Urinary Markers of Fibrosis and Risk of Cardiovascular Events and Death in Kidney Transplant Recipients: The FAVORIT Trial

Park, M.; Katz, Ronit; Shlipak, Michael G.; Weiner, Daniel E.; Tracy, Russell P.; Jotwani, Vasantha; Hughes‐Austin, Jan M.; Gabbai, Francis B.; Hsu, Chi-yuan; Pfeffer, Marc A.; Bansal, Nisha; Bostom, Andrew G.; Gutiérrez, Orlando M.; Sarnak, Mark J.; Levey, Andrew S.; Ix, Joachim H.

doi:10.1111/ajt.14284

Cited by 39 publications

(29 citation statements)

References 39 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the increased expression and deposition of collagen type I alpha 1 in interstitial kidney fibrosis can be attributed to increased expression of procollagen-n-proteinase as it has been shown in the spontaneously hypertensive rat [87]. High levels of urinary procollagen type I have been associated with both cardiovascular disease and death in kidney transplant recipients [88]. Despite that, the importance of procollagen I alpha 1 excretion in urine as a marker of kidney disease progression has not been yet thoroughly evaluated in long prospective large cohorts of patients with CKD.…”

Section: Procollagen I Alphamentioning

confidence: 87%

Biomarkers in Progressive Chronic Kidney Disease. Still a Long Way to Go

Ntrinias

Papasotiriou

Balta

et al. 2019

Prilozi

View full text Add to dashboard Cite

The traditional chronic kidney disease (CKD) biomarkers (eGFR based on serum creatinine, sex and age and albuminuria) cannot predict a patient’s individual risk for developing progressive CKD. For this reason, it is necessary to identify novel CKD biomarkers that will be able to predict which patients are prone to develop progressive disease and discriminate between disease processes in different parts of the nephron (glomeruli or tubules). A good biomarker should change before or simultaneously with lesion development and its changes should correlate strongly with lesion development. Also, there should be a close relationship between severity of injury and amount of detectable biomarker and its levels should decrease with diminishing injury. Among the large number of molecules under investigation, we have reviewed the most promising ones: NGAL and KIM-1, MCP-1, MMP-9, clusterin, MMP-9, TIMP-1, Procollagen I alpha 1 and suPAR. All these, have been studied as biomarkers for prediction of CKD progression in cohorts of patients with chronic kidney disease of different stages and various aetiologies (proteinuric and non-proteinuric, glomerulonephritides, diabetic, hypertensive and polycystic kidney disease). There is evidence that these molecules could be useful as biomarkers for progressive chronic kidney disease, however, the available data are not enough to draw final conclusions. Further studies with large cohorts and long follow-up are required to identify appropriate biomarkers, that will be able to accurately and reliably define the risk for progressive chronic kidney disease.

show abstract

Section: Procollagen I Alphamentioning

confidence: 87%

Biomarkers in Progressive Chronic Kidney Disease. Still a Long Way to Go

Ntrinias

Papasotiriou

Balta

et al. 2019

Prilozi

View full text Add to dashboard Cite

show abstract

“…Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that attracts macrophages to the site of injury [15][16][17], whereas chitinase-3-like protein-1 (YKL-40) functions as a mediator of the reparative response to tubular injury [18,19]. Some studies have demonstrated that urinary markers of tubular damage are associated with higher cardiovascular and mortality risks [17,[20][21][22], whereas other studies found no significant associations [23,24]. Few of the existing studies included large numbers of participants with CKD who may have more extensive tubule damage and higher risk for CVD and death.…”

Section: Introductionmentioning

confidence: 99%

Urinary Biomarkers of Tubular Damage Are Associated with Mortality but Not Cardiovascular Risk among Systolic Blood Pressure Intervention Trial Participants with Chronic Kidney Disease

et al. 2019

View full text Add to dashboard Cite

Background: Kidney tubulointerstitial fibrosis on biopsy is a strong predictor of chronic kidney disease (CKD) progression, and CKD is associated with elevated risk of cardiovascular disease (CVD). Tubular health is poorly quantified by traditional kidney function measures, including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of tubular injury, inflammation, and repair would be associated with higher risk of CVD and mortality in persons with CKD. Methods: We measured urinary concentrations of interleukin-18 (IL-18), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and chitinase-3-like protein-1 (YKL-40) at baseline among 2,377 participants of the Systolic Blood Pressure Intervention Trial who had an eGFR < 60 mL/min/1.73 m². We used Cox proportional hazards models to evaluate biomarker associations with CVD events and all-cause mortality. Results: At baseline, the mean age of participants was 72 ± 9 years, and eGFR was 48 ± 11 mL/min/1.73 m². Over a median follow-up of 3.8 years, 305 CVD events (3.6% per year) and 233 all-cause deaths (2.6% per year) occurred. After multivariable adjustment including eGFR, albuminuria, and urinary creatinine, none of the biomarkers showed statistically significant associations with CVD risk. Urinary IL-18 (hazard ratio [HR] per 2-fold higher value, 1.14; 95% CI 1.01–1.29) and YKL-40 (HR per 2-fold higher value, 1.08; 95% CI 1.02–1.14) concentrations were each incrementally associated with higher mortality risk. Associations were similar when stratified by randomized blood pressure arm. Conclusions: Among hypertensive trial participants with CKD, higher urinary IL-18 and YKL-40 were associated with higher risk of mortality, but not CVD.

