chronic kidney disease

end stage kidney disease

end stage kidney disease

CKD being treated by dialysis or transplantation

glomerular filtration rate

measure of filtering capacity of kidney, estimation

used to assess degree of impairment and follow disease course

**cannot measure directly

ways to estimate GFR

cockcroft gault (CrCl)
MDRD (modification of diet in renal disease)
CKD-EPI

G1

GFR >/= 90

G2

60-89 GFR

G3a

45-59

G3b

30-44

G4

15-29

G5

<15

A1

albumin excretion rate <30mg/24hr, albumin to creatinine ratio <3mg/mmol

A2

albumin excretion rate 30-300mg/24hr

albumin to creatinine ratio 3-30mg/mmol

A3

albumin excretion rate >300mg/24hr

albumin to creatinine ratio >30mg/mmol

hemodialysis

blood and a physiologically balanced solution (dialysate) are simultaneously pumped through a dialysis machine on opposite sides of a semipermeable membrane

two mechanisms of solute transport in HD

diffusion

ultrafiltration/convection

options for hemodialysis

in centre 3x weekly for 3-4hr

short daily 5-6x per week at home

nocturnal 8-10hr per night at home

continuous renal replacement therapy (CRRT):

• critical care, less hemodynamic change, gentler, drug dosing different

peritoneal dialysis

dialysate instilled into the peritoneal cavity via an intra abdominal catheter

peritoneal membrane acts as a semi permeable membrane across waste products pass into the dialysate and are removed

advantages of peritoneal dialysis

can be done at home

less risk of hypotensiom

continuous ambulatory peritoneal dialysis (CAPD)

usually 2L of dialysate changed 4-5x daily, present continuously 24hr a day

etiologies of CKD

diabetes 36% (he said 40-45)

renal vascular disease (htn) 13%

primary renal diseases:

• glomerulonephritis (10%)

• polycystic kidney disease (3.3%)

• drug induced (1.9%)

• other (12.3%)

• unknown/unreported (21.3%)

signs + symptoms of CKD

vague and non specific

• fatigue and malaise

• edema

• decreased urine output (later stages)

• htn

• HF

• pericarditis

• anorexia, nausea and vomiting (later)

• pruritis

• pallor

• restless leg syndrome

• impaired cognition

• bone pain

diagnosis of CKD

measurement of SCr and estimation of GFR can identify patients with reduced kidney fxn

proteinuria is an early and sensitive marker of kidney damage

• single random measure of albumin to creatinine ratio in the urine preferred

• albumin creatinine ratio (ACR)- >60mg/mmol- high risk of progression to ESRD

• microalbuminuria >/=2.5mg/mmol (male) or >/=3mg/mmol (female)

lifestyle management to improve CKD progression/CV risk

smoking cessation

healthy body weight- BMI 20-25

protein- lower to 0.8g/kg/day if GFR <30mL/min

alcohol- 2 drinks per day for men, 1 for women

exercise- 30min mod intensity 5 days per week as otlerated

dietary salt <90mmol/day (<5g NaCl)

hypertension management to improve CKD progression and CV risk

CKD-ND without diabetes target </=140/90

CKD-ND with diabetes target </=130/80mmHg

elderly- CHEP: SBP <150mmHg for very elderly 80+

2-3 agents or more, no strong evidence for particular class except ACEI/ARB with proteinuria

choice of agents less important than BP reduction achieved

consider renal dosing, efficacy, accumulation

antihypertensives CKD considerations

thiazides GFR <30-50mL/min less effective

loop is best choice in CKD 4-5, edema

K sparing usually avoided

BB accumulate in advanced CKD (atenolol, bisoprolol)- most are dialyzed out therefore not big deal if on dialysis

CCB- avoid DHPs with increased urinary albumin excretion, esp if not on ACEI/ARB (once on dialysis usually switch to DHP tho)

when to use ACEI/ARB in CKD

diabetic- urine albumin excretion >30mg/24hr

non diabetic with indication for BP lowering drug: urine albumin excretion >30mg/24hr

RAAS blockers CKD considerations

ACEI/ARB- hyperkalemia and decline in GFR can occur, monitor, increased Cr as much as 30-35% acceptable if stabilizes in 2-4mo - happens early within 3-5 days

aldosterone antagonists- caution- eplerenone, spironolactone

target A1C in CKD

7%- evidence that it prevents microvascular complications of disease

do not treat to <7% if at risk of hypo

in pts with comorbidities or limited life expectancy and risk of hypoglycemia extend target HBA1C above 7%

hyperglycemia drug considerations in CKD

metformin avoid when <30mL/min, caution <60mL/min; hold if acutely unwell

sulfonylureas:

• avoid glyburide (esp <30mL/min)

