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Saudi Journal of Kidney Diseases and Transplantation
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EDITORIAL Table of Contents   
Year : 1997  |  Volume : 8  |  Issue : 4  |  Page : 405-409
The Etiology of End-Stage Renal Disease: Its Implications for the Patient and the Profession

Department of Nephrology, Apollo Hospital, Madras, India

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How to cite this article:
Mani M K. The Etiology of End-Stage Renal Disease: Its Implications for the Patient and the Profession. Saudi J Kidney Dis Transpl 1997;8:405-9

How to cite this URL:
Mani M K. The Etiology of End-Stage Renal Disease: Its Implications for the Patient and the Profession. Saudi J Kidney Dis Transpl [serial online] 1997 [cited 2022 Aug 9];8:405-9. Available from: https://www.sjkdt.org/text.asp?1997/8/4/405/39338
The nephrologist has a simplistic response to end-stage renal disease (ESRD), whatever its cause. Every patient goes on dialysis, peritoneal or hemodialysis, or receives a renal transplant. Why then should we bother with finding out the etiology of the renal disease? Is it just that we feel it is more scientific to put a label on every patient, or does it have greater value to us and to him or her?

Renal replacement therapy is very expensive, and quite beyond the reach of developing countries. Availability of kidneys is limited. The tradition of cadaver organ donation has not been established, and the bulk of transplants are performed from live donors. Not every patient has willing or healthy related donors, and the gap between supply and demand is filled with unrelated live donors. Much has been written and said about the ethics of unrelated live donor transplantation, and I will not go over the arguments again, except to state my personal view that the practice is reprehensible. It amounts to exploitation of the poor, and it militates against cadaver donor programs. In the absence of transplantation, the only alternative is long-­term dialysis. Even the affluent West finds it difficult to pay the never ending cost of dialysis, and is short of kidneys for transplantation. The more efficiently one runs a dialysis program, the longer will patients survive. The number of patients on dialysis continues to grow each year as new patients enter the dialysis pool; also, few leave the program when there are not enough transplants. Thus, the burden of supporting large numbers on dialysis will grow ever heavier. In most Asian and African countries, the cost of a transplant is approximately the amount spent on health and medical relief for more than a thousand of the population in a year. Hence, it is essential that we channel our resources into the prevention of chronic renal failure, and to achieve this a knowledge of its causes is essential.

There are other gains to be made from knowing the etiology of chronic renal failure. Geographical variation may help to identify environmental factors which may play a part in the causation of different diseases, and may help in prevention or even in achieving a cure. Genetic predisposition may be found and may promote understanding of the disease. While no dramatic results have come from this approach so far, the possibilities are endless.

   India: The hard economic facts Top

I will use India as an example of a developing country, to illustrate my thesis. India is a nation of 900 million people, expanding apace. It threatens to overtake China as the most populous country before long, but its rank is 150 among the countries of the world, both in terms of gross domestic product per person and in human development Index [1] . The per capita income in 1995-96 was Rupees (Rs) 9,321/- a year [2] (one US$ = Rs 35.8). The income above which an individual is liable to pay income tax is Rs 40,000/- [3] , and only 1.3% of the population pay tax. The government declared the poverty line to be Rs 1,300/- a year, and no less than 37% of the population was below this level.

The vast majority of the population is dependent on health care provided by the government. The average expenditure on health by all the states of the country works out to Rs 74/- per head per year [4] . This sum covers not just medical relief, but also sanitation, water supply, immunization, and family planning. The central government spent Rs 69/- per head per year, but much more of this was on health and less on medical relief. The average Primary Health Centre spent Rs 30/- per capita per year on medicines and equipment [5] . The cost of renal transplantation must be considered in this perspective. The average cost of a renal transplant at a private hospital is Rs 200,000/- which was the amount spent by the state and the central governments on health and medical relief for 1,400 citizens.

Despite these gloomy figures, renal transplantation is being performed regularly in India. How do the patients pay for it? [6] . Only 4% pay from pooled family resources. About 26% take loans, 30% sell property or jewelry, and 63% take help from their employers or accept charity. The total exceeds 100% because many in the last three categories raise funds in more ways than one. Since the earning of the average Indian is only Rs 9,321/- a year, it is unlikely that the patient would ever earn enough to restore the family wealth. So, a transplant, however successful, invariably leaves the family poorer. Renal transplantation in India must be viewed in this light.

