10 ckd faq’s & practice tips mark thomas royal perth hospital
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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
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