10 CKD FAQ’s & 10 CKD FAQ’s & Practice TipsPractice Tips

Mark ThomasMark Thomas

Royal Perth HospitalRoyal Perth Hospital

10 CKD FAQ’s & Practice 10 CKD FAQ’s & Practice TipsTips

Grading CKD severity: eGFR & uACRGrading CKD severity: eGFR & uACR eGFR: estimate or guess-timate?eGFR: estimate or guess-timate? CKD: 6 red flagsCKD: 6 red flags Drug modification in CKDDrug modification in CKD BP Drug #1: ACEi or ARB (& when not)BP Drug #1: ACEi or ARB (& when not) High K+: how to keep the ACEi goingHigh K+: how to keep the ACEi going BP Drug #2: CCB before diuretic (& when BP Drug #2: CCB before diuretic (& when

not)not) Gout in CKD: Tread carefullyGout in CKD: Tread carefully How many diabetics have CKD?How many diabetics have CKD? Metformin, incretins & SGLT2i in Metformin, incretins & SGLT2i in

diabetic CKDdiabetic CKD

CKD Stages by GFRCKD Stages by GFR

1+.1+. HyperfiltrationHyperfiltration >120 >120 mls/minmls/min

1.1. N N (but abn US/MSU)(but abn US/MSU) 90-120 90-120 mls/min mls/min

2.2. Mild Mild < 90 < 90 mls/minmls/min

3.3. Mod Mod < 60 < 60 mls/minmls/min

3a3a >45, >45, 3b3b <45 <454.4. SevereSevere < 30 < 30 mls/minmls/min

5.5. Severe/ESKDSevere/ESKD < 15 < 15 mls/min mls/min

5d5d or or 5t5t ESKD: HD/PD or ESKD: HD/PD or TxTx

New Australian CKD staging by GFR New Australian CKD staging by GFR & ACR& ACR

Albuminuria Stage Albuminuria Stage (urine ACR mg/mmol)(urine ACR mg/mmol)

GFR GFR StageStage

GFR GFR (mL/min/(mL/min/1.73m1.73m22))

NormalNormalMale: < 2.5Male: < 2.5

Female: < 3.5Female: < 3.5

Microalbuminuria Microalbuminuria Male: 2.5-25Male: 2.5-25

Female: 3.5-35Female: 3.5-35

MacroalbuminuriMacroalbuminuriaa

Male: > 25Male: > 25Female: > 35Female: > 35

11 ≥≥9090 Abnormal MSU, renal US or renal

biopsy22 60-8960-89

3a3a 45-5945-59

3b3b 30-4430-44

44 15-2915-29

55<15 or on <15 or on dialysisdialysis

↓↓eGFR & ↑uACR: death or eGFR & ↑uACR: death or dialysis?dialysis?

Macro ACR >30Micro ACR 3-30Normo ACR <3

NB Log scale Y axis Hazard RatioAdapted from Levey et al, 2010, Kidney

International

eGFR: estimate or guess-eGFR: estimate or guess-timate?timate?

Can’t apply if s. Can’t apply if s. creatinine unstable, creatinine unstable, different assaydifferent assay

50-100% false high/low 50-100% false high/low eGFR in outliers:eGFR in outliers: True GFR higher: True GFR higher:

muscular, tall muscular, tall True GFR lower: True GFR lower: muscle wasting, muscle wasting,

shortshort

CKD-EPI better on CKD-EPI better on average than MDRD average than MDRD formulaformula

Levey, Ann Int Med 2009

CKD vs AKI: grading CKD vs AKI: grading severityseverity

CKDCKD AKIAKI

eGFReGFR % change in sCr% change in sCr

uACRuACR Urine output/hrUrine output/hr

Glomerular Glomerular Hyperfiltration Hyperfiltration

Excess renal Excess renal demanddemand

High protein dietHigh protein diet HypertensionHypertension HyperglycaemiaHyperglycaemia PregnancyPregnancy ObesityObesity

Reduced renal Reduced renal reservereserve

Small/premature Small/premature birthbirth

NephrectomyNephrectomy Kidney diseaseKidney disease

Jenny age 23: wants to be Jenny age 23: wants to be a muma mum

2kg baby, smoking mother2kg baby, smoking mother Chubby teenagerChubby teenager Coke and chips dietCoke and chips diet BP 130/85BP 130/85

