Tubulo-interstitial nephritis and uveitis syndrome in a 6-year-old boy: case report

A 6-year-old boy presented with a 4-month history of anorexia, weight loss and fatigue and was found to have tubulo-interstitial nephritis and uveitis (TINU) syndrome. After 2 months of corticosteroid therapy, resolution of the uveitis was almost complete but renal function showed only partial improvement. He was still in renal failure 6 months after diagnosis, but there was no relapse of the uveitis. Although the prognosis of TINU in children and adults is reported to be excellent, the outcome in young children can be less favourable, probably owing to delayed diagnosis and initiation of treatment.     

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 (subtype 2) in a patient with methylmalonic acidaemia

A 10-month-old male infant with vitamin B₁₂ non-responsive methylmalonic acidaemia is reported. Laboratory results revealed hyperkalaemic, hyperchloraemic, metabolic acidosis with slight azotaemia. The urinary pH decreased (below 5.5) to compensate for acidaemia. Levels of plasma renin activity and plasma aldosterone concentration were low. The renal biopsy showed tubulo-interstitial nephritis. We suggested the diagnosis of type 4 renal tubular acidosis, subtype 2, i.e. hyporeninaemic hypoaldosteronism. We suggest that chronic renal disease may be a common complication of methylmalonic acidaemia.     

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.     

Laurence-Moon-Bardet-Biedl syndrome, chronic diffuse tubulo-interstitial nephritis and liver involvement

The authors report the case of a 6-year-old girl with Laurence-Moon-Bardet-Biedl syndrome and chronic tubulo-interstitial nephritis with glomerulosclerosis requiring chronic peritoneal dialysis, then haemodialysis. One year later, minimal hepatic involvement occurs, leading to portal hypertension. The liver biopsy reveals periportal fibrosis with many small bile ducts.     

Severe epithelio-exfoliative colitis in infants. I. Clinical data

Two cases of colitis with neonatal onset are reported. They were characterized by their severity which made early exclusive parenteral nutrition necessary, by the lack of ulcerations visible at endoscopy and of biological inflammatory signs and by an associated neural deafness. In spite of prolonged digestive and corticosteroid treatment, a colectomy had to be performed in both cases. The specificity of the histologic abnormalities of the colon individualizes this severe colitis in infancy.     

Renal tubular dysfunction in methylmalonic acidaemia

Renal tubular function was assessed in seven patients with methylmalonic acidaemia not responsive to vitamin B₁₂. Five patients failed to concentrate their urine normally and in these patients the glomerular filtration rate was also reduced. Fractional excretion of sodium was increased in four patients, fractional excretion of potassium in one patient and in three there was a decreased tubular reabsorption of phosphate. Although possibly representing primary tubular damage these findings were thought to be consistent with adaptive changes secondary to the reduced glomerular filtration rate. Two patients had evidence of a defect of urinary acidification and several had a degree of hyporeninaemic hypoaldosteronism suggesting type 4 renal tubular acidosis. In one patient with a mild variant no renal disease was detected. Decreased renal function and tubular abnormalities were common in patients with methylmalonic acidaemia. It is likely that they are linked and essentially secondary to the tubulo-interstitial nephritis that is histologically demonstrable on renal biopsy. The failure of urinary concentrating ability and the disturbed urine acidification will contribute to the metabolic derangement during episodes of decompensation.     

Juvenile polyposis in a tropical country

The clinical profile, malignant potential, and management of 17 children with juvenile polyposis (more than five juvenile polyps) were evaluated clinically and endoscopically. Colonoscopy and polypectomy were done three weekly until colonic clearance was achieved, and thereafter two yearly. All polyps were subjected to histological examination. Mean age was 7.7 years, with a male preponderance (3:1). Presentation was with rectal bleeding (94%), pallor (65%), stunted growth (53%), and oedema (47%), and the mean (SD) duration of symptoms was 33 (27) months. None had a positive family history or any congenital anomaly. Two children had six polyps up to the transverse colon; the rest had numerous polyps all over the colon. All children had juvenile polyps on histology and 10 (59%) had adenomatous changes (dysplasia). Total colectomy was done in six for intractable symptoms. Colon clearance was achieved in eight after an average 3.4 polypectomy sessions, and three were still on the polypectomy programme. In conclusion, juvenile polyposis is commonly associated with low grade dysplasia. Serial colonoscopic polypectomy is effective but colectomy is required for intractable symptoms and when clearance of the colon is not possible.     

