18/05/10

Risk of Death in General Population Independently Predicted by Both Low Kidney Filtration Rate and High Albumin:Creatinine Ratio

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 using a blood test and the other estimates kidney damage using a urine test for protein or albumin. The findings appear in an article published in The Lancet on Tuesday 18th 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 from the London School of Hygiene & Tropical Medicine (LSHTM), University of Southampton and Imperial College London.
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 using a blood test and the other estimates kidney damage using a urine test for protein or albumin.

The findings appear in an article published in The Lancet on Tuesday 18th 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 from the London School of Hygiene & Tropical Medicine (LSHTM), University of Southampton and Imperial College London.

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.

An inexpensive dipstick test was nearly as predictive as ACR for stratifying risk based on albuminuria. The study did not directly compare dipstick testing with the more precise albumin to creatinine ratio in the urine.  However, in countries where only dipstick testing is affordable, the study‘s authors say the less-precise test could be useful for risk stratification.

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.

Dr Donal O’Donoghue the National Clinical Director for Kidney Care commented:

“This important collaborative study demonstrates the value of clinical scientific partnership in the UK supported by MRC and KRUK . The findings are directly relevant to improving vascular health which is our biggest challenge in the NHS “

About

The MRC Assessment study at Older Age was one of the 21 studies contributing to the meta-analysis. The  original study was led by Professor Astrid Fletcher at LSHTM and Professor  Christopher Bulpitt at Imperial College and funded by the Medical Research Council. Secondary analysis of kidney function was funded by Kidney Research UK, and these data were  provided to the collaboration for those at ages beyond 75 years.  Dr Dorothea Nitsch (LSHTM) analysed the data in collaboration with Professor Paul Roderick (University of Southampton).

The publication of this paper will coincide with the annual British Renal Society/Renal Association meeting in Manchester.

Contact:

To interview Paul Roderick, Dorothea Nitsch or Astrid Fletcher, contact Sally Hall sally.hall@lshtm.ac.uk / 0207 927 2073 / 07790 992797 or Gemma Howe gemma.howe@lshtm.ac.uk / 0207 927 2802 in the London School of Hygiene & Tropical Medicine Press Office.

Paul Roderick 07799880014

Dorothea Nitsch 07753414381

Donal O’Donoghue National Clinical Director for Kidney Care 07801834202

Notes for Editors:

Chronic Kidney Disease Prognosis Consortium Participating Investigators/Collaborators:

AKDN Marcello Tonelli, Brenda Hemmelgarn; ARIC Josef Coresh, Brad C Astor, Kunihiro Matsushita, Yaping Wang; AusDiab Robert C Atkins, Kevan R Polkinghorne, Steven J Chadban; Beaver Dam Anoop Shankar, Ronald Klein, Barbara E K Klein; Beijing HaiYan Wang, Fang Wang, Luxia Zhang, Lisheng Liu; CHS Michael Shlipak, Mark J Sarnak, Ronit Katz, Linda P Fried; COBRA Tazeen Jafar, Muhammad Islam, Juanita Hatcher, Neil Poulter, Nish Chaturvedi;  ESTHER Dietrich Rothenbacher, Hermann Brenner, Elke Raum, Wolfgang Koenig; Framingham Caroline S Fox, Shih-Jen Hwang, James B Meigs; Gubbio Massimo Cirillo; HUNT Stein Hallan, Stian Lydersen, Jostein Holmen; MESA Michael Shlipak, Mark J Sarnak, Ronit Katz, Linda P Fried; MRC Older People Paul Roderick, Dorothea Nitsch, Astrid Fletcher, Christopher Bulpitt; NHANES III Brad Astor, Josef Coresh; Ohasama Takayoshi Ohkubo, Hirohito Metoki,  Masaaki Nakayama, Masahiro Kikuya, Yutaka Imai; PREVEND Ron T Gansevoort, Paul E de Jong, Marije van der Velde; Rancho Bernardo Simerjot Kaur Jassal, Elizabeth Barrett-Connor, Jaclyn Bergstrom; REGARDS David G Warnock, Paul Muntner, Suzanne Judd, William M McClellan, Mary Cushman, George Howard, Leslie A McClure; Severance Sun Ha Jee, Heejin Kimm, Ji Eun Yun; Taiwan Chi-Pang Wen, Sung-Feng Wen, Chwen-Keng Tsao, Min-Kuang Tsai; ULSAM Johan Ärnlöv.

KDIGO Guideline Development Process

KDIGO is a global organization, managed by the National Kidney Foundation (NKF), with the mission to improve patient care and outcomes through the development and implementation of evidence-based clinical practice guidelines.

KDIGO employs an evidence-based approach that is modeled on the guideline development process used in the NKF-Kidney Disease Outcome Quality Initiative (KDOQI™) guidelines.  It empowers an independent work group supported by evidence review experts to rigorously examine the published evidence and formulate practice guidelines.  Before they are finalized, the draft guidelines undergo a two-stage review process: internal review by the KDIGO Board, followed by open peer review by interested organizations, agencies and individuals worldwide.  Reviewer comments are carefully reviewed by the work group, and incorporated as appropriate, before the guidelines are finalized and published in Kidney International.