269 research outputs found
Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease
No full textBackground: Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor antagonists (AIIRA) are considered to be equally effective for patients with diabetic kidney disease (DKD), but renal and not mortality outcomes have usually been considered. Objectives: To evaluate the benefits and harms ACEi and AIIRA in patients with DKD. Search strategy: We searched MEDLINE (1966 to December 2005), EMBASE (1980 to December 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library issue 4 2005) and contacted known investigators. Selection criteria: Studies comparing ACEi or AIIRA with placebo or each other in patients with DKD were included. Data collection and analysis: Two authors independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) with 95% confidence intervals (CI). Heterogeneity among studies was explored using the Cochran Q statistic and the I2 test, subgroup analyses and random effects metaregression. Main results: Fifty studies (13,215 patients) were identified. Thirty eight compared ACEi with placebo, five compared AIIRA with placebo and seven compared ACEi and AIIRA directly. There was no significant difference in the risk of all-cause mortality for ACEi versus placebo (RR 0.91, 95% CI 0.71 to 1.17) and AIIRA versus placebo (RR 0.99, 95% CI 0.85 to 1.17). A subgroup analysis of studies using full-dose ACEi versus studies using half or less than half the maximum tolerable dose of ACEi showed a significant reduction in the risk of all-cause mortality with the use of full-dose ACEi (RR 0.78, 95% CI 0.61 to 0.98). Baseline mortality rates were similar in the ACEi and AIIRA studies. The effects of ACEi and AIIRA on renal outcomes (ESKD, doubling of creatinine, prevention of progression of micro-to macroalbuminuria, remission of micro- to normoalbuminuria) were similarly beneficial. Reliable estimates of effect of ACEi versus AIIRA could not be obtained from the three studies in which they were compared directly because of their small sample size. Authors' conclusions: Although the survival benefits of ACEi are known for patients with DKD, the relative effects on survival of ACEi with AIIRA are unknown due to the lack of adequate direct comparison studies. In placebo controlled studies, only ACEi (at the maximum tolerable dose, but not lower so-called renal doses) were found to significantly reduce the risk of all-cause mortality. Renal and toxicity profiles of these two classes of agents were not significantly different. Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Statins in patients with chronic kidney disease: evidence from systematic reviews and randomized clinical trials.
No full textAldosterone antagonists for preventing the progression of chronic kidney disease
No full textBackground: Treatment with angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is increasingly used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). But some patients do not attain complete resolution of proteinuria and might have higher aldosterone levels within few months of treatment. The addition of aldosterone antagonists may be beneficial to these patients for reduction of progression of renal damage. Objectives: We evaluated the benefits and harms of adding aldosterone antagonists in patients with CKDcurrently treated with ACEi and/or ARB. Search strategy: We searched MEDLINE, EMBASE, CENTRAL, and hand-searched reference lists of textbooks, articles and scientific proceedings for relevant articles. Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs comparing aldosterone antagonists in addition to ACEi and/or ARB versus ACEi and/or ARB alone were included. Data collection and analysis: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and heterogeneity was tested formally using the Cochran Q and I2 statistic. Results were expressed as mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes with 95% confidence intervals (CI). Main results: Ten studies (845 patients) were included. Compared to ACEi and/or ARB plus placebo, non-selective aldosterone antagonists along with ACEi and/or ARB significantly reduced 24 hour proteinuria (7 studies, 372 patients;MD -0.80 g, 95% CI -1.23 to -0.38). There was a significant reduction in both systolic and diastolic blood pressure at the end of treatment with the addition of non-selective aldosterone antagonists to ACEi and/or ARB. This did not translate into an improvement in glomerular filtration rate (5 studies, 306 patients; MD -0.70 mL/min/1.73 m 2, 95% CI -4.73 to 3.34). There was a significant increase in the risk of hyperkalaemia with the addition of non-selective aldosterone antagonists to ACEi and/or ARB (8 studies, 436 patients; RR 3.06, 95% CI 1.26 to 7.41). In two studies, the addition of selective aldosterone antagonists to ACEi resulted in an additional reduction in 24 hour proteinuria but without any impact on BP and renal function. Data on cardiovascular outcomes, long-term renal outcomes and mortality were not available. Authors' conclusions: Aldosterone antagonists contribute to reduction of proteinuria in patients with CKD who are already on ACEi and ARB but increase the risk of hyperkalaemia. Available studies are small and have short follow-up. Long-term effects on renal outcomes, mortality and safety are unknown. