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Chronic Kidney Disease Identification, management, and prevention in the general public

Deborah H. Brooks MSN, ANP-BC, CNN-NP

February 20, 2015

Advanced Practice Registered Nurses Conference

Charleston, SC

Take home message

• Check blood pressure

• Check urine protein or albumin

• Check creatinine especially elders and at risk

• Treat hypertension

• Treat diabetes

• Work on life style: diet, exercise, smoking

• Refer for nephrology consult

Chronic Kidney Disease (CKD)

• 2011 UN recognized kidney disease is a major health burden with risks but not as a common non-communicable disease (NCD).

• WHO recognizes 4 NCDs: CVD, cancer, DM and chronic lung disease.

• CKD would benefit from being a separate NCD.

• Prevention and early recognition are key factors in CKD.

USRDS Annual Data Report 2014, V1,P1

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CKD in the US

• ~637,000 on dialysis or transplant

• Includes ~115,000 new kidney patients in 2012

• Kidney disease new cases have declined from 2010 to 2012

US

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Data Source: Medicare 5 percent sample. See Table A at the beginning of this chapter for a description of ICD-9-CM codes and CKD stages.

vol 1 Figure 2.1 Temporal trends in CKD prevalence, overall and by CKD stage, among Medicare patients age 65+, 2000-2012

Vol 1, CKD, Ch 2 6

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Types of patients

46 year old male

Hypertension

Creatinine 3.5; eGFR 38ml/min

Drives cement truck

Father was on dialysis

• 21 year old female

• Systemic lupus erythematosus

• Creatinine 1.8; eGFR 31ml/min

• 24hr urine 1.3 gms protein

• No hypertension

84 year old female

Hypertension & osteoarthritis

50 kg; albumin 2.9

Creatinine 5.6; eGFR 12ml/min

Starting dialysis?

• 68 year old male

• Diabetes

• 110 kg, BMI 41

• Creatinine 6.2; potassium 5.4

• Desires a transplant

Definition of CKD

1. Estimated glomerular filtration rate (eGFR) <60ml/min

AND/OR

2. Evidence of kidney damage especially proteinuria – (urine dipstick of 1+ or greater. Spot albumin/creatinine ratio >200mg/g)

These factors need to be assessed and shown to be consistent for greater than 90 days before CKD is diagnosed.

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eGFR on routine labs

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Classification of CKD Stage or GFR category

GFR ml/min

Severity Treatment

1 (G1) >90 Normal Screen & treat risk

2 (G2) 60-89 Mild decrease* Diagnose & treat

3a (G3a) 45-59 Mild to moderate Treat comorbidities

3b (G3b) 30-44 Moderate to severe Consider referral to nephrology

4 (G4) 15-29 Severe decrease Prepare for KRT or transplant

5 (G5) <15 Kidney failure KRT, transplant, or death

GFR: mL/min/1.73 m2

KRT kidney replacement therapy

*May be normal for age National Kidney Foundation, 2009; KDIGO 2012

Vol 1, CKD, Ch 1 11

vol 1 Figure 1.11 NHANES participants with CKD aware of their kidney disease, 1999-2010

Data Source: National Health and Nutrition Examination Survey (NHANES), 1988–1994, 1999-2004 & 2007–2012 participants age 20 & older. Abbreviations: CKD, chronic kidney disease.

Less than 10% are aware of their kidney disease!

High risk individuals • Diabetes

• Hypertension

• Autoimmune diseases (e.g. SLE, scleroderma)

• Systemic infections (HIV) • Exposure to drugs/procedures associated w/ acute decline in

function • Recovery from acute kidney injury (AKI)

• Age >60 years

• Family history of kidney disease

• Reduced kidney mass (includes kidney donors & transplant

recipients)

KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification (2002); KDIGO CKD 2012

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Primary Diagnoses for Patients Who Start Dialysis

Diabetes 50%

Hypertension 27%

Glomerulonephritis 13%

Other 10%

www.hypertensiononline.org

United States Renal Data System (USRDS) 2012 Annual Data Report • WWW.USRDS.ORG

Original diagnosis for starting dialysis before 1973 was a primary kidney disease

Cumulative probability of a physician visit by month 12 after CKD diagnosis in 2011

Patients alive & eligible all of 2011. CKD diagnosis represents date of first CKD claim during 2010 and 2011; physician claims searched during the 12 months following that date.

abstracted from USRDS 2013 ADR Table 2.9 (Volume 1)

