Showing papers by "Giovanni F.M. Strippoli published in 2023"

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease.

Abstract: BACKGROUND Chronic kidney disease (CKD) is a long-term condition that occurs as a result of damage to the kidneys. Early recognition of CKD is becoming increasingly common due to widespread laboratory estimated glomerular filtration rate (eGFR) reporting, raised clinical awareness, and international adoption of the Kidney Disease Improving Global Outcomes (KDIGO) classifications. Early recognition and management of CKD affords the opportunity to prepare for progressive kidney impairment and impending kidney replacement therapy and for intervention to reduce the risk of progression and cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are two classes of antihypertensive drugs that act on the renin-angiotensin-aldosterone system. Beneficial effects of ACEi and ARB on kidney outcomes and survival in people with a wide range of severity of kidney impairment have been reported; however, their effectiveness in the subgroup of people with early CKD (stage 1 to 3) is less certain. This is an update of a review that was last published in 2011. OBJECTIVES To evaluate the benefits and harms of ACEi and ARB or both in the management of people with early (stage 1 to 3) CKD who do not have diabetes mellitus (DM). SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to 6 July 2023 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 Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA Randomised controlled trials (RCTs) reporting the effect of ACEi or ARB in people with early (stage 1 to 3) CKD who did not have DM were selected for inclusion. Only studies of at least four weeks duration were selected. Authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria. DATA COLLECTION AND ANALYSIS Data extraction was carried out by two authors independently, using a standard data extraction form. The methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. When more than one study reported similar outcomes, data were pooled using the random-effects model. Heterogeneity was analysed using a Chi² test and the I² test. Results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach MAIN RESULTS: Six studies randomising 9379 participants with CKD stages 1 to 3 (without DM) met our inclusion criteria. Participants were adults with hypertension; 79% were male from China, Europe, Japan, and the USA. Treatment periods ranged from 12 weeks to three years. Overall, studies were judged to be at unclear or high risk of bias across all domains, and the quality of the evidence was poor, with GRADE rated as low or very low certainty. In low certainty evidence, ACEi (benazepril 10 mg or trandolapril 2 mg) compared to placebo may make little or no difference to death (any cause) (2 studies, 8873 participants): RR 2.00, 95% CI 0.26 to 15.37; I² = 76%), total cardiovascular events (2 studies, 8873 participants): RR 0.97, 95% CI 0.90 to 1.05; I² = 0%), cardiovascular-related death (2 studies, 8873 participants): RR 1.73, 95% CI 0.26 to 11.66; I² = 54%), stroke (2 studies, 8873 participants): RR 0.76, 95% CI 0.56 to 1.03; I² = 0%), myocardial infarction (2 studies, 8873 participants): RR 1.00, 95% CI 0.84 to 1.20; I² = 0%), and adverse events (2 studies, 8873 participants): RR 1.33, 95% CI 1.26 to 1.41; I² = 0%). It is uncertain whether ACEi (benazepril 10 mg or trandolapril 2 mg) compared to placebo reduces congestive heart failure (1 study, 8290 participants): RR 0.75, 95% CI 0.59 to 0.95) or transient ischaemic attack (1 study, 583 participants): RR 0.94, 95% CI 0.06 to 15.01; I² = 0%) because the certainty of the evidence is very low. It is uncertain whether ARB (losartan 50 mg) compared to placebo (1 study, 226 participants) reduces: death (any-cause) (no events), adverse events (RR 19.34, 95% CI 1.14 to 328.30), eGFR rate of decline (MD 5.00 mL/min/1.73 m2, 95% CI 3.03 to 6.97), presence of proteinuria (MD -0.65 g/24 hours, 95% CI -0.78 to -0.52), systolic blood pressure (MD -0.80 mm Hg, 95% CI -3.89 to 2.29), or diastolic blood pressure (MD -1.10 mm Hg, 95% CI -3.29 to 1.09) because the certainty of the evidence is very low. It is uncertain whether ACEi (enalapril 20 mg, perindopril 2 mg or trandolapril 1 mg) compared to ARB (olmesartan 20 mg, losartan 25 mg or candesartan 4 mg) (1 study, 26 participants) reduces: proteinuria (MD -0.40, 95% CI -0.60 to -0.20), systolic blood pressure (MD -3.00 mm Hg, 95% CI -6.08 to 0.08) or diastolic blood pressure (MD -1.00 mm Hg, 95% CI -3.31 to 1.31) because the certainty of the evidence is very low. AUTHORS' CONCLUSIONS There is currently insufficient evidence to determine the effectiveness of ACEi or ARB in patients with stage 1 to 3 CKD who do not have DM. The available evidence is overall of very low certainty and high risk of bias. We have identified an area of large uncertainty for a group of patients who account for most of those diagnosed as having CKD.

