A threshold trajectory was revealed by isolating the effects of hemoglobin rate of rise in anemia of chronic kidney disease

Background: To assess cardiovascular risk among various hemoglobin (Hb) rates of rise (RoR) in chronic kidney disease (CKD) patients with anemia who have initiated therapy with erythropoiesis stimulating agents (ESAs). Methods: Observational cohort of CKD patients initiating ESA therapy from the Centricity® database, 1990–2011. Proportional hazards models tested the hypothesis that a slower Hb RoR (0 < g/dl/month ⩽ 0.125) is associated with a lower cardiovascular (CV) incidence [composite of fatal/nonfatal myocardial infarction (MI) and stroke] compared with faster RoR (0.125 < g/dl/month ⩽ 2.0, and >2.0 g/dl/month). Results: A total of 9220 patients receiving ESAs were followed for an average of 3.1 years. Slow (group B) RoR versus medium (group C′) and fast (group D′) RoR in Hb, throughout all Hb milestones, was associated with lower risk of the composite endpoint [B (slow) versus D′ (fast) [hazard ratio (HR) = 0.20 (0.11, 0.39), p < 0.0001]; B versus C′ (medium) [HR = 0.34 (0.19, 0.62), p = 0.0004], and C′ versus D′ [HR = 0.60 (0.42, 0.85), p = 0.005]]. Within achieved Hb milestones, HRs were: B versus D′ at milestone ⩾ 14.1 g/dl [HR = 0.17 (0.05, 0.56); p = 0.004] and at milestone 12.6−14.0 [HR = 0.18 (0.07, 0.46), p = 0.0004]. Conclusion: Rapid Hb rise is associated with adverse CV outcomes, with markedly lower risk for rates below a threshold trajectory of 0.125 g/dl/month, even with complete correction.

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Comparison of N-terminal proB-type natriuretic peptide levels at different stages of visceral leishmaniosis and in patients with chronic kidney disease

Veterinary Record ◽

10.1136/vr.105205 ◽

2019 ◽

Vol 185 (20) ◽

pp. 630-630

Author(s):

Domingo Casamian-Sorrosal ◽

Rafael Barrera-Chacon ◽

Luis Gómez ◽

Silvia Belinchón-Lorenzo ◽

Javier Galapero Arroyo ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Left Ventricular Mass ◽

Natriuretic Peptide ◽

Left Ventricular ◽

Systemic Hypertension ◽

Ventricular Mass ◽

Group A ◽

Group B ◽

Group D

N-terminal proB-type natriuretic peptide (NT-proBNP) may be a useful marker in canine leishmaniosis (CanL). The aim was to compare NT-proBNP in dogs at different LeishVet stages of CanL and with idiopathic chronic kidney disease (CKD). Dogs diagnosed with CanL or CKD and a group of healthy dogs were included (group A, five normal dogs; group B, six dogs LeishVet 1–2; group C, 13 dogs LeishVet 3–4; group D, six dogs with CKD). NT-proBNP was higher (P<0.001) in group C (7.616 pmol/l, interquartile range (IQR) 3537–10,000 pmol/l) than in group A (293 pmol/l, IQR 257–373), group B (388.5 pmol/l, IQR 324–793) and group D (740 pmol/l, IQR 557–962 pmol/l). International Renal Interest Society (IRIS) kidney stage was not different between groups C and D or between groups A and B, but was different within all the rest of the group comparisons (P<0.001). In group C all dogs had echocardiographic increase in left ventricular mass index. NT-proBNP had negative correlation with haematocrit (P<0.001, r=0.749) and positive correlation with systemic blood pressure (P<0.001, r=0.728). NT-proBNP is consistently elevated in dogs with advanced CanL and is strongly correlated with the degree of systemic hypertension and anaemia. Moreover, dogs with advanced CanL exhibit increase in left ventricular mass. NT-proBNP may however be a less desirable cardiac marker as unlike cardiac troponin I it is often not elevated at earlier stages of CanL.

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Acute coronary syndromes in chronic kidney disease patients: the good, the bad or the ugly?