30%

Applies to both CKD and AKI diagnosis

Vol 1, CKD, Ch 2 15

Data Source: Medicare 5 percent sample.

vol 1 Figure 2.2 Temporal trends in CKD prevalence by race among Medicare patients age 65+, 2000-2012

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Data source: Medicare 5 percent sample. January 1, 2012 point prevalent patients age 66 and older. Adj: age/sex/race/prior year hospitalization/comorbidities. Ref: all patients, 2012. Abbreviations: CKD, chronic kidney disease; CVD, cardiovascular disease; DM, diabetes mellitus.

vol 1 Figure 3.4 Adjusted mortality rates (per 1,000 patient years at risk) in Medicare patients aged 66 and older, by cardiovascular disease, diabetes mellitus, and CKD status, 2012

Vol 1, CKD, Ch 3

vol1 Figure 4.1 Cardiovascular disease in patients with or without CKD, 2012

Vol 1, CKD, Ch 4 17

Data Source: Medicare 5 percent sample. Patients age 66 and older, alive, without end-stage renal disease, and residing in the U.S. on 12/31/2012 with fee-for-service coverage for the entire calendar year. Abbreviations: AFIB, atrial fibrillation; AMI, acute myocardial infarction; ASHD, atherosclerotic heart disease; CHF, congestive heart failure; CKD, chronic kidney disease; CVA/TIA, cerebrovascular accident/transient ischemic attack; CVD, cardiovascular disease; PAD, peripheral arterial disease; SCA/VA, sudden cardiac arrest and ventricular arrhythmias.

2X

prevalence

of CVD in

CKD

vol1 Figure 4.2 Survival of patients with a cardiovascular diagnosis or procedure, by CKD status, 2010-2012 (cont.)

Vol 1, CKD, Ch 4 18

•CHF

Data Source: Medicare 5 percent sample. Patients age 66 and older, alive, without end-stage renal disease, and residing in the U.S. on 12/31/2012 with fee-for-service coverage for the entire calendar year. Abbreviations: CHF, congestive heart failure; CKD, chronic kidney disease; CVA/TIA, cerebrovascular accident/transient ischemic attack.

*CHF most

common CVD in

CKD

*lower survival

with more kidney

disease

<60% stage 4-5

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Data Source: Medicare patients from the 5 percent sample, age 65 or older with Part A & B coverage in the prior year. Tests tracked during each year. Abbreviations: DM, diabetes mellitus; HTN, hypertension.

vol 1 Figure 2.3 Unadjusted cumulative probability for urine albumin & serum creatinine testing, among Medicare patients age 65+ WITHOUT a diagnosis of CKD, 2000-2012

USRDS 2014 Vol 1, CKD, Ch 2

(B) Serum creatinine

Data Source: Medicare patients from the 5 percent sample, age 65 or older with Part A & B coverage in the prior year. Tests tracked during each year. Abbreviations: DM, diabetes mellitus; HTN, hypertension.

vol 1 Figure 2.4 Unadjusted cumulative probability for urine albumin & serum creatinine testing, among Medicare patients age 65+ WITH a diagnosis of CKD, 2000-2012

USRDS 2014 Vol 1, CKD, Ch 2

(B) Serum creatinine

Good!

Prediction equations for estimating renal function

• Cockcroft-Gault • Estimation of creatinine clearance

• 1976

• MDRD • Estimation of glomerular filtration rate (eGFR)

• 1999

• CKD-EPI • Estimation of glomerular filtration rate (eGFR)

• 2009

Michels et al., 2010; O’Hare & Hemmelgarn, 2011,465/MacGregor & Methven, 2011,1 – Hdbk CKD Manage

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* For women ( x 1.0 for men) Cockcroft, 1976; O’Hare & Hemmelgarn, 2011

estimates creatinine clearance (Ccr) (oldest method & used for drug calculations)

Ccr = (140 – age [y])(body wt [kg]) x 0.85*)

(72)(SCr [mg/dL])

Cockcroft-Gault (C-G) - 1976

• Example: – 62yo woman, 100kg, SCr 1.8 mg/dLr

• Formula result: – Ccr= 51 mL/min

*May overestimate severity of CKD in pts >65yo

STAGE 3(a) KIDNEY DISEASE

MDRD calculation - 1999 (Modification of Diet in Renal Disease)

Example:

62yo 100kg black female

SCr 1.8 = 34ml/min

Stage 3(b) CKD

• Calculation based on age, gender, race, creatinine

• More accurate if eGFR <60ml/min/1.73m2

• Accurate all age adults

• Used for most lab reports

• Web based apps available

Levey et al. 1999; MacGregor & Methven, 2011,1 Hdbk CKD Manage

CKD-EPI - 2009 (CKD Epidemiology Collaboration)

• Based on race, gender, creatinine

• More accurate for eGFR >60ml/min

Example:

• 62 yo, black female

SCr 1.8 = 34ml/min; stage 3(b) CKD

• 50 yo, white female

SCr 0.6 = 106 ml/min; SCr 1 = 76ml/min

Levey et al. 1999; MacGregor & Methven, 2011,1 Hdbk CKD Manage

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Referral to nephrology

• eGFR <30ml/min

• Proteinuria is persistent despite RAAS therapy

• Hyperkalemia

• Resistant hypertension

• Unexplained 30% decrease in eGFR over 4 months

• CKD etiology unclear

• Anemia requiring erythropoietin therapy

• Elevated phosphorus and/or parathyroid hormone

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Proteinuria

www.unckidneycenter.org/kidneyhealthlibrary

Albuminuria

• Molecules are filtered depending on size and charge

• Anion particles >3.4 nm are not filtered in urine

• Albumin is 3.6 nm (nanometer)

• Charge selectivity is lost in diseases of the glomerulus e.g. nephrotic syndrome

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Transient urine protein • Pregnancy

• Fever

• Infections

• Exercise

Repeat urine test several times before providing final diagnosis

Albuminuria Categories in CKD

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the

Evaluation and Management of Chronic Kidney Disease. Kidney inter., Suppl. 2013; 3: 1–150.

Is albuminuria seen in patients with normal GFR?

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What is an ACR and how do you measure it?

People whose ACRs (and therefore

risk) that fall into these categories

will be dipstick negative.

This is the only column of people

who will be dipstick positive.

ACR= albumin to creatinine ratio

What is an ACR and how do you measure it?

1. To convert microalbumin and urine creatinine to the useful ratio first

make sure both values are expressed in the same unit.

2. Divide the microalbumin concentration by the creatinine concentration

3. Multiply the resulting ratio by 1,000 to get mg albumin over grams

creatinine.

For example: A patient had the following labs:

Microalbumin urine: 5.6 mg/dL

Creatinine urine: 91.2 mg/dL

Dividing the albumin by creatinine gives: 0.061

Multiply that by 1,000 to get 61 mg albumin/g creatinine

Data Source: Medicare patients from the 5 percent sample, age 65 or older with Part A & B coverage in the prior year. Tests tracked during each year. Abbreviations: DM, diabetes mellitus; HTN, hypertension.

vol 1 Figure 2.3 Unadjusted cumulative probability for urine albumin & serum creatinine testing, among Medicare patients age 65+ WITHOUT a diagnosis of CKD, 2000-2012

USRDS 2014 Vol 1, CKD, Ch 2

(A) Urine albumin

Better with DM

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Data Source: Medicare patients from the 5 percent sample, age 65 or older with Part A & B coverage in the prior year. Tests tracked during each year. Abbreviations: DM, diabetes mellitus; HTN, hypertension.

vol 1 Figure 2.4 Unadjusted cumulative probability for urine albumin & serum creatinine testing, among Medicare patients age 65+ WITH a diagnosis of CKD, 2000-2012

USRDS 2014 Vol 1, CKD, Ch 2

(A) Urine albumin

Not even 50%

Albuminuria

• PMH:

• HTN

• DM

• A fib

• HTN & DM management

• Prepare for dialysis

One year apart: sCr (eGFR)3.4(14) 3.9 (12)

Proteinuria and hypertension

P/C (gm/d) 3 3.7 1.9 1.2

sCr(eGFR) 2.1(29) 2.7(22) 2(31) 1.8(35)

Jan Oct June Apr

PMH: decades of HTN, DM, CAD w/ CABG, CHF, OSA

Events: CHF w/ edema, HTN, diuretic increased. Goal - HTN

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Urine Casts

Hyaline CKD, pyelonephritis

Erythrocyte (red cell) Glomerulonephritis, Contact sports

Leukocyte Pyelo, GN, interstitial nephritis, inflammation

Granular Advanced CKD

www.aafp.org/afp/2005/0315/p1153.html

Vol 1, CKD, Ch 1 38

vol 1 Figure 1.12 NHANES participants at target blood pressure, 1998-2012

Data Source: National Health and Nutrition Examination Survey (NHANES), 1988–1994, 1999-2004 & 2007–2012 participants age 20 & older. Single-sample estimates of eGFR & ACR; eGFR calculated using the CKD-EPI equation. Figure represents all hypertensives plus those hypertensive participants that are at target blood pressure, probably due to medication. Abbreviations: ACR, urine albumin/creatinine ratio; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.

