PREVALENCE OF KIDNEY IMPAIRMENT AMONG SHISHA SMOKERS

1.0 Introduction

1.1 Background of Study​

Shisha is a method of smoking tobacco invented in the 16th century by a physician named Hakim Abul-Fath Gilani. The purpose of the device was to pass smoke through water in an attempt to ‘purify’ the smoke, an unproven concept that has been repeatedly questioned by the medical community (Maziak, 2013). The shisha device consists of a head that contains tobacco separated from an array of coal by foil. The head is connected to a system of air tight pipes that draw tobacco smoke into a bowl which contains water. Then, as the user inhales through the hose, smoke is drawn in from the bowl to the smoker (Maziak, 2013). Smoking of cigarettes or shisha is a major means of heavy metal intoxication. Cigarettes contain tobacco, which in turn, contains some toxic substances, which may directly affect the kidney (Pappas, 2011). In the nephrons of each kidney, heavy metals are primarily absorbed through the apical membrane and accumulate at the basolateral membrane. These heavy metals do not readily exit from this membrane, and overtime, can cause chronic inflammation, fibrosis and renal failure (Sabolic, 2006). Kidney failure is a worldwide public health problem, with increasing incidence and prevalence, high costs, and poor outcomes (Eknoyan et al., 2004). Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially there are no symptoms seen, but later symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. On the other hand, complications that can be related to the condition include high blood pressure (often related to activation of the renin–angiotensin system system), bone disease, and anemia (Zhang et al., 2012). Additionally, CKD patients have markedly increased cardiovascular complications with increased risks of death and hospitalization (Go et al., 2004). The major causes of chronic kidney disease include diabetes, high blood pressure, glomerulonephritis, and polycystic kidney disease (Wilson, 2017). Risk factors include a family history of chronic kidney disease. Diagnosis is by blood tests to measure creatinine levels and calculate estimated glomerular filtration rate (eGFR), and a urine test to measure albumin. Ultrasound or kidney biopsy may be performed to determine the underlying cause (Wilson, 2017).  Several severity-based staging systems are in use (Ferri, 2017). Screening of at-risk people is recommended. Initial treatments may include medications to lower blood pressure, blood sugar, and cholesterol. Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARBs) are generally first-line agents for blood pressure control, as they slow progression of the kidney disease and the risk of heart disease (Xie et al., 2016). Loop diuretics may be used to control edema and, if needed, to further lower blood pressure (Wile, 2012). Other recommended measures include staying active, and certain dietary changes such as a low-salt diet and the right amount of protein. Treatments for anemia and bone disease may also be required. Severe disease condition requires hemodialysis, peritoneal dialysis, or a kidney transplant for survival. Chronic kidney disease affected 753 million people globally in 2016 - 417 million females and 336 million males (Bikbov et al., 2018). In 2015, it caused 1.2 million deaths, up from 409,000 in 1990 (Thomas et al., 2013). The causes that contribute to the greatest number of deaths are high blood pressure at 550,000, followed by diabetes at 418,000, and glomerulonephritis at 238, 00 (Wang et al., 2015).

1.2 Statement of Research Problem

Smoking of cigarettes or shisha is a major means of heavy metals intoxication, in nephrons of each kidney, those metals accumulate at the basolateral membrane, and overtime can cause chronic inflammation, fibrosis and renal failure.

1.3 Justification

Kidney is the major organ in the body that is involve in the removal of unwanted toxic substances. Shisha smoking can affect that function of the kidney as a result of the nephrotoxic substances contained in the shisha smoke. Prolong exposure to the shisha smoke will lead to chronic inflammation, fibrosis and renal failure, thus resulting in an increase in morbidity and mortality of the persons involve in the practice. Early detection of the kidney impairment among these people will therefore reduce the mortality and morbidity of these patient.

1.4 Aim and Objectives

1.4.1 Aim

The aim of this study is to determine the prevalence of kidney impairment among shisha smokers based on estimated glomerular filtration rate (eGFR) within Kano Metropolis.

1.4.2 Objectives

1. To determine, serum creatinine level among shisha smokers.

2. To calculate glomerular filtration rate using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) based on the levels of the serum creatinine determined among the smokers.

3. To determine the prevalence of the various stages of kidney disease based on CKD stages classification using the MDRD and CKD-EPI equations.

1.5 Significance of the study

 

This study will help in the determining the prevalence of kidney impairment among shisha smokers based on eGFR and the effect of this smoking on the kidney of those involve in the practice of shisha smoking. The study will also create awareness to those involve in the practice and to the general public on the effect of shisha smoking on the kidney.

  
         

 

 

CHAPTER TWO

2.0 Literature Review

2.1 Definition of Shisha

Hookah (Narghile, Shisha) smoking is an ancient mode of tobacco use which has not posed any particular public health problem over the past centuries (Chaouachi, 2007) and is a method of smoking tobacco invented in the 16th century by a physician named Hakim Abul-Fath Gilani. A device is use and the purpose of the device was to pass smoke through water in an attempt to ‘purify’ the smoke, an unproven concept that has been repeatedly questioned by the medical community (Maziak, 2013), although the assembly of the device has become significantly simpler. The Shisha device consists of a head that contains tobacco separated from an array of coal by foil (Maziak, 2013). The head is connected to a system of air tight pipes that draw tobacco smoke into a bowl which contains water. Then, as the user inhales through the hose, smoke is drawn in from the bowl to the smoker (Maziak, 2013). Despite the belief that shisha allows the smoker to inhale purified smoke, a misconception that remains prevalent in society today, shisha has been shown to be associated with a wide range of detrimental health effects. Several studies have been carried out comparing shisha to cigarette smoking in an attempt to provide an evidence-based comparison between them. In one study conducted in London in 2013, the authors described shisha smoking as acutely stressful to the cardiovascular system in a similar way to cigarettes, supporting the fact that the action of passing the smoke through water is not ‘purifying (Kadhum et al., 2014).  Smoking of cigarettes or shisha is a major means of heavy metal intoxication. Cigarettes contain tobacco, which in turn, contains some toxic substances, which may directly affect the kidney (Pappas, 2011). In the nephrons of each kidney, heavy metals are primarily absorbed through the apical membrane and accumulate at the basolateral   membrane. These heavy metals do not readily exit from this membrane, and overtime, can cause chronic inflammation, fibrosis and renal failure (Sabolic, 2006).

