Spectrum Of Chronic Kidney Disease Research Articles

Echocardiographic parameters and renal outcomes in patients with preserved renal function, and mild- moderate CKD

BackgroundEchocardiographic characteristics across the spectrum of chronic kidney disease (CKD) have not been well described. We assessed the echocardiographic characteristics of patients with preserved renal function and mild or moderate CKD referred for echocardiography and determined whether echocardiographic parameters of left ventricular (LV) and right ventricular (RV) structure and function were associated with changes in renal function and mortality.MethodsThis retrospective cohort study enrolled all adult patients who had at least one trans-thoracic echocardiography between 2004 and 2014 in our institution. The composite outcome of doubling of serum creatinine or initiation of maintenance dialysis or kidney transplantation was the primary outcome. Mortality was the secondary outcome.Results29,219 patients were included. Patients with worse renal function had higher prevalence of structural and functional LV and RV abnormalities. Higher estimated glomerular filtration rate (eGFR) was independently associated with preserved LV ejection fraction, preserved RV systolic function, and lower LV mass, left atrial diameter, pulmonary artery pressure, and right atrial pressure, as well as normal RV structure. 1041 composite renal events were observed. 8780 patients died during the follow-up. Pulmonary artery pressure and the RV, but not the LV, echocardiographic parameters were independently associated with the composite renal outcome. In contrast, RV systolic function, RV dilation or hypertrophy, LV ejection fraction group, LV diameter quartile, and pulmonary artery pressure quartile were independently associated with all-cause mortality.ConclusionsEchocardiographic abnormalities are frequent even in early CKD. Echocardiographic assessment particularly of the RV may provide useful information for the care of patients with CKD.

Strategies to manage cardiovascular risk in chronic kidney disease.

Cardiovascular disease (CVD) remains the leading cause of death across the spectrum of chronic kidney disease (CKD), including CKD not requiring dialysis and for patients requiring dialysis or kidney transplantation. There is a high prevalence of ‘conventional’ cardiovascular risk factors in patients with CKD such as hypertension, dyslipidaemia, diabetes mellitus, smoking, low physical activity/obesity and prior cardiovascular events. Many risk factors contribute to the aetiology and pathogenesis of CKD or are shared risk factors for CKD progression [1]. Furthermore, there are contributors to accelerated CVD specific to, or exaggerated in CKD. Examples include left ventricular hypertrophy (LVH), fluid and electrolyte shifts, proteinuria, functional vitamin D deficiency, hyperphosphataemia, chronic inflammation, vascular stiffness and/or vascular calcification. There are multiple other putative mechanisms for accelerated CVD in CKD patients, identified by phenotyping using state of the art imaging, physiological studies and molecular biology, although these are yet to translate to clinical practice. This NDT Digest will discuss the current clinical evidence for addressing CVD risk in CKD.

The spectrum of biopsy-proven secondary glomerular diseases: A cross-sectional study in China .

The distribution of the spectrum of chronic kidney disease (CKD) has been found to vary with time. Limited information is available regarding the changing spectrum of secondary glomerular diseases (SGDs). To further investigate changes in the spectrum of SGDs, we performed a cross-sectional study. From June 2010 to May 2015, 5,935 patients from 37 hospitals in Shandong Province were involved in this study. The study was divided into five periods according to 1-year intervals. The patients were divided into four age groups. Of the 5,935 patients with qualified specimens, 1,038 (17.5%) were diagnosed with a SGD. Lupus nephritis (LN) (27.6%) was the most frequently identified SGD, followed by Henoch-Schönlein purpura glomerulonephritis (HSPN) (21.7%) and diabetic nephropathy (DN) (21.6%). The prevalence rate of DN demonstrated an increasing trend, and this condition became the leading cause of renal biopsy in period 3 (29.3%). The proportion of patients with hepatitis B virus-associated nephritis (HBVAN) decreased from 14.7% in period 2 to 5.1% in period 5 (p<0.001). The proportion of patients with amyloidosis nephropathy (AN) increased from 2.2% in period 1 to 7.0% in period 5 (p=0.088). The prevalence rate of DN was 0.6% in pediatric patients and 40.7% in elderly patients (p<0.001). In our study, SGD was the second leading cause of renal biopsy. The distribution of the spectrum of SGD varied with time and age. Given the possibility of a detection bias, larger prospective cohort studies are needed in the future. .

