scholarly journals Elevated lipoxygenase and cytochrome P450 products predict progression of chronic kidney disease

2018 ◽  
Vol 35 (2) ◽  
pp. 303-312 ◽  
Author(s):  
Farsad Afshinnia ◽  
Lixia Zeng ◽  
Jaeman Byun ◽  
Stefanie Wernisch ◽  
Rajat Deo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Cytochrome P450 ◽  
Kidney Disease ◽  
Metabolic Pathways ◽  
Risk Estimation ◽  
Ckd Progression ◽  
Standard Deviation Increase ◽  
Logistic Regression Models ◽  
Major Cardiovascular Events ◽  
End Stage

Abstract Background The clinical relevance of arachidonic acid (AA) metabolites in chronic kidney disease (CKD) progression is poorly understood. We aimed to compare the concentrations of 85 enzymatic pathway products of AA metabolism in patients with CKD who progressed to end-stage kidney disease (ESKD) versus patients who did not in a subcohort of Chronic Renal Insufficiency Cohort (CRIC) and to estimate the risk of CKD progression and major cardiovascular events by levels of AA metabolites and their link to enzymatic metabolic pathways. Methods A total 123 patients in the CRIC study who progressed to ESKD were frequency matched with 177 nonprogressors and serum eicosanoids were quantified by mass spectrometry. We applied serum collected at patients’ Year 1 visit and outcome of progression to ESKD was ascertained over the next 10 years. We used logistic regression models for risk estimation. Results Baseline 15-hydroxyeicosatetraenoate (HETE) and 20-HETE levels were significantly elevated in progressors (false discovery rate Q ≤ 0.026). The median 20-HETE level was 7.6 pmol/mL [interquartile range (IQR) 4.2–14.5] in progressors and 5.4 pmol/mL (IQR 2.8–9.4) in nonprogressors (P < 0.001). In an adjusted model, only 20-HETE independently predicted CKD progression. Each 1 standard deviation increase in 20-HETE was independently associated with 1.45-fold higher odds of progression (95% confidence interval 1.07–1.95; P = 0.017). Principal components of lipoxygenase (LOX) and cytochrome P450 (CYP450) pathways were independently associated with CKD progression. Conclusions We found higher odds of CKD progression associated with higher 20-HETE, LOX and CYP450 metabolic pathways. These alterations precede CKD progression and may serve as targets for interventions aimed at halting progression.

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

Circulation ◽  
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.

scholarly journals Protein carbamylation and chronic kidney disease progression in the Chronic Renal Insufficiency Cohort (CRIC) Study

2020 ◽  
Author(s):  
Sahir Kalim ◽  
Anders Berg ◽  
S Ananth Karumanchi ◽  
Ravi Thadhani ◽  
Andrew S Allegretti ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Protein Modification ◽  
Smoking Status ◽  
Case Control Studies ◽  
Ckd Progression ◽  
Increased Risk ◽  
Posttranslational Protein Modification ◽  
End Stage ◽  
Nested Case Control

Abstract Background Protein carbamylation is a posttranslational protein modification caused, in part, by exposure to urea’s dissociation product cyanate. Carbamylation is linked to cardiovascular outcomes and mortality in dialysis dependent end stage kidney disease (ESKD), but its effects in earlier pre-dialysis stages of chronic kidney disease (CKD) are not established. Methods We conducted two nested case-control studies within the CRIC Study. First, we matched 75 cases demonstrating CKD progression (50% eGFR reduction or reaching ESKD) to 75 controls (matched on baseline eGFR, 24-hour proteinuria, age, sex, and race). In the second study, we similarly matched 75 subjects who died during follow up (cases) to 75 surviving controls. Baseline carbamylated albumin levels (C-Alb, a validated carbamylation assay) were compared between cases and controls in each study. Results At baseline, in the CKD progression study, other than blood urea nitrogen (BUN) and smoking status, there were no significant differences in any matched or other parameter. In the mortality group, the only baseline difference was smoking status. Adjusting for baseline differences, the top tertile of C-Alb was associated with an increased risk of CKD progression (odds ratio [OR], 7.9; 95% CI, 1.9-32.8; P = 0.004) and mortality (OR 3.4; 95% CI, 1.0-11.4; P = 0.05) when compared to the bottom tertile. C-Alb correlated with eGFR but was more strongly correlated with BUN. Conclusions Our data suggest protein carbamylation is a predictor of CKD progression, beyond traditional risks including eGFR and proteinuria. Carbamylation’s association with mortality was smaller in this limited sample size.

