FACULTY OF HEALTH SCIENCE

SEMESTER 2

NDN 10402

NUTRITIONAL BIOCHEMISTRY AND METABOLISM

Lecturer’s name : Madam Norhayati Bt. Abd Hadi

Course name : Bachelor of Dietetic with Honour

Topic : Diet-Health Link

Date : 19 April 2018

Group members : Alia Nadhirah Binti Abd Rahim (BHBL17047261)

: Nur Farah Hanani Binti Johaizar (BHBL17046159)

INTRODUCTION

Chronic kidney disease also known as CKD is a progressive loss of renal function
over a period of months or years. Chronic kidney disease can leads to kidney failure and end-
stage renal disease (ESRD), the fifth stage of CKD which are the final stage. CKD also linked
to poor health outcomes such as higher risk of cardiovascular disease (CVD) and even death.
Many kidney related diseases like Polycystic Kidney Disease, Diabetic Nephropathy,
Nephrotic Syndrome, Glomerular Nephritis and Hypertensive Nephritis and so on can be
regarded as Chronic Kidney Disease. According to Glomerular Filtration Rate (GFR),
Chronic Kidney Disease is divided into five stages.

The first stage of CKD, the glomerular filtration rate (GFR) is more than 90 ml/min
per 1.73 m2 and the kidney damage are with normal or increased GFR. In the early stage,
there is no obvious symptom, so Chronic Kidney Disease is not easy to be detected and easier
to be ignored, which is the reason why many patients are diagnosed at final stages of CKD
with kidney failure when they realize they have kidney problem. In second stage, the patients’
GFR have reduce to 60-89 ml/min per 1.73 m2 and the kidney has been damaged mildly. The
third stage of CKD is when the kidney has been damaged moderately and the GFR dropped
between 30 to 59 ml/min per 1.73 m2. Stage 4 chronic kidney disease is a severe impairment
to the kidneys with GFR reduced to 15-30 ml/min per 1.73 m 2. The final stage is when the
GFR declines to less than 15 ml/min per 1.73 m2 which in most cases the patients need to
start kidney replacement therapy such as dialysis or kidney transplantation.

Based on the Management of Chronic Kidney Disease for Adult, June 2011, the
prevalence of CKD and end-stage renal disease (ESRD) is increasing worldwide and
becoming a global public health problem that affects the United States (US), United Kingdom
(UK), Europe, and other regions in the world such as Malaysia itself. In US, the estimated
prevalence of CKD was 16.8% while in Asia the prevalence ranged from 12.1% to 17.5%. In
Malaysia, the incidence and prevalence of patients with ESRD on dialysis had increased from
88 and 325 per million population (pmp) respectively in 2001 to 170 and 762 pmp
respectively in 2009. The increase in ESRD was largely because of the increasing incidence
of diabetic kidney disease (DKD) accounting for 58% of new patients accepted for dialysis.
The growing number of ESRD places an enormous human, economic and social burden on
the healthcare system. In an economic evaluation among Ministry of Health dialysis centres
in Malaysia, the cost of dialysis and erythropoietin was RM2, 500 per month. While in the
US, the cost of medical care was 1.7 times higher in patients with CKD stage 3 and 2.6 times
higher in those with stage 4 CKD.

PATHOGENESIS/ MECHANISM OF THE CHRONIC KIDNEY DISEASE

When discussing the pathogenesis of CKD, it is important to consider the renal

structural and physiological characteristics. The initial developments of abnormalities in
kidney function has been linked to chronic obesity and insulin resistant conditions, such as
the metabolic syndromes. Sympathetic hyperactivity, activation of the renin-angiotensin-
aldosterone system (RAAS) and the related development of hypertension are implicated and
further aggravated by the excess dietary intake of salt and effects of insulin resistance and
hyperinsulinemia on sodium retention.

Hypertension is often a first sign of CKD and hypertension in CKD also known as
Hypertensive Nephritis. Its result from the glomerular and the vascular changes. An elevated
systemic blood pressures cause a hypertrophic response leading to the intimal thickening of
the large and small vasculature. The blood flows decrease thus decreases the GFR. The
RAAS system were activated and increase the heart rate and further increases the
hypertension. The mechanisms are compensatory at first, but later lead to glomerular damage
such as global sclerosis, the ischemic injury to the nephrons that can causes death and the
focal segmental sclerosis, the glomerular enlargement for compensation of the loss of
nephrons in other kidney areas. Chronic changes in the vascular and the glomerular lead to
both loss that can cause nephrons loss. When some nephrons dies, it is less available to
maintain the GFR. Gradual decrease in GFR can be seen as the nephrons continue to die.

