World Kidney Day 2010: Diabetic Kidney Disease—Act Now or Pay Later

The Global Threat of Type 2 Diabetes 

The 21st century has the most diabetogenic environment in human history.2, 3 Over the past 25 years or so, the prevalence of type 2 diabetes in the United States has almost doubled, with 3- to 5-fold increases in India, Indonesia, China, Korea, and Thailand.4 In 2007, there were 246 million people with diabetes in the world, but by 2025, that number is estimated to reach 380 million.5 People with impaired glucose tolerance, a “prediabetic state,” numbered 308 million in 2007 and will increase to 418 million by 2025.5 The increase in prevalence of diabetes will be greater in the developing countries. In Mexico for example, 18% of its adult population will have type 2 diabetes by 2025. According to the World Health Organization (WHO), by 2025 China and India will have about 130 million inhabitants with diabetes, who will consume about 40% of their country's health care budget in addition to reducing productivity and hindering economic growth.

It was against this background that on December 21, 2006, the United Nations General Assembly unanimously passed Resolution 61/225 declaring diabetes an international public health issue and identifying World Diabetes Day as a United Nations Day, making diabetes only the second disease after human immunodeficiency virus (HIV)/AIDS to attain that status. For the first time, governments acknowledged that a noninfectious disease poses as serious a threat to world health as infectious diseases like HIV/AIDS, tuberculosis, and malaria. The problems of diabetes are now seen as a major global public health concern, especially in the developing world, which can least afford it. The first step to act on diabetic kidney disease must encompass public health campaigns aimed at preventing the development of type 2 diabetes.

Diabetic Kidney Disease 

Diabetes is now the major cause of end-stage kidney failure throughout the world in both developed and emerging nations.6 It is the primary diagnosis causing kidney disease in 20%-40% of people starting treatment for end-stage renal disease worldwide.7 In Australia, new type 2 diabetes patients starting dialysis increased 5-fold between 1993 and 2007.8 Between 1983 and 2005, there was a 7-fold increase in new patients starting renal replacement therapy in Japan because of diabetes, accounting for 40% of all incident patients.9 Thus, some 30% of the predicted $1.1 trillion medical costs of dialysis worldwide during this decade will result from diabetic nephropathy.10

In the UK Prospective Diabetes Study (UKPDS), the rates of progression of newly diagnosed type 2 diabetic individuals between the stages of normoalbuminuria, microalbuminuria, macroalbuminuria, and renal failure were 2%-3% per year.11 Over a median of 15 years of follow-up of 4,000 participants, almost 40% developed microalbuminuria.12 In the DEMAND (Delapril and Manidipine for Nephroprotection in Diabetes) study of 32,208 people from 33 countries with known type 2 diabetes attending their family doctor, 39% had microalbuminuria and prevalence increased with age, duration of diabetes, and presence of hypertension.13 About 30% of the UKPDS cohort developed renal impairment, of which almost 50% did not have preceding albuminuria.12 Reduced glomerular filtration rate and albuminuria caused by diabetic nephropathy are independent risk factors for cardiovascular events and death.14 Therefore, a strategy to detect early diabetic kidney disease by screening for albuminuria as well as reduced glomerular filtration rate is the second step in taking action on diabetic kidney disease.

An added difficulty to overcome is the remarkable lack of awareness among patients about their condition. In population-based surveys, for every known diabetic patient, there is at least one more that is unknown;15 only 8.7% of the general population were able to identify diabetes as a risk factor for kidney disease.16 For patients with diabetic kidney disease, very few are aware of their condition, with some community surveys putting patient awareness of their disease as low as 9.4%, particularly in those with milder impairment.17 Thus, public education is the third step required for acting on diabetic kidney disease in the community. The IFKF has a long-term goal for all kidney patients worldwide to not only be aware of their disease, but to actively know, for example, their blood pressure and the treatment objectives.

