Council of Advanced

Practitioners

Finding the Sweet Spot: Renal Diabetic Management

and Dosing

Amy Mosman, PA-C SLU Division of Nephrology Disclosures: none

Council of Advanced

Practitioners

Objectives

1) Identify the types of albumin and normal vs. abnormal levels 2) Highlight albumin testing and lab deviations with emphasis on patient care 3) Discuss methods of decreasing proteinuria with an eye on the outcome of CKD progression 4) Using sample patients, discuss who/when/how to treat the proteinuric diabetic patient

Council of Advanced

Practitioners

24 y/o obese female here to establish care. No PMH. Strong FH of DM, HTN, CKD PE: 132/78, 240 lbs, no edema, no sx Labs: SCr 0.9mg/dL, UA + albuminuria, A1C 6.8% Worried if she has DM, HTN, and CKD

Alexis

What is the next step? A. Stage her CKD B. Reassure her that the albuminuria and A1C are not

significant C. Repeat the UA in 6 weeks and if present quantify* D. Refer for kidney biopsy E. Refer to endocrinologist

Council of Advanced

Practitioners

Council of Advanced

Practitioners

Stages of CKD 2002

KDIGO CKD Guidelines, AJKD Supplement, 2002

Council of Advanced

Practitioners

Stages of CKD 2013

KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of CKD, Kidney International, Jan 2013, Vol 3, Issue 1

Council of Advanced

Practitioners

Trends in adjusted* ESRD incidence rate (per million/year), by primary cause

of ESRD, in the U.S. population, 1996-2014

USRDS 2016 Annual Report, Vol 2, ESRD, Ch1

Council of Advanced

Practitioners

Estimated prevalence of self-reported kidney disease by state (%), 2014

USRDS 2016 Annual Report, Vol 1, CKD, Ch1

Council of Advanced

Practitioners

Ralph35 y/o male with Hx HTN and DM well controlled with meds X 10 years. Father had CKD 2/2 ESRD requiring dialysis 2/2 HTN and DM. Ralph is worried he is at increased risk for developing CKD and needing dialysis PE: 120-125/70 X 3 readings, no edema, no

SOB

What is your next step? A. Refer for more lab work* B. Refer to kidney biopsy C. Add ACEi or ARB D. Refer for genetic testing APOL1

Council of Advanced

Practitioners

CKD Risk Factors

• Diabetic • Hypertensive/CVD • Older age (>60y/o) • Recurrent UTI • Kidney stones • History of AKI • Polycystic Kidney

Disease • Genetics

• Autoimmune disease: Lupus, Sjogrens, RA, MCTD…

• Family history of CKD • Neoplasm: multiple

myeloma, Wilms, kidney cancer

• Previous transplant • Previous kidney donor

1. KDOQI guidelines 2002 2. http://www.uspreventiveservicestaskforce.org/uspstf/uspsckd.htm

Council of Advanced

Practitioners

CKD Screening & Evaluation

• Screening: • Renal function panel (S Cr, albumin) • Proteinuria assay • UA with microscopy

• Follow up with: • Renal Ultrasound • Blood borne Pathogens

(at least once) • Vitamin D, iPTH

Council of Advanced

Practitioners

• Urine Protein to Creatinine ratio • Used when you expect higher degrees of proteinuria • Usually lab gives you a Random Total Protein (mg/dL),

Random Creatinine (mg/dL) • Protein/Creatinine = UPCR • Usually represented as g/g (0.5 g/g, 2 g/g, etc)

• Urine Albumin to Creatinine ratio • More accurate when there is <1-2 g proteinuria;

BEST SCREENING LAB • Usually lab gives you Random Albumin (mcg/mL),

Random Creatinine (mg/dL), and UACR • Usually represented as mg/g

• 24 hour urine - Gold Standard?

CKD Screening for Proteinuria

Council of Advanced

Practitioners

Lois65 y/o with HTN, HLD, DM PMH: retinopathy, nephropathy, neuropathy PE: 150/88, trace edema, RRR, CTA Labs: SCr 2.3mg/dL (GFR 29ml/min), K 4.5 BUN 45, BG 142, A1C 6.5%, UACR 1700mg/g Meds: glargine (Lantus), lispro (Humalog), lisinopril, furosemide (lasix), atorvastatin

What adjustments would you make to her management? A. None, she is stable B. Increase the lispro C. Increase the lisinopril* D. Increase the atorvastatin

Council of Advanced

Practitioners

• BEST PREDICTOR OF PROGRESSION

• Check at least annually in DM patients to screen

• Check every 6-12 months in CKD patients

• Goal: as low as possible – Ideally <0.5 g/g – Partial remission: 0.2-2 g/g – Complete remission: <0.2 g/g

Proteinuria

Council of Advanced

Practitioners

Albuminuria As Risk Factor

Proteinuria and Rate of Change in Kidney Function in a Community Based Population, JASM 2013