Juxtaglomerular Apparatus

http://renalfellow.blogspot.com/2008/10/review-juxtaglomerular-apparatus.html

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Renin Angiotensin Aldosterone System (RAAS)

McPherson & Pincus (2006) 21st ed

ACEi (Angiotensin Converting Enzyme inhibitor

Renin inhibitor

ARB (Angiotensin Receptor Blocker)

Aldosterone receptor blockers

A I = angiotensin I A II = angiotensin II

angiotensinogen

2014 Evidence Based Guideline for Management of High Blood Pressure in Adults (>18 yrs)

CKD BP target 1st agent Add on med

18-70yo;

DM+/-;

proteinuria +/-

<140/90

(E*)

ACE or

ARB (B*)

Thiazide Diuretic

or CCB

>75yo <150/90 but

no firm goal

ACE or

ARB?

Thiazide Diuretic

or CCB

Black & CKD <140/90 ACE or

ARB with

proteinuria

Thiazide diuretic,

CCB, ACE or

ARB (1st line if

no proteinuria)

* 9 recommendations; A=strong, B=moderate, E=expert opinion James et al.,2014 JAMA

Medications - RAAS RAAS Action Result Benefit Monitor

ACEi Block conversion of angiotensin I to angiotensin II in lungs

Relaxed blood vessels including efferent arteriole

Less proteinuria; ↓ rate of kidney decline

Angioedema, ↑creatinine & potassium, teratogenic

ARB Block angiotensin II AT1 receptors in kidney

Blocks aldosterone from adrenal glands

Less proteinuria; ↓ rate of kidney decline

↑creatinine & potassium, teratogenic

Renin inhibitor

Block release of renin from juxtoglomerular cells

↓conversion of angiotensin-ogen (liver) to angiotensin I

Less proteinuria

↑creatinine & potassium; don’t combine w/ ACE/ARB; teratogenic

Aldosterone [potassium sparing]

Exchange Na for K; blocks reabsorption of Na & H2O

↓plasma aldosterone levels

Diuresis; augment ACE/ARB

↑ potassium, gynecomastia

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GFR monitoring w/ ACE/ARB

NKF-K/DOQI guidelines HTN and antiHTN agents

Medications - Diuretics

Diuretics Action Result Benefit Monitor

Thiazide e.g. HCTZ, chlorthalidone

Inhibits DCT Na/Cl resorption

diuresis Augments RAAS

↑Uric acid, ↑glucose, ↓potassium

Loop e.g. furosemide

Inhibits Na/Cl resorption in entire glomerular loop

Diuresis, lower b/p

use if eGFR <40ml/min; augments RAAS

↓potassium, ↑creatinine, Electrolyte imbalances

Potassium sparing e.g. spironolactone, eplerenone

Blocks mineralcorti-coid receptors in DCT to prevent Na resorption

↓ Na/water resorption ↑ potassium retention

Can use with other diuretics

↑potassium, ↑creatinine; use w/ caution w/ RAAS

JNC VII, JAMA, 2003; Kalaitzidis & Bakris, 2011

CKD patients with at least one claim for a diuretic in the 12 months following the disease-defining entry period, by CKD diagnosis code, 2011 Figure 5.16 (Volume 1)

Point prevalent Medicare CKD patients age 65 & older.

USRDS 2013 ADR

~30%

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Medications – Blockers (Antagonists)

Blockers action results benefits monitor

Calcium – non Dihydropyridine e.g. diltiazem, verapamil

Inhibits Ca+ ion entry into arterial vascular smooth muscle and myocardium

↓PVR, dilate coronary art, prolong AV node refractory time; Bp control

Less proteinuria, arrhythmia control

Heart block 2nd or 3rd

Calcium – dihydropyridine e.g. amlodipine, nifedipine, felodipine

Inhibits Ca+ ion entry into vascular smooth muscle & myocardium

SBP control w/ ↓ systemic vascular resistance

↓ large vessel stiffness especially helpful in elderly

Don’t use as monotherapy w/ proteinuria; peripheral edema common

Medications – Blockers (Antagonists)

