Marinella Ruospo

Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis

BACKGROUND The comparative efficacy and safety of pharmacological agents to lower blood pressure in adults with diabetes and kidney disease remains controversial. We aimed to investigate the benefits and harms of blood pressure-lowering drugs in this population of patients. METHODS We did a network meta-analysis of randomised trials from around the world comparing blood pressure-lowering agents in adults with diabetic kidney disease. Electronic databases (the Cochrane Collaboration, Medline, and Embase) were searched systematically up to January, 2014, for trials in adults with diabetes and kidney disease comparing orally administered blood pressure-lowering drugs. Primary outcomes were all-cause mortality and end-stage kidney disease. We also assessed secondary safety and cardiovascular outcomes. We did random-effects network meta-analysis to obtain estimates for primary and secondary outcomes and we presented these estimates as odds ratios or standardised mean differences with 95% CIs. We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking (SUCRA) probabilities. FINDINGS 157 studies comprising 43,256 participants, mostly with type 2 diabetes and chronic kidney disease, were included in the network meta-analysis. No drug regimen was more effective than placebo for reducing all-cause mortality. However, compared with placebo, end-stage renal disease was significantly less likely after dual treatment with an angiotensin-receptor blocker (ARB) and an angiotensin-converting-enzyme (ACE) inhibitor (odds ratio 0·62, 95% CI 0·43-0·90) and after ARB monotherapy (0·77, 0·65-0·92). No regimen significantly increased hyperkalaemia or acute kidney injury, although combined ACE inhibitor and ARB treatment had the lowest rank among all interventions because of borderline increases in estimated risks of these harms (odds ratio 2·69, 95% CI 0·97-7·47 for hyperkalaemia; 2·69, 0·98-7·38 for acute kidney injury). INTERPRETATION No blood pressure-lowering strategy prolonged survival in adults with diabetes and kidney disease. ACE inhibitors and ARBs, alone or in combination, were the most effective strategies against end-stage kidney disease. Any benefits of combined ACE inhibitor and ARB treatment need to be balanced against potential harms of hyperkalaemia and acute kidney injury. FUNDING Canterbury Medical Research Foundation, Italian Medicines Agency.

Prevalence and Correlates of Self-Reported Sexual Dysfunction in CKD: A Meta-analysis of Observational Studies

BACKGROUND Sexual dysfunction is an under-recognized problem in men and women with chronic kidney disease (CKD). The prevalence, correlates, and predictors of this condition in patients with CKD have not been evaluated comprehensively. STUDY DESIGN Systematic review and meta-analysis. SETTING & POPULATION Patients treated using dialysis (dialysis patients), patients treated using transplant (transplant recipients), and patients with CKD not treated using dialysis or transplant (nondialysis nontransplant patients with CKD). SELECTION CRITERIA FOR STUDIES Observational studies conducted in patients with CKD only or including a control group without CKD. PREDICTOR Type of study population. OUTCOMES Sexual dysfunction in men and women with CKD using validated tools, such as the International Index of Erectile Function, the Female Sexual Function Index (FSFI), or other measures as reported by study investigators. RESULTS 50 studies (8,343 patients) of variable size (range, 16-1,023 patients) were included in this review. Almost all studies explored sexual dysfunction in men and specifically erectile dysfunction. The summary estimate of erectile dysfunction in men with CKD was 70% (95% CI, 62%-77%; 21 studies, 4,389 patients). Differences in reported prevalence rates of erectile dysfunction between different studies were attributable primarily to age, study populations, and type of study tool used to assess the presence of erectile dysfunction. In women, the reported prevalence of sexual dysfunction was assessed in only 306 patients from 2 studies and ranged from 30%-80%. Compared with the general population, women with CKD had a significantly lower overall FSFI score (8 studies or subgroups, 407 patients; mean difference, -9.28; 95% CI, -12.92 to -5.64). Increasing age, diabetes mellitus, and depression consistently were found to correlate with sexual dysfunction in 20 individual studies of patients with CKD using different methods. LIMITATIONS Suboptimal and lack of uniform assessment of outcome measures. CONCLUSIONS Sexual dysfunction is highly prevalent in both men and women with CKD, especially among those on dialysis. Larger studies enrolling different ethnic groups, using validated study tools, and analyzing the influence of various factors on the development of sexual dysfunction are needed.

