OMICS in Chronic Kidney Disease: Focus on Prognosis and Prediction

Chronic kidney disease (CKD) patients are characterized by a high residual risk for cardiovascular (CV) events and CKD progression. This has prompted the implementation of new prognostic and predictive biomarkers with the aim of mitigating this risk. The ‘omics’ techniques, namely genomics, proteomics, metabolomics, and transcriptomics, are excellent candidates to provide a better understanding of pathophysiologic mechanisms of disease in CKD, to improve risk stratification of patients with respect to future cardiovascular events, and to identify CKD patients who are likely to respond to a treatment. Following such a strategy, a reliable risk of future events for a particular patient may be calculated and consequently the patient would also benefit from the best available treatment based on their risk profile. Moreover, a further step forward can be represented by the aggregation of multiple omics information by combining different techniques and/or different biological samples. This has already been shown to yield additional information by revealing with more accuracy the exact individual pathway of disease.

Download Full-text

The Role of Prognostic and Predictive Biomarkers for Assessing Cardiovascular Risk in Chronic Kidney Disease Patients

BioMed Research International ◽

10.1155/2020/2314128 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Michele Provenzano ◽

Michele Andreucci ◽

Luca De Nicola ◽

Carlo Garofalo ◽

Yuri Battaglia ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Specific Treatment ◽

Predictive Biomarkers ◽

Major Complication ◽

Global Dimension ◽

Prognostic Biomarkers ◽

Improve Risk Stratification ◽

Markers Of Inflammation ◽

Cv Disease

Chronic kidney disease (CKD) is currently defined as the presence of proteinuria and/or an eGFR<60 mL/min/1.73m2 on the basis of the renal diagnosis. The global dimension of CKD is relevant, since its prevalence and incidence have doubled in the past three decades worldwide. A major complication that occurs in CKD patients is the development of cardiovascular (CV) disease, being the incidence rate of fatal/nonfatal CV events similar to the rate of ESKD in CKD. Moreover, CKD is a multifactorial disease where multiple mechanisms contribute to the individual prognosis. The correct development of novel biomarkers of CV risk may help clinicians to ameliorate the management of CKD patients. Biomarkers of CV risk in CKD patients are classifiable as prognostic, which help to improve CV risk prediction regardless of treatment, and predictive, which allow the selection of individuals who are likely to respond to a specific treatment. Several prognostic (cystatin C, cardiac troponins, markers of inflammation, and fibrosis) and predictive (genes, metalloproteinases, and complex classifiers) biomarkers have been developed. Despite previous biomarkers providing information on the pathophysiological mechanisms of CV risk in CKD beyond proteinuria and eGFR, only a minority have been adopted in clinical use. This mainly depends on heterogeneous results and lack of validation of biomarkers. The purpose of this review is to present an update on the already assessed biomarkers of CV risk in CKD and examine the strategies for a correct development of biomarkers in clinical practice. Development of both predictive and prognostic biomarkers is an important task for nephrologists. Predictive biomarkers are useful for designing novel clinical trials (enrichment design) and for better understanding of the variability in response to the current available treatments for CV risk. Prognostic biomarkers could help to improve risk stratification and anticipate diagnosis of CV disease, such as heart failure and coronary heart disease.

Download Full-text

Analysis of blood gas beyond bicarbonate in outpatients with stage 3–5 chronic kidney disease

Turkish Journal of Biochemistry ◽

10.1515/tjb-2020-0073 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Ilter Bozaci ◽

Ali Nazmi Can Doğan ◽

Merve Aktar ◽

Alev Mahşer ◽

Gizem Yıldırım ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Metabolic Acidosis ◽

