Renin-angiotensin system blockades and contrast-induced nephropathy: a meta-analysis

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.     

The effect of withdrawal of ACE inhibitors or angiotensin receptor blockers prior to coronary angiography on the incidence of contrast-induced nephropathy

Background

The effect of continuing or discontinuing chronic angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy prior to coronary angiography on the incidence of contrast-induced nephropathy (CIN) is not clear. We undertook a randomized trial to evaluate the effect of withdrawing ACEIs or ARBs 24 h prior to coronary angiography on the incidence of CIN associated with coronary angiography.

Methods

A total of 220 patients with chronic kidney disease (CKD) stages 3–4 (glomerular filtration rate 15–60 ml/min/1.73 m²) on ACEI or ARB therapy were randomized before angiography to either ACEI/ARB continuation group or discontinuation group. A third group of patients with CKD stages 3–4 but not on angiotensin blockade therapy were also followed. The primary outcome measure was the incidence of CIN defined by a rise in serum creatinine by 25% or 0.5 mg/dl (44 μmol/l) from baseline.

Results

There was no statistically significant difference in the incidence of CIN between the three groups (P = 0.66). The incidences were 6.2%, 3.7%, and 6.3% for the continuation, discontinuation, and angiotensin blockade naïve group, respectively. There was also no significant difference found between the groups in mean serum creatinine and glomerular filtration rate values at baseline and post contrast administration.

Conclusion

Withholding ACEIs and ARBs 24 h before coronary angiography does not appear to influence the incidence of CIN in stable patients with CKD stages 3–4.     

Will the addition of pentoxifylline reduce proteinuria in patients with diabetic glomerulosclerosis refractory to maximal doses of both an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker?

BACKGROUND: While interruption of angiotensin synthesis and angiotensin blockade are well know to reduce proteinuria and preserve renal function in patients with diabetic glomerulosclerosis, many patients still have significant proteinuria after having reached maximal doses of those medications. We chose to examine the effect of the addition of pentoxifylline to the therapeutic regimen of patients with significant proteinuria and chronic renal insufficiency who had reached maximal does of an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin receptor blocker (ARB), on the reduction of proteinuria and the preservation of renal function. METHODS: Seven male patients with diabetic glomerulosclerosis with proteinuria of at least 1.5 g/24 hours and a creatinine clearance of at least 15 ml/min despite maximal doses of an ACEI and an ARB for over 12 months were treated with pentoxifylline adjusted for creatinine clearance. They were then compared with 7 similar patients matched for age, duration of medications, proteinuria, creatinine clearance and mean arterial pressure. The groups were compared for any significant differences on at baseline and at 12 months. RESULTS: Although proteinuria decreased in the pentoxifylline group (5.657 +/- 3.5227 to 3.799 +/- 3.647 g/24 hours) there was no significant difference from the control group (4.743 +/- 2.320 to 4.986 +/- 2.941 g/24 hours). Similarly both groups lost creatinine clearance (41.0 +/- 27.44 to 29.33 +/- 22.21 ml/min with pentoxifylline and 45.57 +/- 21.854 to 27.33 +/- 27.105 ml/min in controls), but there was no significant difference in either clearance or mean arterial pressure. CONCLUSION: Although there was a trend toward the reduction of proteinuria, we found no statistical benefit in proteinuria reduction or preservation of renal function by the addition of pentoxifylline to maximal doses of ACEIs and ARBs.     

Renal protection in diabetes: is it affected by glucose control or inhibition of the renin-angiotensin pathway?

BACKGROUND: Recent reports indicate increased risk of renal failure with long-term use of angiotensin-converting enzyme inhibitors (ACEI) in diabetes. End-stage renal disease (ESRD) in diabetes has increased despite ACEI and angiotensin receptor blocker (ARB) use. This study questions renal protection by ACEI or ARB. Our hypothesis is that uncontrolled hyperglycemia is central to diabetic ESRD while tight glucose control is renoprotective. Cultured endothelial cells show morphological damage that increases with duration of exposure to high glucose and is prevented by insulin and more so by a combination of insulin and heparin. METHODS: Findings from individual patients are compared to clinical trial results wherein ACEI or ARB was emphasized as the prime therapy to prevent progression of diabetic nephropathy to ESRD. Serum creatinine (Scr) changes were the main indicator of renoprotective effects in clinical trials. Creatinine clearance (Ccl), an important marker of glomerular filtration rate, was seldom reported. RESULTS: Our observations show that ACEI-treated patients develop progressive renal failure, whereas renal function remains stable with optimum glucose control. Clinical trials showed that reduction of proteinuria, with ACEI, reduces the risk of ESRD. Our studies show that reduction of proteinuria with use of ACEI or ARB parallels a reduction in Ccl, suggesting that a change in proteinuria is related to Ccl changes. Scr changes are small, giving a deceptive view of renal protection. CONCLUSIONS: Our observations find no evidence of renal protection with ACEI or ARB use in diabetes. Laboratory studies and clinical observations suggest that adequate glucose control is the key to renal protection in diabetes.     