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Aldosterone antagonists for preventing the progression of chronic kidney disease
No full textBackgroundTreatment with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is increasingly used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). However, resolution of proteinuria may be incomplete with these therapies and the addition of an aldosterone antagonist may be added to further prevent progression of CKD. This is an update of a review first published in 2009.ObjectivesTo evaluate the effect of aldosterone antagonists (both selective (eplerenone) and non-selective (spironolactone)) alone or in combination with ACEi or ARB in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including major cardiovascular events, hospitalisation and all-cause mortality; kidney function (proteinuria, glomerular filtration rate (GFR), serum creatinine, and need for renal replacement therapy; and adverse events (including gynaecomastia and hyperkalaemia).Search methodsFor this update, we searched the Cochrane Renal Group's Specialised Register to 30 January 2013 using search terms relevant to this review.Selection criteriaWe included randomised controlled trials (RCTs) and quasi-RCTs that compared aldosterone antagonists alone or in combination with ACEi or ARB (or both) with other anti-hypertensive strategies or placebo.Data collection and analysisTwo authors independently assessed study quality and extracted data. Data were summarised using random effects meta-analysis. We tested for heterogeneity in estimated treatment effects using the Cochran Q test and I-2 statistic. We expressed summary treatment estimates as a risk ratio (RR) for dichotomous outcomes together with their 95% confidence intervals (CI) and mean difference (MD) for continuous outcomes, or standardised mean difference (SMD) when different scales were used.Main resultsWe identified 27 studies (1549 participants) that were eligible for inclusion. These studies provided no data relating to aldosterone antagonists in addition to ACEi or ARB (or both) on patient-level outcomes including major cardiovascular events and mortality and progression to end-stage kidney disease (ESKD) requiring dialysis or transplantation.Compared with ACEi or ARB (or both), non-selective aldosterone antagonists (spironolactone) combined with ACEi or ARB (or both) significantly reduced 24-hour protein excretion (11 studies, 596 participants): SMD -0.61, 95% CI -1.08 to -0.13). There was a significant reduction in both systolic and diastolic blood pressure (BP) at the end of treatment with additional non-selective aldosterone antagonist therapy (systolic BP (10 studies, 556 participants): MD -3.44 mm Hg, 95% CI -5.05 to -1.83) (diastolic BP (9 studies, 520 participants): MD -1.73 mm Hg, 95% CI -2.83 to -0.62).However, we found that aldosterone antagonist treatment had imprecise effects at the end of treatment on GFR (9 studies, 528 participants; MD -2.55 mL/min/1.73 m(2), 95% CI -5.67 to 0.51), doubled the risk of hyperkalaemia (11 studies, 632 patients): RR 2.00, 95% CI 1.25 to 3.20; number needed to treat for an additional harmful outcome (NNTH): 7.2, 95% CI 3.4 to) and increased the risk of gynaecomastia compared to ACEi or ARB (or both) (4 studies, 281 patients): RR 5.14, 95% CI 1.14 to 23.23; NNTH: 14.1, 95% CI 8.7 to 37.3).Most studies enrolled few patients (range 12 to 268) and were powered to observe differences in surrogate end points rather than patient-focused outcomes. Nine studies had a cross-over design and the majority of studies did not adequately report study methods to assess methods and study quality.Authors' conclusionsAldosterone antagonists reduced proteinuria and blood pressure in adults who had mild to moderate CKD and were treated with ACEi or ARB (or both), but increase hyperkalaemia and gynaecomastia. Whether adding aldosterone antagonists to ACEi or ARB (or both) reduced the risk of major cardiovascular events or ESKD in this population is unknown
Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease
