Prevalence of chronic renal failure in adults in Delhi, India

Nephrol Dial Transplant (2005) 20: 1638 1642 doi:10.1093/ndt/gfh855 Advance Access publication 26 April 2005 Original Article Prevalence of chronic renal failure in adults in Delhi, India Sanjay Kumar Agarwal 1, Suresh Chand Dash 1, Mohammad Irshad 2, Sreebhuasn Raju 1, Ravinder Singh 1 and Ravinder Mohan Pandey 3 Departments of 1 Nephrology, 2 Laboratory Medicine and 3 Biostatistics, All India Institute of Medical Sciences, New Delhi, India Abstract Background. Chronic renal failure (CRF) is a debilitating condition responsible for high morbidity and mortality and is a financial burden on government and society. Because of its costs and the complexity of its treatment, proper care is available to very few patients in India. A community-based study has not been done to determine the prevalence of CRF in India. Methods. We used a multi-stage cluster sampling method in the South Zones of Delhi. In each area, we first contacted the local social leader and explained the study and the medical information pamphlets. On pre-scheduled days, the study team canvassed the study zone. The individuals contacted responded to a detailed questionnaire, and had a physical examination, a dipstick urine test for albumin and sugar and a blood test for serum creatinine. A serum creatinine >1.8 mg% defined renal failure. A repeat test for serum creatinine was done after 8 12 weeks to confirm chronicity of renal failure. If it was >1.8 mg% after 3 months in the absence of reversible factors, CRF was diagnosed. The person found to have CRF was asked to attend a hospital renal clinic for further investigations and individualized management. Results. A total of 4972 persons were contacted for the study. Their mean age was 42±13 years; 56% were males. Out of the 4972 who were initially approached, 4712 agreed to give the blood sample, and thus were included for the evaluation of CRF. CRF was found in 37 of them. Thus, the prevalence of CRF in that adult population was 0.785% or 7852/million. Conclusions. The prevalence of CRF in India makes it a serious problem in need of urgent efforts to contain it. Correspondence and offprint requests to: Dr Sanjay Kumar Agarwal, Department of Nephrology, AIIMS, New Delhi-110029, India. Email: skagarwal58@yahoo.co.in Keywords: chronic renal failure; Delhi; India; prevalence Introduction Chronic renal failure (CRF) is the most debilitating condition in patients with renal disease. Not only does it cause significant morbidity, but it also has a high mortality. Because of the costs and the complexity of its treatment, very few patients are able to obtain adequate treatment, and CRF places a heavy financial burden on any society. At a time when the prevention of CRF is becoming an important issue worldwide, determining the prevalence of CRF, in any country, is important for planning the care of patients afflicted by it. A community-based epidemiological study has not been done in India to determine the prevalence of CRF. There are some Indian studies that comment on various aspects of the problem of CRF [1 4], but all these studies are hospital-based. As the patients seeking care in a hospital depend on many factors, these hospital-based studies may reflect the problem falsely. Furthermore, none of those studies have indicated the prevalence of CRF. A recently published study reported a prevalence of 0.16% in a village in south India [5]. However, the study did not test for serum creatinine in all the subjects screened, and also its aim was not to determine the prevalence of CRF. The present study was conducted to find out the prevalence of CRF in the city of Delhi by using blood tests for renal dysfunction in all the subjects screened. Subjects and methods We adopted a multi-stage cluster sampling method for this study. Population statistics data of the National Capital Territory of Delhi, published by The Directorate of ß The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Chronic renal failure in Delhi, India 1639 Economics and Statistics, were reviewed for information about the zones of Delhi. The study was funded by the Indian Council of Medical Research, New Delhi for a fixed period of time. As per the recommendation of the funding agency and of the initial feasibility study, only the South Zones of Delhi were investigated. In the population statistics data, the South Zones of Delhi are further divided into 13 charges, with each charge comprising different areas. Each charge was taken as one cluster. It was planned to include each of the charges in the South Zones and apply a multistage cluster sampling method. Accordingly, study teams went to the centre of a charge and proceeded to evaluate the residents in one direction until the number of subjects required for each cluster was achieved. If the number of subjects needed was not acquired going in one direction, staff returned to the centre and proceeded in the opposite direction until the required number was reached. Adults (16 years or older) of either gender were included in the study. Determination of sample size For a long time, it has been assumed that each year 100 000 new patients with end-stage renal disease (ESRD) require renal replacement therapy (RRT) in India [6]. We calculated the required sample size of our study based on that information. The 1998 report of the third cycle of the National Health and Nutrition Examination Survey (NHANES III), conducted