Mum diabeticMum diabetic Uncle on dialysisUncle on dialysis

Jenny’s results: Jenny’s results: what’s wrong and by how what’s wrong and by how

much?much?Age 23Age 23

Ht: 165 cm, Wt: 85 Kg Ht: 165 cm, Wt: 85 Kg

BP 130/85BP 130/85

Serum creatinine 40 umol/L, eGFR > 90 Serum creatinine 40 umol/L, eGFR > 90 mls/min/m^2mls/min/m^2

Urine albumin: creatinine ratio 2.5 mg/mmolUrine albumin: creatinine ratio 2.5 mg/mmol

Rules of thumbRules of thumb Lean weight (BMI25) = height (cm) – 100Lean weight (BMI25) = height (cm) – 100

Expected s. creatinine ( ♀) = height (cm) – 100Expected s. creatinine ( ♀) = height (cm) – 100

Expected s. creatinine ( ♂) = {height (cm) – 100} x Expected s. creatinine ( ♂) = {height (cm) – 100} x 1.231.23

Expected GFR for age = 140 – age (yrs)Expected GFR for age = 140 – age (yrs)

Calculated GFR = (140 – age) x Calculated GFR = (140 – age) x Lean weight Lean weight x 1.23 x 1.23 ( ♂) ( ♂)

(for size outliers)(for size outliers) S. creatinineS. creatinine

Jenny’s eGFRJenny’s eGFRAge 23, Ht: 165 cm, Wt: 85 Kg Age 23, Ht: 165 cm, Wt: 85 Kg

but lean wt = 165 -100 = 65Kgbut lean wt = 165 -100 = 65Kg

i.e. i.e. 20kg overweight20kg overweight

BP 130/85 vs 95/50 5 years earlier,BP 130/85 vs 95/50 5 years earlier, SBP 35SBP 35mmHgmmHg too too highhigh

Serum creatinine 40 umol/LSerum creatinine 40 umol/L

But expected creatinine (umol/L) = lean weight (kg)But expected creatinine (umol/L) = lean weight (kg)

i.e. i.e. creatinine 25 creatinine 25 umol/Lumol/L too low too low

Jenny’s C&G eGFR = (140-Jenny’s C&G eGFR = (140-2323) x ) x 6565 / / 4040 = = 189189 mls/min mls/min

Vs Age-normal GFR = (140-Vs Age-normal GFR = (140-2323) = ) = 117117 mls/min mls/min

i.e. i.e. GFR 71 GFR 71 mls/minmls/min (60%) too high(60%) too high

Glomerulomegaly Glomerulomegaly hypothesishypothesis

Sick mothers Sick mothers Small babies Small babies Small kidneys with fewer glomeruliSmall kidneys with fewer glomeruli

Over-feeding Over-feeding Enlarged glomeruli Enlarged glomeruli Hyperfiltration Hyperfiltration ProteinuriaProteinuria

Left: Non-ATSI, Right: ATSI (same magnification)

GFR precedes GFR precedes ACR in ACR in BP BP patientspatients

N = 502 stage 1 N = 502 stage 1 BPBP72% male, mean age 34, 72% male, mean age 34, BMI 25, 147/94, no Rx, f/up BMI 25, 147/94, no Rx, f/up 7.8 yrs7.8 yrs

Microalb RR Microalb RR predictors:predictors: GFRGFR 4.94.9 24hr SBP24hr SBP 3.23.2 FemaleFemale 2.72.7 AgeAge 1.91.9

Palatini, Palatini, Kidney IntKidney Int 20062006

02468

101214161820

<94 115-124

>150

M'alb %

GFR (mls/min)

-14

-12

-10

-8

-6

-4

-2

0

2 <1.11.1-3.3 3.4-33 34-99 100-199 200+

GFR Loss

(mls/min/yr)

Hoy, 1998

ACR categories (mg/mmol)

ACR Predicts Progressive ACR Predicts Progressive CKDCKD

CKD: 6 Red FlagsCKD: 6 Red Flags

CKD eGFR

MSU, uACRRenal US

AKI Risk•Pre-renal•Renal•Post-renal

ProgressionCKD Education:AV fistula & Tx donoror ?palliative pathway

Resistant high BPACEi/ARB, CCB, diuretic

Metabolic Wastes↓Hb, ↑K, ↓HCO3, Bones (↓Ca, ↑PO4, ↑PTH, ↑ALP)