Kidney Disease ◽

Odds Ratio ◽

Mixed Type ◽

Base Excess ◽

Blood Gas ◽

Ckd Progression ◽

Group 1

AbstractObjectivesMetabolic acidosis is a common disorder seen in course of chronic kidney disease (CKD). In this study, we aimed to investigate the association of Base excess (BE), Anion gap (AG) and Delta Ratio with progression of CKD, renal replacement therapy (RRT) requirement and mortality in patients with stage 3–5 CKD.MethodsA total of 212 patients with stage 3–5 CKD were included in this study. Patients were divided into two groups according to the baseline BE level. Patients were also grouped according to the delta ratio such as non- AG, High AG and mixed type.ResultsMean BE level was significantly lower (−4.7 ± 4.0 vs. −3.3 ± 4.3; p=0.02) in patients with CKD progression. The patients in group 1 (n: 130) (Be<−2.5) revealed more CKD progression (%53 vs. %32; p=0.002), and RRT requirement (%35 vs. %15; p=0.001). Baseline BE <−2.5 (odds ratio, 0.38; 95% CI, 0.16 to 0.91; p<0.05) and baseline GFR (odds ratio, 0.94; 95% CI, 0.90 to 0.97; p<0.001) were independently related to RRT requirement. Delta BE was independently associated with mortality (odds ratio, 0.90; 95% CI, 0.85–0.96; p<0.01).ConclusionsLow BE levels were associated with CKD progression and RRT requirement. BE change is associated with mortality during the follow-up of those patients.

Download Full-text

Serum Magnesium, Blood Pressure, and Risk of Hypertension and Chronic Kidney Disease Progression in the CRIC Study

Hypertension ◽

10.1161/hypertensionaha.121.17694 ◽

2021 ◽

Author(s):

Simon Correa ◽

Xavier E. Guerra-Torres ◽

Sushrut S. Waikar ◽

Finnian R. Mc Causland

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Disease Progression ◽

Lower Risk ◽

Serum Magnesium ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Ckd Progression ◽

Baseline Serum

Magnesium is involved in the regulation of blood pressure (BP). Abnormalities in serum magnesium are common in chronic kidney disease (CKD), yet its association with the development of hypertension and CKD progression in patients with CKD is unclear. We analyzed data from 3866 participants from the CRIC Study (Chronic Renal Insufficiency Cohort). Linear regression assessed the association of serum magnesium with baseline systolic BP (SBP) and diastolic BP (DBP). Logistic regression explored the association of serum magnesium with various definitions of hypertension. Cox proportional hazards models explored assessed the risk of incident hypertension and CKD progression. Mean serum magnesium was 2.0 mEq/L (±0.3 mEq/L). Higher magnesium was associated with lower SBP (−3.4 mm Hg [95% CI, −5.8 to −1.0 per 1 mEq/L]) and lower DBP (−2.9 mm Hg [95% CI, −4.3 to −1.5 per 1 mEq/L]). Higher magnesium was associated with a lower risk of American Heart Association–defined hypertension (SBP≥130 mm Hg or DBP≥80 mm Hg) at baseline (adjusted hazard ratio, 0.65 [95% CI, 0.49–0.86 per 1 mEq/L]), a lower risk of suboptimally controlled BP (SBP≥120 mm Hg or DBP≥80 mm Hg; adjusted odds ratio, 0.58 [95% CI, 0.43–0.78 per 1 mEq/L]). In time-to-event analyses, higher baseline serum magnesium was associated with a nominally lower risk of incident CRIC-defined hypertension (adjusted hazard ratio, 0.77 [95% CI, 0.46–1.31 per 1 mEq/L]). Higher magnesium was associated with a significantly lower risk of CKD progression (adjusted hazard ratio, 0.68 [95% CI, 0.54–0.86 per 1 mEq/L]). In patients with CKD, higher serum magnesium is associated with lower SBP and DBP, and with a lower risk of hypertension and CKD progression. In patients with CKD, whether magnesium supplementation could optimize BP control and prevent disease progression deserves further investigation.

Download Full-text

Non-linear progression of chronic kidney disease and associated factors in hypertensive patients: a 4-year cohort study

10.21203/rs.3.rs-42323/v1 ◽

2020 ◽

Author(s):

Luciana Saraiva da Silva ◽

Tiago Ricardo Moreira ◽

Rodrigo Gomes da Silva ◽

Rosângela Minardi Mitre Cotta

Keyword(s):