Prevalence and severity of oral disease in adults with chronic kidney disease: a systematic review of observational studies

BACKGROUND Oral disease may be increased in people with chronic kidney disease (CKD) and, due to associations with inflammation and malnutrition, represents a potential modifiable risk factor for cardiovascular disease and mortality. We summarized the prevalence of oral disease in adults with CKD and explored any association between oral disease and mortality. METHODS We used systematic review of observational studies evaluating oral health in adults with CKD identified in MEDLINE (through September 2012) without language restriction. We summarized prevalence and associations with all-cause and cardiovascular mortality using random-effects meta-analysis. We explored for sources of heterogeneity between studies using meta-regression. RESULTS Eighty-eight studies in 125 populations comprising 11 340 adults were eligible. Edentulism affected one in five adults with CKD Stage 5D (dialysis) {20.6% [95% confidence interval (CI), 16.4-25.6]}. Periodontitis was more common in CKD Stage 5D [56.8% (CI, 39.3-72.8)] than less severe CKD [31.6% (CI, 19.0-47.6)], although data linking periodontitis with premature death were scant. One-quarter of patients with CKD Stage 5D reported never brushing their teeth [25.6% (CI, 10.2-51.1)] and a minority used dental floss [11.4% (CI, 6.2-19.8)]; oral pain was reported by one-sixth [18.7% (CI, 8.8-35.4)], while half of patients experienced a dry mouth [48.4% (CI, 37.5-59.5)]. Data for kidney transplant recipients and CKD Stages 1-5 were limited. CONCLUSIONS Oral disease is common in adults with CKD, potentially reflects low use of preventative dental services, and may be an important determinant of health in this clinical setting.

Phosphate-Binding Agents in Adults With CKD: A Network Meta-analysis of Randomized Trials

BACKGROUND Guidelines preferentially recommend noncalcium phosphate binders in adults with chronic kidney disease (CKD). We compare and rank phosphate-binder strategies for CKD. STUDY DESIGN Network meta-analysis. SETTING & POPULATION Adults with CKD. SELECTION CRITERIA FOR STUDIES Randomized trials with allocation to phosphate binders. INTERVENTIONS Sevelamer, lanthanum, iron, calcium, colestilan, bixalomer, nicotinic acid, and magnesium. OUTCOMES The primary outcome was all-cause mortality. Additional outcomes were cardiovascular mortality, myocardial infarction, stroke, adverse events, serum phosphorus and calcium levels, and coronary artery calcification. RESULTS 77 trials (12,562 participants) were included. Most (62 trials in 11,009 patients) studies were performed in a dialysis population. Trials were generally of short duration (median, 6 months) and had high risks of bias. All-cause mortality was ascertained in 20 studies during 86,744 patient-months of follow-up. There was no evidence that any drug class lowered mortality or cardiovascular events when compared to placebo. Compared to calcium, sevelamer reduced all-cause mortality (OR, 0.39; 95% CI, 0.21-0.74), whereas treatment effects of lanthanum, iron, and colestilan were not significant (ORs of 0.78 [95% CI, 0.16-3.72], 0.37 [95% CI, 0.09-1.60], and 0.55 [95% CI, 0.07-4.43], respectively). Lanthanum caused nausea, whereas sevelamer posed the highest risk for constipation and iron caused diarrhea. All phosphate binders lowered serum phosphorus levels to a greater extent than placebo, with iron ranked as the best treatment. Sevelamer and lanthanum posed substantially lower risks for hypercalcemia than calcium. LIMITATIONS Limited testing of consistency; short follow-up. CONCLUSIONS There is currently no evidence that phosphate-binder treatment reduces mortality compared to placebo in adults with CKD. It is not clear whether the higher mortality with calcium versus sevelamer reflects whether there is net harm associated with calcium, net benefit with sevelamer, both, or neither. Iron-based binders show evidence of greater phosphate lowering that warrants further examination in randomized trials.

Treatment Options for Sexual Dysfunction in Patients with Chronic Kidney Disease: A Systematic Review of Randomized Controlled Trials

BACKGROUND AND OBJECTIVES Sexual dysfunction is very common in patients with chronic kidney disease (CKD), but treatment options are limited. The benefits and harms of existing interventions for treatment of sexual dysfunction were assessed in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS MEDLINE (1966 to December 2008), EMBASE (1980 to December 2008), and the Cochrane Trial Registry (Issue 4 2008) were searched for parallel and crossover randomized and quasi-randomized trials. Treatment effects were summarized as mean differences (MD) or standardized mean difference (SMD) with 95% confidence intervals (CI) using a random effects model. RESULTS Fourteen trials (328 patients) were included. Phosphodiesterase-5 inhibitors (PDE5i) compared with placebo significantly increased the overall International Index of Erectile Function-5 (IIEF-5) score (three trials, 101 patients, MD 1.81, 95% CI 1.51 to 2.10), all of its individual domains, and the complete 15-item IIEF-5 (two trials, 80 patients, MD 10.64, 95% CI 5.32 to 15.96). End-of-treatment testosterone levels were not significantly increased by addition of zinc to dialysate (two trials, 22 patients, SMD 0.19 ng/dl, 95% CI -2.12 to 2.50), but oral zinc improved end-of-treatment testosterone levels. There was no difference in plasma luteinizing and follicle-stimulating hormone level at the end of the study period with zinc therapy. CONCLUSIONS PDE5i and zinc are promising interventions for treating sexual dysfunction in CKD. Evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for male and female sexual dysfunction in CKD considering the significant disease burden.

