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In this trial, 947 patients with renal-artery stenosis were assigned to renal-artery stenting or medical therapy. At a median of 43 months, there was no significant between-group difference in the rate of a composite end point of adverse cardiovascular and renal events. Renal-artery stenosis, which is present in 1 to 5% of people with hypertension, 1 , 2 often occurs in combination with peripheral arterial or coronary artery disease. 3 , 4 Results of community-based screening suggest that the prevalence among persons older than 65 years of age may be as high as 7%. 5 Renal-artery stenosis may result in hypertension, ischemic nephropathy, and multiple long-term complications. 6 Uncontrolled studies performed in the 1990s suggested that renal-artery angioplasty or stenting resulted in significant reductions in systolic blood pressure 7 , 8 and in the stabilization of chronic kidney disease. 9 , 10 Subsequently, there were rapid increases in the rate of renal-artery . . .

Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and ISRCTN54137607. 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0·85 mmol/L (SE 0·02; with about two-thirds compliance) during a median follow-up of 4·9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11·3%] simvastatin plus ezetimibe vs 619 [13·4%] placebo; rate ratio [RR] 0·83, 95% CI 0·74–0·94; log-rank p=0·0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4·6%] vs 230 [5·0%]; RR 0·92, 95% CI 0·76–1·11; p=0·37) and there were significant reductions in non-haemorrhagic stroke (131 [2·8%] vs 174 [3·8%]; RR 0·75, 95% CI 0·60–0·94; p=0·01) and arterial revascularisation procedures (284 [6·1%] vs 352 [7·6%]; RR 0·79, 95% CI 0·68–0·93; p=0·0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%]), or cancer (438 [9·4%] vs 439 [9·5%], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13). Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council.

The previous conventional wisdom that survivors of acute kidney injury (AKI) tend to do well and fully recover renal function appears to be flawed. AKI can cause end-stage renal disease (ESRD) directly, and increase the risk of developing incident chronic kidney disease (CKD) and worsening of underlying CKD. In addition, severity, duration, and frequency of AKI appear to be important predictors of poor patient outcomes. CKD is an important risk factor for the development and ascertainment of AKI. Experimental data support the clinical observations and the bidirectional nature of the relationships between AKI and CKD. Reductions in renal mass and nephron number, vascular insufficiency, cell cycle disruption, and maladaptive repair mechanisms appear to be important modulators of progression in patients with and without coexistent CKD. Distinction between AKI and CKD may be artificial. Consideration should be given to the integrated clinical syndrome of diminished GFR, with acute and chronic stages, where spectrum of disease state and outcome is determined by host factors, including the balance of adaptive and maladaptive repair mechanisms over time. Physicians must provide long-term follow-up to patients with first episodes of AKI, even if they presented with normal renal function.

Acute kidney injury may increase the risk for chronic kidney disease and end-stage renal disease. In an attempt to summarize the literature and provide more compelling evidence, we conducted a systematic review comparing the risk for CKD, ESRD, and death in patients with and without AKI. From electronic databases, web search engines, and bibliographies, 13 cohort studies were selected, evaluating long-term renal outcomes and non-renal outcomes in patients with AKI. The pooled incidence of CKD and ESRD were 25.8 per 100 person-years and 8.6 per 100 person-years, respectively. Patients with AKI had higher risks for developing CKD (pooled adjusted hazard ratio 8.8, 95% CI 3.1–25.5), ESRD (pooled adjusted HR 3.1, 95% CI 1.9–5.0), and mortality (pooled adjusted HR 2.0, 95% CI 1.3–3.1) compared with patients without AKI. The relationship between AKI and CKD or ESRD was graded on the basis of the severity of AKI, and the effect size was dampened by decreased baseline glomerular filtration rate. Data were limited, but AKI was also independently associated with the risk for cardiovascular disease and congestive heart failure, but not with hospitalization for stroke or all-cause hospitalizations. Meta-regression did not identify any study-level factors that were associated with the risk for CKD or ESRD. Our review identifies AKI as an independent risk factor for CKD, ESRD, death, and other important non-renal outcomes.