European Heart Journal ◽

10.1093/ehjci/ehaa946.1514 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C Saleiro ◽

D De Campos ◽

J Lopes ◽

R Teixeira ◽

J.P Sousa ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Systolic Function ◽

Lv Function ◽

Angiotensin Ii Antagonist ◽

All Cause Mortality ◽

Group A ◽

Lv Ejection Fraction ◽

Group B ◽

Lv Systolic Function

Abstract Background Patients with chronic kidney disease (CKD) are at increased risk of composite cardiovascular (CV) events and all-cause mortality. However, current aggressiveness of therapeutic strategies may minimize the course of the disease. Aim To assess the prognostic impact of optimized medical treatment in a CKD population with acute coronary syndrome (ACS). Methods 355 ACS patients admitted to a single coronary care with CKD who were discharged from hospital were included. Those with end-stage renal disease were excluded. Three groups were created based on the KDIGO classification: Group A (Stage 3A, eGFR [estimated glomerular filtration rate] 45–59mL/min/1.73 m2) N=190; Group B (Stage 3B, eGFR 30–44mL/min/1.73 m2) N=113; and Group C (Stage 3B, eGFR 15–29mL/min/1.73 m2) N=52. The primary endpoint was long-term all-cause mortality. Kaplan-Meyer survival curves and Cox regression were done. The median of follow-up was 32 (IQ 15–70) months. Results Groups were similar regarding demographics, CV risk factors, ACS type, heart failure diagnosis, left ventricular (LV) systolic function, peak troponin, multivessel disease, treatment option (PCI, CABG or OMT) and medical therapy at discharge. More advance renal failure patients had a higher prevalence of diabetes mellitus (DM), a lower haemoglobin, a higher NT-proBNP and were less likely to receive ACE inhibitors/angiotensin II antagonist at discharge. 170 patients met the primary outcome. Kaplan-Meyer curves showed decreased survival with worse renal function (Group A 68% vs Group B 57% vs Group C 37%, Log Rank P=0.006 – Figure 1). After adjustment for age, DM, haemoglobin, NT-proBNP, LV systolic function and ACE inhibitors/angiotensin II antagonist at discharge, eGFR was not associated with increased death (HR 1.00, 95% CI 0.98–1.01). In this model, only age (HR 1.04, 95% CI 1.01–1.07), haemoglobin (HR 0.86, 95% CI 0.979–0.94), Nt-proBNP (HR 1.00, 95% CI 1.00–1.00) and impaired LV function (LV ejection fraction 40–49%: HR 2.95, 95% CI 1.89–4.81; LV ejection fraction <40%: HR 2.15, 95% CI 1.44–3.21) remained associated with the outcome. Conclusion The worse outcome attributed to CKD after an ACS seems to be related not the eGFR itself but to associated comorbidities such as age, anaemia, fluid overload and impaired LV function. The fact that some of these comorbidities may be altered by intensive therapy indicates that CKD patients should also be candidates to optimized medical treatment. Funding Acknowledgement Type of funding source: None

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Association of Dyskalemias with Ischemic Stroke in Advanced Chronic Kidney Disease Patients Transitioning to Dialysis

American Journal of Nephrology ◽

10.1159/000516902 ◽

2021 ◽

pp. 1-9

Author(s):

Ankur A. Dashputre ◽

Keiichi Sumida ◽

Fridtjof Thomas ◽

Justin Gatwood ◽

Oguz Akbilgic ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Ischemic Stroke ◽

