scholarly journals Changes in FGF-23, Neutrophil/Platelet Activation Markers, and Angiogenin in Advanced Chronic Kidney Disease and Their Effect on Arterial Stiffness

2019 ◽  
Vol 44 (5) ◽  
pp. 1166-1178
Author(s):  
Hye-Min Choi ◽  
Young-Eun Kwon ◽  
Sol Kim ◽  
Dong-Jin Oh

Aims: The aims of this study were to measure changes in fibroblast growth factor 23 (FGF-23), neutrophil (elastase, lactoferrin)/platelet activation marker (mean platelet volume-to-platelet count ratio [MPR]), and angiogenin according to the stage of chronic kidney disease (CKD), and to evaluate the association of FGF-23, elastase, lactoferrin, MPR, and angiogenin with arterial stiffness using brachial-ankle pulse wave velocity (ba-PWV) in CKD patients. Methods: According to the estimated glomerular filtration rate (eGFR) calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the patients were allocated to five groups: (1) normal controls (eGFR ≥90 mL/min/1.73 m2 without pathologic, urine [proteinuria], blood [electrolyte], and imaging abnormalities; n = 22); (2) CKD stage 2 (eGFR 60–89 mL/min/1.73 m2; n = 17); (3) CKD stage 3 (eGFR 30–59 mL/min/1.73 m2; n = 22); (4) CKD stage 4 (eGFR 15–30 mL/min/1.73 m2; n = 17); and (5) CKD stage 5-hemodialysis (HD) (n = 30). All the patients were free of clinically apparent cardiovascular disease. Serum FGF-23, elastase, lactoferrin, and angiogenin concentrations and the MPR were measured to study the association of the above parameters with the clinical (age, sex, presence of diabetes mellitus, and blood pressure), biochemical (calcium, phosphorus, uric acid, intact parathyroid hormone [PTH], low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein), and ba-PWV values of the CKD patients. Results: (1) The mean ba-PWV values were 1,497.2 ± 206.4 cm/s in the controls, 1,649.0 ± 247.9 cm/s in the CKD stage 2 group (p < 0.05 vs. controls), 1,655.8 ± 260.3 cm/s in the CKD stage 3 group (p < 0.05 vs. controls), 1,823.0 ± 402.4 cm/s in the CKD stage 4 group (p < 0.05 vs. controls and CKD stages 2 and 3), and 1,905.2 ± 374.1 cm/s in the CKD stage 5-HD group (p < 0.05 vs. controls and CKD stage 2). (2) The mean log10(FGF-23) concentration values were 0.77 ± 0.27, 0.97 ± 0.48, 1.10 ± 0.35 (p < 0.05 vs. controls and CKD stage 2), 1.35 ± 0.48 (p < 0.05 vs. controls and CKD stages 2 and 3), and 2.12 ± 0.82 (p < 0.05 vs. controls and CKD stages 2–4); the mean angiogenin levels were 230.6 ± 70.5 pg/mL, 283.0 ± 53.5 pg/mL (p < 0.05 vs. controls), 347.3 ± 76.9 pg/mL (p < 0.05 vs. controls and CKD stage 2), 445.9 ± 90.6 pg/mL (p < 0.05 vs. controls and CKD stages 2 and 3), and 370.9 ± 142.4 pg/mL (p < 0.05 vs. controls and CKD stages 2 and 3). (3) In the stage 3–4 CKD/HD patients, the mean elastase-to-neutrophil and lactoferrin-to-neutrophil ratios were significantly lower than in the controls and the stage 2 CKD patients. (4) Our multivariate linear regression analyses showed that age, pulse pressure, mean arterial pressure, PTH, and FGF-23 were independently associated with ba-PWV values. Conclusions: Circulating FGF-23 and angiogenin concentrations gradually increased as CKD advanced, whereas neutrophil activation markers were significantly lower in the stage 3–4 CKD/HD patients than in the controls and stage 2 CKD patients. FGF-23 was weakly associated with ba-PWV values in patients with CKD/HD and no previous cardiovascular disease.