The glamour of medicine lies in the treatment of disease, in taking a patient in desperate condition, and in making him whole again. Transplantation fascinates us, because of all the hype about the gift of life. All over the world, transplant teams and associations of renal patients try to persuade people to donate organs and money for transplant programs. We tend to forget the old adage about the ounce of prevention being worth the pound of cure. It is time we reminded ourselves of this. It would be far, far better for mankind if we could prevent people from going into end stage renal disease, rather than to treat all the renal failure in the world, and this is the importance of knowing the cause of the problem.

   The causes of chronic renal failure Top

Seven diseases are responsible for 96.43% of all the chronic renal failure I see in Madras [Table - 1]. I believe it is important to make a diagnosis in every patient, though it may not be possible to prove it. The criteria on which diagnosis was made are detailed in an earlier paper [7] , in which I presented five years experience encompassing 2028 patients. An objection raised has been that histological diagnosis was not available in all, especially in the large group of chronic interstitial nephritis, in whom the diagnosis was often made late because of the insidious onset of the disease. Not many studies are available in which histological diagnosis was available in the majority of patients, but one is an analysis of autopsy data in 300 patients with chronic renal failure from Chandigarh [8] [Table - 2]. The main difference between this and my presumed diagnosis lies in the large number of patients listed as nephrosclerosis. Diabetic nephropathy, chronic interstitial nephritis, and chronic glomerulonephritis are in approximately the same proportions recorded in my patients. A chi square analysis done of these three diseases in the two reports shows no significant difference between them (x 2 =1.58, p = 0.453). The difference lies in the large number of patients with amyloidosis and nephrosclerosis reported from Chandigarh. It is well known that Chandigarh sees a large number of patients with amyloid, perhaps because it drains an area with very high and poorly controlled tuberculosis, and the real difference lies in the high prevalence of nephrosclerosis.

There is much debate about whether hypertension is a cause of chronic renal failure. Freedman, Iskandar and Appel [9] suggest that patients classified as having hypertensive nephrosclerosis actually have renal parenchymal disease. Many primary renal diseases can lead to hypertension, and the changes wrought by hypertension may mask the original renal disease, so a diagnosis of nephrosclerosis may be made. They go further and suggest that the changes attributed to hypertension may in fact be due to a primary renal vascular disease, and hypertension may be a consequence of this condition. Be that as it may, it has been demonstrated beyond doubt by an excellent prospective randomized clinical trial [10] that "lowering diastolic blood pressure to a range of 81 to 87 mmHg in patients with hypertensive nephrosclerosis is associated with stable or improving renal function in the majority of patients". The actual nature of hypertensive nephrosclerosis, may be, left to the experts. What matters to us is that we can prevent it, or at least keep renal function stable in this condition.

The point that has been well made is that diabetes and hypertension are responsible for a large percentage of chronic renal failure in any country. The United States Renal Data System lists the causes of end­stage renal disease in the USA [Table - 3] [11] . Again you will see that diabetes and hypertension head the list. A total of 40.38% of my patients, 36.11% of those from Chandigarh, and 67.5% of US patients have renal failure attributed to these causes. Good control of blood pressure has been documented to reduce damage to the kidneys and other organs [12] , and to slow down progression in all other renal diseases [13] . The evidence is strong that tight control of diabetes will prevent the development of nephropathy in a significant number of diabetics, and slow down progression in those who already have renal involvement [14] . My proposal is that good control of these diseases from the outset will reduce the burden of renal failure in any society.

   Primary prevention of renal disease Top

Any preventive programme will be worthwhile only if (a) there are diseases in the community which can be effectively prevented, (b) predisposing causes are present in sufficient numbers to be easily detected, and to make a significant difference by neutralizing them, (c) there are measures available to prevent them, (d) the cost of prevention is not excessive and (e) this cost is substantially less than that of treating the established disease.

