Philip Masson

Antihypertensives for kidney transplant recipients: systematic review and meta-analysis of randomized controlled trials.

In nontransplant populations, effects of different antihypertensive drug classes vary. Relative effects in kidney transplant recipients are uncertain. We performed a systematic review including random effects meta-analysis of randomized controlled trials, using Cochrane Collaboration methodology. We identified 60 trials, enrolling 3802 recipients. Twenty-nine trials (2262 patients) compared calcium channel blockers (CCB) with placebo or no treatment, 10 trials (445 patients) compared angiotensin-converting enzyme inhibitors (ACEi) with placebo or no treatment, and seven studies (405 patients) compared CCB with ACEi. CCB compared with placebo or no treatment (plus additional agents in either arm as required) reduced graft loss (risk ratio [RR] 0.75, 95% confidence intervals [CI] 0.57–0.99) and improved glomerular filtration rate (GFR; mean difference [MD] 4.5 mL/min, 95% CI 2.2–6.7). Data on ACEi versus placebo or no treatment were inconclusive for GFR (MD −8.1 mL/min, 95% CI −18.6–2.4) and inconsistent for graft loss, precluding meta-analysis. In direct comparison with CCB, ACEi decreased GFR (MD 11.5 mL/min, 95% CI 7.2–15.8), proteinuria (MD 0.28 g/day, 95% CI 0.10–0.47), hemoglobin (MD 11.5 g/L, 95% CI 7.2–15.8), and increased hyperkalemia (RR 3.7, 95% CI 1.9–7.7). Graft loss data were inconclusive (RR 7.4, 95% CI 0.4–140). These data suggest that CCB may be preferred as first-line agents for hypertensive kidney transplant recipients.

Induction and Maintenance Treatment of Proliferative Lupus Nephritis: A Meta-analysis of Randomized Controlled Trials

BACKGROUND Lupus nephritis accounts for ~1% of patients starting dialysis therapy. Treatment regimens combining cyclophosphamide with steroids preserve kidney function but have significant side effects. Newer immunosuppressive agents may have improved toxicity profiles. STUDY DESIGN Systematic review and random-effects meta-analysis, searching MEDLINE (1966 to April 2012), EMBASE (1988-2011), and the Cochrane Renal Group Specialised Register. SETTING & POPULATION Patients with biopsy-proven proliferative lupus nephritis (classes III, IV, V+III, and V+IV). SELECTION CRITERIA Randomized controlled trials. INTERVENTION Immunosuppressive treatment regimens used for induction and maintenance therapy of lupus nephritis. OUTCOMES Mortality, renal remission and relapse, doubling of creatinine level, proteinuria, incidence of end-stage kidney disease, ovarian failure, alopecia, leukopenia, infections, diarrhea, vomiting, malignancy, and bladder toxicity. RESULTS 45 trials (2,559 participants) of induction therapy and 6 (514 participants) of maintenance therapy were included. In induction regimens comparing mycophenolate mofetil (MMF) with intravenous cyclophosphamide, there was no significant difference in mortality (7 studies, 710 patients; risk ratio [RR], 1.02; 95% CI, 0.52-1.98), incidence of end-stage kidney disease (3 studies, 231 patients; RR, 0.71; 95% CI, 0.27-1.84), complete renal remission (6 studies, 686 patients; RR, 1.39; 95% CI, 0.99-1.95), and renal relapse (1 study, 140 patients; RR, 0.97; 95% CI, 0.39-2.44). MMF-treated patients had significantly lower risks of ovarian failure (2 studies, 498 patients; RR, 0.15; 95% CI, 0.03-0.80) and alopecia (2 studies, 522 patients; RR, 0.22; 95% CI, 0.06-0.86). In maintenance therapy comparing azathioprine with MMF, the risk of renal relapse was significantly higher (3 studies, 371 patients; RR, 1.83; 95% CI, 1.24-2.71). LIMITATIONS Heterogeneity in interventions and definitions of remission and lack of long-term outcome reporting. CONCLUSIONS MMF is as effective as cyclophosphamide in achieving remission in lupus nephritis, but is safer, with a lower risk of ovarian failure. MMF is more effective than azathioprine in maintenance therapy for preventing relapse, with no difference in clinically important side effects.

