In the same way that blood cholesterol became widely recognised in the 1980s and 1990s as a marker indicating a major risk of vascular disease, so blood levels of creatinine – a normal breakdown product of muscle metabolism – will tell doctors who is developing kidney disease, now also recognised as a risk for heart disease.

This was the message delivered in Glasgow on 15th July by Professor Jorge Cannata Andia, the President of Europe’s premier meeting of kidney disease specialists, the ERA-EDTA (European Renal Association – European Dialysis and Transplant Association.

Creatinine is normally cleared by the kidneys and excreted in urine, so when levels in blood are higher than normal it can indicate suboptimal functioning of declining kidneys. A further test (glomerular filtration rate) can then confirm if the kidney’s glomeruli cells that filter blood and produce urine are malfunctioning. If kidney disease is not picked up in the early stages, Professor Cannata Andia warned, the disease becomes chronic leading to progressive loss of renal function along with complications of anaemia and an overactive parathyroid gland; two factors which can be difficult to manage in advanced disease and that can ultimately cause severe heart disease. The problem is that kidney damage progresses silently for some time without causing symptoms so tests are needed to alert doctors to the disease’s presence at a time when treatment is most likely to be effective.

Professor Cannata Andia, is a nephrology specialist based at Hospital Universitario Central de Asturias, Oviedo, Spain. Speaking in Glasgow he said: “Chronic kidney disease (CKD) is becoming epidemic in Europe. At least 30 million Europeans are affected.” CKD is a slow and initially asymptomatic loss of renal function caused by numerous factors. He believes the chief cause underpinning the epidemic is nephrosclerosis – the build up of atheroma (fatty plaques) – in renal blood vessels making them stiff and dysfunctional. The process occurs because of high levels of cholesterol in blood, and because of type 2 diabetes and high blood pressure – in other words, the products of an unhealthy lifestyle. “Some people say 40 per cent of the general population have nephrosclerosis beyond middle age,” he noted.

“Serum creatinine will be the cholesterol of the new millennium,” he predicted. “Everyone knows high cholesterol is dangerous but they don’t know that an elevated creatinine is just as dangerous. Measuring it more often may help alert us to the need to act and improve the situation.”

Drugs to help in CKD

New drugs are in development that may help reverse renal dysfunction but other important drugs already available can help protect patients with CKD from dying prematurely of heart disease, said other specialists attending the meeting who want to see treatments started sooner rather than later.

Aranesp (darbepoeitin alfa) is a treatment, produced by the biotechnology company Amgen, stimulating production of red blood cells that carry oxygen via haemaglobin to the body tissues. When kidneys fails they produce less of the naturally occurring hormone erythropoietin that stimulates red blood cell production. Too few red blood cells and therefore insufficient oxygen deprives all parts of the body of energy required to function properly.

Dr Fernando Carrero, a Senior Consultant Nephrologist from Eurodial Clinic, Leiria, Portugal said: “CKD patients often die on the waiting list for dialysis because of heart disease.” He and others believe Aranesp treatment will reduce both fatal and non-fatal heart attacks and strokes. A major study TREAT, involving 4000 patients with CKD and type 2 diabetes, is currently investigating whether Aranesp therapy will reduce deaths and non-fatal heart attacks or strokes.

Another cardiovascular complication of CKD, of major importance, is the result of disruption of the parathyroid gland in the neck caused by a fall in blood calcium levels. This occurs when kidneys are unable to excrete phosphorous properly. Dr Martin Wilkie, Consultant Renal Physician at Northern General Hospital, Sheffield, UK said that when the parathyroid malfunctions, the body is unable to regulate calcium and phosphorous to appropriate levels needed to maintain health. Compensatory mechanisms can mean calcium leaching out of bones leaving them susceptible to fracture and the dumping of calcium in the muscle and valves of the heart and walls of blood vessels, he explained. “The consequences of calcification of the heart and arteries can be catastrophic and lead to a greatly increased risk of death.”

A recently-introduced treatment called cinacalcet HCl, marketed by Amgen as Mimpara or Sensipar, mimics calcium and stops the parathyroid gland from over-producing the hormone governing how much calcium and phosphorous is retained in the bones and the blood, he said. The E.V.O.L.V.E trial (Evaluation Of cinacalcet HCl therapy to Lower cardiovascular Events) announced during the ERA-EDTA meeting is now going to investigate the value of giving cinacalcet HCl to patients on dialysis to see if it protects them from dying of heart disease or developing heart attacks, angina, heart failure or strokes caused by calcification. Of the 3800 patients participating half will get cinacalcet HCl and half, a placebo, on top of the traditional treatment used for these patients.

Earlier smaller studies suggest the treatment is protective. The E.V.O.L..V.E trial will give doctors the answers they need to be sure, said Dr Wilkie. Results are expected in 2011.

Ny: Olwen Glynn Owen