between 1988 and 1994 in the USA, estimated that, if serum creatinine >1.7 mg% were taken as the cut-off for CRF, then in the period studied the number of cases of CRF was 12 times the number of cases of ESRD [7]. As the care of ESRD in India is not as good as in the USA, we expect that the ratio of CRF to ESRD will be higher. Thus, we presumed that the number of cases of CRF would be 15 times that of ESRD. Therefore, the incidence of new cases of CRF will be 15 10 5. Further, as the adult population in India is 60% of the total population, the total number of adults in India will be 60 10 7. Thus, the incidence of CRF in Indian adults will be 0.0025 (or 0.25%) (15 10 5 /60 10 7 ). The prevalence of any condition is regarded as incidence average survival. Since there are no data available for the average survival of patients with CRF in India, assuming that the average survival is 5 years, the prevalence of CRF in Indian adults will be 0.0125 or 1.25% [incidence of CRF in Indian adults (0.0025) average survival of CRF in Indian adults (5 years)]. Further, as the number of cases required for any study of prevalence is calculated by the formula 4 p (1 p)/d 2 (where p ¼ presumed prevalence and d ¼ 25% of prevalence), the cases required in our study will be 5056 [4 (0.0125)(0.9875)/(0.003125) 2 ]. However, this sample size would hold true only if we were using a simple random sampling method. Since the field conditions in this study did not make that feasible, and as we planned to conduct the study using a multi-stage cluster sampling method, we had to double the number of individuals evaluated. Thus we needed to have 10 112 cases in our present study. In each area, we first contacted the local community leader and explained the study, showed him the medical information pamphlet, and we apprised him about CRF and its implications, explaining in detail the study plan and the steps involved. Local leaders and the potential subjects in the area were informed in advance of the date and time of the visit of our team of investigators, comprised of a doctor, field supervisor and laboratory technician, all of whom had been trained in the use of the questionnaire, taking blood pressure, and carrying out and interpreting the dipstick urine test. In the study area, team members administered the detailed questionnaire. After the history had been taken, a physical examination was done, including blood pressure measurement before which the subject was allowed to sit for 5 min, with the arm supported at the level of the heart. At least two blood pressure measurements were done, and the two were averaged. Then the person was asked to provide a midstream sample of urine, which was examined in the field with a dipstick for albumin and sugar. Next, a blood sample was drawn to take to the hospital for measuring serum creatinine using the kinetic Jaffe method on an Echoautoanalyser (Italy). Although not part of the study, random blood sugar was also measured as a device to enhance the cooperation of the subjects in the field. The medical examination report was recorded on a printed form, and any abnormal findings (of physical examination or urine and blood tests) were mentioned in the report. On the next visit of the team to the area, the individual report thus generated on each person was given to the person concerned. If any person was found to have some medical illness, medications were also given during the visit to him/her for a short period. This gesture acted as an incentive to get better cooperation from the community in the conduct of the study. A person found to have an abnormal physical examination, urine test or blood test was asked to come to the hospital for further appropriate tests. A serum creatinine >1.8 mg% (the upper limit of the normal in our laboratory) defined renal failure. Any person whose serum creatinine was >1.8 mg% was instructed to come to the hospital for a repeat serum creatinine after a few days. In addition, serum creatinine was tested again after 8 12 weeks to ascertain the chronicity of its elevation. A serum creatinine persistently >1.8 mg% for 8 12 weeks in the absence of any reversible factor was the criterion to diagnose CRF. These patients were investigated further and were treated as appropriate. Hypertension was classified following the guidelines of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of Blood Pressure [8]. In addition, hypertension in persons already controlled on antihypertensive drugs was classified according to the number of drugs with which blood pressure was controlled: mild (one drug), moderate (two drugs), severe (three drugs). Further, a person with different severity of blood pressure reading in systolic and diastolic hypertension was classified overall into the higher severity class. For example, a person having severe diastolic hypertension and mild systolic hypertension was classified as having severe hypertension. We also classified hypertensive patients who did not know about their hypertension into a separate category cases of so-called new hypertension. The total cases of hypertension included pre-existing hypertension and newly diagnosed hypertension. In the absence of fasting blood sugar values, and since the assessement of diabetes was not among the aims of this study, some of the conclusions drawn about diabetes are approximate. Insulin-dependent diabetes mellitus was labelled if the onset of diabetes was before the age of 30 years,

