| Abstract|| |
Both the incidence and prevalence of chronic kidney disease (CKD) are rising with immense pace worldwide. People living in developing countries are speculated to suffer the consequences due to economic deprivation and high cost of treatment. The prevalence of CKD is highly variable in different parts of the world, due to various environmental, ethnic, socioeconomical, and rural-urban differences. It has become very important for the developing countries to understand the true nature of the disease and its prevalence, rather than to hypothesize or make supposition on the bases of Western data. It is imperative to understand the risk factors in our region or country. Few studies have reported that the prevalence of CKD in Pakistan and its risk factors. Through the internet, we searched the terms prevalence of CKD, and included articles that discussed the CKD prevalence in different regions. We reviewed all studies along with the global as well as regional data to have better insight into the problem.
|How to cite this article:|
Imtiaz S, Salman B, Qureshi R, Drohlia MF, Ahmad A. A review of the epidemiology of chronic kidney disease in Pakistan: A global and regional perspective. Saudi J Kidney Dis Transpl 2018;29:1441-51
|How to cite this URL:|
Imtiaz S, Salman B, Qureshi R, Drohlia MF, Ahmad A. A review of the epidemiology of chronic kidney disease in Pakistan: A global and regional perspective. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2019 Jan 23];29:1441-51. Available from: http://www.sjkdt.org/text.asp?2018/29/6/1441/248307
| Introduction|| |
There is a major rise in the incidence of chronic kidney disease (CKD) all over the world. It was ranked 27th in the list of causes of total number of worldwide deaths in 1990, but rose to 18th in 2010. It is unique among other chronic ailments, due to its perplexing epidemiology. CKD significantly reduces the lifespan of a person by increasing the risk of cardiovascular mortality and its progression to end-stage renal disease (ESRD). In a comprehensive review and meta-analysis, the world-wide prevalence of CKD was found to be 23.4% in Stage 1–5 and 10.6% in Stage 3–5.
| Global Review|| |
A gross regional difference in the prevalence of CKD has been observed globally. For example, in the United States, the adjusted prevalence of CKD Stages 3 to 5 in adult white general population ranged from 4.3% in the states of Delaware and Pennsylvania to 16.7% in Florida. Among African-Americans, it ranged from 6.7% in California to 13.4% in the Mid-west states. Similar heterogeneity has been observed across European countries. For example, the adjusted prevalence of CKD Stages 1 to 5 varied between 3.31% in Norway and 17.3% in northwest Germany and the adjusted prevalence of CKD Stages 3 to 5 varied between 1.0% in central Italy and 5.9% in northwest Germany. Likewise, in Asian countries, for example in China, the adjusted prevalence of CKD Stages 1 to 5 showed large variation from 6.7% in south China to 18.3% in southwest China. The factors which can contribute in this observed variability could be an error in the sampling technique of the study which gathered an unrepresentative population, the differences in demographic characteristics of the population, for example, ethnicity and response rate of the population, difference in laboratory technique to measure creatinine and type of equation used to measure the estimated glomerular filtration rate (eGFR).
Diabetes mellitus (DM), hypertension (HTN), obesity and cardiovascular disease have attributed to the rapid rise in the incidence of CKD in most parts of the world, especially in developing countries. It is speculated that the prevalence of CKD will increase in future, because of the increase in the burden of risk factors in this region. This increase in CKD load puts prevention strategy as a most appropriate approach in this part of the world. Despite the increasing prevalence of DM, HTN and obesity globally, and their effects on increasing the prevalence of CKD, there are examples where these rising trends are now reverting, at least in some developed countries. For example, in the USA and Norway, the prevalence of CKD has not increased, rather stabilized in the last decade and has even reduced in the United Kingdom. The possible explanation for this is better control of HTN and DM and use of angiotensin-converting enzyme inhibitors in the last decade. There has been a remarkable change in clinical practice in the last decade; for example, understanding of blood pressure targets in DM for instance. When the UKPDS trial was conducted in 1980, it was an acceptable idea to allow patients with type-2 DM in the control arm to have blood pressure as high as 200/105 mm Hg which, according to the JNC-7, has now been reduced to <130/80 mm Hg. Similarly, there seems to be a better control of DM by targeting a lower HBA1c in the general population over time.
