Updates in Chronic Kidney Disease Management. Delphine S. Tuot, MDCM, MAS Associate Professor of Medicine UCSF-ZSFG

Transcription

1 Updates in Chronic Kidney Disease Management Delphine S. Tuot, MDCM, MAS Associate Professor of Medicine UCSF-ZSFG

2 No disclosures Research Funding: NIH, Blue Shield of California Foundation

3 Objectives Importance of early CKD identification Recognize the existence of disparities in CKD Review basics of CKD management and when to refer to nephrology

4 Case: Ms. S 50yo AA woman PmHx: hypertension Meds: chlorthalidone 25mg daily PE: 125/75 mmhg, 80 bpm Older brother just initiated dialysis at age 58. She asks about her risk for dialysis. Is she at risk for CKD? Does she have CKD?

5 Kidney dysfunction is associated with increase risk of early mortality 11.5% adult population 23 million adults Low egfr is associated with high mortality and CV morbidity Setting: KP of Northern California Go et al. NEJM. 2004

6 For every level of egfr, higher albuminuria confers higher mortality risk Astor. Am J Epi Study population: 14,586 NHANES participants ( ) All-cause mortality

7 Risk of CKD progression to ESRD KDIGO, Levy, KI, KI,

8 CKD prevalence: racial/ethnic disparities Study population: NHANES adult participants, USRDS Data USRDS, Report, 2015

9 CKD prevalence: racial/ethnic disparities Study population: NHANES adult participants, USRDS Data Report, USRDS, 2015

10 CKD prevalence: SES disparities HANDLS: Healthy Aging in Neighborhood Diversity across the Lifespan Setting: community adults from 12 representative census tracts in Baltimore; equal numbers by sex, race, SES (high/low) Low SES: < 125% federal poverty level Crews. AJKD, 2010

11 CKD prevalence: SES disparities HANDLS: Healthy Aging in Neighborhood Diversity across the Lifespan Setting: community adults from 12 representative census tracts in Baltimore; equal numbers by sex, race, SES (high/low) Low SES: < 125% federal poverty level Crews. AJKD, 2010

12 ESRD Incidence: race/ethnic disparities ESRD is nearly 3x greater among African Americans **slide courtesy of Neil Powe, MD USRDS Data Report, 2015

13 CKD disparities: plausible mechanisms System Patient Provider Traditional biological risk factors DM/HTN, obesity Genetics (ApoL1) Non-traditional biologic risk factors Viral infections (HIV, HCV) Depression Substance abuse Periodontal disease Social determinants of health Poor patient CKD awareness/health related behaviors Mistrust of medical system Homelessness Health system barriers Poor access to care (insurance issues, fragmented care) Communication barriers

14 Levy, AJKD, Paradigm shift: early detection of CKD So where does Ms. S fall along this spectrum?

15 Screening for CKD 2013 ACP recommendation #1: No screening for CKD in asymptomatic adults without risk factors of CKD. Grade: weak recommendation, low quality evidence Risk factors for CKD morbidity/mortality Diabetes (presence and glycemic control) HTN (presence and control) Family history of ESRD Low socioeconomic status Racial/ethnic minorities

16 Case: Ms. S 50yo AA woman PmHx: hypertension Meds: chlorthalidone 25mg daily PE: 125/75 mmhg, 80 bpm Labs: Cr=0.7 mg/dl; egfraa: >60 ml/min/1.73 m 2 UACR: 500mg/g Next steps: 1. You start low-dose AceInh (i.e., Benazepril 10mg daily) 2. Feel comfortable with etiology of CKD

17 Proteinuria helps identify potential etiology of CKD Intrinsic Renal Disease Vascular -Hypertension -Emboli Interstitial -Meds/NSAIDS -Herbs Tubular -prolonged low flow -Drugs Glomerular -Diabetes -Myeloma/Amyloid - GN < 1g/day Protein ~1g/Day Protein ~1.5g/Day Protein 3.5g/Day Protein Normal amount of albuminuria: <30mg/day

18 3. Titrate ACEi/ARB to minimize proteinuria Setting: 31,732 Swedes Predictor: change in UACR over 2 years Outcome: ESRD or mortality Main results: 4-fold decreases in UACR over 2 years associates with decreased risk of ESRD (aor: 0.34, ) Decreases in UACR were not associated with decreased risk of early mortality Carrero et al, KI, 2016.