Blockers action results benefits monitor

Beta Block catechola-mine e.g epinephrine, release; ↓ renin

↓b/p & pulse; ↓oxygen demand on heart; ↓ Na & H2O retention

Add on to RAAS or vasodilator; some proteinuria decrease

Don’t use w/ non-di Ca blocker – bradycardia or heart block

Alpha – peripheral e.g. doxazosin, prazosin

Blocks peripheral alpha 1 adrenergic receptors

bp control BPH, add on b/p med; no renal adjustment

Hypotension especially 1st dose

Alpha/beta [central] e.g. labetalol

Selective block of alpha 1 & nonselective beta 1 & 2

↑vasodialation from 2 blocking sites w/ ↑ BP control

Add on med; no renal adjustment

hypotension

Medications – Other antihypertensives

Drug action results benefits monitor

Central alpha adrenergic agonists e.g. clonidine, guanfacine, methyldopa

Counter block sympathetic activity

↓b/p & pulse Add on b/p med; patch has less side effects

Don’t use w/ beta blocker; monitor for sedation, dry mouth, bradycardia; severe rebound HTN w/ withdrawal

Vasodilator e.g. minoxidil, hydralazine

Dilates peripheral vessels – arterial and venous

Bp lowering but tachycardia

Add on b/p med; use w/ BB

Fluid retention, pericardial effusion, hair growth, lupus syndrome

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Monitoring GFR w/ BP meds

NKF-K/DOQI guidelines HTN and antiHTN agents

Fluid overload & mortality in CKD

Current Research • Fluid overload may be an independent risk for all cause mortality &

CV morbidity in CKD 4/5

• Fluid overload was >7% extracellular fluid (measured by body composition monitor)

• Group had lower eGFR, more HTN, DM, Cerebral VD

• Used more diuretics, CCB, BB

• Factors to consider: sodium intake, meds

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Heart Kidney connection

Current Research Heart disease is the major cause of death in CKD

• Elevated cardiac markers (troponins & NT-proBNP) even without evidence of HF were associated with rapid decline in kidney function.

• Provide opportunity to identify subclinical CVD & intervene to control CKD

• Use of cardiac markers may guide therapy to prevent cardiac disease and protect kidneys

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Dyslipidemia: 2013 Guidelines

Goals

• No longer treating to number goals

• Treat to reduce atherosclerotic cardiovascular disease (ASCVD) risk

• Use statins (LDL targeted statin therapy)

• Non statins don’t risk

• Monitor LDL for % change

• Individualize care

Treat individuals with:

• Clinical ASCVD

• LDL cholesterol levels ≥190 mg/dL, e.g. familial hypercholesterolemia.

• 40 to 75 yo w/ diabetes & LDL 70 to 189 mg/dL w/out evidence of ASCVD

• No evidence of CVD or DM but LDL 70 - 189 mg/dL & a 10-year risk of ASCVD ≥7.5%

Stone et al. 2013 ACC/AHA guidelines; ADA Guidelines, 2014

Dyslipidemia

Goals

• Meta analysis of 12 studies showed lipid lowering agents slowed GFR decline *

• Prevention of primary or secondary ASCVD

• Monitor for (TG>150, LDL >70-189, HDL<40)

• Guidelines do not apply to hemodialysis

Treatments

• Diet and TLC therapeutic lifestyle changes

• Statins safe in CKD

• Fibrates use dose

• Niacin TG & LDL

• Ezetimibe gut absorption of Chol

• Bile acid sequestrants work in gut

•*Fried, Orchard, Kasiske. KI, 2001; NKF/KDOQI 2007; Chan, Irish, Watts, 2011; Stone et al. 2013

Statin and AKI

Current Research • Meta analysis (14 RCT, 1689 pt) indicates short term (<7day) high

dose atorvastatin (40-80 v 10-20mg) before CAG and PCI procedures with contrast media may prevent acute kidney injury especially in eGFR>60ml/min

• Need more and longer f/u studies for other clinical outcomes.

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Anemia definition in CKD

• Hemoglobin <12 (women)<13 (men)gm/dl

• If normal: screen annually Stage 3; Q6mon Stage 4-5

• Low but no active treatment: screen every 1-3 months

• Use reference tables for child age appropriate Hb

• Hematocrit not as stable and varies with analytical instrument

KDIGO guidelines, 2012; Macdougall, Hdbk CKD Manage, 2011, 333

Adapted from Hillman, 1998.

