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Cuban Nephrologists Present
Isle of Youth Study at Nephrology 2005

By Gail A. Reed

Dr. Raúl Herrera, Director of Cuba’s Institute of Nephrology, presenting ISYS Phase One at the Congress.

Reporting on what international experts are calling a groundbreaking study for prevention of chronic kidney disease, Cuban nephrologists presented initial findings of the Isle of Youth Study (ISYS) to the 9th Central American and Caribbean Congress on Nephrology and Hypertension (May 14-18, Varadero, Cuba).

ISYS is the "flagship" in a trilogy of Cuban population-based studies aimed at identifying risk markers for chronic kidney disease (CKD), and their association with the development and progression of related conditions such as cardiovascular disease (CVD) and diabetes mellitus (DM). The research is expected to add significantly to information currently available globally, and provide the basis for a nationally applied prevention program in Cuba. ISYS is of particular importance, since it is a longitudinal study in total population, and could thus become the "Framingham" of renal and associated conditions.

"This is a unique study," commented Dr. Giuseppe Remuzzi, chair of the Research Committee of the International Society of Nephrology's Commission for the Global Advancement of Nephrology (COMGAN). "It is important not simply for emerging countries, but equally so for industrialized countries, and for those making health policy decisions in both. The study places Cuba in a unique position to convince the world about the need for prevention."

The International Society of Nephrology (ISN) has called for urgent action regarding preventive strategies to stem the global epidemic of CKD, since research suggests that the one million people worldwide currently in dialysis are just the tip of an iceberg whose underlying mass reaches some 600 million people already suffering from some degree of kidney damage. "This is a disease that can be characterized today as catastrophic for the world population, for health systems and for governments," declared Dr. Raúl Herrera, Director of Cuba's Institute of Nephrology, in his ISYS report to the Congress, "because the epidemic's implications now far surpass the debilitating effects on individuals and families, implying social and economic consequences to be faced by political decision-makers in both developed and developing countries."

ISYS Phase One: Results and Comments

Dr. Herrera, who heads the ISYS team, reported that Phase One of the study - a community-based mass screening in urine for chronic kidney disease markers - is nearly complete. From November 15, 2004 through April 30, 2005 (5-1/2 months), over 90% of the Isle of Youth's total population of 86,614 was screened to determine markers for renal damage.

During this period, 103 family physicians and 115 family nurses applied individual questionnaires and laboratory tests to participants, after obtaining written informed consent. Dipstick urinalysis (Roche Combur-10-Test) was performed initially on all participants, regarding as abnormal results of proteinuria e > 1+ and hematuria e > 1+. If the Combur Test was negative for proteinuria and hematuria, then microalbuminuria dipstick urinalysis (Roche Micral-Test) was performed in risk groups - including those with diabetes mellitus, hypertension, low birthweight antecedent, CKD family history, cardiovascular disease antecedent, pregnancy, obesity, renal disease antecedent, and in children <5 years or persons e > 60 years. Considered abnormal were results of microalbuminuria e > 20 mg/L.

While Phase One will continue until virtually all of the Isle of Youth's population is surveyed, initial findings indicate that over 17% of persons tested so far have positive markers (proteinuria, hematuria, or microalbuminuria) for renal disease, and are now being studied for serum creatinine levels.

Dr. Herrera emphasized that the ongoing research will inform design and implementation of prevention strategies for CKD, but also for related conditions. "Phase One implies early detection of markers for kidney damage leading to identification of epidemiological characteristics and stratification of population for CKD, as well as for cardiovascular disease, diabetes and hypertension," he told the Congress. "This will permit development of comprehensive preventive strategies for these non-communicable chronic diseases that have vascular damage in common."

Drs. John Dirks and Andre Jacques Neusy confer at the Congress in Cuba.

Specialists attending the Congress said they have high hopes for the Isle of Youth Study. "ISYS is a model program for the detection and prevention of chronic kidney disease," noted Dr. Meguid El Nahas, Director of the UK's Sheffield Kidney Institute, who noted that one million people are dying annually from end-stage renal disease. Canadian specialist Dr. John Dirks, Chair of the ISN's Commission for the Global Advancement of Nephrology, told MEDICC Review "(The study's) strong integration of specialists, family doctors, scientists and other health professionals with the community is a truly amazing achievement. Cuba may well replicate what it's done for its people in reduction of infectious diseases with long-term reduction in morbidity and mortality from chronic diseases such as kidney failure. Prevention is a central part of the mindset for the Cuban health system and individual practitioners."