In this study, APOL1 variants were associated with an increased risk of progression of chronic kidney disease in black patients, as compared with white patients, regardless of the cause of kidney disease or diabetes status. In the United States, black patients have approximately twice the risk of end-stage renal disease observed among white patients, after accounting for differences in socioeconomic and clinical risk factors. 1 – 4 This increased risk occurs despite a similar prevalence in earlier stages of chronic kidney disease 5 – 8 in the two racial groups, which suggests that kidney function declines more rapidly after the onset of chronic kidney disease in black patients. However, there is little direct evidence in support of this hypothesis. 9 – 13 The identification of factors that mediate differences in the progression of chronic kidney disease between black patients and white . . .

Acute kidney injury (AKI) is associated with progression to advanced chronic kidney disease (CKD). We tested whether patients who survive AKI and are at higher risk for CKD progression can be identified during their hospital admission, thus providing opportunities to intervene. This was assessed in patients in the Department of Veterans Affairs Healthcare System hospitalized with a primary diagnosis indicating AKI (ICD9 codes 584.xx). In the exploratory phase, three multivariate prediction models for progression to stage 4 CKD were developed. In the confirmatory phase, the models were validated in 11,589 patients admitted for myocardial infarction or pneumonia during the same time frame that had RIFLE codes R, I, or F and complete data for all predictor variables. Of the 5351 patients in the AKI group, 728 entered stage 4 CKD after hospitalization. Models 1, 2, and 3 were all significant with ‘c’ statistics of 0.82, 0.81, and 0.77, respectively. In model validation, all three were highly significant when tested in the confirmatory patients, with moderate to large effect sizes and good predictive accuracy (‘c’ 0.81–0.82). Patients with AKI who required dialysis and then recovered were at especially high risk for progression to CKD. Hence, the severity of AKI is a robust predictor of progression to CKD.

ObjectivesREVEAL-CKD aims to estimate the prevalence of, and factors associated with, undiagnosed stage 3 chronic kidney disease (CKD).DesignMultinational, observational study.SettingData from six country-specific electronic medical records and/or insurance claims databases from five countries (France, Germany, Italy, Japan and the USA [two databases]).ParticipantsEligible participants (≥18 years old) had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements (calculated from serum creatinine values, sex and age) taken from 2015 onwards that were indicative of stage 3 CKD (≥30 and <60 mL/min/1.73 m2). Undiagnosed cases lacked an International Classification of Diseases 9/10 diagnosis code for CKD (any stage) any time before, and up to 6 months after, the second qualifying eGFR measurement (study index).Main outcome measuresThe primary outcome was point prevalence of undiagnosed stage 3 CKD. Time to diagnosis was assessed using the Kaplan-Meier approach. Factors associated with lacking a CKD diagnosis and risk of diagnostic delay were assessed using logistic regression adjusted for baseline covariates.ResultsThe prevalence of undiagnosed stage 3 CKD was 95.5% (19 120/20 012 patients) in France, 84.3% (22 557/26 767) in Germany, 77.0% (50 547/65 676) in Italy, 92.1% (83 693/90 902) in Japan, 61.6% (13 845/22 470) in the US Explorys Linked Claims and Electronic Medical Records Data database and 64.3% (161 254/250 879) in the US TriNetX database. The prevalence of undiagnosed CKD increased with age. Factors associated with undiagnosed CKD were female sex (vs male, range of odds ratios across countries: 1.29–1.77), stage 3a CKD (vs 3b, 1.81–3.66), no medical history (vs a history) of diabetes (1.26–2.77) or hypertension (1.35–1.78).ConclusionsThere are substantial opportunities to improve stage 3 CKD diagnosis, particularly in female patients and older patients. The low diagnosis rates in patients with comorbidities that put them at risk of disease progression and complications require attention.Trial registrationNCT04847531.

