Transcript Chronic Kidney Disease

Chronic Kidney
Disease
Identification and Management
Amy L. Hazel, CNP
Kidney & Hypertension Consultants
Chronic Kidney Disease
One in 10 Americans have Chronic Kidney
Disease
Chronic Kidney Disease
Chronic Kidney Disease is most common in
those > 70 years old
Chronic Kidney Disease
Incidence of Chronic Kidney Disease is
increasing most rapidly in people 65 years
and older
Chronic Kidney Disease
Kidney disease is the 8TH leading cause of
death in the United States
Chronic Kidney Disease
People with Chronic Kidney Disease are 16-40
times more likely to die than reach EndStage Renal Disease
Chronic Kidney Disease
The 1-year mortality for heart attack patients
without identified Chronic Kidney Disease is
36% , compared with 51% for patients with
stage 3 to 5 CKD
Chronic Kidney Disease
Early detection and education can help
prevent the progression of kidney disease to
kidney failure
Chronic Kidney Disease
Objectives
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Define Chronic Kidney
Disease
Classify the disease by
Glomerulofiltration rate,
and amount of proteinuria
Discuss stages of disease
and its risk factors
Treatment in hypertensive
and diabetic renal disease
Consequences of disease
Medications in ckd patient
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We will NOT be discussing
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Renal Replacement
therapies including
transplant
Acute Kidney Injury
Chronic Kidney Disease
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KDOQI (Kidney Disease Outcomes Quality Initiative)
 2002 National Kidney Foundation classification
system
 Stages of Chronic Kidney Disease
KDIGO (Kidney Disease: Improving Global Outcomes)
 Updated, more clearly defined (2004)
 Classified based on cause, GFR category and
albuminuria category (2012)
Chronic Kidney Disease
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Defined
 Abnormalities in structure or function > 3 months
with implications for health
 eGFR < 60 ml/min/1.73m
 A loss of half or more of the adult level of normal
kidney function
 albuminuria or proteinuria
 Casts or blood in urine
 Structural
 Hydronephrosis, small kidneys, congenital
kidneys, polycystic kidney disease
 History of kidney transplant
Chronic Kidney Disease
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What is GFR?
 GFR (glomerular filtration rate) is equal to the total of
the filtration rates of the functioning nephrons in the
kidney.
 In young adults it is approximately 120-130
mL/min/1.73 m2 and declines with age.
Chronic Kidney Disease
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MDRD (Modification of Diet in Renal Disease)
 Preferred method for estimating GFR using the 4variable equation based on Serum Creatinine, age,
gender, and ethnicity.
 Includes body surface area
 eGFRs per 1.73m2
 May be the best estimate for eGFR in older population
 Current gold standard
More accurate than measured creatinine clearance from
24-hour urine collections or estimated by the CockroftGault formula
Chronic Kidney Disease
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Stages of disease
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Limitations of CR
 Age < 18 or >70
 Gfr > 60
 Extreme body size
 Severe malnutrition
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Paraplegia or
quadriplegia
Does not adjust for
Hispanic or Asian
populations
Tends to overestimate
gfr
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Urinary creatinine
excretion is lower in ckd,
therefore overestimating
gfr from serum
creatinine.
Chronic Kidney Disease
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Cockroft-Gault Formula
 Does not includes body weight, reflecting muscle
mass….main determinant of creatinine generation.
 May overestimate individuals having ckd after age
of 70 yrs, obese or edematous pts
 Less accurate than mdrd and ckd-epi
Chronic Kidney Disease
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CKD-Epidemiology Collaboration (CKD-EPI)
 Uses the 4 variables found in MDRD equation, with
addition of serum cystatin C to provide more
accurate eGFR than MDRD in gfr >60
 May raise the number of older individuals with ckd
 CKD-EPI and MDRD Study equations can therefore
be applied to determine level of kidney function,
regardless of a patient’s size.
Chronic Kidney Disease
To use the free GFR calculator on the NKF web site: Go to
www.kidney.org/gfr
To download NKF’s new GFR calculator to your
smartphone: Go to www.kidney.org/apps
Chronic Kidney Disease
Because of greater cardiovascular disease risk and risk of
disease progression at lower eGFRs, CKD Stage 3 is
sub-divided into Stages 3A (45–59 mL/min/1.73 m2) and
3B (30–44 mL/min/1.73 m2).