Effect of intensive blood pressure on the progression of non-diabetic chronic kidney disease at varying degrees of proteinuria

2021 ◽  
pp. jim-2020-001702
Author(s):  
Paul J Der Mesropian ◽  
Gulvahid Shaikh ◽  
Kelly H Beers ◽  
Swati Mehta ◽  
Mauricio R Monrroy Prado ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Pooled Analysis ◽  
Ckd Progression ◽  
Glomerular Filtration Rate Decline ◽  
Multivariable Regression ◽  
Stage Renal Disease ◽  
End Stage

The ideal blood pressure (BP) target for renoprotection is uncertain in patients with non-diabetic chronic kidney disease (CKD), especially considering the influence exerted by pre-existing proteinuria. In this pooled analysis of landmark trials, we coalesced individual data from 5001 such subjects randomized to intensive versus standard BP targets. We employed multivariable regression to evaluate the relationship between follow-up systolic blood pressure (SBP) and diastolic blood pressure (DBP) on CKD progression (defined as glomerular filtration rate decline by 50% or end-stage renal disease), focusing on the potential for effect modification by baseline proteinuria or albuminuria. The median follow-up was 3.2 years. We found that SBP rather than DBP was the primary predictor of renal outcomes. The optimal SBP target was 110–129 mm Hg. We observed a strong interaction between SBP and proteinuria such that lower SBP ranges were significantly linked with progressively lower CKD risk in grade A3 albuminuria or ≥0.5–1 g/day proteinuria (relative to SBP 110–119 mm Hg, the adjusted HR for SBP 120–129 mm Hg, 130–139 mm Hg, and 140–149 mm Hg was 1.5, 2.3, and 3.3, respectively; all p<0.05). In grade A2 microalbuminuria or proteinuria near 0.5 g/day, a non-significant but possible connection was seen between tighter BP and decreased CKD (aforementioned HRs all <2; all p>0.05), while in grade A1 albuminuria or proteinuria <0.2 g/day no significant association was apparent (HRs all <1.5; all p>0.1). We conclude that in non-diabetic CKD, stricter BP targets <130 mm Hg may help limit CKD progression as proteinuria rises.

scholarly journals Polymorphisms inPPARGenes (PPARD,PPARG, andPPARGC1A) and the Risk of Chronic Kidney Disease in Japanese: Cross-Sectional Data from the J-MICC Study

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Asahi Hishida ◽  
Kenji Wakai ◽  
Mariko Naito ◽  
Takashi Tamura ◽  
Sayo Kawai ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Risk Estimation ◽  
Cross Sectional ◽  
Increased Risk ◽  
Invader Assay ◽  
Study Population ◽  
Stage Renal Disease ◽  
End Stage ◽  
Study Participants

Chronic kidney disease (CKD) is well known as a strong risk factor for both end stage renal disease and cardiovascular disease. To clarify the association of polymorphisms in thePPARgenes (PPARD,PPARG, andPPARGC1A) with the risk of CKD in Japanese, we examined this association among the Japanese subjects using the cross-sectional data of J-MICC (Japan Multi-Institutional Collaborative Cohort) Study. The subjects for this analysis were 3,285 men and women, aged 35–69 years, selected from J-MICC Study participants; genotyping was conducted by multiplex polymerase chain reaction-based Invader assay. The prevalence of CKD was determined for CKD stages 3–5 (defined as eGFR < 60 ml/min/1.73 m2). Participants with CKD accounted for 17.3% of the study population. When those withPPARDT-842CT/Twere defined as reference, those withPPARDT-842CT/CandC/Cdemonstrated the OR for CKD of 1.26 (95%CI 1.04–1.53) and 1.31 (95%CI 0.83–2.06), respectively. There were no significant associations between the polymorphisms in otherPPARgenes and the risk of CKD. The present study found a significantly increased risk of CKD in those with theCallele ofPPARDT-842C, which may suggest the possibility of personalized risk estimation of this life-limiting disease in the near future.

