Currently, the prevalence of CKD in the US adult population was 11% (19.2 million). By stage, an estimated 5.9 million individuals (3.3%) had stage 1 (persistent albuminuria with a normal GFR), 5.3 million (3.0%) had stage 2 (persistent albuminuria with a GFR of 60 to 89 mL/min/1.73 m 2 ), 7.6 million (4.3%) had stage 3 (GFR, 30 to 59 mL/min/1.73 m 2 ), 400,000 individuals (0.2%) had stage 4 (GFR, 15 to 29 mL/min/1.73 m 2 ), and 300,000 individuals (0.2%) had stage 5, or kidney failure. Interestingly, between stages 2 and 3/ AND 4, patients are dying mostly from CV disease. And we will spend some time talking about risk factor modification in order to improve survival in CKD patients shortly.
This rise in ESRD is depicted in the graph. The X axis is # of new patients and the y axis is time in years. You can see that while HTN and glomerulonepritis, each causes of CKD are remaining stable, Diabetes—the #1 cause of ESRD is increasing. And this is fueling the rise in ESRD patients. The end-stage renal disease (ESRD) population in the United States continues to increase. While the incidence of ESRD was approximately 45,000 in 1989, the number of new ESRD patients almost doubled to over 80,000 by 1998. Incident counts are projected to rise to almost 173,000 by 2010. This means the total number of ESRD patients in 2010 could reach over a half million, a 77% rise in prevalence. Diabetes mellitus is the primary etiology of ESRD in the United States, and the number of new ESRD cases due to diabetes has increased more rapidly than for any other diagnosis. For example, incidence of diabetes in hemodialysis patients rose by 9.0% between 1990 and 1994 and by 9.9% between 1994 and 1998. Diabetes accounted for over 43.1% of new cases of ESRD in 1994 through 1998. The second most frequent primary etiology of ESRD is hypertension, which occurred in 27.3% of new ESRD cases from 1994 to 1998. Other primary diagnoses, including g lomerulonephritis and polycystic kidney disease, occur in far smaller numbers of people. Reference: US Renal Data System. 2000 Atlas of ESRD in the United States . Bethesda, Md: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; 2000.
CVD mortality is 10 to 30 times higher in patients treated by dialysis than in patients in the general population, despite stratification for sex, race, and the presence of diabetes.6 After stratification for age, CVD mortality remains 5-fold higher in dialysis patients than in the general population, even at the extremes of age (Figure 1). The high mortality rate is likely due to both a high case fatality rate and a high prevalence of CVD.
Complications associated with chronic kidney (CKD) disease arise earlier in the course of the disease than is appreciated by many physicians. These sequelae are often interrelated. Complications of chronic renal insufficiency (CRI) arise early and progress in concert with the underlying disease. Reference : Zabetakis PM, Nissenson AR. Complications of chronic renal insufficiency: beyond cardiovascular disease. Am J Kidney Dis . 2000;36(suppl 3):S31-S38.
Haemoglobin (Hgb) levels are known to be associated with numerous adverse outcomes in both chronic kidney disease (CKD) and non-CKD patients. This analysis evaluates the association of baseline haemoglobin levels on survival in CKD patients, who are followed by nephrologists, irrespective of glomerular filtration rate (GFR), prior to initiation of renal replacement therapy (RRT) and erythropoietin hormone replacement therapy. Analysis of data from the provincial database (PROMIS, Patient Registration and Outcome Management Information System) in British Columbia, Canada, was undertaken. Records used for the analysis included all CKD patients at first registration: GFR <60 ml/min/1.73 m(2), not yet on dialysis, starting from May 1998 to October 2002, and who had complete data (defined as age and gender, diabetic status, eGFR and Hgb levels). The primary objective of this study was to determine the association of Hgb and survival controlling for eGFR at first registration value, age, gender and diabetic status. Multivariate Cox proportional hazards analysis with time to death as outcome variable was performed. The cohort included 3028 patients: the mean age was 65 years, 28% were diabetic, and the mean eGFR in the cohort was 21 ml/min/1.73 m(2). The cohort is representative of the BC CKD and dialysis population regarding ethnicity: 64% Caucasian, 32% Asian. Median follow-up was 27 months, 1 year survival was 0.92, 2 year survival was 0.85. Hgb at initial registration is a statistically independent predictor of survival (RR = 0.875 for every 10 g/l, 95% CI: 0.835-0.917, P = 0.0001), after adjusting for age, gender, diabetic status and baseline eGFR. Further analysis, controlling for RRT, demonstrated a similar association between Hgb and survival (RR = 0.853 for every 10 g/l, 95% CI: 0.799-0.910, P = 0.0001), after adjusting for above variables. Substantial variation in Hgb values exists at all GFR levels. These findings underscore the importance of evaluating Hgb at all GFR levels, and the need to study the impact of modification of Hgb at different GFR levels on survival.