The association between angiotensin converting enzyme inhibitor or angiotensin receptor blocker use during postischemic acute transplant failure and renal allograft survival

BACKGROUND: Postischemic acute renal transplant failure occurs in approximately one fourth of all dead donor transplantations. Uncertainty exists regarding the putative association between the use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) and kidney transplant graft survival in patients with delayed allograft function. METHODS: We conducted an open cohort study of all 436 patients who experienced an acute renal transplant failure out of all 2,031 subjects who received their first kidney transplant at the Medical University of Vienna between 1990 and 2003. Actual and functional graft survival was compared between users and nonusers of ACEI/ARB using exposure propensity score models and time-dependent Cox regression models. RESULTS: Ten-year actual graft survival averaged 44% in the ACEI/ARB group, but only 32% in patients without ACEI/ARB (P=0.002). The hazard ratio of actual graft failure was 0.58 (95% confidence interval: 0.35-0.80, P=0.002) for ACEI/ARB users compared with nonconsumers. Seventy-one percent of subjects with ACEI/ARB had a functional graft at 10 years versus 64% of ACEI/ARB nonusers (P=0.027). The hazard ratio of functional graft loss was 0.48 (95% confidence interval: 0.24-0.91, P=0.025). CONCLUSIONS: Use of ACEI/ARB in patients experiencing delayed allograft function was associated with longer actual and functional transplant survival.     

Angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist therapy is associated with prolonged patient and graft survival after renal transplantation

Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) reduce cardiovascular death in the general population, but data for renal transplant recipients remain elusive. Similarly, ACEI/ARB have been shown to reduce proteinuria, but data on graft survival are lacking. Therefore a retrospective open cohort study was conducted of 2031 patients who received their first renal allograft at the Medical University of Vienna between 1990 and 2003 and survived at least 3 mo. Patient and graft survival was compared between patients with versus without ACEI and/or ARB therapy. Data were analyzed with and without propensity score models for ACEI/ARB therapy. Medication and comorbidities were analyzed as time-dependent variables in the Cox regression analyses. Ten-year survival rates were 74% in the ACEI/ARB group but only 53% in the noACEI/ARB group (P<0.001). The hazard ratio (HR) of ACEI/ARB use for mortality was 0.57 (95% confidence interval [CI] 0.40 to 0.81) compared with nonuse. Ten-year actual graft survival rate was 59% in ACEI/ARB patients but only 41% in nonusers (P=0.002). The HR of actual graft failure for ACEI/ARB recipients was 0.55 (95% CI 0.43 to 0.70) compared with nonusers; the HR of functional graft survival was 0.56 (95% CI 0.40 to 0.78). Ten-year unadjusted functional graft survival rates were 76% among ACEI/ARB patients and 71% in noACEI/ARB recipients (P=0.57). In summary, the use of ACEI/ARB therapy was associated with longer patient and graft survival after renal transplantation. More frequent use of these medications may reduce the high incidence of death and renal allograft failure in these patients.     

Defining incidence and outcome of contrast-induced nephropathy among trauma: is it overhyped?

