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1.
Summary: IgA nephropathy (IgAN) is polyphormic in its clinical manifestation, course and prognosis. Patients with isolated IgA deposit in glomeruli tend to have a high incidence of macroscopic haematuria and carry a better prognosis. In contrast, patients with deposits of IgA and IgG and IgM have a higher incidence of nephrotic syndrome and hypertension. In parallel, patients with IgA and IgG and IgM tend to have more glomerulosclerosis and tubulointestitial lesions. Recently, the angiotensin converting enzyme (ACE) gene polymorphism and its association in disease risk provided interesting exploration leading us to speculate about a possible mechanism to explain the variation in the rate of progression of IgAN; although, the results are still controversial. The variability of plasma ACE concentration has been shown to be associated with an insertion/deletion polymorphism. The frequencies of ACE genotype in 177 Chinese patients with IgAN has been observed. We found that patients with IgAN showed a higher frequency of DD genotype than normal population. In contrast to the previous reports, we did not find any association between ACE genotype and the rate of progression of IgAN. As different genotypes of IL-1 receptor antagonist (IL-1 ra) are also responsible for the circulating levels of IL-1 ra, the polymorphism of IL-1 ra gene has been analyzed in 100 IgAN patients. There was no significant difference in the frequency of IL1RN*2 allele between normal subjects and IgAN. However, patients with recurrent macroscopic haematuria showed a higher carriage rate of IL1RN*2. Hereditable factors, in combination with a number of recognized environmental risk factors, are important determinants of the pathogenesis and natural history of IgAN. The notion that the gene polymorphism might be responsible for the clinical features and progression of IgAN is both intriguing and provocative. The lessons from previous multiple small size studies have produced conflicting results illustrating the need for observation of large numbers of cases in further studies to verify these observed associations. 相似文献
2.
Monika Buraczynska Piotr Ksiazek Andrzej Drop Wojciech Zaluska Danuta Spasiewicz Andrzej Ksiazek 《Nephrology, dialysis, transplantation》2006,21(4):979-983
BACKGROUND: End-stage renal disease (ESRD) is a complex phenotype resulting from underlying kidney diseases of different etiologies as well as from environmental and genetic factors. The responsible genes influencing the development and rate of progression to ESRD have yet to be defined. We examined an association of the three renin-angiotensin system (RAS) gene polymorphisms with renal disease and progression to ESRD in dialyzed patients. METHODS: Genotyping was performed in 745 ESRD patients and 520 control subjects for the angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T and angiotensin II type 1 receptor (AT1R) A1166C gene polymorphisms using polymerase chain reaction and gel analysis. RESULTS: Allele and genotype frequencies of the ACE polymorphism did not differ significantly between ESRD patients and controls. The patient group showed an increased frequency of the T allele of the AGT polymorphism (P = 0.02) and the C allele and CC genotype of the AT1R polymorphism (P<0.01). There was an association of the AT1R gene polymorphism with the progression of renal disease to end-stage failure. The time from diagnosis to the onset of ESRD was significantly shorter in patients carrying the C allele than in subjects with the homozygous AA genotype (4.7 years vs 12.6 years, P<0.001). The observed effect was not associated with hypertension in studied subjects. CONCLUSION: The results of our study demonstrate the association between the AT1R A/C polymorphism and renal disease progression. The CC/AC genotype of this polymorphism might serve as a predictor for early ESRD and might be useful in planning therapeutic strategies for individual patients. 相似文献
3.