MO605INFLAMMATION-BASED MODIFIED GLASGOW PROGNOSTIC SCORE AND CHRONIC KIDNEY DISEASE PROGRESSION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Gabriel Stefan ◽  
Simona Stancu ◽  
Adrian Dorin Zugravu ◽  
Cristina-Stela Capusa
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Prognostic Score ◽  
Glasgow Prognostic Score ◽  
Rapid Progression ◽  
Ckd Progression ◽  
Loss To Follow Up ◽  
Reactive Protein ◽  
Modified Glasgow Prognostic Score ◽  
End Stage

Abstract Background and Aims The modified Glasgow prognostic score (mGPS), based on combination between albumin (sAlb) and C-reactive protein (CRP), has been derived from oncology and validated in multiple diseases. Since chronic kidney disease (CKD) progression is related to inflammation, we aimed to evaluate the relationship between the mGPS and CKD outcome. Method The present retrospective unicentric cohort study included 547 CKD patients (age 60.2 years, 53% male, eGFR 42.0 mL/min, mean change -2 mL/min/year) admitted between January 1, 2007 and December 31, 2012. The mGPS assessment: zero points if CRP ≤10 mg/L and sAlb ≥3.5 g/dL; one point if CRP &gt;10 mg/L and sAlb ≥3.5 g/dL, two points if CRP &gt;10 mg/L and sAlb &lt;3.5 g/dL. Patients records were reviewed from the CKD diagnosis to one of the four outcomes: end-stage kidney disease (ESKD), death, loss to follow-up, or until July 31, 2017. Results The mGPS score was 0 for 420 (78%), 1 for 110 (19%), and 2 for 17 (3%) patients. Rapid progression defined as a sustained decline in eGFR of more than 5 mL/min/year was found in 17% of the studied patients. More patients with rapid CKD progression were found in the group with the highest mGPS (30% vs 17%, vs 16%, p=0.05). In the multivariate analysis, mGPS was associated with the eGFR slope (OR 1.42 (95%CI 0.29, 2.55), p 0.01). Moreover, mGPS was negatively correlated with baseline eGFR (OR -3.74 (95%CI 7.8, 0.33), p 0.05) and positively with albuminuria (0.87 (95%CI 0.51, 1.23), p 0.001). During the study period, 130 patients (24%) died and 109 (20%) reached ESKD. The mean kidney survival time was 8.1 (95%CI 7.9, 8.4) years. Kidney survivals at 12, 24, 36, 48, 60, and 72 months were 96, 95, 89, 86, 83 and 82%, respectively. In univariate time-dependent analysis, patients with zero mGPS had better kidney survival than those with the score of one and two (99.9 (95%CI 96.9, 102.9) vs 92.1 (95%CI 85.2, 99.0) vs 78.1 (95%CI 60.4, 95.4) months, log rank p=0.02). However, the kidney survival differences were not present after adjusting for CKD progression risk factors (HR 1.12 (95%CI 0.78, 1.62), p 0.5). Conclusion The inflammation-based mGPS score was associated with eGFR decline in CKD patients. Therefore, could prove useful in improving risk stratification of CKD patients.

scholarly journals Effect of zinc deficiency on chronic kidney disease progression and effect modification by hypoalbuminemia

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251554
Author(s):  
Atsuyuki Tokuyama ◽  
Eiichiro Kanda ◽  
Seiji Itano ◽  
Megumi Kondo ◽  
Yoshihisa Wada ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Zinc Deficiency ◽  
Primary Outcome ◽  
Proportional Hazards ◽  
Serum Zinc ◽  
Cox Proportional Hazards ◽  
Ckd Progression ◽  
Cox Proportional Hazards Models ◽  
End Stage

Serum zinc (Zn) levels tend to be low in chronic kidney disease (CKD) patients. This cohort study was conducted to investigate the relationship between zinc deficiency and CKD progression. Patients were classified into two groups based on Zn levels < 60 μg/dl (low-Zn group, n = 160) and ≥ 60 μg/dl (high-Zn group, n = 152). The primary outcome was defined as end-stage kidney disease (ESKD) or death and was examined over a 1-year observation period. Overall, the mean Zn level was 59.6 μg/dl and the median eGFR was 20.3 ml/min/1.73 m2. The incidence of the primary outcome was higher in the low-Zn group (p<0.001). Various Cox proportional hazards models adjusted for baseline characteristics showed higher risks of the primary outcome in the low-Zn group than in the high-Zn group. Competing risks analysis showed that low Zn levels were associated with ESKD but not with death. Moreover, in propensity score-matched analysis, the low-Zn group showed a higher risk of the primary outcome [adjusted hazard ratio 1.81 (95% confidence interval 1.02, 3.24)]. Furthermore, an interaction was observed between Zn and serum albumin levels (interaction p = 0.026). The results of this study indicate that zinc deficiency is a risk factor for CKD progression.