Contrast-induced nephropathy (CIN) in trauma patients is uncommon and the incidence is unknown. We studied the incidence of CIN and its outcome. A retrospective chart review of trauma patients 16 years of age and older who were admitted to our Level I trauma center during 2005 was performed. Patients who received the intravenous contrast CT scan and had their serum creatinine (Cr) monitored at admission and at 48 to 72 hours were identified. CIN was defined as a 0.5-mg/dL rise of serum Cr or a 25 per cent increase from the baseline if the baseline Cr was abnormal. We excluded patients transferred from an outside facility, patients without repeated serum Cr measurements, patients who had cardiac arrest or persistent hypotension, and patients who had received N-acetylcysteine (Mucomyst) before their CT scan. We compared CIN and non-CIN groups. During 2005, 543 fit our study criteria, of whom 19 (3.5%) had CIN. CIN (vs non-CIN) had a higher baseline serum Cr (1.48 + 0.23 vs 1.06 + 0.02, P < 0.001), a longer intensive care unit stay (17 vs 5 days, P < 0.001), and a longer hospital stay (19 vs 8 days, P < 0.001); the mortality rate was not different (10 vs 4%, P = 0.2). We found elevated baseline serum Cr (OR, 1.92; 95% CI, 1.13 to 3.27; P = 0.016) to be associated with increased risk for CIN. All but two serum Cr levels peaked within 48 hours; all returned to baseline. One patient with an underlying congenital kidney disease required temporary dialysis. CIN incidence in trauma is low and the clinical course is benign.     

Barriers to blood pressure control and angiotensin enzyme inhibitor use in Canadian patients with chronic renal insufficiency.

BACKGROUND: Current recommendations for the management of chronic renal insufficiency (CRI) include the use of angiotensin-converting enzyme inhibitors (ACEI) and achieving target blood pressure control. We designed this study to describe the use of these therapeutic strategies, and to investigate barriers to their implementation. METHODS: This was a prospective study of 304 consecutive CRI patients, seen at follow-up in four nephrology clinics across Canada. The use of blood pressure control and antihypertensive medication (AHM) in each of these clinics was recorded, and a questionnaire was administered to nephrologists to determine the basis for decisions concerning AHM regimens and ACEI use/non-use. RESULTS: Mean age was 60.8+/-15.7 years, mean creatinine clearance was 30.3+/-18 ml/min, and underlying renal diseases were similar to registry data. Mean arterial pressure (MAP) achieved was 99.4+/-14.4 and 98.9+/-11.9 mmHg in individuals with >1 and 相似文献   

A positive effect of AII inhibitors on peritoneal membrane function in long-term PD patients

Background. Experimental studies showed that inhibition of AIIeffects attenuates the development of peritoneal membrane fibrosisand neoangiogenesis. The latter leads to an increase of peritonealsolute transport and ultrafiltration failure. The results ofa single-centre study showed that use of ACEI/ARB can preventthe increase of small solute transport in long-term PD patients.Our aim was to investigate whether these results would alsobe present in a larger population and influence patient andtechnique survival in long-term PD. Methods. We analysed data from 217 long-term CAPD patients,participating in the Netherlands Cooperative Study on Adequacyof Dialysis (NECOSAD). Included patients underwent CAPD therapyfor at least 2 years; 120 of them were treated with the ACE/AIIinhibitors-ACEI/ARB group. The control group consisted of 87patients who received none of the above drugs and 10 patientswho had them for <25% of their time on PD. Results. A significant difference in the time course of peritonealtransport was found between the two groups. The value of 24-hD/P creatinine was associated with the PD duration (P = 0.01)and its time course was influenced by use of ACEI/ARB (P = 0.05).We found no effect of ACEI/ARB on patient survival, but somebenefit was found for the technique survival: in a multivariatemodel the hazard ratio for the group with the longest use ofACEI/ARB was 0.5 (CI 0.22–1.4), P = 0.19. Conclusions. We conclude that AII inhibition prevents the increasein small solute transport in long-term PD. These drugs may alsohave some positive influence on PD technique survival.     

Frequency and risk factors of contrast-induced nephropathy after cardiac catheterization in type II diabetic patients: a study among Egyptian patients