Woo KT Lau YK Choong LH Zhao Y Tan HB Fook-Chong S Tan EK Yap HK Wong KS 《Nephrology (Carlton, Vic.)》2004,9(5):304-309
BACKGROUND AND AIMS: Individuals are prone to disease because of certain disease-susceptible genes. The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D), the angiotensinogen (AGT) gene, M235T, and the angiotensin II type 1 receptor (ATR) gene, A1166C, polymorphisms have been associated with IgA nephropathy (IgAN) and its progression. Several studies on Caucasians and Japanese patients have reported contradictory results. We determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese subjects to assess their clinical impact. METHODS: Genotyping was performed with DNA isolated from peripheral leucocytes, polymerase chain reaction amplification of the polymorphic sequence, restriction enzymes digestion, and separation and identification of DNA fragments. Clinical data at renal biopsy and final status on renal function were determined from patients' records. RESULTS: Comparing all IgAN patients with controls, AGT and ATR genotype distributions were similar, whereas there was a significant increase in the ACE DD genotype (P < 0.05). When comparing patients with end-stage renal failure (IgAN-ESRF) and those without (IgAN-nonESRF), there was no difference among the three gene polymorphisms. In contrast, there were significant differences in higher male prevalence (P < 0.05), increased serum creatinine at presentation (P < 0.05), more sclerosis (P < 0.01) and higher tubulointerstitial lesion score (P < 0.001) in the IgAN-ESRF group. CONCLUSION: Among the ACE, AGT and ATR gene polymorphisms, only the DD genotype may predispose the individual to IgAN in the Chinese population. None are significant for prognosticating ESRF. 相似文献
4.
Genetic polymorphisms of the renin-angiotensin system and complications of insulin-dependent diabetes mellitus. 总被引:6,自引:0,他引:6
F J van Ittersum A M de Man S Thijssen P de Knijff E Slagboom Y Smulders L Tarnow A J Donker H J Bilo C D Stehouwer 《Nephrology, dialysis, transplantation》2000,15(7):1000-1007
OBJECTIVE: Patients with insulin-dependent diabetes mellitus (IDDM) have a high risk of developing diabetic nephropathy, retinopathy and cardiovascular diseases. The contribution of gene polymorphisms of the renin angiotensin system to these complications is controversial and may differ among populations. METHODS: In 257 Dutch IDDM patients (188 with urinary albumin excretion (UAE) <30 mg/24 h), logistic regression analysis was used to study the relationships among, on the one hand, the insertion/deletion gene polymorphism of the angiotensin-converting enzyme gene (ACE-ID), the M235T gene polymorphism of the angiotensinogen gene (AGT-M235T), and the A1166C gene polymorphism of the angiotensin type 1 receptor gene (AT1-A1166C), and, on the other hand, UAE, retinopathy, hypertension, and coronary heart disease. RESULTS: The T-allele of the AGT-M235T polymorphism was associated with an increased risk of an elevated UAE (odds ratio (OR) 3.03; 95% confidence interval (CI) 1.06-8.61), but only when interaction with the D-allele of the ACE-ID polymorphism was considered. A previously described positive interaction between the T-allele of the AGT-M235T polymorphism and the D-allele of the ACE-ID polymorphism could not be confirmed. The T-allele was also associated with an increased risk of retinopathy (OR 3.89, 95% CI 1.79-8.47). The CC-genotype of the AT1-A1166C polymorphism was associated with hypertension (OR 3.58; 95% CI 1. 23-10.37). CONCLUSIONS: In a Dutch IDDM population, including 69 patients with (incipient) diabetic nephropathy, the T-allele of the AGT-M235T polymorphism is associated with an elevated UAE and diabetic retinopathy and the CC-genotype of the AT1-A1166C polymorphism is associated with hypertension. A previously described interaction between the AGT-M235T and the ACE-ID polymorphisms could not be confirmed. Since the number of nephropathic patients in this study is small, these conclusions must be interpreted with caution. 相似文献
5.