Red blood cells O2 delivery

Erythropoietin Erythroid marrow

Iron

RE cells

RE=reticuloendothelial

X

Erythropoiesis in CKD

Anemia Possible Consequences include:

• Cardiac output

• myocardial oxygen availability

• Volume overload, heart failure

• Left ventricular dysfunction e.g. LVH

• Prolonged bleeding time

• exercise tolerance & cognitive function

• Hb less than 10, decrease of >1gm Hb over a month showed greater mortality.

Macdougall, Hdbk of CKD Management 2011, 333; Locatelli et al. Neph Clin Practice 2014

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Iron deficiency anemia in CKD

• Iron deficiency: Normocytic, normochromic

• Ferritin

• <100ng/ml in children; <500ng/ml in adults

• <30 absolute iron deficiency

• Transferrin saturation [(iron/TIBC)x100]

• <20% in children; <30% in adults

In the presence of low Hb a trial of iron, oral or IV, may be considered.

KDIGO guidelines, 2012; Macdougall, Hdbk CKD Manage, 2011, 333

Iron delivered to developing erythroblasts

Infection & Inflammation May Also Lead to Functional Iron Deficiency

Andrews NC. J Clin Invest. 2004;113(9):1251-3. Coleman M. In: Rodak BF, ed. Hematology: Clinical Principles and Applications, 2nd ed. Philadelphia, PA: W.B. Saunders Company; 2002:chap 10. Adapted from: Lee GR, et al. In: Lee GR, et al, eds. Wintrobe’s Clinical Hematology, 10th ed. Baltimore, MD: Williams & Wilkins; 1999:chap 11.

Iron stored in ferritin/hemosiderin

Liver

Iron released to transferrin

Hepcidin

Circulating RBCs

Old RBCs phagocytized in reticuloendothelial

system

Anemia management eGFR 27ml/min

Fatigue, cold, ice pica

Female

Gi intolerance to oral iron

Postmenopausal

Colonoscopy negative

Iron repletion before ESA

%sat = available iron

Ferritin = storage iron

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Diabetes & CKD

• CKD – alterations in peripheral insulin resistance, increased acidosis, decreased insulin excretion

• Therapy Goals - slow progression in type 1 & 2 • Glycemic control - HgbA1C < 7% [~154mg/dL] • Blood pressure control - <140/80-90

• Screening – at diagnosis type 2, at 5yrs type 1 • Urine albumin – annually if normal; 3-6 months if present • Retinopathy – annually if present; every 2 yrs if normal

NKF/KDOQI, DM guideline 2; ADA Guidelines 2014

Diabetes & CKD

Medication recommendations • Aspirin low dose – primary or secondary prevention

type 1 & 2 if CVD present or a > 10 year risk; otherwise bleeding risk outweighs benefit

• ACE/ARB – won’t prevent CKD in diabetes if HTN or albuminuria not present

• Treatment cautions:

No Metformin if <40ml/min – Lactic acidosis

Sulfonylureas accumulate in renal failure

Insulin 1/3 degraded by the kidney

Glitazones aggravate edema and CHF

NKF/KDOQI, DM guideline 2; ADA Guidelines 2014

Vol 1, CKD, Ch 1 63

vol 1 Figure 1.15 Diabetic NHANES participants with glycohemoglobin <7%, 1998-2012

Data Source: National Health and Nutrition Examination Survey (NHANES), 1988–1994, 1999-2004 & 2007–2012 participants age 20 & older. Single-sample estimates of eGFR & ACR; eGFR calculated using the CKD-EPI equation. Figure represents all hypertensives plus those hypertensive participants that are at target blood pressure, probably due to medication. Abbreviations: ACR, urine albumin/creatinine ratio; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.

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Mineral Bone Disorder in CKD

www.medical.siemens.com/webapp

Unadjusted survival probabilities in patients with or without CKD & walking disabilities (Medicare 65+yo)

general Medicare patients, 2005, age 65 & older, with Medicare as primary payor & surviving through the end of 2005.

Walking disability diagnoses include 782.1 “abnormal gait,” 719.7 “difficulty walking,” V15.88 “history of fall,” or an

E-code indicating a fall. Assistive devices are canes, walkers, & wheelchairs. Comorbidities identified from Medicare

claims during 2005; one-year survival & mortality determined from January 1, 2006.

