Dr Rajendra Prasad Mathur MD, DM, FICP, ISN Scholar Seniour consultant & HOD, Batra hospital Heart and Kidney: Protect Your Kidneys to Save Your Heart

Overview CKD – Global and Indian scenario World Kidney Day CVD and Kidney Proteinuria and CVD Treatment of CKD reduce CVD risk Conclusions

Now we know why the titanic sank !!

CKD – A scary Challenge for Us all !! CKD – Chronic kidney disease

CKD – A Silent Killer CKD – Increased DeathCKD at a glance CKD – A Global Pandemic CKD 1-2 are asymptomatic Third after CVD, Cancer 1 in 10 Indians have CKD 10 million people of CKD Term ‘CRF’ no longer used Dialysis ↑ death rate 100 x Small ↑ in Creat - ↑ ↑ in CV

ESRD versus Total CKD ESRD - end-stage renal disease

Global profile of ESRD

India: Kidney disease burden India is the world’s largest democracy with a population of around 1.13 billion and faces tremendous challenges to provide basic healthcare for its masses The incidence rates of ESRD in India 232 per million population (age adjusted rate) NDT Plus 2010; 3: 203–207

India: Kidney disease burden The Indian CKD registry is an initiative by the Indian Society of Nephrology, and out of the latest total of CKD patients, (74.5%) amongst the CKD patients were not receiving any form of RRT (renal replacement therapy) and only 880 (2.5%) received renal transplantation (RT) It is estimated that >90% of patients with ESRD in South Asia die within months of diagnosis because they cannot afford treatment NDT Plus 2010; 3: 203–207

World Kidney Day World Kidney Day (WKD) Annual event jointly sponsored by the International Society of Nephrology and the International Federation of Kidney Foundations, Inception in 2006 Being celebrated 2 nd Thursday every March Nephrol Dial Transplant 2011;26: 395–398

World Kidney Day World Kidney Day (WKD) 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) Nephrol Dial Transplant 2011;26: 395–398

World Kidney Day 2011 Theme World Kidney Day (WKD) This year on 10 th March, 2011 WKD was celebrated with theme Protect Your Kidneys, Save Your Heart Nephrol Dial Transplant 2011;26: 395–398

Kidney disease is common, harmful and treatable

Cardiovascular disease (CVD) and the kidney CVD The most common of the chronic non-communicable diseases (NCDs) that impact global mortality About 30% of all deaths worldwide and 10% of all healthy life lost to disease are accounted for by CVD alone Nephrol Dial Transplant 2011;26: 395–398

CVD and kidney The presence of CKD significantly increases the risk of a CV event in both diabetes and hypertension 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 factors This is especially true when an increase in proteinuria, a major target of any CKD screening programme, is present Nephrol Dial Transplant 2011;26: 395–398

CVD and kidney 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 Study by Go et al, published in NEJM Nephrol Dial Transplant 2011;26: 395–398

CVD and kidney Go et al Study Methods: Estimated the longitudinal GFR among 1,120,295 adults within a large, integrated system of health care delivery in whom Serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation Examined the multivariable association between the Estimated GFR and the risks of death, cardiovascular events, and hospitalization N Engl J Med 2004;351:

CVD and kidney Go et al Results N Engl J Med 2004;351:

CVD and kidney Go et al Results N Engl J Med 2004;351:

CVD and kidney Go et al Results N Engl J Med 2004;351:

CVD and kidney Go et al Conclusions An independent, graded association was observed between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization in a large, community based population These findings highlight the clinical and public health importance of chronic renal insufficiency N Engl J Med 2004;351:

CVD and kidney 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 is present in a majority of these patients? The independent effect of CKD alone has now been well documented in many studies J Am Soc Nephrol 2006; 17: 2034–2047

CVD and kidney The risk of cardiac death is increased (46%) in people with a GFR between 30 and 60 mL/min (stage 3 CKD) Independent of traditional CV risk factors including diabetes and hypertension J Am Soc Nephrol 2008; 19: 158–163

CVD and kidney The increased risk for CV events and mortality in people >55 years with CKD alone is equivalent, or even higher, to that seen in patients with diabetes or previous myocardial infarcts Am J Cardiol 2008; 102: 1668–1673

CVD and kidney Both general * and high-risk populations ** 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 *N Engl J Med 2004; 351: 1296–1305, Am J Kidney Dis 2008; 51: S38–S45 **Arch Intern Med 2007; 167: 1122–1129 Am Heart J 2008; 156:277–283

Kidney dysfunction increases the risk of cardiovascular disease significantly

Proteinuria and CV risk In considering the value of recommending screening for CKD along with conventional CVD risk factors in selected individuals, the data showing that The risk of CVD is better correlated with proteinuria (albuminuria) than with GFR alone are particularly relevant because Proteinuria is virtually always a marker of kidney disease and is not a conventional CVD risk factor Nephrol Dial Transplant 2011;26: 395–398

Proteinuria and CV risk With regard to proteinuria as a predictor of later CVD, The PREVEND study showed A direct linear relationship population even at levels of albumin excretion generally considered within the ‘normal’ range (15–29 mg/day) and was increased >6-fold when albumin excretion exceeded 300 mg/day Circulation 2002; 106: 1777–1782

Proteinuria and CV risk 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 In patients with congestive heart failure but without diabetes, hypertension or reduced GFR, Increased urinary albumin predicts both CV and all cause mortality Nephrol Dial Transplant 2011;26: 395–398

Proteinuria and CV risk Similar results are obtained studying patients with coronary disease or previous myocardial infarcts in whom Proteinuria conferred a greater risk of mortality than reduced GFR, Although both adversely impacted outcomes BMJ 2006; 332: 1426

Proteinuria and CV risk 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 Nephrol Dial Transplant 2011;26: 395–398