Kidney Disease ◽

Lower Risk ◽

Chronic Exposure ◽

Cox Regression ◽

Acute Exposure ◽

Continuous Exposure ◽

Advanced Chronic Kidney Disease

Introduction: Hypo- and hyperkalemia are associated with a higher risk of ischemic stroke. However, this association has not been examined in an advanced chronic kidney disease (CKD) population. Methods: From among 102,477 US veterans transitioning to dialysis between 2007 and 2015, 21,357 patients with 2 pre-dialysis outpatient estimated glomerular filtration rates <30 mL/min/1.73 m2 90–365 days apart and at least 1 potassium (K) each in the baseline and follow-up period were identified. We separately examined the association of both baseline time-averaged K (chronic exposure) and time-updated K (acute exposure) treated as categorized (hypokalemia [K <3.5 mEq/L] and hyperkalemia [K >5.5 mEq/L] vs. referent [3.5–5.5 mEq/L]) and continuous exposure with time to the first ischemic stroke event prior to dialysis initiation using multivariable-adjusted Cox regression models. Results: A total of 2,638 (12.4%) ischemic stroke events (crude event rate 41.9 per 1,000 patient years; 95% confidence interval [CI] 40.4–43.6) over a median (Q1–Q3) follow-up time of 2.56 (1.59–3.89) years were observed. The baseline time-averaged K category of hypokalemia (adjusted hazard ratio [aHR], 95% CI: 1.35, 1.01–1.81) was marginally associated with a significantly higher risk of ischemic stroke. However, time-updated hyperkalemia was associated with a significantly lower risk of ischemic stroke (aHR, 95% CI: 0.82, 0.68–0.98). The exposure-outcome relationship remained consistent when using continuous K levels for both the exposures. Discussion/Conclusion: In patients with advanced CKD, hypokalemia (chronic exposure) was associated with a higher risk of ischemic stroke, whereas hyperkalemia (acute exposure) was associated with a lower risk of ischemic stroke. Further studies in this population are needed to explore the mechanisms underlying these associations.

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Abstract P098: Slower Gait Speed is Associated with Increased Mortality Risk in Chronic Kidney Disease.

Circulation ◽

10.1161/circ.125.suppl_10.ap098 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Baback Roshanravan ◽

Cassiane Robinson-Cohen ◽

Kushang V Patel ◽

Greg Levin ◽

Ian H de Boer ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Gait Speed ◽

Proportional Hazards ◽

Prognostic Significance ◽

Continuous Variable ◽

Hazard Ratio ◽

Risk Of Death ◽

Social Security Death Index

Objective: Skeletal muscle dysfunction (sarcopenia) is an under-recognized complication of chronic kidney disease (CKD) that may have important clinical consequences. Gait speed is associated with sarcopenia and comorbid disease burden among older adults; however, little is known about the prognostic significance of gait speed in CKD. We determined the association of gait speed with all-cause mortality in a prospective cohort of non-dialysis CKD patients. Methods: We measured usual gait speed over 4-meters in 309 participants from a prospective study of non-dialysis CKD. Included subjects had an estimated glomerular filtration rate (eGFR ckdepi ) <90mL/min/1.73m 2 , were stroke-free and did not require a wheelchair for ambulation. Study coordinators assessed mortality during follow-up by phone contacts, medical record review, and the social security death index. We evaluated gait speed continuously, and using a cut point of 0.8 m/s, consistent with previous studies. We used Cox's proportional hazards to estimate the association of gait speed with mortality after adjustment for age, sex, race, smoking, diabetes, pre-existing CAD, BMI, eGFR and hemoglobin. Results: Median follow-up time was 2.7 years; range 27 days to 4.8 years. The mean age was 58.9 ± 13 years and mean eGFR by cystatin C (eGFR cysc ) was 48.5 ± 23mL/min/1.73m 2 . There were a total of 31 deaths (10.4%) during follow-up. Unadjusted mortality rates were 23 and 80 deaths per 1,000 person-years among participants who had a gait speed of >0.8m/s versus ≤0.8m/s, respectively. After full adjustment, gait speed ≤0.8m/s was associated with a 2.8-fold greater risk of death compared to a gait speed >0.8 m/s. Gait speed was also strongly associated with mortality when analyzed as a continuous variable ( Table ) and a stronger predictor of death than age, history of CAD, or diabetes. No. Deaths (%) Model 1 + Model 2 # Hazard Ratio 95% CI Hazard Ratio 95% CI Gait speed * 32(10) 0.74 (0.64-0.86) 0.75 (0.64-0.87) >0.8m/s 13 (6) Reference Reference ≤0.8m/s 19(19) 3.49 (1.54-7.95) 2.84 (1.25-6.48) * Gait speed analyzed continuously per 10cm/s increase in speed. +Model 1: Adjusted for age, sex, race, study site #Model 2: adds smoking, BMI, eGFR cysc , diabetes, prevalent coronary disease. Conclusion: Gait speed is strongly associated with death in a cohort of middle-aged CKD patients.

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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.

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Abstract MP012: Plasma Galectin-3 Levels and Subsequent Risk of Incident Chronic Kidney Disease

Circulation ◽

10.1161/circ.135.suppl_1.mp012 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Casey M Rebholz ◽

Elizabeth Selvin ◽

Menglu Liang ◽

Christie M Ballantyne ◽

Ron C Hoogeveen ◽

...

