Concern regarding technique failure is a major barrier to increased uptake of peritoneal dialysis (PD), and the first year of therapy is a particularly vulnerable time.
A cohort study using ...competing-risk regression analyses to identify the key risk factors and risk periods for early transfer to hemodialysis therapy or death in incident PD patients.
All adult patients who initiated PD therapy in Australia and New Zealand in 2000 through 2014.
Patient demographics and comorbid conditions, duration of prior renal replacement therapy, timing of referral, PD modality, dialysis era, and center size.
Technique failure within the first year, defined as transfer to hemodialysis therapy for more than 30 days or death.
Of 16,748 patients included in the study, 4,389 developed early technique failure. Factors associated with increased risk included age older than 70 years, diabetes or vascular disease, prior renal replacement therapy, late referral to a nephrology service, or management in a smaller center. Asian or other race and use of continuous ambulatory PD were associated with reduced risk, as was initiation of PD therapy in 2010 through 2014. Although the risk for technique failure due to death or infection was constant during the first year, mechanical and other causes accounted for a greater number of cases within the initial 9 months of treatment.
Potential for residual confounding due to limited data for residual kidney function, dialysis prescription, and socioeconomic factors.
Several modifiable and nonmodifiable factors are associated with early technique failure in PD. Targeted interventions should be considered in high-risk patients to avoid the consequences of an unplanned transfer to hemodialysis therapy or death.
Background
The outcomes of patients with focal segmental glomerulosclerosis (FSGS) on kidney replacement therapy (KRT) have not been well described. This study evaluated the outcomes of patients with ...kidney failure due to FSGS on KRT including dialysis and kidney transplantation.
Method and materials
All adult patients with kidney failure who commenced KRT in Australia and New Zealand from 15
th
of May 1963 to 31
st
of December 2018 were retrospectively extracted from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Outcomes of patients with FSGS were compared to those with other causes of kidney failure (non-FSGS).
Results
85,052 patients commenced KRT during the study period, of whom 2991 (3.5%) were patients with FSGS. Compared to patients with non-FSGS, patients with FSGS experienced similar mortality on dialysis (adjusted hazard ratio aHR 0.98, 95% CI 0.90–1.06, p = 0.55) and following kidney transplantation (aHR 0.92, 95% CI 0.73–1.15, p = 0.47). The risk of first kidney allograft loss was higher in patients with FSGS (aHR 1.20, 95% CI 1.04–1.37, p = 0.01). However, when death was analysed as a competing risk, the survival in both groups was similar (sub-hazard ratio SHR 1.09, 95% CI 0.94–1.28, p = 0.26). Patients with FSGS had a longer waiting time for kidney transplantation (aHR 0.92, 95% CI 0.86–0.98, p = 0.02) and experienced an increased risk of disease recurrence in the allograft (aHR 1.73, 95% CI 1.35–2.21, p<0.001). Compared to patients with other forms of glomerular disease, patients with FSGS experienced similar dialysis and transplant patient survival and death-censored rate of kidney transplantation and allograft loss but higher rates of primary kidney disease recurrence.
Conclusion
FSGS was associated with similar dialysis and transplant patient survival and death-censored first allograft loss compared to non-FSGS and other forms of glomerular disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AbstractObjectiveTo evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and ...renal risk.DesignNetwork meta-analysis.Data sourcesMedline, Embase, and Cochrane CENTRAL up to 11 August 2020.Eligibility criteria for selecting studiesRandomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias.Main outcome measuresFrequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review.Results764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 3 to 40 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes.ConclusionsIn patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with some differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review.Systematic review registrationPROSPERO CRD42019153180.
