Chronic Kidney Disease in Primary Care

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1 Clinical Stream Chronic Kidney Disease in Primary Care Dr Gerald Waters

2 Dr Gerald Waters Renal Physician Chronic Kidney Disease

3 Chronic Kidney Disease Normal functions of Kidneys Management of CKD Drugs in CKD Antihypertensives Proteinuria Cardiovascular Risk Calcium/Phosphate/Vit D Anaemia/Erythropoietin/Iron Drugs

4 Reduced kidney function lasting longer than 3 months Nephrons do not regenerate, once lost are lost forever Some hyperplasia however can occur, max 30-40% increase in function

5 Aims of management Slow progression (BP and proteinuria control) Address increased cardiovascular risk (Advanced CKD) - Manage Mineral and Bone Disorder, Anaemia, and plan for renal replacement therapy

6 (short version) Creatinine is a muscle protein, renally excreted, no other form of clearance* Serum creatinine depends on muscle mass and glomerular filtration rate = amount of blood filtered by the kidneys per unit time (ml/min, ml/sec, L/day) Easy to measure vs actual GFR measurement (radioisotope) * Also is secreted into tubule and therefore CrCl slightly overestimates GFR

7 25 yr old Male, Creatinine 140? GFR

8 GFR can be estimated from the serum creatinine using one of several formulas (Constant is 1.23 for men and 1.04 for women) (for Cr in mg/dl, k is 0.7 for females and 0.9 for males, a is for females and for males) 4 variable MDRD and CKD EPI widely used, weight not required. Not accurate for GFR>60, large or small people.

9 Rough estimate of normal range of GFR = (120-age) to (200-age) Cockroft and Gault has terrible performance 50-70% of C&G ecrcl is within 30% of true GFR compared with 83% of MDRD egfr. Conversely, 20% of MDRD egfr is more than 30% different from the true GFR. This error gets worse with increasing GFR.

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11 Stage 1 GFR>90ml/min and a kidney disease or proteinuria Stage 2 GFR Stage (3A, 45-60, 3B 30-45) Stage Stage 5 - <15, (5D on dialysis) End Stage Renal Failure Need dialysis to survive. Usually GFR<10 Can append a P for proteinuria if you like

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13 4,200 8, , ,000 42, m Ack. Kelvin Lynn

14 45 CVD Risk with CKD > <15 Age-Standardized Rate of Cardiovascular Events (per 100 person-yr)

15 2-year follow-up and comparison with prevalent dialysis patients: risk of death vs. end-stage renal disease. Collins et al 2003

16 500x as likely to die! 10x as likely 30yr old = 85 yr old

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18 Aims of treatment Slow progression Prevent complications of CKD Prevent death from CVD

19 Aggressive control of BP slows progression of CKD Targets <140/90 or 130/80 if proteinuria present CKD causes hypertension, HTN causes CKD Vicious circle Multiple drugs almost always needed

20 First line treatment in the setting of CKD especially with proteinuria / diabetes Antiproteinuric effect in addition to antihypertensive effect Alter blood flow through glomerulus physiological effect on GFR 20% reduction However over a longer time frame, slows deterioration of GFR (see next slide) Side effects can limit use persistent cough, angio-oedema, high K, others

21 30 10 Expected benefit of ACEI slower decline in GFR following the initial drop. This initial drop does not represent permanent nephron loss - GFR typically increases following discontinuation of ACEI

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23 Group 1 Cr Group 2 Cr

24 Probably similar in effect to ACEI, without the cough Candesartan available on special authority Losartan does not need special authority

25 Rate of Rise more important than absolute level 6.0 or under no concern dietary restriction, hold ACEI/ARB >6.5 refer hospital Dietary restriction avoid bananas Cut up, boil, drain veges, avoid dried fruits, low K fruit/veges = apple, pear berries, canned, avoid hot chips, kumara, fruit/vege juices, milk, soups

26 (Low Potassium) (High Potassium)

27 Thiazides Less effective in CKD, still used however Combination with ACEI particularly effective Hence Inhibace Plus, Accuretic, Co-Renitec etc Thiazide-likes much better chlorthalidone long acting, probably better for HTN Loop diuretics - Frusemide, bumetanide Generally used in advanced CKD, for BP and fluid control Often combined with long acting thiazides or thiazide-like diuretics in advanced CKD

28 Dihydropyridine - Felodipine, amlodipine Non-dihydropyridine Diltiazem Most commonly used as a 2 nd or 3 rd line agent after ACEI/ARB and thiazide. The 2 types of CCB can be combined for additional antihypertensive effect if required (generally as a 5 th or 6 th - line agent)