The beliefs and expectations of patients and caregivers about home haemodialysis: an interview study

Objectives To explore the beliefs and expectations of patients and their caregivers about home haemodialysis in Italy where the prevalence of home haemodialysis is low. Design Semistructured, qualitative interview study with purposive sampling and thematic analysis. Setting Four dialysis centres in Italy without home haemodialysis services (Bari, Marsala, Nissoria and Taranto). Participants 22 patients receiving in-centre haemodialysis and 20 of their identified caregivers. Results We identified seven major themes that were central to patient and caregiver perceptions of home haemodialysis in regions without established services. Three positive themes were: flexibility and freedom (increased autonomy, minimised wasted time, liberation from strict dialysis schedules and gaining self-worth); comfort in familiar surroundings (family presence and support, avoiding the need for dialysis in hospital) and altruistic motivation to do home haemodialysis as an exemplar for other patients and families. Four negative themes were: disrupting sense of normality; family burden (an onerous responsibility, caregiver uncertainty and panic and visually confronting); housing constraints; healthcare by ‘professionals’ not ‘amateurs’ (relinquishing security and satisfaction with in-centre services) and isolation from peer support. Conclusions Patients without direct experience or previous education about home haemodialysis and their caregivers recognise the autonomy of home haemodialysis but are very concerned about the potential burden and personal sacrifice home haemodialysis will impose on caregivers and feel apprehensive about accepting the medical responsibilities of dialysis. To promote acceptance and uptake of home haemodialysis among patients and caregivers who have no experience of home dialysis, effective strategies are needed that provide information about home haemodialysis to patients and their caregivers, assure access to caregiver respite, provide continuous availability of medical and technical advice and facilitate peer patient support.

Healthy Dietary Patterns and Risk of Mortality and ESRD in CKD: A Meta-Analysis of Cohort Studies

BACKGROUND AND OBJECTIVES Patients with CKD are advised to follow dietary recommendations that restrict individual nutrients. Emerging evidence indicates overall eating patterns may better predict clinical outcomes, however, current data on dietary patterns in kidney disease are limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This systematic review aimed to evaluate the association between dietary patterns and mortality or ESRD among adults with CKD. Medline, Embase, and reference lists were systematically searched up to November 24, 2015 by two independent review authors. Eligible studies were longitudinal cohort studies reporting the association of dietary patterns with mortality, cardiovascular events, or ESRD. RESULTS A total of seven studies involving 15,285 participants were included. Healthy dietary patterns were generally higher in fruit and vegetables, fish, legumes, cereals, whole grains, and fiber, and lower in red meat, salt, and refined sugars. In six studies, healthy dietary patterns were consistently associated with lower mortality (3983 events; adjusted relative risk, 0.73; 95% confidence interval, 0.63 to 0.83; risk difference of 46 fewer (29-63 fewer) events per 1000 people over 5 years). There was no statistically significant association between healthy dietary patterns and risk of ESRD (1027 events; adjusted relative risk, 1.04; 95% confidence interval, 0.68 to 1.40). CONCLUSIONS Healthy dietary patterns are associated with lower mortality in people with kidney disease. Interventions to support adherence to increased fruit and vegetable, fish, legume, whole grain, and fiber intake, and reduced red meat, sodium, and refined sugar intake could be effective tools to lower mortality in people with kidney disease.

Prevalence and correlates of erectile dysfunction in men on chronic haemodialysis: a multinational cross-sectional study

BACKGROUND Factors associated with erectile dysfunction in men on haemodialysis are incompletely identified due to suboptimal existing studies. We determined the prevalence and correlates of erectile dysfunction and identified combinations of clinical characteristics associated with a higher risk of erectile dysfunction using recursive partitioning and amalgamation (REPCAM) analysis. METHODS We conducted a multinational cross-sectional study in men on haemodialysis within a collaborative network. Erectile dysfunction and depressive symptoms were evaluated using the erectile function domain of the International Index of Erectile Function questionnaire and the Center for Epidemiological Studies-Depression Scale, respectively. RESULTS Nine hundred and forty-six (59%) of 1611 eligible men provided complete data for erectile dysfunction. Eighty-three per cent reported erectile dysfunction and 47% reported severe erectile dysfunction. Four per cent of those with erectile dysfunction were receiving pharmacological treatment. Depressive symptoms were the strongest correlate of erectile dysfunction [adjusted odds ratio 2.41 (95% confidence interval (CI) 1.57-3.71)]. Erectile dysfunction was also associated with age (1.06, 1.05-1.08), being unemployed (1.80, 1.17-2.79) or receiving a pension (2.05, 1.14-3.69) and interdialytic weight gain (1.9-2.87 kg, 1.92 [CI 1.19-3.09]; >2.87 kg, 1.57 [CI 1.00-2.45]). Married men had a lower risk of erectile dysfunction (0.49, 0.31-0.76). The prevalence of erectile dysfunction was highest (94%) in unmarried and unemployed or retired men who have depressive symptoms. CONCLUSIONS Most men on haemodialysis experience erectile dysfunction and are untreated. Given the prevalence of this condition and the relative lack of efficacy data for pharmacological agents, we suggest that large trials of pharmacological and non-pharmacological interventions for erectile dysfunction and depression are needed.

