Chronic Kidney Disease: Detection and Management in Primary Care - PowerPoint Presentation

Chronic Kidney Disease: Detection and Management in Primary Care Julia Scialla, MD, MHS, FASN Associate Professor of Medicine and Public Health Sciences University of Virginia Adjunct Associate Professor of Medicine Duke University

Disclosure Research Support : Eli Lilly, Glaxo Smith Kline, Sanofi: Clinical Event Committee

Objectives Rationale for CKD as a Disease “Measuring” Kidney Function and Staging CKD Common Complications of CKD Considering Renal Replacement Therapy Areas to Watch

Rationale for CKD as a ‘Disease’

Adjusted incident rates of ESRD & annual percent change Incident ESRD patients. Adj : age/gender/race; ref: 2005 ESRD patients. Is Kidney Disease an Epidemic?

2002 Definition of Chronic Kidney Disease Abnormalities of kidney structure or function present for > 3 months Kidney damage AlbuminuriaAbnormalities in the urine sedimentStructural abnormalities of the kidneyGlomerular filtration rate <60 ml/min/1.73m2

“Age Related” GFR Decline Davies DF. J Clin Invest, 1950

CKD Prognosis Consortium. Lancet 2010

KDIGO 2012 CPG for CKD. Kidney Int 2013.

KDIGO 2012 CPG for CKD. Kidney Int 2013.

Chronic Kidney Disease Paradigm Improved ability to detect and monitor CKD Need for unambiguous terminology Understanding of common disease pathwaysNew therapeutic strategiesShifts focus from RRT to early kidney diseaseHighlight opportunities for prevention

CKD Prognosis Consortium. Lancet 2010

Progressive Disease Wright J et al. JAMA 2002; 288(19):2421-31.

Copyright © 2012 American Medical Association. All rights reserved. From: Age and Association of Kidney Measures With Mortality and End-stage Renal Disease JAMA. 2012;308(22):2349-2360. doi:10.1001/jama.2012.16817 Relative Risk Perspective

Copyright © 2012 American Medical Association. All rights reserved. From: Age and Association of Kidney Measures With Mortality and End-stage Renal Disease JAMA. 2012;308(22):2349-2360. doi:10.1001/jama.2012.16817 Absolute Risk Perspective

US Population Case Increasingly common disease High lifetime risk 50-60% for early stage disease10-20% for late stage diseaseNear doubling of risk in African American communities for late stage diseaseConsequences for risk of ESRD, mortality, morbidities and costGrams ME et al. Am J Kidney Dis 2013; 62(2):254-52. Coresh J et al. JAMA 2007; 298(17):2038-47.

Measuring Kidney Function

Ann Intern Med. 1999;130(6):461-470. Mitch WE et al. Lancet, 1976

Hsu C and Chertow GM, Am J Kidney Dis, 2000 “Chronic Renal Confusion”

Creatinine -Based Estimation of GFR

1940 1950 1960 1970 1980 1990 2000 2010 KDOQI guidelines Equations KDIGO guidelines Chronic Kidney Disease First successful dialysis treatment First successful kidney transplant Establishment of US organ donation program USRDS C-G Equation MDRD Equations CKD- Epi Equations

Levey et al. Ann Int Med 2009A New Equation

Cystatin C Small protein Produced by all nucleated cells Freely filteredMetabolized in proximal tubule

Shlipak et al Am J Kidney Dis 2013

Shlipak et al. N Engl J Med 2013

Shlipak et al. N Engl J Med 2013

Albuminuria Preferred by guidelines over proteinuria More sensitive in the low range Can be standardizedGold standard is albumin excretion rate (mg/24 hours)Estimated by ACR (mg/g)Biased by creatinine production rateDipstick less sensitive and specificBiased by urine concentration

KDIGO 2012 CPG for CKD. Kidney Int 2013.Regarding the C in CGA Staging: “This statement has been included so as to ensure that clinicians are alerted to the fact that CKD is not a diagnosis inand of itself, and that the assignment of cause is importantfor prognostication and treatment.”

Evaluation for Cause History Urinary tract infections NephrolithiasisToxic Drugs including OTCSystemic ConditionsViral InfectionsBlood Pressure and ExamKidney ImagingUrinalysisUACR 31

When to Refer to Nephrology Hematuria Heavy Proteinuria Accompanied by Symptoms of a Renal SyndromeEdemaHypertensionSystemic DiseasesRapid ProgressionCKD G3b32

KDIGO Guidance 1.4.3.1: We recommend using serum creatinine and a GFR estimating equation for initial assessment. (1A) 1.4.3.2: We suggest using additional tests (such as cystatin C or a clearance measurement) for confirmatory testing in specific circumstances when eGFR based on serum creatinine is less accurate. (2B) KDIGO 2012 CPG for CKD. Kidney Int 2013.