Next, the common cause of the CKD is diabetes. Diabetic nephropathy will eventually
leads to chronic kidney failure because prolonged exposure to high blood glucose can impairs
the functional units of kidneys and make the kidneys lose their filtering ability. Poorly
controlled of high blood glucose and high blood pressure will rapid the progression to the
stage five CKD. The primary cause of diabetic nephropathy is the chronic hyperglycaemias.
Unlike other tissues in the body, the transmembrane glucose transporter (GLUT) receptors do
not facilitate intracellular glucose transport in the kidney. This effect is mediated by the
number of mechanisms including glomerular hyperfiltration, direct effects of hyperglycaemia
and the advanced glycosylation end products (AGE) and the cytokine secretion. Glomerular
hyperfiltration is mediated by dilatation the afferent arteriole causing rise in the GFR and the
renal blood flow. This dilatation also mediated by a number of mechanism in diabetic
neuropathy. The hyperglycaemia and high insulin-like growth factor-1 (IGF-1) cause a rise in
GFR increases the renal flow. Hyperfiltration of glucose also leads to augment of the sodium-
glucose transport in the proximal convoluted tubule causing enhanced sodium transport.
Hyperfiltration causes the expansion of blood volume which leads to rise of GFR and
proximal reabsorption. The rise in proximal reabsorption leads to reduce in distal fluid
delivery which activates the tubuloglomerular feedback with the renin-angiotensin system
which works to increase the GFR. The other cause of diabetic neuropathy is cytokines.
Cytokines cause elevation in vascular endothelial growth factor, transforming growth factor
beta and profibrotic proteins increase the damage to the nephrons at the different levels.

The next cause that lead to the CKD is glomerulonephritis. It happens when
glomerular injury occurs because of inflammatory injury and non-inflammatory injury.
Common examples of non-inflammatory injury include podocytophies; the minimal change
of nephrotic syndrome and membranous nephropathy. Several cytokines such as IL-13 and
members of the complement system C3, C5b-9 lead to the glomerular basement membranes
to thicken as well as podocyte damage, apoptosis, detachment and excretion in urine. This
induces glomerular sclerosis. The common examples of inflammatory injury are post-
streptococcal glomerulonephritis, IgA nephropathy and various vasculitides. This injury has
been found to be mediated by many mechanisms. Some members of complement system such
as C5a are implicated in inflammatory by inducing antibody deposition and recruitment of
polymorphonuclear cells unlike podocyte targeting in the non-inflammatory injury, disorders
in which glomerular endothelial and mesangial cell are involved in exhibiting more dramatic
response to immune injury. This response is characterized by the cell proliferation and
phenotype change.
PROPOSED DIET

Foods that contain antioxidants can help neutralize free radicals and protect the body.
Many foods that protect against oxidation are included in the kidney diet and make excellent
choices for people with chronic kidney disease (CKD). One of food that are suitable for
people with CKD is red bell peppers. This is because red bell peppers contain powerful
cancer fighting agents, vitamin C, vitamin A, vitamin B6, folic acid and the powerful
antioxidant lycopene which all are beneficial for chronic kidney failure patients. We know
failed kidneys cannot discharge excess potassium, because of which, chronic kidney failure
patients are running a high risk for hyperkalemia which can cause unnecessary health tissues.
Red bell peppers are low in potassium which is good for a kidney diet. Therefore, adding
some foods containing red bell peppers is a wise choice for chronic kidney failure patients.
Bell pepper is one of most healthy foods. Firstly, bell peppers especially red ones contain
almost 300 percent of your daily vitamin C intake, so bell pepper can be used as a natural
antioxidant that can help rid the body of free radicals and inflammations. Therefore, kidney
disease patients become more resistant to their illness and disease.

Oxidation is the loss of an electron from a chemical species. Removal of loss of an

electron from a chemical compound produces a free radical. Free radicals are highly reactive
as they search for an electron from surrounding molecules to stabilize their structure. Free
radicals are able to attack numerous compounds in the body, including lipids, proteins, and
nucleic acids. Oxidative damage to these core biological components has been hypothesized
to be involved in the etiology or the progression of a number of diseases or condition
including cancer, atherosclerosis, arthritis, aging, cardiovascular disease, and diabetes
mellitus. Free radical damage has also been implicated as contributing factor in the
progression of chronic kidney disease (CKD) in humans.

