Tuesday, 18 May 2010

STOP PRESS: Raised urinary albumin predicts death

Two simple tests of kidney function and damage predict total and cardiovascular mortality risk in a wide range of populations according to a systematic analysis of 21 studies including more than 1.2 million participants in Europe, USA, Australia and Asia. One measure estimates the kidneys’ filtration function (the eGFR) using a blood test and the other estimates kidney damage using a urine test for protein or albumin (the ACR ).

The findings appear in an article published in The Lancet on Tuesday 18 May, written by academics from the Chronic Kidney Disease Prognosis Consortium established last year by Kidney Disease: Improving Global Outcomes (KDIGO), which includes UK collaborators Dr Dorothea Nitsch from the London School of Hygiene & Tropical Medicine (LSHTM), and Professor Paul Roderick from the University of Southampton who is also a member of the Renal Advisory Group for the Renal National Service Framework at the Department of Health .
Chronic kidney disease (CKD) is recognised as a major global public health problem. The disease affects 10–16% of the adult population in Asia, Australia, Europe and the USA and increases the risk of all-cause mortality, cardiovascular disease and progression to kidney failure which may need costly dialysis of transplantation, even after accounting for traditional risk factors such as hypertension and diabetes. The prevalence of chronic kidney disease is increasing worldwide with the global obesity epidemic and as populations age. This is of particular importance in low and middle income countries who face an increasing burden of non-communicable disease .

The new findings are part of a comprehensive effort to refine the definition and staging of chronic kidney disease. Current guidelines from the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) define chronic kidney disease based on the presence for greater than three months of either: (1) estimated kidney filtration function below 60 ml/min/1·73 m2 (approximately half the level in a young healthy adult) or (2) kidney damage most commonly detected by protein in the urine (the most sensitive test is an albumin-creatinine ratio (ACR) of 30 mg/g or greater).

Staging aims to categorize the severity of an illness to help in guiding treatment. Based on the large amount of data analyzed, the study confirmed earlier suggestions that adding information about the level of protein in the urine can improve the current staging system for chronic kidney disease, which centers on the kidney’s filtration function. The level of protein in the urine added information about the risk of mortality at all levels of kidney function.

Kidney filtration function was unrelated to mortality risk in the 75-105 ml/min/1•73 m2 range; a reduction to 60 was already an independent risk factor for total and cardiovascular mortality with 18% increased risk of mortality, rising to over 50% increased risk at eGFR level 45 and the risk increased threefold at an estimated filtration rate of 15 ml/min/1•73 m2, when people often need dialysis.

Mortality risk also increased progressively with increasing albumin in the urine starting at the lowest levels. The risk of mortality was elevated by approximately 50% at 30 mg/g albumin to creatinine ratio, the threshold for defining chronic kidney disease, and rose to more than four-fold at high levels of albuminuria (1 gram/g) compared to an optimal level of 5 mg/g. Even people with high normal levels of albumin in the urine were at statistically significantly greater risk of mortality than people with low (optimal) levels of albumin in the urine.

Measurement of urinary albumin creatinine ratio is now part of the Chronic Kidney Disease domain of the primary care quality outcomes framework in the UK and is becoming a fundamental part of assessing cardiovascular risk and risk of progressive kidney disease in this population .

The authors found that kidney filtration and measures of urine albumin/protein acted independently and multiplied risks of mortality, confirming that both urine and blood measurements are needed together to fully capture the mortality risk that is associated with chronic kidney disease.

Data presented in this meta-analysis confirm beyond any doubt that the current thresholds are indicative of increased all-cause and cardiovascular mortality risk,” Roberto Pontremoli of the University of Genoa in Italy and his colleagues write in a Comment accompanying the article. They go on to say that this sort of testing, while it bears “powerful prognostic value,” remains “largely underused in risk calculators as well as in daily clinical practice,” “These results indicate that the kidney may provide useful information about our future health. Therefore, they will hopefully promote greater use of renal function parameters in clinical practice aimed at global risk assessment.”Kidney Disease: Improving Global Outcomes (KDIGO) has already appointed a workgroup to develop a revised global chronic kidney disease guideline.