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
A B Md Radzi ◽  
S S Kasim

Abstract Background Arterial damage in chronic kidney disease (CKD) is characterized by aortic stiffness. This is seen in elderly patients with advanced CKD. The association between arterial stiffness and early CKD is not well established. Objective: We aimed to study arterial stiffness using pulse wave velocity (PWV) among patients with chronic kidney disease (CKD) stage 2 to 4 and normal renal function in younger-age population. Design and Method: Patients with confirmed CKD stage 2 to 4 were recruited from various clinics from Universiti Teknologi MARA Medical Center, Sungai Buloh, Malaysia from 1st August 2015 until 31st January 2018. Sociodemographic and anthropometric indices were recorded on recruitment. Each patient underwent carotid-femoral (aortic) PWV measurement to determine arterial stiffness. PWV is determined using a one-probe device (SphygmoSore XCEL). Results: 87 patients with CKD stage 2–4 and 87 control patients were recruited. The mean age was 47 ± 5.4 years. CKD patients had a higher mean PWV (7.8 m/s ± 1.7) than healthy controls (5.6 m/s ± 1.0) (p &lt; 0.001, 95% CI –2.59, –1.77). There was significant difference of mean PWV between control (5.6 m/s ± 1.0) and CKD stage 2 (7.6 m/s ± 1.5) (p &lt; 0.001, 95% CI –2.40, –1.49). Our results showed a stepwise increase in PWV from control subjects, CKD stage 2 through stage 4 (p &lt; 0.001). The mean difference of PWV between CKD stage 2 (7.6 m/s, ± 1.5) and stage 4 (9.0 m/s, ± 0.8) was 1.43 (p &lt; 0.001, 95% CI –2.50, -0.35). There was significant difference of mean PWV between diabetes mellitus (DM) (8.2 m/s ± 1.8) and non-DM (7.3 m/s ± 1.3) patients with CKD stage 2–4 (p = 0.022, 95% CI –1.50, –0.12). Mutiple linear regression analysis showed only age (β = 0.078, p = 0.014), mean arterial pressure (MAP) (β = 0.031, p = 0.007) and diuretics usage as the combination antihypertensive medication (β = 0.839, p = 0.018) were independently associated with PWV (r2 = 0.249, p &lt; 0.001). Conclusions: This study shows that arterial stiffness as assessed by PWV occurs early in CKD patient and increased arterial stiffness occurs in parallel with decline of glomerular filtration rate in patients with mild-to-moderate CKD of younger age population.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Trisha Sachan ◽  
Anita Saxena ◽  
Amit Gupta