Meta-analyses in Prevention and Treatment of Urinary Tract Infections

Urinary tract infections (UTI) are common, and complications result in significant morbidity and mortality and also consume resources. This overview summarizes the current evidence for the prevention and treatment of UTI in adults and children from meta-analyses. The quality and applicability of this evidence in clinical practice for different patient groups is discussed. Suggestions are made for future research, because it is apparent that there are evidence gaps for particular subgroups of people.

Early Precut Sphincterotomy Does Not Increase Risk During Endoscopic Retrograde Cholangiopancreatography in Patients With Difficult Biliary Access: A Meta-analysis of Randomized Controlled Trials

BACKGROUND & AIMS Use of precut sphincterotomy during endoscopic retrograde cholangiopancreatography (ERCP) can increase the odds for cannulation success but is associated with increased risk of post-ERCP pancreatitis. Earlier, rather than delayed, use of precut sphincterotomy for cases with difficult biliary access might reduce this risk. We performed a meta-analysis of randomized controlled trials to determine how early use of precut sphincterotomy affects the risk of pancreatitis and rate of cannulation success compared with persistent standard cannulation. METHODS We searched MEDLINE, EMBASE, and the Cochrane central register of controlled trials, along with meeting abstracts, through August 2014 for randomized controlled trials in which early precut sphincterotomy was compared with persistent standard cannulation in adults with difficult biliary access. Outcomes considered included primary cannulation success, overall cannulation success, incidence of post-ERCP pancreatitis, and overall adverse event rate. Findings from a random-effects model were expressed as pooled risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS We analyzed data from 5 studies (523 participants). The incidence of post-ERCP pancreatitis and success of overall cannulation did not differ significantly between the early precut and persistent standard therapy groups. Early use of precut sphincterotomy was associated with increased odds for primary cannulation success (RR, 1.32; 95% CI, 1.04-1.68). In subgroup analysis of studies that involved only fully qualified biliary endoscopists (not fellows), we found a significant reduction in risk of pancreatitis among patients receiving early precut vs the standard technique (RR, 0.29; 95% CI, 0.10-0.86). CONCLUSION Compared with standard therapy, early use of precut sphincterotomy did not increase the risk of post-ERCP pancreatitis in a meta-analysis. When the procedure is performed by qualified biliary endoscopists, early precut can reduce the risk of post-ERCP pancreatitis. Rates of primary cannulation increase with early precut. Further studies are needed to confirm these findings.

Prognostic value of cardiac tests in potential kidney transplant recipients: a systematic review.

Background Whether abnormal myocardial perfusion scintigraphy (MPS), dobutamine stress echocardiography (DSE) or coronary angiography, performed during preoperative evaluation for potential kidney transplant recipients, predicts future cardiovascular morbidity is unclear. We assessed test performance for predicting all-cause mortality, cardiovascular mortality and major adverse cardiac events (MACE). Methods We searched MEDLINE and EMBASE (to February 2014), appraised studies, and calculated risk differences and relative risk ratios (RRR) with 95% confidence intervals (95% CI) using random effects meta-analysis. Results Fifty-two studies (7401 participants) contributed data to the meta-analysis. Among the different tests, similar numbers of patients experienced MACE after an abnormal test result compared with a normal result (risk difference: MPS 20 per 100 patients tested [95% CI, 0.11–0.29], DSE 24 [95% CI, 0.10–0.38], and coronary angiography 20 [95% CI, 0.08–0.32; P = 0.91]). Although there was some evidence that coronary angiography was better at predicting all-cause mortality than MPS (RRR, 0.69; 95% CI, 0.49–0.96; P = 0.03) and DSE (RRR, 0.72; 95% CI, 0.50–1.02; P = 0.06), noninvasive tests were as good as coronary angiography at predicting cardiovascular mortality (RRR, MPS, 0.89; 95% CI, 0.38–2.10; P = 0.78; DSE, 1.09; 95% CI, 0.12–10.05; P = 0.93), and MACE (RRR: MPS, 1.09; 95% CI, 0.64–1.86; P = 0.74; DSE, 1.56; 95% CI, 0.71–3.45; P = 0.25). Conclusions Noninvasive tests are as good as coronary angiography at predicting future adverse cardiovascular events in advanced chronic kidney disease. However, a substantial number of people with negative test results go on to experience adverse cardiac events.

Consistency and completeness of reported outcomes in randomized trials of primary immunosuppression in kidney transplantation.