Spectrum of renal osteodystrophy in children on continuous ambulatory peritoneal dialysis

BACKGROUND: The prevalence of different types of bone disease in chronic renal failure (CRF) has changed significantly during the last decade. The aim of the present study is to evaluate the spectrum of bone disease in children with CRF undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: Seventeen children with CRF on CAPD aged 7-20 years were evaluated. All patients had received regular vitamin D and calcium carbonate therapy during the 6 months preceding the bone biopsy. Serum calcium, phosphate, alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) levels were measured and hand X-rays were performed. Transiliac bone biopsies were analyzed for histologic diagnosis. RESULTS: High turnover renal osteodystrophy (ROD) was the most common bone disease, present in eight patients (47%). Five patients (29%) had low turnover bone disease, and four (24%) had mixed ROD. The mean age of the high turnover ROD group was higher than that of the low turnover group (14 +/- 3 vs. 11 +/- 3 years, P < 0.05). Seven of the nine patients who had tubulo-interstitial nephritis were found to have high turnover bone disease. In contrast, none of the patients with glomerulonephritis exhibited high turnover bone lesions. Mean serum calcium levels were found to be significantly higher in the low turnover group compared with the patients with high turnover bone disease (P < 0.001). A serum iPTH level > 200 pg/mL was 100% sensitive and 66% specific in identifying patients with high turnover ROD. CONCLUSION: The spectrum of bone disease of the children with CRF undergoing CAPD seems to depend on the rate of CRF and primary disease. The risk of developing overt hyperparathyroid bone disease is high in children with slowly progressing forms of renal pathology and especially in those with tubulo-interstitial disease. In contrast, children with glomerular diseases who had a more rapidly progressive course may have a lesser risk of developing high turnover bone disease. The results of the present study indicate that even routinely prescribed regular vitamin D therapy early in the course of disease may lead to low turnover bone lesion in small children who have CRF due to rapidly progressive forms of renal pathology.     

Preliminary results of studying the effectiveness of hemosorption in the complex treatment of children with lupus nephritis

Hemosorption was employed in multi-modality treatment of 12 children aged 10-15 years with lupus nephritis. Of these, 5 patients suffered from nephritis associated with the nephrotic syndrome (NS), 4 patients had active pronounced nephritis without the NS, and 3 patients presented with latent nephritis. One case was characterized by transitory renal failure in the acute phase while 3 cases by chronic renal failure. Hemosorption produced a beneficial effect on the renal process and on electrolyte balance. The long-term observation over the patients evidences a short-term effect of hemosorption. After the attainment of that effect the further disease course depended on the adequacy of the conservative therapy administered to the patients with lupus nephritis.     

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.     

Alternate day corticosteroid therapy and growth in renal transplant children

Corticosteroid therapy is probably the main factor inducing stunted growth in pediatric renal transplant recipients. Results of a randomized study in 35 children who received their kidney between 1981 and 1984 are reported. All patients had normal renal function and were taking azathioprine and prednisone to ensure immunosuppression. Eighteen months after transplantation, patients with normal renal biopsy results were randomized to receive further daily corticosteroid therapy (group A) for an additional year or to alternate-day corticosteroid therapy (group B). Chronologic age, bone age, renal function, and previous growth retardation were strictly comparable, in the two groups. During the first year, only prepubertal children in group B exhibited catch-up growth. In children undergoing puberty, annual statural gain was greater in group B (5.6 cm versus 3.2 cm in group A: p less than 0.001). Group A children were switched to alternate-day corticosteroid therapy one year after initiation of the study and exhibited improved growth after this change. No patient had renal function deterioration under alternate-day corticosteroid therapy, throughout the study period. Alternate-day prednisone should be offered to pediatric renal transplant recipients with satisfactory renal function as a mean for protecting growth potential.     

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.     

Real-time ultrasound-guided renal biopsy with a biopsy gun in children: safety and efficacy

Real-time ultrasound-guided renal biopsy (RB) with a biopsy gun has become a standard procedure in the treatment of children. The purpose of the study was to establish the complication rate after real-time ultrasound-guided RB with a biopsy gun, the adequacy of renal tissue samples for pathohistological tests, the rate of concurrence between clinical and pathohistological diagnoses, and the benefits of the procedure. From January 1994 to October 1999, 88 renal biopsies were performed on 82 children, 81 of whom (35M, 46F, aged 3-20 y) were included in this retrospective study. The nephrotic syndrome (in infants, older children, those with evidence of nephritis or failing corticosteroid therapy) was the most frequent indication of RB. Other indications were non-nephrotic proteinuria, nephritic syndrome, glomerular haematuria, renal allograft dysfunction, unexplained acute or chronic renal failure, and kidney disease progression monitoring. No serious complications were noted. The adequacy rate of renal tissue samples ranged from 93.1 to 96.6%, depending on which definition of the adequacy of renal tissue samples was used. Clinical and pathohistological diagnoses matched in 81.4% of the cases. Data obtained by RB were very beneficial to patients in terms of establishing, confirming or altering the diagnosis and, consequently, the treatment.