2.2 Origin of Shisha

Hookah, an ancient smoking mode of tobacco use, (Chaouachi, 2007) has seen a recent revival in the Middle East and its transformation into a worldwide fashionable habit. This has coincided with the emergence of the ETS (environmental tobacco smoke) taken as synonymous with the SHS (second hand smoke) prevalent in the early 1980s, particularly in North America and Western Europe. The reasons behind the growing popularity in the second-hand smoke phenomenon in these regions were early described (Chaouachi, 2007). The reason for the increase prevalence of the second-hand smoking phenomenon could be attributed to fifteen reasons. The most important assumes that the powerful anti-cigarette campaigns of the last decades would have, as a backlash effect, pushed a certain number of cigarette smokers towards a tobacco use mode viewed as less hazardous to health and, above all, less addictive. Indeed, a recent study has confirmed the latter aspect, as it was found that more than 90% of so-called “mild smokers” (3 pipes or less per week) and about 50% of the so-called “moderate” ones (3 to 6 pipes per week) were considered as non-dependent (Salameh et al., 2008). Two teams from Asia and Africa have elicited a substantial advancement of research in this field of shisha smoking. The first team analyzed the potential health hazards associated with radioactivity in the smoking mixtures used in the Narghile and found no great differences with cigarettes (Khater et al., 2008). The other team led the first aetiological study on hookah smoking and cancer using selection criteria of exclusive/ever hookah smokers who have been using, for decades, huge amounts of tobacco in their pipes. Using carcinoembryonic antigen (CEA) as a cancer biomarker, they found a weaker association than that with cigarette smoking (Sajid et al 2008). This study has helped in clearing up a growing confusion caused, among others, by the dismissal of early biomedical and anthropological research on the subject (Chaouachi, 2005).

2.3 Structural identification of shisha (Waterpipe) and how it works

2.3.1 Structural identification

The Bowl: the holds the shisha tobacco. 

The Stem: the stem is the vertical pipe from the bowl to the vase.

The vase: the vase is made up of glass vase and is fill with water.

The hose: this is use for inhaling the smoke from the vase.

2.3.2 How shisha pipe works

The shisha tobacco is loaded in the bowl. The bowl is covered with aluminum foil that is punched with a toothpick or a needle to make small holes. On the foil is placed hot charcoals. The charcoals heat up the tobacco and also heat up the air that passes through the charcoals which put even more heat to the tobacco as the user inhales through the hose, the existing air in the vase is removed, an under pressure is created in the vase. Because of the under pressure, new air passes throught the coals, heats up and then passes through the bowl and warms up the tobacco. The warm tobacco releases vapors that blend with the air and produce the shisha smoke. The shisha smoke passes through the vertical stem and come out from the tip of the stem which sits 2-3 cm below the water surface. As the smoke leave the tip and moves upward to the water surface, it is filtered and cooled down before it reaches the user through the hose. 

2.4 Constituents of shisha smoke

Smoking of cigarettes or shisha is a major means of heavy metal intoxication. Cigarettes contain tobacco, which in turn, contains some toxic substances, which may directly affect the kidney (Pappas, 2011). The source of heavy metals such as lead (Pb) and chromium (Cr) in the smoke is thought to be the charcoalused for waterpipe smoke (Elsayed et al., 2016). Shisha smoking involves burning flavoured tobacco, known as molasses, using coal. When an individual breathes in from the mouthpiece, air is pulled through the apparatus into the tobacco and heated by the coal to produce smoke. As a result, the smoke contains components from both the tobacco and coal. These include polycyclic aromatic hydrocarbons (PAH), volatile aldehydes, carbon dioxide (CO0, nitric oxide (NO), nicotine, furans and nanoparticles (Cobb et al., 2012). Both tobacco-containing and tobacco-free molasses contain high levels of PAH, a carcinogenic compound (Sepetdjian et al., 2010). These high levels are caused mostly due to the combustion of coal (Sepetdjian et al., 2010). Coal is generally found either in lumps or briquettes (Sepetdjian et al., 2010). Lump coal is found in various forms, sizes and originates from biomass. The briquette form can be found as either ‘easy-light’, which contains an ignition agent, or as a coconut-shell based product (Sepetdjian et al., 2010). All these forms of coal contain high levels of PAH residues, especially benzo(a)pyrene, a potent carcinogen (Sepetdjian et al., 2010).  Interestingly, in one study, the coconut-shell based coal contained approximately six times more PAH products than any other type of coal ((Sepetdjian et al., 2010). On the other hand, lump coal was shown to contain the least amount of PAH ((Sepetdjian et al., 2010). The significant exposure to PAH may be causal in the development of various malignancies after shisha smoking (Sepetdjian et al., 2010).  In addition, the presence of volatile aldehydes has also been reported in shisha smoke, including formaldehyde, acetaldehyde, acrolein, propionaldehyde and methacrolein(Hammal et al., 2015). These chemicals have been associated with various respiratory disorders, respiratory tract infections, chronic obstructive pulmonary disease and lung cancer (Hammal et al., 2015).  Specifically, formaldehyde and acroleinare both potent carcinogens that may promote the development of leukemia (Hammal et al., 2013).  The approximate levels of volatile aldehydes in shisha smoke have been found to be significantly higher than in cigarettes, highlighting that shisha may result in a higher incidence of aldehyde-associated diseases (Hammal et al., 2015). In addition, carbonmonoxide (CO) levels have been observed to significantly increase after shisha smoking. A Typically, carboxyhemoglobin concentrations are greater than 10% in shisha smokers, compared with 6.5% in cigarette smokers and 1.6% in non-smokers (Lafauci et al.,2012). One recent study also noted that acute levels of CO increased significantly, possibly contributing to CO poisoning (Kadhum et al., 2014). In these cases, carboxyhemoglobin levels can reach between 20–30% and patients may present with a loss of consciousness, headaches and shortness of breath (Lafauci et al., 2012). In addition, nicotine levels increase significantly from 2 to 6 ng/ml after smoking shisha for five minutes. Increasing nicotine levels have been shown to induce increases in heart rate and may contribute to various cardiovascular diseases (Eissenberg and shihadeh, 2009).