Chronic Kidney Disease
Proteinuria
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Proteinuria (most important marker of disease
progression)
 Ratio of the concentrations of urine albumin (mg/dl) to
that of urine creatnine (g/dl) on a spot untimed
specimen (or early morning?????)
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Mg albumin/g creatinine (UACR)
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Normal <30 mg albumin/g creatinine
Microalbuminemia > 30-300 mg albumin /g creatinine
Macroalbuminemia > 300 albumin/ g creatinine
Ckd if 2 of 3 tests are abnormal
Chronic Kidney Disease
Proteinuria
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Albuminuria
 Presence of excessive amounts of the protein albumin in
urine
 Microalbuminuria
 UACR 2.5-25mg/mmol in men
 UACR 3.5-35mg/mmol in women
 Macroalbuminuria
 UACR > 25mg/mmol in men
 UACR > 35mg/mmol in women
 (Urinary creatinine excretion is influenced by muscle
mass, urinary creatinine excretion higher in men, on
average, than women)
 The preferred method: urinary albumin-to-creatinine ratio
(UACR) in first void. Spot urine is acceptable if first void not
practical.
Chronic Kidney Disease
Proteinuria
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Proteinuria
 Presence of excessive amounts of proteins in urine
 Includes: albumin, low-molecular weight
immunoglobulin's, lysozyme, insulin and microglobin
 Total protein (mg/dl) to creatinine (g/dl) on a spot urine
sample
 Normal < 200 mg/g
 Urine pr mg/dl 200
 Urine cr mg/dl 100
 Ratio 200/100 = 2gm protein/24hours
 Increased excretion of protein leads to progression of ckd
and increases cvd risks
 Albuminuria and proteinuria are related, but not
interchangeable.
Chronic Kidney Disease
Proteinuria
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Persistant microalbuminemia:
 Tx lipid disorders and /or htn
 Retest in 6mo
Affect urinary albumin excretion
 UTI
 High protein diet
 Acute febrile illness
 Heavy exercise within 24 hrs
 Menstruation
 Drugs (NSAIDS, ACEI, ARB)
Chronic Kidney Disease
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Stage 1 and 2 new guidelines American College of
Physicians 2013
 Do not recommend screening for ckd in asymptomatic
adults without risk factors for ckd
 False positive test results, disease labeling
 No benefit of early treatment
 Treat hypertension in stage 1-3 ckd with acei or arb
 No need to test urine for protein in adults with or
without diabetes if currently taking acei or arb
 Manage elevated LDL in pt with stage 1-3 ckd
Chronic Kidney Disease
Risk Factors
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Diabetes
 44% of new cases of
ckd
Hypertension
 28% of new cases of
ckd
Cardiovascular
disease
Obesity
High cholesterol
Lupus
Family history of CKD
UTI/urinary stones
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Systemic infections
Recovery from Acute
Kidney Injury (AKI)
Exposure to certain
drugs
Socio-demographic
groups
 Elderly
 minority population
 African American,
Native American,
Hispanic, and Asian.