Osteocyte dysfunction and renal osteodystrophy: not just calcium and phosphorus anymore

In an important new cross-sectional analysis in this issue, Graciolli and colleagues present bone data from 148 adult patients across the spectrum of chronic kidney disease that confirm that disrupted osteocyte function and abnormal bone histology characterize all stages of chronic kidney disease and suggest that osteocytic Wnt signaling and osteocyte maturation may play a role in the pathogenesis of renal osteodystrophy. These concepts may alter how the skeletal, cardiovascular, and infectious complications of chronic kidney disease are managed.

Kidney disease and venous thromboembolism: Does being woman make the difference?

The risk of venous thromboembolism (VTE) is increased across the spectrum of chronic kidney disease (CKD), from mild to more advanced CKD, and typically characterizes nephrotic syndrome (NS). VTE risk in patients with kidney disease may be due to underlying hemostatic abnormalities, including activation of pro-thrombotic factors, inhibition of endogenous anticoagulation systems, enhanced platelet activation and aggregation, and decreased fibrinolytic activity. The mechanisms involved differ depending on the cause of the kidney impairment (i.e. presence of NS or CKD stage). Sex and gender differences, as well as, environmental factors or comorbidities may play a modulating role; however, specific sex and gender data on this topic are still rare. The aim of the present review is to discuss the VTE risk associated with impairment of kidney function, the potential mechanism accounting for it and the impact of sex differences in this clinical setting.

Economic burden of comorbid chronic kidney disease and diabetes

Objective: To estimate real-world healthcare utilization and expenditures across the spectrum of chronic kidney disease (CKD), as determined by estimated glomerular filtration rate (eGFR) categories in patients with diabetes.Methods: This study employed a retrospective cohort study design using the Truven Healthcare and Claims Dataset from 2009–2012. Index date was defined as the first eGFR value during a continuous enrollment period of 24 months. Cohorts of patients were stratified by Kidney Disease: Improving Global Outcomes CKD stage based on eGFR (stages 1: ≥90 mL/min/1.73 m2; 2: 60–89; 3A: 45–59; 3B: 30–44; 4: 15–29; 5: <15). Healthcare expenditures (total patient and payer paid claims) and utilization (number of claims or visits) were estimated 12-months post-index date using generalized linear modeling and negative binomial modeling, respectively, after adjusting for baseline characteristics.Results: Of 130,098 patients with an index eGFR value and 24-months continuous enrolment, 64,521 (49.59%) were in stage 1 CKD, 47,816 (36.75%) were in stage 2, 13,377 (10.28%) were in stage 3A, 3,217 (2.47%) were in stage 3B, 898 (0.69%) were in stage 4, and 269 (0.21%) were in stage 5. Patients in stages 3A, 3B, and 4 CKD had 1.32 (95% CI = 1.22–1.43), 1.59 (95% CI = 1.41–1.80), and 2.65 (95% CI = 2.23–3.14) times higher rates of diabetes-associated inpatient visits, respectively, compared with stage 1 CKD patients. Patients in stages 3A, 3B, and 4 CKD had increased incremental total annual healthcare expenditures of $1,732 (95% CI = $1,109–$2,356), $2,632 (95% CI = $1,647–$3,619), and $6,949 (95% CI = $5,466–$8,432), respectively, compared with stage 1 CKD patients.Limitations: The claims data were generated for billing and reimbursement, not for research purposes.Conclusions: These real-world data suggest an incremental and significant increase in economic burden in diabetes as kidney function declines, starting with moderate (stage 3A) CKD.

