A boy with IgA nephropathy complicated by tubulointerstitial nephritis and uveitis (TINU) syndrome.

BACKGROUND: Abnormal cellular and humoral immunity underlie both immunoglobulin A (IgA) nephropathy and tubulointerstitial nephritis and uveitis (TINU) syndrome. We encountered a teenage boy who developed TINU syndrome during the course of IgA nephropathy. CASE REPORT: 1 year after onset of IgA nephropathy following acute enteritis, a 14-year-old boy again experienced acute enteritis caused by Campylobacter jejuni, which was followed by TINU syndrome with prominent low-molecular-weight proteinuria. Renal histologic examination showed T-cell-dominant tubulointerstitial infiltration of marked immune cells including CD54-positive cells. Steroid therapy improved renal function, reversing aggravation of IgA nephropathy by TINU syndrome. CONCLUSIONS: The boy's human leukocyte antigen profile suggested predisposition to these two diseases, triggered by which were intestinal infections. The enteritis probably induced abnormalities in cellular and humoral immunity. Low-molecular-weight proteinuria, which reflected our patient's tubulointerstitial lesions, should call for consideration of TINU syndrome, including ophthalmologic assessment for possible uveitis.

Cyclosporin A may cause injury to undifferentiated glomeruli persisting in patients with Alport syndrome.

BACKGROUND/AIMS: Alport syndrome (AS) is a renal disorder caused by a genetic abnormality of type IV collagen α3 and α4, or α5 genes and shows a poor prognosis. Since the defect of type IV collagen synthesis disturbs the maturation process of the glomerular capillary loop, residual immature glomeruli persist after birth. The therapeutic efficacy of cyclosporin A (CyA) for AS patients seems to be controversial. We recently noted that renal specimens obtained from a child with AS who was treated with CyA and then developed CyA nephropathy included an increased number of undifferentiated embryonic-type glomeruli. METHODS: We analyzed renal histologic and immunohistologic findings in children with AS who did (n = 3) or did not (n = 2) develop CyA-induced nephropathy despite appropriately low serum CyA concentrations (<100 ng/mL) being maintained over a period of 2 years. To discriminate embryonic-type from mature glomeruli, staining for type IV collagen α1, laminin ß1, and laminin ß2 accompanied by light microscopic observation were employed. Staining patterns were used to semiquantitatively assess glomerular immaturity (glomerular immaturity index, or GII). RESULTS: In initial biopsy specimens, residual embryonic-type glomeruli were observed in each patient. Patients with early-onset CyA nephropathy had a high GII (median value 2.91 vs 1.23 ± 0.62 normal kidney tissues). In the follow-up biopsy after CyA treatment, surviving embryonic-type, collapsing embryonic-type, and sclerotic glomeruli that had failed to differentiate were observed. Taken together, the number of these glomeruli essentially equaled the total number of embryonic-type glomeruli in specimens obtained before CyA treatment. CONCLUSIONS: Our findings indicate a need for caution in CyA therapy for patients with AS, even for a relatively short course of administration, because some patients may have an unexpected number of embryonic-type glomeruli that predispose to CyA nephropathy.

Tubulointerstitial nephritis complicating IVIG therapy for X-linked agammaglobulinemia.

BACKGROUND: Patients with X-linked agammaglobulinemia (XLA) develop immune-complex induced diseases such as nephropathy only rarely, presumably because their immunoglobulin (Ig) G concentration is low. We encountered a patient with XLA who developed tubulointerstitial nephritis during treatment with intravenous immunoglobulin (IVIG). CASE PRESENTATION: A 20-year-old man was diagnosed with XLA 3 months after birth and subsequently received periodic γ-globulin replacement therapy. Renal dysfunction developed at 19 years of age in association with high urinary ß2-microglobulin (MG) concentrations. A renal biopsy specimen showed dense CD3-positive lymphocytic infiltration in the tubulointerstitium and tubular atrophy, while no IgG4-bearing cell infiltration was found. Fibrosclerosis and crescent formation were evident in some glomeruli. Fluorescent antibody staining demonstrated deposition of IgG and complement component C3 in tubular basement membranes. After pulse steroid therapy was initiated, urinary ß2-MG and serum creatinine concentrations improved. CONCLUSION: Neither drug reactions nor collagen disease were likely causes of tubular interstitial disorder in this patient. Although BK virus was ruled out, IgG in the γ-globulin preparation might have reacted with a pathogen present in the patient to form low-molecular-weight immune complexes that were deposited in the tubular basement membrane.

Non-invasive renal artery embolization for renal dysplasia accompanied by hypertension.