2.5 Epidemiology

The world's disease profile is changing, and chronic diseases now account for the majority of global morbidity and mortality, rather than infectious diseases. The causes of chronic kidney diseases reflect this change and diabetes, together with hypertension, is now the major cause of end-stage renal failure worldwide, not only within the developed world, but also increasingly within the emerging world. Diabetes is of epidemic proportions, and its prevalence will double in the next 25 years, particularly in the developing countries. This will place an enormous financial burden on countries, including the cost of the management of end-stage renal failure. Thus, it is medically and economically imperative for awareness, detection, and prevention programs to be introduced across the world, particularly in the developing countries. This will require concerted action from global institutions, governments, health service providers, and medical practitioners. (Atkins, 2005)

2.6 Risk Factors of Chronic Kidney Disease

Chronic kidney disease has become a serious public health issue. There are currently over 1.4 million patients receiving renal replacement therapy worldwide. One way to reduce the economic burden of chronic kidney disease would be early intervention. In order to achieve this, we should be able to identify individuals with increased risk of renal disease. An individual's genetic and phenotypic make-up puts him/her at risk for kidney disease. Factors such as race, gender, age, and family history are highly important. For instance, being of African-American decent, older age, low birth weight and family history of kidney disease are considered to be astrong risk factors for chronic kidney disease. Moreover, smoking, obesity, hypertension, and diabetes mellitus can also lead to kidney disease. An uncontrolled diabetic and/or hypertensive patient can easily and quickly progress to an end-stage kidney disease patient. Exposure to heavy metals, excessive alcohol consumption, smoking, and the use of analgesic medications also constitute risks. Experiencing acute kidney injury, a history of cardiovascular disease, hyperlipidemia, metabolic syndrome, hepatitis C virus, HIV infection, and malignancy are further risk factors. Determination of serum creatinine levels and urinalysis in patients at risk of chronic kidney disease will usually be sufficient for initial screening (Kazancioğlu, 2013).

2.6.1 Family History

Chronic kidney disease (CKD) has familial predispositions. Some diseases, such as the polycystic syndromes and Alportdisease, have well established patterns of Mendelian inheritance. On the other hand, the genetic architecture of the more common causes of CKD is more complex. Over 20 years ago, Ferguson and colleagues reported that a family history of CKD was a significant risk factor for end-stage renal disease (ESRD) (Ferguson, et al., 1988)

 

2.6.2 Gender

CKD progression may differ depending on sex (Carrero, 2010). Male patients show a substantially higher prevalence of CKD and incidence rate of ESRD than those observed in female patients (Yang et al., 2014). A survey conducted by the Japanese Society for Dialysis Therapy indicated sex differences in mean age at the start of dialysis (Iseki, 2008). Men with diabetes have a higher risk of nephropathy than women with diabetes (Abbate et al., 2012). By contrast, women have a higher risk of accelerated disease progression than men (Maric, 2009). Furthermore, a survey conducted in the United States reported that the percentages of male and female patients with CKD were 21.42% and 27.11% among those with an estimated glomerular filtration rate (eGFR) ≥90, 32.95% and 29.12% among those with an eGFR 60 to 89, 10.95% and 5.68% among those with stage 3, 0.70% and 0.31% among those with stage 4, and 0.12% and 0.04% among those with stage 5, respectively ( Chronic Kidney Disease Surveillance System United State. 2015).

2.6.3 Ethnicity

Recent epidemiological studies conducted in Western populations have provided estimates on the prevalence of CKD (Coresh et al., 2007), with some suggesting significant interracial/ethnic disparities in both the prevalence (Feehally, 2005) and risk factors of CKD (Mau et al., 2007). Asians have been suggested to have an increased risk for renal disease compared to whites (Hall et al., 2005) and the contribution of some of the risk factors of CKD also appears to be different among Asian populations (Iseki and Kohagura, 2007).

 

2.6.4 Age

Although there is consensus that persistent presence of abnormal albuminuria indicates CKD, the appropriateness of using a single eGFR threshold to define CKD, regardless of albuminuria, has been debated (Levey et al., 2015), because eGFR declines with advancing age (Denic et al., 2016). A definition based on a fixed eGFR threshold may lead to under diagnosis in young individuals and over diagnosis in elderly individuals, whose eGFR physiologically declines with aging (Delanaye et al., 2019). A fixed-threshold definition may result in overestimation of the CKD burden in an aging population, largely attributable to people who may not have increased risks of adverse outcomes. An age-adapted CKD definition has been proposed, with eGFR thresholds of 75, 60, and 45 mL/min/1.73 m2 for younger than 40, 40 to 64, and 65 years or older, respectively (Delanaye et al., 2019).

2.6.5 Obesity

Over the last 3 decades, the prevalence of overweight and obese adults (BMI ≥25) worldwide has increased substantially (Forouzanfar et al., 2017). In the US, the age-adjusted prevalence of obesity in 2013-2014 was 35% among men and 40.4% among women (Flegal et al., 2016). The problem of obesity also affects children. In the US in 2011-2014, the prevalence of obesity was 17% and extreme obesity 5.8% among youth 2-19 years of age. The rise in obesity prevalence is also a worldwide concern (Cattaneo et al., 2010), as it is projected to grow by 40% across the globe in the next decade. Low- and middle-income countries are now showing evidence of transitioning from normal weight to overweight and obesity as parts of Europe and the United States did decades ago (Subramanian et al., 2021). This increasing prevalence of obesity has implications for cardiovascular disease (CVD) and also for CKD. A high body mass index (BMI) is one of the strongest risk factors for new-onset CKD (Tsujimoto et al., 2014).

2.6.6 Smoking    

Tobacco smoke contains over 4,000 particles and gases, some of which nephrotoxic (Cooper, 2006). Particles include heavy metals known to cause tubular injury such as cadmium and lead, which may reach serum concentrations above 40% in smokers (Satarug and Moore, 2004). The action of nicotine on specific cholinergic receptors causes hemodynamic changes such as elevations in blood pressure, heart rate and peripheral vascular resistance (Hansen et al., 1996).                                   

2.6.7 Hypertension

Hypertension is a major risk factor for cardiovascular and renal disease. Conversely, chronic kidney disease (CKD) is the most common form of secondary hypertension and mounting evidence suggests it is an independent risk factor for cardiovascular morbidity and mortality (Chertow et al., 2004). The prevalence of CKD has been better characterized since the National Kidney Foundation issued a standard classification based on the level of glomerular filtration rate (GFR) and the presence or absence of evidence of renal injury. Patients with stages 1 and 2 CKD need to show evidence of renal injury (e.g., proteinuria), and GFR of ≥90 and 60–89 mL/minute, respectively. Stages 3, 4, and 5 correspond to GFR of 30–59, 15–29, and <15 mL/minute, respectively, regardless of any other evidence of renal damage (Levey et al., 2002). It is estimated that 10–13% of adults in the USA suffer from some degree of CKD (Coresh et al., 2007).

