TRANSITIONAL EPIDEMIOLOGY AND THE CHRONIC KIDNEY DISEASE EPIDEMIC

Carmine Zoccali, Reggio Calabria, Italy

Chair: Adrian Covic, Iasi, Romania

Netar P. Mallick, Manchester

Prof C. Zoccali Unità di Nefrologia, Dialisi, Trapianto e Ipertensione OO.RR and CNR Istituto di Biomedicina Laboratorio di Epidemiologia Clinica e Fisiopatologia delle Malattie Renali e dell'Ipertensione Reggio Calabria, Italy

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Slide 1

The topic of my talk today is transitional epidemiology also applied to chronic kidney disease.

Slide 2

This topic is so far away from the clinical practice for what the nephrologists do everyday, so I will take let’s say a broad approach to the topic. I will start by asking the question, how do we approach scientific inquiry? You see questions as related to life sciences are very complex and we try to circumscribe questions and to segment questions. That is we break down the question in a series of small questions whose answers will compose, will hopefully compose and articulate solutions to the original problem. This is very common. This is a very common approach in scientific inquiry. Another approach, an emerging approach is networking questions. That is linking the original questions to a series of inter-related questions. The idea underlying this approach is that complex questions cannot be solved by simplification. We should face complexity but let’s be practical.

Slide 3

Take the case of blood pressure research focused on blood pressure control. Here we have two opposing approaches. You remember the Irving Page approach and the modern approach by Arthur Guyton.

Slide 4

The Irving Page approach is the mosaic approach. According to Page, if we separate problems like we do when we build up a mosaic by adding a tile to another tile, we maybe able to understand the final picture. This approach is called reductionism and the concept of this approach is that knowing the isolated effect of putative causative factors may eventually lead to the full elucidation of disease by combining these separate tiles. The Guyton approach. If we have a variable like the blood pressure and if you know a series of dominant influences on this variable, you can predict the effect but if the set of variables changes, the effects may be exactly the opposite. This is the system analysis by Guyton and you are all familiar with these kind of inter-related graphs by Guyton.

Slide 5

Now, in clinical medicine we focus on the single patient. The patients we have in front. In epidemiology we look at population. Even here you can have the mosaic approach that is an approach like that in hypertension and also a systemic approach.

Slide 6

Let’s start with the mosaic approach. In the mosaic approach we can think to disease as a separate entity, infectious disease, neoplasia, cardiac and vascular events, chronic kidney disease. All these are separate entities. With the systemic approach everything changes. We think to disease as a series of inter-related phenomena. We look at the evolution of disease patterns rather than to the isolated historical trend of a single disease.

Slide 7

Now the founder of global epidemiology is a man from Egypt, Omran. Omran is not a very productive scientist. In all his life he’s published 27 papers in Pubmed. Far less than many of the people that are in the audience. But Omran was eventually successful but it took a very long time for him to be successful. His paper that was published in 1971 remained without any quotation till ‘96 when another epidemiologist Ron LaPorte wrote a paper on him in the British Medical Journal. The paper by Omran started to be quoted and 3 years ago it was re-published by the same journal and thanks to another review, an editorial by Ron LaPorte the interest rose in an exponential manner and now this paper is among the most quoted in epidemiology.

Slide 8

Now with a bit of exaggeration some epidemiologists compare Omran’s work with Darwin’s work. Like Darwin envisaged the evolution of the species, Omran looks at evolution of diseases.

Slide 9

Now, let’s go back to clinical medicine. Let’s see how we conceive disease states in clinical medicine. We conceive disease states as separate entities as I said. In a way we apply what Omran defines as disease channelling, separate entities.

Slide 10

The global approach to epidemiology tries to establish links between the historical trends of disease. In other words, this approach holds that if you are studying the time trend evolution of infectious disease, you should always look at what happens with the other diseases. The pattern, the time pattern of change of this disease.

Slide 11

Now this idea of a global approach to epidemiology is rooted in an initial analysis of human life duration. You see from the year 0 to the middle age to the renaissance years till the start of the last century human life has changed very little.

Slide 12

During the epidemiologic transition it’s not only life duration that changes but also the human phenotype. From a slim pale phenotype to a fat obese phenotype. You know that these phenotypes are associated with chronic conditions like cardiovascular disease.