Cardiovascular risk assessment in hemodialysis patients: relation to malnutrition, inflammation, and body fluid determined by bioelectrical impedance

Background Cardiovascular disease prevalence increases as the renal function declines across the spectrum of chronic kidney disease. In end-stage renal disease (ESRD), cardiovascular mortality may even account for 50% of mortality. The coexistence of malnutrition, inflammation, and atherosclerosis (the so-called MIA syndrome) has been observed in hemodialysis (HD) patients and is considered one of the cardiovascular risk factors unique to this population. In addition, chronic fluid overload is frequently present in HD patients. Objective The aim of the present study was to investigate the relationship between nutrition, inflammation, atherosclerosis, the presence of overhydration (OH) measured using multifrequency bioimpedance analysis, and the cardiac condition as assessed using echocardiography in HD patients. Patients and methods Thirty HD patients (mean age: 41.13±12.77 years, 15 were male and 15 were female) were enrolled in the Dialysis Unit of the Alexandria Main University Hospital. Serum albumin was used as a nutritional marker, and serum C-reactive protein (CRP) was used as an inflammatory marker. Doppler ultrasonography was performed to measure the carotid artery intimamedia thickness (CA-IMT) to assess the presence of atherosclerosis. Extracellular water (ECW), OH, and OH/ECW were measured using multifrequency bioimpedance analysis to detect OH. Cardiac condition was determined by means of echocardiographic measurement of the left ventricular mass index and ejection fraction (EF). Results Only two (6.6%) of the studied patients had a low albumin, 26 (86.6%) patients had a positive CRP, 23 (76.6%) patients had high carotid intimamedia thickness (CIMT), and nine (30%) patients had atherosclerotic plaques in the carotid artery. Bioimpedance showed OH in 15 (50%) patients, who had an OH/ECW ratio of more than 0.15. Echocardiography showed high left ventricular mass index in 55.5% and low EF in 16.6%. The presence of inflammation as indicated by CRP was associated with higher CIMT (r=0.520, P=0.003), higher interventricular wall thickness (IVWT) (r=0.469, P=0.007), and lower EF (r=−0.610, P Conclusion Inflammation, atherosclerosis, and fluid overload are prevalent in ESRD patients on MHD. Both inflammation and OH are correlated with increased CIMT and low EF, implicating them in the cardiovascular diseases commonly found in ESRD patients.

Factors influencing pathological ankle-brachial index values along the chronic kidney disease spectrum: the NEFRONA study.

The ankle-brachial index (ABI) is widely used to diagnose subclinical peripheral artery disease (PAD) in the general population, but data assessing its prevalence and related factors in different chronic kidney disease (CKD) stages are scarce. The aim of this study is to evaluate the prevalence and associated factors of pathological ABI values in CKD patients. NEFRONA is a multicentre prospective project that included 2445 CKD patients from 81 centres and 559 non-CKD subjects from 9 primary care centres across Spain. A trained team collected clinical and laboratory data, performed vascular ultrasounds and measured the ABI. PAD prevalence was higher in CKD than in controls (28.0 versus 12.3%, P < 0.001). Prevalence increased in more advanced CKD stages, due to more patients with an ABI ≥1.4, rather than ≤0.9. Diabetes was the only factor predicting both pathological values in all CKD stages. Age, female sex, carotid plaques, higher carotid intima-media thickness, higher high-sensitivity C-reactive protein (hsCRP) and triglycerides, and lower 25-hydroxi-vitamin D were independently associated with an ABI ≤0.9. Higher phosphate and hsCRP, lower low-density lipoprotein (LDL)-cholesterol and dialysis were associated with an ABI ≥1.4. A stratified analysis showed different associated factors in each CKD stage, with phosphate being especially important in earlier CKD, and LDL-cholesterol being an independent predictor only in Sage 5D CKD. Asymptomatic PAD is very prevalent in all CKD stages, but factors related to a low or high pathological ABI differ, revealing different pathogenic pathways. Diabetes, dyslipidaemia, inflammation and mineral-bone disorders play a role in the appearance of PAD in CKD.