Abstract Background and Aims Changes in dietary phosphorus regulate serum FGF-23, parathyroid hormone, 1,25(OH)(2)D and Klotho concentrations . Cardiovascular disease (CVD) is the principal killer of patients with chronic kidney disease and hyperphosphetemia is a potent risk factor it. Of many causative factors for CVD in CKD, dietary interventions involving restriction of dietary phosphorous intake can help reduce onset of CVD at early stages of CKD with other corrective measures. Muscle wasting is a consequence of uremic syndrome which alters body composition. The aim of the study was to study effect of dietary phosphorous restriction on FGF-23, iPTH, Klotho, 1,25(OH)(2)D and body composition in chronic kidney disease patients. Method This is a longitudinal study with 12 months intervention, approved by Ethics Committee of the institute. A total 132 subjects were recruited (66 healthy controls, 66 CKD patient. of 66 patients 33 were in CKD stage 1 and 33 in stage 2. GFR was calculated with the help of MDRD formula. Biochemical parameters of subjects were evaluated at baseline, 6 and 12 months along with the anthropometric measurements (body weight, height, mid upper arm circumference (MUAC), and skin folds). Three days dietary recall was taken to evaluate energy, protein and phosphorous intake. CKD patients whose dietary phosphorous intake was more than 1000 mg/day, were given intense dietary counseling and prescribed dietary modifications by restricting dietary phosphorous between 800-1000 mg/day. Results The mean age of controls and patients was 37.01±9.62 and 38.27±12.06 and eGFR of 136.94±11.77 and 83.69±17.37 respectively. One way ANOVA showed significant difference among controls and the study groups in hemoglobin (p&lt;0.001), s albumin (p&lt;0.001), FGF-23 (p&lt;0.001), klotho (p&lt;0.001), urinary protein (p&lt;0.001) and Nephron Index (p&lt;0.001).The mean energy intake (p = 0.001) and dietary phosphorous intake (p&lt;0.001) of the CKD patients decreased significantly with the decline in the renal function along with the anthropometric measures i.e. BMI (p = 0.041),WHR (p = 0.015) and all four skin folds (p&lt;0.001). On applying Pearson’s correlation, eGFR correlated negatively with urinary protein (-0.739, 0.000), FGF-23 (-0.679, 0.000) and serum phosphorous (-0.697, 0.000) and positively with klotho (0.872, 0.000). FGF-23 correlated negatively with klotho (-0.742, 0.000). Dietary phosphorous was found to be positively correlated with urinary protein (0.496, 0.000), serum phosphorous (0.680, 0.000) and FGF-23 (0.573, 0.000) and negatively with Klotho (-0.602, 0.000). Nephron index revealed a positive correlation with eGFR (0.529, 0.000). Urinary protein correlated negatively with klotho (-0.810, 0.000). A multiple linear regression was run to predict eGFR from anthropometric variables such as BMI, WHR, MUAC, skin folds thickness and handgrip strength. All anthropometric variables predicted decline in eGFR (p&lt;0.05, R2 =0.223). At 6 and 12 months; repeated ANOVAs analysis showed a statistically significant difference in serum creatinine (p=0.000), serum phosphorous (p=0.000), FGF-23(p=0.000) and klotho (p=0.000). Conclusion Elevated levels of FGF-23 and decreased Klotho levels, with the moderate decline in renal function improved with the restricted phosphorous diet at 6 and 12 months emphasizing the importance of phosphorus restriction at an early stage.


Author(s):  
Shashank Kotian ◽  
Ashok S. Naik ◽  
Manjunath Revanasiddappa ◽  
Maniyankode Krishnamohan Goutham

Abstract Objectives To compare the proportion of sensorineural hearing impairment (SHI) among patients of chronic kidney disease (CKD) stages 3&4 with CKD stage 5. Materials and Methods This is a cross-sectional study of 30 patients with CKD stages 3 and 4 and 30 patients in stage 5. All patients had an audiological evaluation with pure tone audiometry. Results Our study had 49 males (82%) and 11 females (18%), with the age ranging from 20 to 60 years (mean: 45.13 years). The mean SHI values in stage 3&4 were 28.44 dB and in CKD stage 5 was 31.22 dB. In the right ear, the mean hearing loss in stage 3, stage 4, and stage 5 was 28.17 dB, 28.67 dB, and 31.84 dB, respectively. In the left ear, the mean SHI values in stage 3, stage 4, and stage 5 were 27.05 dB, 31.89 dB, and 30.61 dB, respectively.The mean SHI in stage 3&4 for age group 20 to 30 years was 13.66 dB, for 31 to 40 years was 26.33 dB, for 41 to 50 years was 35.18 dB, for 51 to 60 years was 37.12 dB. The mean SHI in stage 5 for the age group of 20 to 30 years was 16.48 dB, for 31 to 40 years was 28.29 dB, for 41 to 50 years was 31.82 dB, for 51 to 60 years was 34.35 dB. There was a significant correlation between hearing loss and CKD with respect to age (p < 0.001). The duration of renal illness and associated comorbidities was not a significant contributor to hearing loss in our study (p > 0.05). Conclusion As per our study, with progression in the stage of chronic kidney disease, the hearing loss also increased indicating a possible link between the two. We also noted that the hearing loss increased with the increasing age.


2019 ◽  
Vol 41 (1) ◽  
pp. 29-37
Author(s):  
Josefina Maria Sousa Santos Lascasas ◽  
Isabel Fonseca ◽  
Jorge Malheiro ◽  
Sofia Santos ◽  
Andreia Campos ◽  
...  

