Multiple drug-resistant gene 1 in children with steroid-sensitive nephrotic syndrome.

BACKGROUND: A full dose of corticosteroid is required to induce complete remission (CR) in steroid-sensitive nephrotic syndrome (SSNS), unless it is possible to taper and discontinue along with the course after CR. But the mechanism of this change in steroid sensitivity remains unknown. P-glycoprotein (PGP) can eliminate given corticosteroids from cytoplasm, which results in corticosteroid resistance. Therefore, drug delivery was analyzed using real-time polymerase chain reaction (PCR) of multiple drug-resistant gene 1 (MDR1; encoding PGP) mRNA expression. METHODS: Fourteen patients with SSNS (male/female: 14/0; age: 1-23 years; mean 10.4 years) were enrolled in the study. MDR1 mRNA gene expression of peripheral blood nucleated cells (PBNC), before and after CR (19 sets of blood samples), was quantified using real-time PCR. RESULTS: The MDR1 mRNA levels before CR were variable in each patient, but there was an apparent decrease in the MDR1 gene expression of PBNC after CR (P < 0.003). CONCLUSION: PGP may play a role in the tapering of corticosteroids after CR in SSNS.

Molecular Assembly of Wheat Gliadins into Nanostructures: A Small-Angle X-ray Scattering Study of Gliadins in Distilled Water over a Wide Concentration Range.

Gliadin, one of the major proteins together with glutenin composing gluten, affects the physical properties of wheat flour dough. In this study, nanoscale structures of hydrated gliadins extracted into distilled water were investigated primarily by small-angle X-ray scattering (SAXS) over a wide range of concentrations. Gliadins are soluble in distilled water below 10 wt %. Guinier analyses of SAXS profiles indicate that gliadins are present as monomers together with small amounts of dimers and oligomers in a very dilute solution. The SAXS profiles also indicate that interparticle interference appears above 0.5 wt % because of electrostatic repulsion among gliadin assemblies. Above 15 wt %, gliadins form gel-like hydrated solids. At greater concentrations, a steep upturn appears in the low-q region owing to the formation of large aggregates, and a broad shoulder appears in the middle-q region showing density fluctuation inside. This study demonstrates that SAXS can effectively disclose the nanostructure of hydrated gliadin assemblies.

Triggers of relapse in steroid-dependent and frequently relapsing nephrotic syndrome.

An awareness of the triggers of relapse is critical for the control of steroid-dependent, frequently relapsing nephrotic syndrome (SDFRNS). We have investigated the triggers, usually described as 'episodes', to such relapses within a temporal context. Thirty-five patients with SDFRNS were analyzed retrospectively. A total of 442 relapses occurred in 2499 patient-months. The relapses were classified into two groups: those with episodes (E+) and those without episodes (E-). There were 135 E+ relapses and 296 E- relapses. The common cold was the most common episode (52%) of E+ relapse, followed by school events (18%). These E+ relapses occurred almost evenly throughout the 4 weeks between each follow-up visit. Conversely, 161 (55%) of the 296 E-z relapses occurred within the 3-day period preceding the patient's appointment (relapse-related hospital visit, RRHV). McNemar's test revealed that the concentration of relapses in this period was statistically significant (P < 0.00011). In addition, 15 out of 26 RRHV without additional therapy showed a spontaneous remission. From a chronological perspective, the common cold and school events as well as up-coming hospital visits may trigger relapses in SDFRNS patients.

Cockayne syndrome with recurrent acute tubulointerstitial nephritis.

A 12-year-old girl, who had been diagnosed as having Cockayne syndrome (CS), was admitted for emaciation and dehydration. On admission the patient had mild chronic renal failure (glomerular filtration rate: GFR 50 mL/min) and hyperuricemia. After rehydration, allopurinol was commenced for her hyperuricemia. Then, her renal function rapidly deteriorated (GFR 20 mL/min) with enhancement of proximal tubular dysfunction and hypertension. A renal biopsy showed that the patient had acute tubulointerstitial nephritis (ATIN). Based on this diagnosis, allopurinol was stopped and prednisolone was started (2 mg/kg per day), following which the renal tubular function improved. However, the proteinuria intensified to become nephrotic syndrome. After 1 month the patient developed a gastric ulcer. Famotidine was commenced but GFR deteriorated and renal proximal tubular dysfunction re-occurred. The renal pathology was evaluated by referring to the previous reports of renal pathology in CS. It is suggested that rapid deterioration of the renal function in CS patients might be the result of ATIN. In addition, the present nephrotic syndrome seemed to be accompanied by ATIN, as in other reports.

Charge selective function in childhood glomerular diseases.

The charge selectivity (CS) function in human renal disease has not been unequivocally demonstrated to date. However, the clearance ratio of IgA to IgG may be theoretically useful in estimating CS in humans, since IgA and IgG have similar sizes and tertiary structures, but distinct isoelectric points (3.5-5.5 [IgA] and 4.5-9.0 [IgG]), and Stokes-Einstein radius: 61 A (IgA) and 49-60 A (IgG). Two-dimensional electrophoresis with the following immunoblotting revealed that the considerably anionic portion (isoelectric points [pI] <4.0) of IgA, visible in serum, was absent in the urine in steroid-sensitive nephrotic syndrome (SSNS) but present in the same during IgA nephropathy (IgAN) and membranoproliferative glomerulonephritis (MPGN). A latex assay revealed the CS index (CSI) was significantly low in patients with podocyte disease (group A), including SSNS, focal and segmental glomerulosclerosis (FSGS) and Finnish-type congenital nephrotic syndrome (FCNS), but high in those with Alport syndrome (AS), IgAN, Henoch-Schönlein purpura nephritis (HSPN), and MPGN (group B). The linear regression analysis of the IgA size selectivity index (IgA SSI; clearance ratio of IgA to transferrin) and SSI (clearance ratio of IgG to transferrin), which represents the clearance ratio of IgA to IgG referring to the transferrin clearance, revealed the influence of the charge more accurately. Indeed, the slope of the regression lines of IgA SSI (y) to SSI (x) were concluded to be y = 0.39x (group A) and y = 1.05x (group B), respectively. These results suggested that the charge selective barrier among podocyte diseases (group A) is preserved to some degree, but lost in cases of nephritis and AS (group B).