 Low income/education
Chronic Kidney Disease
Diabetic Nephropathy
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Diabetic Kidney Disease
 Glomerulosclerosis 5-7 yr after dx
 Hypertrophy and hyperfiltration in glomerulus
 Strict glycemic control
 ACEi
 ARB
Chronic Kidney Disease
Diabetic Nephropathy
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Blood pressure control
 Goal
 Diabetic or Non diabetic with Albumin-tocreatinine ratio > 30 mg/g <130/80
 Diabetic or Non diabetic with albumin-to-creatinine
ratio < 30gm/g <140/90
Protein restriction, individualize
Smoking cessation
Chronic Kidney Disease
Diabetic Nephropathy
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Hypoglycemics Agents
 Sulfonylureas, biguanides, DPP-4 inhibitors, GLP-1
agonists, and insulin require dose adjustments
 All second generation sulfonylureas can be used in
ckd pts
 Glyburide not recommended with crcl < 50%
 Glipizide, no adjustment
Chronic Kidney Disease
Diabetic Nephropathy
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Hypoglycemic Agents
 Metformin
 Lactic Acidosis
 Avoid in gfr < 30 ml/min/1.73m2
 Insulin
 Thiazolidinediones
 Decreased renal glucogenesis
 Decreased renal clearance of sulfonylureas
Chronic Kidney Disease
Hypertensive Nephropathy
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Hypertensive Kidney Disease
 Both a cause and consequence of the disease
 Primarily: Inappropriate sodium reabsorption
 Activation of RAAS
 Erythropoietin administration
 RAS
 Extracellular fluid
 Calcified arterial tree
Cardiovascular disease
 Antiplatelet agents are recommended
 BNP in gfr <60, interpret with caution
Chronic Kidney Disease
Hypertensive Nephropathy
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Management
 RAAS blockade
 Reduce proteinuria
 Lowers systemic BP and intraglomerular pressure
 More difficult d/t increase in vascular resistance and
increased blood volume
 Low sodium diet (DASH diet not recommended in
CKD stage 3-5)
 Combination of ace/arb significantly slowed disease
progression, greater reduction in proteinuria
 Use of non-dihydropyridine CCB have shown to
decrease proteinuria (if failed ace/arb)
Chronic Kidney Disease
Hypertensive Nephropathy
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Goals
 Diabetic or Non-diabetic with Albumin-to-creatinine
ratio > 30 mg/g <130/80
 Diabetic or Non-diabetic with albumin-to-creatinine
ratio < 30gm/g <140/90
 Delay progression of disease
 Reduce cardiovascular risk
Chronic Kidney Disease
Hypertensive Nephropathy
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Diuretics
 Enhances antihypertensive therapy
 Decreasing tubular sodium reabsorption, increasing
sodium excretion, reversing ECF volume expansion
and lowering bp.
 Thiazides (qd) for gfr > 30 (stage 1-3)
 Loops (qd-bid) for gfr < 30 (stages 4 & 5)
 Potassium sparing diuretics
 Risk of hyperkalemia, esp with ACEI/ARB
Chronic Kidney Disease
Complications
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Chronic Kidney Disease-Metabolic Bone Disorder (CKDMBD)
 Systemic disorder
 Renal osteodystrophy
 Extraskeletal (vascular) calcification
 Increases in morbidity and mortality of ckd pts
 Abnormalities in
 Calcium
 Phosphorus
 Parathyroid Hormone
 Vitamin D
 25(OH)D
 1,25(OH)2D
 Osteoporosis (ckd 1-3) versus renal osteodystrophy (later
stages)
Chronic Kidney Disease
Complications
GFR falls
Rise in phosphorus
decrease in calcium
decreased production of calcitriol
Triggers increase in Parathyroid hormone (PTH)
production
Increased absorption of Phosphorus in kidneys
Normalize phosphorus with high PTH
Chronic Kidney Disease
Complications
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Treat complications
 High phosphorus
 Low Phosphorus diet
 Phosphorus Binders
 Correct low Vitamin D levels
 Ergocalciferol/cholecalciferol
 Watch for high Calcium
 Active Vitamin D to suppress PTH
 Seen more in late stages of disease
Chronic Kidney Disease
Complications
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Anemia (hgb < 13g/dL in males, < 12g/dL in females)
 A decline in production of erythropoietin (EPO)
 Not measured, assumed
 Check red cell indices, absolute reticulocyte count,
vitamin B12 and folate levels, and iron panel
 Goal
 Hemoglobin???
 Serum transferrin saturation (TSAT) > 30%
 Serum ferritin <500ng/ml
 Acute phase reactant, elevated with
infection/inflammation
Chronic Kidney Disease
Complications
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Anemia Treatment
 Iron therapy
 Most common cause of anemia in ckd
 Oral vs IV
 Erythropoiesis-stimulating Agents (ESA)
 Prevent need for transfusions
 Improve QOL?