ABSTRACT Introduction: Chronic kidney disease (CKD) is an independent risk factor for several unfavorable outcomes including cardiovascular disease (CVD), particularly in the elderly, who represent the most rapidly growing segment of the end-stage kidney disease (ESKD) population. Portugal has the highest European unadjusted incidence and prevalence rates of ESKD. In 2012, we started to follow a cohort of elderly CKD patients, we describe their baseline characteristics, risk profile, and cardiovascular disease burden. Methods: All CKD patients aged 65 years and older referred to our department during 2012 were enrolled. Baseline data included: demographic, CKD stage, medication, comorbid conditions. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI formula. Results: A total of 416 patients, 50% referred by primary care physicians, aged 77 ± 7 years, 52% male, with a median eGFR of 32 mL/min/1.73m2 participated in the study. Fifty percent had diabetes (DM), 85% dyslipidemia, 96% hypertension; 26% were current/former smokers, and 24% had a body mass index > 30 kg/m2. The prevalence of CVD was 62% and higher in stage 4-5 patients; in diabetics, it gradually increased with CKD progression (stage 3a < stage 3b < stage 4-5) (39, 58, 82%; p < 0.001). Conclusions: At baseline, our CKD elderly cohort had a higher burden of CVD. The prevalence of CVD was greater than in other European CKD cohorts. Lower level of eGFR was associated with a greater burden of CVD and was more pronounced in diabetics, highlighting the importance of strategically targeting cardiovascular risk reduction in these patients.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Basma Sultan ◽  
Hamdy Omar ◽  
Housseini Ahmed ◽  
Mahmoud Elprince ◽  
Osama Anter adly ◽  
...  

Abstract Background and Aims Vascular calcification (VC) plays a major role in cardiovascular disease (CVD), which is one of the main causes of mortality in patients with chronic kidney disease (CKD). The study aims at early detection of breast arterial calcification (BAC) in different stages of CKD (stage 2, 3& 4) patients as an indicator of systemic VC. Method A case control study was conducted targeting CKD women, aged 18- 60 years old. The sample was divided into 3 groups; A,B,C (representing stage 2, 3 & 4 of CKD) from women who attended nephrology and Internal medicine clinics and admitted in inpatient ward in Suez Canal University Hospital. A 4th group (D) was formed as a control group and included women with normal kidney functions (each group (A, B, C, D) include 22 women). The selected participants were subjected to history taking, mammogram to detect BAC and biochemical assessment of lipid profile, Serum creatinine (Cr), Mg, P, Ca, PTH and FGF23. Results Our study detected presence of BAC in about 81.8% of hypertensive stage 4 CKD patients compared with 50% in stage 3 CKD, also in the majority of stage 4 CKD patients who had abnormal lipid profile parameters and electrolyte disturbance. Most of the variables had statistical significance regarding the presence of BAC. Conclusion Although it is difficult to determine the definite stage at which the risk of VC begins but in our study, it began late in stage 2 CKD, gradually increased prevalence through stage 3 and became significantly higher in stage 4. These results suggest that preventive strategies may need to begin as early as stage 2 CKD.


Medicina ◽  
2020 ◽  
Vol 57 (1) ◽  
pp. 15
Author(s):  
Altynay Balmukhanova ◽  
Kairat Kabulbayev ◽  
Harika Alpay ◽  
Assiya Kanatbayeva ◽  
Aigul Balmukhanova

Background and objectives: Chronic kidney disease (CKD) in children is a complex medical and social issue around the world. One of the serious complications is mineral-bone disorder (CKD-MBD) which might determine the prognosis of patients and their quality of life. Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone which is involved in the pathogenesis of CKD-MBD. The purpose of the study was to determine what comes first in children with CKD: FGF-23 or phosphate. Materials and Methods: This cross-sectional study included 73 children aged 2–18 years with CKD stages 1–5. We measured FGF-23 and other bone markers in blood samples and studied their associations. Results: Early elevations of FGF-23 were identified in children with CKD stage 2 compared with stage 1 (1.6 (1.5–1.8) pmol/L versus 0.65 (0.22–1.08), p = 0.029). There were significant differences between the advanced stages of the disease. FGF-23 correlated with PTH (r = 0.807, p = 0.000) and phosphate (r = 0.473, p = 0.000). Our study revealed that the elevated level of FGF-23 went ahead hyperphosphatemia and elevated PTH. Thus, more than 50% of children with CKD stage 2 had the elevating level of serum FGF-23, and that index became increasing with the disease progression and it achieved 100% at the dialysis stage. The serum phosphate increased more slowly and only 70.6% of children with CKD stage 5 had the increased values. The PTH increase was more dynamic. Conclusions: FGF-23 is an essential biomarker, elevates long before other markers of bone metabolism (phosphate), and might represent a clinical course of disease.