Effects of exercise in the whole spectrum of chronic kidney disease: a systematic review.

Chronic kidney disease (CKD) is a public health problem. Although physical activity is essential for the prevention and treatment of most chronic diseases, exercise is rarely prescribed for CKD patients. The objective of the study was to search for and appraise evidence on the effectiveness of exercise interventions on health endpoints in CKD patients. A systematic review was performed of randomized clinical trials (RCTs) designed to compare exercise with usual care regarding effects on the health of CKD patients. MEDLINE, EMBASE, Cochrane Central, Clinical Trials registry, and proceedings of major nephrology conference databases were searched, using terms defined according to the PICO (Patient, Intervention, Comparison and Outcome) methodology. RCTs were independently evaluated by two reviewers. A total of 5489 studies were assessed for eligibility, of which 59 fulfilled inclusion criteria. Most of them included small samples, lasted from 8 to 24 weeks and applied aerobic exercises. Three studies included only kidney transplant patients, and nine included pre-dialysis patients. The remaining RCTs allocated hemodialysis patients. The outcome measures included quality of life, physical fitness, muscular strength, heart rate variability, inflammatory and nutritional markers and progression of CKD. Most of the trials had high risk of bias. The strongest evidence is for the effects of aerobic exercise on improving physical fitness, muscular strength and quality of life in dialysis patients. The benefits of exercise in dialysis patients are well established, supporting the prescription of physical activity in their regular treatment. RCTs including patients in earlier stages of CKD and after kidney transplantation are urgently required, as well as studies assessing long-term outcomes. The best exercise protocol for CKD patients also remains to be established.

Analysis of spectrum of chronic kidney disease in IPD and OPD

The health care burden due to chronic kidney disease has increased worldwide in past decade. Elucidating the spectrum of chronic kidney disease may help in identifying strategies for prevention of chronic kidney disease. So the present study was conducted in 2 tertiary care centers of Lucknow to analyze the spectrum of chronic kidney disease in IPD and OPD renal patients. 100 chronic kidney disease patients (50 from indoor patient department and 50 from outdoor patient department) of more than 15 years of age, belonging to different socio-economic status were selected and surveyed. A questionnaire-cum-interview schedule method was used which included demographic profile of patients, risk factors, severity of disease etc. The findings concluded diabetes as a most prevalent risk factor among patients of both groups, followed by hypertension and other glomerular diseases. Other diseases like urinary tract infections, chronic tubulointerstitial nephritis and CVD cause greater levels of morbidity and mortality among the population as a whole and kidney disease is important in large part because of its relationship with more common diseases. Early treatment can reduce the risk of developing more serious disease or can at least slow the rate at which the disease progresses.

Etiological Spectrum of Chronic Kidney Disease in Young: A Single Center Study from South India

Background and objectives: Chronic kidney disease (CKD) is an important, chronic, noncommunicable disease epidemic that affects the world. Lack of registries precludes an accurate estimation of the number of patients with CKD. Only a few studies are done in our country to assess etiology of CKD in young patients. This study was aimed to assess the etiology of CKD in young patients. Materials and Methods: Data were collected from 50 patients of CKD between 15 and 40 years age who presented to Government General Hospital, Kurnool from July 2012 to June 2013. They were clinically evaluated and underwent relevant investigations including renal biopsy in indicated cases. Results: Of the 50 patients studied, there was an overall male preponderance over all age groups with a mean age of 27.6 ± 4.9 years. Small kidneys were seen in 70% of patients. 92% of patients had proteinuria. Most common symptoms of presentation were related to gastrointestinal disturbances, breathlessness, easy fatigability, and urinary disturbances. Pallor, pedal edema, and facial puffiness were major clinical features. Majority (62%) had CKD of unknown etiology. In this unknown etiology patients, majority were found to have glomerular disease (42%) based on clinical presentation and other supporting investigations. 92% presented in stage IV or stage V CKD. Histopathologically etiology was proven among 19 patients (38%) with renal biopsy. Conclusion: It is concluded that male patients in the third and fourth decades were in the majority requiring medical care. Chronic Glomerulonephritis of unknown causes constitutes a major etiology among the young presenting in late stages of CKD.