And the reason for this is on slide. There are many things that affect the production and elimination of creatinine, which is both filtered and secreted in the kidney. GFR CrCl in normal individuals and patients with mild CRI The relationship between serum creatinine and GFR is affected by the generation and extra-renal excretion of creatinine, as well as the filtration and secretion of creatinine by the kidney. Numerous factors can affect serum creatinine concentration including reduced muscle mass, malnutrition, drugs (such as trimethoprim, cimetidine, and some cephalosporins) and, of course, kidney disease. Ideally, GFR should be measured by determining the clearance of a substance that is freely filtered through the glomerular capillary wall, that is biologically inert, and that is neither secreted nor reabsorbed by the tubules. Inulin possesses all of these qualities and is the substance most widely used as an ideal marker for determining GFR in research laboratories. In this cross-sectional study, 171 patients with glomerular disease were evaluated using 3 true filtration markers of graded size (diethylenetriamine-penta acetic acid [DTPA], dextran, and inulin) to determine the reliability of creatinine as a measure of the GFR. This graph demonstrates that creatinine clearance (CrCl) is maintained in a normal or near-normal range despite reductions in GFR (as measured by inulin concentration). The CrCl is maintained in the normal range by an absolute increase in the rate of creatinine secretion. The enhancement of CrCl by this significant secretory component blunts the elevation of serum creatinine concentration even after glomerular disease has reduced GFR to very low levels. This study therefore demonstrates that serum creatinine is an unreliable means of evaluating kidney function.
Clinical Decisions in Elderly Patients with ESRD
Clinical Decisions in Elderly Patients with ESRD Donna S. Hanes, M.D., F.A.C.P. Associate Professor of Medicine Director, Internal Medicine Clerkship and Senior Rotations Medical Director, Chestnut Dialysis Unit ACP February 2008
Disclosures <ul><li>No financial or other conflicts of interest </li></ul>
CKD: An Epidemic Coresh et al. AJKD 2003. 41; 1-12. 5.9 0.3 0.4 7.6 5.3 Stage 5 Stage 4 Stage 3 Stage 2 Stage 1 Millions of individuals (19.2)
US Renal Data System. 2000 Atlas of ESRD in the United States. 0 20,000 40,000 60,000 80,000 100,000 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 All ESRD Diabetes Hypertension Glomerulonephritis Incidence of New Patients
CV Mortality in the General Population and in Patients with Kidney Failure Annual Mortality (%) GP Male GP Female GP Black GP White Dialysis Male Dialysis Female Dialysis Black Dialysis White Transplant 100 10 1 0.1 0.01 25 – 34 35 – 44 45 – 54 55 – 64 65 – 74 75 – 84 > 85 Age (years) 0.001 Sarnak, MJ et al. Hypertension 2003; 42: 1050-1065 .
Octogenarians and Nonagenarians Starting Dialysis <ul><li>Incident dialysis patients 13,577 </li></ul><ul><li>57% increase over 6 years </li></ul><ul><li>One year mortality 46% </li></ul>Kurella, Ann Intern Med 2007
Survival Rates <ul><li>Age 40 to 44 </li></ul><ul><li>Age 60 to 64 </li></ul><ul><li>Age over 65 </li></ul><ul><li>7 to 11 years </li></ul><ul><li>4 to 6 years </li></ul><ul><li>5 year survival of 15% </li></ul>
Guidelines for Withholding Care <ul><li>Permanently unconscious </li></ul><ul><li>Severe dementia </li></ul><ul><li>Severe mental disability </li></ul><ul><li>Death imminent within 60 days </li></ul><ul><li>End stage disease confined to bed </li></ul><ul><li>Unremediable pain </li></ul><ul><li>Hospitalized patients with MOF </li></ul>
Withdrawal of Dialysis – Third Leading Cause of Death <ul><li>Shared decision making </li></ul><ul><li>Informed consent </li></ul><ul><li>Estimate prognosis </li></ul><ul><li>Advanced directives </li></ul><ul><li>Time limited trials </li></ul><ul><li>Palliative care </li></ul>RPA/ASN
Special Considerations in the Elderly <ul><li>12 to 20% PCPs (and 9% nephrologists) believe there should be an age limit </li></ul><ul><li>Ninety percent less likely to be offered dialysis </li></ul><ul><li>Advanced Directives </li></ul><ul><li>Dialysis modality </li></ul><ul><li>Cost </li></ul>Tussin, AJKD 2004
Survival Benefit of Nephrologic Care Tseng, Arch Intern Med 2008
Benefits of Early Referral <ul><li>Informed selection </li></ul><ul><li>Timely access placement </li></ul><ul><li>Non-emergent initiation of dialysis </li></ul><ul><li>Lower morbidity </li></ul><ul><li>Lower cost </li></ul><ul><li>Improved survival </li></ul>
Current Guidelines <ul><li>PTH </li></ul><ul><li>Hg </li></ul><ul><li>Calcium and Phosphorus </li></ul><ul><li>Protein </li></ul>
Complications Worsen with Progression of CKD Zabetakis et al. Am J Kidney Dis. 2000; 36(suppl 3):S31-S38. ESRD GFR (mL/min/1.73 m 2 ) Increasing Severity of Complications CKD Continuum CKD Anemia Malnutrition Metabolic acidosis Secondary hyperparathyroidism Hyperkalemia 75 55 25 15 5