Inconsistent and incomplete outcome reporting may make estimates of treatment effects from published randomized trials unreliable. We aimed to determine outcome reporting practices and source of differences in reporting quality among randomized trials of primary immunosuppression in kidney transplantation. We searched the Cochrane Renal Groups Specialized Register, 2000–2012, specified four core outcomes we expected trials to report, and recorded if and how completely each was reported. We identified 179 trials. One hundred sixty‐eight (94%) reported death, 145 (81%) as number dead and 119 (66%) as time to death. One hundred sixty‐five (92%) reported graft loss, 158 (88%) as number with graft loss and 127 (71%) as time to graft loss. One hundred twenty‐one (68%) reported creatinine and 114 (64%) estimated GFR (eGFR). One hundred forty‐one (79%) provided complete reports of number dead, 95 (53%) censored and 99 (55%) uncensored number with graft loss. Seventy‐three (41%) provided complete reports of time to death, 67 (37%) censored and 31 (17%) uncensored time to graft loss. Complete reporting of graft function was infrequent: 62 (35%) eGFR and 50 (28%) creatinine. All four outcomes were reported in any form in 61 (34%) and completely in 28 (16%) trials. No single trial or journal characteristic was consistently associated with complete outcome reporting. Outcome reporting in kidney transplant trials is inconsistent and frequently incomplete, and published estimates of treatment effects may be unreliable.

Risk of Stroke in Patients with ESRD

BACKGROUND AND OBJECTIVES This study aimed to determine absolute and excess stroke risks in people with ESRD compared with the general population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This cohort study used data linkage between the Australia and New Zealand Dialysis and Transplant Registry and hospital and death records for 10,745 people with ESRD in New South Wales from 2000 to 2010. For the general population, Australian Institute of Health and Welfare hospital usage records and Australian Bureau of Statistics census data were used. Rates and standardized incidence rate ratios of hospitalization with a stroke were calculated. RESULTS People with ESRD had 640 hospitalizations with stroke in 49,472 person-years of follow-up (1294 per 100,000 person-years), and people in the general population had 338,392 hospitalizations with stroke (212 per 100,000 person-years), an incidence rate ratio of 3.32 (95% confidence interval, 3.31 to 3.33). Excess risk was greater for women (incidence rate ratio, 5.14; 95% confidence interval, 5.11 to 5.18) than men (incidence rate ratio, 2.52; 95% confidence interval, 2.51 to 2.54; P for interaction <0.001) and decreased with age. People ages 35-39 years old with ESRD had an 11 times increased risk of stroke (incidence rate ratio, 11.08; 95% confidence interval, 9.41 to 13.05), and risk in people ages ≥85 years old increased 2-fold (incidence rate ratio, 2.04; 95% confidence interval, 1.87 to 2.23; P for interaction <0.001). Excess risk was greater for intracerebral hemorrhage (incidence rate ratio, 4.18; 95% confidence interval, 4.11 to 4.26) than ischemic stroke (incidence rate ratio, 3.43; 95% confidence interval, 3.40 to 3.45; P for interaction <0.01). CONCLUSIONS People with ESRD have a substantially higher risk of stroke, particularly women and young people, and hemorrhagic stroke. Future work could investigate effective and safe interventions for primary and secondary prevention of stroke in people with ESRD.

Pulmonary Vein Isolation Compared to Rate Control in Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis

BACKGROUND Atrial fibrillation (AF) often coexists with congestive cardiac failure (CCF), with multiple treatment options available. METHODS Systematic review and meta-analysis of randomised control trials (RCT) comparing pulmonary vein isolation (PVI), pharmacological rate control, and atrioventricular junction ablation with pacemaker insertion (AVJAP) for AF, with a subgroup analysis in patients with CCF. We analysed changes in left ventricular ejection fraction (LVEF), Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, six-minute walk distance (6MWD), treadmill exercise time, and treatment complications. Results were expressed as weighted mean differences (WMD) with 95% Confidence-Intervals (95%CI). RESULTS We included seven RCT (425 participants). PVI was associated with a greater increase in LVEF (WMD+6.5%, 95%CI:+0.6to+12.5) and decrease in MLHFQ score (WMD-11.0, 95%CI:-2.6to-19.4) than pharmacological rate control in patients with CCF. PVI was also associated with a greater increase in LVEF (WMD+9.0%, 95%CI:+6.3to+11.7) and 6MWD (WMD+55.0metres, 95%CI:+34.9to+75.1), and decrease in MLHFQ score (WMD-22.0, 95%CI:-17.0to-27.0), compared to AVJAP in patients with CCF. Irrespective of cardiac function, pharmacological rate control had similar effects to AVJAP on LVEF (WMD+0.6%, 95%CI:-8.3to+9.4) and treadmill exercise time (WMD+0.5minutes, 95%CI:-0.4to+1.3). CONCLUSIONS Our results support the clinical implementation of PVI over AVJAP or pharmacological rate control in AF patients with CCF, who may or may not have already trialled pharmacological rhythm control.