In a project now in progress, the Kidney Help Trust of Madras, with which I am associated, is attempting to prevent renal disease in a rural community in Tamil Nadu in India. The Government of Tamil Nadu has set up Primary Health Centers each of which cover 25,000 of the population. Patients can report there, and are examined and provided free treatment. In the rural areas, people live in villages of between 1,000 and 3,000 persons, and in hamlets of a few hundred. They may have to travel anywhere up to 15 km across dirt roads and in some cases across open fields to reach the center. It would take them half a day at least to visit the center and return, and they would receive a week's supply of medicine. However, they lose a day's wages, and must meet the cost of their transport by bus. The result is that a person goes to the Primary Health Centre only if he is incapacitated from working. Chronic ailments like diabetes and hypertension which do not cause symptoms are neglected. The only way to treat them is to offer domiciliary care.

In a more affluent society, the problem may not be that of getting to the doctor and being able to afford the cost of medicine, but the reluctance of an asymptomatic person to take medicines which might produce symptoms, that were non-existent before. In either case, there may be need to reach out to the patient rather than to wait for him to go to the doctor. Both hypertension and diabetes are widely prevalent in the community. Ramachandran [15] found the prevalence to be 8.2% in an urban population in India, and the general practitioners of an area of Bombay [16] found that 15.52% of people aged over 20 years in that city had hypertension. The Kidney Help Trust has shown that 3.9% of the rural population has diabetes mellitus and 7% has hypertension, and barely 5% of these patients are on treatment for these diseases. A team of preventive health workers, people drawn from the villages and trained to record blood pressure and test the blood and urine for glucose, administers treatment under the supervision of a doctor who sees the patients once a month, and the Trust hopes to establish good control of hypertension, and reasonable control of diabetes, before long.

Will this effort serve to prevent renal disease? About the changes due to hypertension there is little doubt. We will be able to do some good, both in disease due to hypertension itself, and in all other diseases in which hypertension occurs, which includes the majority of renal diseases. Tight control of diabetes is beyond our means. We hope that some good will come to the patients by at least reducing hyperglycemia, and by control of hypertension. We are unable to afford ACE inhibitors for this project, but there is evidence that other agents including diuretics have some effect [17] .

   Recurrence of the original disease in the graft Top

Another reason why knowing the cause of end-stage renal disease is important is that it might help us to choose the ideal form of renal replacement therapy. A number of diseases have been reported to recur in the graft after transplantation [18],[19],[20] . What is relevant to us is whether this will affect the survival of the graft or the well-being of the patient. While recurrent disease is common, only between 1.5% and 2% of graft failures in adults are attributed to this. However, recurrence is more sinister in children, and causes between 5.6% and 7% of graft failure in them. Grafts from live related donors are especially vulnerable, and glomerulonephritis is especially dangerous [20] . Membranoproliferative glomeruli­nephritis Type II is associated with early recurrence, and progresses to renal failure in 12% to 13% as reported in one large series and more frequently, in some smaller ones [20] . Focal and segmental glomerulosclerosis recurs in 30%, and leads to graft failure within two years in 50% of the cases [20] . Again, children are more severely affected. Primary hyperoxaluria carries the worst prognosis, recurrence being universal, and associated with disastrous consequences to the graft. Special techniques have been described, including early transplantation before the oxalate load builds up in the body, vigorous dialysis before transplantation to deplete the accumulated load, use of pyridoxine to help the break down of oxalate and maintenance of large urine output after transplantation. The best results are reported with simultaneous liver and kidney transplantation, to provide the missing enzyme which will enable the body to metabolize the oxalate.

Other methods of treatment like CAPD and maintenance hemodialysis are better understood and applied these days, and the patient in end-stage renal disease has a meaningful option. He must be given full information about his prospects on each system of treatment, and that can be done only if we know exactly what disease he has. This makes it all the more important for us to establish the diagnosis in every patient. Non­invasive methods are getting better and better, but in many patients there is no substitute for a histological diagnosis. It is imperative that we establish the diagnosis while the disease is still not far advanced, for two reasons. The first and most important is that we must make every effort to cure the disease, or at least to prevent decline to the end-stage. The second is that, along with such decline, the kidney contracts in most diseases, and histological diagnosis will no longer be possible.