Uraemic toxins and cardiovascular disease across the chronic kidney disease spectrum: An observational study

Background and aimsThere is a growing body of evidence supporting the nephrovascular toxicity of indoxyl sulphate (IS) and p-cresyl sulphate (PCS). Nonetheless, a comprehensive description of how these toxins accumulate over the course of chronic kidney disease (CKD) is lacking. Methods and resultsThis cross-sectional observational study included a convenience sample of 327 participants with kidney function categorised as normal, non-dialysis CKD and end-stage kidney disease (ESKD). Participants underwent measurements of serum total and free IS and PCS and assessment of cardiovascular history and structure (carotid intima-media thickness [cIMT, a measure of arterial stiffness]), and endothelial function (brachial artery reactivity [flow-mediated dilation (BAR-FMD); glyceryl trinitrate (BAR-GTN)]).Across the CKD spectrum there was a significant increase in both total and free IS and PCS and their free fractions, with the highest levels observed in the ESKD population. Within each CKD stage, concentrations of PCS, total and free, were significantly greater than IS (all p < 0.01). Both IS and PCS, free and total, were correlated with BAR-GTN (ranging from r = −0.33 to −0.44) and cIMT (r = 0.19 to 0.21), even after adjusting for traditional risk factors (all p < 0.01). Further, all toxins were independently associated with the presence of cardiovascular disease (all p < 0.02). ConclusionMore advanced stages of CKD are associated with progressive increases in total and free serum IS and PCS, as well as increases in their free fractions. Total and free serum IS and PCS were independently associated with structural and functional markers of cardiovascular disease. Studies of therapeutic interventions targeting these uraemic toxins are warranted.

Prediction and management of hyperkalemia across the spectrum of chronic kidney disease.

Hyperkalemia commonly limits optimizing treatment to slow stage 3 or higher chronic kidney disease (CKD) progression. The risk of hyperkalemia is linked to dietary potassium intake, level of kidney function, concomitant diseases that may affect potassium balance such as diabetes, and use of medications that influence potassium excretion. The risk predictors for developing hyperkalemia are an estimated glomerular filtration rate of less than 45 mL/min/1.73 m(2) and a serum potassium level greater than 4.5 mEq/L in the absence of blockers of the renin-angiotensin-aldosterone system (RAAS). Generally, monotherapy with RAAS blockers does not increase risk substantially unless hypotension or volume depletion occur. Dual RAAS blockade involving any combination of an angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, renin inhibition, or aldosterone-receptor blocker markedly increases the risk of hyperkalemia in patients with stage 3 or higher CKD. Moreover, dual RAAS blockade further reduces albuminuria by 25% to 30% compared with monotherapy, it has failed to show a benefit on CKD progression or cardiovascular outcome, and thus is not indicated in such patients because of its marked increase in hyperkalemia potential. Although sodium polystyrene resins exist to manage hyperkalemia in patients requiring therapy that increases serum potassium levels, they are not well tolerated. Newer, more predictable, better-tolerated polymers to bind potassium are on the horizon and may be approved within the next 1 to 2 years.

Hepatitis C virus core antigen test in monitoring of dialysis patients.

