The Role of the Primary Physician and the Nephrologist in the Management of Chronic Kidney Disease () By Brian Young, M.D. Assistant Clinical Professor of Medicine David Geffen School of Medicine at UCLA Recognize the prevalence of in the U.S. End Stage Renal Disease (ESRD): The Problem Pre-dialysis : The Problem 60 Expe cte d Remaining Life (Years) 50 40 30 20 10 0 Age General Population (2004) Dialysis Patients (2006) Adapted from USRDS 2008 Annual Data Report. Am J Kidney Dis 2009; 1(Suppl 1):S1. 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+ Pre-dialysis is also associated with significant mortality Chronic kidney disease and the risk of death, cardiovascular events, and hospitalization. N Engl J Med 2004; 351:1296. Pre-dialysis : The Problem Recognize the prevalence of in the U.S. Chronic kidney disease and the risk of death, cardiovascular events, and hospitalization. N Engl J Med 2004; 351:1296. 1
Steps to Defining : K/DOQI Definition of : K/DOQI 1995: National Kidney Foundation (NKF) launched the DOQI = Dialysis Outcomes Quality Initiative Panel of experts to develop clinical guidelines for dialysis patients 1999: NKF moved to approach kidney disease from a broader perspective and began K/DOQI = Kidney Disease Outcomes Quality Initiative Expanded to include pre-dialysis patients 2000: K/DOQI Advisory Board approved development of clinical practice guidelines to define and classify stages of chronic kidney disease Hematuria Proteinuria Biopsy Ultrasound, CT, MRI K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266 Staging: K/DOQI The Increasing Prevalence of ESRD Number of Patients (in thousands) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266 USRDS 2008 Annual Data Report. Am J Kidney Dis 2009; 1(Suppl 1):S1. The Increasing Prevalence of I-IV Recognize the prevalence of in the U.S. Adults aged 20 years or older GFR estimated by abbreviated MDRD equation Prevalence of chronic kidney disease in the United States. JAMA. 2007 Nov 7;298(17):2038-47. 2
Possible Risk Factors Associated with the Development of Diabetes Hypertension Cardiovascular disease Obesity Age > 60 years Autoimmune disease Exposure to nephrotoxic medications Chronic UTIs Urinary obstruction Chronic kidney stones HIV or Hepatitis C Reduction in renal mass Neoplasia Family history of kidney disease Initial Screening for All patients should be evaluated for risk of as part of routine health encounters Those patients at risk for should have further assessment of kidney function Clinical Evaluation for Markers of : Proteinuria BP measurements Routine electrolytes Serum creatinine and estimated GFR Urinalysis and microscopy to evaluate sediment Urine albumin/cr ratio or protein/cr ratio Total protein Albumin +/- Renal imaging (i.e. ultrasound) Markers of : Hematuria Estimating Glomerular Filtration Rate (GFR) Exogenous filtration markers: Inulin, 125I-iothalamate, 99mTc-DTPA, 51chromium- EDTA 24 hour urine creatinine clearance Estimation equations: Cockroft-Gault (serum creatinine, age, sex, weight) MDRD equation (4 variable = serum creatinine, age, sex, race) 3
Modification of Diet in Renal Disease (MDRD) Study Equation Abbreviated form: Estimated GFR (ml/min/1.73m 2 ) = 175 x (standardized Scr) 1.154 x (age) 0.203 x 0.742 (if the subject is female) x 1.212 (if the subject is black) More elaborate version of the MDRD equation includes serum albumin and BUN Calculators are available (www.kidney.org/professionals /KLS/gfr_calculator.cfm) R 2 = 0.88 Assessing kidney function--measured and estimated glomerular filtration rate. N Engl J Med. 2006 Jun 8;354(23):2473-83. MDRD Equation Limitations Problem populations: Understimates GFR in patients without, particularly in GFR estimates > 60 ml/min/1.73m 2 Less accurate at extremes of dietary habits or body habitus (i.e. cachectic = overestimate; overweight = underestimate) Inaccurate in setting of rapidly changing GFR (i.e. acute renal failure) Newer equations may ultimately come to the forefront to address the limitations of the MDRD equation Chronic Kidney Disease Epidemiology Collaboration (-EPI) Equation More accurate and precise than MDRD, especially at higher GFR -EPI Equation May Reduce Rate of False-Positive Diagnoses Creatinine Equation A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009 May 5;150(9):604-12. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009 May 5;150(9):604-12. Recognize the prevalence of in the U.S. Clin J Am Soc Nephrol. 2009 Feb;4(2):323-8 4