The Progression of CKD: A 10-year population-based study of the effects of gender and age. KI 2006

The relationship between magnitude of proteinuria reduction and the risk of ESRD: Results of the AASK study of kidney disease and hypertension Ach Intern Med 2001

Combining GFR and albuminuria to classify CKD improves prediction of ESRD, JASN 2009

Alberta Kidney Disease Network: Relation between kidney function, proteinuria, and adverse outcomes, JAMA 2010

Council of Advanced

Practitioners

Aldosterone

+

Inhibition of RAAS: leads to less proteinuria 1. ACEIs • Block conversion of angiotensin I

to angiotensin II • Increase availability of

bradykinin

2. ARBs • Selectively antagonize angiotensin II • May also modulate the effects of

angiotensin II breakdown products

Weir MR. Clin Ther. 2007;29(9):1803-1824.

Renin

Angiotensinogen Angiotensin IACE

Angiotensin II

Renin-Angiotensin-Aldosterone System (RAAS)

RAAS inhibition provides nephroprotection independent of blood pressure lowering

Council of Advanced

Practitioners

Main Diabetic CKD Goals• Blood Pressure Control

• ACCORD: 140/90 • SPRINT: 120/80 • KDIGO: <140/90, <130/80 with proteinuria • Keep the patient and the med list in mind!

• Glycemic Control • Proteinuria Reduction • CVD management

• Kills more than CKD • SHARP trial: Vytorin benefits CKD patients • Lipid panel less indicative of true CV risk - set it and forget itName of the Game: Slow it down, delay progression of CKD!

Council of Advanced

Practitioners

55 y/o with family history of HTN and DM BP trending up into the 140-165/85-90 range S Cr 1.6mg/dL (GFR 58) & UACR 400mg/g

Sherman

Which of the following is the best HTN medication for Sherman?

A. Loop diuretics B. Thiazide diuretics C. ACE inhibitors* D. ARB inhibitors* E. Calcium channel blockers F. Beta blockers

Council of Advanced

Practitioners

Rose74 y/o routine visit, PMH: PVD, HL, HTN, Meds: metoprolol, HCTZ, amlodipine, ASA, atorvastatin PE: 168/98, home 150-160s Labs: SCr 1.2mg/dL, UACR 50mg/dL, GFR 56ml/min 2 weeks ago, lisinopril added for BP/UACR lowering F/U labs: 2 weeks later reveal SCr 1.4mg/dL with K 5.4mEq/L. BP 150/90

What is the cause of the rise in SCr? A. Medication induced AIN B. Renovascular Disease (RAS) C. Rhabdomyolysis from statins D. Usual rise from ACE inhibitor* E. Essential hypertension

Council of Advanced

Practitioners

Rose74 y/o routine visit PMH: PVD, HL, HTN, Meds: metoprolol, HCTZ, amlodipine, ASA, atorvastatin PE: 168/98, home 150-160s Labs: SCr 1.2mg/dL, UACR 50mg/dL, GFR 56ml/min 2 weeks ago, lisinopril added for BP/UACR lowering F/U labs: 2 weeks later reveal SCr 1.4mg/dL. BP 150/90

What is the cause of the rise in SCr?

A. Medication induced AIN B. Renovascular Disease (RAS) C. Rhabdomyolysis from statins D. Usual rise from ACE inhibitor E. Essential hypertension

Acceptable rise in SCr due to RAAS is 20-25%

Council of Advanced

Practitioners

Fred81 y/o poorly controlled DM x 20 years, bilateral BKA, often forgets meds, has passing ‘acquaintance’ with diabetic diet, has issues w/exercise due to chronic leg ulcers Labs: A1C historically 11.5-12% most recent A1C 7.5%, GFR 20ml/min Meds: metformin, lisinopril, furosemide, ASA, atorvastatin

Why is his A1C closer to goal now? A. McDonald's has changed their menu B. A1C is not reliable at lower GFRs* C. He doubled his metformin D. He has taken up marathon running

Council of Advanced

Practitioners

KDOQI Goals in 2014Evidence that intensive treatment has an effect on loss

of glomerular filtration rate (GFR) is sparse* 2.1: We recommend a target HbA1c of 7.0% to prevent or

delay progression of the microvascular complications of diabetes, including DKD. (1A)

2.2: We recommend not treating to an HbA1c target of <7.0% in patients at risk of hypoglycemia. (1B)

2.3: We suggest that target HbA1c be extended above 7.0% in individuals with co-morbidities or limited life expectancy and risk of hypoglycemia. (2C)

*NKF-KDIGO Clinical Practice Guideline for Diabetes and CKD, Guideline 2: Management of Hyperglycemia and General Diabetes Care in CKD, AJKD, Vol 60, #5, Nov 2012

