Abstract P456: The Association Between Clonal Hematopoiesis Of Indeterminate Potential And Inflammatory Biomarkers Among Chronic Kidney Disease Patients

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related disorder associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). Mechanistic studies of CHIP implicate inflammatory pathways underlying this relationship. Although inflammation is a well-established component of chronic kidney disease (CKD), linked to both CKD progression and ASCVD in CKD patients, CHIP has not been investigated in a CKD setting. Objective: To estimate the prevalence of CHIP in patients with CKD and to examine the cross-sectional associations between CHIP and biomarkers that were previously related to CKD progression and ASCVD among CKD patients. Methods: The current study was conducted among 598 Chronic Renal Insufficiency Cohort (CRIC) study participants with whole-exome sequencing data and baseline measures of fibrinogen, interleukin (IL)-6, serum albumin, and tumor necrosis factor-α. CHIP was detected from sequencing data using MuTect2. CHIP was defined as the presence of a somatic hematologic malignancy-associated mutation with a variant allele frequency (VAF) of at least 2%. CHIP was also categorized ordinally by clone size as no CHIP, small CHIP clone (VAF<10%), and large CHIP clone (VAF ≥10%). Ordinal logistic regression was used to test associations of CHIP with each biomarker in age- and multivariable-adjusted models. Multivariable models adjusted for age, sex, ancestry, body mass index, estimated glomerular filtration rate, systolic blood pressure, low-density lipoprotein cholesterol, fasting plasma glucose, and blood pressure, lipid, and glucose lowering medications. Results: CHIP was detected in a total of 28 individuals from the WES study (4.7%). Among those 70 years of age and older, we detected a CHIP prevalence of nearly 16%. As expected, participants with CHIP were older than those without CHIP (mean age: 67 and 58 years, respectively; P<0.0001). Other demographic and clinical variables were similar between groups . Age-adjusted models showed strong associations between CHIP and both fibrinogen and IL-6 with odds ratios of 2.49 (95% CI: 1.09, 5.71) and 2.45 (95% CI: 1.05, 5.72), respectively. After multivariable adjustment, only fibrinogen remained associated with CHIP with an odds ratio of 4.70 (95% CI: 1.69, 13.0). Consistent with these findings, there was a strong dose-dependent association between CHIP clone size and fibrinogen in multivariable adjusted analyses (P for linear trend=0.009). Compared to those without CHIP, odds ratios for higher fibrinogen tertile were 3.0 (95% CI: 0.84, 11.3) and 4.7 (95% CI: 1.29, 16.7) among those with small and large CHIP clone sizes, respectively. Conclusions: CHIP prevalence was higher among CKD patients in the current study compared to previous estimates from the general population. Furthermore, a strong, dose-dependent association between CHIP and fibrinogen was identified.

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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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Evaluation of Urinary Big Endothelin-1 in Feline Spontaneous CKD

Animals ◽

10.3390/ani10112144 ◽

2020 ◽

Vol 10 (11) ◽

pp. 2144

Author(s):

Marco Giraldi ◽

Saverio Paltrinieri ◽

Camilla Piazza ◽

Paola Scarpa

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Serum Creatinine ◽

Urine Samples ◽

Ckd Progression ◽

Creatinine Concentration ◽

Endothelin 1 ◽

Urine Creatinine ◽

Advanced Stages

The endothelin-1 (ET-1) system has been implicated in the development and progression of chronic kidney disease (CKD). No information on big ET-1 in feline urine is available. The purpose of this study was to evaluate if urinary big endothelin-1 (bigET-1) is associated with feline CKD. Sixty urine samples were prospectively collected from 13 healthy cats at risk of developing CKD and 22 cats with CKD of different International Renal Interest Society (IRIS) stages (1–4). Urinary bigET-1 was measured using a commercially available ELISA. BigET-1 normalized to urine creatinine (bigET-1:UC) was compared amongst stages and substages, as proposed by IRIS, and correlated with serum creatinine concentration, proteinuria and blood pressure. BigET-1:UC at the time of inclusion was compared between cats that remained stable and cats that progressed after 12 months. BigET-1:UC was significantly higher (p = 0.002) in cats at IRIS stages 3–4 (median: 21.9; range: 1.88–55.6), compared to all other stages, and in proteinuric (n = 8, median: 11.0; range: 0.00–46.4) compared with nonproteinuric cats (n = 38 median: 0.33; range: 0.00–55.6) (p = 0.029). BigET-1:UC was not associated with CKD progression. Urinary bigET-1 increased in advanced stages of CKD and in proteinuric patients, suggesting that ET-1 may be indicative of the severity of feline CKD.

