ABSTRACT: Obesity and other renal disorders like high cholesterol

ABSTRACT:

 Chronic kidney disease
(CKD) is one of the major life threatening condition characterized by
progressive and irreversible loss of renal function. Chronic kidney disease (CKD) is a precursor to end-stage renal disease (ESRD), which is associated with increased risk of morbidity and mortality. Over 10% of Indian population are
suffering with CKD. Risk factors of Chronic kidney disease (CKD) includes Age,
Diabetes, Hypertension, Smoking, Alcohol, Obesity. There is a chance to stop
the progress of the disease by proper choice of Reno protective combinations
and should make patient to adhere to the medication for better outcomes.

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Key words: Chronic kidney disease, Risk
factors, ACE Inhibitors, ARB`s, Disease progression.

 

Introduction:

The
kidneys are bean-shaped paired organs and also it is like filtering sponge, the
major function of the kidney is complex filtration from capillaries to urinary
spaces. Normally, glomerular filtration rate (GFR) is about 125ml/minute. It
filters for about 113 to 114 litres of blood to set 0.94 to 1.8 litres of urine
per day 1. Kidney just acts as filters of the blood, it retains
the useful components like proteins and drains the waste material from the
blood. If kidneys get damaged then the proteins get leaked into urine, in later
stages kidney loses its ability to filter which is a slow process, if this
condition exists for more than 3months then it is called as Chronic kidney
disease (CKD) 1.1.

Chronic
kidney Disease (CKD) is the worldwide health problem, and is more prevalent in
elderly population of Age above 60 years 2.it is age related
disease and triggered by hypertension 3, diabetes, Obesity and
other renal disorders like high cholesterol and poly cystic kidney disease. For about 10%
of the Indian population is suffering from chronic kidney diseases 4.

Classification of CKD 4.1: –

Chronic
kidney disease was classified based on the rate of glomerular filtration rate
and they are of about five stages.

 

The 5 stages of CKD, they are: –

Stage 1:  GFR (>90 mL/min/1.73 m 2).
Stage 2:  GFR (60-89 mL/min/1.73 m 2).
Stage 3a:  GFR (45-59 mL/min/1.73 m 2).
Stage 3b: GFR (30-44
mL/min/1.73 m 2).
Stage 4: GFR (15-29 mL/min/1.73
m 2).
Stage 5: GFR 30 mg/24 hr
or albumin: creatinine ratio >30 mg/g >3 mg/m.mol).

2)     Urine sediment abnormalities.

3)     Electrolyte and other abnormalities because of
the tubular disorders.

4)    Histologic abnormalities.

5)    Detection of Structural
abnormalities by imaging.

6)     Kidney transplantation history, in such cases.

 

RISK FACTORS:

OBESITY:

·       
Though people do not have
history of hypertension or diabetes, a study states that they are at three-fold
risk of developing CKD 5.

SMOKING:

·       
In a retrospective
study,4142 participants of about 65yrs old with history of smoking. There
creatinine level is raised about 0.3% than the normal. This study reveals
smoking causes CKD 6

·       
Smoking is also the risk
factor for urinary stone formation 7 it eventually leads to CKD
8.

·       
In a 5 years cross
sectional study on Heavy smokers(>30pack/year) revealed that Smoking is the
factor for CKD 9

·       
Smoking increase the
mortality in dialysis patients although there was not a corresponding increased
risk of Cardiovascular events 10.

ALCOHOL:

Progress
of CKD to ESRD is more due to consumption of alcohol 11. Alcohol consumption of more than two
alcoholic drinks per day, on average, was associated with an increased risk of
kidney failure in the general population 12

 

Diabetes
Mellitus: –

In
2000, India (31.7 million) topped the world with the highest number of people
with diabetes mellitus followed by china and US 13. Recent 2015
data of WHO India states that about 69.2 million people are living with diabetes
(8.7%) in India 14.

Mechanisms that lead to kidney disease in diabetes include hyper
filtration injury, advanced glycosylation end products, and reactive oxygen species
15.