Another very interesting aspect of the epidemiology CKD is the discrepancy between the various CKD risk factors and the prevalence of CKD in different parts of the world. The magnitude of this discrepancy clearly points out that there are still undefined risk factors which modify the risk for CKD. For example, developing countries such as Poland, northern Tanzania, Italy, and India had a CKD prevalence of 5.8%, 7.0%, 7.1%, and, 7.5%, respectively, but had a higher prevalence of HTN 31.9%, 28.0%, 50.1%, 32.5%, and DM 6.7%, 12.7%, 11.8%, 19.0%, respectively. In contrast, in developed countries such as Australia, England, Canada, and USA where the overall prevalence of CKD is high 11.5%, 11.9% 12.5%, and 13.0%, respectively, the prevalence of HTN (29.0%, 34.1%, 16.3%, 27.1%, respectively) and DM (8.5%, 7.4%, 6.3% and 6.8%, respectively) was lower [Table 1].
|Table 1: Comparison of chronic kidney disease, hypertension, diabetes mellitus prevalence in developing and developed countries.|
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This discrepancy indicates that genetic and environmental risk factors such as ethnicity, industrial pollution, low birth weight, infection, herbal medications and, dietary habits, deserve attention to explain the local prevalence of CKD [Table 1].
| Regional Review|| |
CKD in the South Asian region has the same pattern of widely varying prevalence as observed in developed countries. The causes of CKD are different and some of the regions have shown a high prevalence of CKD caused by glomerulonephritis and obstructive nephro-pathy and those of unknown etiology. To this date, very few studies have been conducted to evaluate the epidemiology of CKD in this region. India is now in a process of developing a CKD registry. In India, although the data are sparse, a few population-based studies have been performed. These studies have shown variable results; however, they at least give some idea for future planning. For example, in a study conducted in Delhi, investigators found a prevalence of 0.785% of CKD Stage-3 and above, as compared with another study carried out in Northern India, where it was 4.2%. On the other hand, in another study from Agra city, the prevalence of CKD Stage 1–3 was 13% as compared with the SEEK trial conducted all over India, wherein the prevalence of CKD Stages 1–5 was 17.2% [Table 2].
| Chronic Kidney Disease in Pakistan|| |
The epidemiology of CKD and its risk factors are not well studied in Pakistan, and very few hospital-based studies have been performed in the past. These studies have shown that DM and HTN are the major causes of CKD in urban areas while CKD of unknown etiology, glomerulonephritis and kidney stones were prevalent in the rural areas., The incidence of DM is also increasing in this region due to various reasons mentioned in the literature. This increased prevalence of DM in the community is manifested by an increased number of diabetic patients who are coming to the nephrology clinics with nondiabetic kidney disease. In a biopsy series of 212 diabetic patients, 91 (42.9%) were having nondiabetic kidney disease, while 45 (21.2%) had non-diabetic lesions with the background of diabetic kidney disease. In another study from the same city, in a renal biopsy series of 62 diabetic patients, 34 patients (52%) had non-diabetic kidney disease.
| Prevalence of Diabetes|| |
Since DM has emerged as a leading cause of CKD, the prevalence of DM as well as HTN has become an important factor to predict the future burden of CKD. There were two large community-based studies that were conducted to evaluate the prevalence of DM, which are worth mentioning here. The National Health Survey of Pakistan was conducted between 1990 and 1994, while Pakistan National Diabetic Survey was performed between 1994 and 1998 in all four provinces of the country. The national health survey of Pakistan was patterned on Third National Health and Nutrition Examination Survey, USA., The rural and urban areas of each of four provinces of Pakistan were taken as strata. A total of 18,315 persons were examined. This data were compared with the health status of the USA and Pakistan which obviously showed the gross differences in all indicators and parameters which a well-developed country and a developing country may have. The most important message or conclusion which emerged out from this landmark study was the conception at that time, that Pakistan was experiencing first, a “Double Burden,” one in which diseases associated with under development such as infectious diseases and nutritional deficiencies had not yet been controlled, along with risk factors for diseases associated with development such as cardiovascular diseases and cancer risk factors, which were also significant. Second, important inequalities also exist within Pakistan both between urban and rural residents and between economic status groups.
After 10 years of publishing this remarkable study, Jafar et al reanalyzed the data on many aspects such as DM, obesity, proteinuria, HTN in five ethnic groups. This distinguished work gave important insight into the volume of these important conditions at community level. They found an overall prevalence of DM of 5.4%, this was highest among Muhajirs (5.7%) and lowest among Baluchis (2.9%) [Table 3]. Similarly, central obesity was also evaluated and found important ethnic differences. The overall mean waist circumference was 79.5 (11.9%) and the age-standardized waist circumference was highest in Sindhis and Muhajir women; 81.9 (12.2%) and 81.8 (12.6%), respectively [Table 3].
|Table 3: Analysis of National health survey of Pakistan data by Jafar et al in five ethnic groups of Pakistan between 1990 and 1994.|
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As mentioned earlier, the second largest study was performed by the Pakistan National Diabetic Survey, which included all four provinces between 1994 and 2000.,,,, The prevalence in the provinces of Sind, Baluchistan, Punjab and NWFP [Khyber Pakhtunkhwa (KPK)] is shown in [Table 4].