IMPORTANCE: Numerous glucose-lowering drugs are used to treat type 2 diabetes. OBJECTIVE: To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin. DATA ...SOURCES: Cochrane Library Central Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016. STUDY SELECTION: Randomized clinical trials of 24 weeks’ or longer duration. DATA EXTRACTION AND SYNTHESIS: Random-effects network meta-analysis. MAIN OUTCOMES AND MEASURES: The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight. RESULTS: A total of 301 clinical trials (1 417 367 patient-months) were included; 177 trials (56 598 patients) of drugs given as monotherapy; 109 trials (53 030 patients) of drugs added to metformin (dual therapy); and 29 trials (10 598 patients) of drugs added to metformin and sulfonylurea (triple therapy). There were no significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality. Compared with metformin, sulfonylurea (standardized mean difference SMD, 0.18 95% CI, 0.01 to 0.34), thiazolidinedione (SMD, 0.16 95% CI, 0.00 to 0.31), DPP-4 inhibitor (SMD, 0.33 95% CI, 0.13 to 0.52), and α-glucosidase inhibitor (SMD, 0.35 95% CI, 0.12 to 0.58) monotherapy were associated with higher HbA1C levels. Sulfonylurea (odds ratio OR, 3.13 95% CI, 2.39 to 4.12; risk difference RD, 10% 95% CI, 7% to 13%) and basal insulin (OR, 17.9 95% CI, 1.97 to 162; RD, 10% 95% CI, 0.08% to 20%) were associated with greatest odds of hypoglycemia. When added to metformin, drugs were associated with similar HbA1C levels, while SGLT-2 inhibitors offered the lowest odds of hypoglycemia (OR, 0.12 95% CI, 0.08 to 0.18; RD, −22% −27% to −18%). When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60 95% CI, 0.39 to 0.94; RD, −10% 95% CI, −18% to −2%). CONCLUSIONS AND RELEVANCE: Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality. Metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug classes. All drugs were estimated to be effective when added to metformin. These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations.
Background
Biocompatible peritoneal dialysis (PD) solutions, including neutral pH, low glucose degradation product (GDP) solutions and icodextrin, have previously been shown to favourably influence ...some patient‐level outcomes, albeit based on generally sub‐optimal quality studies. Several additional randomised controlled trials (RCT) evaluating biocompatible solutions in PD patients have been published recently. This is an update of a review first published in 2014.
Objectives
This review aimed to look at the benefits and harms of biocompatible PD solutions in comparison to standard PD solutions in patients receiving PD.
Search methods
The Cochrane Kidney and Transplant Specialised Register was searched up to 12 February 2018 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 Search Portal and ClinicalTrials.gov.
Selection criteria
All RCTs and quasi‐RCTs in adults and children comparing the effects of biocompatible PD solutions (neutral pH, lactate‐buffered, low GDP; neutral pH, bicarbonate(± lactate)‐buffered, low GDP; glucose polymer (icodextrin)) in PD were included. Studies of amino acid‐based solutions were excluded.
Data collection and analysis
Two authors extracted data on study quality and outcomes. Summary effect estimates were obtained using a random‐effects model, and results were expressed as risk ratios and 95% confidence intervals (CI) for categorical variables, and mean differences (MD) or standardised mean differences (SMD) and 95% CI for continuous variables.
Main results
This review update included 42 eligible studies (3262 participants), including six new studies (543 participants). Overall, 29 studies (1971 participants) compared neutral pH, low GDP PD solution with conventional PD solution, and 13 studies (1291 participants) compared icodextrin with conventional PD solution. Risk of bias was assessed as high for sequence generation in three studies, allocation concealment in three studies, attrition bias in 21 studies, and selective outcome reporting bias in 16 studies.
Neutral pH, low GDP versus conventional glucose PD solution
Use of neutral pH, low GDP PD solutions improved residual renal function (RRF) preservation (15 studies, 835 participants: SMD 0.19, 95% CI 0.05 to 0.33; high certainty evidence). This approximated to a mean difference in glomerular filtration rate of 0.54 mL/min/1.73 m2 (95% CI 0.14 to 0.93). Better preservation of RRF was evident at all follow‐up durations with progressively greater preservation observed with increasing follow up duration. Neutral pH, low GDP PD solution use also improved residual urine volume preservation (11 studies, 791 participants: MD 114.37 mL/day, 95% CI 47.09 to 181.65; high certainty evidence). In low certainty evidence, neutral pH, low GDP solutions may make little or no difference to 4‐hour peritoneal ultrafiltration (9 studies, 414 participants: SMD ‐0.42, 95% CI ‐0.74 to ‐0.10) which approximated to a mean difference in peritoneal ultrafiltration of 69.72 mL (16.60 to 122.00 mL) lower, and may increase dialysate:plasma creatinine ratio (10 studies, 746 participants: MD 0.01, 95% CI 0.00 to 0.03), technique failure or death compared with conventional PD solutions. It is uncertain whether neutral pH, low GDP PD solution use led to any differences in peritonitis occurrence, hospitalisation, adverse events (6 studies, 519 participants) or inflow pain (1 study, 58 participants: RR 0.51, 95% CI 0.24 to 1.08).
