Calcium channel blockers for people with chronic kidney disease requiring dialysis.

Calcium channel blockers (CCBs) are used to manage hypertension which is highly prevalent among people with chronic kidney disease (CKD). The treatment for hypertension is particularly challenging in people undergoing dialysis. To assess the benefits and harms of calcium channel blockers in patients with chronic kidney disease requiring dialysis. We searched the Cochrane Kidney and Transplant Register of Studies to 27 April 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. All randomised controlled trials (RCTs) and quasi-RCTs that compared any type of CCB with other CCB, different doses of the same CCB, other antihypertensives, control or placebo were included. The minimum study duration was 12 weeks. Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random-effects model and results expressed as risk ratio (RR), risk difference (RD) or mean difference (MD) with 95% confidence intervals (CI). This review included 13 studies (24 reports) randomising 1459 participants treated with long-term haemodialysis. Nine studies were included in the meta-analysis (622 participants). No studies were performed in children or in those undergoing peritoneal dialysis. Overall, risk of bias was assessed as unclear to high across most domains. Random sequence generation and allocation concealment were at low risk of bias in eight and one studies, respectively. Two studies reported low risk methods for blinding of participants and investigators, and outcome assessment was blinded in 10 studies. Three studies were at low risk of attrition bias, eight studies were at low risk of selective reporting bias, and five studies were at low risk of other potential sources of bias. Overall, the certainty of the evidence was low to very low for all outcomes. No events were reported for cardiovascular death in any of the comparisons. Other side effects were rarely reported and studies were not designed to measure costs. Five studies (451 randomised adults) compared dihydropyridine CCBs to placebo or no treatment. Dihydropyridine CCBs may decrease predialysis systolic (1 study, 39 participants: MD -27.00 mmHg, 95% CI -43.33 to -10.67; low certainty evidence) and diastolic blood pressure level (2 studies, 76 participants; MD -13.56 mmHg, 95% CI -19.65 to -7.48; I2 = 0%, low certainty evidence) compared to placebo or no treatment. Dihydropyridine CCBs may make little or no difference to occurrence of intradialytic hypotension (2 studies, 287 participants; RR 0.54, 95% CI 0.25 to 1.15; I2 = 0%, low certainty evidence) compared to placebo or no treatment. Other side effects were not reported. Eight studies (1037 randomised adults) compared dihydropyridine CCBs to other antihypertensives. Dihydropyridine CCBs may make little or no difference to predialysis systolic (4 studies, 180 participants: MD 2.44 mmHg, 95% CI -3.74 to 8.62; I2 = 0%, low certainty evidence) and diastolic blood pressure (4 studies, 180 participants: MD 1.49 mmHg, 95% CI -2.23 to 5.21; I2 = 0%, low certainty evidence) compared to other antihypertensives. There was no evidence of a difference in the occurrence of intradialytic hypotension (1 study, 92 participants: RR 2.88, 95% CI 0.12 to 68.79; very low certainty evidence) between dihydropyridine CCBs to other antihypertensives. Other side effects were not reported. Dihydropyridine CCB may make little or no difference to predialysis systolic (1 study, 40 participants: MD -4 mmHg, 95% CI -11.99 to 3.99; low certainty evidence) and diastolic blood pressure (1 study, 40 participants: MD -3.00 mmHg, 95% CI -7.06 to 1.06; low certainty evidence) compared to non-dihydropyridine CCB. There was no evidence of a difference in other side effects (1 study, 40 participants: RR 0.13, 95% CI 0.01 to 2.36; very low certainty evidence) between dihydropyridine CCB and non-dihydropyridine CCB. Intradialytic hypotension was not reported. The benefits of CCBs over other antihypertensives on predialysis blood pressure levels and intradialytic hypotension among people with CKD who required haemodialysis were uncertain. Effects of CCBs on other side effects and cardiovascular death also remain uncertain. Dihydropyridine CCBs may decrease predialysis systolic and diastolic blood pressure level compared to placebo or no treatment. No studies were identified in children or peritoneal dialysis. Available studies have not been designed to measure the effects on costs. The shortcomings of the studies were that they recruited very few participants, had few events, had very short follow-up periods, some outcomes were not reported, and the reporting of outcomes such as changes in blood pressure was not done uniformly across studies. Well-designed RCTs, conducted in both adults and children with CKD requiring both haemodialysis and peritoneal dialysis, evaluating both dihydropyridine and non-dihydropyridine CCBs against other antihypertensives are required. Future research should be focused on outcomes relevant to patients (including death and cardiovascular disease), blood pressure changes, risk of side effects and healthcare costs to assist decision-making in clinical practice.