Piero Stratta Francesca Bermond Simonetta Guarrera Caterina Canavese Sonia Carturan Annamaria Dall'Omo Giovannino Ciccone Laura Bertola Gina Mazzola Edvige Fasano Giuseppe Matullo 《Nephrology, dialysis, transplantation》2004,19(3):587-595
BACKGROUND: The renin-angiotensin system (RAS) and nitric oxide synthase (NOS) play a key role in the progression of primary glomerulonephritis (GN). Although previous studies have examined genetic risk associated with single gene variations, experiments assessing risk conferred by multiple gene variations are still scanty. METHODS: The effect of combination of variant alleles of four genes encoding for three components of the RAS [angiotensin converting enzyme insertion/deletion (ACE I/D), angiotensin II receptor 1 (AT1R 1166A/C), angiotensinogen (AGT M235T)] and for NOS (ecNOS4b/a) on the development and progression of membranous GN (MGN) were evaluated in a longitudinal study comparing 117 patients with serum creatinine (s-Cr) <1.5 mg/dl at renal biopsy and follow-up > or = 5 years (Kaplan-Meier and Cox multivariate analysis). The control group consisted of DNA from 171 organ donors. RESULTS: We found no relationship between single or combined variations of the four gene polymorphisms and development of MGN. Among single gene variations, there were no independent genetic risk factors for the progression of renal disease, after adjustment for age, sex, hypertension, proteinuria, s-Cr, chronicity and activity index. However, double variation coincidences such as the combination of the allele a of ecNOS4b/a and both the allele D of ACE I/D (chi(2) =4.80, P = 0.028; HR = 1.97, 95% CI 0.98-3.96) and the allele T of AGT (M235T) (chi(2) = 5.09, P = 0.024; HR = 2.84, 95% CI 1.39-5.82) exerted an additional effect that was higher than that of the single gene variations. CONCLUSION: This study is the first to demonstrate a role for an interaction between simultaneous variations of genes encoding for NOS and components of RAS in the progression of MGN. Interactions between various polymorphisms may explain conflicting results obtained in previous studies that examined single gene variations, since the effect of a single locus variation may be influenced by the simultaneous presence of other variant alleles in polygenic diseases such as primary GN. However, the small sample sizes and possible multiple interactions limited the interpretation of the current findings, which may represent true biological interaction or simply statistical interactions or spurious results due to the small sample sizes. 相似文献
6.
Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy. 总被引:7,自引:0,他引:7
Peter Jacobsen Steen Andersen Kasper Rossing Birgitte V Hansen Hans-Henrik Parving 《Nephrology, dialysis, transplantation》2002,17(6):1019-1024
BACKGROUND: Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetes. Approximately 30% of type 1 patients with diabetic nephropathy (DN) have albuminuria >1 g/day, and blood pressure >135 and/or >85 mmHg despite antihypertensive therapy with recommended doses of ACE inhibitor (ACEI) and diuretics. We tested the effect of dual blockade of the renin-angiotensin system (RAS) in these patients. METHODS: We performed a randomised double blind crossover trial with 2 months treatment with Irbesartan 300 mg o.d. and placebo added on top of previous antihypertensive treatment. We included 21 type 1 patients with DN responding insufficiently to ACEI and diuretics, as defined above. At the end of each treatment period, albuminuria, 24-h blood pressure and glomerular filtration rate (GFR) were measured. RESULTS: Addition of 300 mg Irbesartan to the patients' usual antihypertensive therapy induced a mean reduction in albuminuria of 37% (95% CI 20-49, P<0.001); from 1574 mg/24 h (95% CI 1162-2132) to 996 mg/24 h (95% CI 699-1419), a reduction in 24-h blood pressure of 8 mmHg systolic (95% CI -2 to 18) and 5 mmHg diastolic (95% CI 1-9) (P=0.11 and 0.01, respectively) (from placebo, mean (SE) 146 (4)/80 (2) mmHg). GFR remained unchanged. Serum potassium increased (mean 4.3 to 4.6 mmol/l, P=0.02). Intervention to reduce serum potassium was needed in two patients with GFR <35 ml/min/1.73 m(2). Otherwise the dual blockade with Irbesartan was safe and well tolerated. CONCLUSIONS: Dual blockade of the RAS may offer additional renal and cardiovascular protection in type 1 patients with DN responding insufficiently to conventional antihypertensive therapy, including recommended doses of ACEI and diuretics. 相似文献
7.