USRDS 2008

CKD w/

Walking disability 77%

CKD w/o walking

Disability ~87%

Life style changes

• QoL and physical strength improved

• 6min walk, sit to stand, gait speed improved

• Sarcopenia is common in CKD morbidity/mortality

Rossi et al.2052 & Sharma et al. 2079 CJASN Dec 2014 9(12)

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Lower creatinine and atrophy

Current Research • Among older adults, lower Clcr is associated with muscle

atrophy, reduced walking speed, and more rapid declines in lower-extremity strength over time

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Metabolic Bone Disease - MBD

Prevent bone breakdown is the goal

Begins in stage 3 eGFR<60ml/min

Phosphorus retention (nl 3.5-5.5 mg/dl)

Inadequate vitamin D conversion w/ low Vit D levels

Decreased calcium absorption (nl 8.4-9.5 mg/dl)

2nd hyperparathyroidism develops - intact PTH increases

FGF-23 and other factors are not yet clinically measurable

• CALCIUM 9.2 MG/DL

• PHOSPHORUS (PO4) 5.6 mg/dl (2.4 - 4.7) H

• PARATHYROID HORMONE 427.0 pg/ml (14.0-72.0) H INTACT PTH

• 25 Hydroxy Vitamin D 20ng/ml (25-80) L

KDOQI 2003

Therapy Goals for MBD

Prevent and control 2nd hyperparathyroidism • Phosphorus control w/ diet &/or calcium or noncalcium

binders

• Active vitamin D e.g. calcitriol or analog e.g. paricalcitol or doxercalciferol

• Inactive vitamin D replacement as needed

• Cinacalcet alters Ca+ sensing PTH cells: dialysis approved

• Calcium replacement if needed; use Ca based binders

• Must monitor labs with therapy

• calcitriol (ROCALTROL) 0.25 MCG capsule daily

• D3 1000 IU /day

KDIGO, 2009

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Metabolic Acidosis

• Inadequate excretion of hydrogen and ammonium

• Inadequate production of or a loss of bicarbonate

• Consequences include increased serum potassium, bone resorption, muscle catabolism, progression of CKD.

Perumal & Argekar, Hdbk CKD Manage 2011, 171; KDIGO, 2012

Treatment of acidosis in CKD

• Goal

• Serum HCO3 > 22 but less than 32mEq/l

• Agents

• Sodium bicarbonate 650mg tab = ~8mEq HCO3

• Sodium citrate (Bicitra) 1mL= ~1mEq HCO3

• Dose of HCO3 • 1-1.5mEq/kg/day – depends on renal insufficiency

Perumal & Argekar, 2011

Case Study: Metabolic Acidosis • SODIUM (NA) 141.0 MMOL/L

• POTASSIUM (K) 5.20 MMOL/L H

• CHLORIDE 115.0 MMOL/L H

• CO2 CONTENT (BICARBONATE)16 MMOL/L L

Treatment

• sodium bicarbonate 650 MG tablet 2 times a

day

• Dietary counseling

• Are uremic symptoms evident?

• What is the albumin?

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Nutritional Considerations

Turban & Miller, Hdbk of CKD Manage 2011, 70

Sodium (Na)

• 2.3-2.4g/day stage 1-4 • 2.9-4.3g/d average US diet

• LVH & stroke linked to high sodium intake

• Lower sodium intake • b/p; 5-10mm SBP

• Improved diuretic action

• proteinuria

• RAAS drugs augmented

Potassium (K)

• 2-4g/d stage 1-4 • 2.4-3.4g/d average US diet

• Increased K intake • b/p; 3-8mm SBP

• CV events

• risk of kidney stone

• bone loss

• Animal models show kidney protection

• Monitor serum K levels

Dietary considerations

Current Research

• High sodium diets can activate inflammatory products

• Sodium: low salt diet decreased albuminuria

• RAAS meds work better in a lower sodium diet

Ho Hwang et al. CJASN Dec 2014, 9(12) 2059

Nutritional considerations - protein

• 0.8gm/kg/IBW/day is the minimum recommended daily allowance (RDA)

• Need to use ideal body weight for assessment

• Complete amino acids necessary for body to make protein – or it converts to fat & carbohydrate

• Protein

Fouque & Juillard, 2011

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Nutritional considerations – protein and CKD

Protein in CKD

• protein = proteinuria in many studies

• protein may = PO4, sodium, lipids, & insulin resistance

• If <0.6gm/kg/day will need to supplement with essential amino acids

• Monitor for malnutrition (albumin, prealbumin, cholesterol)

• TOTAL PROTEIN 6.7 G/DL

• ALBUMIN 2.9 G/DL

(3.5 - 4.8) L

• Dietary evaluation as well

as evaluate RAAS

protection to decrease

proteinuria

• What is the BUN (falling

BUN can indicate

malnutrition)?