IM Resident Perception of Indications for Referral for Management IM Resident Perceptions of Threshold GFR for Referral for Renal Replacement Preparation Indications for Referral Significant proteinuria (> 1 g/g) Fast progression of (egfr 70 50 in 1 year) % Total Perception 44.7% 78.9% Criterion egfr (ml/min/1.73m 2 ) 45-60 % Total Perception 3.8 Uncontrolled BP despite 4 antihypertensives 64.5% 30-45 17.2 Hyperkalemia due to medications 26.1% 15-30 58.8 egfr < 30 ml/min/1.73m 2 Anemia of Bone and mineral disorder of 89.6% 28.0% 44.9% <15 Not known 18.2 2.0 Adapted from Perception of indications for nephrology referral among internal medicine residents: a national online survey.clin J Am Soc Nephrol. 2009 Feb;4(2):323-8 Adapted from Perception of indications for nephrology referral among internal medicine residents: a national online survey.clin J Am Soc Nephrol. 2009 Feb;4(2):323-8 Proposed Clinical Action Plan for Patients with Timing of Metabolic Complications of K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266 Timing of onset of -related metabolic complications. J Am Soc Nephrol. 2009 Jan;20(1):164-71. Late Referral is Associated with Poorer Outcomes in Schmidt, R, Domico, J, Sorkin, M, Hobbs, G. Early referral and its impact on emergent first dialyses, health care costs, and outcome. Am J Kidney Dis 1998; 32:278. Arora, P, Obrador, G, Ruthazer, R, et al. Prevalence, predictors and consequences of late nephrology referral at a tertiary care center. J Am Soc Nephrol 1999; 10:1281. Lorenzo, V, Martn, M, Rufino, M, et al. Predialysis nephrologic care and a functioning arteriovenous fistula at entry are associated with better survival in incident hemodialysis patients: an observational cohort study. Am J Kidney Dis 2004; 43:999. Wauters, JP, Lameire, N, Davison, A, Ritz, E. Why patients with progressing kidney disease are referred late to the nephrologist: On causes and proposals for improvement. Nephrol Dial Transplant 2005; 20:490. Chan, MR, Dall, AT, Fletcher, KE, et al. Outcomes in patients with chronic kidney disease referred late to nephrologists: a metaanalysis. Am J Med 2007; 120:1063. Predialysis Care Influences Post- Dialysis Mortality Greater First-Year Survival on Hemodialysis in Facilities in Which Patients Are Provided Earlier and More Frequent Pre-nephrology Visits. Clin J Am Soc Nephrol 2009 4: 595-602. 5
Late Referral Is Associated with Lower Likelihood of Kidney Transplant Possible Benefits of Early Referral Improved control of metabolic complications and risk factors for progression Informed discussion of renal replacement options and avoidance of emergent dialysis initiation Early placement of dialysis access Decreased hospital days and costs Improved survival Preemptive transplant Late referral to a nephrologist reduces access to renal transplantation. Am J Kidney Dis 2003; 42:1043. Recognize the prevalence of in the U.S. Risk Factors for Progression Progressive underlying disease: DM, HTN, autoimmune, obstruction, etc. Continued nephrotoxic insults Hypertension Proteinuria Hypercholesterolemia Metabolic acidosis Smoking Risk Factors for Progression Hypertension Proteinuria Hypercholesterolemia Metabolic acidosis Smoking 6
Intraglomerular Hypertension and Glomerular Hypertrophy ACE inhibitors and ARBs are Anti- Hypertensive Agents of Choice Adaptive hyperfiltration occurs after glomerular injury Remaining normal nephrons increase filtration rate to compensate for lost nephron mass Short-term = attempt at maintenance of GFR Long-term = chronic stress that results in future damage Manifest as proteinuria and progressive renal insufficiency and hypertension Injury may be ameliorated by inhibition of angiotensin II The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993 Nov 11;329(20):1456-62. Goals of Treatment for Hypertension and Proteinuria Kidney Disease Type Therapeutic Target Preferred Agent Angiotensin Inhibition Benefits Even Those with Advanced Diabetic Kidney Disease Nondiabetic kidney disease with proteinuria (spot urine total protein-tocreatinine ratio 200 mg/g) <130/80 and total protein excretion <500-1000 mg daily <130/80 and total protein excretion <500-1000 mg daily ACE inhibitor or ARB ACE inhibitor or ARB Creatinine 1.5-3 mg/dl Creatinine 3.1-5 mg/dl Nondiabetic kidney disease without proteinuria (spot urine total protein-tocreatinine ratio <200 mg/g) <130/80 None preferred Adapted from K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis 39:S1-S266, 2002 (suppl 2). Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006 Jan 12;354(2):131-40. Risk Factors for Progression Hypertension Goal < 130/80; ACEI/ARB Proteinuria Goal < 500-1000mg; ACEI/ARB Hypercholesterolemia Goal LDL < 100; Statin Metabolic acidosis Smoking Risk Factors for Progression Hypertension Goal < 130/80; ACEI/ARB Proteinuria Goal < 500-1000mg; ACEI/ARB Hypercholesterolemia Goal LDL < 100; Statin Metabolic acidosis Goal HCO3 > 22; Oral bicarbonate Smoking 7
Risk Factors for Progression Hypertension Goal < 130/80; ACEI/ARB Proteinuria Goal < 500-1000mg; ACEI/ARB Hypercholesterolemia Goal LDL < 100; Statin Metabolic acidosis Goal HCO3 > 22; Oral bicarbonate Smoking Smoking cessation Risk Factors for Progression Hypertension Goal < 130/80; ACEI/ARB Proteinuria Goal < 500-1000mg; ACEI/ARB Hypercholesterolemia Goal LDL < 100; Statin Metabolic acidosis Goal HCO3 > 22; Oral bicarbonate Smoking Smoking cessation Controversial; 0.8 g/kg per day of protein; Should be done with dietician and/or nutritionist supervision Conclusions stages 3-5 are common and associated with significant morbidity and mortality Patients with risk factors for should be identified and evaluated for markers of renal disease, including estimation of GFR and urine studies Consider referral to a nephrologist at stage 3 and above given possible improved outcomes with early referral Risk factors for progression should be modified, optimally with assistance from a nephrologist 8