 2.6.8 Diabetes mellitus

Despite rates of diabetes-related complications such as cardiovascular disease decreasing significantly in the past two decades, it has not translated nearly as well as kidney complications (Gregg et al., 2014). Approximately 10% of deaths in people with type 2 diabetes mellitus are attributable to kidney failure (Van Dieren et al., 2010). It is well-established that diabetes-related chronic kidney disease (CKD) is the leading cause of end-stage kidney disease (ESKD) in type 2 diabetes mellitus patients worldwide (Saran et al., 2019). In the United States, 2013–2016, approximately 36% of patients with diabetes develop diabetic kidney disease resulting in persistent albuminuria, a reduced estimated glomerular filtration rate (eGFR), or both (Saran et al., 2019). Interestingly, the risk of diabetes-related CKD is observed much higher in Asian countries than in Western countries (Kong et al., 2013). Moreover, diabetes patients in developing countries are at a particularly increased risk of developing kidney complications compared to those in developed countries (Zimmet et al., 2014). As the global burden of diabetes increases dramatically due to type 2 diabetes mellitus (Mayer Devis et al., 2017).                        

2.6.9 Nephrotoxins

Nephrotoxicity is defined as rapid deterioration in the kidney function due to toxic effect of medications and chemicals. There are various forms, and some drugs may affect renal function in more than one way. Nephrotoxins are substances displaying nephrotoxicity. Nephrotoxicity should not be confused with the fact that some medications have a predominantly renal excretion and need their dose adjusted for the decreased renal function (e.g., heparin). The nephrotoxic effect of most drugs is more profound in patients already suffering from kidney failure. About 20% of nephrotoxicity is induced and caused by drugs; this percentage is augmented in the elderly due to an increase in the life span and poly-medications (Al kuraishy et al., 2019).

2.6.10 Acute kidney injury

 Acute kidney injury (AKI) occurs in up to 20% of patients admitted to hospital and results in significant morbidity and mortality (Bellomo et al., 2012). The upfront poor outcomes include in hospital mortality rates exceeding 50% in critically ill patients requiring renal replacement therapy (Bellomo et al.,2012).   Amongst the survivors of an episode of AKI, there is an increasing understanding of long-term consequences that may include an increased mortality risk, the development of chronic kidney disease (CKD), and the progression from CKD to end-stage renal disease (ESRD) (Heung and Chawla, 2012). Incomplete recovery from a severe episode of AKI is a well-recognized pathway to persistent and progressive CKD. Interestingly, more recent studies have demonstrated that even apparent complete recovery from AKI is associated with a subsequent risk for CKD development (Chawla and Kimmel, 2012). This has emerged as an important area for investigation because the majority of these patients will not receive follow-up care with a nephrologist, and there remains significant room for improvement in the care of this population (Chawla and Kimmel, 2012).

2.7 Signs and Symptoms of chronic kidney disease

Signs and symptoms of chronic kidney disease develop over time if kidney damage progresses slowly. Loss of kidney function can cause a buildup of fluid or body waste or electrolyte problems. Depending on how severe it is, loss of kidney function can cause.

2.7.1 Appearance

Whiteness secondary to anaemia of chronic kidney disease.

2.7.2 Hypertension

It is common in chronic kidney disease either as a primary or secondary effect.

2.7.3 Shortness of Breath

It may be due to any of the following; aneamia cardiomyopathy, or occult ischaemic heart disease, fluid overload.

2.7.4 Kidneys

On imaging kidney shape may give clues to cause of CKD. 

Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemiadue to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease (Webster et al., 2017).

2.7.5 Itch and Cramps 

Itching of the skin with a desire to scratch (also called uraemicpruritus) is common in people with advanced chronic kidney disease (CKD). It can be a serious problem for many people and can have a major effect on your quality of life. Cramps especially leg cramps are common for those with kidney disease. Cramps are thought to be caused by imbalances in fluid and electrolytes, or by nerve damage or blood flow problems.

2.7.6 Cognitive Changes

Patients with chronic kidney disease (CKD) are at substantially higher risk for developing cognitive impairment compared with the general population, and both lower glomerular filtration rate and the presence of albuminuria are associated with the development of cognitive impairment and poorer cognitive function.

2.7.7 Gastrointestinal symptoms

Vomiting, anorexia and taste disturbance may occur with advanced chronic kidney disease. In advanced chronic kidney disease, breakdown of urea by saliva causes uraemic odour.

.2.7.8 Change in urine output

Chronic kidney disease causes many problems throughout the body, when loss of kidney function is mild, moderately or severe, the kidneys cannot absorb water from the urine and reduce the volume of urine and concentrate it.

2.7.9 Heamaturia

Hematuria is defined as the presence of red blood cells in the urine originating from the kidney or the urinary tract (Davis et al., 2012). Underlying conditions producing hematuria, like diabetes, can be associated with progressive decline in kidney function in the setting of CKD. Also, hematuria, per se may play a mechanistic role in renal disease progression (Morena et al., 2012).

2.7.10 Proteinuria

When kidneys are not working as well as they should, protein can leak through kidney's filters and into urine. Protein in urine is called proteinuria or albuminuria. It is a sign that the kidneys are damaged. Proteinuria is a strong marker for progression of chronic kidney disease,

2.7.11 Peripheral edema

Excess swelling also known as edema can be caused by kidneys not being able to remove excess fluid from the body. For people with either chronic kidney disease (CKD) or end stage renal disease (ESRD), this can be a symptom of hypervolemia, when the body has too much fluid.

2.8 Causes of Chronic kidney disease

Diabetes and high blood pressure are the most common causes of chronic kidney disease (CKD).

2.8.1 Diabetes

Hyperglycemia (too much glucose, also called sugar), in the blood damages the kidneys’ filters. Over time, the kidneys can become severely damaged that they can no longer perform the filtering of wastes and extra fluid from the blood. Often, the first sign of kidney disease from diabetes is protein in the urine. When the filters are damaged, a protein (albumin), passes out of the blood and into the urine. A healthy kidney doesn’t let albumin pass from the blood into the urine. Diabetic kidney disease is the medical term for kidney disease caused by diabetes.