Hepatitis C virus infection is a persistent worldwide public health concern. The prevalence of HCV infection is much higher in patients on chronic haemodialysis (HD) than in the general population. HCV infection can detrimentally affect patients throughout the spectrum of chronic kidney disease. Despite the control of blood products, hepatitis C virus transmission is still being observed among patients undergoing dialysis. Detection systems for serum HCV antibodies are insensitive in the acute phase because of the long serological window. Direct detection of HCV depends on PCR test but this test is not suitable for routine screening. Recent studies have highlighted the importance of HCV core antigen detection as an alternative to PCR. Few studies exist about the efficacy of HCV core antigen test in dialysis population. We studied the utility of HCV core antigen test in routine monitoring of virological status of dialysis patients. We screened 92 patients on long-term dialysis both by PCR HCV-RNA and HCV core antigen test. The sensitivity of HCVcAg test was 90%, the specificity 100%, the positive predictive power 100%, the negative predictive power 97%, and the accuracy 97%. We think serological detection of HCV core antigen may be an alternative to NAT techniques for routine monitoring of patients on chronic dialysis.

A Comparison of Herpes Zoster Incidence across the Spectrum of Chronic Kidney Disease, Dialysis and Transplantation

Background: The effect of different renal replacement therapies on the risk of developing herpes zoster in renal failure patients is unknown. We aimed to investigate the incidence of herpes zoster attack among renal failure patients who were receiving different dialysis modalities, renal transplantation (RT), or not receiving any of the above mentioned therapies yet. Methods: A retrospective cohort study of the national health insurance register database was conducted. This observational cohort study involved 79,581 study controls, 15,802 chronic kidney disease patients, 3,694 hemodialysis (HD) patients, 317 peritoneal dialysis (PD) patients, and 159 RT patients. Results: The RT group had the worst risk of herpes zoster (hazard ratio, HR, 8.46; 95% CI 5.85–12.2), followed by PD (HR 3.61; 95% CI 2.49–4.83) and HD (HR 1.35; 95% CI 1.18–1.55), compared with the comparison group (p < 0.0001). The RT group had also the highest risk of developing herpes zoster with complications among all groups (adjusted HR 15.3). The HRs of the PD group were higher than the HRs of the HD group in terms of herpes zoster or its complications (p < 0.0001 and p = 0.0002, respectively). Conclusions: This study suggests that different treatment modalities are associated with different risks of herpes zoster attacks in renal failure patients. PD patients had higher risks than the HD group in terms of herpes zoster or its complications.

Prevalence and spectrum of chronic kidney disease in HIV-positive patients

BackgroundChronic kidney disease (CKD) is currently an important complication of HIV infection once HAART treatment has been introduced.PurposeThe aim of this study was to investigate the prevalence of CKD and...

Chronic kidney disease associated with perinatal HIV infection in children and adolescents

This study describes the incidence, clinical and demographic characteristics, and spectrum of chronic kidney disease (CKD) in youths with perinatal HIV-1 infection. Retrospective analysis between May 1993 and December 2006 of subjects with renal disease followed in the Pediatric AIDS Clinical Trials Group 219/219C multicenter study examining the long-term consequences of perinatal HIV infection. Diagnosis confirmation was made utilizing a questionnaire mailed to research sites. Participants with CKD of other etiology than HIV were excluded. Outcome measures were biopsy-diagnosed CKD and, in the absence of biopsy, HIV-associated nephropathy (HIVAN) using established clinical criteria. Questionnaires on 191 out of 2,102 participants identified 27 cases of CKD: 14 biopsy-diagnosed and 6 clinical cases of HIVAN, and 7 biopsy-diagnosed cases of immune complex-mediated kidney disease (lupus-like nephritis, 3; IgA nephropathy, 2; membranous nephropathy, 2). Incidence rates for CKD associated with HIV in pre-highly active antiretroviral therapy (HAART) (1993-1997) and HAART (1998-2002, 2003-2006) eras were 0.43, 2.84, and 2.79 events per 1,000 person years respectively. In multivariate analysis, black race and viral load ≥100,000 copies/mL (rate ratios 3.28 and 5.05, p ≤ 0.02) were associated with CKD. A variety of immune complex-mediated glomerulonephritides and HIVAN occurs in this population. Black race and uncontrolled viral replication are risk factors for CKD associated with HIV.

