Kidney transplantation is the best treatment for patients with end-stage renal failure, but uncertainty remains about the best immunosuppression strategy. Long-term graft survival has not improved substantially, and one possible explanation is calcineurin inhibitor (CNI) nephrotoxicity. CNI exposure could be minimized by using more potent induction therapy or alternative maintenance therapy to remove CNIs completely. However, the safety and efficacy of such strategies are unknown.

Simvastatin, 20mg, plus ezetimibe, 10mg, daily (simvastatin plus ezetimibe) reduced major atherosclerotic events in patients with moderate to severe chronic kidney disease (CKD) in the Study of Heart and Renal Protection (SHARP), but its cost-effectiveness is unknown.

The inverse association between educational attainment and mortality is well established, but its relevance to vascular events and renal progression in a population with chronic kidney disease (CKD) is less clear. This study aims to determine the association between highest educational attainment and risk of vascular events, cause-specific mortality, and CKD progression.

The impact of chronic kidney disease (CKD) on income is unclear. We sought to determine whether CKD severity, serious adverse events, and CKD progression affected household income.

Markers of inflammation, including plasma C-reactive protein (CRP), are associated with an increased risk of cardiovascular disease, and it has been suggested that this association is causal. However, the relationship between inflammation and cardiovascular disease has not been extensively studied in patients with chronic kidney disease. To evaluate this, we used data from the Study of Heart and Renal Protection (SHARP) to assess associations between circulating CRP and LDL cholesterol levels and the risk of vascular and non-vascular outcomes. Major vascular events were defined as nonfatal myocardial infarction, cardiac death, stroke or arterial revascularization, with an expanded outcome of vascular events of any type. Higher baseline CRP was associated with an increased risk of major vascular events (hazard ratio per 3x increase 1.28; 95% confidence interval 1.19-1.38). Higher baseline LDL cholesterol was also associated with an increased risk of major vascular events (hazard ratio per 0.6 mmol/L higher LDL cholesterol; 1.14, 1.06-1.22). Higher baseline CRP was associated with an increased risk of a range of non-vascular events (1.16, 1.12-1.21), but there was a weak inverse association between baseline LDL cholesterol and non-vascular events (0.96, 0.92-0.99). The efficacy of lowering LDL cholesterol with simvastatin/ezetimibe on major vascular events, in the randomized comparison, was similar irrespective of CRP concentration at baseline. Thus, decisions to offer statin-based therapy to patients with chronic kidney disease should continue to be guided by their absolute risk of atherosclerotic events. Estimation of such risk may include plasma biomarkers of inflammation, but there is no evidence that the relative beneficial effects of reducing LDL cholesterol depends on plasma CRP concentration.

Angiotensin receptor blockers (ARBs) and β blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments.

Gastroprotectant drugs are used for the prevention and treatment of peptic ulcer disease and might reduce its associated complications, but reliable estimates of the effects of gastroprotectants in different clinical settings are scarce. We aimed to examine the effects of proton-pump inhibitors (PPIs), prostaglandin analogues, and histamine-2 receptor antagonists (H2RAs) in different clinical circumstances by doing meta-analyses of tabular data from all relevant unconfounded randomised trials of gastroprotectant drugs.

Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.

Alport syndrome, historically referred to as hereditary glomerulonephritis with sensorineural deafness and anterior lenticonus, is a genetic disease of collagen α3α4α5(IV) resulting in renal failure. The collagen α3α4α5(IV) heterotrimer forms a network that is a major component of the kidney glomerular basement membrane (GBM) and basement membranes in the cochlea and eye. Alport syndrome, estimated to affect 1 in 5000-10,000 individuals, is caused by mutations in any one of the three genes that encode the α chain components of the collagen α3α4α5(IV) heterotrimer: COL4A3, COL4A4, and COL4A5. Although angiotensin-converting enzyme inhibition is effective in Alport syndrome patients for slowing progression to end-stage renal disease, it is neither a cure nor an adequate long-term protector. The 2014 International Workshop on Alport Syndrome, held in Oxford, UK, from January 3-5, was organized by individuals and families living with Alport syndrome, in concert with international experts in the clinical, genetic, and basic science aspects of the disease. Stakeholders from diverse communities-patient families, physicians, geneticists, researchers, Pharma, and funding organizations-were brought together so that they could meet and learn from each other and establish strategies and collaborations for the future, with the overall aim of discovering much needed new treatments to prolong kidney function.