Vascular RiskTraditional & other factors

Adverse Drug ReactionsRenal excretionNephrotoxic↑CKD feature

Drug modificationDrug modification Renally-excreted:Renally-excreted: dose-adjust to dose-adjust to

GFRGFR eg Metformin 2g/day x GFR 40% = 800mg/dayeg Metformin 2g/day x GFR 40% = 800mg/day

Nephrotoxic:Nephrotoxic: cease and repeat cease and repeat GFRGFR eg NSAID, diuretic, ACEI eg NSAID, diuretic, ACEI

↑↑CKD complication:CKD complication: reduce or reduce or ceasecease ↑↑BP: NSAID, decongestants, steroidsBP: NSAID, decongestants, steroids ↓↓Hb, ↑bleeding time : aspirin & clopidogrelHb, ↑bleeding time : aspirin & clopidogrel ↑↑urea: steroidsurea: steroids

AntihypertensivesAntihypertensives

Drug 1 = ACEi or ARBsDrug 1 = ACEi or ARBs Better CV benefit and persistenceBetter CV benefit and persistence Less new-onset diabetesLess new-onset diabetes Caution if Caution if ↑↑K+, no proteinuria, dry or K+, no proteinuria, dry or

peri-op peri-op Drug 2 = Add CCB’s before diureticsDrug 2 = Add CCB’s before diuretics

Better CV benefit and persistenceBetter CV benefit and persistence Less new-onset diabetesLess new-onset diabetes Caution if oedema, tachycardiaCaution if oedema, tachycardia

BP medication BP medication persistencepersistence

MedicationMedication No 2nd script No 2nd script MedianMedian

ARBARB 19%19% 20 mths20 mths Best candesartan, telmisartanBest candesartan, telmisartan

ACEiACEi 18%18% 23 mths23 mths Best perindopril, ramiprilBest perindopril, ramipril

CCBCCB 28%28% 7 mths 7 mths Best lercanidipineBest lercanidipine

N = 48,690 PBS scripts, 2004-2006.N = 48,690 PBS scripts, 2004-2006.Simons, MJA 2008 Simons, MJA 2008

Initial BP Rx and 1 year Initial BP Rx and 1 year discontinuation ratesdiscontinuation rates

Corrao J Hypert 2008

0.5 1.0 2.0

Diuretics

Beta-blockers

Alpha-blockers

Calcium channel blockers

ACE-inhibitors

Angiotensin-receptorblockers

1.83 (1.81-1.85)

1.64 (1.62-1.67)

1.23 (1.20-1.27)

1.08 (1.06-1.09)

0.92 (0.90-0.94)

Lombardia Database; n=445,356

BP Rx & risk of new T2DMBP Rx & risk of new T2DM

143,153 patients in 22 clinical trials

Elliott WJ and Meyer PM. Lancet 2007; 369:201-207

ACEi & ARB’s: when notACEi & ARB’s: when not

With careWith care CCFCCF Low BPLow BP No proteinuriaNo proteinuria Previous coughPrevious cough

WithholdWithhold High K+High K+ DryDry Peri-operativePeri-operative Serious angio-Serious angio-

oedemaoedema PregnantPregnant

Which medications Which medications increase serum Kincrease serum K++??

ACE/ARBACE/ARB FrusemideFrusemide Cox2-NSAIDCox2-NSAID PrednisolonePrednisolone Amiloride, spironolactone Amiloride, spironolactone TrimethoprimTrimethoprim DigoxinDigoxin

Which medications Which medications increase serum Kincrease serum K++??