29 3 rd or 4 th line treatment for HTN Not well tolerated by young patients Lethargy, erectile dysfunction Alpha blockers postural hypotension problematic in elderly Large doses may be required Combined alpha/beta carvedilol, labetolol Poorly tolerated

30 Spironolactone? avoided in CKD Hyperkalaemia, acute kidney injury due to dehydration However, good trial evidence of benefit in resistant hypertension Older antihypertensives rarely used, methyldopa, hydralazine etc Very poorly tolerated, long and nasty side effect list

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32 Minor damage to glomeruli leads to leakage of protein Protein damages kidney tubules and leads to nephron loss Caused by diabetes, and many other diseases Nephrotic syndrome = heavy proteinuria (PCR>350, ACR>300) AND oedema AND low albumin (<30)

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34 Reducing the amount of proteinuria slows progression of CKD ACEI, ARB primary drugs used Dual blockade (ACEI and ARB) (or super-dose ACEI) has additional antiproteinuric effect with minimal BP effect Aim for maximum tolerated does ACEI/ARB reduce other antihypertensives if needed

35 Mineral and Bone Disorder (MBD) CKD causes derangement of the Ca-Phos homeostatic mechanisms key problem is poor renal excretion of phosphate Secondary hyperparathyroidism can develop at GFR<80 despite normal serum calcium and phosphate Normalising phosphate prevents development of hyperparathyroidism and bone mineralisation disease.?? CVD

36 Phosphate level for people with kidney disease NOT ON DIALYSIS 3 years of high phosphate = 40% have died. Good phosphate 10-20% have died.

37 Phosphate and other levels for dialysis patients After 3 years on dialysis, good phosphate (etc) levels = 80% alive. Bad phosphate (etc) = 55% alive

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41 FGF-23

42 Main source of phosphate is dietary Dietary restriction of phosphate is most important measure Phosphate binders are secondary means of reducing phosphate Calcium carbonate and aluminium hydroxide Ca3(PO4)2 and Al(PO4) are insoluble hence not absorbed from the gut Sevelamer (Renagel), lanthanum carbonate used overseas, expensive, no better

43 Must be taken with meals, at the start of the meal immediately before eating. Should ideally be taken with every meal Patients often forget to take binders, particular with lunch or if away from home Serum calcium and Aluminium levels must be monitored. High Aluminium can cause bone disease

44 Cholecalciferol or unhydroxylated Vit D3 is the raw inactive form (the 1.25mg monthly form) Kidneys convert 25-hydroxy-Vit D3 to 1 alpha-25 hydroxy vit D which is the active form (also called calcitriol) Therefore patients with CKD require the active form (calcitriol or One Alpha which needs 25- hydroxylating) rather than cholecalciferol However, there is some suggestion that the inactive form does have some biological activity such as in the immune system, and therefore some Nephrologists prescribe cholecalciferol as well

45 1,25 vit-d3 suppresses Parathyroid hormone production, preventing hyperparathyroidism However, also increases dietary absorption of calcium and phosphate Administration 2 or 3 days per week maintains PTH suppression while minimising Ca/PO4 absorption

46 Vitamin D nomenclature Alfacalcidol ( One Alpha ) 1 hydroxycholecalciferol (needs double dose cf calcitriol)

47 Aim to maintain phosphate at or near normal range with binders, dietary restriction and dialysis Calcium normal range Calcium supplement Maintain PTH in normal range (?) Phosphate control, vitamin D, parathyroidectomy or calcimimetics Once on dialysis maintain at 2-9x normal KDIGO

48 Complex Iron deficiency common. IV Iron often required. Erythropoietin may be required at GFR < 45 in diabetics and GFR<30 in non diabetics. Over those GFR levels renal anaemia very rare. PHARMAC approval - Hb < 100, GFR <30, or <45 in diabetic Any specialist

49 High risk for cardiovascular disease Aspirin, statins, beta-blockers reduce risk of cardiovascular death in CKD patients. Once on dialysis, conventional risk reduction therapies show no benefit? Different mechanism? Phosphate driven? Statins show no benefit in primary prevention Warfarin for AF no benefit

50 Common drugs Metformin increased risk lactic acidosis Sotalol renal excretion, accumulation and bradycardia Digoxin monitor levels closely Gabapentin large dose reduction needed Antibiotics don t worry

51 NSAIDS Fibrates = bezalip Unexplained AKI? Interstitial nephritis Penicillins, cephalosporins, other antibiotics NSAIDS RARE: PPIs (omeprazole), allopurinol, others Chinese herbals with aristocholic acid

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