End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.

Among those with moderate-to-advanced chronic kidney disease, the relationship between blood pressure (BP) and cardiovascular disease seems U shaped but is loglinear in apparently healthy adults. The SHARP (Study of Heart and Renal Protection) randomized 9270 patients with chronic kidney disease to ezetimibe/simvastatin versus matching placebo and measured BP at each follow-up visit. Cox regression was used to assess the association between BP and risk of cardiovascular disease among (1) those with a self-reported history of cardiovascular disease and (2) those with no such history and, based on plasma troponin-I concentration, a low probability of subclinical cardiac disease. A total of 8666 participants had a valid baseline BP and troponin-I measurement, and 2188 had at least 1 cardiovascular event during follow-up. After adjustment for relevant confounders, the association between systolic BP and cardiovascular events was U shaped, but among participants without evidence of previous cardiovascular disease, there was a positive loglinear association throughout the range of values studied. Among those with the lowest probability of subclinical cardiac disease, each 10 mm Hg higher systolic BP corresponded to a 27% increased risk of cardiovascular disease (hazard ratio, 1.27; 95% confidence interval, 1.11-1.44). In contrast, the relationship between diastolic BP and cardiovascular risk remained U shaped irrespective of cardiovascular disease history or risk of subclinical disease. In conclusion, the lack of a clear association between systolic BP and cardiovascular risk in this population seems attributable to confounding, suggesting that more intensive systolic BP reduction may be beneficial in such patients.

Statin-based treatments reduce cardiovascular disease (CVD) risk in patients with non-dialysis chronic kidney disease (CKD), but it is unclear which regimen is the most cost-effective. We used the Study of Heart and Renal Protection (SHARP) CKD-CVD policy model to evaluate the effect of statins and ezetimibe on quality-adjusted life years (QALYs) and health care costs in the United States (US) and the United Kingdom (UK). Net costs below $100,000/QALY (US) or £20,000/QALY (UK) were considered cost-effective. We investigated statin regimens with or without ezetimibe 10 mg. Treatment effects on cardiovascular risk were estimated per 1-mmol/L reduction in low-density lipoprotein (LDL) cholesterol as reported in the Cholesterol Treatment Trialists' Collaboration meta-analysis, and reductions in LDL cholesterol were estimated for each statin/ezetimibe regimen. In the US, atorvastatin 40 mg ($0.103/day as of January 2019) increased life expectancy by 0.23 to 0.31 QALYs in non-dialysis patients with stages 3B to 5 CKD, at a net cost of $20,300 to $78,200/QALY. Adding ezetimibe 10 mg ($0.203/day) increased life expectancy by an additional 0.05 to 0.07 QALYs, at a net cost of $43,600 to $91,500/QALY. The cost-effectiveness findings and policy implications in the UK were similar. In summary, in patients with non-dialysis-dependent CKD, the evidence suggests that statin/ezetimibe combination therapy is a cost-effective treatment to reduce the risk of CVD.

SGLT2 inhibitors reduce risk of kidney progression, AKI, and cardiovascular disease, but the mechanisms of benefit are incompletely understood. Bioimpedance spectroscopy can estimate body water and fat mass. One quarter of the EMPA-KIDNEY bioimpedance substudy CKD population had clinically significant levels of bioimpedance-derived "Fluid Overload" at recruitment. Empagliflozin induced a prompt and sustained reduction in "Fluid Overload," irrespective of sex, diabetes, and baseline N-terminal pro B-type natriuretic peptide or eGFR. No significant effect on bioimpedance-derived fat mass was observed. The effects of SGLT2 inhibitors on body water may be one of the contributing mechanisms by which they mediate effects on cardiovascular risk.

UK cardiovascular disease (CVD) incidence and mortality have declined in recent decades but socioeconomic inequalities persist.

Validated prediction scores are required to assess the risks of end-stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD).

It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration.

The aim of this study was to develop prediction models for the individual-level impacts of cardiovascular events on UK healthcare costs.

Fibroblast growth factor-23 (FGF-23) is associated with a range of cardiovascular and noncardiovascular diseases in conventional epidemiological studies, but substantial residual confounding may exist. Mendelian randomization approaches can help control for such confounding.

The relevance of the cause of kidney disease to prognosis among patients with chronic kidney disease is uncertain.

The net absolute effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors across different patient groups have not been quantified.