ACE/ARBACE/ARB tubular K+ secr’n tubular K+ secr’n

FrusemideFrusemide Cox2-NSAIDCox2-NSAID tubular K+ secr’n tubular K+ secr’n

PrednisolonePrednisolone Amiloride, spironolactone Amiloride, spironolactone tubular K+ tubular K+

secr’nsecr’n

TrimethoprimTrimethoprim tubular K+ secr’n tubular K+ secr’n

DigoxinDigoxin cellular Na/K+ ATPase cellular Na/K+ ATPase

Hyperkalaemia: causes & Hyperkalaemia: causes & RxRx IntakeIntake

Fruit, juices, nuts Fruit, juices, nuts Chocolate, branChocolate, bran

RedistributionRedistribution Acidosis, ßblockersAcidosis, ßblockers

ExcretionExcretion Renal failureRenal failure DrugsDrugs ConstipationConstipation

SO …SO … ?New pills?New pills ?New diet?New diet Reduce Reduce

ACEi/ARB doseACEi/ARB dose Add diuretic Add diuretic (if (if

wet)wet) Add HCO3 Add HCO3 (watch (watch

BP)BP)

ACEi/CCB better than ACEi/CCB better than ACEi/TZDACEi/TZD

ACCOMPLISH ACCOMPLISH n = 11500, n = 11500, ↑↑BP & CV BP & CV

risk risk → → CV event or †CV event or † Benazepril Benazepril ++ amlodip amlodip

5-10mg or HCT 12.5-5-10mg or HCT 12.5-2525

Trial stopped early at Trial stopped early at 4yrs due to 4yrs due to 20% 20% benefit for CCB armbenefit for CCB arm: :

Both CV & CKDBoth CV & CKD

CV

CKD

CCB’s & Diuretics: when CCB’s & Diuretics: when notnot

CCB’sCCB’s OedemaOedema Tachycardia Tachycardia (for (for

“idipines”)“idipines”) Bradycardia or beta-Bradycardia or beta-

blockers blockers (for (for verapamil or verapamil or diltiazem)diltiazem)

DiureticsDiuretics DryDry Low Na+ or low K+Low Na+ or low K+ High K+ High K+ (for (for

amiloride, amiloride, spironolactone, spironolactone, triamterene)triamterene)

Active goutActive gout High HCO3High HCO3 ?Pre-diabetic?Pre-diabetic

In CKD, use all 3 to counterbalance

ACEi/ARB↓GFR, ↑K+

CCB↑RBF,

↑oedema

Diuretic↓volume, ↓GFR,

↓K+

Gout in CKD: tread Gout in CKD: tread carefullycarefully

Gout:Gout: inflammation inflammation →→ ↑↑CRP, creatinineCRP, creatinine

NSAIDs:NSAIDs: ↑↑oedema, BP, creatinine, K+oedema, BP, creatinine, K+ Colchicine:Colchicine: renally-excreted; short-term GI renally-excreted; short-term GI

toxic; long-term nerve, muscle, marrow, hair toxic; long-term nerve, muscle, marrow, hair lossloss

Prednisolone:Prednisolone: ↑↑oedema & BP, oedema & BP, ↓↓K+K+

Allopurinol:Allopurinol: gouty flares if too fast; rarely gouty flares if too fast; rarely allergic rash, fever & hepatitis; safe in high-dose allergic rash, fever & hepatitis; safe in high-dose in CKDin CKD

Tip-toe through the Tip-toe through the minefieldminefield

Allopurinol if uric acid >0.40Allopurinol if uric acid >0.40 Start 50mg/day, increase 2-4 weekly by 50mgStart 50mg/day, increase 2-4 weekly by 50mg Target uric acid <0.25Target uric acid <0.25 No dose reduction for CKDNo dose reduction for CKD

If gouty flareIf gouty flare Settle with short-term colchicine, prednisolone, Settle with short-term colchicine, prednisolone,

NSAID or allNSAID or all Return to previously tolerated allopurinol doseReturn to previously tolerated allopurinol dose Escalate again when attack fully settled, but:Escalate again when attack fully settled, but:

1-2 monthly allopurinol increases 1-2 monthly allopurinol increases Low-dose pred or colchicine cover (e.g. 1-3 x/week)Low-dose pred or colchicine cover (e.g. 1-3 x/week)

Pathophysiology of Hyperglycaemia: missing

3?

Adapted from DeFronzo RA. Diabetes. 2009;58:773-795.

