INTRODUCTION TO RESEARCH (PDMS 4243)

ASSIGNMENT 2 WEEK 3

LITERATURE REVIEW

PREPARED BY:
No. NAME MATRIC NUMBER
1. ANISATULWIDAD BINTI SAMHANULRAFHAN DMS09210003
2. NUR ALIA SYAFIQAH BINTI MOHAMAD AUSRI DMS09210018
3. NURUL NAJAH BINTI MOHAMAD NAZRI DMS09210026
4. HUDA ATIQAH BINTI MUHAMAD FAUZI DMS09212070
5. NURIN FARHANA BINTI NOR AZMAN DMS09212088
6. YNA IRYANI BINTI ANAS DMS09212102

PREPARED FOR:
MISS ZULFA BINTI ZAKUAN
TITLE OF RESEARCH :

Haematological and Renal Biomarker Parameter among B40.

OBJECTIVE OF RESEARCH :

To identify haematological and renal biomarker parameter among low-income community.

SUBTOPICS:

1. Relation of hypertension and diabetes mellitus for renal failure.

2. Major factor influencing hypertension among B40.
3. Identification of renal function test using blood.
4. AKI (Acute Kidney Injury) biomarker test.
5. Neutrophil Gelatinase-associated Lipocalin (NGAL) test.

1) Relation of hypertension and diabetes mellitus for renal failure

Renal failure or also known as kidney disease is a serious condition that characterized by loss
function of kidney gradually, that collected wasted and fluid in body and if being in stage 4 or
5 the patient need to go thru with dialysis until end of life. Those 2 common diseases that
related to development of renal failure, which is hypertension and diabetes.

In hypertension, the high blood pressure can cause damage to the blood vessels in the
kidneys, leading to a condition called nephrosclerosis. This can eventually lead to chronic
kidney disease and kidney failure (Jia & Sowers, 2021) 10. Furthermore, Verma et al. (2016)
mentioned that hypertensive patients were found to have a lower estimated glomerular
filtration rate (eGFR) which is a major contributing factor for the development of diabetic kidney
disease. Low serum albumin levels were significantly associated with the occurrence of
hypertension, therefore, measures to keep the albumin levels high should be adopted to
reduce the incident of hypertension in diabetes patients 14.

Diabetic nephropathy is characterized by persistent albuminuria, arterial blood pressure

elevation, a relentless decline in glomerular filtration rate (GFR) (Vyas et al., 2016)14. However,
Jia & Sowers (2021) has reported in their journal that, high blood sugar levels can also damage
the blood vessels in the kidneys, leading to a condition called diabetic nephropathy. This can
also eventually lead to chronic kidney disease and kidney failure 10.
2. Major factor influencing hypertension among B40

There are many reasons major for hypertension. Related to the situation low socio-economics
and not getting regular medical check-up. Hypertension is attributed from genetic and
environmental factor. Genetic factors also contribute in this disease and can lead to stroke,
heart disease, kidney disease and other diseases8.

Other than that, circulating protein in serum are also known contribute to development of
hypertension. People who get this hypertension mostly at the aged of 30-79 years old. Some
biomarkers, including C-reactive protein, fibrinogen, B-type natriuretic peptide, plasminogen
activator inhibitor-1, aldosterone, renin, has linked to an increased risk of developing
hypertension (Li, Y. et al.,2023)10.

Risk set sampling was used to identify control but people with prior history of cancer and
diabetes were not eligible for inclusion in these blood biomarker studies. Examine between
people using set of biomarkers related to inflammatory response by extract blood sample and
to get the result11.

3. Identification of renal function test using blood.

The markers of renal function test assess the normal functioning of kidneys. These markers
may be radioactive and non-radioactive. They indicate the glomerular filtration rate,
concentrating and diluting capacity of kidneys (tubular function). If there is an increase or
decrease in the valves of these markers it indicates dysfunction of kidney (Gowda,2010) 7 .

Previous studies have determined that RBC’s parameters and their correlation with renal
functions, as well as diabetes mellitus (DM) patients show a significant derangement in various
hematological parameters including changes affecting the red blood cells (RBCs). All these
derangements have an imposing effect on any of the RBC indices (Adane,2020)1 . Edward et
al. (2003)6 have done investigated of relationships between RVD, blood pressure and renal
function using cross sectional method in an unselected free-living sample of elderly
Americans. The presence of RVD showed significant and independent associations with
clinical hypertension, increased systolic blood pressure, excretory renal insufficiency, and
increased serum creatinine level. Furthermore, the observed relationship between the
presence of RVD and elevated measures of serum creatinine was dependent on an interaction
with elevated systolic blood pressure.