1640 S. K. Agarwal et al. and non-insulin dependent diabetes mellitus if the onset of diabetes was above the age of 30 years. Pre-existing diabetes was diagnosed if the subject already was on some antidiabetic medication; new diabetes was diagnosed if the patient had random blood sugar >200 mg/dl along with a urine positive for sugar. Results A total of 4972 subjects were contacted during the 3 years of the study. As the study was funded only for 3 years, the calculated required sample size could not be achieved. Out of the 4972, 4712 individuals agreed to give the requisite blood sample, a participation rate of 94.8%. As the diagnosis of CRF depends on the measurement of serum creatinine, the 260 persons who did not give blood samples were excluded from the analysis. The mean age of all the participants was 42.38±12.54 years, and 56.16% were male. CRF was found in 37 of 4712 participants (0.785%). Thus, the prevalence of CRF in India can be calculated as follows. CRF in the studied adult population ¼ 37=4712 ðor 0:785%Þ Adult population of India ¼ 60% of 10 9 ¼ 600 10 6 Prevalence of CRF in Indian adults ¼ 37 600 10 6 =4712 ¼ 4 711 375 To conform to the usual way of presenting data on CRF, i.e. number of cases per million population (p.m.p.), we make the following additional calculation. CRF prevalence ¼ 37 106=4712 ¼ 7852 p:m:p: Compared with the mean age (42.38±12.54 ) of the study population as a whole, the mean age of patients with CRF was 59.91±13.53 years (range 32 86), and 48.65% of them were males. Their mean serum creatinine was 2.89±2.2 mg% (range 1.9 10.7). Defining the aetiologies of CRF was not among the aims of this study (the sample size calculation would have had to be different); however, we tried to determine the aetiologies of CRF in the cohort we assessed. Diabetic nephropathy was defined if the subject had long-standing diabetes mellitus with diabetic retinopathy and significant proteinuria. We are, however, aware that some patients with type 2 diabetes with diabetic nephropathy may not have retinopathy. Thus, relying on the presence of retinopathy to diagnose diabetic nephropathy may in fact underestimate diabetes as an aetiology of CRF. Of the 37 cases of CRF, diabetic nephropathy was the cause in 41%. Two other patients had diabetes, but their CRF was due to hypertension in one and renal calculus disease in the other. Designating hypertension as a cause of CRF is somewhat more controversial. We attributed renal failure to hypertension if, before developing CRF, the person had long-standing hypertension along with hypertensive changes in other organs, such as retinopathy or left ventricular hypertrophy. CRF caused by hypertension was found in 22% of the cases; though hypertension as such was present in 70.3% of all cases of CRF. The mean duration of hypertension in the patients in whom the diagnosis was hypertensive nephrosclerosis was 17.05±12.07 years (range 4.2 41.6), compared with 3.9±4.5 years (range 0.08 15) in the patients in whom the causes of CRF were other than hypertension. The prevalence of all diabetes and hypertension (either known or discovered during this study) in persons without CRF was 10.70 and 22.13%, respectively. Chronic glomerulonephritis (CGN) was defined if before the onset of CRF a person had significant proteinuria along with bilateral small sized kidneys (radiological documentation). CRF caused by CGN was found in 16% of the cases. A patient was diagnosed as having tubulointerstitial disease if that patient had no significant proteinuria, clinically evident oedema and a known cause of CRF. Tubulointerstitial disease was found in two cases: one had vesico-ureteric reflux, and the other had a long history of analgesic intake for osteoarthritis. Two cases were found to have ischaemic nephropathy. They were 75 and 80 years old and had renovascular disease with CRF. The cause of CRF in one case was obstructive uropathy due to nephrolithiasis. The remaining three cases did not come for regular followup for assessment of the aetiologies of their CRF. It is important to note that, of the 37 cases, only 10 were aware that they had some sort of renal disease, of whom five knew that they had CRF. Of the 27 persons who were not aware of renal disease, three had histories of oedema, 19 had histories of hypertension, one had a history of renal stone disease and 14 had histories of diabetes mellitus. Again, since this study was not planned to identify aetiologies of CRF, this analysis of the aetiologies of CRF, though it provides some insight, does not indicate the true prevalences of various aetiologies of CRF in the community. In all, hypertension was found in 1122 of the persons studied (22.8%); 765 were known hypertensives and 357 were discovered to be hypertensive during the study. In 61.2% of those who had known hypertension, blood pressure was controlled with drugs; in 38.8% of them it was not controlled. Among the newly diagnosed hypertensives, 5.04% had stage 1 hypertension, and 94.96% had stage 2 and 3 combined. As for diabetes, 8.17% of the subjects were known to have diabetes and were on some medication; in 2.99% diabetes was discovered during the study. Thus, 11.16% (at least) of the adults evaluated in this community-based study had diabetes. Urine examination with dipstick was positive for proteinuria in 208 (4.41%) subjects. Some of them had CRF, hypertension or diabetes mellitus; however, some of them did not have any of those three diagnoses.