Chronic Kidney Disease ◽

Cohort Study ◽

Kidney Disease ◽

Associated Factors ◽

Multivariate Analyses ◽

Multivariate Logistic Regression ◽

Ckd Progression ◽

Hypertensive Patients ◽

Explanatory Variables ◽

Non Linear

Abstract Background Recent studies suggest that the progression of chronic kidney disease (CKD) is not linear, but we do not have clear evidence on this issue, especially in hypertensive patients. We sought to evaluate the progression of CKD and associated factors over four years in a cohort of hypertensive patients. Methods We conducted a prospective cohort study during the years 2012 and 2016, with hypertensive patients diagnosed with CKD (n = 113). The progression of CKD was assessed through the evolution of the glomerular filtration rate (GFR) and the change in the stage of CKD between 2012 and 2016. Sociodemographic, economic, lifestyle, clinical, anthropometric, and biochemical variables were evaluated. The strength of the association between CKD progression and explanatory variables was assessed by odds ratio (OR) and their respective 95% confidence intervals using univariate and multivariate logistic regression. Results Regarding progression, 78.1% of the CKD patients did not progress over four years. When assessing the CKD trajectory (2012–2016) through the evolution of GFR, there was a mean reduction of 1.3 mL/min/1.73m² in four years. In the group that progressed, there was a reduction of 13 mL/min/1.73m², while in the group that did not progress, there was an increase of 2 mL/min/1.73m². In the multivariate analyses, age (p = 0.047), diabetes mellitus (DM) (p = 0.042), and urea (p = 0.050) were independently associated with CKD progression. Conclusions The findings of the present study showed a non-linear progression of CKD over the four years, contrary to what is traditionally expected. Age, DM and urea were independently associated with CKD progression.

Download Full-text

Plant-Dominant Low-Protein Diet for Conservative Management of Chronic Kidney Disease

10.20944/preprints202005.0516.v1 ◽

2020 ◽

Author(s):

Kamyar Kalantar-Zadeh ◽

Shivam Joshi ◽

Rebecca Schlueter ◽

Joanne L. Cooke ◽

Amanda Brown-Tortorici ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Disease Risk ◽

Protein Diet ◽

Low Protein Diet ◽

Uremic Toxin ◽

Functional Impairments ◽

Ckd Progression ◽

Meat Intake ◽

Low Protein

Chronic kidney disease (CKD) affects >10% of the adult population. Each year approximately 120,000 Americans develop end-stage kideny disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6-0.8 g/kg/day comprised of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, can be promising. The scientific premise of the PLADO is based on the observations that high protein diets with high meat intake are not only associated with higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of hyperkalemia, given constipation from the typical low fiber intake. Plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk in CKD patients. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.

Download Full-text

HMOX1 and Acute Kidney Injury in Sickle Cell Anemia

Blood ◽

10.1182/blood.v130.suppl_1.686.686 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 686-686

Author(s):