Contrast-induced nephropathy (CIN) is the third leading cause of acute kidney injury (AKI) in hospitalized patients. Diabetes mellitus remains a consistent independent predictor of contrast nephropathy. Aim: To determine frequency and predictors of contrast-induced nephropathy after cardiac catheterization in type II diabetic patients. Patients and methods: The study included 200 type II diabetic patients who underwent cardiac catheterization; serial measurement of serum creatinine and creatinine clearance (Before contrast exposure and 48?h), creatinine clearance was calculated using Cockcroft–Gault formula. Contrast-induced nephropathy was defined as rise in serum creatinine 48?h after contrast exposure of ≥0.5?mg/dL or increased >25% compared to base line creatinine. Results: incidence of CIN in type II diabetic patients was 21.5%; incidence of CIN in diabetic patients with microalbuminuria was 17%, while incidence of CIN in patients with macroalbuminuria levels was 26%. There was a statistically significant difference between the patients who suffered from CIN post-procedure and patients who did not suffer from CIN regarding the ejection fraction and age with low ejection fraction and older patients in CIN group. Multiple logistic regression analysis for CIN predictors showed that pre-contrast serum creatinine to be the strongest predictor for being at risk of contrast-related, followed by age, and lastly albumin/creatinine ratio. Conclusion: Our findings suggest that diabetic patients, despite having a normal baseline creatinine are at an increased risk of developing CIN post-coronary angiography, patients at risk of CIN are older patients with high pre-contrast serum creatinine and high urine albumin/creatinine ratio.     

ACEI和（或）ARB基础上联合安体舒通治疗IgA肾病的研究

目的探讨应用血管紧张素转化酶抑制剂（ACEI）和（或）血管紧张素受体拮抗剂（ARB）联合安体舒通治疗IgA肾病患者,观察其降低尿蛋白及肾脏保护作用。方法将54例IgA肾病患者随机分为安体舒通组（A组）27例,对照组（B组）27例。A组在应用ACEI和（或）ARB基础上联合安体舒通20mg／d;B组按原量服用ACEI和（或）ARB药物。检测2组在第0、4、8、12、16周时24h尿蛋白、血肌酐、血钾、血浆醛固酮、血压、估算肾小球滤过率（eGFR）。结果A组治疗后第8周时尿蛋白较治疗前下降18．5％（P〈0．05）,至第16周时下降35．1％（P〈0．01）;B组至治疗终点仅下降5．3％,无统计学差异（P〉0．05）。2组血钾、血肌酐、eGFR、血浆醛固酮、血压较治疗前无显著变化（P〉0．05）。结论在应用ACEI和（或）ARB基础上联合安体舒通对降低kA肾病患者尿蛋白有显著作用。     

A randomized trial of saline hydration to prevent contrast-induced nephropathy in patients on regular captopril or furosemide therapy undergoing percutaneous coronary intervention

Contrast-induced nephropathy (CIN) is characterized by acute deterioration of renal function that occurs after parenteral administration of contrast media in the absence of other causes. Although no definite proof has been obtained yet, the risk of diuretics or angiotensin-converting enzyme inhibitors (ACEI) to exacerbate CIN has been reported because of their effects on renal perfusion. This study was conducted to assess the protective effect of hydration alone in the prevention of CIN after percutaneous coronary intervention (PCI) in patients on diuretics or ACEI. This randomized clinical trial was conducted at the Chamran Hospital, Isfahan University of Medical Sciences, Iran, during the years 2006-2007. The study patients were divided into four groups, each group containing 60 patients. Patients in groups A and B were on regular treatment with ACEI (captopril) and patients in groups C and D were on regular diuretic (furosemide) therapy. About 36 h before PCI, captopril in group A and furosemide in group C were discontinued. The serum creatinine (Cr) levels were measured at the time of performing PCI and 24 h and 48 h after PCI in all patients. All patients received 1 mL/kg/h normal saline (0.9%) 12 h before and 24 h after PCI. The occurrence of CIN after PCI was diagnosed based on the following formula: Cr level after PCI - Cr level before PCI. If this value was greater than 0.5 mg/dL, it was coded as one and if the value was less than 0.5 mg/dL, it was coded as zero. The mean difference was analyzed and compared among the four groups by the ANOVA test. Three patients (5%) in group A, two patients (3.3%) in group B, two patients (3.3%) in group C and one patient (1.6%) in group D had a >0.5 mg/dL difference in serum Cr. The difference seen between these groups was not statistically significant (P > 0.05). This study shows that although furosemide and captopril can exacerbate CIN by impairment of renal perfusion, this can be prevented by hydration and discontinuation of furosemide and captopril may not be required.     