Renovascular hypertension caused by renal dysplasia often is resistant to drug therapy. For a 14-year-old girl with such refractory hypertension, a non-invasive right renal ablation by embolization with anhydrous ethanol using a shepherd 's-crook' balloon catheter, was done. Blood pressure then rapidly normalized. Apart from mild fever after the procedure, no adverse effects occurred. In patients with mild renal artery stenosis and hypertension resistant to anti-hypertensive drug therapy, renal artery embolization may be a useful option.

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

BACKGROUND: Secondary 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. METHODS: We encountered two patients with a nonfunctioning ECT2 genotype who later developed FSGS. Both developed proteinuria associated with acute renal failure in early childhood. RESULTS: Renal 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. CONCLUSIONS: ECT2 is important for tight junction function and maintenance of cell polarity. Nonfunction of this gene may cause renal tubulointerstitial injury, progressing to glomerular sclerosis.

Pathogenesis of focal segmental glomerular sclerosis in a girl with the partial deletion of chromosome 6p.

Focal segmental glomerular sclerosis (FSGS) is a leading cause of the nephrotic syndrome and characterized by the sclerosing lesions that affect one or more segments of some glomeruli. We encountered a female patient with a partial deletion of chromosome 6p, who presented proteinuria at age 3 years. Detailed chromosomal analysis disclosed an interstitial deletion of 6p: del(6)(p22.1p22.3). No abnormality such as hydronephrosis or renal agenesis was disclosed by imaging, but FSGS was present in a renal biopsy specimen. The patient is currently 11 years old and shows mental retardation with mild deterioration in the renal function. To address the defective genes in the present patient, we carried out comparative genomic hybridization (CGH), showing that E2F3 on chromosome 6p is absent in this patient. E2F3, a member of the E2F family transcription factors, inhibits expression of vascular endothelial growth factor (VEGF) and induces apoptosis during vascular development. The deletion of E2F3 was also detected by employing a PCR method, suggesting that glomerular architecture had been compromised in this patient. Serum VEGF concentrations were elevated to 177 ± 21.4 pg/mL (upper limit of 33.3 pg/mL), when she was 6 years old, associated with the enhanced expression of VEGF in glomeruli. These findings suggest that the dysregulation of VEGF synthesis caused by the deletion of E2F3 may be associated with development of FSGS. In conclusion, among patients with idiopathic FSGS, an abnormality of E2F3 may exist on chromosome 6p. Therefore, one might consider chromosomal analyses in children with FSGS who have mental retardation.

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.

Guillain-Barré syndrome and Crohn disease: a case report.

Development of both Crohn disease and Guillain-Barré syndrome likely involves autoimmunity associated with excessive inflammatory cytokines. We treated a girl who developed Guillain-Barré syndrome during the course of Crohn disease. Although high-dose γ-globulin therapy administered initially for Guillain-Barré syndrome was ineffective, plasmapheresis ameliorated her acute neuropathic symptoms. Crohn disease was managed with Salazopyrin administration and enteral feeding. Chronic inflammation of the intestinal mucosa caused by Crohn disease can allow presentation of microbial intestinal antigens normally hidden from the immune system. Such presentation could incite an extraintestinal immune response on the basis of molecular mimicry, leading to activation of systemic autoimmunity against the nervous system. Accordingly, concurrence of Guillain-Barré syndrome and Crohn disease in our patient appeared to result from shared autoimmune mechanisms and systemic and local increases in cytokine concentrations. The patient also developed erythema nodosum and gall stones, relatively common complications of Crohn disease. However, Guillain-Barré syndrome is rare.

Intravitreal injection of bevacizumab for retinopathy of prematurity in an infant with peters anomaly.

PURPOSE: To report our findings in an infant with Peters anomaly type II whose retinopathy of prematurity (ROP) was treated with an anti-VEGF agent and surgeries. CASE REPORT: A male infant weighing 548 g was born prematurely at 23 weeks and 1 day with corneal opacity and shallow anterior chambers in both eyes. At the postmenstrual age of 35 weeks and 3 days, the infant was tentatively diagnosed with stage 3 ROP because of a dilated tunica vasculosa lentis and ultrasonographic findings. The boy was treated with bilateral intravitreal injections of bevacizumab (IVB) because laser photocoagulation of the retina could not be performed due to the corneal opacity. The retina in the right eye detached 3 times, namely 5 days, 16 days, and 7 months after the IVB; encircling the scleral buckle and a vitrectomy with endolaser photocoagulation were therefore required. In his left eye, the retina was reattached after the initial IVB, and no additional treatment was required. ROP was not reactivated in both eyes until the last examination at the age of 2 years and 6 months. CONCLUSIONS: Our results showed that IVB is a useful treatment for ROP in patients with Peters anomaly. However, a retinal detachment can be a complication after IVB. The optimal timing of IVB for ROP in infants with hazy media needs to be determined.