Dr. Andre-Jacques Neusy, Director of New York University Medical School's Center for Global Health, and Chief of Nephrology at New York's Bellevue Hospital, placed the study in the context of the growing momentum to achieve global health equity: "Renal replacement therapy (dialysis and transplantation) is testimony to the failure of health systems. Prevention is the way to go: it is cost effective, and more importantly, will save millions of lives," he said. "In today's world," he told MEDICC Review , "it is unacceptable that someone dies from preventable conditions just because they are poor. This makes global health equity the challenge of the 21st Century. We must learn from the Cubans' experience and from research projects like ISYS, for which they should be congratulated. ISYS is the result of careful planning and also total commitment to improving health."

ISYS Phase One: Opening the Door to Prevention

ISYS' contribution to the evidence base that will inform prevention and treatment will grow over time, but aspects of its design and initial implementation already provide key guideposts:

• ISYS is a study in total population, not a sampling from which results are extrapolated. Thus, it will be the first study in Cuba that actually "photographs" CKD, CVD, hypertension and DM risk markers and development in an entire population group. In addition, the Isle of Youth is a virtual mosaic of the entire Cuban population, having been settled by immigrants from all parts of the main island.
  
  
• ISYS includes all children over one day old (even approximately 1200 under one year old), which allows for recording significant base-line and follow-up information on this vital population group.
  
  
• ISYS uses the family as the basic unit of study, permitting better follow-up of hereditary factors in risk, development and progression of CKD and other chronic diseases sharing the vascular-damage root.
  
  
• ISYS, through the Isle of Youth health system, guarantees treatment for all newly detected patients with CKD or other conditions.
  
  
• ISYS, through the Isle's health system, can lead to the application of a community-based prevention and intervention model covering the whole population.

ISYS Phase One Methodology,
Step by Step

Step One: The protocol. ISYS began in August-September, 2004 with completion of the study's protocol, designed by Dr. Miguel Almaguer at Havana's Institute of Nephrology.

Step Two: Specific training for health professionals. Over 200 health professionals from the Isle of Youth enrolled in small groups in a four-day seminar led by Institute of Nephrology specialists, as a pre-requisite to participate in the study. These included 103 family physicians and 115 family nurses throughout the Isle, as well as public health department personnel, directors and staff at the Isle's three community polyclinics and the Heroes de Baire Hospital, where nephrology services and dialysis are also located. The Hospital also served as headquarters for the study, led locally by Dr. Rafael Aguilera Copello, Chief Nephrologist and his colleague, Dr. José Chipi Cabrera.

Step Three: Public information on the study's aims and benefits was provided through the municipal government and health system; municipal radio, newspaper and television; and local organizations.

Step Four: Home visits were made by family doctors and nurses , to provide more detailed information to families, seek written informed consent, give instructions for collecting urine samples, and make appointments with family doctors to begin the screening.

Step Five: Actions at the family doctor-and-nurse office were undertaken to: register study participants, fill out participant questionnaires, measure height, weight and BP; carry out urinalysis with Combur-10-Test (Roche) measuring density, ph, leukocytes, nitrates, proteins, glucose , ketones, urobilinogen, bilirubin and blood. If negative for proteinuria and hematuria, Micral-Test (Roche) were carried out for microalbuminuria in risk groups. If proteinuria, hematuria or microalbuminuria was positive, then serum creatinine study in blood was indicated.

Step Six: Actions at the community polyclinic , around which family doctor offices are clustered, were taken to: Collect participant questionnaires from family doctor offices; file cumulative reports on questionnaires received and positive urine tests; receive blood samples; obtain sera and transfer to hospital; and implement quality control mechanisms.

Step Seven: Actions at the municipal hospital are being taken to receive and store sera, carry out serum creatinine studies, and inform creatinine values to polyclinics/family doctors.

Step Eight: Project Coordinating Center Actions are being carried out to receive questionnaires from polyclinics, introduce data into database, estimate GFR (Cockroft-Gault and Schwartz formulas), proceed to stratify CKD, calculate body mass index (BMI), classify patients according to BP, and provide this information to polyclinics and family doctors. The University of Informatics Sciences (UCI) in Havana, the municipal Medical Sciences Information Center, and the municipal Polytechnical Informatics School are collaborating in data processing and validation.

When the various phases of the study are completed, the information is expected to yield stratification of the Isle of Youth population for CKD, provide additional insight into related conditions, and inform prevention strategies at every stage of the disease.