Keyword(s):

Heart Failure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Proportional Hazards ◽

Disease Risk ◽

Positive Association ◽

Cox Proportional Hazards ◽

Diabetes Status ◽

Incident Chronic Kidney Disease ◽

Galectin 3

Introduction: Galectin-3 is a 35 kDa β-galactoside-binding lectin which has been proposed as a novel biomarker of heart failure primarily due to its involvement in myocardial fibrosis. Elevated levels of galectin-3 may be associated with fibrosis of other organs, such as the kidney, and increase the risk of developing kidney disease. Methods: Using Cox proportional hazards regression, we prospectively analyzed Atherosclerosis Risk in Communities (ARIC) study participants with measurements of plasma galectin-3 levels at baseline (visit 4, 1996-98) and without prevalent kidney disease or heart failure (N=9,647). Incident chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 accompanied by 25% eGFR decline, chronic kidney disease-related hospitalization or death, or end-stage renal disease between baseline and December 31, 2013. Results: 2,105 participants (22%) developed incident chronic kidney disease over a median follow-up of 16 years. The mean (standard deviation) plasma level of galectin-3 was 14.7 (4.4) ng/mL. At baseline, galectin-3 was cross-sectionally associated with eGFR (r = -0.31) and urine albumin-to-creatinine ratio (UACR) (r = 0.19). After adjusting for demographics and kidney disease risk factors, there was a significant, graded, and positive association between galectin-3 and incident chronic kidney disease (quartile 4 vs. 1 HR: 1.84, 95% CI: 1.62, 2.09, p for trend <0.001). The association between galectin-3 and incident chronic kidney disease was attenuated but remained significant after accounting for eGFR and UACR (quartile 4 vs. 1 HR: 1.58, 95% CI: 1.39, 1.80, p for trend <0.001). The association was similar by diabetes status (p for interaction = 0.33) and stronger among those with hypertension (p for interaction = 0.004). Conclusion: In this community-based population, higher plasma galectin-3 levels were associated with elevated risk of developing incident chronic kidney disease, particularly among those with hypertension.

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Effect of Renamezin upon attenuation of renal function decline in pre-dialysis chronic kidney disease patients: 24-week prospective observational cohort study

PLoS ONE ◽

10.1371/journal.pone.0252186 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252186

Author(s):

Hayne Cho Park ◽

AJin Cho ◽

Do Hyoung Kim ◽

Kyu-sang Yun ◽

Juhee Kim ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Renal Function ◽

Cohort Study ◽

Kidney Disease ◽

Adverse Events ◽

Serum Creatinine ◽

Observational Cohort Study ◽

Prospective Observational Cohort Study ◽

Renal Function Decline ◽

Observational Cohort

Renamezin® is a modified capsule-type oral spherical adsorptive carbon which lowers indoxyl sulfate levels in patients with advanced chronic kidney disease (CKD). This 24-week prospective observational cohort study was performed to evaluate the effect of Renamezin® upon attenuation of renal function decline. A total of 1,149 adult patients with baseline serum creatinine 2.0–5.0 mg/dL were enrolled from 22 tertiary hospital in Korea from April 2016 to September 2018. Among them, a total of 686 patients completed the study and were included in the intention-to-treat analysis. A total of 1,061 patients were included in the safety analysis. The mean age was 63.5 years and male patients were predominant (63.6%). Most of the patients (76.8%) demonstrated high compliance with study drug (6g per day). After 24 week of treatment, serum creatinine was increased from 2.86±0.72 mg/dL to 3.06±1.15 mg/dL (p<0.001), but estimated glomerular filtration rate was not changed significantly during observation period (22.3±6.8 mL/min/1.73m2 to 22.1±9.1 mL/min/1.73m2, p = 0.243). Patients with age over 65 years old and those under good systolic blood pressure control <130 mmHg were most likely to get benefit from Renamezin® treatment to preserve renal function. A total of 98 (9.2%) patients out of 1,061 safety population experienced 134 adverse events, of which gastrointestinal disorders were the most common. There were no serious treatment-related adverse events. Renamezin® can be used safely to attenuate renal function decline in moderately advanced CKD patients.