‘Complications’ of CKD

Figure 2 The Lancet  2013 382, 158-169DOI: (10.1016/S0140-6736(13)60439-0) Copyright © 2013 Elsevier Ltd

↓ erythropoetin production ↓ ammoniagenesis Impaired natiuresis ↓ calcitriol production Hypertension Edema Metabolic Acidosis Secondary hyperparathyroidism Anemia Impaired kaliuresis Hyperkalemia Physiologic Complications of CKD ↓ phosphorus excretion Hyperphosphatemia

Inker LA et al. J Am Soc Nephrol 2011

Normal Phosphorus Homeostasis Hruska KA et al. Kidney International (2008) 74, 148–157 FGF23 Major Processes Phosphorus Intake Phosphorus Absorption Exchange with Intracellular and Bone Pool Phosphorus Excretion Major Hormonal Control Vitamin D Fibroblast Growth Factor 23 (FGF23) Parathyroid Hormone (PTH) Vitamin D PTH

Wolf M. CJASN doi:10.2215/CJN.04430415 ©2015 by American Society of Nephrology Patho physiologic Changes in Kidney Disease

Go et al. N Engl J Med, 2004. CKD, CVD and Death

Considering Renal Replacement Therapy

Trends in the distribution of eGFR (ml/min/1.73 m 2 ) among incident ESRD patients, 1996-2015 42 Data Source: Special analyses, USRDS ESRD Database. Population only includes incident cases with CMS form 2728. eGFR calculated using the CKD-EPI equation (CKD-EPI eGFR (ml/min/1.73 m 2 ) for those aged ≥18 and the Schwartz equation for those aged <18. Abbreviations: CKD-EPI; chronic kidney disease epidemiology calculation; eGFR , estimated glomerular filtration rate; ESRD, end-stage renal disease. USRDS 2017 Annual Data Report. Volume 2, Chapter 1 

Distribution of documented clinical signs and/or symptoms at the time of initiation in 2000–2004 versus 2005–2009. O’Hare et al . J Am Soc Nephrol 2015;26:1975-1981

Cooper BA et al . N Engl J Med 2010;363:609-619.

Cooper BA et al . N Engl J Med 2010;363:609-619.

Kurella Tamura M et al . N Engl J Med 2009;361:1539-1547. Change in Functional Status after Initiation of Dialysis

Indication for Dialysis Rivera M et al. Am J Kidney Dis 2017 69(1):41-50.

Tamura MK et al. N Engl J Med 2009. Adverse Impact of Dialysis Initiation on Functional Status of Nursing Home Residents

Guideline Evolution in the US National Kidney Foundation KDOQI 1997: Initiate when eGFR is approximately 10.5 ml/min/1.73m2National Kidney Foundation KDOQI 2006: Initiation considered when patients reach eGFR<15 ml/min/1.73m2; certain considerations may prompt earlier initiationNational Kidney Foundation KDOQI 2015: Removed eGFR as a component of the decision making Referral for Transplant Should be Driven by GFR

Areas to Watch

Wanner C et al. N Engl J Med 2016;375:323-334 SGLT-2 Inhibitors and Renal Outcomes

V Perkovic et al. N Engl J Med 2019;380:2295-2306. SGLT2 Inhibitors and Renal Events: CREDENCE

Moledina DG and Parikh CR. Seminars in Nephrology 2018; 38(1):3-11.

Chronic Kidney Disease: Detection and Management in Primary Care Audience Response Questions

Question 1 82 year-old AA man Well-controlled hypertension Losing weight with poor appetiteDecreased muscle mass on physical examBMI 17.5 kg/m2Cr 2.6 mg/dlNephSAP Volume 12, Number 4, September 2013. Authors Choi MJ and Fried LF

Answers Which ONE estimating equation will most accurately estimate his kidney function: MDRD Creatinine clearanceCKD-EPI creatinine formulaCKD-EPI cystatin C formula

Question 2 25 year old BP 140/90 EdemaCr 0.9 mg/dlUA with 3+ protein; no glucose; 1-2 RBCs; 2-3 WBCs UACR 2470 mg/gAdapted from NephSAP Volume 12, Number 4, September 2013. Authors Choi MJ and Fried LF

Answers Which ONE represents the best next course of action: Start an angiotensin converting enzyme inhibitor Referral to Nephrologist for possible kidney biopsyFollow estimated GFR over the next 6 months to determine next stepsScreen for hepatitis B, C and HIVA, B and D

Question 3 You are seeing a 42 year old female with CKD Stage G3b A2 related to a prior history of obstructive nephrolithiasis. She has been doing well with stable kidney function over the last 5 years. She uses losartan 50 mg daily for control of her blood pressure which measures 118/76 on average home readings. She is concerned about risks of bone disease due to her CKD which she read about on line. Her mother had osteoporosis. What can you tell her about CKD-related bone disease?

Answers Which of the following is the best answer: Obtaining a DEXA scan can help rule out and monitor CKD-related bone disease. Bone disease is no more common in CKD than in patients without CKD.Clinical trials show that treating early with vitamin D can prevent fractures from CKD-related bone disease.Monitoring blood calcium, phosphorus and parathyroid hormone is recommended in CKD.

Question 4 Mr. M is a 55 year old Caucasian male who comes to clinic for management and follow up of hypertension. He has BP 138/78, BMI 29, HbA1c of 6.0% and total cholesterol of 200 mg/dl and HDL-C of 50 mg/dl. He is a lifetime non-smoker. He has never had a cardiovascular event but is interested in doing all that he can to prevent cardiovascular disease because his father had an MI at age 67. He is trying to eat a healthful diet and belongs to a gym where he walks on the treadmill about 3 times a week. You tell him that he has a calculated 10 year risk of ASCVD of 7.4%. On review of labs his serum creatinine is 1.7 mg/dl and UACR is 28 mg/g. In addition to blood pressure mangement what additional treatment should you consider for Mr. M?

Answers Which ONE represents the best recommendation related to cardiovascular disease risk: Predicted cardiovascular risk is borderline and further therapy is needed at this time. Start aspirin 81 mg daily.Discuss use of moderate intensity statin with Mr. M.Start atorvastatin 80 mg daily.