#2613 dietary fiber intake, their sources and mortality in adults on hemodialysis: the diet-hd study

Abstract: Higher fiber intake is associated with lower cardiovascular and all-cause mortality in the general population, but their benefits and which sources of fiber are healthier in patients on hemodialysis are uncertain. Daily fiber intake (DFI) and their sources (vegetable and fruit, staple food and other sources) were ascertained by the Global Allergy and Asthma European Network food frequency questionnaire within the DIET-HD study, a multinational cohort study of adults on hemodialysis. Adjusted Cox regression analyses were conducted to evaluate the association of DFI and fiber sources (vegetable and fruit, staple foods, others[including dressing sauce etc.]) (both as tertiles and continuous) with all-cause and cardiovascular mortality. Estimates were calculated as hazard ratio (HR) with 95% confidence interval (CI). 8,110 patients were followed for median of 3.8 years (26,074 person-years). There were 2,953 deaths, of which 1160 cardiovascular-related. The median (interquartile range) DFI was 12.0 (8.1-17.5) gram per day and vegetables and fruits (49%) were the major source. Each unit increase in total DFI was not associated with either all-cause (hazard ratio [HR], 0.99; 95%CI:0.98-1.00, p = 0.37)or cardiovascular mortality (HR,0.99;95%CI:0.98-1.00, p = 0.08). Compared with patients in the lowest DFI tertiles (<9.5mg/day), the adjusted HRs for cardiovascular mortality among those in the middle (9.5-15.3 g/day) and highest tertiles (≥15.3 g/day) were respectively 0.97 [95% CI, 0.84-1. 13] and 0.79 (95%CI, 0.65-0.96) (P value per trend = 0.02). Each unit increase in fraction of DFI from vegetable and fruit was associated with lower all-cause (HR,0.70;95%CI: 0.57-0.86, p = 0.001) but not with cardiovascular mortality (HR,0.75;95%CI: 0.54-1.04, p = 0.08). Each unit increase in the fraction of DFI from other sources (including dressing sauce etc.) was associated with higher all-cause mortality (HR, 1.66; 95%CI, 1.22-2.27, p = 0.001) but not with cardiovascular mortality (HR, 1. 63; 95%CI, 0.83-2.24, p = 0.23). No association were observed between fiber from staple food and all-cause or cardiovascular mortality. Fiber intake in the hemodialysis population is low. A higher fiber intake from vegetable and fruit, and a lower fiber intake from other sources (including dressing sauce etc.) is associated with lower all-cause death.

Acetazolamide for metabolic alkalosis complicating respiratory failure with chronic obstructive pulmonary disease or obesity hypoventilation syndrome: a systematic review

Abstract: Background Metabolic alkalosis may lead to respiratory inhibition and increased need for ventilatory support or prolongation of weaning from ventilation for patients with chronic respiratory disease. Acetazolamide can reduce alkalaemia and may reduce respiratory depression. Methods We searched Medline, EMBASE and CENTRAL from inception to March 2022 for randomised controlled trials comparing acetazolamide to placebo in patients with chronic obstructive pulmonary disease, obesity hypoventilation syndrome or obstructive sleep apnoea, hospitalised with acute respiratory deterioration complicated by metabolic alkalosis. The primary outcome was mortality and we pooled data using random-effects meta-analysis. Risk of bias was assessed using the Cochrane RoB 2 (Risk of Bias 2) tool, heterogeneity was assessed using the I2 value and χ2 test for heterogeneity. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology. Results Four studies with 504 patients were included. 99% of included patients had chronic obstructive pulmonary disease. No trials recruited patients with obstructive sleep apnoea. 50% of trials recruited patients requiring mechanical ventilation. Risk of bias was overall low to some risk. There was no statistically significant difference with acetazolamide in mortality (relative risk 0.98 (95% CI 0.28 to 3.46); p=0.95; 490 participants; three studies; GRADE low certainty) or duration of ventilatory support (mean difference −0.8 days (95% CI −7.2 to 5.6); p=0.36; 427 participants; two studies; GRADE: low certainty). Conclusion Acetazolamide may have little impact on respiratory failure with metabolic alkalosis in patients with chronic respiratory diseases. However, clinically significant benefits or harms are unable to be excluded, and larger trials are required. PROSPERO registration number CRD42021278757.

Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: a network meta-analysis.

Abstract: BACKGROUND Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anaemia in people with chronic kidney disease (CKD). However, their use has been associated with cardiovascular events. This is an update of a Cochrane review first published in 2014. OBJECTIVES To compare the efficacy and safety of ESAs (epoetin alfa, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, and biosimilar ESAs against each other, placebo, or no treatment) to treat anaemia in adults with CKD. SEARCH METHODS In this update, we searched the Cochrane Kidney and Transplant Register of Studies up to 29 April 2022 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 Randomised controlled trials (RCTs) that included a comparison of an ESA (epoetin alfa, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, a biosimilar epoetin or a biosimilar darbepoetin alfa) with another ESA, placebo or no treatment in adults with CKD were considered for inclusion. DATA COLLECTION AND ANALYSIS Two independent authors screened the search results and extracted data. Data synthesis was performed using random-effects pairwise meta-analysis (expressed as odds ratios (OR) and their 95% confidence intervals (CI)) and network meta-analysis. We assessed for heterogeneity and inconsistency within meta-analyses using standard techniques and planned subgroup and meta-regression to explore sources of heterogeneity or inconsistency. We assessed certainty in treatment estimates for the primary outcomes (preventing blood transfusions and death (any cause)) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS Sixty-two new studies (9237 participants) were included in this update, so the review now includes 117 studies with 25,237 participants. Most studies were at high or unclear risk of bias in most methodological domains. Overall, results remain similar in this update compared to our previous review in 2014. For preventing blood transfusion, epoetin alfa (OR 0.28, 95% CI 0.13 to 0.61; low certainty evidence) and epoetin beta (OR 0.19, 95% CI 0.08 to 0.47; low certainty evidence) may be superior to placebo, and darbepoetin alfa was probably superior to placebo (OR 0.27, 95% CI 0.11 to 0.67; moderate certainty evidence). Methoxy polyethylene glycol-epoetin beta (OR 0.33, 95% CI 0.11 to 1.02; very low certainty evidence), a biosimilar epoetin (OR 0.34, 95% CI 0.11 to 1.03; very low certainty evidence) and a biosimilar darbepoetin alfa (OR 0.37, 95% CI 0.07 to 1.91; very low certainty evidence) had uncertain effects on preventing blood transfusion compared to placebo. The comparative effects of ESAs compared with another ESA on preventing blood transfusions were uncertain, in low to very low certainty evidence. Effects on death (any cause) were uncertain for epoetin alfa (OR 0.79, 95% CI 0.51 to 1.22; low certainty evidence), epoetin beta (OR 0.69, 95% CI 0.40 to 1.20; low certainty evidence), methoxy polyethylene glycol-epoetin beta (OR 1.07, 95% CI 0.67 to 1.71; very low certainty evidence), a biosimilar epoetin (OR 0.80, 95% CI 0.47 to 1.36; low certainty evidence) and a biosimilar darbepoetin alfa (OR 1.63, 95% CI 0.51 to 5.23; very low certainty evidence) compared to placebo. There was probably no difference between darbepoetin alfa and placebo on the odds of death (any cause) (OR 0.99, 95% CI 0.81 to 1.21; moderate certainty evidence). The comparative effects of ESAs compared with another ESA on death (any cause) were uncertain in low to very low certainty evidence. Epoetin beta probably increased the odds of hypertension when compared to placebo (OR 2.17, 95% CI 1.17 to 4.00; moderate certainty evidence). Compared to placebo, epoetin alfa (OR 2.10, 95% CI 1.22 to 3.59; very low certainty evidence), darbepoetin alfa (OR 1.88, 95% CI 1.12 to 3.14; low certainty evidence) and methoxy polyethylene glycol-epoetin beta (OR 1.98, 95% CI 1.05 to 3.74; low certainty evidence) may increase the odds of hypertension, but a biosimilar epoetin (OR 1.88, 95% CI 0.96 to 3.67; low certainty evidence) and biosimilar darbepoetin alfa (OR 1.98, 95% CI 0.84 to 4.66; low certainty evidence) had uncertain effects on hypertension. The comparative effects of all ESAs compared with another ESA, placebo or no treatment on cardiovascular death, myocardial infarction, stroke, vascular access thrombosis, kidney failure, and breathlessness were uncertain. Network analysis for fatigue was not possible due to sparse data. AUTHORS' CONCLUSIONS: The comparative effects of different ESAs on blood transfusions, death (any cause and cardiovascular), major cardiovascular events, myocardial infarction, stroke, vascular access thrombosis, kidney failure, fatigue and breathlessness were uncertain.

