CD80 expression and infiltrating regulatory T cells in idiopathic nephrotic syndrome of childhood.

BACKGROUND: CD80 (also known as B7-1) is a co-stimulatory molecule that is expressed in biopsies and also excreted in urine in patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). CD80 is inhibited by the cytotoxic T-lymphocyte-associated-antigen 4 (CTLA4), which is mainly expressed on regulatory T cells (Tregs). Ineffective circulating Treg response is involved in the pathogenesis of nephrotic syndrome. In this study, we evaluated CD80 expression and infiltrating Tregs in children with MCD and FSGS. METHODS: Evaluation of CD80 expression and semi-quantitative evaluation of Tregs (FOXP3-positive CD4 T cells) were carried out in 31 kidney biopsies (12 MCD, 19 FSGS) with immunofluorescence and immunohistochemistry staining. RESULTS: All MCD sections were stained negative; whereas six out of 19 FSGS sections (all from steroid-resistant (SR) patients), including one from a Wilms' tumor 1 (WT1) mutation-positive FSGS patient, stained positive for anti-CD80 goat antibody, and negative for anti-CD80 rabbit antibody. FSGS biopsy specimens had significantly higher FOXP3-positive cells/mm2 compared with MCD and control samples (P < 0.001). Biopsy samples from SR-FSGS patients (n = 12) with positive CD80 staining (n = 6) had significantly less Tregs (FOXP3-positive CD4 T cells) compared with CD80 (-) biopsies (n = 6; P = 0.004). CONCLUSION: CD80 expression was not detected in the majority of the archival biopsy sections and the results were not consistent across the different antibodies. In the SR-FSGS sections, however, CD80-positive biopsies had decreased FOXP3-positive CD4 T cells, suggesting that a decreased anti-inflammatory milieu may be the cause of increased CD80 expression.

The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis.

BACKGROUND AND OBJECTIVES: Infantile nephropathic cystinosis is a severe disease that occurs due to mutations in the cystinosis gene, and it is characterized by progressive dysfunction of multiple organs; >100 cystinosis gene mutations have been identified in multiple populations. Our study aimed to identify the clinical characteristics and spectrum of cystinosis gene mutations in Turkish pediatric patients with cystinosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We identified the clinical characteristics and spectrum of cystinosis gene mutations in Turkish patients with cystinosis in a multicenter registry that was established for data collection. The data were extracted from this registry and analyzed. RESULTS: In total, 136 patients (75 men and 61 women) were enrolled in the study. The most common clinical findings were growth retardation, polyuria, and loss of appetite. None of the patients had the 57-kb deletion, but seven novel mutations were identified. The most common mutations identified were c.681G>A (p.Glu227Glu; 31%), c.1015G>A (p.Gly339Arg; 22%), and c.18_21 del (p.Thr7Phefs*7; 14%). These mutations were associated with earlier age of disease onset than the other mutations. To understand the effects of these allelic variants on clinical progression, the mutations were categorized into two major groups (missense versus deletion/duplication/splice site). Although patients with missense mutations had a better eGFR at the last follow-up visit, the difference was not significant. Patients in whom treatment began at age <2 years old had later onset of ESRD (P=0.02). Time to ESRD did not differ between the patients with group 1 and group 2 mutations. CONCLUSIONS: The most common cystinosis gene mutations identified in Turkey were c.681G>A (p.Glu227Glu), c.1015G>A (p.Gly339Arg), and c.18_21 del (p.Thr7Phefs*7). Patients with less severe cystinosis gene mutations tend to have better kidney outcome.

Management of stone disease in infants.

Evaluating and treating renal stone disease in infants are technically challenging. In this study, we evaluated the surgical treatment of renal stones in children under 1 year of age. We retrospectively reviewed the records of patients under 1 year old who were treated with ESWL, endourological or open surgical procedures for renal stone disease between January, 2009 and December, 2012. The patients' age, gender, stone size, stone location and number, complications, stone-free status, and postoperative complications were recorded. 19 of 121 infants with a mean age of 10.2 ± 3.07 months were treated with surgical procedures. Six (75%) of eight cystinuria patients required a surgical intervention. Retrograde endoscopic management was performed in thirteen patients (63.4%) as an initial surgical approach. There were three major (15.7%) complications. The rate of open surgical procedures was 31.6% (6 of 19 infants). The cutoff value of stone size for open surgery was 10 mm. There was a significant relationship between the conversion to open procedures and stone size, stone location, and symptom presentation especially the presence of obstruction (p < 0.05). After repeated treatments, the stone clearance rate of RIRS reached 84.6%. Retrograde intrarenal surgery is an effective and safe treatment method for renal stones in infants and can be used as a first-line therapy in most patients under 1 year old. This is especially important if an associated ureteral stone or lower pole stone that requires treatment is present and for patients with cystinuria, which does not respond favorably to ESWL.