`Early detection of kidney disease is important'

Interview with Dr.A. Vishnu Moorthy.

"India cannot afford to manage its rapidly rising chronic kidney disease (CKD) patients. The best long-term option for the country is to resort to preventive and early detection methods," says Dr. A. Vishnu Moorthy, Professor, Department of Medicine, University of Wisconsin, who was in Chennai recently on a Fulbright Fellowship. According to him, the subject of early diagnosis of kidney disease in India raises three questions: why should we diagnose early? How does one diagnose? And what does one do after diagnosis?

A graduate of Chennai's Stanley Medical College, Dr. Vishnu Moorthy has been on the faculty of the University of Wisconsin's Medical School as a nephrologist since 1977. As a clinician educator, he teaches medical students, internal medicine residents and nephrology fellows.

In 2003-04, on sabbatical from his university, he taught undergraduate and senior medical students at seven medical colleges in Chennai and Vellore in Tamil Nadu and Manipal and Mangalore in Karnataka, where he also lectured large groups of practising nephrologists and primary physicians. He had support from the Fulbright International Scholar Exchange Program and the International Society of Nephrology.

Dr. Vishnu Moorthy lays emphasis on early diagnosis and use of measures to prevent progression of kidney failure. According to him, medical colleges in India do not deal with kidney disease at the undergraduate level. The curriculum covers nephrology selectively, practically ignoring recent developments in early diagnosis and prevention. He feels that the medical students in India are tested more on clinical diagnostic skills and less on laboratory studies or therapeutics. According to him, it is important to address this issue.

Excerpts from the interview he gave Asha Krishnakumar:

What are the reasons for the rising incidence of kidney diseases in India?

Diabetic kidney disease is a worldwide epidemic caused largely by lifestyle changes. People of the Indian subcontinent are more susceptible to diabetes mellitus. Perhaps genetic factors along with lifestyle changes are responsible for the high incidence. WHO [World Health Organisation] estimates are that there will be 57.2 million diabetics in India by 2025; the country will have the dubious distinction of being the diabetes capital of the world.

Why is it important to diagnose CKD early?

CKD is a silent epidemic of the 21st century. Its occurrence is universal; not confined to the developed countries. The numbers afflicted with CKD are going to rise sharply because of the rising incidence of diabetes mellitus and hypertension (two of the major causes of CKD). Now, when patients develop kidney disease, they are managed by renal replacement therapy including haemodialysis, peritoneal dialysis and kidney transplantation. These programmes are also increasingly available in the developing world. Unfortunately, they are not sustainable in the long run due to lack of resources.

Over a million people are on dialysis worldwide, 90 per cent of them in the developed world, which accounts for less than 20 per cent of the world population. So, it is obvious that not all patients in the world have access to renal replacement therapy. That is why early detection of CKD is important.

Despite the effort and expenditure on dialysis, the outcome is not great. The median survival period of patients (aged 55 to 65) on dialysis in the United States today is as low as 2.7 years. This is much less than the outcome of many patients with several kinds of cancer. Kidney transplantation, which is more effective as a renal replacement therapy, is limited by the limited availability of organs. Kidney transplantation is not available in many parts of the world. Hence, it is obvious that early diagnosis and prevention of need for dialysis and transplantation are crucial to prevent CKD fatalities.

Is early diagnosis possible particularly as most often patients tend to meet a nephrologist only when one kidney has failed and the other is working at less than 10 per cent of its capacity? What is your experience in India?

Early diagnosis is possible and prevention of kidney failure requiring renal replacement therapy is feasible. For many patients early diagnosis is actually the difference between life and death.

Information on the incidence and outcome of CKD in India is not available. Unlike elsewhere in the world, there is no end-stage renal disease (ESRD) registry in India. According to information gathered by nephrologists of New Delhi and published in the journal Kidney International in 2002, (Volume 62, page 350), diabetes mellitus is still the main cause of kidney disease in adults in the 40-60 age group. Hypertension accounts for 5 to 15 per cent of the patients.