Renoprotective effects of angiotensin II receptor blocker,candesartan cilexetil,in patients with stage 4–5 chronic kidney disease

BACKGROUND: To investigate the renoprotective effects and safety of angiotensin II receptor blocker (ARB) for patients with stage 4-5 chronic kidney disease. METHODS: An ARB, candesartan cilexetil, was administered to 13 patients (ARB group, n = 7; control group, n = 6) with a serum creatinine level of 2.52-5.95 mg/dl whose blood pressure had been maintained below 140/90 mmHg by the use of drugs other than ARBs. Routine measurements were conducted for 48 weeks, and renal survival analysis was observed for up to 3 years with the endpoints being doubling of the serum creatinine level, entry to hemodialysis, or death. The results were compared with those of the control group that was not treated with ARB. RESULTS: No significant changes were observed in the blood pressure in either group. Proteinuria significantly decreased from 0.95 +/- 0.51 to 0.39 +/- 0.12 g/day (paired t test, P = 0.033) in the ARB group, but did not change in the control group. Creatinine clearance in the control group decreased significantly from 16.2 +/- 5.7 to 10.4 +/- 4.8 ml/min per 1.73 m2 (paired t test, P = 0.011), but did not change in the other group. Thus, the slopes of the reciprocal serum creatinine values became less steep in the ARB group as compared with the control (-0.002 +/- 0.015 vs. -0.025 +/- 0.015 dl/mg per month; unpaired t test, P = 0.019). Kaplan-Meier analysis revealed that ARB exhibited more favorable renal outcome at 3 years (log-rank, P = 0.025). No serious adverse events were noted in the study. CONCLUSION: These results show that ARB reduces proteinuria and protects renal function even in the advanced renal failure.     

舒洛地特对糖尿病肾病患者尿蛋白的影响

目的：观察舒洛地特对已应用ACEI/ARB类药物的2型糖尿病肾病患者尿蛋白的影响。方法：据尿白蛋白排泄率将92例2型糖尿病肾病患者分为微量白蛋白尿组和大量白蛋白尿组,患者在入组前至少服用一种ACEI或ARB类降压药6个月,入组后先接受10d舒洛地特注射剂60mg/d静脉滴注,再接受110d舒洛地特软胶囊100mg/d口服。用药前、用药4周、8周、12周及120d分别检测患者血压、空腹血糖、肝肾功能、凝血功能、24h尿蛋白定量等指标。结果：两组患者治疗12周后均出现尿蛋白显著降低（P0.05）。结论：对已应用ACEI/ARB的伴有微量白蛋白尿或大量白蛋白尿的2型DN患者,舒洛地特能有效降低其尿蛋白。     

Effects of sulodexide in patients with type 2 diabetes and persistent albuminuria.

BACKGROUND: Urinary albumin excretion frequently persists in diabetic patients who are treated with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Sulodexide, a glycosaminoglycan mixture of 80% heparan sulfate and 20% dermatan sulfate, has been hypothesized to reduce persistent albuminuria. We have conducted a multi-center randomized double-blind pilot study in order to determine the effect of 6 months' therapy with sulodexide on urinary albumin excretion and to address logistical issues for a full-scale trial. METHODS: A total of 149 patients with type 2 diabetes and an albumin:creatinine ratio (ACR) between 20 and 300 mg/g were randomized with equal allocation to either placebo, 200 mg of sulodexide or 400 mg of sulodexide. The primary endpoint was the achievement, at 6 months, of either 3(1) return to normoalbuminuria (ACR < 20 mg/g with a decrease of at least 25%) or (2) a decrease in ACR of at least 50% from the baseline value. All patients used a maximum tolerated recommended FDA approved dose of an ACEI or ARB for at least 60 days and had stable blood pressure prior to randomization. RESULTS: The primary efficacy endpoint was achieved in 25.3% of the patients in the two sulodexide groups combined versus 15.4% of the placebo-treated patients (P = 0.26). The primary endpoint was achieved in 33.3% (P = 0.075 for the comparison to placebo) in the sulodexide 200 mg group and 18.4% (P = 0.781) in the sulodexide 400 mg group. (No consistent patterns of side effects were observed. CONCLUSION: Based on the experience gained in this pilot study, one full-scale trial is currently being conducted to evaluate the effects of sulodexide on change in ACR in patients with persistent microalbuminuria, and a longer-term trial is underway to evaluate the effects of sulodexide on long-term renal disease progression in patients with overt proteinuria.     