Sang-Woong Han Young-Woong Won Joo-Hark Yi Ho-Jung Kim 《Nephrology, dialysis, transplantation》2007,22(4):1150-1155
BACKGROUND: Renin-angiotensin system (RAS) blockades, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are well accepted for the cardiorenal-protective benefits added to antihypertensive effects in chronic kidney diseases (CKD), but associated with an increased risk of hyperkalaemia. However, few studies have investigated the effect of RAS blockades on serum potassium in dialysis patients. METHODS: Hyperkalaemia associated with RAS blockades by ACEI and/or ARB was evaluated in 69 patients on maintenance haemodialysis, who underwent a three-period crossover study in four groups (no exposure to RAS blockades, ACEI or ARB alone and ACEI plus ARB treatments), lasting one month in each period. RESULTS: Sixty-two patients completed this prospective 3-month study, and no one stopped the study because of the development of hyperkalaemia and/or complications. Mean serum K was similar among the four periods (no exposure, 5.54+/-0.67 mmol/l; ACEI alone, 5.54+/-0.75 mmol/l; ARB alone, 5.50+/-0.66 mmol/l; ACEI+ARB combination, 5.42+/-0.66 mmol/l) and was also equal when compared between the two groups with and without exposure to RAS blockades (5.48+/-0.68 vs 5.54+/-0.67 mmol/l, P=NS). The incidence of severe hyperkalaemic episodes (>6.0 mmol/l) upon monthly predialysis serum K determination was 25.8% with no exposure to RAS blockades, 29.8% for ACEI alone, 19.6% for ARB alone and 17.7% for ACEI+ARB combination without statistically significant differences among the four periods (P=NS). Among covariables, the degree of Kt/V, intakes of other medications interfering with potassium homeostasis and diabetes mellitus did not result in any significant hyperkalaemic changes during the 3-month study period except anuric patients compared with non-anuric patients (5.58+/-0.69 vs 5.19+/-0.65 mmol/l, P<0.001). CONCLUSION: Neither monotherapy (ACEI or ARB) nor combination therapy (ACEI plus ARB) is associated with the additional risk of hyperkalaemia in patients on maintenance haemodialysis. However, those patients with anuria on RAS blockades warrant the cautious monitoring of serum K to prevent hyperkalaemia. 相似文献
8.
Maruyama K Yoshida M Nishio H Shirakawa T Kawamura T Tanaka R Nakamura H Iijima K Yoshikawa N 《Pediatric nephrology (Berlin, Germany)》2001,16(4):350-355
We investigated whether polymorphisms of the renin-angiotensin system genes are involved in IgA nephropathy in Japanese children.
We identified the M235T polymorphism of the angiotensinogen (AGT) gene, the I/D polymorphisms of the angiotensin-converting
enzyme (ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor gene in 95 Japanese children with IgA
nephropathy and 99 healthy Japanese adults. There were no differences in the genotype and allele frequencies of these genes
between patients with IgA nephropathy and controls. Urinary protein excretion at the time of biopsy was significantly greater
in patients with the TT genotype of the AGT gene than in those with the MM/MT genotypes of the AGT gene (1.32± 1.42 versus
0.75±0.78 g/day; P=0.01) and in patients with the ID/DD genotypes of the ACE gene than in those with the II genotype of the ACE gene (1.45±1.50
versus 0.63±0.56 g/day; P=0.001). Thus, the TT genotype of the AGT gene and the ID/DD genotype of the ACE gene are associated with increased severity
of proteinuria, suggesting that AGT and ACE gene polymorphisms may play a significant role in the progression of IgA nephropathy
in Japanese children.
Received: 21 July 2000 / Revised: 8 December 2000 / Accepted: 11 December 2000 相似文献
9.
