Hitomi Nishi

Childhood Cogan syndrome with aortitis and anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.

Cogan syndrome is a systemic disease manifesting interstitial keratitis, sensorineural hearing loss, tinnitus, and rotatory vertigo. Renal complications of this syndrome are very rare. We encountered an adolescent with Cogan syndrome complicated by aortitis and anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. At the age of 14, the patient showed proteinuria in a screening urinalysis at school and was found to lack a right radial pulse. Magnetic resonance angiography disclosed right subclavian artery stenosis. Examination of a renal biopsy specimen showed ANCA-positive crescentic glomerulonephritis. Steroid and immunosuppressant treatment improved renal function and histopathology, but repeated recurrences followed. At 18, the patient developed rotatory vertigo, a sense of ear fullness, and sensorineural hearing loss. The patient was diagnosed with Cogan syndrome. We know of no previous description of ANCA-positive crescentic glomerulonephritis in children with Cogan syndrome. Accordingly, evaluation of aortitis in childhood should include not only otolaryngologic and ophthalmologic examinations, but also periodic urine examination and renal function tests.

Pediatric Left Renal Vein Entrapment Syndrome Diagnosed by 99mTc-Albumin-Conjugate Scintigraphy

Background/Aims: Procedures for diagnosis of left renal vein entrapment syndrome (LRVES) in children have been either invasive or limited in accuracy. We examined scintigraphy with 99mTc-diethylene triamine pentaacetic acid-conjugated human serum albumin (99mTc-HSA-D) scintigraphy in childhood LRVES, demonstrating selective left renal nuclides excretion. We also measured peak velocity using pulse Doppler ultrasonography, calculating pressure differences between inferior vena cava and left renal vein using a simplified Bernoulli equation. Methods: Thirteen patients provisionally diagnosed with LRVES by ultrasonography combined with other imaging such as magnetic resonance angiography and three-dimensional computer tomography (CT) were examined. Results: Four children showing repeated gross hematuria all showed pressure differences exceeding 3.0 mm Hg. Selective left renal albumin excretion was demonstrated by 99mTc-HSA-D scintigraphy. Single-photon emission CT also showed accumulation in a site consistent with the left renal pelvis. Among 9 children manifesting mainly orthostatic proteinuria, selective left renal albumin excretion examined by 99mTc-HSA-D scintigraphy was demonstrated only in those with proteinuria exceeding 1 g/g Cr after standing in a lordotic position. Pressure differences in patients with orthostatic proteinuria were unrelated to proteinuria severity. Conclusions: Combining pulse Doppler ultrasonography with 99mTc-HSA-D scintigraphy, both noninvasive and safe in children, may suffice for diagnosis of LRVES, especially with gross hematuria.

Effect and therapeutic mechanisms of tonsillectomy for childhood IgA nephropathy

Aim:  We investigated efficacy and therapeutic mechanisms of tonsillectomy for intractable childhood IgA nephropathy. Five patients refused tonsillectomy. Among 25 patients, 19 patients were able to evaluate histological findings before and after surgery. Patients with poor (n = 7) or relatively poor (n = 18) histologically determined prognosis and an age of at least 7 years, together with proteinuria of at least 0.3 g/day or severe persisting despite ongoing drug treatment, are candidates for surgery. Patients were grouped by interval between diagnosis of IgA nephropathy and tonsillectomy (within 3 years; early group vs 3 years or later; later group). Patients underwent kidney biopsy shortly before and 1 to 2 years after tonsillectomy.

Nonfunction of the ECT2 gene may cause renal tubulointerstitial injury leading to focal segmental glomerulosclerosis.

BackgroundSecondary focal segmental glomerulosclerosis (FSGS) follows congenital or acquired tubulointerstitial alterations such as in Dent’s disease, Lowe syndrome, and reflux nephropathy. Failure of adequate regeneration after tubulointerstitial injury, or abnormal tubulogenesis, can disturb intrarenal blood circulation, causing excessive glomerular filtration. The epithelial cell-transforming sequence 2 gene (ECT2) contributes to tight junction function in epithelial cells.MethodsWe encountered two patients with a nonfunctioning ECT2 genotype who later developed FSGS. Both developed proteinuria associated with acute renal failure in early childhood.ResultsRenal biopsy specimens showed marked tubulointerstitial nephritis at the onset of proteinuria, later progressing to FSGS consequent to tubulointerstitial injury. The patients did not respond to corticosteroids and attained only incomplete remission upon cyclosporine A administration. One patient received a maternal renal transplant with good function and no rejection.ConclusionsECT2 is important for tight junction function and maintenance of cell polarity. Nonfunction of this gene may cause renal tubulointerstitial injury, progressing to glomerular sclerosis.

Heterozygous p.S811F RET gene mutation associated with renal agenesis, oligomeganephronia and total colonic aganglionosis: a case report.

BackgroundSeveral shared common gene networks participate in development of interstinal ganglia and also nephron formation; the glial cell line-derived neurotrophic factor/Ret/glial cell line-derived neurotrophic factor receptor gene network is particularly important.Case presentationWe encountered a patient with total colonic aganglionosis as well as right renal agenesis and oligomeganephronia. Gene analysis in this patient disclosed a heterozygous p.S811F mutation was in Ret gene exon 14, resulting in a substitution of phenylalanine for serine. The large side chain of phenylalanine obstructed the opening of the hydrophobic pocket of the Ret molecule causing interference with its interaction with adenosine triphosphate and consequent marked reduction in its enzyme activity. This could account for our patients severe intestinal disease and renal dysplasia. We know of no previous reports of concomitant Hirschsprung’s disease and oligomeganephronia.ConclusionsThe patients overall illness could be considered a novel Ret gene mutation syndrome.