19 the decreased risk of ESRD was seen across many population sub-groups Carrero et al, KI, 2016.

20 Titrate ACEi/ARB to minimize proteinuria Setting: China, ROAD trial Study population: 360 non-diabetics with mean scr of 2.7 mg/dl Intervention: titrated dose of ACEi or ARB vs. standard dose Outcome: ESRD + doubling scr + death Main results: Titration of ACEi/ARB in pts with moderate CKD was associated with decreased composite endpoint, independent of BP control. Hou. JASN, 2007.

21 Other CKD management strategies Proteinuria minimization titrate up ACEi/ARB Combine with diuretic to avoid hyperkalemia Aggressive BP control Glycemic control CV risk reduction (statin) Minimize NSAIDS Treatment of viral diseases (HCV, HIV) Consult Nephrology

22 BP control Prior to this year, BP recommendations were: < 140/90 mmhg without proteinuria < 130/80 mmhg if proteinuria Cumulative Incidence: doubling of scr, ESRD, death Population: 1094 Black patients with hypertensive kidney disease AASK trial. 2010

23 but. Systolic BP Intervention Trial (SPINT) RCT: 120 mmhg vs. 140 mmhg 9361 patients with high CV risk but no DM 2646 patients with CKD Mean scr = 1.4 mg/dl Mean UACR = 80 mg/g Trial was stopped early due to overall mortality benefit in strict BP control arm Outcome: all-cause mortality among CKD patients Strict BP Cheung, JASN, 2017

24 BUT. there was greater egfr decline in the strict BP arm, even though no difference in incident ESRD Slope: -0.3 ml/min/1.73m 2 per year P=0.03 for difference in slope Slope: ml/min/1.73m 2 per year Cheung, JASN, 2017

25 My strategy for BP control My target for patients with CKD 120/80 mmhg if no diabetes and > 50 years 130/80 mmhg if diabetes is present mmhg if frail Preferred agents in CKD: start with ACE or ARB A diuretic is second line (Loop if egfr < 45) Add CCB or beta blocker Spironolactone is an excellent medication, but be careful with hyperkalemia

26 Glycemic control improves renal outcomes UKPDS: UK Prospective Diabetes Study n=4209 newly diagnosed DM2 Strict control vs. conventional (HgA1c 7.0% vs. 7.9%) 10 years median follow-up In group with strict glycemic control (A1c 7%), statistically significant decreases in risk of: RR at 12 years microalbuminuria overt proteinuria doubling of Cr 0.67 (p<0.001) 0.66 (p=0.04) 0.26 (p=0.003) UKPDS Lancet 1998

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28 Current metformin recommendations (ADA, KDIGO, NKF, FDA) egfr > 60: metformin is first-line agent egfr 45-59: metformin is first-line agent egfr 30-44: dose reduce and use metformin with caution egfr < 30: do not use metformin

29 Hepatitis C infection has systemic implications Cacoub, J Hepatology; 2016

30 HCV is associated with poor Renal/CV outcomes Molnar, Hepatology, 2015

31 Improvements in HCV treatment over time BUT. timing of HCV treatment important to consider due to kidney transplant considerations Wait list for HCV+ kidney is much, much shorter Can safely treat HCV post-transplant Webster, Lancet; 2015

32 When to refer to nephrology? Underlying cause of CKD is not clear Rapid progression of kidney disease (> 5 ml/min loss/year) Significant proteinuria in absence of DM Persistent post-partum proteinuria (> 6 months post) Consider consult at stage 3b CKD (egfr < 45) Definitely consult at stage IV (egfr < 30) Bottom Line: whenever you aren t comfortable!

33 What to Do Before Consultation econsult with consult question Urinalysis Spot urine protein (or albumin)/ creatinine Renal panel CBC If U/A has ++ protein or blood: SPEP/UPEP, ANA, C3, C4 HIV, Viral Hepatitis serologies Renal Ultrasound (not required, but nice to have) Large: DM, Amyloid, HIV-associated, PCKD Small: HTN, chronic tubulo-interstitial disease Asymmetric: Renovascular, Congenital atresia

34 Summary Points SFHN patients are high risk for CKD CKD confers high risk for early mortality and CV dz Quantify proteinuria as part of initial evaluation Treat to goal: Blood pressure Albuminuria minimization Glycemic control (use metformin!) HCV eradication when appropriate Refer when: You are uncomfortable Patients don t fit the norm

35 Thank you!