AIM: The aim of this study was to investigate whether the angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (A1166C) gene polymorphisms were associated with the renal scar formation secondary to recurrent urinary tract infection in children without uropathy. METHODS: The polymorphisms were investigated by polymerase chain reaction in 97 children (81 females, 16 males; age, 2.5-13 years) with recurrent urinary tract infection and 100 healthy controls as a single centre study. Children with vesicoureteral reflux, bladder dysfunction and other uropathies were excluded. The dimercaptosuccinic acid (DMSA) scan performed at least 3 months after a proven urinary tract infection and the result of the last DMSA was taken into consideration. RESULTS: Renal scarring was found in 30 patients (30.9%) using DMSA scan. The number of urinary tract infection attacks was significantly higher in patients with renal scarring compared with children without scarring (P<0.05). The follow-up period and male/female ratio of patients with or without renal scarring was similar (P>0.05). Age at the first urinary tract infection was lower in the group with scarring. The ACE insertion/deletion genotype distribution and D allele frequency were similar between patients and controls (P>0.05), and in patients with renal scarring and those without renal scarring. Also, the angiotensin II type 1 receptor gene polymorphism was not associated with renal parenchymal damage (P>0.05). CONCLUSION: The results indicated that the ACE insertion/deletion and angiotensin II type 1 receptor gene polymorphisms were not independent risk factors for renal scar formation in recurrent urinary tract infection of paediatric patients without uropathy. 相似文献
10.
Torsten Slowinski Petra Diehr Patrick Kleemann Lutz Fritsche Lutz Renders Klemens Budde Ingeborg A Hauser Hans H Neumayer Berthold Hocher 《Nephrology, dialysis, transplantation》2004,19(11):2846-2851
BACKGROUND: Genes determining the activity of the renin-angiotensin system (RAS) may be alloantigen-independent factors influencing kidney allograft function. We determined if gene polymorphisms of the RAS are associated with early and long-term post-transplantation graft dysfunction in 405 Caucasian kidney recipients with graft survivals of >2 years. METHODS: We calculated the slopes of serum creatinine(-1)/year and urinary protein excretion/year to follow graft function over time. Subjects were genotyped for the deletion (D) polymorphism of the gene encoding angiotensin I-converting enzyme, the angiotensin II-receptor type1 gene 1166A-C polymorphism and the M235T polymorphism of the angiotensinogen gene. RESULTS: The frequencies of factors predicting graft function were similar in patients with different genotypes. None of the polymorphisms influenced need for dialysis in the first week after transplantation, occurrence of at least one rejection episode, the slope of serum creatinine(-1)/year or the slope of urinary protein excretion/year. Results were independent of blood pressure or the use of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers or calcineurin inhibitors. The combination of genotypes did not influence the indicators of early and long-term graft dysfunction. CONCLUSIONS: Neither the investigated gene polymorphisms of the RAS in kidney allograft recipients nor their combinations have an impact on early and long-term graft dysfunction. 相似文献
11.
12.
Objective To evaluate the effects of renin-angiotensin system (RAS) blockades [angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB)]on contrast-induced nephropathy (CIN) in patients undergoing angiography. Methods Pubmed, Embase, Cochrane library, Wanfang database and CNKI were searched. The literature limited range was from their start year to July 2015. Randomized controlled trials (RCTs) and non-randomized controlled trials of renin-angiotensin system blockades in influencing CIN were assessed. Two investigators extracted data and performed quality analysis independently from all trials included. Rev man 5.3 software was used. Results 16 trials with a total of 15 897 patients were identified. There were 7490 patients who received renin-angiotensin system blockades and 8407 patients in control group. The meta analysis revealed a higher CIN incidence in ACEI/ARB group than that in control group (14.35% vs 12.13%, P=0.04, OR=1.44, 95%CI 1.01-2.04). For patients with renal insufficiency, ACEI/ARB group had a higher CIN incidence than control group (12.23% vs 7.32%, P= 0.02, OR=1.80, 95%CI 1.10-2.94), and the serum creatinine changes in ACEI/ARB group were higher than those in control group. There was statistical difference in serum creatinine changes between groups (P=0.02, MD=0.08, 95%CI 0.02-0.15). Conclusions Renin-angiotensin system blockades can increase the incidence of CIN in patients undergoing angiography. Renin-angiotensin system blockades can contribute to CIN for patients with renal insufficiency. 相似文献
13.
14.