Glucose polymer (icodextrin) versus conventional glucose PD solution
In moderate certainty evidence, icodextrin probably reduced episodes of uncontrolled fluid overload (2 studies, 100 participants: RR 0.30, 95% CI 0.15 to 0.59) and augmented peritoneal ultrafiltration (4 studies, 102 participants: MD 448.54 mL/d, 95% CI 289.28 to 607.80) without compromising RRF (4 studies, 114 participants: SMD 0.12, 95% CI ‐0.26 to 0.49; low certainty evidence) which approximated to a mean creatinine clearance of 0.30 mL/min/1.73m2 higher (0.65 lower to 1.23 higher) or urine output (3 studies, 69 participants: MD ‐88.88 mL/d, 95% CI ‐356.88 to 179.12; low certainty evidence). It is uncertain whether icodextrin use led to any differences in adverse events (5 studies, 816 participants) technique failure or death.
Authors' conclusions
This updated review strengthens evidence that neutral pH, low GDP PD solution improves RRF and urine volume preservation with high certainty. These effects may be related to increased peritoneal solute transport and reduced peritoneal ultrafiltration, although the evidence for these outcomes is of low certainty due to significant heterogeneity and suboptimal methodological quality. Icodextrin prescription increased peritoneal ultrafiltration and mitigated uncontrolled fluid overload with moderate certainty. The effects of either neutral pH, low GDP solution or icodextrin on peritonitis, technique survival and patient survival remain uncertain and require further high quality, adequately powered RCTs.
Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist. However, it is not known whether CKD is an independent risk factor for incident AF. Therefore, we evaluated the association ...between markers of CKD—estimated glomerular filtration rate (eGFR) and albuminuria—and incident AF.
Systematic review and meta-analysis of cohort studies and randomized controlled trials.
Participants with measurement of eGFR and/or albuminuria who were not receiving dialysis.Selection Criteria for Studies: Cohort studies and randomized controlled trials were included that reported incident AF risk in adults according to eGFR and/or albuminuria.
Age- or multivariate-adjusted risk ratios (RRs) for incident AF were extracted from cohort studies, and RRs for each trial were derived from event data. RRs for incident AF were pooled using random-effects models.
38 studies involving 28,470,249 participants with 530,041 incident AF cases were included. Adjusted risk of incident AF was greater among participants with lower eGFR than those with higher eGFR (eGFR<60 vs≥60mL/min/1.73m2: RR, 1.43; 95% CI, 1.30-1.57; and eGFR<90 vs≥90mL/min/1.73m2: RR, 1.42; 95% CI, 1.26-1.60). Adjusted incident AF risk was greater among participants with albuminuria (any albuminuria vs no albuminuria: RR, 1.43; 95% CI, 1.25-1.63; and moderately to severely increased albuminuria vs normal to mildly increased albuminuria: RR, 1.64; 95% CI, 1.31-2.06). Subgroup analyses showed an exposure-dependent association between CKD and incident AF, with the risk increasing progressively at lower eGFR and higher albuminuria categories.
Lack of patient-level data, interaction between eGFR and albuminuria could not be evaluated, possible ascertainment bias due to variation in the methods of AF detection.
Lower eGFR and greater albuminuria were independently associated with increased risk of incident AF. CKD should be regarded as an independent risk factor for incident AF.
Irregular heartbeat, or atrial fibrillation (AF), is the commonest abnormal heart rhythm. AF occurs commonly in people with chronic kidney disease (CKD), and CKD is also common in people with AF. However, CKD in not widely recognized as a risk factor for new-onset or incident AF. In this research, we combined data on more than 28 million participants in 38 studies to determine whether CKD itself increases the chances of incident AF. We found that both commonly used markers of kidney disease (estimated glomerular filtration rate and albuminuria, ie, protein in the urine) were independently associated with a greater risk of incident AF. This finding suggests that CKD should be recognized as an independent risk factor for incident AF.
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Non-randomized studies suggest an association between serum uric acid levels and progression of chronic kidney disease (CKD). The aim of this systematic review is to summarize evidence from ...randomized controlled trials (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal outcomes.
Medline, Excerpta Medical Database and Cochrane Central Register of Controlled Trials were searched with English language restriction for RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment on renal outcomes. Treatment effects were summarized using random-effects meta-analysis.
Eight trials (476 participants) evaluating allopurinol treatment were eligible for inclusion. There was substantial heterogeneity in baseline kidney function, cause of CKD and duration of follow-up across these studies. In five trials, there was no significant difference in change in glomerular filtration rate from baseline between the allopurinol and control arms mean difference (MD) 3.1 mL/min/1.73 m2, 95% confidence intervals (CI) -0.9, 7.1; heterogeneity χ2=1.9, I2=0%, P=0.75. In three trials, allopurinol treatment abrogated increases in serum creatinine from baseline (MD -0.4 mg/dL, 95% CI -0.8, -0.0 mg/dL; heterogeneity χ2=3, I2=34%, P=0.22). Allopurinol had no effect on proteinuria and blood pressure. Data for effects of allopurinol therapy on progression to end-stage kidney disease and death were scant. Allopurinol had uncertain effects on the risks of adverse events.