Management of Diabetic Kidney Disease 

There is little use in screening populations or “at risk” groups unless follow-up is undertaken and effective treatment is begun and assessed.18 Fortunately, there is evidence that early therapeutic intervention in patients with chronic kidney disease or diabetes can delay onset of complications and improve outcomes. For example, the UKPDS,19, 20 Steno-2,21 and ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) studies22, 23, 24 all demonstrated that tight control of blood glucose level and blood pressure (and lipids in Steno-2) significantly reduced incidence and progression of diabetic kidney disease. In people with type 2 diabetes, inhibition of the renin-angiotensin-aldosterone system using an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) decreased the progression from normoalbuminuria to microalbuminuria,25 reduced the progression from microalbuminuria to macroalbuminuria,26 and slowed the development of end-stage renal disease.27 Thus the use of an ACE inhibitor or ARB is now standard therapy for patients with diabetic nephropathy as well as glucose, lipid, and blood pressure control. Effective management using evidence-based therapies is the fourth step in tackling diabetic kidney disease.

The fifth step is development of new therapies. Many new agents are now in clinical trials to reduce renal damage and fibrosis, including blockade of formation of advanced glycation end products and other signaling pathways. Other novel agents may potentially prove to be effective in large randomized double-blind clinical trials.28

How Can We Act Now? 

The steps to be taken are clear: campaigns aimed at (1) prevention of type 2 diabetes, (2) screening for early diabetic kidney disease, (3) increasing patient awareness of kidney disease, (4) using medications of proven strategy, and finally (5) researching and trialing of new therapies. The ultimate challenge is to get action from primary health care to all higher levels—from the individual patient to those at risk—in various health jurisdictions and in all countries despite varying economic circumstances and priorities. The problem is a global one and yet requires action at a local level: prevention screening and treatment strategies; education, including increasing awareness both in diabetic patients and those at risk of developing diabetes; and health priorities and governments. Basic research and clinical trials searching for a new understanding and therapies must be supported.

The United Nations, as noted earlier, recognized the importance of diabetes in 2006 by establishing a World Diabetes Day. Both the ISN and the IDF are working closely with the WHO to provide increasing understanding of the challenge that diabetic kidney disease poses to world health and health care budgets. However, World Kidney Day also provides a focus for other international agencies, government ministries of health, nongovernmental organizations, foundations and academic institutions to come together with national kidney foundations to be involved in the effort to prevent and manage diabetic kidney disease.

The ISN, through its Commission for the Global Advancement of Nephrology (COMGAN) Research and Prevention Committee, has developed a web-based program called KHDC (Program for Detection and Management of Chronic Kidney Disease, Hypertension, Diabetes and Cardiovascular Disease in Developing Countries)29 as a global template involving a detection management and data assessment program. The program has so far screened some 42,000 people in 25 developing countries and the data are being stored and analyzed at the Kidney Disease Data Center at the committee headquarters at the Mario Negri Institute in Bergamo, Italy. This program can be tailored to any individual country's needs and resources. The IFKF also has a program initiated by the National Kidney Foundation in the United States called the Kidney Early Evaluation Program (KEEP), which is a screening program for people at high risk of kidney disease. KEEP has now been implemented in many countries and will again screen and manage patients with diabetic kidney disease.

The focus on diabetic kidney disease for World Kidney Day 2010 brings awareness of the magnitude of the problem and ramifications for global health for people with diabetes and kidney disease. It is therefore time to act and act urgently. It is time for strategies that prevent diabetes and its sequelae. It is time for programs for health care workers to diagnose and treat people with diabetic kidney disease. It is time for governments to pass legislation to enable the diabetes pandemic to be controlled. After all, diabetic kidney disease, like the epidemics of infectious diseases that have long dominated public health agendas, is potentially preventable. Indeed, March 11, 2010 is time to act on diabetic kidney disease and to sustain that action long after World Kidney Day.