Gut

Pancreas

Hyperglycaemia

Decreased Insulin SecretionIncreased Glucagon Secretion

DecreasedIncretin Effect

Fat

Increased Lipolysis

Liver

IncreasedHepatic Glucose Production

Muscle

DecreasedGlucose Uptake

32

Kidney

IncreasedGlucoseReabsorption

Adrenal

↑Adrenalin, ↑cortisol

Brain

Stress, Impaired satiety

Sites/Modes of Action of Pharmacotherapy for

T2DM

Adapted from DeFronzo RA. Diabetes. 2009;58:773-795.

Gut

Pancreas

Hyperglycaemia

Fat

TZDsMetformin

Liver

Muscle

TZDsMetformin

33

Kidney

MetforminTZDsDPP-4i

SulfonylureasMeglitinidesGLP-1/DPP-4i

α-Glucosidase inhibitorsGLP-1/DPP-4i

SGLT2 inhibitors

Adrenal

CBT, SSRI

Brain

CBT, SSRI

How many diabetics have How many diabetics have CKD?CKD?

10%10% GFR < 60 GFR < 60 & & normal uACRnormal uACR

25%25% uACR uACR & normal & normal GFRGFR

50%50% Either or bothEither or both

MJA 2006; 185 (3): 140-144MJA 2006; 185 (3): 140-144

MetforminMetformin

Dose-related GI side-effectsDose-related GI side-effectsRenal excretion: Renal excretion: Dose-adjust to GFRDose-adjust to GFR

Idiosyncratic lactic acidosisIdiosyncratic lactic acidosisBlocks liver glucose release & lactic acid uptake:Blocks liver glucose release & lactic acid uptake: Stop if unwellStop if unwell

Rates of lactic acidosis/10^5 patient-years:Rates of lactic acidosis/10^5 patient-years: 57 (12-168) 57 (12-168) onon metformin (n = 3) metformin (n = 3) 28 (3-100) 28 (3-100) off off metformin (n = 2), metformin (n = 2), p = nsp = ns

Kamber, Davis et al. MJA 2008;188:446

Efficacy & safety: Efficacy & safety: DPP4 inhibitors vs GLP-1DPP4 inhibitors vs GLP-1

DPP-4 inhibitorsDPP-4 inhibitors

(gliptins)(gliptins)GLP-I GLP-I

(exenatide)(exenatide)

HbA1c % HbA1c % reductionreduction

0.74 (0.6-0.8)0.74 (0.6-0.8) 0.97 (0.8-1.1)0.97 (0.8-1.1)

Wt loss (kg)Wt loss (kg) 00 1.4kg vs 1.4kg vs placeboplacebo

4.8kg vs insulin4.8kg vs insulin

SafetySafety Infections 1.2 xInfections 1.2 x

Headache 1.4 xHeadache 1.4 x

↑↑LFTs, CCFLFTs, CCF

?No CV benefit?No CV benefit

Nausea 2.9 xNausea 2.9 x

Vomiting 3.2 xVomiting 3.2 x

→ → Pre-renal AKIPre-renal AKI

Interstitial Interstitial nephritisnephritis

Amori JAMA 2007; Engel Diabetes Ther. 2013; Scirica NEJM 2013

1yr Gliptin vs SU in CKD & 1yr Gliptin vs SU in CKD & ESKDESKD

CKDCKD ESKDESKDNumberNumber 426426 129129

HbA1c HbA1c ΔΔ -0.8 v -0.6-0.8 v -0.6 -0.7 v -0.9-0.7 v -0.9

Hypo’sHypo’s 6 v 17%6 v 17% 6 v 11%6 v 11%

Wt Wt ΔΔ -0.6 v +1.2-0.6 v +1.2 -0.2 v +0.8-0.2 v +0.8OtherOther All equivAll equiv Cellulitis/headacheCellulitis/headache

Ferreira et alFerreira et al Diabetes Care 2012Diabetes Care 2012 Am J Kidney Dis Am J Kidney Dis 20132013

Sodium glucose co-Sodium glucose co-transporter (SGLT2) transporter (SGLT2)

inhibitorsinhibitorsInduce prox tubular Induce prox tubular glycosuriaglycosuria

Benefits: Benefits: reduce HbA1c 1% with few reduce HbA1c 1% with few or no hypo’s if used aloneor no hypo’s if used alonelower weight & BPlower weight & BP