Uric acid-lowering therapy with allopurinol may retard the progression of CKD. However, adequately powered randomized trials are required to evaluate the benefits and risks of uric acid-lowering therapy in CKD.
Background
Diabetes is the commonest cause of chronic kidney disease (CKD). Both conditions commonly co‐exist. Glucometabolic changes and concurrent dialysis in diabetes and CKD make glucose‐lowering ...challenging, increasing the risk of hypoglycaemia. Glucose‐lowering agents have been mainly studied in people with near‐normal kidney function. It is important to characterise existing knowledge of glucose‐lowering agents in CKD to guide treatment.
Objectives
To examine the efficacy and safety of insulin and other pharmacological interventions for lowering glucose levels in people with diabetes and CKD.
Search methods
We searched the Cochrane Kidney and Transplant Register of Studies up to 12 February 2018 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
All randomised controlled trials (RCTs) and quasi‐RCTs looking at head‐to‐head comparisons of active regimens of glucose‐lowering therapy or active regimen compared with placebo/standard care in people with diabetes and CKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) were eligible.
Data collection and analysis
Four authors independently assessed study eligibility, risk of bias, and quality of data and performed data extraction. Continuous outcomes were expressed as post‐treatment mean differences (MD). Adverse events were expressed as post‐treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI).
Main results
Forty‐four studies (128 records, 13,036 participants) were included. Nine studies compared sodium glucose co‐transporter‐2 (SGLT2) inhibitors to placebo; 13 studies compared dipeptidyl peptidase‐4 (DPP‐4) inhibitors to placebo; 2 studies compared glucagon‐like peptide‐1 (GLP‐1) agonists to placebo; 8 studies compared glitazones to no glitazone treatment; 1 study compared glinide to no glinide treatment; and 4 studies compared different types, doses or modes of administration of insulin. In addition, 2 studies compared sitagliptin to glipizide; and 1 study compared each of sitagliptin to insulin, glitazars to pioglitazone, vildagliptin to sitagliptin, linagliptin to voglibose, and albiglutide to sitagliptin. Most studies had a high risk of bias due to funding and attrition bias, and an unclear risk of detection bias.
Compared to placebo, SGLT2 inhibitors probably reduce HbA1c (7 studies, 1092 participants: MD ‐0.29%, ‐0.38 to ‐0.19 (‐3.2 mmol/mol, ‐4.2 to ‐2.2); I2 = 0%), fasting blood glucose (FBG) (5 studies, 855 participants: MD ‐0.48 mmol/L, ‐0.78 to ‐0.19; I2 = 0%), systolic blood pressure (BP) (7 studies, 1198 participants: MD ‐4.68 mmHg, ‐6.69 to ‐2.68; I2 = 40%), diastolic BP (6 studies, 1142 participants: MD ‐1.72 mmHg, ‐2.77 to ‐0.66; I2 = 0%), heart failure (3 studies, 2519 participants: RR 0.59, 0.41 to 0.87; I2 = 0%), and hyperkalaemia (4 studies, 2788 participants: RR 0.58, 0.42 to 0.81; I2 = 0%); but probably increase genital infections (7 studies, 3086 participants: RR 2.50, 1.52 to 4.11; I2 = 0%), and creatinine (4 studies, 848 participants: MD 3.82 μmol/L, 1.45 to 6.19; I2 = 16%) (all effects of moderate certainty evidence). SGLT2 inhibitors may reduce weight (5 studies, 1029 participants: MD ‐1.41 kg, ‐1.8 to ‐1.02; I2 = 28%) and albuminuria (MD ‐8.14 mg/mmol creatinine, ‐14.51 to ‐1.77; I2 = 11%; low certainty evidence). SGLT2 inhibitors may have little or no effect on the risk of cardiovascular death, hypoglycaemia, acute kidney injury (AKI), and urinary tract infection (low certainty evidence). It is uncertain whether SGLT2 inhibitors have any effect on death, end‐stage kidney disease (ESKD), hypovolaemia, fractures, diabetic ketoacidosis, or discontinuation due to adverse effects (very low certainty evidence).