|Table 4: Studies performed by Shera et al in four provinces of Pakistan between 1994 and 1998.|
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Both studies were performed in the same decade and apparently Jafar et al underestimated and Shera et al overestimated the prevalence of DM as evident from the recently completed diabetic survey of Pakistan 2017 which showed a prevalence of 26% (19 August 2017 newspapers). Both showed a gross difference in the overall prevalence of DM; Shera et al showed a relatively high prevalence of DM.
| Prevalence of Hypertension|| |
The prevalence of HTN was also evaluated by Jafar by analyzing National Health Survey of Pakistan (NHSP) data in five ethnic groups. They found that HTN was more prevalent in urban (22.7%) versus rural dwellers (18.1%), and the age-standardized prevalence of HTN was highest among Baluchi women (41%) and lowest among Sindhi women (9.9%) [Table 3].
| Prevalence of Chronic Kidney Disease|| |
CKD was evaluated at community level in few studies. Jafar et al. evaluated the prevalence of proteinuria, which is one of the markers of CKD, in five ethnic groups. They found the highest prevalence among Sindhis (men 9.5%, women 10.3%) and Muhajirs (men 8.2%, women 4.7%) and lowest prevalence among Baluchis (men 2.4% and women 4.2%) and the Pashtuns (men 2.5%, women 1.2%) [Table 3].
The prevalence of DM appears to reflect the ethnic distribution of proteinuria, while it did not show any association with HTN. The study has the following limitations: first, its cross-sectional design, second, only urinary protein was measured and third, serum creatinine was not performed, and therefore, only stage 1 kidney disease was evaluated. One thing that was very obvious from this novel study was that strong ethnic differences existed in the odds for proteinuria.
The prevalence of CKD was also evaluated in a community-based cross-sectional study conducted by Jessani et al, in Karachi, the largest metropolitan city of Pakistan. The study was not designed to measure the prevalence of CKD, rather it was a secondary analysis of the study, which was performed to promote intervention that can ensure blood pressure control at community level. The data were collected through a factorial design cluster randomized controlled trial. In a population of 3143 adults aged 40 years or older, they found a crude prevalence of reduced eGFR [eGFR CKD-Epi (pk) <60.0 mL/min 1.73 m2] in 5.3% (4.5%–6.2%), albuminuria (UACR ≥ μg/mmol) in 9.4% (8.4%–10.5%) and CKD in 12.5% (11.4%–13.8%) of the patients. The prevalence of CKD and reduced eGFR was higher in women compared to men, and it increased with age. When the CKD prevalence was standardized with age, it turned out to be 15.3% (13.7%–16.9%) while that of reduced eGFR and albuminuria, was 7.4% (6.2%–8.6%) and 11.1% (9.8%–12.4%), respectively. In another study, Jafar et al evaluated 262 subjects > 40 years of age, from a Pashtun community of Karachi, to determine the prevalence of reduced GFR. They found an overall prevalence of reduced GFR of 29.9% (24.2% to 35.1%) in men and 32.5% (24.8%–41.3%) in women.
| Chronic Kidney Disease of Unknown Etiology|| |
It is not uncommon for a nephrologist to encounter young patients with bilateral small sized kidneys with no associated comorbid conditions. The etiology remains unknown despite all possible clinical and laboratory work-up. CKD of unknown etiology is recognized as a severe form of kidney disease. It causes considerable morbidity and mortality, resulting in death in young and middle-aged patients, without any known etiological factors for CKD, such as DM and HTN. The exact risk factors are not known but attributed to occupational or environmental exposure and low birth weight.
This form of nephropathy is typically reported from regions which are warm, located in low altitude in coastal and tropical and subtropical regions. Recently, four forms have been recognized in different regions of the world including, Mesoamerican nephropathy, Sri Lankan nephropathy, Uddanam nephro-pathy of India, and El-mina nephropathy of Egypt. Characteristically, the disease is prevalent in rural inhabitants of low socioeconomic status, especially in males working in agricultural fields. Typically, all regional nephropathies have a histological appearance of chronic tubulointerstitial nephritis and mostly, the clinical features have similarities, such as late presentation, a long asymptomatic phase, nonglomerular proteinuria and an absence of HTN at the beginning of the disease. Chronic tubulointerstitial nephritis is the biopsy finding in most of the studies mentioned above. In Pakistan, despite massive urbanization, the population in rural areas is >60% in all four provinces, and most of them rely on agriculture as their occupation. The climate is hot in these areas. In an analysis of kidney biopsy, pathological data of 1200 patients performed at our center, it was shown that chronic tubulointerstitial nephropathy was found in 11% of the patients. In a further analysis of those who had been diagnosed to have tubulointerstitial nephropathy (unpublished data), we found that most patients presented with similar clinical features and were from rural areas. The exact cause of kidney injury, such as water deprivation due to excessive sweating in warm humid climate, or drinking plenty of contaminated water, still remains a question.
