Renal resistive index correlates with peritubular capillary loss and arteriosclerosis in biopsy tissues from patients with chronic kidney disease.

BACKGROUND: The renal resistive index (RI) is a Doppler-derived measure that reportedly correlates with renal histological changes and renal disease severity and outcome. The aim of this study was to investigate the factors related to the RI elevation in chronic kidney disease (CKD). METHODS: Using Doppler ultrasonography, RIs were determined in 30 patients with CKD, after which they were correlated with interstitial fibrosis, arteriosclerosis, arteriolosclerosis and peritubular capillary (PTC) density. PTC-positive areas were determined based on CD34 immunostaining. Interstitial fibrosis was detected with Masson trichrome staining. All histological markers were assessed using quantitative and semi-quantitative analyses and evaluated statistically using Pearson correlation tests, unpaired t tests and stepwise multiple regression analysis. RESULTS: RI correlated positively with age (r = 0.603, p = 0.0004), systolic blood pressure (r = 0.775, p < 0.0001), diastolic blood pressure (r = 0.575, p = 0.001), interstitial fibrosis (r = 0.381, p = 0.038) and arteriosclerosis (r = 0.520, p = 0.003), and negatively with creatinine clearance (r = -0.471, p = 0.009) and CD34+ (PTC) areas (r = -0.437, p = 0.016). Patients with hypertension or diabetes mellitus showed higher RIs (p < 0.05) than those without the ailments. Multivariate analysis showed PTC and arteriosclerosis to be independent variables correlating with RI (r (2) = 0.321, p < 0.05). CONCLUSIONS: To our knowledge, this is the first report of using RI measurements to evaluate peritubular capillary loss. Our findings indicate that increases in RI are associated with both arteriosclerosis and loss of PTCs.

Double-Filtration Plasmapheresis plus Interferon-ß for HCV-1b Patients with Non-Sustained Virological Response to Previous Combination Therapy.

BACKGROUND AND AIMS: Double-filtration plasmapheresis (DFPP) together with interferon (IFN) administration produces a substantial reduction in the viral load during the early stages of treatment. METHODS: Based on their responses to previous pegylated IFN and ribavirin (PEG-IFN/RBV) therapy, 20 patients were divided into null virological response (NVR; n = 12) and relapse (n = 8) groups. DFPP was used in combination with IFN-ß/RBV with subsequent administration of PEG-IFN-α2a/RBV therapy (DFPP + IFN-ß/RBV then PEG-IFN/RBV). Early viral dynamics was assessed, focusing especially on complete early virological response (cEVR) associated with sustained virological response. Additionally, the interleukin 28B gene, the IFN/RBV resistance-determining region, the IFN sensitivity-determining region and the core regions were analyzed. RESULTS: Rapid virological response was achieved in 0% (0/12) of NVR and in 75% (6/8) of relapse patients, with a significant difference between the two groups (p = 0.001). Similarly, cEVR was achieved in 8% (1/12) of NVR and in 88% (7/8) of relapse patients, with a significant difference between the two groups (p = 0.037). By multivariate logistic regression analysis, interleukin-28B major was a significant determiner of cEVR (odds ratio = 24.19, p = 0.037). CONCLUSION: DFPP + IFN-ß/RBV then PEG-IFN/RBV therapy is indicated more for relapse than for NVR patients.

Convenient one-pot synthesis of 2-oxazolines from carboxylic acids.

Simple one-pot methods for preparation of 2-oxazolines have been developed using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). Treatment of a mixture of carboxylic acids and 2-haloethylammonium salts with DMT-MM in methanol followed by refluxing in the presence of KOH gives oxazolines.

[Combined effect of cyclosporin and prednisolone for minimal change nephrotic syndrome: comparison with prednisolone therapy].

BACKGROUND: Minimal change nephrotic syndrome (MCNS) is the most common type of glomerular disease and treated mainly with corticosteroids, usually prednisolone(PSL). The recurrence rate during PSL treatment is approximately 20-30 %. In addition, the adverse effects of long term PSL treatment include diabetes, osteoporosis, infection etc, most of which are serious. We treated MCNS with PSL and cyclosporin (CyA) as an initial therapy to reduce PSL dosage and its side effects, and compared various clinical parameters in MCNS treated with the conventional PSL therapy. SUBJECTS AND METHODS: MCNS patients were divided to two groups. Group A consisted of 10 patients, average age 40 years old, treated initially with PSL 20 mg and CyA (2 mg/kg B.W.). Group B consisted 15 patients, average age 43 years old, treated PSL, initial dose 34.7+/-11.9 mg. Data evaluated included whole admission term, reduction of body weight at the discharge, total PSL dosage, period of urinary protein excretion more than 1.0 g/day and side effects. RESULTS: Average admission term was significantly shorter in Group A(19.3+/-8.8 days) than in Group B (56.5+/-22.3 days) (p= 0.0008). Reduction of body weight at discharge from admission was comparable in both Groups (A: 8.3+/-4.8 kg, B: 7.8+/-5.8 kg, p=0.8388). Total PSL dosage in Group A in hospital (386+/-173 mg) was smaller than in Group B (1,884+/-1,573 mg) (p=0.0067). PSL dosage out hospital for 6 months showed the same results A: 1,926+/-776 mg, B: 15,474+/-3,863 mg (p<0.0001). Periods with urinary protein excretion more than 1.0 g/day was slightly shorter in Group A (12.9+/-8.4 days) than Group B (23.7+/-18.3 days) (p= 0.0963). SIDE EFFECTS: One patient in Group B had steroid induced diabetes. Other patients did not show significant side effects. RECURRENCE: Two patients in Group A had recurrence after CyA stopped, but were improved by treatment. CONCLUSION: Initial therapy with PSL and CyA for MCNS is effective for the resolution of nephrotic syndrome, the reduction of PSL amount and whole admission term.