Compared to placebo, DPP‐4 inhibitors may reduce HbA1c (7 studies, 867 participants: MD ‐0.62%, ‐0.85 to ‐0.39 (‐6.8 mmol/mol, ‐9.3 to ‐4.3); I2 = 59%) but may have little or no effect on FBG (low certainty evidence). DPP‐4 inhibitors probably have little or no effect on cardiovascular death (2 studies, 5897 participants: RR 0.93, 0.77 to 1.11; I2 = 0%) and weight (2 studies, 210 participants: MD 0.16 kg, ‐0.58 to 0.90; I2 = 29%; moderate certainty evidence). Compared to placebo, DPP‐4 inhibitors may have little or no effect on heart failure, upper respiratory tract infections, and liver impairment (low certainty evidence). Compared to placebo, it is uncertain whether DPP‐4 inhibitors have any effect on eGFR, hypoglycaemia, pancreatitis, pancreatic cancer, or discontinuation due to adverse effects (very low certainty evidence).
Compared to placebo, GLP‐1 agonists probably reduce HbA1c (7 studies, 867 participants: MD ‐0.53%, ‐1.01 to ‐0.06 (‐5.8 mmol/mol, ‐11.0 to ‐0.7); I2 = 41%; moderate certainty evidence) and may reduce weight (low certainty evidence). GLP‐1 agonists may have little or no effect on eGFR, hypoglycaemia, or discontinuation due to adverse effects (low certainty evidence). It is uncertain whether GLP‐1 agonists reduce FBG, increase gastrointestinal symptoms, or affect the risk of pancreatitis (very low certainty evidence).
Compared to placebo, it is uncertain whether glitazones have any effect on HbA1c, FBG, death, weight, and risk of hypoglycaemia (very low certainty evidence).
Compared to glipizide, sitagliptin probably reduces hypoglycaemia (2 studies, 551 participants: RR 0.40, 0.23 to 0.69; I2 = 0%; moderate certainty evidence). Compared to glipizide, sitagliptin may have had little or no effect on HbA1c, FBG, weight, and eGFR (low certainty evidence). Compared to glipizide, it is uncertain if sitagliptin has any effect on death or discontinuation due to adverse effects (very low certainty).
For types, dosages or modes of administration of insulin and other head‐to‐head comparisons only individual studies were available so no conclusions could be made.
Authors' conclusions
Evidence concerning the efficacy and safety of glucose‐lowering agents in diabetes and CKD is limited. SGLT2 inhibitors and GLP‐1 agonists are probably efficacious for glucose‐lowering and DPP‐4 inhibitors may be efficacious for glucose‐lowering. Additionally, SGLT2 inhibitors probably reduce BP, heart failure, and hyperkalaemia but increase genital infections, and slightly increase creatinine. The safety profile for GLP‐1 agonists is uncertain. No further conclusions could be made for the other classes of glucose‐lowering agents including insulin. More high quality studies are required to help guide therapeutic choice for glucose‐lowering in diabetes and CKD.
Several clinical practice guidelines noted the potential benefits of urate-lowering therapy on cardiovascular disease and CKD progression; however, the effect of this regimen remains uncertain. In ...this systematic review, we aimed to evaluate the efficacy of urate-lowering therapy on major adverse cardiovascular events, all-cause mortality, kidney failure events, BP, and GFR.
We systematically searched MEDLINE, Embase, and the Cochrane databases for trials published through July 2020. We included prospective, randomized, controlled trials assessing the effects of urate-lowering therapy for at least 6 months on cardiovascular or kidney outcomes. Relevant information was extracted into a spreadsheet by two authors independently. Treatment effects were summarized using random effects meta-analysis.
We identified 28 trials including a total of 6458 participants with 506 major adverse cardiovascular events and 266 kidney failure events. Overall urate-lowering therapy did not show benefits on major adverse cardiovascular events (risk ratio, 0.93; 95% confidence interval, 0.74 to 1.18) and all-cause mortality (risk ratio, 1.04; 95% confidence interval, 0.78 to 1.39) or kidney failure (risk ratio, 0.97; 95% confidence interval, 0.61 to 1.54). Nevertheless, urate-lowering therapy attenuated the decline in the slope of GFR (weighted mean difference, 1.18 ml/min per 1.73 m
per year; 95% confidence interval, 0.44 to 1.91) and lowered the mean BP (systolic BP: weighted mean difference, -3.45 mm Hg; 95% confidence interval, -6.10 to -0.80; diastolic BP: weighted mean difference, -2.02 mm Hg; 95% confidence interval, -3.25 to -0.78). There was no significant difference (risk ratio, 1.01; 95% confidence interval, 0.94 to 1.08) in the risk of adverse events between the participants receiving urate-lowering therapy and the control group.
Urate-lowering therapy did not produce benefits on the clinical outcomes, including major adverse cardiovascular events, all-cause mortality, and kidney failure. Thus, there is insufficient evidence to support urate lowering in patients to improve kidney and cardiovascular outcomes.
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