This literature review’s purpose is to help the reader understand that renal function tests
utilizing blood samples have crucial role in assessing kidney health. Serum creatinine, blood
urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), cystatin C, and electrolyte
levels emerge as key markers evaluated through these tests (Dharmarajan & Pitchumoni,
2020)5. Studies affirm their significance in estimating kidney function, diagnosing renal
disorders, and monitoring disease progression. Ongoing research explores the accuracy,
sensitivity, and specificity of these tests, aiming to improve early detection and management
of renal conditions. Understanding these blood-based renal function tests remains crucial in
clinical practice for comprehensive kidney health assessment.

4. AKI (Acute Kidney Injury) biomarker test

A prevalent clinical illness known as acute kidney injury (AKI) is characterized by impaired
renal function and structure. After symptoms appear, serum creatinine, urine microscopy, and
urine output are among the diagnostic tests that can be used to diagnose AKI. However, their
capacity to detect subclinical AKI is that limited. Acute kidney injury (AKI) affects millions of
people in the US and increases morbidity, mortality, and healthcare expenditures (Rizvi &
Kashani, 2017)12. Furthermore, numerous possible indicators have been researched.
Interleukin-18(IL-18),N-acetyl-β-D-glucosaminidase (NAG), kidney injury molecule-1 (KIM-
1
),and neutrophil gelatinase-associated lipocalin (NGAL) are promising injury markers found
in urine. Next, Waikar and Bonventre (2008), mentioned that serum creatinine (SCr) and blood
urea nitrogen (BUN), two biomarkers that were discovered and introduced into clinical practice
several decades ago, are the current diagnostic tests for AKI 15.

Strong pro-inflammatory cytokine interleukin-18 (IL-18) controls both the innate and acquired
immune responses and aids in the host's defence against infections. Both hematopoietic and
non-hematopoietic cells, such as mesenchymal cells, keratinocytes, monocytes, and
macrophages, produce IL-18. Autoimmunity may result from IL-18-induced cytotoxic and
inflammatory immune cell activity (Ihim,S. A. et al.,2022)9.Next, Rizvi and Kashani
(2017),mentioned that urine IL18 levels may be easily and quickly tested and appear to rise
early in ischemia kidney injury (about 12 hours before clinical AKI). IL18's predictive accuracy
varies with age (children and teenagers have better diagnostic accuracy), time of collection,
and reference range12.

The proximal tubule lysosomal enzyme N-acetyl-β-glucosaminidase (NAG) has been the
subject of much research and has shown itself to be a reliable, sensitive, and long-lasting
indication of tubular damage. Nephrotoxicant exposure, delayed renal allograft function,
chronic glomerular disease, diabetic nephropathy, and after cardiopulmonary bypass
surgeries have, all been linked to elevated NAG levels (Vaidya, V. S. et al.,2008) 13.
Furthermore, Waikar and Bonventre (2008) reported by using a PCR-based method, kidney
injury molecule-1 (also known as "KIM-1" in humans or "Kim-1" in rodents) was found to be
the single most elevated gene in postischemic rat kidney. The type I cell membrane
glycoprotein encoded by KIM-1 has an extracellular region that contains a new domain
resembling sixcysteine immunoglobulin and a threonine/serine and proline-rich domain typical
of mucin-like O-glycoslyated proteins, indicating its possible involvement in cell-cell15.

5. Neutrophil Gelatinase-associated Lipocalin (NGAL) test

Neutrophil gelatinase-associated lipocalin (NGAL) is a protein belonging to the lipocalin
superfamily initially found in activated neutrophils, accordance with its role as an innate
antibacterial factor. However, it was subsequently shown that many other types of cells,
including those in the kidney tubule, may produce NGAL in response to various injuries. NGAL
may become one of the most promising next-generation biomarkers in clinical nephrology and
beyond (Bolignano,D . et al.,2008)3. Human NGAL was first discovered as a new protein
isolated from human neutrophil secondary granules. It was later shown to be a 25-kDa protein
covalently linked to neutrophil gelatinase. NGAL mRNA is normally expressed in a variety of
adult human tissues, including bone marrow, uterus, prostate, salivary gland, stomach, colon,
trachea, lung, liver and kidney4.

Previous studies also have shown that NGAL can be used as an early diagnostic biomarker
for AKI in typical clinical scenarios, and that it is a sensitive measure of established AKI in
people. The measurement of NGAL is quick, low-cost, and non-invasive, utilising either urine
or blood. In addition, it pinpoints the main site of damage within the kidney, has a high gradient
to enable risk categorization, and is sensitive enough to make an early diagnosis.
Nonetheless, other concomitant factors, such as systemic infections, inflammatory diseases,
anaemia, hypoxia, malignancies, chronic renal disease, and chronic hypertension, may affect
NGAL's efficacy as an AKI biomarker. urine NGAL is also a marker of chronic kidney disease
and its severity (Devajaran, P. 2010)4.
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