Eagleton MJ Cho B Lynch E Roelofs K Woodrum D Stanley JC Upchurch GR 《The Journal of surgical research》2006,132(1):69-73
BACKGROUND: The renin-angiotensin system (RAS) has been implicated in vessel wall remodeling. This investigation tested the hypothesis that the RAS is altered during experimental rodent aneurysm formation. MATERIALS AND METHODS: Rat aortas were perfused with saline (controls, N = 45) or elastase (6 U/ml, N = 45). At 4, 7, and 14 days after aortic perfusion, aortic diameters were measured (n = 15/time point/group) and aortic wall mRNA and protein were extracted. Real time polymerase chain reation (PCR) measured RNA levels of angiotensin, angiotensin converting enzyme (ACE), angiotensin II receptor 1 (AT(1)), and angiotensin II receptor 2 (AT(2)). Western blot analysis measured ACE protein levels. Immunohistochemical studies localized ACE within the aortic wall. Statistical analyses were performed with the unpaired t-test and ANOVA. RESULTS: Elastase perfusion significantly increased aortic diameter (P < 0.01), with no significant changes in saline control aortic diameters. ACE mRNA did not become elevated in elastase-perfused aortas, yet ACE protein levels were elevated on days 4 and 7 of perfusion (P < 0.01) compared to controls, and ACE staining was noted in these aortas. This difference resolved by 14 days. In neither group were there significant alterations in AT(1), AT(2), or An mRNA levels, although ACE mRNA was elevated in controls after 7 days of perfusion compared to elastase perfused aortas (P < 0.005). CONCLUSIONS: Experimental aortic aneurysm formation may be associated with increased aortic wall ACE protein levels. The mechanisms by which these proteins contribute to, or serve as markers of, aneurysm formation in vivo requires further intervention. 相似文献
15.
The benefits of renin-angiotensin blockade in renal transplant recipients with biopsy-proven allograft nephropathy. 总被引:3,自引:0,他引:3
Jeffrey S Zaltzman Michelle Nash Rick Chiu Ramesh Prasad 《Nephrology, dialysis, transplantation》2004,19(4):940-944
BACKGROUND: Allograft nephropathy, regardless of aetiology, leads to progressive renal injury and eventual graft loss. In native kidney disease, treatment of hypertension, in particular with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), has proven beneficial in retarding renal function decline. In the present study, we reviewed the clinical course of a renal transplant recipient cohort that was prescribed either an ACEi or ARB for biopsy-proven allograft nephropathy. METHODS: Patients were followed from the time of post-biopsy initiation of ACEi/ARB and were stratified based on biopsy findings. Outcomes of interest included safety, allograft survival, renal function and change in slope of renal function pre- and post-ACEi/ARB. RESULTS: The 5 year allograft survival after biopsy diagnosis of allograft nephropathy was 83%. Serum creatinine was 191+/-97 (86-377) micromol/l at the time of biopsy and 228+/-102 (102-575) micromol/l at last follow-up. The slopes of reciprocal creatinine vs time were used to calculate the decline in renal function and were compared pre- and post-ACEi/ARB. The mean slope+/-SD was -0.06+/-0.21 l/micromol x 10(-3) per month in the 12 months prior to therapy and -0.03+/-0.09 l/micromol x 10(-3) per month following therapy. The absolute difference in slopes was 0.03 (P =<0.0001). CONCLUSIONS: Treatment with ACEi/ARB may be beneficial in the management of allograft nephropathy. 相似文献
16.
Polymorphism of renin-angiotensin system genes in dialysis patients--association with cerebrovascular disease. 总被引:2,自引:0,他引:2
Attilio Losito Kamini Kalidas Stefania Santoni Luigi Ceccarelli Steve Jeffery 《Nephrology, dialysis, transplantation》2002,17(12):2184-2188
BACKGROUND: Polymorphisms of genes of the renin-angiotensin system (RAS) have been found in association with cerebrovascular and cardiovascular diseases in the general population. In dialysis patients, RAS gene polymorphisms have been studied in combination and separately and have yielded conflicting results. METHODS: In this study we have analysed, in 160 dialysis patients, the distribution of the following genetic polymorphisms: M235T and T174M of the angiotensinogen gene, A1166C of the angiotensin II type 1 receptor gene and the insertion/deletion (I/D) of the ACE gene. The association of these polymorphisms with cerebrovascular and cardiovascular diseases was also tested. Healthy blood donors and hospital staff (169) were the control group for the distribution of the polymorphisms. RESULTS: The distribution of the polymorphisms in dialysis patients as a whole did not differ significantly from that of healthy controls. However, for patients with severe cerebrovascular disease, 70% carried the D allele compared with 52% of patients without cerebrovascular disease (P=0.035). We also found that the degree of carotid artery stenosis was significantly correlated with the presence of the ACE 'D' allele in subjects on dialysis (P=0.0348). CONCLUSIONS: The distribution of RAS genes in dialysis patients is similar to that of the normal population. The presence of the D allele of ACE gene is associated with cerebrovascular disease and the degree of carotid artery stenosis. We postulate that the ACE gene polymorphism is a risk factor for cerebrovascular disease in dialytic patients. 相似文献
17.