Chronic renal failure in Delhi, India 1641 Table 1. The association of dipstick-positive proteinuria and disease Dipstick-positive n CRF HT Diabetes No CRF, HT, proteinuria or diabetes þ 93 2 23 14 54 þþ 59 14 20 15 10 þþþ 35 7 21 7 0 þþþþ 21 7 7 7 0 Total 208 30 71 43 64 HT ¼ hypertension; CRF ¼ chronic renal failure. Table 2. The associations of proteinuria (dipstick test) and disease The numbers in each group are shown in Table 1. Details regarding CRF, hypertension, diabetes and smoking among the subjects who had no proteinuria (dipstick) and those who did are compared in Table 2. Glycosuria was identified with dipstick in 227 (4.82%) subjects. Of these, 86 were known to have diabetes; diabetes was discovered in 140 during this study. One subject was found to have renal glycosuria. Furthermore, our study also revealed that 3.07% of the subjects had a history of renal stone disease. In fact, in two cases, renal stones contributed to CRF: in one as obstructive uropathy, and in another along with diabetic nephropathy. As we did not assess patients for stone disease in this study, we cannot comment on the true prevalence of renal stone disease in our community. Discussion Dipstick-positive Dipstick-negative P-value No. of cases 208 4504 Hypertension 34.1% 16.4% 0.01 Diabetes 20.7% 10.9% <0.001 CRF 14.4% 0.15% <0.001 Smoking 8.1% 5.9% 0.05 CRF ¼ chronic renal failure. CRF and ESRD are among major causes of morbidity and mortality worldwide. Two approaches are adopted for defining the magnitude of CRF. The first is to establish the prevalence of ESRD p.m.p. and the second is to establish the acceptance rate of patients with ESRD for RRT. Since in our country the government does not support the treatment of the majority of these patients, and the majority of patients are not able to afford any form of RRT, the acceptance rate would grossly underestimate the magnitude of ESRD. Furthermore, in India, there is no registry of patients with CRF itself or of patients with ESRD accepted into an RRT programme. Given a health care system quite different from Western ones, finding out the incidence of CRF in India will be very difficult: individual patients do not always go to one specific dispensary, so medical records are fragmented. The only data that we can collect in our country can be on the prevalence of CRF as an indicator of the magnitude of the problem in the community. The present study showed the prevalence of CRF in one community as 0.785%. We could not estimate the glomerular filtration rate in all individuals, in the absence of clinical data, and thus had to depend only on serum creatinine for defining CRF, an approach that has its own limitations. However, because we adopted a higher limit of 1.8 mg% as the cut-off value for defining renal failure, the prevalence of CRF in our study is likely to be an underestimation. The only other study done in India from which such information can be extracted is from South India [5], where the prevalence of CRF was 0.16%, though evidence of renal diseases per se was found in 0.7% of individuals. Other demographic details were not reported on the subjects of this study. Furthermore, this study by Mani had not set out to find the prevalence of CRF, and thus did not include blood samples from all the subjects. Another possible limitation of our study may be that the sample population was taken from one part of one city, and thus it may not be representative of the country. The city of Delhi has a mixed population representing all communities. According to the recent census of India [9], the three major communities in Delhi are the Hindu (83.7%), Muslim (9.4%) and Sikh (4.8%); and the proportion of males is 54.9%. In our study, 84.5% were Hindu, 8.3% Muslim and 5.3% Sikh, and 56.16% were males [95% confidence interval (CI) of males being 54.7 57.5]. Thus, we can conclude with reasonable confidence that our study sample represented the city of Delhi as a whole, though perhaps not the country. Logistically, doing this type of study countrywide is quiet difficult. In our study, the mean age of patients with CRF was 59 years, with 48% being males. This is an important issue if we consider the difference between the aetiologies of CRF determined by other, hospitalbased studies done in India [1 4] and