[Clinical and pathological features and the misdiagnosis of childhood Alport syndrome: a retrospective analysis of 91 cases].

OBJECTIVE: To explore the clinical and pathological features and the diagnosis of childhood Alport syndrome (AS). METHODS: A retrospective analysis was performed on clinical data of 91 children with AS. RESULTS: Hematuria was observed in all 91 patients, of whom 86 were accompanied with proteinuria. Sixty-one children with X-Linked AS (XL-AS) had positive family history. Renal biopsy was performed on 82 children. Mild to moderate mesangial proliferation was observed in 74 cases. Small amounts of immune complexes deposits in the glomerular mesangial area were observed in 48 cases. Glomerular basement membrane (GBM) attenuation, thickening and layering were observed in 53 cases by electron microscopy (EM). In 63 cases receiving renal tissue type IV collagen α3 and α5 chain immunofluorescence detection, 58 were diagnosed with AS, including 53 cases of XL-AS and 5 cases of autosomal recessive AS. In 91 cases of AS, 58 were diagnosed as AS by renal tissue type IV collagen α3 and α5 chain immunofluorescence, 21 were diagnosed by EM, one was diagnosed by skin biopsy, and 12 were diagnosed by gene detection. Six novel mutations of COL4A5 gene were found. Forty-five cases were misdiagnosed before the diagnosis of AS. Forty-one of the 45 cases received steroids and/or immunosuppressant therapy. CONCLUSIONS: The clinical manifestations and pathological changes are not specific in children with AS, resulting in a higher rate of misdiagnosis. Typical lesions of GBM under EM are only observed in a part of patients. There is a high novel mutation rate of COL4A5 in the detected AS children.

[Clinical and pathological features of Denys-Drash syndrome: report of 3 cases].

OBJECTIVE: To study the clinical and pathological features of Denys-Drash syndrome (DDS). METHOD: Three DDS cases who were treated in our department from December 2009 to June 2011 were subjected to this study by reviewing of literature. RESULT: Both case 1 and case 2 were female, with karyotype 46, XX. Case 3 was male with bilateral cryptorchidism. The ages of nephropathy onset of the three cases were 1 year and 9 months, 2 years and 8 moths, and 3 months respectively. Proteinuria in case 2 and case 3 were evidenced to be resistant to steroid. Case 1 was partially responsive to tacrolimus, plasma albumin and cholesterol were improved, although proteinuria was persistent after Tacrolimus was administered. Remission was achieved in case 2 after administration of cyclosporine A and later tacrolimus, and her renal function remains normal till present (4 years and 9 months). Residue renal histology revealed diffused mesangial sclerosis (DMS) in all three patients. All of the three patients had developed right unilateral Wilms tumor. A novel WT1 missense mutation exon 9 c.1213C > G was detected in case 1. WT1 exon 9 c.1168C > T nonsense mutation and exon 8 c.1130A > T missense mutation were detected in case 2 and case 3, respectively. CONCLUSION: The clinical manifestation of nephropathy in DDS is variable. The majority present with early onset nephropathy and reach renal failure before the age of 4 years. But in a few patients, nephropathy can also be present much later and progress slowly. Proteinuria in DDS is resistant to steroid but is responsive to calcineurin inhibitors, including Cyclosporine A. The effectiveness of tacrolimus was also observed in this study. DDS is evidently caused by WT1 mutation. DMS is the characteristic renal pathological change in DDS.

Expression and significance of TGF-beta1/Smad signaling pathway in children with IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) exhibits an indolent but slowly progressive course, and about 30% of children with IgAN are found to deteriorate to end-stage renal failure characterized by overaccumulation of extracellular matrix, diffuse glomerular sclerosis, and tubulointerstitial fibrosis. The TGF-beta/Smad signaling pathway plays an important role in glomerulosclerosis and tubulointerstitial fibrosis. The present study aimed to elucidate the significance of expressions of TGF-beta1, phosphorylated Smad3 (p-Smad3), Smad7 and fibronectin (FN) in the renal tissue of children with IgAN. METHODS: Forty-six children with IgAN were divided into 3 groups according to their clinical features: isolated hematuria group (IH group, 8 patients), hematuria and proteinuria group (HP group, 24), and nephritic syndrome group (NS group, 14). Patients were also divided into three groups according to their pathologic grade: grade I+II (22 patients), grade III (12) and grade IV (12) groups. Five normal renal specimens were used as the control group. The expression of TGF-beta1, p-Smad3, Smad7 and FN in renal biopsy specimens was detected by two-step PowerVision. The degrees of renal tubular injury and interstitial fibrosis were scored according to the Katafuchi semi-quantitative criteria. RESULTS: The expression of TGF-beta1, p-Smad3, Smad7 and FN in children with IgAN was significantly higher than that in the control group (in glomeruli: P<0.05, P<0.01, P<0.05 and P<0.01, respectively; in tubulointerstitium: P<0.05, P<0.05, P<0.01 and P<0.05, respectively) and the highest expression levels were found in the NS and grade IV groups (P<0.05, P<0.01). The expression levels of the four proteins were not only positvely correlated with each other, but also with the grade of renal tubular injury and renal interstitial fibrosis (P<0.05). CONCLUSION: The TGF-beta1/Smad signaling pathway plays an important role in the progress of glomerular sclerosis, renal tubular injury and interstitial fibrosis in children with IgAN.