Conclusion : The results confirm that real-time ultrasound-guided RB with a biopsy gun is a safe procedure and provides information that is very beneficial to patients.     

Hyporeninemic hypoaldosteronism in children with chronic renal failure

The syndrome of hyporeninemic hypoaldosteronism (SHH) is not infrequent in adults with chronic renal failure caused by chronic tubulointerstitial nephritis, but it has been reported rarely in children. We present a systematic study of the interrelation between renal excretion of potassium and the renin-aldosterone axis in 23 children with CRF of different and unselected causes. Twenty children with chronic renal failure never had hyperkalemia, and both renin and aldosterone were normally stimulated by intravenous administration of furosemide, whereas three patients had moderate hyperkalemia (serum potassium concentration between 5.3 and 5.6 mEq/L) and failed to raise plasma renin activity and aldosterone values in response to furosemide. There three patients with SHH had lower basal and stimulated values of fractional potassium excretion than did patients with normokalemic chronic renal failure. Fractional potassium excretion was curvilinearly related to glomerular filtration rate (GFR), but in all three patients with SHH it was lower than expected for the level of GFR present. Fractional sodium excretion was also related to GFR, but no abnormalities were found. Two patients had hyperchloremic metabolic acidosis. After furosemide administration, they excreted an acid urine with low ammonium content, features characteristic of type 4 or hyperkalemic renal tubular acidosis. Prostaglandin E2 excretion was also significantly related to GFR, and appeared appropriate in two patients with SHH. The identification of three patients with SHH among 23 with chronic renal failure of unselected causes suggests that this entity is not rare in childhood.     

Sarkoidose

We report the case of a 13-year-old boy who presented with impaired exercise tolerance, loss of weight and fever. Laboratory data indicated systemic inflammation and renal failure suggestive of tubular dysfunction. A kidney biopsy showed epithelioid granulomatous tubulointerstitial nephritis. The boy developed granulomatous uveitis during follow-up. TINU syndrome (tubulointerstitial nephritis and uveitis) was diagnosed and sarcoidosis was considered to be the most probable cause. Treatment was started with prednisone and methotrexate and renal function completely recovered, whereas after 2 years of treatment the uveitis is still mildly active. Sarcoidosis is a rare disease of childhood; nevertheless it must be considered in the differential diagnosis of granulomatous uveitis and tubulointerstitial nephritis.     

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.     

Sarcoidosis with an uncommon presentation: apropos of a case

A 17-year-old male presenting with chronic renal failure whose supporting clinical manifestations of the disease had appeared independently over a four-year period is reported. The renal biopsy specimen of the patient revealed tubulointerstitial nephritis and membranous glomerulonephritis. He never had hilar adenopathy, but maculopapular rashes, erythema nodosum, arthritis, chronic lymphocytopenia, hepatomegaly, splenomegaly, and lymphadenomegaly had been observed at different periods over four years. The presence of non-caseating granulomatous lesions in the liver biopsy accompanying uveitis verified the diagnosis of sarcoidosis. Low dose steroid was applied to this hepatitis-C carrier, and uveitis was suppressed. No recurrence has been observed in two-year follow-up.     

Systemic lupus erythematosus with nephritis.

Thirty-six patients with the onset of symptoms of systemic lupus erythematosus before age 20 years (23 aged less than 15 years at onset) were studied during a 15-year period. All had clinical evidence of nephritis. They were followed for a mean of 5 years (range 6 months to 13 years) or until death. Survival was calculated to be 77% at 10 years for those aged less than 15, and 74% for those aged less than 20, from the onset of clinical nephritis. At referral, renal function was already impaired in two-thirds of patients. Renal biopsies showed mild focal or proliferative changes in 19% of patients, membranous lesions in 11%, and diffuse proliferative lesions in 70%. Three (8%) patients died during follow-up, all from sepsis, and 3 (8%) others required chronic haemodialysis for terminal renal failure. The prognosis even of severe lupus nephritis in childhood and adolescence has improved in recent years. Side effects of treatment remain an important cause of death and morbidity.     

Acute Tubulointerstitial Nephritis in Two Siblings and Concomitant Uveitis in One

Two sisters with acute tubulointerstitial nephritis (ATIN) are reported. The elder sister had concomitant uveitis which recurred twice. The younger sister became ill five years after the onset in the elder. Both patients had identical HLA haplotypes and also suffered from mild chronic sialoadenitis. A renal biopsy specimen of the elder sister showed not only marked interstitial infiltration of immunoglobulin-containing mononuclear cells but also immune-complex-related glomerulonephritis. The younger sister had immune complexes in the serum. These findings suggest that glomerulonephritis and uveitis may be secondary phenomena of ATIN with participation of circulating immune complexes. Once the uveal involvement has occurred, uveitis may undergo relapses without any renal manifestations.