Comparison of three different cystatin C measurement procedures in a pediatric chronic kidney disease cohort: Calibration for longitudinal measurements and implications for clinical estimation of GFR.

Introduction: Serum cystatin C (CysC) is used to estimate glomerular filtration rate (eGFR), including in the Chronic Kidney Disease in Children (CKiD) Under 25 years (U25eGFR) equations. Several CysC measurement procedures available from diagnostic vendors include reference material for calibration, but the extent of heterogeneity across manufacturers is unclear. Since heterogeneity may have clinical and research implications for eGFR, we evaluated three CysC procedures in samples from the CKiD study representing a wide spectrum of kidney function.

CKD Prevalence and Incidence in Older Adults Using Estimated GFR With Different Filtration Markers: The Atherosclerosis Risk in Communities Study.

Rationale & Objective: The prevalence of chronic kidney disease (CKD) is known to increase with age; however, creatinine may be a less reliable filtration marker in older adults. Few studies have investigated the prevalence and progression of CKD using different filtration markers for estimating glomerular filtration rate (GFR).

Study Design: A prospective observational cohort study.

Iohexol plasma clearance measurement protocol standardization for adults: a consensus paper of the European Kidney Function Consortium.

International consensus supports the development of standardized protocols for measured glomerular filtration rate (mGFR) to facilitate the integration of mGFR testing in both clinical and research settings. To this end, the European Kidney Function Consortium convened an international group of experts with relevant experience in mGFR. The working group performed an extensive literature search to inform the development of recommendations for mGFR determination using 1-compartment plasma clearance models and iohexol as the exogenous filtration marker.

Age of Diabetes Diagnosis and Lifetime Risk of Dementia: The Atherosclerosis Risk in Communities (ARIC) Study.

Objective: The impact of age of diabetes diagnosis on dementia risk across the life course is poorly characterized. We estimated the lifetime risk of dementia by age of diabetes diagnosis.

Research Design And Methods: We included 13,087 participants from the Atherosclerosis Risk in Communities Study who were free from dementia at age 60 years.

Longitudinal Trajectories of Biomarkers of Kidney Tubular Function in Type 1 Diabetes.

Introduction: Tubular biomarkers may shed insight into progression of kidney tubulointerstitial pathology complementary to traditional measures of glomerular function and damage.

Methods: We examined trajectories of tubular biomarkers in the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC Study) of type 1 diabetes (T1D). Biomarkers were measured in a subset of 220 participants across 7 time points over 26 years.

Associations of Kidney Tubular Biomarkers With Incident Macroalbuminuria and Sustained Low eGFR in DCCT/EDIC.

Objective: Tubulointerstitial injury contributes to diabetic kidney disease (DKD) progression. We tested tubular biomarker associations with DKD development in type 1 diabetes (T1D).

Research Design And Methods: We performed a case-cohort study examining associations of tubular biomarkers, measured across seven time points spanning ∼30 years, with incident macroalbuminuria ("severely elevated albuminuria," urinary albumin excretion rate [AER] ≥300 mg/day) and sustained low estimated glomerular filtration rate (eGFR) (persistent eGFR <60 mL/min/1.

Urine Albumin Measurements in Clinical Diagnostics.

Background: Measurement of urine albumin is critical for diagnosis, risk classification, and monitoring of chronic kidney disease (CKD). Guidelines recommend clinical decision cutoffs for the urine albumin-to-creatinine ratio (ACR) of 30 and 300 mg/g (3 and 30 mg/mmol). However, differences among manufacturers' routine urine albumin measurement procedures have been found to exceed 40%, suggesting CKD diagnosis and risk classification may vary depending upon the specific measurement procedure implemented in the laboratory.

Quantification of Mycophenolic Acid in Plasma by High Performance Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

Mycophenolate mofetil (MMF) and sodium mycophenolate are commonly prescribed immunosuppressive drugs for patients who have undergone solid organ transplant. Therapeutic drug monitoring (TDM) of these drugs is performed by assessing mycophenolic acid (MPA) in plasma. Due to the large inter-individual variability and narrow therapeutic range, the precise determination of systemic MPA concentration carries great clinical significance.

Evaluation of novel candidate filtration markers from a global metabolomic discovery for glomerular filtration rate estimation.

Creatinine and cystatin-C are recommended for estimating glomerular filtration rate (eGFR) but accuracy is suboptimal. Here, using untargeted metabolomics data, we sought to identify candidate filtration markers for a new targeted assay using a novel approach based on their maximal joint association with measured GFR (mGFR) and with flexibility to consider their biological properties. We analyzed metabolites measured in seven diverse studies encompasing 2,851 participants on the Metabolon H4 platform that had Pearson correlations with log mGFR and used a stepwise approach to develop models to < -0.