show abstract

“…To evaluate the potential association between serum T50 and the composite CVD outcome, we utilized an efficient, preexisting case-cohort selection scheme employed for prior FAVORIT ancillary studies [11][12][13], especially the report of Park et al [13]. Briefly, a 530-participant subcohort with complete baseline data for key laboratory variables, including serum creatinine and lipid studies, as well as urine albumin to creatinine ratio (UACR), was selected at random from the entire cohort, regardless of whether or not the T50, Fetuin-A, and CVD in Kidney Transplantation participants had experienced a fatal or nonfatal CVD outcome during follow-up [11][12][13].…”

Section: Study Populationmentioning

confidence: 99%

“…Briefly, a 530-participant subcohort with complete baseline data for key laboratory variables, including serum creatinine and lipid studies, as well as urine albumin to creatinine ratio (UACR), was selected at random from the entire cohort, regardless of whether or not the T50, Fetuin-A, and CVD in Kidney Transplantation participants had experienced a fatal or nonfatal CVD outcome during follow-up [11][12][13]. We also selected all participants in the full cohort who were identified as having experienced a CVD event, irrespective of whether they were sampled in the random subcohort.…”

Section: Study Populationmentioning

confidence: 99%

Serum Calcification Propensity and Fetuin-A: Biomarkers of Cardiovascular Disease in Kidney Transplant Recipients

et al. 2018

View full text Add to dashboard Cite

Background: “T50,” shortened transformation time from primary to secondary calciprotein particles may reflect deranged mineral metabolism predisposing to vascular calcification and cardiovascular disease (CVD). The glycoprotein fetuin-A is a major T50 determinant. Methods: The Folic Acid For Vascular Outcome Prevention In Transplantation (FAVORIT) cohort is a completed, large, multiethnic controlled clinical trial cohort of chronic, stable kidney transplant recipients (KTRs). We conducted a longitudinal case-cohort analysis using a randomly selected subcohort of patients, and all individual cases who developed CVD. Serum T50 and fetuin-A were determined in this total of n = 685 FAVORIT trial participants at randomization. Results: During a median surveillance of 2.18-years, 311 incident or recurrent CVD events occurred. Shorter T50 (minutes) or reduced fetuin-A concentrations (g/L) were associated with CVD after adjustment for treatment assignment, systolic blood pressure, age, sex, race, preexisting CVD and diabetes, smoking, body mass index, total cholesterol/HDL cholesterol, kidney allograft vintage and type, calcineurin inhibitor, or lipid-lowering drug use, estimated glomerular filtration rate, and urinary albumin/creatinine: tertile 1 (lowest) to tertile 3 (highest) comparisons, T50, (hazard ratio [HR] 1.86; 95% CI 1.20–2.89); fetuin-A, (HR 2.25; 95% CI 1.38–3.69). Elevated high sensitivity c-reactive protein (hsCRP) was an effect modifier of both these associations. Conclusions: Shortened T50, as well as reduced fetuin-A levels, ostensible promoters of vascular calcification, remained associated with greater risk for CVD outcomes, after adjustment for major CVD risk factors, measures of kidney function and damage, and KTR clinical characteristics and demographics, in a large, multiethnic cohort of long-term KTRs. Increased hsCRP was an effect modifier of these CVD risk associations.

show abstract

Urinary Markers of Fibrosis and Risk of Cardiovascular Events and Death in Kidney Transplant Recipients: The FAVORIT Trial

Cited by 39 publications

References 39 publications

Biomarkers in Progressive Chronic Kidney Disease. Still a Long Way to Go

Biomarkers in Progressive Chronic Kidney Disease. Still a Long Way to Go

Urinary Biomarkers of Tubular Damage Are Associated with Mortality but Not Cardiovascular Risk among Systolic Blood Pressure Intervention Trial Participants with Chronic Kidney Disease

Serum Calcification Propensity and Fetuin-A: Biomarkers of Cardiovascular Disease in Kidney Transplant Recipients

Contact Info

Product

Resources

About