Priscilla Kincaid-Smith Kenneth Fairley David Packham 《Nephrology, dialysis, transplantation》2002,17(4):597-601
BACKGROUND: Proteinuria and hypertension have independent deleterious effects on the progression of chronic renal disease. The objectives of this study were to determine whether the addition of Candesartan, an angiotensin II receptor antagonist, would reduce proteinuria and blood pressure in normotensive patients with chronic renal disease already receiving an angiotensin converting enzyme inhibitor (ACEI). METHODS: This was an open randomized controlled crossover study conducted in a private consultant practice in Melbourne. Sixty patients, aged 23-75, who had chronic renal disease and stable proteinuria over 0.5 g in 24 h and were receiving an ACEI, were enrolled in the study. The patients were randomized to have 8 mg of Candesartan added in the first or second of two 12-week study periods. The primary end point was urine protein excretion, which was measured every 2 weeks for the 24-week period. Secondary end points included systolic and diastolic blood pressure, serum creatinine, urea and potassium levels. Candesartan was added against a background of standard care, which included other blood pressure lowering therapy. RESULTS: Lower urine protein excretion 2.4 vs 2.0 g in 24 h (P<0.04, difference 0.45, CI 0.01, 0.9) and lower levels of systolic blood pressure 134 vs 128 mmHg (P<0.001, difference 6.4, CI 3.2, 9.6) and diastolic blood pressure 82 vs 80 mmHg (P<0.008, difference 2.7, CI 0.7, 4.6) were observed when Candesartan, 8 mg, was added to a regimen, which included an ACEI. No rise in serum creatinine occurred but there was a significant rise in urea, during the Candesartan arm of the study, from 12.3 to 13.8 mmol/l (P<0.001). The addition of 8 mg of Candesartan in normotensive patients with chronic renal disease receiving ACEI appeared safe and was not accompanied by adverse effects apart from postural hypotension in three patients and a serum potassium level of 6.3 mmol/l in one. CONCLUSIONS: In a private consulting practice setting, the addition of 8 mg of Candesartan in normotensive patients with chronic renal disease and proteinuria receiving an ACEI reduced proteinuria and blood pressure. The combination of Candesartan and ACEI appeared safe in this setting and may offer additional protection in preventing progression in chronic renal disease. Although the reduction of proteinuria was small (0.45 g/24 h) this reflected in part a lack of response in diabetic nephropathy and in part a marked rise in proteinuria after ceasing Candesartan in patients who did not complete the Candesartan arm of the study. 相似文献
18.