 Based on weight
 Not recommended in hgb > 10g/dL
 Treat <10g/dL on individual basis
Chronic Kidney Disease
Complications
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Metabolic acidosis
 Result of decreased production of ammonia by the
kidney
 Seen in stages 3-5
 Treatment: supplement Bicarbonate
 Complications
 Bone loss
 Anorexia
 Hypoalbuminemia
 Insulin resistance
 Muscle wasting
Chronic Kidney Disease
Diet
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Sodium
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Restriction reduces
blood pressure and
may reduce
albuminuria
Dash diet, not rec.
for ckd stage 3-5
High sodium diet
limits effectiveness
of ACEi/ARBs
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Potassium
 Low: loop diuretics
 High: Common in
stage 4/5 &
aldactone/ACEi/ARB
/BB/NSAIDS
 Diet? Salt
substitutes?
 Constipation
 Treatment
 Kayexlate
 education
Chronic Kidney Disease
Diet
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Phosphorus
 High levels contribute to vascular calcification
 High phosphorus is risk factor for cvd
 high phosphorus leads to a more rapid decline in
kidney function
 Phosphate salts added to processed foods in form of
additives and preservatives
 These are > 90% absorbed versus 40-60% absorption
from organic phosphorus (ie: beans, peas, nuts)
 Beverages (clear)
 Nutrition labeling
 Treatment: Low phosphorus diet, phosphorus binders
with meals
Chronic Kidney Disease
Diet
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Protein
 Restriction should not be used in severe ckd
 Restriction among selected patients
 Restriction, controversial
 0.6-0.8g/kg per day
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Provide a small reduction in rate of decline of gfr
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Follow body weight, serum albumin, pre-albumin in
advanced ckd
Monitored by dietician
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Chronic Kidney Disease
& Medications
Pharmacokinetics
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Bioavailability of oral meds can be increased or
decreased
 Changes in gastric pH
 Increases in metabolism
 Decreases in absorption
Chronic Kidney Disease
& Medications
Pharmacokinetics
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Distribution affected by hypoalbuminemia, uremia and
alterations in protein binding sites
 Possibility leading to toxicity of unbound drug
Chronic Kidney Disease
& Medications
Pharmacokinetics
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Metabolism of drugs may be increased, decreased or
unchanged.
 Reduced activity of cytochrome P-450
Chronic Kidney Disease
& Medications
Pharmacokinetics
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Elimination of drugs may cause accumulation of drug
and prolong its action, active metabolites may have toxic
effects
Chronic Kidney Disease
& Medications
Diabetic meds
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Sulfonylureas metabolized by liver, however
GLYBURIDE AND GLIMEPIRIDE produce active
metabolites and may contribute to hypoglycemia.
Glyburide not recommended. Glipizide, no decrease
needed.
Biguinides, metformin eliminated unchanged by kidney.
Contraindicated risk of lactic acidosis. Hold in women cr
>1.4 men 1.5mg/dl per package insert
Inctretins are eliminated by kidney, so not
recommended in crcl < 30ml/min
Insulin, with 40-50% elimination by kidneys, dose
reductions are recommended
Chronic Kidney Disease
& Medications
Statins
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Metabolized by liver, however, active metabolites
renally eliminated.
 Not atorvastatin (lipitor)
 Inc risk of myopathy with inc doses and
declining gfr
Chronic Kidney Disease
& Medications
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Antibiotics (ATN)
Most penicillins, cephalosporins, and all
fluroquinolones except moxifloxacin are eliminated
by kidneys. Require reduction
Aminoglycosides (gent, tobra) can cause
nephrotoxicity especially when used with
vancomycin
Nitrofurantoin (macrobid). Excreted by kidneys.
contraindicated in crcl <60
Sulfamethoxazole-trimethoprim (bactrim).
Nephrotoxicity. Dose reduction of ½ in CrCl 15-30
and avoid in < 15.