Risk factors for foot ulceration and lower extremity amputation in adults with end-stage renal disease on dialysis: a systematic review and meta-analysis

BACKGROUND Adults with end-stage renal disease are at increased risk of foot ulceration and lower extremity amputation. However, the central determinants of lower limb injury and loss are incompletely understood. METHODS We conducted a systematic review of non-randomized studies that quantified the major risk factors for foot ulceration and amputation in adults treated with dialysis and analysed patient populations in which risks were greatest. Random-effects meta-analysis was used to generate summary estimates. RESULTS Thirty studies (48 566 participants) were identified. Risk factors for foot ulceration and amputation included previous foot ulceration (odds ratios, OR, 17.56 and 70.13), peripheral arterial disease (OR, 7.52 and 9.12), diabetes (OR, 3.76 and 7.48), peripheral neuropathy (OR, 3.24 and 3.36) and coronary artery disease (OR, 3.92 and 2.49). Participants with foot ulceration or amputation had experienced a longer duration of diabetes (mean difference, MD, 4.04 and 6.07 years) and had lower serum albumin levels (MD, -0.23 and -0.13 g/dL). Risk factors for foot ulceration also included retinopathy (OR, 3.03), previous amputation (OR, 15.50) and higher serum phosphorus levels (MD, 0.40 mg/dL), while risk factors for amputation also included male sex (OR, 1.50), current smoking (OR, 2.26) and higher glycated haemoglobin levels (MD, 0.75%). CONCLUSIONS Dialysis patients who have markedly higher risks of ulceration or amputation include those with previous foot ulceration or amputation, peripheral neuropathy, diabetes or macrovascular disease. The temporal relationship between these risk factors and the development of foot ulceration and/or limb loss is uncertain and requires further study. Stable estimates of the key risk factors for ulceration and amputation can inform the design of future trials investigating clinical interventions to reduce the burden of lower limb disease in the dialysis population.

Chromoendoscopy for Surveillance in Ulcerative Colitis and Crohn’s Disease: A Systematic Review of Randomized Trials

BACKGROUND & AIMS: Key international guideline agencies recommend dysplasia surveillance in inflammatory bowel diseases with chromoendoscopy. We performed a systematic review of randomized trials comparing chromoendoscopy vs other endoscopic techniques for dysplasia surveillance in inflammatory bowel diseases. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for relevant studies published through September 2016. We estimated risk ratios (RRs) for dichotomous outcomes (all‐cause/colorectal cancer‐related mortality, time to interval cancer, patients with dysplasia, total/subtypes of dysplastic lesions, dysplasia detected by targeted biopsies, adverse events), mean differences for continuous outcomes (procedural time, costs, total/targeted biopsies), and their 95% confidence intervals (CIs) using a random‐effects model. Subgroup analyses included technique compared with chromoendoscopy, type of disease, and type of dye. We estimated sensitivity and specificity of the techniques with reference to histology. RESULTS: We identified 10 randomized trials (n = 1500 participants). There was a higher likelihood of detecting patients with dysplasia with chromoendoscopy compared with other techniques (RR, 1.37; 95% CI, 1.04–1.79). Subgroup analyses confirmed this effect only if chromoendoscopy was compared with standard‐definition white‐light endoscopy (RR, 2.12; 95% CI, 1.15–3.91). Chromoendoscopy required a significantly longer procedural time compared with other techniques (mean difference, 8.91 min; 95% CI, 1.37–16.45). There was no difference in the likelihood of detecting dysplastic subtypes and dysplasia by targeted biopsies between groups. Test sensitivity and specificity were similar between groups. CONCLUSIONS: In surveillance of inflammatory bowel diseases, chromoendoscopy identifies more patients with dysplasia only when compared with standard‐definition white‐light endoscopy. It is associated with longer procedural time with no direct evidence of effect on preventing all‐cause/cancer‐specific mortality or time to interval cancer.