Risks: Risks: dehydration (esp if on dehydration (esp if on diuretics)diuretics)hypo’s with SU or insulinhypo’s with SU or insulinUTIs, vulvovaginitis, balanitisUTIs, vulvovaginitis, balanitisLess effective with lower GFRLess effective with lower GFR

Cefalu, Lancet Sept 2013

↓GFR →↑retention but ↓efficacy

Kasichayanulaet al, Dapagliflozin pharmacokinetics in moderate and severe CKD, BJCP 2012

50mg stat

20mg 1 week

AUC

20mg 1 week

uGlucloss

SGLT2i & CKD: ↓wt, BP, GFR & uACR

Yale et al. doi:10.1111/dom.12348

Wt

BP

GFR

uACR

Therapy PRO CON

Metformin Experience / Proven outcomes / Cost

GI symptoms/ CKD

Sulfonylurea Experience / Cost Hypo’s/ Wt. gain / CKD

DPP4-i (gliptin)

Wt. neutral / Low risk of hypo’s

Cost / CCF (saxa) / CKD (except lina) / LFT’s (vilda)

TZD (glitazone)

Low risk of hypo’sCost / Fluid retention / Wt. gain / Fracture risk / ?Bladder ca (pio)

SGLT2-i (gliflozin)

Wt. loss / SBP reduction / Low risk of hypo’s

Limited experience / Dehydration $ / UTI & thrush / CKD inefficacy

Acarbose Low risk of hypo’ / Wt. neutral / Cost

Limited efficacy / GI tolerability

GLP-1 (incretin analogue)

Wt. loss / Low risk of hypoglycaemia

Cost / Injection / GI symptoms

Insulin Experience / Effective Injection / Wt. gain / Hypo’s

42

Therapy PRO CON

Metformin Experience / Proven outcomes / Cost

GI symptoms/ CKD

Sulfonylurea Experience / Cost Hypo’s/ Wt. gain / CKD

DPP4-i (gliptin)

Wt. neutral / Low risk of hypo’s

Cost / CCF (saxa) / CKD (except lina) / LFT’s (vilda)

TZD (glitazone)

Low risk of hypo’sFluid retention / Wt. gain / Fracture risk / ?Bladder ca (pio)

SGLT2-i (gliflozin)

Wt. loss / SBP reduction / Low risk of hypo’

Limited experience / Dehydration $ / UTI & thrush / CKD inefficacy

Acarbose Low risk of hypo’ / Wt. neutral / Cost

Limited efficacy / GI tolerability

GLP-1 (incretin analogue)

Wt. loss / Low risk of hypoglycaemia

Cost / Injection / GI symptoms

Insulin Experience / Effective Injection / Wt. gain / Hypo’s 43

TOO RISKY

TOO WEAK

BASELINE

Therapy PRO CON

Metformin Experience / Proven outcomes / Cost

GI symptoms/ CKD

Sulfonylurea Experience / Cost Hypo’s/ Wt. gain / CKD

DPP4-i (gliptin)

Wt. neutral / Low risk of hypo’s

Cost / CCF (saxa) / CKD (except lina) / LFT’s (vilda)

SGLT2-i (gliflozin)

Wt. loss / SBP reduction / Low risk of hypo’

Limited experience / Dehydration $ / UTI & thrush / CKD inefficacy

GLP-1 (incretin analogue)

Wt. loss / Low risk of hypoglycaemia

Cost / Injection / GI symptoms

Insulin Experience / Effective Injection / Wt. gain / Hypo’s

44

HYPOs/WT GAIN

HYPOs/WT GAIN

BASELINE

Problems with the reactive approach

6

7

8

9

10

Years

HbA

1c (

%)

Diagnosis 5 10 15 20

Diet + met +insulin+ SU

An alternative proactive approach

6

7

8

9

10

Years

HbA

1c (

%)

Diagnosis 5 10 15 20

DietDiet + MET + Incretin + SGLT2i

+basal insulin

+complex insulin

Don’t beat up your beta-cells

Maintain beta-cell mass Avoid pancreatitis Tight BSL control Statins: ↓lipotoxicity Incretins: ↑proliferation,

↓apoptosis ?Glitazones:

↑proliferation, ↓apoptosis

ACE-I/ARB: ↓ fibrosis ?Immunotherapy for Type I

(rituximab 2009; anti IL-1 2013)