Hypoxia reduces the expression and anti-inflammatory effects of peroxisome proliferator-activated receptor-gamma in human proximal renal tubular cells.

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)-gamma may counteract tissue fibrosis via its anti-inflammatory actions, while hypoxia, a new pro-fibrotic factor, reportedly modifies PPAR-gamma expression. However, the effects of hypoxia on the expression and anti-inflammatory actions of PPAR-gamma have yet remained to be clarified in renal tubular cells. METHODS: Confluent human proximal renal tubular epithelial cells (HPTECs) were exposed to hypoxia (1% O2) and/or TNF-alpha at 10 ng/ml for up to 48 h. The cells were incubated with PPAR-gamma agonists, 15d-PGJ2 or pioglitazone, for 30 min before stimulation. Precise amounts of PPAR-gamma and MCP-1 mRNA and protein were measured by TaqMan quantitative PCR and immunoblot or ELISA, respectively. RESULTS: A cDNA array analysis identified PPAR-gamma as one of the hypoxia-affected genes in HPTECs. Hypoxia reduced mRNA levels of PPAR-gamma at 24 and 48 h and protein levels at 6 and 48 h. Knockout of hypoxia-inducible factor-1alpha (HIF-1alpha) with its dominant negative form did not block the hypoxia-induced reduction in PPAR-gamma expression. PPAR-gamma's activation with 15d-PGJ2 or pioglitazone reduced basal and TNF-alpha-stimulated MCP-1 expression at mRNA and protein levels at 24 h under normoxia. MCP-1 reduction rates at basal mRNA and protein levels were slightly but significantly lower during hypoxia than normoxia (9 vs 69% and 36 vs 42%, respectively, for 15d-PGJ2, and 0 vs 34% and 12 vs 21%, respectively, for pioglitazone). Finally, a specific inhibitor for PPAR-gamma, GW9662, weakened the MCP-1-decreasing effect of 15d-PGJ2 by about 30%, under basal conditions, while it abolished the effect of pioglitazone almost completely. CONCLUSIONS: Hypoxia-induced loss of function of PPAR-gamma reduces anti-inflammatory effects of PPAR-gamma activation, possibly modulating inflammatory responses in the diseased kidney.

Synthetic/secreting and apoptotic phenotypes in renal biopsy tissues from hypertensive nephrosclerosis patients.

The major glomerular abnormalities in hypertensive nephrosclerosis are described as glomerular obsolescence (GO), glomerulosclerosis (GS), and glomerular collapse (GC). However, glomerular cellular changes caused by hypertensive insults have not been well analyzed. Using an immunoenzyme method, we examined eleven biopsy samples from patients with hypertensive nephrosclerosis for two synthetic and secreting phenotypes, a-smooth muscle actin (alpha-SMA) and collagen type III (Col. III), and two apoptotic phenotypes, pro-apoptotic molecule Bax and anti-apoptotic molecule BcI-2. Together with the glomerular and vascular changes and interstitial fibrosis (IF) area, the results were scored quantitatively and semi-quantitatively and compared to the clinical findings, which included systolic blood pressure (SBP), mean arterial pressure (MAP), serum creatinine levels (sCr) and creatinine clearance (Ccr), using univariate and multivariate analyses. As a result, GS was frequently observed in the mild-to-moderate hypertensive group (140 < or = SBP<180 mmHg), whereas GC was positively correlated with SBP. Furthermore, there was a positive correlation of GS with mesangial alpha-SMA and Col. III, suggesting that GS was the reflection of these synthetic and secreting phenotypic changes in mesangial cells. Endothelial Bax was positively correlated with Ccr (p<0.01); in contrast, podocytic Bax was positively correlated with sCr (p<0.05) and showed a tendency to correlate with MAP (p=0.054). In conclusion, these findings support the view that mesangial synthetic and secreting phenotypic changes may be a reflection of cellular activation caused by mild-to-moderate hypertension and that apoptotic phenotypic expression in podocytes, rather than endothelial cells, may be related to the development of a severe form of hypertensive nephrosclerosis.