Prevalence of sleep disturbances in children and adolescents with chronic kidney disease

Although sleep disorders are common in adults with chronic kidney disease, little is known about the prevalence of sleep problems in children and adolescents with chronic kidney disease and their relationship to health-related quality of life measurements. We performed a clinic-based survey of sleep habits and common symptoms of sleep disturbances in 159 school-aged patients with chronic kidney disease. Three patient groups of chronic kidney disease were assessed: group 1, those not on dialysis and not transplanted; group 2, those on dialysis; and group 3, those with a functioning renal allograft. Four symptom domains for sleep disorders were assessed: excessive daytime sleepiness; sleep disordered breathing; restless legs syndrome symptoms; and insufficient sleep. Patients and the parent-proxy also completed the Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales questionnaire. Ninety-three (93) patients (58.5%) had symptoms of a sleep disturbance. The presence of a sleep disturbance correlated with a decrease in health-related quality of life scores that was independent of the chronic kidney disease study group or estimated glomerular filtration rate. We conclude that sleep disturbances are common throughout the spectrum of chronic kidney disease in children and adolescents and are associated with diminished health-related quality of life scores.

Fibroblast Growth Factor 23 and Risks of Mortality and End-Stage Renal Disease in Patients With Chronic Kidney Disease

A high level of the phosphate-regulating hormone fibroblast growth factor 23 (FGF-23) is associated with mortality in patients with end-stage renal disease, but little is known about its relationship with adverse outcomes in the much larger population of patients with earlier stages of chronic kidney disease. To evaluate FGF-23 as a risk factor for adverse outcomes in patients with chronic kidney disease. A prospective study of 3879 participants with chronic kidney disease stages 2 through 4 who enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008. All-cause mortality and end-stage renal disease. At study enrollment, the mean (SD) estimated glomerular filtration rate (GFR) was 42.8 (13.5) mL/min/1.73 m(2), and the median FGF-23 level was 145.5 RU/mL (interquartile range [IQR], 96-239 reference unit [RU]/mL). During a median follow-up of 3.5 years (IQR, 2.5-4.4 years), 266 participants died (20.3/1000 person-years) and 410 reached end-stage renal disease (33.0/1000 person-years). In adjusted analyses, higher levels of FGF-23 were independently associated with a greater risk of death (hazard ratio [HR], per SD of natural log-transformed FGF-23, 1.5; 95% confidence interval [CI], 1.3-1.7). Mortality risk increased by quartile of FGF-23: the HR was 1.3 (95% CI, 0.8-2.2) for the second quartile, 2.0 (95% CI, 1.2-3.3) for the third quartile, and 3.0 (95% CI, 1.8-5.1) for the fourth quartile. Elevated fibroblast growth factor 23 was independently associated with significantly higher risk of end-stage renal disease among participants with an estimated GFR between 30 and 44 mL/min/1.73 m(2) (HR, 1.3 per SD of FGF-23 natural log-transformed FGF-23; 95% CI, 1.04-1.6) and 45 mL/min/1.73 m(2) or higher (HR, 1.7; 95% CI, 1.1-2.4), but not less than 30 mL/min/1.73 m(2). Elevated FGF-23 is an independent risk factor for end-stage renal disease in patients with relatively preserved kidney function and for mortality across the spectrum of chronic kidney disease.

What makes plaques vulnerable in CKD?: a fresh look at metalloproteinases

Coll et al. show that across the spectrum of chronic kidney disease (CKD), atherosclerosis severity is correlated with metalloproteinase-10 (MMP-10) levels. This suggests that the reduced fibrous content in atherosclerotic plaques may result partly from high MMP-10. Future studies should look at the association of MMPs (and their inhibitors) with the inflammatory component of atherosclerosis, and with stable and unstable atherosclerotic lesions.