Proteinuria as a predictor of renal dysfunction in trauma patients receiving intravenous contrast

Trauma patients have unknown comorbidities, multiple injuries, and incomplete laboratory testing, yet require contrast-enhanced imaging to identify potentially life-threatening problems. Our goal was to characterize contrast-induced nephropathy (CIN) in this population. We retrospectively reviewed characteristics of 402 patients who presented to a Level II trauma center and received contrast-enhanced imaging. CIN was defined as creatinine rise of 0.5 mg/dL or greater or 25 per cent or greater from baseline within 48 hours. CIN occurred in 7.7 per cent and four patients required hemodialysis. Patients with CIN were older, had lower admission hemoglobin, higher Injury Severity Score, and received more blood products. Factors that predicted CIN included: male sex, age older than 46 years, body mass index less than 27 kg/m2, glomerular filtration rate less than 109 mL/min/1.73 m2, hemoglobin less than 12 mg/dL, hematocrit less than 36 per cent, proteinuria, 2 units or more of fresh-frozen plasma in 48 hours, and alcohol use. Odds ratio for developing CIN with two, five, or six of these factors was 3.39, 6.54, and 8.38, respectively. A match-controlled analysis for Injury Severity Score and age in patients with CIN versus non-CIN patients revealed the strongest predictor of CIN was proteinuria (relative risk, 2.5; confidence interval, 1.1 to 5.8). Although it is difficult to truly differentiate CIN from renal dysfunction related to injury severity in trauma patients, proteinuria may be an important factor in identifying nephropathy in this population.     

Angiotensin-converting enzyme inhibition but not angiotensin II receptor blockade regulates matrix metalloproteinase activity in patients with glomerulonephritis

Equivalent long-term effects on the kidney are attributed to angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB). Nevertheless, it is unknown to which degree effects of these compounds on individual inflammatory mediators, including matrix metalloproteinases (MMP), are comparable. On the basis of structural and functional differences, it was hypothesized that ACEI and ARB differentially regulate MMP activity. In a randomized, prospective crossover trial, the effect of an ACEI (fosinopril; 20 mg/d) and of an ARB (irbesartan; 150 mg/d) on MMP activity was evaluated. Ten hypertensive patients with glomerulonephritis and normal or mildly reduced creatinine clearance were studied. MMP activity and tissue inhibitors of metalloproteinase (TIMP) levels were analyzed in serum and urine: without therapy, with ACEI, with ARB, and with both agents combined. Treatment periods continued for 6 wk separated by periods of 4 wk each without therapy. Untreated patients with glomerulonephritis displayed distinctively higher serum levels of MMP-2 but much lower MMP-1/-8/-9 concentrations compared with healthy control subjects. Immunohistology of MMP-2 and MMP-9 in kidney biopsy specimen was accordingly. However, these patients excreted higher amounts of MMP-2 and MMP-9 in urine than healthy control subjects, possibly reflecting ongoing glomerular inflammation. In patients with glomerulonephritis, ACEI significantly reduced overall MMP serum activity to 25%, whereas ARB did not show any effect. Activities of MMP-1/-2/-8/-9 were also significantly inhibited by fosinopril but not by irbesartan. Levels of TIMP-1/-2 remained unaffected. In conclusion, ACEI and ARB differentially regulate MMP activity, which may ultimately have consequences in certain types of MMP-dependent glomerulonephritis.     

Sodium Bicarbonate versus Normal Saline for Protection against Contrast Nephropathy

Contrast-induced nephropathy (CIN) is a form of acute kidney injury and a significant source of morbidity and mortality. We defined CIN as an increase in serum creatinine (SCr) of 25%?or more within 48 hours of receiving contrast. We retrospectively compared sodium bicarbonate with normal saline for prevention of CIN. One hundred and eighty-seven patients exposed to contrast during cardiac angiography, treated prophylactically either with sodium bicarbonate (n?=?89) or with normal saline (n?=?98), were studied. Baseline characteristics of both groups were similar in terms of age, amount of contrast, presence of diabetes mellitus, and use of furosemide and angiotensin-converting enzyme inhibitor. Patients in bicarbonate group had more severe renal disease with higher baseline SCr (1.58?±?0.5 mg/dL vs. 1.28?±?0.3 mg/dL, p?=?0.001) and lower estimated glomerular filtration rate (eGFR, 51.06?±?14.0 mL/min vs. 62.3±13.5 mL/min, p?=?0.001) compared to the normal saline group. After the contrast exposure, there was significant drop in eGFR (6.4%) and increase in SCr (11.3%) in the normal saline group and no significant change in the bicarbonate group. Three patients (3.4%) in the bicarbonate group as opposed to 14 patients (14.3%) in the normal saline group developed CIN (p?=?0.011). Two patients in the normal saline group and none in the bicarbonate group needed dialysis. There was no significant difference in serum creatinine at three-month follow-up in either group. The above findings suggest that hydration with intravenous sodium bicarbonate is more effective than normal saline in preventing contrast-induced nephropathy.     

