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WKD 2011 scientific editorial

World Kidney Day 2011: Protect Your Kidneys, Save Your Heart.

William G Couser, MD
Miguel C Riella, MD

For the Joint International Society of Nephrology (WGC) and International Federation of Kidney
Foundations (MCR) World Kidney Day 2011 Steering Committee*

 Willliam G Couser (ISN), Miguel C Riella (IFKF), co-chairmen. Georgi Abraham, Paul
Beerkens, John Feehally, Guillermo Garcia Garcia, Jan Lantik, Dan Larsen, Philip Li, Mark
Murphy and Bernardo Rodriguez-Iturbe.

Key words: World Kidney Day, kidney, cardiovascular disease, proteinuria, public policy

Correspondence to: Sara Martin <smartin@isn-online.org>

March 10, 2011 will mark the celebration of the 6th World Kidney Day (WKD), an

annual event jointly sponsored by the International Society of Nephrology and the

International Federation of Kidney Foundations. Since its inception in 2006, WKD

has grown dramatically to become the most widely celebrated event associated

with kidney disease in the world and the most successful effort to raise awareness

among both the general public and government health officials about the dangers

of kidney disease, especially chronic kidney disease (CKD).

In 2011, WKD will call attention to the large, and often unappreciated, role played

by kidney dysfunction in increasing premature cardiovascular disease, the most

common cause of morbidity and mortality worldwide (1).

Can a focus on early detection and prevention of kidney disease really improve long

term cardiovascular health? In this editorial, we hope to convey the message that

increased attention to the kidneys can indeed improve long-term health outcomes

by reducing both kidney and cardiovascular disease and should therefore be a

central component of any global health strategy intended to reduce the enormous

and growing burden of chronic NCDs.

2. Cardiovascular Disease and the kidney

30% of all deaths worldwide and 10% of all healthy life lost to disease are

accounted for by CVD alone (1). Although there has been some decline in mortality

from CVD in developed countries, no such decline has been reportedin developing

countries, ethic and socially disadvantaged minority populations or in people with

accompanying CKD (2,3).

The presence of CKD significantly increases the risk of a CV event in both diabetes

and hypertension (4,5). However, less well appreciated is that CKD alone is a strong

risk factor for CVD, independent of diabetes, hypertension or any other

conventional CVD risk factor (6, 7). This is especially true when an increase in

proteinuria, a major target of any CKD screening program, is present (6-9).

The 20-30-fold increase in CVD in patients with ESRD has long been recognized, but

the increased risk for CVD associated with lesser degrees of renal functional

impairment was definitively demonstrated only in 2004. Go et al reported an

independent and graded association between GFR and risk of death, CV events and

hospitalizations was reported in a community-based study of over 1.1 million

individuals (6).

Is this dramatic increase in CVD risk associated with CKD really due to CKD or does it

just reflect the coexistent diabetes or hypertension that are present in a majority of
these patients? The independent effect of CKD alone has now been well

documented in many studies (7), with one study in a high risk population showing

that the risk of cardiac death is increased 46% in those with a GFR between 60 and

90 ml/min and 131% in those with GFR between 30 and 60 ml/min, independent of

traditional CV risk factors including diabetes and hypertension (10). The increased

risk for CV events and mortality in people over 55 with CKD alone is equivalent, or

even higher, to that seen in patients with diabetes or previous myocardial infarcts

(11).Both general (6,12) and high-risk populations (13,14) exhibit an increased risk

of CVD with CKD. This increased risk for CVD is not confined to the elderly – in

volunteers with an average age of 45, the risk for myocardial infarct, stroke and all

cause mortality was doubled in those with CKD (14).

3. Proteinuria and CV Risk

In considering the value of recommending screening for CKDalong with

conventional CVD risk factorsin selected individuals data showing that the risk of

CVD is better correlated with proteinuria (albuminuria) than with GFR alone is

particularly relevant because proteinuria is virtually always a marker of kidney

disease and is not a conventional CVD risk factor (6,8,9,15)

With regard to proteinuria as a predictor of later CVD, The PREVEND study showed

a direct linear relationship between albuminuria and risk of CV death in the general

population even at levels of albumin excretion generally considered within the

“normal” range (15-29 mg/day) and was increased more than 6 fold when albumin
excretion exceeded 300 mg/day (8).

Recent data from the US NHANES database as well as from Japan also document an

independent effect of albuminuria on risk of both CVD and all cause mortality at all

levels of GFR (15,16). In patients with congestive heart failure but without diabetes,

hypertension, increased urinary albumin predicts both CV and all cause mortality

independent of reduced GFR (17). Similar results are obtained studying patients

with coronary disease or previous myocardial infarcts in whom proteinuria

confered a greater risk of mortality than reduced GFR, although both adversely

impacted outcomes (18).