Clinical outcomes associated with drugs for obesity and overweight: A systematic review and network meta-analysis of randomized controlled trials.

Abstract: AIM To compare the benefits and harms of drugs approved for weight management in adults with obesity or overweight. MATERIALS AND METHODS We performed a systematic review of drugs approved for treating obesity and overweight. We searched MEDLINE, Embase and CENTRAL through 26 February 2023. Random-effects network meta-analysis was applied. RESULTS A total of 168 trials (97 938 patients) were included. There was no evidence that drugs approved for weight management had different associations with cardiovascular death (69 trials, 59 037 participants). Naltrexone/bupropion was associated with lower cardiovascular mortality than placebo (odds ratio [OR], 0.62 [95% CI: 0.39, 0.99]; low certainty evidence). All drugs were associated with greater weight loss at 12 months than placebo (33 trials, 37 616 participants), mainly semaglutide (mean difference [MD], -9.02 kg [95% CI: -10.42, -7.63]; moderate certainty) and phentermine/topiramate (MD, -8.10 kg [95% CI: -10.14, -6.05]; high certainty); and with greater waist circumference reduction at 12 months than placebo (24 trials, 35 733 participants), mainly semaglutide (MD, -7.84 cm [95% CI: -9.34, -6.34]; moderate certainty) and phentermine/topiramate (MD, -6.20 cm [95% CI: -7.46, -4.94]; high certainty). Semaglutide and phentermine/topiramate were associated with lower or no difference in the odds of treatment withdrawal compared with all other drugs (87 trials, 70 860 participants). CONCLUSIONS Among adults with obesity or overweight, semaglutide and phentermine/topiramate were associated with greater body weight loss and waist circumference reduction at 12 months than all other drugs, and lower or no significant difference in risks of withdrawal. There was no evidence that drugs approved for weight management had different associations with cardiovascular death.

Perspectives of Nephrologists on Gender Disparities in Access to Kidney Transplantation.

Abstract: BACKGROUND Gender disparities in access to kidney transplantation are apparent with women being up to 20% less likely to receive kidney transplant compared to men across different settings and socioeconomic backgrounds. We aimed to describe nephrologists' perspectives on gender disparities in access to kidney transplantation. METHODS Fifty-one nephrologists (55% women) from 22 countries participated in semi-structured interviews from October 2019 to April 2020. We analyzed the transcripts thematically. RESULTS We identified three themes: caregiving as a core role (coordinators of care for partners; fulfilling family duties over own health; maternal protectiveness; and inherent willingness and generosity), stereotyping and stigma (authority held by men in decision-making; protecting the breadwinner; preserving body image and appearance; and safeguard fertility), social disadvantage and vulnerability (limited information and awareness; coping alone and lack of support; disempowered by language barriers; lack of financial resources; and without access to transport). CONCLUSIONS Gender disparities in access to kidney transplantation are perceived by nephrologists to be exacerbated by gender norms and values, stigma and prejudice, and educational and financial disadvantage that are largely encountered by women compared with men across different socioeconomic settings.

Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes

Abstract: Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: This review aims to assess the benefits and harms of GLP‐1 receptor agonists to treat diabetes in people with CKD.