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Abstract P147: Association Of Rosuvastatin Use With Risk Of Rhabdomyolysis Across Chronic Kidney Disease Status

Circulation ◽

10.1161/circ.143.suppl_1.p147 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Jung-Im Shin ◽

Yao Qiao ◽

Aditya Surapaneni ◽

Lesley Inker ◽

Derek Fine ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Proportional Hazards ◽

Disease Status ◽

Cox Proportional Hazards ◽

Lower Egfr ◽

Threatening Condition ◽

Life Threatening ◽

End Stage

Introduction: Statin-induced rhabdomyolysis is a rare, but potentially life-threatening condition. It is unknown whether specific statins carry a greater risk of rhabdomyolysis and whether the risk differs between patients with and without chronic kidney disease (CKD). The objective of this study was to investigate the association of rosuvastatin use vs. atorvastatin use with the risk of rhabdomyolysis across CKD status. Hypothesis: Rosuvastatin use is associated with a higher risk of rhabdomyolysis as compared to atorvastatin use and the risk is greater among those with CKD than those without CKD. Methods: We identified adult patients who initiated rosuvastatin or atorvastatin between January 1, 2004 and December 31, 2018 and were free of end-stage kidney disease at the time of prescription in the Geisinger Health System. The association between rosuvastatin use and rhabdomyolysis was assessed using Cox proportional hazards regression models with an interaction between rosuvastatin use and CKD (i.e., estimated glomerular filtration rate <60 ml/min/1.73 m 2 ) in an inverse probability of treatment weighted (IPTW) sample. Results: Of 8,748 rosuvastatin users (mean [SD] age, 59.7 [12.6] years; 49.8% female; 11.8% CKD) and 31,770 atorvastatin users (mean [SD] age, 59.1 [12.6] years; 48.2% female; 11.9% CKD), 0.7% and 0.4% patients developed rhabdomyolysis, respectively, during a median follow-up of 5.1 years. Rosuvastatin use was associated with a higher risk of rhabdomyolysis in patients with CKD (hazard ratio [HR], 3.29; 95% CI, 1.53-7.09), but not in those without CKD (HR, 1.29; 95% CI, 0.82-2.03; p-interaction=0.04). A higher risk of rhabdomyolysis associated with rosuvastatin use in lower eGFR was also observed in the analysis with continuous eGFR ( Figure ). Conclusions: The findings suggest that rosuvastatin use in patients with CKD may be associated with excess risk of rhabdomyolysis as compared to atorvastatin.

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An observational study of the effects of telmisartan on insulin resistance in hypertensive patients with chronic kidney disease undergoing hemodialysis

10.21203/rs.2.16056/v1 ◽

2019 ◽

Author(s):

budi suprapti ◽

Bayu Dharma ◽

Mahadri Drik ◽

Zamrottul Izzah ◽

Wenny Nilamsari ◽

...

Keyword(s):

Insulin Resistance ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Antihypertensive Drugs ◽

Model Assessment ◽

Hypertensive Patients ◽

Fasting Plasma ◽

Homeostatic Model Assessment ◽

Observational Cohort ◽

The Mean

Abstract Background In the clinical setting, the activity of telmisartan in decreasing insulin resistance has been proven superior to other antihypertensive drugs in hypertensive patients. However, there has been no published study in determining the effect of telmisartan on insulin resistance in hypertensive chronic kidney disease patients undergoing hemodialysis.Objective To analyze the effect of telmisartan on insulin resistance in hypertensive patients undergoing hemodialysis.Method It was a prospective observational cohort study in 16 chronic kidney disease patients undergoing regular hemodialysis and using telmisartan who met the inclusion criteria.Results Sixteen patients received telmisartan, 12 were male patients and four were female. The mean age was 45 ± 8 years and the mean body mass index was 22.85 ± 1.99. Hypertensive chronic kidney disease was the highest etiology (56%) for hemodialysis. Mean percentage of fasting plasma insulin and homeostatic model assessment of insulin resistance concentratons decreased significantly by 22.6% (P<0.05) and 22.9% (P<0.05) respectively after 3-month administration. On the other hand, the mean percentage of fasting plasma glucose concentrations declined by 2.9% (P=0.187, Zcount<1.96) after 3-month of treatment.Conclusion Administration of telmisartan for three months decreases insulin resistance significantly in hypertensive patients undergoing hemodialysis.

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