Santosh L. Saraf ◽

Maya Viner ◽

Ariel Rischall ◽

Binal Shah ◽

Xu Zhang ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Risk Factor ◽

Kidney Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Kidney Injury ◽

Ckd Progression ◽

Kdigo Guidelines

Abstract Acute kidney injury (AKI) is associated with tubulointerstitial fibrosis and nephron loss and may lead to an increased risk for subsequently developing chronic kidney disease (CKD). In adults with sickle cell anemia (SCA), high rates of CKD have been consistently observed, although the incidence and risk factors for AKI are less clear. We evaluated the incidence of AKI, defined according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines as a rise in serum creatinine by ≥0.3mg/dL within 48 hours or ≥1.5 times baseline within seven days, in 158 of 299 adult SCA patients enrolled in a longitudinal cohort from the University of Illinois at Chicago. These patients were selected based on the availability of genotyping for α-thalassemia, BCL11A rs1427407, APOL1 G1/G2, and the HMOX1 rs743811 and GT-repeat variants. Median values and interquartile range (IQR) are provided. With a median follow up time of 66 months (IQR, 51-74 months), 137 AKI events were observed in 63 (40%) SCA patients. AKI was most commonly observed in the following settings: acute chest syndrome (25%), an uncomplicated vaso-occlusive crisis (VOC)(24%), a VOC with pre-renal azotemia determined by a fractional excretion of sodium <1% or BUN-to-creatinine ratio >20:1 (14%), or a VOC with increased hemolysis, defined as an increase in serum LDH or indirect bilirubin level >1.5 times over the baseline value at the time of enrollment (12%). Compared to individuals who did not develop AKI, SCA adults who developed an AKI event were older (AKI: median and IQR age of 35 (26-46) years, no AKI: 28 (23 - 26) years; P=0.01) and had a lower estimated glomerular filtration rate (eGFR) (AKI: median and IQR eGFR of 123 (88-150) mL/min/1.73m2, no AKI: 141 (118-154) mL/min/1.73m2; P=0.02) by the Kruskal-Wallis test at the time of enrollment. We evaluated the association of a panel of candidate gene variants with the risk of developing an AKI event. These included loci related to the degree of hemolysis (α-thalassemia, BCL11A rs1427407), to chronic kidney disease (APOL1 G1/G2 risk variants), and to heme metabolism (HMOX1) . Using a logistic regression model that adjusted for age and eGFR at the time of enrollment, the risk of an AKI event was associated with older age (10-year OR 2.6, 95%CI 1.4-4.8, P=0.002), HMOX1 rs743811 (OR 3.1, 95%CI 1.1-8.7, P=0.03), and long HMOX1 GT-repeats, defined as >25 repeats (OR 2.5, 95%CI 1.01-6.1, P=0.04). Next, we assessed whether AKI is associated with a more rapid decline in eGFR and with CKD progression, defined as a 50% reduction in eGFR, on longitudinal follow up. Using a mixed effects model that adjusted for age and eGFR at the time of enrollment, the rate of eGFR decline was significantly greater in those with an AKI event (β = -0.51) vs. no AKI event (β = -0.16) (P=0.03). With a median follow up time of 66 months (IQR, 51-74 months), CKD progression was observed in 21% (13/61) of SCA patients with an AKI event versus 9% (8/88) without an AKI event. After adjusting for age and eGFR at the time of enrollment, the severity of an AKI event according to KDIGO guidelines (stage 1 if serum creatinine rises 1.5-1.9 times baseline, stage 2 if the rise is 2.0-2.9 times baseline, and stage 3 if the rise is ≥3 times baseline or ≥4.0 mg/dL or requires renal replacement therapy) was a risk factor for CKD progression (unadjusted HR 1.6, 95%CI 1.1-2.3, P=0.02; age- and eGFR-adjusted HR 1.6, 95%CI 1.1-2.5, P=0.03). In conclusion, AKI is commonly observed in adults with sickle cell anemia and is associated with increasing age and the HMOX1 GT-repeat and rs743811 polymorphisms. Furthermore, AKI may be associated with a steeper decline in kidney function and more severe AKI events may be a risk factor for subsequent CKD progression in SCA. Future studies understanding the mechanisms, consequences of AKI on long-term kidney function, and therapies to prevent AKI in SCA are warranted. Disclosures Gordeuk: Emmaus Life Sciences: Consultancy.

Download Full-text

MO535PREVALENCE OF CHRONIC KIDNEY DISEASE AND ASSOCIATED RISK FACTORS ON THE ISLAND OF MONTSERRAT

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab087.0055 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Keniel Chrysostom ◽

Lori-Ann Fisher ◽

Everard Barton ◽

Adedamola Soyibo ◽

Grethlyn West ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Female Gender ◽

Health Care Facilities ◽

Cluster Sampling ◽

Long Term Effects ◽

Ckd Progression ◽

Cross Sectional ◽

The Caribbean

Abstract Background and Aims Chronic Kidney Disease (CKD) is a global health problem with disproportionate burden in low- and middle-income countries in Latin America and the Caribbean. Despite these disparities, little is known of the prevalence and risk factors of CKD in the Caribbean. We sought to determine prevalence of CKD among patients attending ambulatory centres in Montserrat, an island that to date, has no facilities for renal replacement therapy. Method A cross-sectional observational study of Participants were individuals aged ≥18 years was performed. Random cluster sampling of at least 500 participants who attended clinic from January 1 to July 1, 2020 across all primary health care facilities on island was performed. Patients without lab values for creatinine were excluded. The main outcome measures was estimated CKD prevalence (as defined based on KDIGO 2012 guidelines of eGFR < 60mL/min/1.73m2 using creatinine based CKD-EPI for blacks; and estimated prevalence of CKD risk factors (Self-reported diabetes or hypertension and obesity, BMI> 30kg/m2). Multivariate Logistic regression was used to determine independent predictors of CKD. Results Three hundred and fifty-five participants (n = 355) were selected for participation. Participants’ mean age was 63 ± 17 years, with 60% (n=213) being female. 38% (n=135) had self-reported diabetes and 58% (n=201) had hypertension; and 44% were obese. Mean± SD estimated GFR was 81 ± 30 ml/min/1.73 m2 . One quarter of the participants (25%) had an eGFR <60 ml/min/1.73 m2, indicating CKD. Age [95% CI, OR 1.03 (1.01–1.07)], Self-reported hypertension [95% CI, OR 2.09, (1.13–3.90)] and female gender [95% CI ,OR 0.20 (0.10, 0.39)] were independent predictors of reduced eGFR. Conclusion CKD and its risk factors were prevalent among adults in Montserrat. Consideration must be made for infrastructural and/or policy changes to be mandated, to slow the progression of CKD. Primary prevention initiatives can be implemented to reduce the associated morbidity, mortality and cost associated with CKD. There is room for further longitudinal studies to identify etiology, as well as factors affecting CKD progression. This study will also propel creation of the Montserrat arm of the Caribbean Renal Registry, to allow for future follow up of long-term effects, as well as ascertain risk factors for CKD progression.