D. ROCCATELLO G. MENGOZZI R. MOSSO G. GIGLIOLA G. CACACE R. POLLONI G. CESANO G. PICCIOTTO L. PARADISI E. BANCALE G. PICCOLI LM SENA R. COPPO 《Nephrology (Carlton, Vic.)》1997,3(1):27-30
Summary: While a variety of immunologic factors are likely to be involved in the initial acute phlogistic events in IgA nephropathy (IgAN), progression to renal failure occurs through a relatively silent course histologically related to prevalent sclerotic changes. In this phase of IgAN, haemodynamic mechanisms are likely to play the most important role. Among the others, angiotensin II and endothelin 1 are thought to be critical mediators. Angiotensin II promotes mesangial cell contraction, modulates membrane permselectivity and induces glomerular hypertension. Evidence for a local angiotensin II hyperactivity in IgAN (especially in patients at definite risk of progression) has been previously provided by our group. Endothelin 1 is mitogenetic for mesangial cells and increases matrix production. Moreover, it exerts local vasoconstrictor effects and induces mesangial cell contraction, both resulting in glomerular afterload. Again, plasma and urinary endothelin 1 are elevated in IgAN. Moreover, those patients with increased risk of progression show an increased ratio between urinary endothelin 1 and cyclic guanosine 3′,5′ monophosphate (GMP), a local messanger with counterbalancing effects. Several data of clinical benefits of angiotensin-converting enzyme inhibitors in IgAN have been reported. Less is known about the intrinsic mechanism of the antiproteinuric action, either reduction of filtration fraction or changes in glomerular permselectivity. The clinical usefulness of factors counterbalancing endothelin 1 effects, such as nitric oxide donors, remains to be established. A sample of eight IgAN patients with poor prognostic indicators was enrolled to examine the renal haemodynamic effects of angiotensin receptor antagonism, angiotensin-converting enzyme inhibition and administration of an exogenous source of nitric oxide. Study periods (7 days each) were randomized and spaced out by one week wash-out. Data showed that angiotensin receptor antagonism and angiotensin-converting enzyme inhibition were equally effective in modifying renal haemodynamics, but only the latter condition significantly reduced albuminuria, possibly indicating a prevalent action on membrane permselectivity in the short time period of the study. The antiproteinuric effects of nitric oxide donors were strictly confined to patients with increased urinary endothelin 1/cyclic GMP ratio. Finally, each treatment condition was found to be associated with an increased nitric oxide production, which appeared to be an additional factor in modulation of filtration fraction changes. 相似文献
19.
尿激酶联合苯那普利治疗IgA肾病的随访对照研究 总被引:23,自引:1,他引:22
目的 观察联合应用尿激酶(UK)和血管紧张素转换酶抑制剂(ACEI)苯那普利治疗IgA肾病(IgAN)的效果。方法 将71例Lee分级≥Ⅲ级的IgAN患者随机分为两组:UK+ACEI组及ACEI组,随访观察两组的疗效。结果 (1)12个疗程后,UK+ACEI组24h尿蛋白定量明显下降(P<0.01),血白蛋白(AIb)水平升高(P<0.05),疗效优于ACEI组。(2)治疗前应用Katafuchi IgA肾病积分系统进行IgAN的病理评分,在肾小球积分≥7分的患者中,治疗至12个疗程时,UK+ACEI治疗效果优于ACEI组(P<0.05)。(3)UK+ACEI组中有10例患者进行了重复肾活检,经治疗后多数患者病理改变保持稳定。结论 UK联合ACEI治疗中重度IgAN安全有效,疗效优于单用ACEI者。肾小球硬化及间质炎细胞浸润的程度可作为估计UK治疗IgAN效果的指标。 相似文献
20.
环孢素A对大鼠慢性肾毒性模型肾素-血管紧张素系统的影响 总被引:3,自引:0,他引:3
目的 探讨环孢素A (CsA)慢性肾毒性的发生机理。方法 采用放射免疫分析的方法 ,观察进低盐饮食的大鼠在灌服CsA 30mg·kg- 1 ·d- 1 2 8d后血浆肾素活性 (PRA)、血管紧张素Ⅱ(AngⅡ )、醛固酮水平的变化 ,以及复方丹参注射液、贝那普利对上述改变的防护作用。结果 CsA可引起大鼠血浆PRA、AngⅡ水平明显升高 ;丹参对这些改变影响不明显 ,而贝那普利对大鼠PRA、AngⅡ水平的升高有明显的抑制作用。血浆醛固酮水平 ,各组比较 ,只有给予贝那普利者明显下降 ,其余各组之间血浆醛固酮水平的差异无显著性 (P >0 .0 5)。结论 CsA的慢性肾毒性损伤可能与肾素 血管紧张素系统 (RAS)的激活 ,尤其是与AngⅡ的增加有关 ;CsA不引起血浆醛固酮水平的升高 相似文献