It is estimated that 100,000 patients develop ESRD every year in India but 90 per cent of them never see a nephrologist. A mere 9,000 are started on haemodialysis every year. But a whopping 60 per cent of them do not come back for dialysis, unable to afford the programme. Nearly 20 per cent of the remaining die because of complications or inadequate dialysis. Some 20 per cent of the patients who consult a nephrologist opt for transplantation from either living related or unrelated donors. Only a small set of patients continues on maintenance dialysis. It is obvious that in India dialysis is not possible for all ESRD patients.

More and more patients are opting for kidney transplantation in India. It is estimated that more than 3,000 transplants are done every year in approximately 100 centres in the country. These are from living unrelated or related donors. Cadaver transplantation is extremely uncommon. Not much of follow-up is available on patients after kidney transplantation. Only a few centres provide post-transplantation information. After kidney transplantation, the patient becomes highly susceptible to infections and the mortality rate varies from 20 per cent to 60 per cent.

Renal replacement therapy is, for the most part, paid by the patients or the family. According to the findings of Dr. M.K. Mani (of Apollo Hospitals, Chennai), published in Kidney International in 2002, it is estimated that haemodialysis in India costs the equivalent of $8,500 a year. Kidney transplantation costs the same amount of money for the first year, but thereafter the annual expense for immunosuppressive medication is up to $3,000 a year. But even these costs are significant and beyond the reach of most patients, when one notes that the per capita income in India in 2000 was only $279. The per capita health expenditure by the Government of India is less than $8. It is unlikely that the government will be able to initiate a programme to support renal replacement therapy. Many nephrologists in India agree that the country cannot afford to treat ESRD.

Thus, it is important to diagnose kidney disease early. Renal replacement therapy, as it is practised today with dialysis and kidney transplantation, is not an option for the large number of patients who are likely to develop ESRD.

How does one diagnose CKD early on?

There are four points I wish to make regarding the early diagnosis of CKD. Early CKD does not cause symptoms. One should routinely evaluate asymptomatic persons who are at high risk for CKD. Adults, especially those in the high-risk group - with strong family history of diabetes, the obese and those with hypertension - should be routinely screened for diabetes and kidney disease.

Serum creatinine and blood urea levels are insensitive markers of kidney dysfunction. Measurement of serum creatinine and estimating the glomerular filtration rate (eGFR) using a formula such as Cockcroft and Gault or the MDRD (Modification of Diet in Renal Disease) is the recommended approach for early detection.

The second approach to detect kidney dysfunction is by urinalysis in high-risk patients. The tests should include a urinalysis and if needed a urine-to-protein/creatinine ratio measurement. In those diabetic patients in whom there is no proteinuria, microalbuminuria is the earliest manifestation of kidney disease.

Lastly, blood pressure should be measured in every adult. Hypertension is also often asymptomatic. Currently persons with a blood pressure higher than 140/90 mm of Hg are hypertensives; most with a systolic blood pressure of 120-140 mm of Hg are said to be pre-hypertensive. The latter should be monitored because they are likely to develop hypertension. In diabetics, the desirable blood pressure is less than 130/80 mm of Hg.

What should be the optimal care of CKD patients so that the disease does not progress?

Once kidney disease develops in a patient, it tends to progress with further loss of kidney function. Several controlled clinical trials have shown effective strategies to prevent progressive kidney damage. These measures are simple and can be instituted by primary care physicians. If necessary, a consultation with a nephrologist, if one is available, may be appropriate.

What are the ways of preventing progression of CKD?

There are eight simple principles that are useful in preventing progression of CKD.

One, early diagnosis of diabetes mellitus, hypertension and other diseases that predispose a person to kidney failure. In high-risk patients early detection is possible by estimating the eGFR and measuring urine protein.

Two, in a diabetic, it is crucial to maintain good glycemic control with therapeutic measures, including weight reduction, dietary management, caloric restriction and use of oral anti-diabetic agents or insulin as necessary. The level of haemoglobin, which should be measured every few months, should be less than seven per cent. Poor glycemic control can cause various complications, including CKD.

Three, control of blood pressure. The blood pressure in a diabetic should be less than 130/80 mm of Hg. This may often be difficult to achieve and will require both dietary measures, such as salt restriction, and multiple medication.

Four, urinalysis and measurement of protein in urine. It has been shown that protein in the urine can further damage the kidney. Patients with greater amount of urinary protein show rapid progression of CKD. Drugs such as angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) are effective in reducing both proteinuria and microalbuminuria and have been shown to preserve kidney function. These drugs should be used in patients with diabetes who have proteinuria even when they have normal blood pressure.