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Soluble Urokinase‐Type Plasminogen Activator Receptor, Changes of 24‐Hour Blood Pressure, and Progression of Chronic Kidney Disease

Journal of the American Heart Association ◽

10.1161/jaha.120.017225 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Jong Hyun Jhee ◽

Bo Young Nam ◽

Chan Joo Lee ◽

Jung Tak Park ◽

Seung Hyeok Han ◽

...

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Plasminogen Activator ◽

Interquartile Range ◽

Ckd Progression ◽

Type Plasminogen Activator ◽

Urokinase Type Plasminogen Activator ◽

Plasminogen Activator Receptor ◽

The Relationship

Background Soluble urokinase‐type plasminogen activator receptor (suPAR) is associated with cardiovascular risks and poor renal outcomes. However, whether elevated suPAR levels are associated with 24‐hour blood pressure patterns or kidney disease progression in patients with chronic kidney disease (CKD) is unclear. Methods and Results A total of 751 patients with CKD stage 1 to 5 were recruited from CMERC‐HI (Cardiovascular and Metabolic Disease Etiology Research Center–High Risk) cohort study (2013–2018). The relationship of serum suPAR levels to 24‐hour blood pressure parameters and CKD progression was analyzed. The median serum suPAR level was 1439.0 (interquartile range, 1026.2–2150.1) pg/mL, and the mean estimated glomerular filtration rate was 52.8±28.5 mL/min per 1.73 m 2 at baseline. Patients with higher suPAR levels had significantly higher levels of office, 24‐hour, daytime, and nighttime systolic blood pressure and nighttime diastolic blood pressure than those with lower suPAR levels. The highest suPAR tertile was associated with an increased risk of a reverse dipping pattern (odds ratio, 2.93; 95% CI, 1.27–6.76; P =0.01). During a follow‐up of 43.2 (interquartile range, 27.0–55.6) months, the CKD progression occurred in 271 (36.1%) patients. The highest suPAR tertile was significantly associated with higher risk of CKD progression than the lowest tertile (hazard ratio [HR], 2.09; 95% CI, 1.37–3.21; P =0.001). When the relationship was reevaluated with respect to each dipping pattern (dipper, extreme dipper, nondipper, and reverse dipper), this association was consistent only in reverse dippers in whom the risk of CKD progression increased (HR, 1.43; 95% CI, 1.02–2.01; P =0.03) with every 1‐unit increase in serum suPAR levels. Conclusions Elevated suPAR levels are independently associated with CKD progression, and this association is prominent in reverse dippers.

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

Journal of Investigative Medicine ◽

10.1136/jim-2020-001702 ◽

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.

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Endothelins and their antagonists in chronic kidney disease

10.1093/med/9780199592548.003.0114_update_001 ◽

2018 ◽

Author(s):

Neeraj Dhaun ◽

David J. Webb

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Animal Models ◽

Enzyme Inhibitors ◽

Angiotensin Converting Enzyme Inhibitors ◽

Fluid Retention ◽

Converting Enzyme ◽

Ckd Progression ◽

Converting Enzyme Inhibitors

The endothelins (ETs) are a family of related peptides of which ET-1 is the most powerful endogenous vasoconstrictor and the predominant isoform in the cardiovascular and renal systems. The ET system has been widely implicated in both cardiovascular disease and chronic kidney disease (CKD). ET-1 contributes to the pathogenesis and maintenance of hypertension and arterial stiffness, as well endothelial dysfunction and atherosclerosis. By reversal of these effects, ET antagonists, particularly those that block ETA receptors, may reduce cardiovascular risk. In CKD patients, antagonism of the ET system may be of benefit in improving renal haemodynamics and reducing proteinuria, effects seen both in animal models and in some human studies. Data suggest a synergistic role for ET receptor antagonists with angiotensin-converting enzyme inhibitors in lowering blood pressure, reducing proteinuria, and in animal models in slowing CKD progression. However, in clinical trials, fluid retention or cardiac failure has caused concern and these agents are not yet ready for general use for risk reduction in CKD.