• glimepiride- may accumulate, caution

• gliclazide- safer, may need to reduce dose

TZDs- no adjustment required but CV risk and fluid retention

repaglinide- no adjustment, start lower

acarbose- less effective, not used in stage 4-5

GLP-1 agonists- exenatide do not use <30mL/min, liraglutide not sutdied

DPP-4i

• sitagliptin significant dose reductions <30

• saxagliptin reduce dose <50

• linagliptin- no dose adjustment, use with caution in ESKD

SGLT2i - do not start <60mL/min

insulin- may need reduced dose

dyslipidemia drugs in CKD

>/=50 with GFR <60- statin or statin/ezetimibe

>/=50+ with GFR >60- statin

18-49yo use statin if:

• coronary disease

• diabetes

• prior ischemic stroke

• estimated 10yr incidence of coronary death or non fatal MI >10%

dialysis dependant CKD do not initiate statin or statin/ezetimibe- if receiving can continue

adult kidney transplants- statin

fixed maximum doses when GFR <60

early, characteristic morbid manifestation of CKD

anemia

type of anemia in CKD

normochromic normocytic

anemia of CKD causes

decreased EPO production by kidney

iron deficiency

blood loss

inflammation

secondary hyperparathyroidism

shortened RBC survival

folate, B12 deficiency

_____ is essential for erythropoiesis

iron

why is iron given in CKD

to treat iron deficiency

prevent iron deficiency when on ESA

raise Hb with or without ESA

reduce ESA doses

2 ways to assess iron

serum ferritin- surrogate marker for tissue iron stores and is an acute phase reactant therefore may be elevated for reasons other than high tissue iron stores

transferrin saturation (TSAT)- represents iron which is available

both have limited sensitivity and specificity to predict bone marrow stores and response to iron supplementation

non dialysis vs dialysis ferritin targets

non dialysis >100ng/mL

dialysis >200ng/mL

max 800ng/mL

when to give iron according to ferritin

if ferritin </=500ng/mL and an increase in Hb or a decrease in ESA dose is desired

do not routinely administer IV iron if consistently >500ng/mL- if Hb below desired target, on high ESA dose or desire to d/c ESA may give therapeutic trial after considering risks

consider iron if above 800 and TSAT <25%, high ESA dose and Hb below target

TSAT target

>/=20%

when to give iron according to TSAT

if TSAT </=30% and an increase in Hb or a decrease ESA dose is desired

strongest indication for iron therapy

TSAT </=20% and ferritin </=200ng/mL

first line iron ROUTE in CKD-ND/PD

oral

IV if not meeting targets or can’t tolerate

CKD-HD prefered IRON route

intravenous preferred

what is important for effect of ESA

adequate Iron

differences in the 2 ESAs used

epoetin alfa- recommended dosing 3x a week, less efficient when given IV/less freq

darbepoetin alfa-recommended dosing 1x a week or every 2wks, takes 3-5x longer to reach peak serum conc (lower binding affinity to receptor)

hemoglobin target

95-115

monitoring of ESAs

monitor every 1-2wks during initiation, once stable monitor monthly

desired rise in Hgb 10g/L/month to achieve target in 2-4mo

dose titration 10-25% (sometimes 25-50)

ae of ESAs

htn

increased vascular access clotting

pure red cell alasia- anti erythropoetin antibodies, severe ESA resistant anemia

recommendation of using ESA in malignancy/stroke

not recommended in active malignnacy or history of stroke in last 3mo

CKD effects on bone and mineral

as kidney fxn declines there is progressive detioration in mineral homeostasis- phosphoros, calcium, vit d, PTH

leads to:
- high turnover bone disease (bone marrow fibrosis, weakening, fractures)

-extra skeletal calcification (vascular, calciphylaxis)

-secondary hyperparathyroidism

what happens to phosphorous and active vit d as GFR decreases

phosphorous retention (hyperphosphatemia)- bc active vit D is not produced by kidney, resulting in decrease Ca absorption ehich stimulates bone to release Ca and Po

decreased active vit D - calcitriol-1,25(OH)2D

parathyroid gland role

small endocrine glands in the neck which contain calcium sensing receptors and vitamin D sensing receptors

produce PTH- released when Ca is low in blood

• promotes bone resorption by osteoclasts

• in kidney increases Ca reabsorption and decreases PO4 reabsorption

• increases production of active vit D by kidney

what parts of PTH homeostatis are NOT effective in CKD

kidney cannot increase Ca reabsorption and decrease PO4 reabsorption

kidney cannot increase production of activated vit d in kidney

PTH release is increased by

hypocalcemia

vit d deficiency

hyperphosphatemia

secondary hyperparathyroidism in CKD

hypocalcemia leads to an increased PTH release

vit d is a potent inhibitor of PTH production therefore vit D defiicency leads to an increased PTH production