Get PDFBackground: Treatment with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). However, resolution of proteinuria may be incomplete with these therapies and the addition of an aldosterone antagonist may be added to further prevent progression of CKD. This is an update of a Cochrane review first published in 2009 and updated in 2014. Objectives: To evaluate the effects of aldosterone antagonists (selective (eplerenone), non-selective (spironolactone or canrenone), or non-steroidal mineralocorticoid antagonists (finerenone)) in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including kidney failure (previously know as end-stage kidney disease (ESKD)), major cardiovascular events, and death (any cause); kidney function (proteinuria, estimated glomerular filtration rate (eGFR), and doubling of serum creatinine); blood pressure; and adverse events (including hyperkalaemia, acute kidney injury, and gynaecomastia). Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 13 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. Selection criteria: We included randomised controlled trials (RCTs) and quasi-RCTs that compared aldosterone antagonists in combination with ACEi or ARB (or both) to other anti-hypertensive strategies or placebo in participants with proteinuric CKD. Data collection and analysis: Two authors independently assessed study quality and extracted data. Data were summarised using random effects meta-analysis. We expressed summary treatment estimates as a risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, or standardised mean difference (SMD) when different scales were used together with their 95% confidence interval (CI). Risk of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE. Main results: Forty-four studies (5745 participants) were included. Risk of bias in the evaluated methodological domains were unclear or high risk in most studies. Adequate random sequence generation was present in 12 studies, allocation concealment in five studies, blinding of participant and investigators in 18 studies, blinding of outcome assessment in 15 studies, and complete outcome reporting in 24 studies. All studies comparing aldosterone antagonists to placebo or standard care were used in addition to an ACEi or ARB (or both). None of the studies were powered to detect differences in patient-level outcomes including kidney failure, major cardiovascular events or death. Aldosterone antagonists had uncertain effects on kidney failure (2 studies, 84 participants: RR 3.00, 95% CI 0.33 to 27.65, I2 = 0%; very low certainty evidence), death (3 studies, 421 participants: RR 0.58, 95% CI 0.10 to 3.50, I2 = 0%; low certainty evidence), and cardiovascular events (3 studies, 1067 participants: RR 0.95, 95% CI 0.26 to 3.56; I2 = 42%; low certainty evidence) compared to placebo or standard care. Aldosterone antagonists may reduce protein excretion (14 studies, 1193 participants: SMD -0.51, 95% CI -0.82 to -0.20, I2 = 82%; very low certainty evidence), eGFR (13 studies, 1165 participants, MD -3.00 mL/min/1.73 m2, 95% CI -5.51 to -0.49, I2 = 0%, low certainty evidence) and systolic blood pressure (14 studies, 911 participants: MD -4.98 mmHg, 95% CI -8.22 to -1.75, I2 = 87%; very low certainty evidence) compared to placebo or standard care. Aldosterone antagonists probably increase the risk of hyperkalaemia (17 studies, 3001 participants: RR 2.17, 95% CI 1.47 to 3.22, I2 = 0%; moderate certainty evidence), acute kidney injury (5 studies, 1446 participants: RR 2.04, 95% CI 1.05 to 3.97, I2 = 0%; moderate certainty evidence), and gynaecomastia (4 studies, 281 participants: RR 5.14, 95% CI 1.14 to 23.23, I2 = 0%; moderate certainty evidence) compared to placebo or standard care. Non-selective aldosterone antagonists plus ACEi or ARB had uncertain effects on protein excretion (2 studies, 139 participants: SMD -1.59, 95% CI -3.80 to 0.62, I2 = 93%; very low certainty evidence) but may increase serum potassium (2 studies, 121 participants: MD 0.31 mEq/L, 95% CI 0.17 to 0.45, I2 = 0%; low certainty evidence) compared to diuretics plus ACEi or ARB. Selective aldosterone antagonists may increase the risk of hyperkalaemia (2 studies, 500 participants: RR 1.62, 95% CI 0.66 to 3.95, I2 = 0%; low certainty evidence) compared ACEi or ARB (or both). There were insufficient studies to perform meta-analyses for the comparison between non-selective aldosterone antagonists and calcium channel blockers, selective aldosterone antagonists plus ACEi or ARB (or both) and nitrate plus ACEi or ARB (or both), and non-steroidal mineralocorticoid antagonists and selective aldosterone antagonists. Authors' conclusions: The effects of aldosterone antagonists when added to ACEi or ARB (or both) on the risks of death, major cardiovascular events, and kidney failure in people with proteinuric CKD are uncertain. Aldosterone antagonists may reduce proteinuria, eGFR, and systolic blood pressure in adults who have mild to moderate CKD but may increase the risk of hyperkalaemia, acute kidney injury and gynaecomastia when added to ACEi and/or ARB