Council of Advanced

Practitioners

Sadie85 y/o Type 2 DM, HTN, CKD. Meds: metformin 1000mg BID Labs: Scr 1.7mg/dl (historical 1.3mg/dL), eGFR 31ml/min, A1C 7.0%

What is the next step in management of DM? A. Decrease metformin* B. Discontinue metformin C. Add insulin D. Discontinue metformin and start insulin

Council of Advanced

Practitioners

Metformin Dosing

  SCr Race Age eGFR CKD

Stage

Male 1.5African

American 17 78 2

Male 1.5African

American 70 54 3a

Female 1.5 white 17 50.7 3a

Female 1.5 white 70 35 3b

GFR using CKD-EPI equation

Council of Advanced

Practitioners

Metformin in CKD

Now approved by the FDA for lower GFR’s

Council of Advanced

Practitioners

Non-Insulin Agents & CKD/Dialysis

Incretin mimetics - not recommended for moderate/severe renal impairment (late stage 3 and onward) Hypoglycemia is the largest concern for lower GFR’s

Council of Advanced

Practitioners

Incretins and SGLT-2 Inhibitors

• DPP-4 inhibitors - have showed reductions in albuminuria and – Victoza - cardioprotection

and renoprotection in the LEADER trial

• SGLT-2 - have demonstrated ability to decrease BP, weight, uric acid, and albuminuria beyond what can be explained by its glycemic effect

Council of Advanced

Practitioners

SGLT-2 Inhibition

• CANATU-SU: >1000 diabetics • canagliflozin vs glimepiride • Initial drop in eGFR, then stabilized &

declines slower with canagliflizin at either dose

• Canagliflozin significantly reduced albuminuria, mostly with patients who started with positive UACR

• Results were independent of A1c reductions

• EMPA-REG: ~7000 diabetics • empagliflozin vs placebo • Similar use of ACE/ARB in both

groups • Initial drop in GFR seen in

empagliflozin group (wk 1-4), then later showed stable GFR with empagliflozin vs declining GFR with placebo

• Significant relative risk reduction in progressing albuminuria

Council of Advanced

Practitioners

SGLT2 inhibition for CKD, not DM??

Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic Effects. Heerspink, et, al, JASN August 2016

JASN August 2016

Council of Advanced

Practitioners

CKD and Insulin

• All types are safe and effective for All Stages of CKD • Basal Insulin is VERY easy to dose in CKD • Basal Insulin with Oral Medications is fine • CKD Patients including Dialysis may use pumps • Dosing Requirements decrease with decreasing

Kidney Function • Decreasing Dosing Requirements are NOT

logarithmic no matter what you may have read....

Council of Advanced

Practitioners

http://kdigo.org/home/

https://www.aace.com/publications/guidelines

https://www.kidney.org

Council of Advanced

Practitioners

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health-statistics/Pages/kidney-disease-statistics-united-states.aspx. Accessed April 2, 2017. 17.Liles A. Medication Considerations for Patients With Chronic Kidney Disease Who Are Not Yet on Dialysis, Nephrology Nursing Journal 2011 18.Link DK. Chronic kidney disease: new paradigms in diagnosis and management. JAAPA. 2015; 28 (7): 23 - 28. 19.Making sense of CKD: a concise guide for managing chronic kidney disease in the primary care setting. National Kidney Disease Education Program. July 2014.

NIH Publication No. 14-7989. Available at: http://nkdep.nih.gov/resources/ckd-primary-care-guide-508.pdf 20.Mende CW. Diabetes and kidney disease: the role of sodium–glucose cotransporter-2 (SGLT-2) and SGLT-2 inhibitors in modifying disease outcomes. Current

Medical Research and Opinion. 2017; 33:3, 541-551. 21.Narva A. National Kidney Disease Education Program, NIH, Steering Committee meetings, 2013 22.Navaneethan SD et al. Diabetes control and the risks of ESRD and mortality in patients with CKD [published online ahead of print February 10, 2017]. AJKD. doi:

10.1053/j.ajkd.2016.11.018. 23.Perkovic V et al. Intensive glucose control improves kidney outcomes in patients with type 2 diabetes, Kidney International 2013 Mar;83(3):517-23. 24.Rodby RA. Timed urine collections for albumin and protein: the king is dead, long live the king! Am J Kidney Dis. 2016 Dec;68(6):836-838. 25.Schmitz P. Renal: An Integrated Approach. New York, NY: McGraw Hill; 2012. 26.Sinha AD, Agarwal R. The complex relationship between CKD and ambulatory blood pressure patterns. Advances in Chronic Kidney Disease. 2015(22)2:102-7. 27.Tonelli M, Wanner C and members of KDIGO Lipid Guideline Development Work Group. Lipid management in chronic kidney disease: synopsis of the kidney

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