mesalazine and corticosteroid therapy. We systematically searched the literature for pediatric cases of M‐IIN. There were eight cases. Majority of the cases were boys (75%) with ulcerative colitis (75%). Average duration of mesalazine use prior to the diagnosis of interstitial nephritis was 24 ± 18 months. The median dose was 1.5 g/day. M‐IIN appears to be an idiosyncratic reaction without any relation to dose or duration of mesalazine use. Although there are no guidelines to recommend routine surveillance of renal function, monitoring of serum creatinine in patients on mesalazine remains an inexpensive and non‐invasive test that may lead to early detection and treatment of renal injury.     

Sulfasalazine metabolite pharmacokinetics in pediatric patients with inflammatory bowel disease: effects of disease activity, acetylator phenotype, and age

The pharmacokinetics and protein binding of sulfapyridine (SP) and its major metabolite, acetylsulfapyridine (ACSP) were examined in 17 prepubertal children and 4 postpubertal adolescents receiving sulfasalazine (SASP) for treatment of inflammatory bowel disease (IBD). Five patients were studied in both active disease and remission. Comparisons were made with a group of 24 outpatients (9-62 years) with IBD controlled on SASP and in remission. Acetylator phenotype was calculated from plasma metabolite ratios. Slow acetylators had increased plasma concentrations of SP and ACSP + SP (P less than 0.05). Apparent SP clearance (clearance/availability) was increased in active disease (P less than 0.05) and AUCSP + ACSP and AUCSP were decreased (P less than 0.05). There were no age-related alterations in apparent SP clearance. Side effects were frequent but were unrelated to SASP dose, SP concentrations, or acetylator phenotype. Disease activity did not significantly alter the serum protein binding of SP or ACSP. The decreased SP and ACSP concentrations seen in active disease may be due to a combination of disease related alterations in either cleavage of SASP or absorption and clearance of SP.     

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.     

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.     

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 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.     

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.     

Leflunomide therapy for BK virus allograft nephropathy after pediatric kidney transplantation

The BK virus (BKV) can be reactivated with immunosuppressive treatment in renal allograft recipients, which can result in interstitial nephritis (BKV‐associated nephropathy, BKVAN) and lead to renal allograft failure. Recently, leflunomide has been reported in some case series of BKVAN with favorable results. Most studies have included only adult patients, we herein report a pediatric case and include a literature review. The patient was a nine‐yr‐old female with end‐stage renal disease due to hypoxic kidney injury. A deceased donor renal transplant was performed and good initial allograft function was achieved following treatment with prednisolone, tacrolimus and mycophenolate mofetil. The serum Cr level increased to 1.6 mg/dL over the following four‐month period. A kidney biopsy revealed pathologic findings of acute cellular rejection and BK nephropathy. After methylprednisolone pulse therapy was administered to control acute rejection, the tacrolimus dose was reduced, and intravenous immunoglobulin treatment and leflunomide therapy were administered to control the BKVAN. Over the following 18 months, the viral load steadily decreased and remained below 100 copies/mL in the plasma. Leflunomide therapy in addition to a reduction of the immunosuppressive therapies resulted in a significant decline in the BK viral load without further deterioration of renal function.     

Lupusnephritis

Renal involvement is common in systemic lupus erythematosus (SLE). It can manifest just as proteinuria and/or haematuria, but various serious courses are possible. Detection of haematuria and/or proteinuria in a patient with SLE is an indication for diagnostic tests targeting kidney function. To confirm a diagnosis of nephritis induced by lupus and assess its severity (WHO classification) it is necessary to examine a kidney biopsy specimen. In lupus nephritis type 1 no special treatment is needed in view of the excellent prognosis as far as renal function is concerned. In WHO types 2 and 3A immediate therapy is also not necessary, but close monitoring is essential. In type 3B, in contrast, intensive immunosuppression and consistent blood pressure stabilisation are of importance. In type 4 a terminal kidney failure can rapidly supervene without adequate immunosuppressive therapy. Type 5 patients benefit from administration of an ACE inhibitor in addition. Type 6 is a residual condition in the form of scarring, and in these cases more intensive immunosuppression is pointless. Up to 20% of paediatric patients with lupus nephritis come to need dialysis, though kidney function can be at least partly restored.     

Acute interstitial nephritis in childhood

Three children aged 11 to 14 years with acute interstitial nephritis (AIN) are presented. In one patient AIN developed following antibiotic treatment with trimethoprim/sulfamethoxazole (TMP/SMX). In two patients no infection, drug, or toxin could be implicated. Severe polyuric renal failure without elevation of blood pressure was the predominant clinical feature. Uveitis occurred either simultaneously with the nephritic symptoms or several weeks after complete recovery of renal function. Renal functions were characteristically altered and led to suspicion of AIN even prior to renal biopsy. Renal plasma flow was relatively more reduced than glomerular filtration rate (GFR) with an accordingly increased filtration fraction. Quantitative evaluation of selective tubular functions revealed significant transport deficiencies for glucose, amino acids, inorganic phosphate and low molecular weight proteins. In two patients GFR increased rapidly following initiation of steroid treatment and tubular symptoms simultaneously disappeared. In one patient spontaneous remission occurred. We conclude that—in contrast to adults—the prognosis of AIN in childhood is favorable. Although general clinical features are rather nonspecific, symptoms of decreased tubular reabsorption ability provide a good indication of the diagnosis and may contribute to enhanced recognition of this disease.     

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 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.     

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.     

Oral 5-aminosalicyclic acid in children with colonic chronic inflammatory bowel disease: clinical and pharmacokinetic experience

Five children between the ages of 10 and 17 years with chronic inflammatory bowel disease with involvement of colon had intolerance to sulfasalazine, and desensitization trials had failed in them. In addition, they were steroid dependent. Therefore treatment was tried with an oral 5-aminosalicylic acid (5-ASA) preparation coated with the pH sensitive polymer Asacol. Three of these patients responded to the new drug and were weaned off the steroids. However, the other two patients developed repeated side effects from the medication. Plasma levels and urinary excretion of 5-ASA and its major metabolite in four of these patients were determined and were noted to be similar to those in the adults. Range of variable steady state plasma level of 5-ASA was 0.1-5 mg/L and of its acetyl-metabolite (Ac-5-ASA) was 1-8 mg/L.     

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.     

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.     

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.     

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.