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Objective To observe the circadian blood pressure (BP) rhythms and the phase of heart circadian gene expression in adriamycin (ADR)-induced nephropathy rats,thus exploring the effect of circadian systems on circadian BP variation in nephrotic rats.Methods Sprague-Dawley (SD) male rats (8 weeks) were housed in a 12∶12 hour light/dark cycle in two weeks,and randomly divided into ADR group and control group.ADR rats were injected 6.5 mg/kg adriamycin via vein to establish nephrotic rats model two weeks later,while control rats were injected the equal volume of saline.Five rats in each group were implanted with the radio-telemetry into abdominal aortic.After seven days,systolic blood pressure (SBP),diastolic blood pressure (DBP),mean arterial pressure (MAP) and heart rate (HR) were recorded every one minute during 72 hours via radio-telemetry.Three rats in each group were sacrificed in six time points (zeitgeber time=02:00,06:00,10:00,14:00,18:00,22:00) to get the blood sample and heart tissue,respectively.The mRNA expressions of core clock gene CLOCK,BMAL1,Per1,Per2,Cry1 and Cry2 in heart issue were evaluated by the real-time quantitative PCR.The plasma levels of renin activity angiotensin Ⅱ and aldosterone were measured by radioimmunoassay.All the data were analyzed by a partial Fourier analysis and stepwise regression.Results (1) There was no significant difference in 24 h average of SBP,DBP and MAP between two groups.In control group,there was higher SBP (3.22 mmHg),DBP (1.16 mmHg) and MAP (3.19 mmHg) in dark period than those in light period,only SBP and MAP showing statistical difference (all P ＜ 0.05).However,SBP,DBP and MAP had no significant difference between dark and light in ADR group (all P ＞ 0.05).(2) Control rats had (8.0+24.0) h rhythm of SBP,and their DBP,MAP and HR appeared 24.0-hour normal circadian pattern (all P ＜ 0.05).In ADR group,the rhythm of SBP completely disappeared.And their DBP and MAP remained 24.0 h circadian rhythm,but the peak time advanced 1.5 h to 3.0 h compared with SD rats.(3) In SD controls,daily rhythms period of the core clock genes (CLOCK,BMAL1,Cry1,Cry2,Per1 and Per2) mRNA expression in the heart were (4.8+ 12.0) h,24.0 h,12.0 h,(12.0+24.0) h,(4.8+12.0) h and 12.0 h (all P ＜ 0.05),respectively.In ADR rats,the rhythm of CLOCK,BMAL1,Cry2,Per1 and Per2 mRNA completely disappeared (all P ＞ 0.05).The circadian rhythm of Cry1 mRNA remained,but the period was changed from 12.0 h to (4.8+6.0) h.(4) The plasma renin and aldosterone concentration presented 12.0 h and 24.0 h daily rhythms in SD rats (all P ＜ 0.05).These diurnal changes however completely disappeared in ADR rats (all P ＞ 0.05).Conclusions ADR nephrotic rats lose the circadian rhythm of BP with the disturbances of cardiac circadian clock system.The disrupted diurnal rhythm of the core clock genes (CLOCK,BMAL1,Cry2,Per1 and Per2) mRNA expression in the heart may regulate the pathological circadian rhythms of heart tissue,which is involved with disturbances of circadian rhythm of BP.
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objective To analyze the clinicopathological features and prognosis of antiglomerular basement membrane(GBM)disease,and evaluate the efficacy and safety of double filtration plasmapheresis(DFPP). Methods A total of 35 hospitalized patients diagnosed as anti-GBM disease in our department were enrolled in the study.All the patients were divided into 3 groups according to the manifestations at admission.Group Ⅰ∶24 patients with severe pulmonary hemorrhage or rapidly progressive glomerulonephritis(RPGN)received pulse methylprednisolone with or without DFPP,and then followed by prednisone and CTX.Group Ⅱ∶5 patients without severe pulmonary hemorrhage and RPGN received prednisone and CTX.Group Ⅲ∶5 ESRD patients and 1 normal renal function patient did not receive immunosuppression therapy.Anti-GBM antibody titer of pre-and post-DFPP in 4 patients was measured consecutively,and removal rate was calculated.Results The mean age of all the patients was(41.1±16.6)years.Sixteen patients(45.7%)presented Goodpasture's syndrome.Eighteen patients(51.4%)had anti-GBM glomerulonephritis alone,whereas one suffered solely from pulmonary hemorrhage.20%patients had positive P-ANCA serology.54.2%crescentic glomerulonephritis and 7 with other glomerulonephritis were revealed by kidney biopsy in 24 patients.Patients in Group Ⅰ showed more severe manifestation at admission:higher Scr level,higher titer of anit-GBM antibody,greater percentage of crescents.Within the follow-up period,7 patients died and kidneys of 50%patients survived.No patient died in Group Ⅱ and Ⅲ.The elder age,anemia,higher Scr(＞300 μmol/L),oliguria or anuria,emergency hemodialysis at admission,and more glomerular sclerosis were predictors of poor prognosis.The anti-GBM antibody was negative after 4 to 6 sessions of DFPP.and the mean removal rate was 55%.During total 94 DFPP sessions,there was no unacceptable morbidity. Conclusions Different therapy strategy is necessary for anti-GBM disease with different clinical manifestations.DFPP is an effective and safe clearance way of anti-GBM antibody.