This review considers evidence that acute and chronic kidney diseases are not distinct entities but rather are closely interconnected. The implications of this insight are discussed in terms of the approach to patients with kidney disease. For more than 40 years, nephrologists have classified diminished kidney function as two distinct syndromes — acute and chronic kidney failure. Whereas chronic kidney disease was recognized in the 19th century, acute renal dysfunction became evident during the London Blitz of World War II, with the realization that crush injuries could cause dramatic but often reversible cessation of renal function. The disease states and stages of both acute and chronic renal syndromes are delineated according to the serum creatinine concentration or the glomerular filtration rate (GFR), functional markers that were identified in the early 20th century. 1 Advanced renal impairment in . . .

Chronic kidney disease (CKD) is a public health epidemic that affects millions of people worldwide. Presence of CKD predisposes individuals to high risks of end-stage renal disease (ESRD), cardiovascular disease, and premature death. Disordered phosphate homeostasis with elevated circulating levels of fibroblast growth factor 23 (FGF23) is an early and pervasive complication of CKD. CKD is likely the most common cause of chronically elevated FGF23 levels, and the clinical condition in which levels are most markedly elevated. Although increases in FGF23 levels help maintain serum phosphate in the normal range in CKD, prospective studies in populations of pre-dialysis CKD, incident and prevalent ESRD, and kidney transplant recipients demonstrate that elevated FGF23 levels are independently associated with progression of CKD and development of cardiovascular events and mortality. It was originally thought that these observations were driven by elevated FGF23 levels acting as a highly sensitive biomarker of toxicity due to phosphate. However, FGF23 itself has now been shown to mediate ‘off-target,’ direct, end-organ toxicity in the heart, which suggests that elevated FGF23 levels may be a novel mechanism of adverse outcomes in CKD. This report reviews recent advances in FGF23 biology relevant to CKD, the classical effects of FGF23 on mineral homeostasis, and the studies that established FGF23 excess as a biomarker and novel mechanism of cardiovascular disease. The report concludes with a critical review of the effects of different therapeutic strategies targeting FGF23 reduction and how these might be leveraged in a future randomized trial aimed at improving outcomes in CKD.

INTRODUCTIONAcute kidney injury and chronic kidney disease (CKD) are common in hospitalized patients. To inform clinical decision making, more accurate information regarding risk of long-term progression to kidney failure is required.METHODSWe enrolled 1538 hospitalized patients in a multicenter, prospective cohort study. Monocyte chemoattractant protein 1 (MCP-1/CCL2), uromodulin (UMOD), and YKL-40 (CHI3L1) were measured in urine samples collected during outpatient follow-up at 3 months. We followed patients for a median of 4.3 years and assessed the relationship between biomarker levels and changes in estimated glomerular filtration rate (eGFR) over time and the development of a composite kidney outcome (CKD incidence, CKD progression, or end-stage renal disease). We paired these clinical studies with investigations in mouse models of renal atrophy and renal repair to further understand the molecular basis of these markers in kidney disease progression.RESULTSHigher MCP-1 and YKL-40 levels were associated with greater eGFR decline and increased incidence of the composite renal outcome, whereas higher UMOD levels were associated with smaller eGFR declines and decreased incidence of the composite kidney outcome. A multimarker score increased prognostic accuracy and reclassification compared with traditional clinical variables alone. The mouse model of renal atrophy showed greater Ccl2 and Chi3l1 mRNA expression in infiltrating macrophages and neutrophils, respectively, and evidence of progressive renal fibrosis compared with the repair model. The repair model showed greater Umod expression in the loop of Henle and correspondingly less fibrosis.CONCLUSIONSBiomarker levels at 3 months after hospitalization identify patients at risk for kidney disease progression.FUNDINGNIH.