   Know your enemy Top

The first step to win a war is to know your enemy well; his strengths and his weak points. Our enemy is disease, and we will be better able to win if we know just what we need to fight against. It is therefore imperative that we document the diagnosis of every one of our patients, so that we can plan our strategy against disease, and make the best use of our resources.

   References Top

1.Living standards. The Economist 1996 July 20;340(7975):94.  Back to cited text no. 1    
2.Real GDP growth slows down by 0.1 pc. Indian Express, Chennai 1997 January 24;pl7.  Back to cited text no. 2    
3.Budget in brief. Indian Express, Chennai 1997, March l;pl.  Back to cited text no. 3    
4.Basic statistics relating to the Indian economy. Volume 2: States. Bombay: Centre for Monitoring Indian Economy, 1991.  Back to cited text no. 4    
5.Anand K, Kapoor SK, Pandav CS. Cost analysis of a primary health centre in northern India. Natl Med J India 1993:6:160-3.  Back to cited text no. 5    
6.Bapat U. A study on the psychosocial aspects of chronic renal failure. A project report for the MA degree in social work. Bombay: Tata Institute of Sciences, 1984.  Back to cited text no. 6    
7.Mani MK. Chronic renal failure in India. Ncphrol Dial Transplant 1993;8:684-9.  Back to cited text no. 7    
8.Sharma BK. Aetiopathogenesis of chronic renal failure. In Shankar PS (ed) Medicine Update Vol 5. Bombay. Association of Physicians of India, 1995;325-30.  Back to cited text no. 8    
9.Freedman BI, Iskandar SS, Appel RG. The link between hypertension and nephrosclerosis. Am J Kidney Dis 1995;25:207-21.  Back to cited text no. 9  [PUBMED]  
10.Toto RD, Mitchell HC, Smith RD, Lee HC, Mclntire D, Pettinger WA. "Strict" blood pressure control and progression of renal desease in hypertensive nephrosclerosis. Kidney Int 1995;48:851-9.  Back to cited text no. 10    
11.US Renal Data System: USRDS 1996 Annual Data Report. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disseases, Bethesda, MD, 1996. Am J Kidney Dis 1996;28(Suppl 2):S42.  Back to cited text no. 11    
12.Rutan GH, Cushman WC. Relative benefits of different antihypertensive drugs in the prevention of vascular complications. Curr Opin Nephrol Hypertens 1995;4;240-4.  Back to cited text no. 12    
13.Zucchelli P, Zuccala A, Gaggi R. Comparison of the effects of ACE inhibitors and calcium channel blockers on the progression of renal failure. Nephrol Dial Transplant 1995;10(SuppI 9):46-51.  Back to cited text no. 13    
14.The effect of intensive treatment of diabetes on the development and progression of long term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-86.  Back to cited text no. 14    
15.Ramachandran A. Genetic epidemiology of NIDDM among Asian Indians. Ann Med 1992;24:499-503.  Back to cited text no. 15  [PUBMED]  
16.Dalai PM, Hypertension study group. Hypertension. A report on community survey for casual hypertension in "old" Bombay: Sir HN Hospital Medical Society, 1980.  Back to cited text no. 16    
17.Rossing P, Hommel E, Smidt UM, Parving HH. Reduction in albuminuria predicts diminished progression in diabetic ncphropathy. Kidney Int Suppl 1994;45:S145-9.  Back to cited text no. 17  [PUBMED]  
18.Michielsen P. Recurrence of the original disease. Does this influence renal graft failure? Kidney Int Suppl 1995;52:S79-84.  Back to cited text no. 18    
19.Ramos EL, Tisher CC. Recurrent diseases in the kidney transplant. Am J Kidney Dis 1994;24(1): 142-54.  Back to cited text no. 19    
20.Davison AM. Renal transplantation: recurrence of original disease with particular reference to primary glomerulonephritis. Nephrol Dial Transplant 1995;10 Suppl 1:81-4.  Back to cited text no. 20  [PUBMED]  

Correspondence Address:
M K Mani
Department of Nephrology, Apollo Hospital, Madras
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