Download Full-text

Abstract MP08: Whole Exome Sequencing Study Identified A Novel Variant For Kidney Function And Progression Of Chronic Kidney Disease

Circulation ◽

10.1161/circ.143.suppl_1.mp08 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Changwei Li ◽

Michael Francis ◽

Adrianna Westbrook ◽

Ruiyuan Zhang ◽

Ye Shen ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Kidney Function ◽

Cystatin C ◽

Smoking Status ◽

Missense Variant ◽

Ckd Progression ◽

Whole Exome

Introduction: Most genetic variants for chronic kidney disease (CKD) have been identified in non-coding regions, with functional roles that are difficult to interpret. Hypothesis: A whole exome sequencing study focusing on coding variants will reveal novel mechanisms of kidney function and CKD. Methods: We performed whole exome sequencing analyses of cystatin C among 29,789 UK Biobank (UKB) participants with further confirmation among 4,297 white and 607 African American participants of the Health and Retirement Study (HRS). Conditional analyses for loci achieving exome-wide significance ( P <3.5х10 -7 ) were conducted in UKB using both the exome (n=29,789) and imputed GWAS data (n=295,122). Genomic findings were tested for relevance to baseline estimated glomerular filtration rate (eGFR) and stringently adjudicated CKD progression events among participants of the Chronic Renal Insufficiency Cohort (CRIC) by race and smoking status, using a base model and a full model ( Table ). Results: We identified a common missense variant, CST9 rs2983640, in a previously reported locus ( CST3 intron rs13038305), of which the minor G allele was associated with lower serum cystatin C level (UKB: beta=-0.03 mg/L, P =7.64х10 -92 ; HRS whites: beta=-0.05 mg/L, P =4.71х10 -6 ; HRS African Americans: beta=-0.03 mg/L, P =0.64; and multi-ethnic meta-analysis beta=-0.03 mg/L, P =2.46х10 -91 ). After controlling for the CST3 variant, the G allele was associated with higher cystatin C level (UKB exome: beta=0.003 mg/L, P =0.04; UKB GWAS: beta=0.003 mg/L, P =1.47х10 -10 ). Similar associations were identified in white CRIC participants (direct effect: beta=-0.05 mg/L, P =0.005; conditional effect: beta=0.004 mg/L, P =0.86). The CST9 rs2983640 G allele was associated with lower baseline eGFR (base model beta=-0.33 ml/min/1.73 m 2 , P =1.98х10 -6 ) and higher hazard of developing CKD progression independent of the reported CST3 variant ( Table ). Conclusions: We identified a novel missense variant influencing cystatin C level and CKD progression.

Download Full-text

Abstract MP30: Chronic Kidney Disease Progression and Risk of End-Stage Renal Disease: The Use of Change in Novel Kidney Filtration Markers

Circulation ◽

10.1161/circ.129.suppl_1.mp30 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Casey M Rebholz ◽

Kunihiro Matsushita ◽

Elizabeth Selvin ◽

Morgan E Grams ◽

Josef Coresh

Keyword(s):

