The relationship between serum Fetuin-A and the stages of left ventricular diastolic dysfunction

in patients on haemodialysis

A protocol of thesis
Submitted for partial fulfillment of master degree in internal medicine
By

Noura Abdul Rahim Jouda Abdul Rahim

Diplomate degree of internal medicine
Faculty of medicine for Girls

Al-Azhar University

Supervised By

Pof. Dr. Zeinab Helmy El-sayed

Professor Internal Meicine
Faculity of Medicine for Girls

Pof. Dr. Tarek Gamal Megahed

Consultant of clinical pathology

Medical Academy

Dr. Seham Sabry Qotb Alsayed

Assistant Prof of Medicine

Faculity of medicine for Girls

Al-Azhar Univercity
 (2021)
INTRODUCTION
Chronic kidney disease (CKD) is defined as the presence of kidney damage or an
estimated glomerular filtration rate (GFR) less than 60 ml/min/1.73 mt2, persisting for 3
months or more, irrespective of the cause. It is a state of progressive loss of kidney
function ultimately resulting in the need for renal replacement therapy (dialysis or
transplantation) (Vaidya & Aeddula., 2019)

The 2012 Kidney Disease Improving Global Outcomes (KDIGO) CKD

classification recommends details about the cause of the CKD and classifies into 6
categories based on glomerular filtration rate (G1 to G5 (John A. at el; 2012) with G3
split into 3a and 3b).
(Gianna M.at el; 2009)
CKD may result from disease processes in any of the three categories: pre-renal
(decreased renal perfusion pressure), intrinsic renal (pathology of the vessels,
glomeruli, or tubules-interstitium), or post-renal (obstructive). (Klahr, et al; 1998).
CKD is the major health problem affecting approximately
13% of united states (US) population and Indian scenario approximate 800 per million
case was reported due to diabetes and cardiovascular disease. (Rajauria et al., 2020)

The development of CKD and its progression to end stage renal disease (ESRD)
remains a significant source of reduced quality of life and significant premature
mortality. ESRD is a terminal illness defined as having a glomerular filtration rate of less
than 15 mL/min. The most common cause of ESRD in the US is diabetic nephropathy,
followed by hypertension. (Clements et al., 2020)

ESRD is a progressive disorder, and timely renal replacement therapy is necessary

to prevent death. The mortality rates for patients with ESRD are significantly higher than

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those without the disease. Hemodialysis (HD) is a process used for eliminate the
extracorporeal materials from the blood, Complications associated with renal failure and
hemodialysis is the important factors to be monitor and assess and minimized.

HD is a lifesaving process for the ESRD patient but duration of process different types
complications arise. (Rajauria et al., 2020)

ESRD leads to the development of a variety of hormonal and metabolic disorders.

Myokines and

adipokines, as regulators of metabolism, have recently gained increasing interest. (Di

Raimondo et al., 2016) CKD age-related problem, it is the primary causes of
morbidity and mortality in renal disease due to CVD. (Yang et al., 2020).

Heart failure (HF) is a major comorbidity in patients with ESRD. The presence of
HF is independently associated with mortality in patients on hemodialysis.
Approximately 50% of these patients present heart failure with preserved ejection
fraction (HFpEF), which often accompanies left ventricular diastolic dysfunction
(LVDD). (Yangang Gan et al; 2021).

Diastolic heart failure (DHF) is a clinical syndrome characterized by the symptoms

and signs of heart failure, a preserved ejection fraction (EF), and abnormal diastolic
function. From a conceptual perspective, diastolic heart failure occurs when the
ventricular chamber is unable to accept an adequate volume of blood during diastole, at
normal diastolic pressures and at volumes sufficient to maintain an appropriate stroke
volume. These abnormalities are caused by a decrease in ventricular relaxation and/or an
increase in ventricular stiffness. (Michael R.; et al; 2021).