Five, dietary modifications, including salt and caloric restrictions, as well as low fat intake.

Six, monitoring of serum lipids. Elevation in serum lipids is shown to be significantly associated with increased morbidity and mortality in patients with kidney disease. Use of drugs of the group called statins has been effective in lowering the serum cholesterol level and preventing cardiovascular morbidity as also in limiting kidney failure.

Seven, management of anaemia with iron supplements or vitamins and use of erythropoietin (EPO). Correction of anaemia has been shown to lower chances of cardiovascular failure in patients with CKD.

Eight, stopping smoking. Smoking is a significant cause of worsening of kidney failure and cessation of smoking alone can decrease kidney failure by as much as 30 per cent.

If a patient with 50 per cent kidney failure is managed on the basis of these principles, it is possible to slow the progression of the disease and postpone the need for dialysis and transplantation for a considerable period.

If, however, one were to initiate these preventive measures when the patient's kidney disease is not advanced, then it is possible that one can induce remission in kidney failure and preserve their functioning for the lifetime of the patient. This would make the costly and scarce programmes of renal replacement therapy unnecessary.

Is preventing the progression of CKD only the job of nephrologists?

This effort to prevent the epidemic of CKD will require participation of the primary care physicians. Nephrologists would need to provide support for the programme. Education of the practising primary physician will be useful. Also important is to include prevention of CKD in the undergraduate medical curriculum so that those beginning to practice after graduation are able to detect CKD early on and manage it. Community awareness of CKD and the participation of government and non-governmental agencies will also be necessary.

How expensive are early diagnosis methods?

Not very expensive, particularly when compared to the cost of managing the rapid rise in CKD patients.

Based on your observations and the feedback from physicians, what are your suggestions for addressing the problem of CKD?

I have a few suggestions. While these are specific to India, they may well be applicable to any country.

India has an increasing number of patients with Type-2 diabetes. In the urban areas, the percentage of adults with diabetes is 12 per cent. Hypertension is also common. Studies have noted that more than 1 per cent of asymptomatic adults in the rural areas have hypertension. The problem of obesity has increased considerably in the recent years. Cigarette sales, which are declining in the developed world, are actually rising in India. The general population and even the medical community are not sufficiently aware that all this raises the risk of cardiovascular and renal diseases. Methods to raise this awareness in the general population must be initiated and must involve the government as well as local and international NGOs. This effort may be performed in conjunction with cardiology and diabetology physician groups. Educating the general public on a healthy lifestyle is likely to be useful in the long run.

Students leaving medical schools are not sufficiently aware of the extent of the problem of CKD. In medical school they are not taught diagnostic and therapeutic approaches to address this problem. The medical school curriculum has to be modified to include these topics. The Medical Council of India, which has an important role in this process, is the right body to address this issue.

Programmes must be streamlined to emphasise CKD prevention and early diagnosis. Recertification is another possible method to educate practising physicians on the newer approaches to CKD prevention.

The tools for early diagnosis are not routinely used in India. Early diagnosis of CKD involves laboratory studies - such as microalbuminuria in a diabetic, or estimation of eGFR by the MDRD formula. These are not familiar to the educator in Indian medical colleges or to practising physicians. Efforts to subsidise these lab tests must be considered. Laboratory standardisation is critical to ensuring reliability of results. Many physicians are hesitant to use medication which may be nephrotoxic as they are unable to rely on lab results from anywhere expect their own hospitals.

The task of patient education and follow-up must be shared by physician extenders - nurses, nurse clinicians, dietitian, clinical pharmacists and social workers - individually or in groups. As of now they are few and underutilised.

These long-term approaches are likely to be physician-intensive and expensive. But they are likely to yield good results if implemented properly with long follow-up periods. The preventive approach is particularly suited to India where half the population currently is under 25.

Over the past several years the International Society of Nephrology has been very helpful in developing the subspecialty of nephrology in India and other developing countries. At this time to manage the epidemic of CKD all practising physicians and medical students - the physicians of tomorrow - will have to be brought on board. Daunting though it may be, this endeavour is likely to yield rich rewards.