Metabolic syndrome as a risk factor for contrast-induced nephropathy in non-diabetic elderly patients with renal impairment

BACKGROUND/AIMS: Metabolic syndrome (MS) as a risk factor for contrast-induced nephropathy (CIN) has not been studied. The aim of the present study was to assess the influence of MS on the development of CIN in patients undergoing coronary angiography. METHODS: This was a prospective cohort study. A total of 219 non-diabetic patients with reduced kidney function and age >or=60 years were divided into two groups (MS, n = 107 and non-MS, n = 112). CIN was defined as an increase of >or=25% in creatinine over the baseline value within 48 h of angiography. RESULTS: CIN occurred in 14% of the MS group and 3.6% of the non-MS group (p = 0.006). Serum creatinine increased from 1.06 +/- 0.17 to 1.12 +/- 0.27 mg/dl in the MS group and from 1.03 +/- 0.17 to 1.09 +/- 0.23 mg/dl in the non-MS group (p < 0.001). MS was a risk indicator of CIN [odds ratio (OR) 4.26; 95% confidence interval (95% CI) 1.19-15.25; p = 0.026). Impaired fasting glucose (OR 4.72; 95% CI 1.53-14.56; p = 0.007), high triglyceride (OR 4.06; 95% CI 1.22-13.44; p = 0.022), and multivessel involvement (OR 3.14; 95% CI 1.07-9.82; p = 0.038) in the MS group were predictors of CIN. CONCLUSION: Our data support the hypothesis that patients with MS are at risk of developing CIN.     

Effect of preoperative angiotensin converting enzyme inhibitor or angiotensin receptor blocker use on the frequency of atrial fibrillation after cardiac surgery: a cohort study from the atrial fibrillation suppression trials II and III.

BACKGROUND: Two recent meta-analyses demonstrated that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce the risk of developing new-onset atrial fibrillation (AF) by nearly 50%. However, the ability of ACEIs or ARBs to prevent postoperative atrial fibrillation (POAF) after cardiac surgery has not been adequately evaluated. Objective: To evaluate the impact of preoperative ACEI or ARB use on the incidence of POAF after cardiac surgery. METHODS: Patients undergoing coronary artery bypass grafting and/or valvular surgery from the (atrial fibrillation suppression trials II and III (AFIST II and III) randomized, controlled trials were evaluated in this cohort evaluation. Data in respect to patient demographics, surgical characteristics, medication utilization and the incidence of POAF (defined as AF lasting at least 5 min in duration documented by telemetry) were all uniformly and prospectively collected as part of AFIST II and III. Multivariate logistic regression was utilized to calculate adjusted odds ratios with 95% confidence intervals. RESULTS: A total of 338 patients were evaluated of which 175 (51.8%) received an ACEI or ARB preoperatively and 163 (48.2%) did not. The study population was 65.7+/-9.1 years of age, 77.8% were male, 11.2% underwent valve surgery, 3.6% had prior AF, 10.1% had heart failure and 84.0 and 37.9% received postoperative beta-blockade and prophylactic amiodarone, respectively. In total, 110 (32.5%) patients developed POAF. Upon multivariate logistic regression, the preoperative use of an ACEI or ARB was not found to be associated with a statistically significant reduction in POAF (adjusted odds ratio; 0.71, 95% CIs 0.42-1.20). CONCLUSIONS: Although preoperative ACEI or ARB use reduced the odds of developing POAF by 29%, this association with not found to be statistically significant. A study with approximately 600 subjects would be needed to discern if ACEIs or ARBs truly impact POAF.