Humans with CKD have been shown to have oxidative stress by evidence of lower
concentrations of vitamin E and vitamin C, and high concentrations of markers of lipid
peroxidation. The body contains a number of compounds and systems designed to protect
against oxidative stress. This protective system includes enzymes such as superoxide
dismutase and GSH reductase, peptides such as glutathione, and some vitamins, such as
tocopherols, vitamin A and associated retinoids, and vitamin C. Various minerals are also
required for the activity of many antioxidant enzymes. Nutritional interventions in which
exogenous antioxidants such as vitamin E, vitamin C, taurine, carotenoids, and flavanols are
added to the diet are also an effective way to promote more favourable redox status in the
body so that less oxidative damage can occur. Together, the antioxidant systems collectively
function to scavenge and neutralize free radicals and minimize oxidative stress.

The metabolism of vitamin C includes the formation of oxalic acid, which has limited
solubility in human tissues. When the plasma concentration of oxalate exceeds 40µ., there
is at least the possibility of oxalate crystals forming in variety of tissues, including retina,
skin, joints, and cardiac muscle. This syndrome, called primarily oxalosis, is often found in
children with a metabolic defect that forms excessive oxalate in the liver. Primarily oxalosis
often leads to early kidney failure and death and is only treatable by liver transplantation.
Prior to advent of reliable high flux dialysis therapy, some cases of oxalosis were observed in
patients with end-stage renal disease. Vitamin C intake is particularly likely to be low in
patients with CKD because of the potassium restriction. Oxalate is a metabolite of ascorbic
acid. Urine oxalate and, in renal failure patients, serum oxalate may increase when
individuals ingest supplemental ascorbic acid.5 Thus, high doses of vitamin C traditionally
are not recommended for patients with advanced CKD because of the possible increased risk
for hyperoxalosis. Therefore, the usual guidance provided in nephrology text-books and
manuals on renal nutrition is to limit dietary vitamin C supplements to 60 mg/day, to avoid
oxalosis. However, Vitamin C is a potentially useful but under-utilized adjuvant for ESA
therapy in dialysis-dependent patients since it maintains iron in a reduced state. This, in turn,
potentiates the intestinal absorption of iron and the enzymatic incorporation of iron into
protoporphyrin, an intermediate in heme biosynthesis.

In conclusion, diet plays an important role in the management of patients with CKD.
Nutritional therapy introduced in stages II and III of CKD is aimed at factors that delay
progressions, whereas, once the late stage III/IV disease has been reached, clinical signs of
uremia are evident, and dietary treatment is designed more to improve the quality of life of
the patient than to slow disease progression. Regular monitoring to ensure that dietary and
medical management remains optimal for the needs of the patient is crucial for the long-term
successful treatment of the patient with CKD. Regardless of the disease, the diet must be
tailored to the individual needs of the patient, and adjustments are to be expected throughout
the course of treatment. Clinical studies have clearly proven that nutrition can improve the
life expectancy and significantly minimize the risk of uremic arises in patients with CKD.
REFERENCES

Websites

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407016/

http://www.kidney-cares.org/stage-ckd-3-diet/

https://www.hindawi.com/journals/ijn/2017/2735296/

http://www.biomed.cas.cz/physiolres/pdf/prepress/1128.pdf

http://www.ifcc.org/ifccfiles/docs/20010902.pdf

http://www.pathophys.org/ckd/

http://jpck.zju.edu.cn/jcyxjp/files/ge/07/MT/074C.pdf

Books

Ministry of Health Malaysia, Malaysian Society of Nephrology, Academy Of Medicine in

Malaysia, June 2011: Management of Chronic Kidney Disease for Adult

Fascetti, A. J., & Delaney, S. J. (2012). Applied veterinary clinical nutrition. Ames, IA:.

Wiley-Blackwell

Kopple, J. D., Massry, S. G., & Kalantar-Zadeh, K. (2013). Nutritional management of renal

disease. Place of publication not identified: Publisher non identified.

Ronco, C., & Levin, N. W. (2007). Advances in chronic kidney disease 2007: 9th

international conference on Dialysis, January 24-26, 2007, Austin, Texas. Basel:

Karger.