2.8.2 High blood pressure

High blood pressure can damage blood vessels in the kidneys so they don’t work as well. If the blood vessels in the kidneys are damaged, the kidneys may not work as well to remove wastes and extra fluid from the body. Extra fluid in the blood vessels may then raise blood pressure even more, creating a dangerous cycle.

2.9 Pathophysiology of Chronic kidney disease

The rate of renal blood flow of approximately 400 ml/100g of tissue per minute is much greater than that observed in other well perfused vascular beds such as heart, liver and brain. As a consequence, renal tissue might be exposed to a significant quantity of any potentially harmful circulating agents or substances. Secondly, glomerular filtration is dependent on rather high intra- and transglomerular pressure (even under physiologic conditions), rendering the glomerular capillaries vulnerable to hemodynamic injury, in contrast to other capillary beds. In line with this, Brenner and coworkers identified glomerular hypertension and hyperfiltration as major contributors to the progression of chronic renal disease. Thirdly, glomerular filtration membrane has negatively charged molecules which serve as a barrier retarding anionic macromolecules. With disruption in this electrostatic barrier, as is the case in many forms of glomerular injury, plasma protein gains access to the glomerular filtrate. Fourthly, the sequential organization of nephron’s microvasculature (glomerular convolute and the peritubular capillary network) and the downstream position of the tubuli with respect to glomeruli, not only maintains the glomerulo-tubular balance but also facilitates the spreading of glomerular injury to tubulointerstitialcompartment in disease, exposing tubular epithelial cells to abnormal ultrafiltrate. As peritubular vasculature underlies glomerular circulation, some mediators of glomerular inflammatory reaction may overflow into the peritubular circulation contributing to the interstitial inflammatory reaction frequently recorded in glomerular disease. Moreover, any decrease in preglomerular or glomerular perfusion leads to decrease in peritubular blood flow, which, depending on the degree of hypoxia, entails tubulointerstitial injury and tissue remodeling. Thus, the concept of the nephron as a functional unit applies not only to renal physiology, but also to the pathophysiology of renal diseases. In the fifth place, the glomerulus itself should also be regarded as a functional unit with each of its individual constituents, i.e. endothothelial, mesangial, visceral and parietal epithelial cells - podocytes, and their extracellular matrix representing an integral part of the normal function. Damage to one will in part affect the other through different mechanisms, direct cell-cell connections (e.g., gap junctions), soluble mediators such as chemokines, cytokines, growth factors, and changes in matrix and basement membrane composition. The main causes of renal injury are based on immunologic reactions (initiated by immune complexes or immune cells), tissue hypoxia and ischaemia, exogenic agents like drugs, endogenous substances like glucose or paraproteins and others, and genetic defects. Irrespective of the underlying cause glomerulosclerosis and tubulointerstitialfibrosis are common to CKD (Matovinomic, 2009).

2.10 Stages of Chronic kidney disease

2.10.1 National Institute for Health and Clinical Excellence (NICE) and Kidney Disease Outcomes Quality Initiative (K\DOQI) Guideline on chronic kidney disease staging

The widespread adoption of the Kidney Disease Outcomes Quality Initiative (K/DOQI) classification of chronic kidney disease (CKD) (National Kidney Foundation, 2002),  coupled with the use of estimated glomerular filtration rate (eGFR) to assess excretory renal function has resulted in up to 10% of the population being labeled as having chronic kidney disease (Coresh, et al., 2003). In addition, there has been a staggering rise in the number of patients requiring renal replacement (RRT) – in the UK alone, the prevalent number of patients on RRT between 2000 and 2006 increased by 35% (UK Renal Registry Report 2006) and similar trends have been seen globally. Of course, the increasing prevalence of patients on RRT may reflect improved access to RRT and better survival on RRT rather than a true increase in the incidence or prevalence of antecedent non-end-stage renal disease (non-ESRD). Indeed, there is no clear-cut relationship between CKD prevalence in the community and the need for RRT. Moreover, many have argued that the use of the K/DOQI classification to estimate CKD prevalence is inherently flawed as much of the data are based on single creatinine measurements and inappropriate use of microalbuminuria data to define CKD (Glassock and winearls, 2008). Notwithstanding the concerns about the validity of the epidemiological data, many perceive that the failure to detect CKD early and the late referral of patients with advanced CKD are key factors that underlie this inexorable rise in RRT. The public health and economic ramifications of this ‘epidemic’ are profound and have underpinned numerous international efforts to enable early identification and appropriate management of CKD. In the UK, the National Institute for Health and Clinical Excellence (NICE) has produced clinical guidance aimed at optimizing the care of patients with CKD (http://www.nice.org.uk/cg73). Particular, the guidelines focus on identifying patients at risk of progressive CKD by ensuring that kidney function is measured in high-risk groups [e.g. patients with diabetes, hypertension and cardiovascular disease (CVD)] and by quantifying proteinuria in patients with CKD. Furthermore, specific guidance was provided on blood pressure control, the use of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) and the indications for, and timing of, referral to secondary care (http://www.nice.org.uk/cg73).

2.11 Classification of Chronic Kidney disease

The National Kidney Foundation (NKF) divided kidney disease into five stages. This helps in providing the best care, as each stage calls for different tests and treatments. The stage of kidney disease is calculated using the glomerular filtration rate (GFR), a math formula using a person's age, gender, and serum creatinine level (identified through a blood test). Creatinine, a waste product that comes from muscle activity, is a key indicator of kidney function. When kidneys are working well, they remove creatinine from the blood; but as kidney function slows, blood levels of creatinine rise. Stage 1 with normal or high GFR (GFR > 90 mL/min), Stage 2 Mild CKD (GFR = 60-89 mL/min), Stage 3A Moderate CKD (GFR = 45-59 mL/min), Stage 3B Moderate CKD (GFR = 30-44 mL/min), Stage 4 Severe CKD (GFR = 15-29 mL/min), Stage 5 End Stage CKD (GFR <15 mL/min).

 

Table 1. Classification of CKD as Defined by KDOQI and Modified and Endorsed by KDIGO

GFR stages	GFR               (mL/min/1.73 m2)	Terms
G1	≥90	Normal or   high
G2	60 to 89	Mildly decreased
G3a	45 to 59	Mildly to moderately decreased
G3b	30 to 44	Moderately to severely decreased
G4	15 to 29	Severely decreased
G5	<15	Kidney failure D(dialysis)

KDIGO. Summary of recommendation statements. Kidney Int2013; 3 (Suppl):5.