Reduce insulin demand Small meals with low

glycaemic index Tight control Avoid high-dose SU’s Early insulin

Increase insulin sensitivity Increase exercise & muscle Reduce body fat mass &

stress Use metformin +/- ?

glitazones

Individualise and prioritise therapy targetsIndividualise targets Tight targets: for young motivated compliant

patients, short duration of DM, no micro/macrovascular disease, few co-morbidities

Gentle targets: treat the elderly with respect E.g. Systolic BP 110 vs 140, HbA1c 6 vs 8%

Prioritise targets1. BP and lipids: easier to achieve, bigger mortality

benefit

2. Glucose control and weight loss

Oral Rx Insulin Rx

Too tight vs too loose control

Currie, Lancet 2010

UK GP database 1986-2008: patients > 50yrs intensified from monotherapy to either oral combination (n= 28,000) or regimen inc insulin (n = 20,000)

CV events prevented per 1000 patient yrs

Preiss D , and Ray K K BMJ 2011;343:bmj.d4243

Statins in CKD?Statins in CKD?

High CV risk population: >10% per High CV risk population: >10% per decadedecade

Prescribe for all CKD/Tx > age 50Prescribe for all CKD/Tx > age 50 Prescribe for all CKD/Tx < age 50 with Prescribe for all CKD/Tx < age 50 with

>>1 CV risk factor1 CV risk factor Don’t initiate in HD to reduce CV risk, Don’t initiate in HD to reduce CV risk,

but don’t stop if already on Rxbut don’t stop if already on Rx

Tonelli et al. KDIGO guidelines. Kidney Int Nov 2013

Toxicity vs efficacy

Fernandez et al. Cleveland Clin J Med 2011; 78:393-403; . Baigent et al. Lancet 2011; 377: 2181:2192.

Adapted from Fernandez et al. 2011.22

Aspirin benefits > risks Aspirin benefits > risks in CKDin CKD

1998 HOT study (Hypertension Optimal Treatment) 1998 HOT study (Hypertension Optimal Treatment) – factorial: aspirin vs placebo & 3 target DBPs– factorial: aspirin vs placebo & 3 target DBPs

Post-hoc analysis: eGFR > 60 vs 45-60 vs < 45 Post-hoc analysis: eGFR > 60 vs 45-60 vs < 45 mls/minmls/min

For every 1000 persons with eGFR < 45 mls/min, For every 1000 persons with eGFR < 45 mls/min, aspirin would:aspirin would:

►►Prevent 250 events (ie 76 MACE, 40 MI, 40 CVA, Prevent 250 events (ie 76 MACE, 40 MI, 40 CVA, 40 CV deaths, and 54 all-cause deaths)40 CV deaths, and 54 all-cause deaths)

►►Cause 38 events (ie 27 extra major & 11 minor Cause 38 events (ie 27 extra major & 11 minor bleeds)bleeds)

Jardine, WCN, Milan 2009Jardine, WCN, Milan 2009

Healthy lifestyle

Mediterranean diet Alcohol moderation Physical activity Non-smoking

→ Reduced all-cause mortality by

65%Koops, JAMA 2004

The SELF & the SAAB: 10-second CV protection

Sleep

Exercise

Love

Food

Avoid toxins

Statin

Aspirin

ACEi/ARB

Beta-blocker

Or something

SAFA? (Statin, Aspirin,

Fish oil, ACEi/ARB)

10 CKD FAQ’s & Practice 10 CKD FAQ’s & Practice TipsTips

Grading CKD severity: eGFR & uACRGrading CKD severity: eGFR & uACR eGFR: estimate or guess-timate?eGFR: estimate or guess-timate? CKD: 6 red flagsCKD: 6 red flags Drug modification in CKDDrug modification in CKD BP Drug #1: ACEi or ARB (& when not)BP Drug #1: ACEi or ARB (& when not) High K+: how to keep the ACEi goingHigh K+: how to keep the ACEi going BP Drug #2: CCB before diuretic (& when BP Drug #2: CCB before diuretic (& when

not)not) Gout in CKD: Tread carefullyGout in CKD: Tread carefully How many diabetics have CKD?How many diabetics have CKD? Metformin, incretins & SGLT2i in Metformin, incretins & SGLT2i in

diabetic CKDdiabetic CKD