Mugendi GA ，Mutua FM ，Natale P ，Esterhuizen TM ，Strippoli GF ... -  《Cochrane Database of Systematic Reviews》

Antihypertensive treatment for kidney transplant recipients.

The comparative effects of specific blood pressure (BP) lowering treatments on patient-important outcomes following kidney transplantation are uncertain. Our 2009 Cochrane review found that calcium channel blockers (CCBs) improved graft function and prevented graft loss, while the evidence for other BP-lowering treatments was limited. This is an update of the 2009 Cochrane review. To compare the benefits and harms of different classes and combinations of antihypertensive drugs in kidney transplant recipients. We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 3 July 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. Randomised controlled trials (RCTs) and quasi-RCTs evaluating any BP-lowering agent in recipients of a functioning kidney transplant for at least two weeks were eligible. Two authors independently assessed the risks of bias and extracted data. Treatment estimates were summarised using the random-effects model and expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI). Evidence certainty was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) processes. The primary outcomes included all-cause death, graft loss, and kidney function. Ninety-seven studies (8706 participants) were included. One study evaluated treatment in children. The overall risk of bias was unclear to high across all domains. Compared to placebo or standard care alone, CCBs probably reduce all-cause death (23 studies, 3327 participants: RR 0.83, 95% CI 0.72 to 0.95; I2 = 0%; moderate certainty evidence) and graft loss (24 studies, 3577 participants: RR 0.84, 95% CI 0.75 to 0.95; I2 = 0%; moderate certainty evidence). CCBs may make little or no difference to estimated glomerular filtration rate (eGFR) (11 studies, 2250 participants: MD 1.89 mL/min/1.73 m2, 95% CI -0.70 to 4.48; I2 = 48%; low certainty evidence) and acute rejection (13 studies, 906 participants: RR 10.8, 95% CI 0.85 to 1.35; I2 = 0%; moderate certainty evidence). CCBs may reduce systolic BP (SBP) (3 studies, 329 participants: MD -5.83 mm Hg, 95% CI -10.24 to -1.42; I2 = 13%; low certainty evidence) and diastolic BP (DBP) (3 studies, 329 participants: MD -3.98 mm Hg, 95% CI -5.98 to -1.99; I2 = 0%; low certainty evidence). CCBs have uncertain effects on proteinuria. Compared to placebo or standard care alone, angiotensin-converting-enzyme inhibitors (ACEi) may make little or no difference to all-cause death (7 studies, 702 participants: RR 1.13, 95% CI 0.58 to 2.21; I2 = 0%; low certainty evidence), graft loss (6 studies, 718 participants: RR 0.75, 95% CI 0.49 to 1.13; I2 = 0%; low certainty evidence), eGFR (4 studies, 509 participants: MD -2.46 mL/min/1.73 m2, 95% CI -7.66 to 2.73; I2 = 64%; low certainty evidence) and acute rejection (4 studies, 388 participants: RR 1.75, 95% CI 0.76 to 4.04; I2 = 0%; low certainty evidence). ACEi may reduce proteinuria (5 studies, 441 participants: MD -0.33 g/24 hours, 95% CI -0.64 to -0.01; I2 = 67%; low certainty evidence) but had uncertain effects on SBP and DBP. Compared to placebo or standard care alone, angiotensin receptor blockers (ARB) may make little or no difference to all-cause death (6 studies, 1041 participants: RR 0.69, 95% CI 0.36 to 1.31; I2 = 0%; low certainty evidence), eGRF (5 studies, 300 participants: MD -1.91 mL/min/1.73 m2, 95% CI -6.20 to 2.38; I2 = 57%; low certainty evidence), and acute rejection (4 studies, 323 participants: RR 1.00, 95% CI 0.44 to 2.29; I2 = 0%; low certainty evidence). ARBs may reduce graft loss (6 studies, 892 participants: RR 0.35, 95% CI 0.15 to 0.84; I2 = 0%; low certainty evidence), SBP (10 studies, 1239 participants: MD -3.73 mm Hg, 95% CI -7.02 to -0.44; I2 = 63%; moderate certainty evidence) and DBP (9 studies, 1086 participants: MD -2.75 mm Hg, 95% CI -4.32 to -1.18; I2 = 47%; moderate certainty evidence), but has uncertain effects on proteinuria. The effects of CCBs, ACEi or ARB compared to placebo or standard care alone on cardiovascular outcomes (including fatal or nonfatal myocardial infarction, fatal or nonfatal stroke) or other adverse events were uncertain. The comparative effects of ACEi plus ARB dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone were rarely evaluated. Head-to-head comparisons of ACEi, ARB or thiazide versus CCB, ACEi versus ARB, CCB or ACEi versus alpha- or beta-blockers, or ACEi plus CCB dual therapy versus ACEi or CCB monotherapy were scarce. No studies reported outcome data for cancer or life participation. For kidney transplant recipients, the use of CCB therapy to reduce BP probably reduces death and graft loss compared to placebo or standard care alone, while ARB may reduce graft loss. The effects of ACEi and ARB compared to placebo or standard care on other patient-centred outcomes were uncertain. The effects of dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone and the comparative effects of different treatments were uncertain.