Contamination of drinking water with heavy metals, such as Cadmium (Cd) and Arsenic (As) has been recognized as nephropathic due to their oxidative stress. In a cross-sectional case–control study of more than 6000 individuals, which included 733 cases and 4044 controls from endemic and non-endemic areas, Jaylilka and Mendis found significantly higher urinary excretion of Cd in individuals with CKD compared with controls in endemic areas, 1.039 μg/g versus 0.646 μg/g, respectively; it was 0.345 μg/g in non-endemic areas. They also found a dose-effect relationship between urinary Cd concentration and CKD stages. They advocated that Cd exposure is a risk factor for the pathogenesis of CKD. In a Mexican study of 90 individuals with no previous comorbid conditions, Robles-Osorio and Pérez-Maldonado found a strong correlation between urinary arsenic excretions and αl microglobulin excretion.
In Pakistan, the status of drinking water contaminated with As and Cd is alarming. Abbas and Cheema analyzed 100 drinking water samples from District Sheikhupura, Punjab and found high mean value of As concentration in hand pump sample of 76.22 ± 20.73 ppb and lower in bottle water of 7.742 ± 3.066 ppb as compared with WHO standard of 10 ppb.
Similar high levels different heavy metals have been found in the Sindh province; Arain et al found high levels of 96 μg/L in ground-water and 157 μg/L in surface water. The Pakistan Council of Research in Water Resources (PCRWR 2015–16) evaluated the status of As level regularly in major cities of Pakistan. Due to persistent and increasing contamination of As, a national action plan to mitigate the As effect was introduced between 2007 and 2011. In the Manchar Lake, which is the largest reservoir of the fresh water in Pakistan, the As level was found to range from 35.2–158 μg/L, which is 3–15 fold higher than the limit. Similarly, in Jamshoro, Sindh the highest content of As in surface water sample was found to be 50 μg/L.,
Cd, as discussed above, is also a great concern due to its renal and other toxicities. The safe standard for Cd concentration in drinking water by WHO is 0.0003 ng/L. In Pakistan, high Cd concentration in drinking water was found from effluent discharges of marbles, steel, mining, metal, planting, and aluminum industry. High concentration of Cd was found from many samples collected from different parts of the country. The concentration of Cd in groundwater samples collected from various sites of Pakistan ranged from 0.001 to 0.2 μg/L. The highest value of 0.21 mg/dL was reported in the sample collected from tubewell water of Hayatabad Industrial Estate, KPK. There is large variation in Cd concentration of surface water throughout the country.,
Low birth weight
Low birth weight (LBW) is associated with high risk of ESRD in the 3rd and 4th decades of life. It is estimated that 72% of LBW infants in developing countries are born in Asia. Although there is no study on the prevalence of low birth weight in Pakistan, UNICEF estimates an incidence of 19%. With this high incidence of low birth weight, it will be pivotal to look for this association in this region as well.
Kidney stone disease
Kidney stones are still among the leading cause of kidney failure in Pakistan., Both incidence and prevalence of kidney stones is increasing worldwide. Dietary factors play an important role both in developing and the developed world., Stone disease increases the risk of CKD, albeit not causing ESRD significantly. In a study of 360 patients from a tertiary care hospital of Karachi, Naqvi and Rizvi found that 242 (67%) of the patients had renal failure, 48 (13.33%) remained on hemodialysis, 11 (3.05%) underwent kidney transplant and 58 (16.11%) died from the disease. Similarly, in the pediatric population, high rate of CKD was noted due to delay in detection of kidney stones. Khan et al reported that 16% of the patients who came to their center with kidney stones developed CKD. Likewise, Rizvi et al found that 20% of their pediatric patients who underwent kidney transplantation developed ESRD due to kidney stones.
| Conclusion|| |
This review shows that the pattern of CKD and its risk factors such as DM and HTN is similar to that seen in other parts of the world. There is a wide fluctuation and uncertainty in reporting the prevalence in different studies globally as well as regionally. The number of studies performed in Pakistan is few, under powered, not representative of the population and primarily not designed to evaluate the prevalence of CKD. These studies showed a prevalence of DM of 5.5%–22%, HTN of 19.8% and CKD of 5.0% to 12.5% to 31.2%. The prevalence of CKD is high in women and increases with age in both genders. There is a large population in whom the exact cause of renal failure is obscure, and possibility of environmental factors such as water contamination, low birth weight, and kidney stone disease should be evaluated in large community-based studies.
| Acknowledgment|| |
We greatly acknowledge the support of Ms. Yumna Maheen for reviewing the manuscript.
Conflict of interest: None declared.
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Dr. Salman Imtiaz
Department of Nephrology, Dorab Patel Postgraduate Training and Research Center, The Kidney Center Post Graduate Training Institute, Karachi
[Table 1], [Table 2], [Table 3], [Table 4]