Risk Factors for Stroke in People with End-Stage Kidney Disease: A Cohort Study

Background: It is unclear how traditional cardiovascular risk factors and different treatment modalities for end-stage kidney disease (ESKD) affect stroke risk in people with ESKD. We aimed to identify the risk factors for stroke (ischemic and hemorrhagic) in people with ESKD. Methods: We conducted a retrospective cohort study using data linkage between the Australian and New Zealand Dialysis and Transplant Registry, clinical and administrative datasets. Using Cox proportional hazards models, we estimated the magnitudes of risk of hospitalization with different subtypes of strokes associated with traditional cardiovascular risk factors and ESKD treatment modalities (hemodialysis (HD), peritoneal dialysis (PD) and kidney transplantation). Results were expressed as hazard ratios (HRs) with 95% CIs. Results: A total of 10,745 people received treatment for ESKD in New South Wales, Australia, between 2000 and 2010. We observed 640 hospitalizations for stroke in 49,497 person-years of follow-up (129.4 per 10,000 person years). Some risk factors were consistent with those found in the general population, including smoking and a history of previous stroke. Other risk factors were novel for people with ESKD. Women were 85% more likely to have an intracerebral hemorrhage (HR 1.85, 95% CI 1.22-2.79) and 30% more likely to have an ischemic stroke (HR 1.30, 95% CI 1.01-1.66) than men. Compared to people on HD, people with kidney transplants had a 65% lower risk of intracerebral hemorrhage (HR 0.35, 95% CI 0.18-0.69) but a similar risk of ischemic stroke (HR 0.97, 95% CI 0.64-1.49). People on PD had a 36% higher risk of ischemic stroke (HR 1.36, 95% CI 1.05-1.76) but a similar risk of intracerebral hemorrhage compared to people on HD (HR 0.69, 95% CI 0.43-1.11). Conclusions: These findings could be used to establish reliable estimates of the risk of stroke in people with ESKD and identify those who are most likely to benefit from preventive treatments.

Stroke Mortality in Kidney Transplant Recipients: A Retrospective Population-Based Cohort Study using Data Linkage

the CELESTIAL study. Introduction People with kidney transplants have a higher risk of stroke than the general population but their risk of dying from a stroke remains unclear. We aimed to compare stroke deaths in kidney transplant recipients with the general population. Materials & Methods: We established the primary cause of death for incident kidney transplant recipients using data linkage between the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) and national death registries: Australia, 1980-2013 and New Zealand, 1988-2012. We used indirect standardization to estimate standardized mortality ratios (SMR) with 95% confidence intervals (CI) and a competing risks regression model to identify risk factors for stroke and non-stroke mortality. Results & Discussion Among 17,621 kidney transplant recipients, there were 158 stroke deaths and 5,126 non-stroke deaths in 160,332 person-years of follow-up. Stroke death rates steadily increased from transplantation. Non-stroke deaths rapidly increased from transplantation until 6 months’ follow-up (Fig. 1). All-cause stroke SMR were higher in people who were younger and particularly in females (Fig. 2). Kidney transplant recipients aged 30-49 were over 9 times the expected in the general population (Table 1; Females: SMR 21.3, 95% CI: 13.9-32.7; Males SMR 9.9, 95% CI: 6.2-15.9). A higher risk of stroke death was associated with older age at transplant, earlier year of transplant and cerebrovascular disease (Fig. 3). Previous duration of dialysis prior to transplant was associated with an increased risk of non-stroke mortality only.. Conclusion Stroke mortality is significantly higher among kidney transplant recipients than in the general population, particularly for young people and females. Cardiovascular risk factor control interventions have helped reduce stroke mortality in the general population, but their effectiveness in kidney recipients is less clear. Further randomized-controlled trials in kidney recipients could evaluate the benefits and harms of cardiovascular interventions. Australia and New Zealand Dialysis and Transplant Registry (ANZDATA). Australian Institute of Health and Welfare (AIHW). New Zealand Ministry of Health. Kidney Health Australia. Figure. No caption available. Figure. No caption available. Table. No title available. Figure. No caption available.