Natale P ，Mooi PK ，Palmer SC ，Cross NB ，Cooper TE ，Webster AC ，Masson P ，Craig JC ，Strippoli GF ... -  《Cochrane Database of Systematic Reviews》

Potassium binders for chronic hyperkalaemia in people with chronic kidney disease.

Hyperkalaemia is a common electrolyte abnormality caused by reduced renal potassium excretion in patients with chronic kidney diseases (CKD). Potassium binders, such as sodium polystyrene sulfonate and calcium polystyrene sulfonate, are widely used but may lead to constipation and other adverse gastrointestinal (GI) symptoms, reducing their tolerability. Patiromer and sodium zirconium cyclosilicate are newer ion exchange resins for treatment of hyperkalaemia which may cause fewer GI side-effects. Although more recent studies are focusing on clinically-relevant endpoints such as cardiac complications or death, the evidence on safety is still limited. Given the recent expansion in the available treatment options, it is appropriate to review the evidence of effectiveness and tolerability of all potassium exchange resins among people with CKD, with the aim to provide guidance to consumers, practitioners, and policy-makers. To assess the benefits and harms of potassium binders for treating chronic hyperkalaemia among adults and children with CKD. We searched the Cochrane Kidney and Transplant Register of Studies up to 10 March 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. Randomised controlled trials (RCTs) and quasi-randomised controlled studies (quasi-RCTs) evaluating potassium binders for chronic hyperkalaemia administered in adults and children with CKD. Two authors independently assessed risks of bias and extracted data. Treatment estimates were summarised by random effects meta-analysis and expressed as relative risk (RR) or mean difference (MD), with 95% confidence interval (CI). Evidence certainty was assessed using GRADE processes. Fifteen studies, randomising 1849 adult participants were eligible for inclusion. Twelve studies involved participants with CKD (stages 1 to 5) not requiring dialysis and three studies were among participants treated with haemodialysis. Potassium binders included calcium polystyrene sulfonate, sodium polystyrene sulfonate, patiromer, and sodium zirconium cyclosilicate. A range of routes, doses, and timing of drug administration were used. Study duration varied from 12 hours to 52 weeks (median 4 weeks). Three were cross-over studies. The mean study age ranged from 53.1 years to 73 years. No studies evaluated treatment in children. Some studies had methodological domains that were at high or unclear risks of bias, leading to low certainty in the results. Studies were not designed to measure treatment effects on cardiac arrhythmias or major GI symptoms. Ten studies (1367 randomised participants) compared a potassium binder to placebo. The certainty of the evidence was low for all outcomes. We categorised treatments in newer agents (patiromer or sodium zirconium cyclosilicate) and older agents (calcium polystyrene sulfonate and sodium polystyrene sulfonate). Patiromer or sodium zirconium cyclosilicate may make little or no difference to death (any cause) (4 studies, 688 participants: RR 0.69, 95% CI 0.11, 4.32; I2 = 0%; low certainty evidence) in CKD. The treatment effect of older potassium binders on death (any cause) was unknown. One