our present results. In the hospital-based studies, the mean age of patients was in the low 40s, and 60 70% were males. However, if we only consider the cases of CRF due to diabetes and hypertension in one of these hospitalbased studies [3], their mean age was nearly 50 years. Also, in the subjects over the age of 40, diabetes and hypertension was present in >55% of cases of CRF, a pattern similar to what we found. In the present study, the mean age of patients with CRF is 59 years, probably because the majority of cases (63%) are due to diabetes mellitus and hypertension, diseases that affect the elderly more than the young. Comparing our study and the one recently mentioned, one of the main reasons for these differences in the age and gender of subjects may be that, in India, more males and younger persons visit hospitals than females and the elderly [4]. Though it was not planned to document the aetiologies of CRF, our study appears to show the Western pattern of CRF with regard to age

1642 S. K. Agarwal et al. and aetiology. Whether this is actually true needs to be answered by a multi-centre study, with a larger sample size, and with specific plans to evaluate the aetiologies of CRF. We do understand the limitations of the way we define diabetic nephropathy and hypertensive nephrosclerosis, based on clinical criteria, but then these are common criteria used by many other studies. They give an idea of the spectrum of aetiologies of CRF in a community. We found hypertension in 22.8% of the urban population we studied. In India, epidemiological studies of hypertension have shown a steadily increasing prevalence [10]. The prevalence of hypertension defined by JNC-V criteria increased steeply from 6.2% in 1959 to 30.9% in 1995. Thus, our results in relation to hypertension look similar to other studies from India. As for diabetes in the Indian population, there is evidence from epidemiological studies that its prevalence has been increasing in the last few decades [11] from 2.1% in 1979 to nearly 12% in 2001. We have shown that the prevalence of diabetes was at least 11% in the urban population we studied, similar to figures found by other studies. With both diabetes and hypertension increasing, the magnitude of CRF/ESRD in India is also likely to increase in years to come. To summarize and conclude, we found the magnitude of the problem of CRF in Delhi to be greater than what had been presumed until now for India as a whole. To elucidate this problem further, a large multicentre study of all geographical areas of the country is required. This is much more relevant today than in the past. Planning for the prevention and strategies for the treatment of CRF/ESRD are becoming key issues for all countries, including India. Acknowledgements. We acknowledge and thank Dr Jesni Joseph, Dr P. Bhuvneshwar and Mr Manoj Kumar for their contributions and tireless fieldwork. This study was funded by the Indian Council of Medical Research, New Delhi. Conflict of interest statement. None declared. References 1. Agarwal SK, Dash SC. Spectrum of renal diseases in India in adults. J Assoc Physicians India 2000; 48: 594 600 2. Mittal S, Kher V, Gulati S, Agarwal LK, Arora P. Chronic renal failure in India. Ren Fail 1997; 19: 763 770 3. Sakuja V, Jha V, Ghosh AK, Ahmed S, Saha TK. Chronic renal failure in India. Nephrol Dial Transplant 1994; 9: 871 872 4. Mani MK. Chronic renal failure in India. Nephrol Dial Transplant 1993; 8: 684 689 5. Mani MK. Prevention of chronic renal failure at the community level. Kidney Int 2003; 63 [Suppl 83]: S86 S89 6. Kher V. End stage renal disease in developing countries. Kidney Int 2002; 62: 350 362 7. K/DOQ1 Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation Classification. Chronic kidney disease as a public health problem. Am J Kidney Dis 2002; 39 [Suppl 1]: S37 S45 8. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Arch Intern Med 1997; 157: 2413 2416 9. www.censusindia.net/results/provindia1.html 10. Gupta R. Hypertension in India definition, prevalence and evaluation. J Indian Med Assoc 1999; 97: 74 80 11. Pradeepa R, Mohan V. The changing scenario of the diabetes epidemic: Implications for India. Indian J Med Res 2002; 116: 121 132 Received for publication: 30.7.04 Accepted in revised form: 8.3.05