scholarly journals Association of blood pressure and renal outcome in patients with chronic kidney disease; a post hoc analysis of FROM-J study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mariko Tsuchida-Nishiwaki ◽  
Haruhito A. Uchida ◽  
Hidemi Takeuchi ◽  
Noriyuki Nishiwaki ◽  
Yohei Maeshima ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Outcome ◽  
Ckd Progression ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
One Year ◽  
Stage Renal Disease ◽  
End Stage

AbstractIt is well-known that hypertension exacerbates chronic kidney disease (CKD) progression, however, the optimal target blood pressure (BP) level in patients with CKD remains unclear. This study aimed to assess the optimal BP level for preventing CKD progression. The risk of renal outcome among different BP categories at baseline as well as 1 year after, were evaluated using individual CKD patient data aged between 40 and 74 years from FROM-J [Frontier of Renal Outcome Modifications in Japan] study. The renal outcome was defined as ≥ 40% reduction in estimated glomerular filtration rate to < 60 mL/min/1.73 m2, or a diagnosis of end stage renal disease. Regarding baseline BP, the group of systolic BP (SBP) 120–129 mmHg had the lowest risk of the renal outcome, which increased more than 60% in SBP ≥ 130 mmHg group. A significant increase in the renal outcome was found only in the group of diastolic BP ≥ 90 mmHg. The group of BP < 130/80 mmHg had a benefit for lowering the risk regardless of the presence of proteinuria, and it significantly reduced the risk in patients with proteinuria. Achieving SBP level < 130 mmHg after one year resulted in a 42% risk reduction in patients with SBP level ≥ 130 mmHg at baseline. Targeting SBP level < 130 mmHg would be associated with the preferable renal outcome.Clinical Trial Registration-URL: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000001159 (16/05/2008).

scholarly journals Investigation of the Impact of Endodontic Therapy on Survival among Dialysis Patients in Taiwan: A Nationwide Population-Based Cohort Study

2021 ◽  
Vol 18 (1) ◽  
pp. 326
Author(s):  
Chih-Chien Chiu ◽  
Ya-Chieh Chang ◽  
Ren-Yeong Huang ◽  
Jenq-Shyong Chan ◽  
Chi-Hsiang Chung ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Root Canal ◽  
Dialysis Patients ◽  
Root Canal Therapy ◽  
Risk Of Death ◽  
Stage Renal Disease ◽  
End Stage

Objectives Dental problems occur widely in patients with chronic kidney disease (CKD) and may increase comorbidities. Root canal therapy (RCT) is a common procedure for advanced decayed caries with pulp inflammation and root canals. However, end-stage renal disease (ESRD) patients are considered to have a higher risk of potentially life-threatening infections after treatment and might fail to receive satisfactory dental care such as RCT. We investigated whether appropriate intervention for dental problems had a potential impact among dialysis patients. Design Men and women who began maintenance dialysis (hemodialysis or peritoneal dialysis) between January 1, 2000, and December 31, 2015, in Taiwan (total 12,454 patients) were enrolled in this study. Participants were followed up from the first reported dialysis date to the date of death or end of dialysis by December 31, 2015. Setting Data collection was conducted in Taiwan. Results A total of 2633 and 9821 patients were classified into the RCT and non-RCT groups, respectively. From the data of Taiwan’s National Health Insurance, a total of 5,092,734 teeth received RCT from 2000 to 2015. Then, a total of 12,454 patients were followed within the 16 years, and 4030 patients passed away. The results showed that members of the non-RCT group (34.93%) had a higher mortality rate than those of the RCT group (22.79%; p = 0.001). The multivariate-adjusted hazard ratio for the risk of death was 0.69 (RCT vs. non-RCT; p = 0.001). Conclusions This study suggested that patients who had received RCT had a relatively lower risk of death among dialysis patients. Infectious diseases had a significant role in mortality among dialysis patients with non-RCT. Appropriate interventions for dental problems may increase survival among dialysis patients. Abbreviations: CKD = chronic kidney disease, ESRD = end-stage renal disease, RCT = root canal therapy.

Sign in / Sign up

Export Citation Format

Share Document