Of interest, not only the likelihood but also the time to development of a CV event

is accelerated significantly by the presence of proteinuria at all levels of GFR (19). In

non-diabetic subjects with normal serum creatinine levels undergoing

percutaneous coronary interventions, about 78% have demonstrable CKD when

screened more stringently for eGFR and urine protein (20). Not only is the presence

of CKD a likely factor in accelerating development of coronary disease in these

patients but it has also been associated with an increase in other risks including

hemorrhagic complications, contrast nephropathy, re-stenosis, and death (10). Thus

multiple studies now confirm that proteinuria is a graded risk factor for CVD

independent of GFR, hypertension and diabetes and that this risk extends down

into ranges of albumin excretion generally considered “normal” (21,22). Moreover,

dipsticks were used to screen for increased protein excretion (6, 18, 23). Although

there has been concern that CKD diagnosed by reduced GFR alone identifies

predominately older adults at increased risk because of age alone (24), the

connection between proteinuria as an independent risk factor for CV mortality has

been confirmed by meta-analysis of 22 separate, general population, cohort studies

and in both older (>65) and younger people of several nationalities and racial

groups (23)

4. Can treatment of CKD reduce CVD?

Finally, and most importantly from a clinical perspective, there is provocative data

to suggest that renal-targeted interventions designed to reduce proteinuria and

slow progression of CKD can reduce CVD risk as well. ACEI and/or ARBs are of

documented benefit in slowing progression of established diabetic and non-diabetic

CKD (25-29). Of interest related to slowing progression, the incidence of CVD in CKD

is significantly higher with more rapid loss of GFR independent of other risk factors,

suggesting that interventions that slow progression may also reduce

CVD.(19).PREVEND IT reported a 40% (but not significant) reduction in CV events

over 4 years in patients screened from a general population with no risk factors

except increased albumin in the urine who were treated with ACEI therapy (30). In

this pilot study, this effect was most notable in people with albumin excretion rates

of >50 mg/day; furthermore, a post hoc cost-effectiveness analysis noted that the
intervention is likely cost effective in that population (31). In the RENNAL study, CV

endpoints were significantly reduced in direct proportion to the reduction of

albuminuria with ACEI therapy in type 2 diabetics, and albuminuria proved to be

the only predictor of CV outcome (32). The potential benefit of renal-targeted

therapies has recently been highlighted by observations that higher doses of renin-

angiotensin system (RAS) blockers than required for BP control alone can further

reduce proteinuria independent of effects on BP or GFR, and that addition of salt

restriction or diuretics, both very inexpensive interventions, can further enhance

the proteinuria-reducing effect of RAS blockade (33,34). Data are not yet available

to establish that screening for CKD and subsequent interventions will reduce CV

mortality and be cost-effective in younger people (<55) (35). However, It is now

known that albuminuria is a better predictor of renal and cardiovascular events

than blood pressure alone, that reducing proteinuria is more renal and cardio

protective than lowering blood pressure alone and that identification of CKD can

improve CV outcomes.

5. Conclusion

As celebrations of the sixth World Kidney Day approach on March 10, 2011, it is

worth noting that prior to the past decade, kidney disease was seen by most

government and public health authorities as largely confined to patients with ESRD,

thankfully a rare condition because the enormous cost of renal replacement

therapy disproportionately consumes scarce health care resources and is well

(36,37). Much has changed. We now appreciate that kidney disease is not rare–

some 10% of the population has evidence of renal dysfunction. And we know these

individuals are not of concern just because a few will progress to ESRD, but more

because they carry a greatly enhanced risk of premature death from CVD, the single

largest and most expensive health care threat we confront at a global level (1). Just

as progress is being made in treating most of the traditional CV risk factors, CKD has

emerged as yet another one that causes substantial vascular toxicity independently.

Fortunately, there is good news as well. Biomarkers of CKD (proteinuria, eGFR) are

easy and relatively inexpensive to detect, and one of these, proteinuria, emerges

early in the evolution of generalized vascular disease. Thus kidney-targeted

detection and prevention programs seem to offer a valuable opportunity to

institute early preventive measures that go beyond traditional cardio-protective

approaches. There is now compelling evidence that including selective screening for

CKD in global health programs designed primarily to reduce CVD will significantly

improve the outcomes of not only renal disease, but especially the NCDs like

diabetes and CVD that dominate future health care strategies. Roadmaps for

accomplishing this have already been presented for both developed (38,39) and

emerging (1,40) countries. However, effective implementation of such strategies

will only come when both the general public and the renal community work

together to convince health authorities it is in the public interest to do this. It is our

sincere hope that worldwide celebration of World Kidney Day 2011 will provide an
opportunity to reinforce the message that kidney disease is indeed common,

harmful and treatable and that protecting your kidneys is an important health

strategy that may save your heart.

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