2020 ◽  
pp. BJGP.2020.0871
Author(s):  
Clare Elizabeth MacRae ◽  
Stewart Mercer ◽  
Bruce Guthrie

Background: Many drugs should be avoided or require dose-adjustment in chronic kidney disease (CKD). Previous estimates of potentially inappropriate prescribing rates have been based on data on a limited number of drugs and mainly in secondary care settings. Aim: To determine the prevalence of contraindicated and potentially inappropriate primary care prescribing in a complete population of people with CKD. Method: Cross-sectional study of prescribing patterns in a complete geographical population of people with CKD defined using laboratory data. Drugs were organised by British National Formulary advice. Contraindicated (CI) drugs: “avoid”. Potentially high risk (PHR) drugs: “avoid if possible”. Dose inappropriate (DI) drugs: dose exceeded recommended maximums. Results: 28,489 people with CKD were included in analysis, of whom 70.0% had CKD 3a, 22.4% CKD 3b, 5.9% CKD 4, and 1.5% CKD 5. 3.9% (95%CI 3.7-4.1) of people with CKD stages 3a-5 were prescribed one or more CI drug, 24.3% (95%CI 23.8-24.8) PHR drug, and 15.2% (95% CI 14.8-15.62) DI drug. CI drugs differed in prevalence by CKD stage, and were most commonly prescribed in CKD stage 4 with a prevalence of 36.0% (95%CI 33.7–38.2). PHR drugs were commonly prescribed in all CKD stages ranging from 19.4% (95%CI 17.6-21.3) in stage 4 to 25.1% (95%CI 24.5–25.7) in stage 3b. DI drugs were most commonly prescribed in stage 4, 26.4% (95%CI 24.3-28.6). Conclusion: Potentially inappropriate prescribing is common at all stages of CKD. Development and evaluation of interventions to improve prescribing safety in this high-risk populations are needed.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Magdy M El Sharkawy ◽  
Lina E Khedr ◽  
Ashraf H Abdelmbdy ◽  
Mohamed T Mohamed

Abstract Background Anemia is a severe complication of chronic kidney disease (CKD) that is seen in more than 80% of patients with impaired renal function. Although there are many mechanisms involved in the pathogenesis of anemia of renal disease, the primary cause is the inadequate production of erythropoietin by the damaged kidneys. Aim of the work to assess hepcidin level in non dialysis patients (CKD stage 4 &5) treated from Hepatitis C virus and its relation to iron parameters. Patients and Methods This study was conducted on 20 CKD patients (stage 4 and 5) treated from hepatitis C virus. All candidates included in this study subjected to careful history taking, full clinical examination and investigations (including complete blood count, renal chemistry, HCVAb, serum iron, total iron binding capacity, TSAT%, ferritin and hsCRP. Serum hepcidin was analyzed by ELISA technique. Results Serum hepcidin was 26.35±7.26; 40% in stage III, 37.8% in stage IV and 22.2% in stage V. There was statistically significant difference between GFR stages according to Hb., Drug intake ACE inhibitor/ARB, Plt., Creatinine, BUN, Iron, TIBC, Ferritin, T SAT%, CRP and Serum Hepcidin. We showed significant correlations between serum hepcidin and TIC, Iron, TIBC, Ferritin and TSAT%. Conclusion Median hepcidin value is elevated in nondialysis CKD patients due to increased inflammation and decreased clearance of hepcidin. Furthermore, iron status modifies serum hepcidin level and its association with Hb. Increased hepcidin level leads to iron-restricted erythropoiesis and recombinant human EPO (rhEPO) resistance by inhibiting iron absorption from gut and iron recycling from macrophages. Hence, elevated hepcidin can predict need for parenteral iron to overcome hepcidin-mediated iron-restricted erythropoiesis and need for relatively higher rhEPO doses to suppress hepcidin.