Proteinuria and CV risk In non-diabetic subjects with normal serum creatinine levels undergoing percutaneous coronary interventions, ~78% have demonstrable CKD when screened more stringently for renal function (eGFR and urine protein) 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 haemorrhagic complications, contrast nephropathy, re-stenosis and death Nephrol Dial Transplant 2011;26: 395–398

Proteinuria and CV risk Thus, multiple studies now confirm that Proteinuria is a graded risk factor for CVD independent of GFR, hypertension and diabetes, and This risk extends down into ranges of albumin excretion generally considered ‘normal’ This increased CV risk has been well demonstrated in several studies where only dipsticks were used to screen for increased protein excretion Nephrol Dial Transplant 2011;26: 395–398

Get your blood pressure checked, blood and urine tests done for early detection of kidney dysfunction

Can treatment of CKD reduce CVD? Finally, and most importantly from a clinical perspective, There are provocative data suggesting that Renal-targeted interventions designed to reduce proteinuria and slow progression of CKD can reduce CVD risk as well Nephrol Dial Transplant 2011;26: 395–398

Can treatment of CKD reduce CVD? Angiotensinconverting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) are of documented benefit in slowing progression of established diabetic and non-diabetic CKD Lancet 1999; 354: 359–364 Lancet 1998; 352: 1252–1256 Lancet 1997; 349: 1857–1863 N Engl J Med 2009; 361: 1639–1650

Can treatment of CKD reduce CVD? 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 JAm Soc Nephrol 2009; 20: 2617–2624

Can treatment of CKD reduce CVD? A 44% reduction in CV mortality over 4 years has been reported in patients screened from a general population with no risk factors except increased albumin in the urine and treated with renal-targeted ACEI therapy This effect was seen primarily in people with albumin excretion rates of >50 mg/day in a pilot study, and the Intervention was shown to be cost-effective in that population Circulation 2004; 110: 2809–2816 Clin Ther 2006; 28: 432–444

Can treatment of CKD reduce CVD? CV end points were significantly reduced in direct proportion to the reduction of albuminuria with ACEI therapy, and Albuminuria proved to be the only predictor of CV outcome Other studies have also demonstrated that Changes in proteinuria (in diabetics) better predict outcomes than changes in blood pressure (BP) achieved with ACEI therapy Nephrol Dial Transplant 2011;26: 395–398

Can treatment of CKD reduce CVD? 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 Addition of salt restriction or diuretics, both very inexpensive interventions, can further enhance the proteinuria-reducing effect of RAS blockade Nephrol Dial Transplant 2011;26: 395–398

Can treatment of CKD reduce CVD? Data are not yet available to establish that Sscreening for CKD and subsequent interventions will reduce CV mortality and be cost-effective in younger people (<55 years) It is now known that Albuminuria is a better predictor of renal and cardiovascular events than blood pressure alone, Reducing proteinuria is more renal and cardio-protective than lowering blood pressure alone and Identification of CKD can improve CV outcomes Nephrol Dial Transplant 2011;26: 395–398

Don’t treat Diabetes, to your kidneys. Untreated diabetes can lead to kidney diseases. Protect your kidney, control diabetes

Physicians and Nephrologist in Management of CKD

How to handle CKD ? A A1c < 6.5, ACEi, ARBs BBlood pressure < 125/75 CCholesterol LDL < 100 DDrugs – avoid nephrotoxicity Diet – Moderate in protein Na, K, Ph, Fluids, Cal

CKD – Management Strategy 1. Decrease Cardiovascular Risk 2. Arrest or slow progression to ESRD 3. Manage complications – 1. Anemia (Normocytic normochromic) 2. Bone loss (Renal osteodystrophy)

CKD – Management Goals 1. Blood pressure < 125/75 HT is both a cause and consequence 2. Glycemic control – Hb A1c < Hemoglobin level > 11 g% 4. Calcium x Phosphorous product < 50 Normal values : GFR 120 to 150 ml/min/1.73m2 Ca 9 to10.5mg%, Ph 3 to 4.5mg%, Ca x Ph < 50 iPTH 150 to 300 pg/ml

Early treatment makes a difference in CKD Brenner, et al., 2001

CKD death Stages in Progression of Chronic Kidney Disease and Therapeutic Strategies Complications Screening for CKD risk factors CKD risk reduction; Screening for CKD Diagnosis & treatment; Rx. comorbid conditions; ↓ progression Estimate progression; Rx. complications; Prepare for replacement Replacement by dialysis & transplant Normal Increased risk Kidney failure Damage  GFR

Stage-wise management of CKD Stage 0 Test for CKD, Management of Risk Factors Stage 1 Manage co-morbidity, Rx. of CVD and RF Stage 2 Slow rate of loss of Kidney function - ACEi Stage 3 Prevent Anemia, Bone effects, Ca x Ph Stage 4 Preparation for RRT; refer to nephrology Stage 5 RRT – PD, HD or RT – Donor / Cadavre

Conclusions 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 healthcare threat we confront at a global level

Conclusions 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. Bio markers of CKD (proteinuria and eGFR) are easy and relatively inexpensive to detect, and one of these, Proteinuria, emerges early in the evolution of generalized vascular disease.

Conclusions There is now compelling evidence that including Selective screening for CKD in global health programmes designed primarily to reduce CVD will significantly improve the outcomes of not only renal disease but especially also the NCDs like diabetes and CVD that dominate future healthcare strategies Kidney-targeted detection and prevention programmes seem to offer a valuable opportunity to institute early preventive measures that go beyond traditional cardioprotective approaches

Conclusions Kidney disease is indeed common, harmful and treatable and that Protecting your kidneys is an important health strategy that may save your heart

Let this not happen please! Normal ESRD