 

2.12 Estimated Glomerular Filtration Rate (eGFR) Equations

2.12.1 Cockcroft and Gault Equation (CG)

A commonly used surrogate marker for the estimation of creatinine clearance is the Cockcroft-Gault (CG) formula, which in turn estimates GFR in ml/min.  It is named after the scientists, the asthamologist (Donald William Cockcroft and the nephrologist (Matthew Henry Gault who first published the formula in 1976, and it employs serum creatinine measurements and a patient's weight to predict the creatinine clearance (Cockcroft, 1976).

 

The CG equation is as follows:

For men: CrCl _ml/min= {[(140 – Age in (yr)] × Weight(kg)}/SCr(mg/dl) ×72

Where;

CrCl is creatinine clearance and SCr is serum creatinine. 

For women, the above equation should be multiplied by 0.85.

In cases of persons of extreme weights, some have used lean body mass, whereas others have used correction if the eCrCl to average body surface area.

 

One interesting feature of the Cockcroft and Gault equation is that it shows how dependent the estimation of CCr is based on age. The age term is (140 – age). This means that a 20-year-old person (140 – 20 = 120) will have twice the creatinine clearance as an 80-year-old (140 – 80 = 60) for the same level of serum creatinine. The C-G equation assumes that a woman will have a 15% lower creatinine clearance than a man at the same level of serum creatinine.

2.12.2 Modification of Diet in Renal Disease (MDRD) Equation

Another formula for calculating the GFR is the one developed by the Modification of Diet in Renal Disease Study Group (Levey et al., 1999). Most laboratories in Australia (Mathew et al 2007) and the United Kingdom now calculate and report the estimated GFR along with creatinine measurements and this forms the basis of diagnosis of chronic kidney disease (www.nice.org.uk ,July 2014). The adoption of the automatic reporting of MDRD-eGFR has been widely criticized (Kallner et al., 2008). The most commonly used formula is the "4-variable MDRD", which estimates GFR using four variables: serum creatinine, age, ethnicity, and gender (National Kidney Foundation, February 2002). The original MDRD formula used six variables with the additional variables being the blood urea nitrogen and albumin levels Group (Levey et al., 1999). The equations have been validated in patients with chronic kidney disease; however, both versions underestimate the GFR in healthy patients with GFRs over 60 mL/min (Levey et al., 2006). The equations have not been validated in acute renal failure. 

The six variable MDRD equations are as follows:

 

GFR =170 × (SCr)_0.999 ×(Age)_0.176 × 0.762  (if patient is female) ×1.18 (if patient is black) × (BUN) _0.170 × (Alb) 0.318

 

Where;

BUN is blood urea nitrogen and Alb is albumin.

 

The abbreviated version or four variable version of the MDRD equation (mL/min per 1.73 m2) is as follows:

 

GFR =186 × (SCr) _1.154 × (Age) _0.203 ×0.742 (if patient is female) × 1.212 (if patient is black)

 

The re-expressed MDRD equation (abbreviated version; mL/ min per 1.73m2) after IDMS traceable calibration is as follows:

 

GFR =175 × (SCr)_1.154 ×(Age)_0.203​× 0.742 (if patient is female) × 1.212 (if patient is black) 

(Munikrishnappa and American Society of Nephrology, 2009).

Since these formulae do not adjust for body size, results are given in units of mL/min per 1.73 m2, 1.73 m2 being the estimated body surface area of an adult with a mass of 63 kg and a height of 1.7m.

2.12.3 Chronic Kidney Disease Epidemiology Collaboration Initiative (CKD-EPI) Equation

The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula was published in May 2009. It was developed in an effort to create a formula more accurate than the MDRD formula, especially when actual GFR is greater than 60 mL/min per 1.73 m2. This is the formula currently recommended by NICE in the UK. Researchers pooled data from multiple studies to develop and validate this new equation. They used 10 studies that included 8254 participants, randomly using 2/3 of the data sets for development and the other 1/3 for internal validation. Sixteen additional studies, which included 3896 participants, were used for external validation. The CKD-EPI equation performed better than the MDRD (Modification of Diet in Renal Disease Study) equation, especially at higher GFR, with less bias and greater accuracy. When looking at NHANES (National Health and Nutrition Examination Survey) data, the median estimated GFR was 94.5 mL/min per 1.73 m2 versus 85.0 mL/min per 1.73 m2, and the prevalence of chronic kidney disease was 11.5% versus 13.1%. Despite its overall superiority to the MDRD equation, the CKD-EPI equations performed poorly in certain populations, including black women, the elderly and the obese, and was less popular among clinicians than the MDRD estimate (Hougardy et al., 2014).

The CKD-EPI equation is:  

eGFR = 141 × min (Scr ×0.0113/k, 1)α × max (Scr × 0.0113/k, 1)-1.209 × 0.993 age ×

1.018 [if female] × 1.159 [if black], 

Where;

Scr is serum creatinine, 

k is 0.7 for females and 0.9 for males, 

α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1 (MacIsaac et al., 2015).  The formula CKD-EPI may provide improved cardiovascular risk prediction over the MDRD Study formula in a middle-age population (Matsushita et al., 2010).

2.13 Limitations of Some eGFR Equations

Limitations of various eGFR formulas have been reported in subjects with cardiovascular disease (Zamora et al., 2012). One study calculated similar assessment of cardiovascular risks by the Cockroft-Gault formula and by serum cystatin C level (Zamora et al., 2012). However, a larger study found substantial differences between eGFR values calculated by creatinine-based and cystatin-based formulas in patients with varying severity of cardiac disease, with creatinine-based eGFR values exceeding the cystatin-based values in most patient categories (Akerblomet al., 2015). Another study concluded that measured GFR, not eGFR formulas, should be used for evaluating the relationship between retinal vasculopathy and renal disease (Eriksen et al.,2015). Differences in the association of creatinine-based and cystatin-based eGFR formulas with non-traditional cardiovascular risk factors (asymmetric and symmetric dimethylarginine blood levels, insulin resistance) in subjects without diagnosed cardiovascular disease, diabetes or CKD was reported in another study (Melsom et al., 2015). Finally, eGFRformulas were found to be inaccurate in heart transplant recipients (Kolsrub et al., 2016). Also, a limitation in renal or extra- renal conditions affecting steady state of creatinine in plasma, for example, initially in acute renal failure (ARF), when the serum creatinine is fluctuating or a recovering frail cachectic elderly person. These equations are also limited due to interference with creatinine in the assay by ketones, glucose, and medications such as cephalosporins interfering with assay. In addition, variations in muscle mass such as in extremes of body mass and diet also contirbutes (Munikrishnappa and American Society of Nephrology, 2009).