Phosphate binders for preventing and treating bone disease in chronic kidney disease patients
No full textHow to conduct a randomized trial
No full textRandomized controlled clinical trials represent the gold standard of research into health-care interventions but conducting a randomized trial requires careful planning, structures and procedures. The conduct of a clinical trial is a collaborative effort between investigators, participants and a range of professionals involved both centrally and locally in the coordination and execution of the study. In this article, the key steps to conducting a randomized controlled trial are summarized. © 2010 The Authors. Nephrology © 2010 Asian Pacific Society of Nephrolog
Gut Inflammation in Primary Sclerosing Cholangitis and Autoimmune Sclerosing Cholangitis-Contrasting Pattern of Liver-gut Cross Talk
No full textInterventions for treating sexual dysfunction in patients with chronic kidney disease
No full textSexual dysfunction is very common in patients with chronic kidney disease (CKD), but it is still significantly understudied. Treatment options exist but concerns have been raised relating to their efficacy and safety in CKD. We assessed the benefits and harms of existing interventions for treatment of sexual dysfunction in patients with CKD. In October 2010 we searched the Cochrane Renal Group's specialised register, CENTRAL (The Cochrane Library, issue 10), MEDLINE (from 1966) and EMBASE (from 1980). Randomised controlled trials (RCTs) and quasi-RCTs of any pharmacological and non-pharmacological interventions used to treat sexual dysfunction in male and female CKD patients (predialysis, dialysis and kidney transplant) were included. Two authors independently selected eligible studies, extracted data and assessed study quality. Disagreements were resolved in consultation with an arbitrator. Treatment effects were summarised as risk ratios (RR), mean differences (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) using a random-effects model. Fifteen studies (8 parallel, 7 crossover; 352 patients) were included. Only one study enrolled women. Studies evaluated the effects of phosphodiesterase-5 inhibitors (PDE5i), zinc, vitamin E, vitamin D or bromocriptine compared to placebo. PDE5i significantly increased the overall International Index of Erectile Function-5 (IIEF-5) score (2 studies, 101 patients, MD 10.65, 95% CI 5.34 to 15.96), all its individual domains and the complete 15-item IIEF tool (1 study, 41 patients, MD 2.64, 95% CI 1.32 to 3.96). End of treatment testosterone levels were not significantly increased by addition of zinc to dialysate (2 studies, 22 patients, MD 0.21 ng/mL, 95% CI -2.14 to 2.55) but oral zinc improved end of treatment testosterone levels (1 study, 20 patients, SMD 1.62, 95% CI 0.58 to 2.66). There was no difference in plasma luteinizing and follicle-stimulating hormone levels at the end of the study period with zinc therapy. Only sparse data were available for vitamin E, bromocriptine and dihydroxycholecalciferol in CKD patients and there were no studies of intracavernous injections, transurethral injections, mechanical devices or psychosexual therapies in people with CKD. PDE5i and zinc are promising interventions for treating sexual dysfunction in men with CKD. Evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for both male and female sexual dysfunction in CKD, considering the significant disease burden
Spiritual Bypass: A Defense Against Wholeness
No full textThis thesis explores the spiritual-bypass phenomenon identified by John Welwood and how it can be a defense against wholeness as defined in Jungian psychology. Using hermeneutic and heuristic methodologies, and drawing on depth psychological theories, the author discusses the various forms of spiritual bypass and the underlying shadow dynamics, such as emotional repression. The author examines the nature of psychological and spiritual development through states and stages of consciousness development, healthy transcendence versus unhealthy transcendence, and the Jungian process of individuation toward wholeness. The research also explores contributing factors to spiritual bypass including the effect of early childhood attachment style and demonstrates the significance of integrating psychological development in a spiritual path. Finally, the author provides suggestions for therapists working with clients who may be in spiritual bypass
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