Fouque & Juillard, Hdbk of CKD Manage 2011, 97

Lifestyle recommendations

• Targeting ideal body weight

• proteinuria & b/p, insulin resistance

• Exercise 30/min/day and 30-35kcal/kg/day

• Cessation of smoking including 2nd hand smoke

• proteinuria

• progression of CKD

• Effect seems more pronounced in men

• CVD

• Alcohol – <1/day women, < 2/day men

• Cocaine associated with acute b/p

American Diabetes Association

Anderson, 2011, 52/Connor & Norris, 2011, 44 Hdbk CKD Manage; NKF 2000

Avoid Nephrotoxic Substances

• NSAIDs (COX-2 inhibitors, ibuprofen) are potentially nephrotoxic • Acetaminophen (Tylenol) better choice • Avoid other nephrotoxic substances e.g. intravenous dye,

aminoglycosides, amphotericin B, cyclosporin, tacrolimus, lithium

• ACE inhibitors/ARBs need monitoring Adjust doses or use drugs for short time frame.

Olyaei & Roberti, Hdbk CKD Manage 2011, 376

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Vaccinations

Influenza annually

Pneumococcal polysaccharide vaccine (Pneumovax 23) or pneumococcal 13-valent conjugate vaccine (Prevnar 13) administration depends on age and health factors

Tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine adsorbed (Tdap) ADACEL™ booster vaccine for age 19-64. BOOSTRIX® for ages 10-18. Replaces the former Td (tetanus/diphtheria booster). Given every 10 years but can be given up to 2 years after last Td to protect against pertussis.

Hepatitis B: Recombivax HB™ or Engerix-B® if <19years of age or in high risk category

Zostavax® to prevent shingles (for age >50, previous history of chickenpox, no immunosuppressive therapy e.g. transplant, no HIV)

Centers for Disease Control www.cdc.gov

Considerations for dialysis

• Underlying disease

• Age - AKI most prevelent in >65yo & less likely to recover

• Patient and family preference

• Providing the option of trial dialysis

• Benefits of conservative management vs dialysis

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CKD and Patient Centered Care

• Patient preferences, values, & needs considered

• Quality of life vs quantity of life

• Have discussions before there is a crisis; shared decision making with care team and patient/family

• Dialysis is often presented as a necessity

• Conservative management – symptom relief, medication, palliative care/hospice

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End of Life Considerations

• Last month of life: twice as many days in hospital for patients on dialysis vs cancer.

• Hospital deaths for age matched Medicare -45% on dialysis vs 35% CHF, COPD, dementia, liver disease

• Hospice & palliative care used 50% less in dialysis vs other chronic illnesses.

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Is there a “best “dialysis?

Hemodialysis Accesses

Arterial venous fistula AVF

(preferred)

Graft AVG

Catheter

(can be temporary or

permanent)

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Peritoneal Dialysis

Kidney Transplant

Transplant Criteria • ~100,000 awaiting kidney transplant in US

• 2013 – 16,895 transplants performed

• Criteria changed Dec 2014: longer survival & improved utilization of kidneys

• Match donor & recipient for projected survival

• Highly sensitized patients will have option for kidney from regional or national pool

• Wait time starts when dialysis starts

• More pediatric priority

• B recipients might receive A or AB kidneys

http://optn.transplant.hrsa.gov/

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WAK – wearable artificial kidney

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Weighs 9-10 lbs

Implantable bio-artificial kidney

Goals: • Device size about 750ml • No pump - use cardiac output • No battery • 30ml/min small solute clearance • Albumin loss less than 2gms/day • Fluid excretion about 3 liters/day • Salt & water reabsorption • Vitamin D & EPO capability

Current • Plastic case • Silicon chips with nanopore membranes

(glomerulus) • Anti clotting coating on membrane • Human renal tubule cells from transplant

kidney discards for water, electrolytes, endocrine function

• Large animal testing 2014 • Human testing expected 2017

UCSF at San Francisco-Dr. Shuvo Roy April 2014; image-Bay Area Mercury News, April 2013

Definable Target Treatments

• Blood pressure: < 140/90 mm Hg

• Proteinuria: < 500mg – 1gm/day

• Anemia: Hemoglobin 10-11

• Ca, Phosphate, iPTH: Normal values

• Nutrition: HCO3 & Albumin = Normal

• Sequential measurement of kidney function

• Predict progression

• Education & preparation: multidiscipline team

RPA Clinical Practice Guideline, 2002