     CHAPTER THREE

3.0 Materials and Method   

3.1 Study Area

The study will be conducted in kano metropolis, comprisimg of six local government areas namely; Fagge, Dala, Nassarawa, Tarauni, Gwale, and Kano municipal.

3.2 Study Population

The study will involve shisha smokers in kano metropolis

3.3 Type of Study

The study is cross-sectional.

3.4 Sample Size Determination

The sample size of this study was determined using 

n =                                 (Charan and Biswas, 2013).

Where, 

n = number of samples

z = statistic for level of confidence at 95% 

p = prevalence = 7%

d = allowable error of 5%, (0.05)

 n = 100.03

Minimum sample size is approximately 100.

3.5 Sampling Technique

Simple random sampling technique will be employed for this study.

3.6 Ethical Approval

Ethical approval will be sought from the relevant authorities in accordance with the declaration of Helsinki which established a code of ethics on human experimentation.  

3.6.1 Inclusion Criteria​

All shisha smokers in kano metropolis and who consented to take part in the study will be included.

3.6.2 Exclusion Criteria

1. Patients with cancer, urinary tract infection and inflammatory conditions

2. Patients who declined consent etc.

3.7 Data Collection

3.7.1 Administration of Questionnaire

Questionnaire developed for the study will be administered to each subject (appendix II). Medical history will also be obtained on social habits, health status and family history of non-communicable diseases. 

3.7.2 Informed Consent

The purpose and benefit of the study will be explained to the participants and their consent to be interviewed and for their sample to be collected will be sought. They will also be informed that their participation in the study will be entirely voluntary and any information provided will be treated with the utmost confidentiality.

3.8 Sample Collection Processing and Preservation 

Five milliliters of blood will be collected aseptically from each subject using a sterile syringe and needle. The sample will then be transferred into a gel activator tube and allowed to clot.  Centrifugation of the sample be carried out in a centrifuge at 1500 rpm for 5 minutes and the serum separated and transfer into a pre-labelled container and stored at -20oC until analysis.

3.9 Sample Analysis c

3.9.1 Serum Creatinine Measurement

Creatinine is measured by a colorimetric method in blood and urine invented by Max Jaffé’s in 1886 based on Jaffé reaction.

3.9.1.1 Principle of the Test 

Creatinine in serum and urine is determined by jaffe’s reaction where creatinine produces quantitatively an orange color with picric acid in alkaline medium. After allowing an incubation time of 15 munites at room temperature for color development the color is measured at 520nm.

3.9.1.2 Method

Jaffe’s method for creatinine estimation involves two stages; first stage known as the de-proteination stage and the second stage involves the colour development stage.During the de-proteination stage, proteins are precipitated in acidic medium and then centrifuged. The supernatant is used at the subsequent stage that involves the reaction of creatinine with picric acid in basic medium to form creatinine picrate. The coloured complex formed is directly proportional to the amount of creatinine present originally in the sample and measured spectrophotometrically at a wavelength of 510nm.

3.9.1.3 Procedure

First stage (deproteination stage)

In a clean test-tube, 125 µL of sample (serum) will be added, then 125 µL of sodium tungstate, followed by 250µL of sulphuric acid, and 500µL of distilled water. This will be mixed and then centrifuged at 1500rpm for 5 minutes to precipitate the protein.

Second stage (colour generation stage)

Test tubes will be labelled as test, standard and blank, 500 µL of supernatant from the first stage will be added to the test tube labelled test, then 500µL of creatinine standard to the tube labelled standard and 500µL of distilled water to the tube labelled blank. To all the tubes, 500µL of picric acid and 500 µL of sodium hydroxide will then be added in each test tube. The mixture will then be mixed and incubated at room temperature for 15 minutes then read using a spectrophotometer at 510nm.

3.9.1.4 Calculation    

Concentration of Test (µmol/L) = Absorbance of Test X Concentration of standard                                                             ​​​​​​Absorbance of Standard

3.10 Mdrd Equation Formular

eGFRMDRD =175X (standardized serum creatinine [mg/dl])_1.154 X age_0.203 X (0.742 if female) X (1.212 if black) (Matsushita et al., 2012). 

3.11 Ckd-Epi Equation Formula

eGFR = 141 X min(Scr ×0.0113/k, 1)α Xmax(Scr × 0.0113/k, 1)-1.209X 0.993Age X

1.018 [if female] × 1.159 [if black], 

Where;

Scr = serum creatinine, 

k = 0.7 for females and 0.9 for males, 

α= -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and 

Max = the maximum of Scr/k or 1 (MacIsaac et al., 2015).

3.12 Statistical Analysis

All data collected will be analysed using Statistical Package for Social Sciences (SPSS) for windows version 20.0. Estimated glomerular filtration rate will be calculated using the MDRD and CKD-EPI equations. Pearson correlation will be used to determine correlation between the MDRD and CKD-EPI equations while the prevalence of the various CKD stages will be determined using the Chi-squared test. 

     
        CHAPTER FOUR

4.0 Result​

A total of one hundred subjects were included in this study. All the subjects were active shisha smokers’ residents in Kano Metropolis. Out of these subjects, 84 (84%) were males, while 16 (16%) were females. The mean age of the subjects was 26.26 ± 3.26. In addition, the mean serum creatinine was 54.73 ± 26.61.

Table 4.1 shows the prevalence of the various CKD stages based on estimated glomerular filtration rate as calculated using the CKD- EPI equations. The overall CKD prevalence was 9% and the highest CKD stage observed using the CKD-EPI equation was CKD stage 2 with a prevalence of 7% followed by CKD stage 3A with prevalence of 2%. ​

Table 4.1 Prevalence of CKD stages based on estimated glomerular filtration rate as calculated using the CKD- EPI equation.