Chronic Kidney Disease ◽

Clinical Trials ◽

Kidney Disease ◽

Cystatin C ◽

End Stage Renal Disease ◽

Ckd Progression ◽

Percent Change ◽

Stage Renal Disease ◽

End Stage

Introduction: Chronic kidney disease (CKD) progression assessed by estimated GFR from creatinine (eGFR-Cr) is a risk factor for cardiovascular disease and end-stage renal disease (ESRD) and has been proposed as a surrogate endpoint for clinical trials. It is unclear if CKD progression assessed by change in different filtration markers has similar risk associations with ESRD. Hypothesis: We hypothesized that percent change in novel kidney filtration markers (β 2 -microglobulin and cystatin C) over a 6-year period would be independently associated with increased risk of ESRD during 15 years of follow-up, similar to the risk seen with change in eGFR-Cr. Methods: We conducted prospective analyses of the ARIC study (N=9,703). β 2 -microglobulin, cystatin C, and creatinine were measured at study visits 1 (1990-92) and 2 (1996-98). Incident ESRD (kidney dialysis or transplant) was defined as entry into the U.S. Renal Data System registry between study visit 2 and September 30, 2011. Cox proportional hazards regression was used to estimate the association between percent change in filtration marker and incident ESRD, adjusting for demographics, kidney disease risk factors, and 1 st measurement of the filtration marker. Results: During a median follow-up of 13.1 years, there were 142 incident ESRD cases. Median eGFR-Cr was 97.3 mL/min/1.73 m 2 at 1 st measurement and 89.0 mL/min/1.73 m 2 at 2 nd measurement. Percent change in eGFR-Cr was moderately correlated with percent change in the inverse of β 2 -microglobulin (r = 0.34) and the inverse of cystatin C (r = 0.36). Progression of CKD (10-25% and >25% decline in filtration function) was associated with increased ESRD risk, with novel markers (β 2 -microglobulin, cystatin C) showing an association at least as strong as the creatinine and eGFR-Cr estimates (Table). Conclusions: CKD progression assessed using novel filtration markers is independently associated with ESRD risk, suggesting the potential utility of measuring change in β 2 -microglobulin and cystatin C in clinical trials.

Download Full-text

Abstract MP07: Soluble Urokinase-type Plasminogen Activator Receptor is associated with progression of hypertension-attributed chronic kidney disease in African Americans

Circulation ◽

10.1161/circ.137.suppl_1.mp07 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Shengyuan Luo ◽

Josef Coresh ◽

Adrienne Tin ◽

Casey M Rebholz ◽

Teresa K Chen ◽

...

Keyword(s):

Chronic Kidney Disease ◽

African Americans ◽

Kidney Disease ◽

Plasminogen Activator ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Ckd Progression ◽

Type Plasminogen Activator ◽

Urokinase Type Plasminogen Activator ◽

Plasminogen Activator Receptor

Introduction: Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, has been linked to incident and progressive chronic kidney disease (CKD) in select patient populations, often with few African Americans. Hypothesis: We assessed the hypothesis that higher circulating levels of suPAR are associated with risk for progression of hypertension-attributed CKD in African Americans. Methods: We quantified baseline plasma levels of suPAR in participants of the African-American Study of Kidney Disease and Hypertension (AASK), a clinical trial of African Americans with hypertension-attributed CKD, and regular assessment of measured glomerular filtration rate (mGFR), and proteinuria. We used Cox proportional hazards regression to assess the associations of suPAR with CKD progression (defined as doubling of serum creatinine or end-stage renal disease [ESRD]), ESRD, worsening proteinuria (pre-ESRD doubling of 24-hour urine protein to creatinine ratio [UPCR] to ≥220 mg/g), and all-cause death. Results: Among 955 AASK participants, the median baseline suPAR was 4462 pg/mL (25 th to 75 th percentile: 3425-5923 pg/mL), mean mGFR was 46 mL/min per 1.73 m 2 , and median 24-hour UPCR was 79.6 mg/g. After controlling for baseline demographics, AASK trial arm, mGFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.42-times higher risk for CKD progression per two-fold higher baseline suPAR (HR 1.42, 95% CI: 1.17-1.71, p <0.001). Higher suPAR was also independently associated with ESRD (HR 1.59, 95% CI: 1.26-2.00, p <0.001) and death (HR 1.40, 95% CI: 1.12-1.75, p =0.003). Only in patients with two APOL1 risk alleles was suPAR associated with worsening proteinuria (HR 1.77, 95% CI 1.11-2.82, p =0.016; p interaction =0.008). Conclusion: Our study provides evidence of associations between higher suPAR levels and risk for various adverse outcomes in African Americans with hypertension-attributed CKD, independent of proteinuria and GFR.

Download Full-text