DHF can produce symptoms that occur at rest (New York Heart Association
[NYHA] class IV), symptoms that occur with less than ordinary physical activity

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(NYHA class III), or symptoms that occur with ordinary physical activity (NYHA class
II). (American Heart Association, 2002).

DHF represents a common and potentially harmful clinical condition in CKD,

particularly in patients on hemodialysis treatment who are more susceptible to shifts in
fluid volume. The reasons for this high prevalence are related to the presence of many
traditional risk factors, and the synergistic effects of many peculiar factors related
directly to CKD and HD treatment. The under-recognition of DHF in dialysis patients
may be related to the atypical clinical presentation, and to the under use of simple
methods of myocardial function evaluation, such as the echocardiogram. A broader
recognition of the condition and the development of clinical trials to test interventions
(approaching risk factors both already applied in the general population and those
peculiar to CKD) may allow a significant reduction in morbidity and mortality in this
patient population. (Pecoits-Filho et al.; 2012)

Fetuin-A is a multifunctional glycoprotein (α2Heremans Schmid glycoprotein) is

a 62-kDa liver-derived glycoprotein. Through the formation of soluble colloidal troponin
particles, it strongly inhibits vascular calcification in the circulatory system. Calcium and
phosphorus overload and chronic micro inflammation in patients with ESRD may lead to
excessive consumption of fetuin-A and reduce its levels (Jahnen; et al. 2008). Excess
calcium and phosphorus levels, which cause ectopic and soft tissue calcification, also
promote the development of diastolic dysfunction (Li J.; et al. 2016).

Fetuin-A, a soluble transforming growth factor β (TGFβ) antagonist, regulates cytokine

dependent ontogenesis and fibrosis and inhibits cell proliferation, and continuously low
levels of fetuin-A reduce the inhibitory effect of TGF-β, which indirectly increases
myocardial fibrosis and leads to increased myocardial hypertrophy and stiffness. Serum

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fetuin-A levels in hemodialysis patients are related to diastolic dysfunction. (Yangang
Gan et al; 2021).

Fetuin-A is a potent circulatory inhibitor of vascular calcification, which is down

regulated by
inflammation. Chemically, fetuin-A acts as an inhibitor of spontaneous calcium
phosphate precipitation by forming soluble colloidal calciprotein particles. Fetuin-A-
deficient mice experience enhanced myocardial fibrosis and stiffness, and several studies
have documented an inverse relationship between serum fetuin-A levels and survival in
dialysis patients. (Talib A et al; 2012).
However, data on the association of LVDD with fetuin-A levels in patients with ESRD are limited. At present,
the specific mechanism and biomarkers of LVDD are not clear. (Yangang Gan et al; 2021).

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 AIM OF WORK

The aim of the work is to assess the relationship between serum fetuin-A levels and the stages of left ventricular
diastolic dysfunction (LVDD) among maintenance hemodialysis patients.

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 Patients and Methods

Patients
80 dialysis patients with end-stage renal disease (ESRD) at least 3 months of duration, each patient had a short
demographic and clinical history taken along with a physical examination with the following exclusion criteria:

1- Active angina.

2- Underlying malignancy.

3- Severe infection.

4-Major surgery within 1 month and refusal to provide consent.

5-Severe valvular disease and/or valve prosthesis.

6- Cardiomyopathies.

7-Myocardial infarction within the last 6 ms.

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 Clinical data collection

THE EVALUATION INCLUDING:

The patients’ medical records for history of cardiac disease, and the stage of LVDD. The values of systolic
and diastolic blood pressure.

LABORATORY MEASUREMENTS:
Laboratory tests, including:

1- Fetuin-A levels were determined using an enzymelinked immunosorbent assay (ELISA).

2- CBC

3- Serum albumin

4- S. calcium

5- S. phosphate

6- Lipid profile

7- Creatinine level

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RADIOLOGICAL INVESTIGATION:
Echocardiography

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 References

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