Stages of CKD (mLs/min/1.73m2)	CKD – EPI  (n = 100)
Stage1: n, (%) e-GFR ≥ 90 – normal kidney function	91            (91)
Stage 2: n, (%) e-GFR  60 - 89 – mildly reduced kidney function-mildly reduced kidney function	7               (7)
Stage 3A: n, (%) e-GFR -  45 – 59 - moderately reduced kidney function	2              (2)
Stage 3B: n, (%)  e-GFR 30 – 44 - moderately reduced kidney function	0               (0)
Stage 4: n, (%) e-GFR 15 – 29  - severely reduced kidney function	0              (0)
Stage 5: n, (%)  e-GFR - < 15 - very severe or end stage kidney failure	0              (0)
Overall CKD prevalence rate, n, (%)	9               (9)

 

 

 

 

 

 

Key: n = frequency, % = percentage, CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration Initiative (CKD-EPI) equation.

Table 4.2 shows the prevalence of the various CKD stages based on estimated glomerular filtration rate as calculated using the MDRD equation. The overall CKD prevalence rate was 5% and the highest CKD stage observed using the MDRD equation was CKD stage 2 with a prevalence of 4% followed by CKD stage 3A with prevalence of 1%.

Table 4.2 Prevalence of CKD stages based on estimated glomerular filtration rate as calculated using the MDRD equation

Stages of CKD (mLs/min/1.73m2)	MDRD(n = 100)
Stage1: n, (%) e-GFR ≥90 - normal kidney function	95            (95)
Stage 2: n, (%) e-GFR 60 – 89 - mildly reduced kidney function	4               (4)
Stage 3A: n, (%) e-GFR 45 - 59 - moderately reduced kidney function	1              (1)
Stage 3B: n, (%) e-GFR 30 - 44 - moderately reduced kidney function	0               (0)
Stage 4: n, (%) e-GFR 15 – 29 - severely reduced kidney function	0              (0)
Stage 5: n, (%) e-GFR < 15 - very severe or end stage kidney failure	0              (0)
Overall CKD prevalence rate, n, (%)	5              (5)

 

 Key n= frequency, % = percentage, MDRD = Modification of Diet in Renal Disease.

 

Table 4.3 shows the Pearson correlation analysis of the estimated glomerular filtration rate as calculated using on MDRD with CKD-EPI equations.

Table 4.3 Pearson correlation analysis of the estimated glomerular filtration rate as calculated using MDRD with CKD-EPI equation

Parameter	R	p = value
MDRD	0.184	0.067
CKD-EPI

r = Pearson correlation coefficient,

   
         

CHAPTER FIVE

5.0 Discussion

5.1 Discussion

The global increase in the prevalence of chronic kidney disease(CKD) and the rise in the incidence of patients reaching end-stage renal disease have made it imperative that risk factors for CKD be identified. In recent years, it has become apparent that cigarette smoking, besides its traditionally accepted carcinogenic effects and its detrimental role as a promoter of cardiovascular disease (CVD), is an important independent risk factor for renal disease with a substantial number of studies documenting a deleterious effect of smoking on renal function (Orth and Hallan, 2008). However, several important aspects of smoking-induced renal damage remain unclear. Although there are enough non-renal reasons for not to smoke, establishing smoking as an independent risk factor for kidney failure is important for improving focus and motivation for smoking cessation among CKD patients and to further increase awareness about this renal risk factor. First, it is controversial whether the renal effects of smoking equally affect both genders. A large population-based study from Australia including 11,247 randomly selected subjects found lifetime smoking exposure to be significantly associated with CKD stage 3 or higher in men, but not in women (Briganti et al., 2002).However, other studies have reported similar effects of smoking on the risk of kidney failure in both genders (Yamagata et al., 2006). Second, it is unclear whether the smoking-related risk of kidney failure depends on the amount of cigarettes smoked. Dose-response relationships have only been demonstrated for surrogate end points like renal function decline and urine albumin excretion rate (Bleyer et al., 2000). Third, it is unknown to what extent smoking cessation reduces the risk of kidney failure. Very few studies have investigated this topic, and data are based on a limited number of patients with diabetes mellitus, again using only surrogate markers of renal damage, that is, no hard end points (Gambaro et al., 2001). In the present study, 84 (84%) of the subjects were males, while 16 (16%) were females, both of the two gender groups are shisha smokers. The mean age of the subjects was 26.26 ± 3.26. In addition, the mean serum creatinine was 54.73 ± 26.61. By the use of an estimated glomerular filtration rate equation of chronic kidney disease epidemiology collaboration (CKD-EPI),   the overall CKD prevalence among the subjects was 9% and the highest CKD stage observed using the CKD-EPI equation was CKD stage 2 (e-GFR 60 - 89 – mildly reduced kidney function-mildly reduced kidney function) with a prevalence of 7% followed by CKD stage 3A (e-GFR - 45 – 59 - moderately reduced kidney function) with prevalence of 2%. Also using the modification of diet in renal disease (MDRD) equation, the overall CKD prevalence rate among the subjects was 5% and the highest CKD stage observed using the MDRD equation was CKD stage 2 with a prevalence of 4% followed by CKD stage 3A with prevalence of 1%.  Therefore, comparison of the overall prevalence rate of CKD stages using the MDRD and CKD-EPI equations shows that, higher overall prevalence of CKD stage was observed using the CKD-EPI equation compared with the MDRD equation. The reason that could be attributed to this difference is that, Levey et al, (2010)  noted that, the CKD-EPI equation is the most accurate in estimation of GFR for diverse population compared  to the MDRD equation and that, the MDRD equation have a sub-optimal performance in the early CKD stages compared to the CKD-EPI equation.  Moreover, correlation studies between the MDRD and CKD-EPI equation using Pearson correlation analysis shows no significant association between the two equations (r = 0.184; p = 0.067).

5.2 Conclusion​

The highest CKD stage observed using the MDRD and CKD-EPI equation was CKD stage 2 with a prevalence of 4% and 7% respectively. However, if adequate measures are not taken early, these subjects may progress to CKD and to end stage kidney failure. 

5.3 Limitation of the Study

This study was conducted with small sample size, compare with the general population of the Kano Metropolitan, hence, the finding of the study result cannot be said to be generalizable to the entire population of the study area.

5.4 Recommendation

The sample size used for this study was small and therefore, it is recommended that, future study should use an enlarged sample size in order to fully assess the extent and the effect of shisha smoking in the kidney function of these active smokers.