PO4 thought to increase PTH production directly

PTH stim osteoclast activity which causes bone breakdown to release calcium in serum

eventually hyperplasia occurs and the gland can no longer respond to compensatory stimuli-becomes autonomous

CKD BMD goals of therapy (phosphorous, calcium, PTH)

phosphorous

• stages G3-5 (CKD-ND)- maintain in the normal range

• dialysis lower toward normal range

calcium

• stages G3-5 maintain normal range

PTH

• stages G3-5 (CKD-ND) optimal level unknown, correct PO4, Ca, vit D first if PTH above normal level

• in dialysis maintain in range 2-9x upper limit of normal

how does calcium exist in blood

protein bound (40%), free (48%), complexed to anions (12%)

hyperphosphatemia management

diet

increase dialysis time

phosphate binding agents- calcium carbonate, sevelamer, lanthanum

how to take phosphate binders

MUST be taken with meals to be effective, work in GI tract

best phosphate binder

no evidence - choice should be individualized

side effects of calcium

hypercalcemia- if persistent or recurrent stop or reduce dose, reduce or stop if arterial calcification, adynamic bone disease or persistently low PTH

constipation

nausea

what is sevelamer approved in

dialysis only

how to take sevelamer

swallow whole do not chew,crush split (still take w meals)

ae of sevelamer

nausea, vomiting, diarrhea, dyspepsia, abdominal pain, constipation, pruritis

limb pain, arthralgia

nasopharyngitis, bronchitis

when to avoid sevelamer

dysphagia, swallowing disorders, severe GI motility disorders, major GI surgery

sevelamer interactions

may interact with quinolones, levothyroxine, mycophenolate

what is lanthanum approved for

dialysis only

ae of lanthanum

nausea, vomiting, ab pain, diarrhea, constipation, headache

magnesium risks

hypermagnesemia, GI ae

when to use aluminum

no longer recommended due to aluminum toxicity, CNS tox, osteomalacia, microcytic anemia, hyperK and diarrhea

if used, reserved for situations where PO4 is VERY high and then only for short courses- max 30days

hyperparathyroidism management options

VIt d analogs (calcitriol, alfacalcidiol)

calcimimetic- cinacalcet

parayhtoridectomy (gold standard)

when can you not start vit d analogs

if hypercalcemic or hyperphosphatemic

why are calcitriol and alfacalcidiol the vit d analogues used in CKD

do not require kidney hydroxylation

ae of vit d analogues

hyperphosphatemia and/or hypercalcemia

when to stop vit d analogues

avoid oversuppression of PTH

• stop or reduce dose if PTH below 2x upper limit of normal

• adynamic bone disease

calcimimetic ae

hypocalcemia- careful monitoring, stop or reduce

GI intolerance,myalgia

when to stop calcimemtric

stop or reduce dose if PTH below 2x ULN

adynamic bone disease

hypocalcemia (stop or reduce- monitor carefully)

post parathyroidectomy management

close monitoring and Ca and Vit D supp

how to manage hypervolemia

furosemide, dietary fluid restriction, dietary sodium restriction

how to manage hyperkalemia

sodium polystrene sulfonate

diet

dialysate K

loop diuretic

**caution ACEI/ARB

what occurs in metabolic acidosis

retention of H+

inability of kidneys to regenerate sufficient bicarb

causes a reduction in kidney synthesis of active vit d, bone buffering of excess H+, muscle breakdown

management of metabolic acidosis

recommended to maintain sodium bicarb above 22mEq

po sodium bicarb Rx

immunization recommendations CKD

Hep B GFR <30

annuel influenza vax

polyvalent pneumococcal vax - all GFR <30

• high risk (immunosuppresants, diabetics) re vax in 5yr

assumed CrCl in dialysis

10

hemodialyzability is determined by:

molecular weight

• MW up to 500 removed by low flux membranes

• MW up to 20 000 removed by high flux membranes

soluvility- water soluble substances more likely to diffuse into dialysate that is aqueous

protein binding- only unbound can cross membrane

Vd- large VD less easily removed

type of dialyzer membrane

analgesic dosing in CKD

avoid meperidine

reduce opioid doses GFR <30

consider metabolites, accumulation

NSAIDs avoid GFR<30, short term only <60 (avoid with RAAS or lithium)

gabapentin/pregablin- dose decrease <60

anticoagulants dose reductions

LMWH reduce dose GFR <30 - consider UFH if high bleeding risk

warfarin- increased bleed risk GFR <30- close monitoring

dabigatran reduce dose <30, do not use <15

apixiban >25 usual, no rec <25, do not use <15

rivaroxaban- >30 usual, do not use <30