p66Shc mediates high-glucose and angiotensin II-induced oxidative stress renal tubular injury via mitochondrial-dependent apoptotic pathway.

p66Shc, a promoter of apoptosis, modulates oxidative stress response and cellular survival, but its role in the progression of diabetic nephropathy is relatively unknown. In this study, mechanisms by which p66Shc modulates high-glucose (HG)- or angiotensin (ANG) II-induced mitochondrial dysfunction were investigated in renal proximal tubular cells (HK-2 cells). Expression of p66Shc and its phosphorylated form (p-p66Shc, serine residue 36) and apoptosis were notably increased in renal tubules of diabetic mice, suggesting an increased reactive oxygen species production. In vitro, HG and ANG II led to an increased expression of total and p-p66Shc in HK-2 cells. These changes were accompanied with increased production of mitochondrial H(2)O(2), reduced mitochondrial membrane potential, increased translocation of mitochondrial cytochrome c from mitochondria into cytosol, upregulation of the expression of caspase-9, and ultimately reduced cell survival. Overexpression of a dominant-negative Ser36 mutant p66Shc (p66ShcS36A) or treatment of p66Shc- or PKC-ß-short interfering RNAs partially reversed these changes. Treatment of HK-2 cells with HG and ANG II also increased the protein-protein association between p-p66Shc and Pin1, an isomerase, in the cytosol, and with cytochrome c in the mitochondria. These interactions were partially disrupted with the treatment of PKC-ß inhibitor or Pin1-short interfering RNA. These data suggest that p66Shc mediates HG- and ANG II-induced mitochondrial dysfunctions via PKC-ß and Pin1-dependent pathways in renal tubular cells.

Relationship between clinical predictors and tubulointerstitial damage in adult-onset primary nephrotic syndrome.

BACKGROUND: Tubulointerstitial damage (TID) is an important mediator in the progression of chronic proteinuric nephropathies. Our aim in this study was to evaluate the relationship between several clinical predictors and TID in adult-onset primary nephrotic syndrome in China. METHODS: One hundred ninety-five adult inpatients who were diagnosed with primary nephrotic syndrome based on clinical presentation and biopsy results were enrolled in this study from March 2003 to September 2005. The degree of TID was graded by a semiquantitative method including <2 score and >or=2 score. RESULTS: In all patients, the rate of glomerulosclerosis was correlated with the severity of TID. Serum creatinine and uric acid (r = 0.183, p = 0.012 and r = 0.377, p = 0.00001, respectively) but not serum lipid or total 24-h urinary protein were related with TID. In 64 patients, urinary excretion of IgG (r = 0.443, p = 0.00001) but not of albumin, transferrin, retinal-binding protein, or alpha1-microglobulin were significantly associated with the extent of TID. Proteinuria selectivity index based upon IgG also correlated significantly with the extent of TID (p = 0.0001) (score 0-1 vs. score >or=2). CONCLUSIONS: These results showed that serum creatinine and uric acid, the excretion of urinary IgG and proteinuria selectivity index based upon IgG, were highly correlated with the severity of TID in adult-onset primary nephrotic syndrome. These clinical parameters might be useful for predicting the development and progression of proteinuric nephropathy as independent risk factors.

[Multiple analysis of lead concentration in the air and renal function of lead exposure workers].

OBJECTIVE: To determine the lead concentration in the air (pbA) at the workplace and the renal function of lead exposure workers. METHODS: The lead concentration in the air of 11 printing plants, 4 smelteries and 2 lead mines were measured. Screening urinalysis was performed in 1190 long term lead exposed workers with urine sugar, protein and sigements. It one of the three was abnormal, the workers were given examination of renal function. The relationship between pbA and renal function were confirmed by mutiple linear. RESULTS: The concentrations of pbA in the printing plants, smelteries and lead mines were 0.07 mg/m3, 0.26 mg/m3 and 0.66 mg/m3 respectively. Altogether 157 cases had one and more abnormal renal function. The correlation of concentration PbA in the workplace and the renal function of lead exposure workers was shown (R = 0.894, P < 0.001, R2 = 0.799). The correlation coefficient of skewness of showed that PbA and Bpb. Upb. Bun Scr Usug. Ubeta2MG were positively correlated (P < 0.01 approximately 0.001); Ccr was negatively correlated (P =0.05). Upro, UNAG and Ualb were nonsignificant. CONCLUSION: The lead concentration in the air at the workplace is related to the renal functions of lead exposure workers. It is important to decrease the lead environment and to prevent renal damage.

HPLC determination and clinical significance of serum prednisone in patients with nephrotic syndrome.

AIM: A rapid protocol is necessary to determine the serum concentrations of prednisone. METHODS: The HP1100 high-performance liquid chromatographic (HPLC) system was employed. The HP Lichrosphere C8 column (250 mm × 4 mm, i.d., 5 µm particle size) was used. The mobile phase was methanol, tetrahydrofuran and water in the ratio 25:25:50. The flow rate was 1.0 ml/min. The sample was monitored by UV absorbance at 240 nm. Acetanilide was used as the internal standard, and methanol was added into the serum for depositing the protein. RESULTS: The chromatography was effective and was not interfered with by the serum components. Good linearity was observed, within the range of 10-500 µg/L for prednisone, and the detection limit was 5 µg/L. The serum concentrations of prednisone between the nephrotic syndrome (NS) group and the control group were significantly different (P < 0.05), while there was no significant difference between the females and males of the NS group (P > 0.05). The serum ncentration of prednisone in the steroid-resistant group was lower than that in the steroid-sensitive group (P < 0.05). CONCLUSIONS: HPLC is a practical and reliable method to determine the serum concentration of prednisone with high accuracy, precision, linearity and repeatability.

Influencing factors for saliva urea and its application in chronic kidney disease.

OBJECTIVES: To analyze possible influencing factors on concentration of saliva urea (SaU) and to validate its application in chronic kidney disease(CKD). DESIGN AND METHODS: Level of SaU in patients and normal subjects was researched. RESULTS: The concentration of SaU did not vary with sampling time and genders, but was related to ages and level of serum urea (U). CONCLUSION: SaU concentration is stable and it is useful in application in CKD.