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Predicting Renal Failure Progression in Chronic Kidney Disease Using Integrated Intelligent Fuzzy Expert System

Computational and Mathematical Methods in Medicine ◽

10.1155/2016/6080814 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 24

Author(s):

Jamshid Norouzi ◽

Ali Yadollahpour ◽

Seyed Ahmad Mirbagheri ◽

Mitra Mahdavi Mazdeh ◽

Seyed Ahmad Hosseini

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Renal Failure ◽

Kidney Disease ◽

Diastolic Blood Pressure ◽

Absolute Error ◽

Ckd Progression ◽

Anfis Model ◽

Inference System ◽

Clinical Records

Background.Chronic kidney disease (CKD) is a covert disease. Accurate prediction of CKD progression over time is necessary for reducing its costs and mortality rates. The present study proposes an adaptive neurofuzzy inference system (ANFIS) for predicting the renal failure timeframe of CKD based on real clinical data.Methods.This study used 10-year clinical records of newly diagnosed CKD patients. The threshold value of 15 cc/kg/min/1.73 m2of glomerular filtration rate (GFR) was used as the marker of renal failure. A Takagi-Sugeno type ANFIS model was used to predict GFR values. Variables of age, sex, weight, underlying diseases, diastolic blood pressure, creatinine, calcium, phosphorus, uric acid, and GFR were initially selected for the predicting model.Results.Weight, diastolic blood pressure, diabetes mellitus as underlying disease, and currentGFR(t)showed significant correlation with GFRs and were selected as the inputs of model. The comparisons of the predicted values with the real data showed that the ANFIS model could accurately estimate GFR variations in all sequential periods (Normalized Mean Absolute Error lower than 5%).Conclusions.Despite the high uncertainties of human body and dynamic nature of CKD progression, our model can accurately predict the GFR variations at long future periods.

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Chronic kidney disease in children: problems of arterial hypertension

Nephrology (Saint-Petersburg) ◽

10.24884/1561-6274-2019-23-5-47-55 ◽

2019 ◽

Vol 23 (5) ◽

pp. 47-55

Author(s):

I. A. Karimdzhanov ◽

G. K. Iskanova ◽

N. A. Israilova

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Renal Failure ◽

Risk Factor ◽

Cardiovascular Diseases ◽

Kidney Disease ◽

Arterial Hypertension ◽

Ckd Progression ◽

Vascular Regulation ◽

Target Organs

The review contains materials on the course of chronic kidney disease (CKD) in children with arterial hypertension (AH). The relationship between CKD and AH was shown, where hastening of CKD progression to end-stage renal failure in the presence of AH was established. The regulation of AH in children is necessary for the treatment of CKD, because AH is not established on time, is not well controlled and is often masked. Impaired vascular regulation, fluid overload, increased cardiac output, and peripheral vascular resistance, alone or in combination, can lead to hypertension in CKD. The use of modern methods for monitoring and controlling blood pressure is crucial to improve the management of AH and prevent damage to target organs in children. 24-hour blood pressure measurements are an important tool in determining the prognosis and treatment of children with CKD. To identify impaired renal function in CKD, a large number of biomarkers are used. Glomerular filtration rate (GFR), serum creatinine and cystatin C are currently used as biomarkers for renal failure. Recently, biomarkers, including KIM-1, LFABP, NGAL, and IL-18 have been proposed as markers of acute kidney injury, and they may be useful in the future for early detection of CKD progression in children. In newborns and children of early and older age, hypertension occurs due to renovascular and parenchymal diseases.AH is considered a marker of CKD severity and is a risk factor for progressive deterioration of kidney function, as well as thedevelopment of cardiovascular diseases. Sympathetic hyperactivity, excessive formation of free radicals, reduced bioavailability of nitric oxide (NO) and excessive production of angiotensin II leads to an increase in blood pressure. Obesity or an increase in body mass index (BMI) is currently considered as a risk factor not only for cardiovascular diseases and diabetes but also for CKD. Hyperuricemia and CKD are closely related, as the accumulation of uric acid is associated with hypertension, metabolic syndrome and microalbuminuria, which are also risk factors for the progression of CKD. AH has a detrimental effect on target organs, including the kidneys, eyes, and heart. Lifestyle modifications, weight control, healthy eating, reduced sodium intake, maintenance exercises and basic drug therapy using angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers can slow the progression of CKD in children.

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

Scientific Reports ◽

10.1038/s41598-021-94467-z ◽

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).

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