Pathogenic changes that are associated with diabetic nephropathy
are due to hormones such as transforming growth factor-beta and angiotensin II
16. 

 

AGE: –

 

However, relatively little is known about the clinical course
of CKD in older individuals. Renal damage is common in elderly people
of aged above 6517,18,19. Age is recognised as independent risk
factor for renal disease 20. According to the National Kidney Foundation
Kidney Disease Outcomes Quality Initiative(k/DOQUI)

 

Guidelines- Elderly
population were screened, more than one-half of subjects are and found as CKD
stages 3-5(GFR 60ml/min per 1.73m2) 21

10 years
follow up study revealed that Age group 50above are prone to CKD and Age 60
above are at CKD stage-III or ESRD, irrespective of their gender 22

 

HYPERTENSION:

 SALT restriction should be indicated in
antihypertensive therapy and diuretic therapy for better outcomes 23

Experimental
animal model shows that hypertension can be lead to kidney damage, which is
because of decrease ability of kidney to eliminate salt. Experiment was done on
dogs that was found that 70% of kidney damage is seen and developing
hypertension with in few days. Due to increase intake of salt may lead to
Hypertension thus in-turn leads to the progression of CKD disease 24.  In another experimental study, high salt diet
is given to the rats which shows high increase in levels of transforming growth
factor beta, polypeptides associated with kidney fibrosis thus leads to kidney damage
25. oxidative stress played an important role in the production of
renal damage 26.

 

TREATMENT:

 Treatment of
chronic kidney disease (CKD) can slow its
progression to end-stage renal disease (ESRD). Angiotensin-converting enzyme
(ACE) inhibitors and angiotensin-II receptor blockers are used in order to
maintain blood pressure in CKD27. National kidney foundation was suggesting that combination
therapy like ARB’s and ACE inhibitors can be used to decline the proteinuria in
the patients who are with renal disease 28. By monitoring the
creatinine levels in early stages if (serum creatinine>1.4 mg/dl)
then we can choose the ACE inhibitors and we can stop the progress of the
disease with mono therapy of ACE inhibitors. Thus we can prevent progression of
disease 29

Combination
therapy of ACE inhibitors and ARB’s is better option for complete blockade of
RAAS which gives better Reno protection. A study shown that patients with stable hypertension and
advanced CKD, who are receive therapy with angiotensin-converting enzyme (ACE) inhibitors
and angiotensin-II receptor blockers exhibit an association with
low risk of long-term dialysis 30.

Pentoxifylline is Reno-protective drug when
it is given in combination with Angiotensin-converting
enzyme (ACE) inhibitors and angiotensin-II receptor blockers, we can decrease
the progress of CKD stages 30.

A mono-therapy of short acting Dihydropyridine
calcium channel blockers(CCB`s) worsens proteinuria and accelerate renal damage
in both animal models and human with hypertension or diabetes. But when we give
Non-dihydropyridine CCB`s in combination with ACE inhibitors. It acts as Reno-protective
31

VITAMIN-D SUPPLEMENTATION:

Vitamin-D involves numerous regulatory processes
in the body 32. Vitamin-D is observed in the form of calciferol, hydroxylation
of calciferol occurs in Liver then it forms into 25-hydroxycalciferaol. This
25-hydroxycalciferaol undergoes one more hydroxylation in kidney and develops
1,25 dihydroxycalciferol.

Vitamin-D is not only restricted to its classical
function of maintaining Calcium and phosphate
homeostasis but also Vitamin-D plays crucial role in cell differentiation and
anti-proliferative factors with action upon different tissues i.e., includes immune
system, renal system and cardio vascular system 33-34.

 IRON
SUPPLEMENTS:

Kidney maintains RBC by erythropoietin
production, Impaired production of erythropoietin by failing kidneys leads to
anaemia condition 35.

Iron
based phosphate binders have greater absorption properties, could represent
novel approach for correcting anemia and hyperphosphatemia in CKD patients
36.

 

CONCLUSION: Involvement
of Clinical pharmacist in the therapy, can guide the physician about proper
combination of drug therapy in order to stop the progression of CKD and thus
decrease in pill burden may attains medication adherence.