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Objective To investigate the relationship between the urinary albumin excretion (UAE) and serum uric acid in general population. Methods The study participants were derived from the epidemiological study on the association of metabolic syndrome and chronic kidney disease (CKD) in Pinggu district, Beijing. A total of 992 participants (463 men and 529 women) aged from 30 to 75 years were enrolled in this study. For each participant, UAE, serum uric acid, serum creatinine, and serum lipids were detected and other potential risk factors for CKD were surveyed. Results ( 1 ) The frequencies of microalbuminuria, macroalbuminuria and hyperuricemia were 12.9% , 1.8% and 4.3% respectively. The persons with hyperuricemia had significantly higher frequency of albuminuria than those without hyperuricemia (37. 2% vs 13. 7% , P ＜0. 01). (2) The participants were divided according to the quartiles (25% , 50% , 75% ) of serum uric acid level, and the frequencies of albuminuria in males were 13. 2% , 13. 9% , 17. 2% and 25.4% , while those in females were 8. 4% , 6. 2% , 9. 6% and 24. 8%. ( 3 ) Multivariate logistic regression analysis showed, hyperuricemia was significantly associated with albuminuria in females (OR =2. 31, 95% CI 1. 15-4. 68; P=0.02), but not in males. If the persons with reduced renal function were excluded, similar result still could be gained. Conclusions The prevalence of albuminuria increases gradually with uric acid elevation. Serum uric acid is an independent risk factor of elevated UAE, especially in females.
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Objective To investigate the discriminator value of Han Chinese first morning urine albumin creatinine ratio (ACR) for determining the microalbuminuria. Methods A total of 1056 participants (494 males and 562 females) were selected from epidemiologic study of the metabolic syndrome and chronic kidney disease in Pinggu district, Beijing. Eight-hour overnight urinary albumin excretion (UAE) was regarded as the gold standard for defining the albuminuria,and the ROC curve analysis was used to determine the ACR discriminator value for microalbuminuria. Results (1)Microalbuminuria was found in 12.5% of participants,macroalbuminuria in 1.7%. (2)The ACR discriminator value for microalbuminuria by ROC curve analysis was 1.95 g/mol (sensitivity 97.6% and specitivity 88.6%) for men, 3.62 g/mol(sensitivity 83.8% and specitivity 89.1%) for women, 2.78 g/mol (sensitivity 88.7% and specitivity 85.9%)for overall. The upper boundary of microalbuminuria by ROC curve analysis was 22.59 g/mol (sensitivity 100.0% and specitivity 98.8%) . (3)The inter-rater agreement of the result in this study showed that sensitivity was 91.3% and specitivity was 88.2%, positive likelihood ratio was 7.56 and negative likelihood ratio was 0.10, positive predictive value was 56.9% and negative predictive value was 98.4%. Conclusions The ACR discriminator value for determining microalbuminuria is obviously higher in women than that in men, and is higher than recommendation of international guidelines. The result by ROC curve analysis has better sensitivity and specitivity.
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ObjectiveTo study the effect of astragaloside Ⅳ(AS-Ⅳ) on glucose-induced podocyte adhesion and its possible mechanism. MethodsConditionally immortalized mouse podoeytes were treated with 10, 50, 100 mg/L AS-Ⅳ and with 100 mg/L AS-Ⅳ for 3, 6, 12, 24 h. Cell attachment was measured by fluorescence and centrifugation cell adhesion assays, respectively. Expression of α3β1 integrin mRNA and protein was examined by real-time PCR and Western blot. ResultsHigh glucose induced a significant reduction in adherent podocytes compared to normal glucose group (P<0.05). AS-Ⅳ improved high glucose-induced podocyte adhesion in a time- and dose-dependent manner. Real-time PCR and Western blot analysis revealed that high glucose-induced down-regulation of α3β1 integrin in podocytes were significantly meliorated by AS-Ⅳ (P<0.05). ConclusionAstragaloside Ⅳ improved high glucose-induced podocyte adhesion which may be mediated through α3β1 integrin up-regulation.