Author(s):  
TAOPHEEQ MUSTAPHA ◽  
VARIJA BHOGIREDDY ◽  
HARTMAN MADU ◽  
ADU BOACHIE ◽  
ABDUL OSENI ◽  
...  

BACKGROUND: Heart failure (HF) and Chronic kidney disease (CKD) are major public health problems that often co-exist with a resultant high mortality and morbidity. Most of the studies evaluating their reciprocal prognostic impact have focused on mortality in majority populations. There is limited literature on the impact of CKD on HF morbidities in ethnic minorities. AIMS: Our study seeks to compare HF outcomes in patients with or without CKD in an African-American predominant cohort. METHODS: We obtained data from the NGH at Meharry Heart Failure Cohort; a comprehensive retrospective HF database comprised of patient care data (HF admissions, non-HF admissions, and emergency room visits) were assessed from January 2006 to December 2008. The study group consist of 306 subjects with a mean age of 65±15 years. 81% were African-American (AA), 19% Caucasian and 48.5% are females. Following the NKF KDOQI guidelines, 5 stages of CKD were outlined based on GFR. RESULTS: The overall prevalence of CKD in this population is 54.2%. CKD stage 1 was most prevalent with 45.8%, prevalence for stages 2-5 are 21.6%, 18.3%, 9.5% and 4.9% respectively. The comparison of the mean of ER visits, non HF hospitalizations and HF hospitalizations between normal and CKD patients was done using independent t-test and showed no significant difference in the mean number of ER visits (p=0.564), or HF hospitalizations(p=0.235). However, there is a statistically significant difference in the mean number of non -HF hospitalizations between normal and CKD patients (p=0.031). CONCLUSION: This study shows that the prevalence of CKD in this minority -predominant HF cohort is similar to prior studies in majority populations. However, only the non-HF hospitalizations were significantly increased in the CKD group. Future prospective studies will be needed to define the implications of this in the management of HF patients with CKD.


2020 ◽  
Author(s):  
Priyank Patel ◽  
Andrew Frankel

Abstract Background Renin–angiotensin–aldosterone system (RAAS) inhibitors provide significant cardiorenal benefits with improved long-term outcomes for patients. This is most significant for patients receiving maximal RAAS inhibition, but some patients are unable to tolerate this therapy because of hyperkalaemia. Recently published National Institute for Health and Care Excellence (NICE) technology appraisal guidance recommended using sodium zirconium cyclosilicate (SZC) and patiromer for patients with chronic kidney disease (CKD) stage 3b to 5 or heart failure with reduced ejection fraction, who are not taking an optimised dosage of RAAS inhibitor because of hyperkalaemia. Objective Determine the impact of a locally produced guideline on effective implementation of NICE recommendation for use of SZC or patiromer to help maximise inhibition of the renin–angiotensin–aldosterone system within the general nephrology clinic. Methods A local guideline to practically support the implementation of recommendations made by NICE in the chronic use of new potassium binders was produced. One hundred sequential patients in a general nephrology clinic with non-immune chronic kidney disease (CKD 3 to 5) had their electronic records reviewed. Those with an indication for RAAS inhibition were identified. Results Of the 100 consecutive patients audited, 46 were female and 54 were male. The mean age of these patients was 64 and the mean estimated glomerular filtration rate (eGFR) was 33. Sixty-eight patients had an indication for being on RAAS inhibition with only 10 on maximal doses. Of the remaining 58 patients, 26 (45%) were limited by hyperkalaemia. Of these 26 patients, 12 of these patients (46%) had hyperkalaemia associated with an episode of acute kidney injury (AKI). Therefore, 14% of patients attending a general nephrology clinic were identified suitable for SZC and patiromer. Conclusions A significant proportion (14%) of unselected patients attending a general nephrology clinic were not on optimum RAAS inhibition due to hyperkalaemia. These patients would meet the criteria established within a working guideline for the implementation of the chronic use of SZC or patiromer and are likely to attain prognostic long-term benefit by using these new potassium binders to maximise RAAS inhibition. This analysis has implications for renal centres across the UK.


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