cardiovascular death was reported with potassium binder in one study, showing that there was no difference between patiromer or sodium zirconium cyclosilicate and placebo for cardiovascular death in CKD and HD. There was no evidence of a difference between patiromer or sodium zirconium cyclosilicate and placebo for health-related quality of life (HRQoL) at the end of treatment (one study) in CKD or HD. Potassium binders had uncertain effects on nausea (3 studies, 229 participants: RR 2.10, 95% CI 0.65, 6.78; I2 = 0%; low certainty evidence), diarrhoea (5 studies, 720 participants: RR 0.84, 95% CI 0.47, 1.48; I2 = 0%; low certainty evidence), and vomiting (2 studies, 122 participants: RR 1.72, 95% CI 0.35 to 8.51; I2 = 0%; low certainty evidence) in CKD. Potassium binders may lower serum potassium levels (at the end of treatment) (3 studies, 277 participants: MD -0.62 mEq/L, 95% CI -0.97, -0.27; I2 = 92%; low certainty evidence) in CKD and HD. Potassium binders had uncertain effects on constipation (4 studies, 425 participants: RR 1.58, 95% CI 0.71, 3.52; I2 = 0%; low certainty evidence) in CKD. Potassium binders may decrease systolic blood pressure (BP) (2 studies, 369 participants: MD -3.73 mmHg, 95%CI -6.64 to -0.83; I2 = 79%; low certainty evidence) and diastolic BP (one study) at the end of the treatment. No study reported outcome data for cardiac arrhythmias or major GI events. Calcium polystyrene sulfonate may make little or no difference to serum potassium levels at end of treatment, compared to sodium polystyrene sulfonate (2 studies, 117 participants: MD 0.38 mEq/L, 95% CI -0.03 to 0.79; I2 = 42%, low certainty evidence). There was no evidence of a difference in systolic BP (one study), diastolic BP (one study), or constipation (one study) between calcium polystyrene sulfonate and sodium polystyrene sulfonate. There was no difference between high-dose and low-dose patiromer for death (sudden death) (one study), stroke (one study), myocardial infarction (one study), or constipation (one study). The comparative effects whether potassium binders were administered with or without food, laxatives, or sorbitol, were very uncertain with insufficient data to perform meta-analysis. Evidence supporting clinical decision-making for different potassium binders to treat chronic hyperkalaemia in adults with CKD is of low certainty; no studies were identified in children. Available studies have not been designed to measure treatment effects on clinical outcomes such as cardiac arrhythmias or major GI symptoms. This review suggests the need for a large, adequately powered study of potassium binders versus placebo that assesses clinical outcomes of relevance to patients, clinicians and policy-makers. This data could be used to assess cost-effectiveness, given the lack of definitive studies and the clinical importance of potassium binders for chronic hyperkalaemia in people with CKD.

Natale P ，Palmer SC ，Ruospo M ，Saglimbene VM ，Strippoli GF ... -  《Cochrane Database of Systematic Reviews》

Low dialysate sodium levels for chronic haemodialysis.

Dunlop JL ，Vandal AC ，Marshall MR 《Cochrane Database of Systematic Reviews》

Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD).

Ruospo M ，Palmer SC ，Natale P ，Craig JC ，Vecchio M ，Elder GJ ，Strippoli GF ... -  《Cochrane Database of Systematic Reviews》