Discrepancies between Cystatin C-Based and Creatinine-Based eGFR.

Background: Recent guidance suggests clinicians increase use of cystatin C for the estimation of GFR. Discrepant levels of creatinine- versus cystatin C-based eGFR (eGFRcr versus eGFRcys) can occur and might signify inaccurate estimation of GFR using creatinine alone. This study sought to enhance the knowledge of the risk factors and clinical implications of having a large eGFR discrepancy.

Association of urine and plasma ADMA with atherosclerotic risk in DKD cardiovascular disease risk in diabetic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study.

Background: Chronic kidney disease (CKD) is associated with atherosclerotic cardiovascular disease (ASCVD) risk, especially among those with diabetes. Altered metabolism of solutes that accumulate in CKD [asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and trimethylamine N-oxide (TMAO)] may reflect pathways linking CKD with ASCVD.

Methods: This case-cohort study included Chronic Renal Insufficiency Cohort participants with baseline diabetes, estimated glomerular filtration rate <60 mL/min/1.

Prediabetes, intervening diabetes and subsequent risk of dementia: the Atherosclerosis Risk in Communities (ARIC) study.

Aims/hypothesis: The aim of this work was to evaluate whether the association of prediabetes with dementia is explained by the intervening onset of diabetes.

Methods: Among participants of the Atherosclerosis Risk in Communities (ARIC) study we defined baseline prediabetes as HbA 39-46 mmol/mol (5.7-6.

Assessment of circulating insulin using liquid chromatography-mass spectrometry during insulin glargine treatment in type 2 diabetes: Implications for estimating insulin sensitivity and β-cell function.

Aim: To determine the potential impact of the cross-reactivity of insulin glargine U-100 and its metabolites on insulin sensitivity and β-cell measures in people with type 2 diabetes.

Materials And Methods: Using liquid chromatography-mass spectrometry (LC-MS), we measured concentrations of endogenous insulin, glargine and its two metabolites (M1 and M2) in fasting and oral glucose tolerance test-stimulated plasma from 19 participants and fasting specimens from another 97 participants 12 months after randomization to receive the insulin glargine. The last dose of glargine was administered before 10:00 PM the night before testing.

Estimated Kidney Tubular Secretion and Kidney, Cardiovascular, and Mortality Outcomes in CKD: The Systolic Blood Pressure Intervention Trial.

Rational & Objective: Many drugs, metabolites, and toxins are cleared by the kidneys via tubular secretion. Whether novel endogenous measures of tubular secretion provide information about kidney, cardiovascular, and mortality risk is uncertain.

Study Design: Longitudinal subgroup analysis of clinical trial participants.

Association of Uremic Solutes With Cardiovascular Death in Diabetic Kidney Disease.

Rationale & Objective: Cardiovascular disease (CVD) is a major cause of mortality among people with diabetic kidney disease (DKD). The pathophysiology is inadequately explained by traditional CVD risk factors. The uremic solutes trimethylamine-N-oxide (TMAO) and asymmetric and symmetric dimethylarginine (ADMA, SDMA) have been linked to CVD in kidney failure with replacement therapy (KFRT), but data are limited in populations with diabetes and less severe kidney disease.

Self-reported Race, Serum Creatinine, Cystatin C, and GFR in Children and Young Adults With Pediatric Kidney Diseases: A Report From the Chronic Kidney Disease in Children (CKiD) Study.

Rationale & Objective: Recent reassessment of the use of race in estimated glomerular filtration rate (eGFR) in adults has instigated questions about the role of race in eGFR expressions for children. Little research has examined the associations of self-reported race with measured GFR (mGFR) adjusting for serum creatinine or cystatin C in children and young adults with chronic kidney disease (CKD). This study examined these associations and evaluated the performance of the previously published "U25" (under the age of 25 years) eGFR equations in a large cohort of children and young adults with CKD.

New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race.

Background: Current equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct.

Methods: We developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.

A Low-Sodium DASH Dietary Pattern Affects Serum Markers of Inflammation and Mineral Metabolism in Adults with Elevated Blood Pressure.

Background: The blood pressure-lowering effects of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and reduced sodium intake are well established. The effects on other biomarkers related to vascular health are of interest and might assist in explaining the effects of the DASH diet and sodium reduction.

Objectives: We hypothesized that a low-sodium DASH diet improves (lowers) biomarkers of inflammation [C-reactive protein (CRP) and soluble urokinase plasminogen activator receptor (suPAR)] and mineral metabolism [phosphorus and fibroblast growth factor-23 (FGF23)].