Slide 13

Now overweight and obesity we know that they are a cluster of risk factors. Behind obesity there is hypertension and there is diabetes and the figures of this epidemic are truly frightening because if we think on a world scale 3 years ago there were 1.6 billion of obese or overweight patients and now the figure is 2.5. Hypertension, there were 1.3 hypertensive patients 4 years ago and it is projected that in 2030 there will be 2.5 billion of hypertensive subjects. But the most frightening epidemic is diabetes. From 120 million at the start of the millennium it is projected that just in 4 years in 2010 there will be 240 million of diabetics.

Slide 14

Now obesity, hypertension and diabetes cause cardiovascular disease but these are also risk factors for renal disease and establish the link between the kidney and the heart. The perverse cardio renal link and we know that eventually the kidney acts as a risk amplifier.

Slide 15

But we are aware that richness in the world is unequally distributed. We have established market economies where the transition epidemiology has completed its course. Life duration is now 75 years but in less developed countries life duration is still 40 years or even less. So the transition in these countries has yet to occur. The disease burden, for this reason, is profoundly different. If you look at chronic disease cancer, lymphoma, cardiovascular disease in market economies, 90% of disease burden is caused by chronic disease while in India and sub-Sahara and Africa the correspondent figures are 30% and 20% and the burden of disease here is represented by infectious transmissible disease.

Slide 16

But in the Western world there are signs that the situation is changing. Coronary heart disease, the tide of that due to coronary heart disease rose till the ‘50s. From the ‘50s on it went down but please note that most of the change occurred within 1950-1970 that is immediately after the Framingham Heart study, a study that prompted primary prevention and after the application of new therapy beta-blockers, ACE inhibitors, aspirin. Before the use of the last marvellous drug, series of drugs, the statins.

Slide 17

Now what about chronic kidney disease? Is there any sign that the mounting tide of chronic kidney disease is changing on a world scale? We have data from the United States Renal Data System. As you can see the prevalence of end-stage renal disease in this database is continually growing, but if we look at incidence rate, the picture is different. Because as you can see between ‘88 and ‘94 the incidence rate rose linearly. Now if we project, if we extrapolate the incidence rate till 3 years ago and compare this extrapolated projection to the actual incidence rate increase, you see that the incidence rate increase was less than expected that means that the tide is relenting.

Slide 18

We have a clear sign, if we look at some particular diseases. For example, diabetes in particularly aged groups. For example in middle aged Caucasian the line is flat starting from the 90s. In African-American the line even starts to decline, starting from ‘96 and an identical trend is demonstrable with hypertensive kidney disease.

Slide 19

The trend is even more convincing with glomerulonephritis, young Caucasian the line was flat for 1990. In African-American the line is declined starting from 1994.

Slide 20

Now we can be in a way reassured by the fact that the incidence rate starts to be less and less but we should always be aware that the prevalence rate is still rising.

Slide 21

We should be aware that behind this kidney and heart disease we have overweight and obesity. You may say we have now the opportunity to prevent this epidemic by treating overweight and obesity but establishing nutrition policies targeted at obesity is not an easy task and recently McClellan commented that the evidence upon which any policy and primary prevention strategy for a kidney disease can be based is sparse to non existent.

Slide 22

We should be aware that policies targeted at nutrition should not be necessarily the same in Europe and in the United States. If we concentrate just in Europe and we look at the prevalence of obesity in various European countries, we get very surprising data. Because in Italy the prevalence of obesity and in France is about 7% but the prevalence is much higher about 5% higher in Belgium, Austria, Germany and Great Britain and almost 3 times higher in the Czech Republic, in Russia, in Latvia and in Hungary. So the challenge posed by this mounting obesity tide and perhaps also risk factors that cluster with obesity is very diverse in European countries and these findings call for nationally and regionally calibrated prevention strategies.

Slide 23

But the most challenging problem remains that of developing countries because in these developing countries the incidence rate of end-stage renal disease is just increasing now and however good the programs of primary prevention and secondary prevention we can put into action, however good these programs can be we will have an increasing tide of end-stage renal disease also in these countries.

Slide 24

It’s time to summarise. The epidemiologic transition is an epochal phase of mankind. Longer life span due to defeat of infectious disease has led to the emergence of chronic disease. Chronic kidney disease is an important element in the much concerning epidemics of chronic disease. The evidence upon which we should base policies and primary prevention strategies for kidney disease, for chronic kidney disease is still very scarce. Longer life in emerging countries will soon create an enormous burden of cardiovascular renal disease in these countries and this is one of the major problems ever faced by mankind.
Thank you for your attention.