Chronic Kidney Disease
& Medications
Analgesics (prerenal)
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NSAIDS
 Inhibit the synthesis of prostaglandin leading to
vasoconstriction and reduced renal blood flow
to kidneys
 Cause a decline in gfr and impaired sodium,
water, potassium and hydrogen excretion
COX-2 inhibitors work similarly to NSAIDS in that
they inhibit synthesis of prostaglandin production
Chronic Kidney Disease
& Medications
Antihypertensives
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All ACEi have some renal elimination. Use lower
doses. High risk for high k+, increase in serum
creatinine and hypotension
All ARBs are metabolized by liver, however, watch
k+, serum creatinine and blood pressure in ckd
BetaBlockers
 Many eliminated by kidney. Dose adjustments are
recommended and follow hr and blood pressure
Chronic Kidney Disease
& Medications
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Diuretics
 Thiazide are recommended in those with gfr >30
 Loop are recommended in those with gfr <30
 Potassium-sparing should be used with
caution in those with gfr < 30
Chronic Kidney Disease
& Medications
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Gabapentin (neurontin). Primarily removed by the
kidneys. Use with caution.
 Stage 3 400-1400 in two divided doses
 Stage 4 200-700 once daily
 Stage 5 100-300 once daily
Gout medications
 CKD patient at increased risk for hypersensitivity
reactions from drug. Use of low dose colchicine or
xanthine oxidase inhibitors (uloric, allopurinol)
 Inject glucocorticoids for flare
 Avoid NSAIDs
Chronic Kidney Disease
& Medications
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Cancer therapies
(ATN)
 Toxicity, impaired gfr
Immunosuppressive
agents (ATN)
Antithrombotics
 Many not studied in
renal population
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Diagnostic agents (ATN)
 Use of low osmolar
contrast (but still
problem with high risk
pts) less nephrotoxic
 Hold potentially
nephrotoxic agents
before and after
procedure
 Adequately hydrate with
saline before, during and
after procedure
 Avoid gadoliniumcontaining contrast in gfr
< 15
Chronic Kidney Disease
& Medications
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Over-the-counter
Medications
Pseudoephedrine
Nsaids
Magnesium
Bismuth
Phosphorus-containing
enemas
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Sodium bicarbonate
PPI
Zantac
Calcium-based reflux
meds
Salt substitutes
Herbal remedies and
dietary supplements
Questions?
Thank You!
References
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Willems, J.M, et al Performance of Cockroft-Gault, MDRD, and CKD-EPI in estimating prevalence of renal function and
predicting survival in the oldest old. BioMed Central 2013
National Kidney and Urologic Diseases Information Clearinghouse
Matzke, G. R, et al. Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from
Kidney Disease: Improving Global Outcomes (KDIGO). Kidney International 2011
Qassem, A. Screening, Monitoring, and Treatment of Stage 1 to 3 Chronic Kidney Disease: A clinical practice guideline from
the clinical guidelines committee of the American College of Physicians. American College of Physicians. 2013
Perazella, M. A. Core Curriculum in Nephrology. Toxic Nephropathies: Core Curriculum 2010. American Journal of Kidney
Disease. Feb 2010
Zuber, K., et al. Medication dosing in patients with chronic kidney disease. Journal of the American Academy of Physician
Assistants. 2013
Liles, A. M., Medication considerations for patients with chronic kidney disease who are not yet on dialysis. Nephrology
Nursing Journal, May-June 2011
Johnson, D. W., Chronic kidney disease and measurement of albuminuria or proteinuria: a position statement. Medical
Journal of Australia, August 2012
Eknoyan, G, et al. Proteinuria and other markers of chronic kidney disease: A position statement of the National Kidney
Foundation (NKF) and the National Institute of Diabetes and Kidney Diseases (NIDDK)
Bakris, G. L., Slowing Nephropathy Progression: Focus on Proteinuria Reduction. American Society of Nephrology, 2008
James, P. A., 2014 Evidence-Based Guidelines for the Management of High Blood Pressure in Adults: Report From the
Panel Members Appointed to the Eight Joint National Committee (JNC 8). Journal of American Medical Association, 2013
National Kidney Foundation: Kidney Disease Outcomes Quality Initiative Guidelines
Summary of Recommendation Statements. Kidney Disease International Supplement, 2012
Ferrari, P. Serum iron markers are inadequate for guiding iron repletion in chronic kidney disease. American Society of
Nephrology, 2011
Kopple, J. D., Risks of chronic metabolic acidosis in patients with chronic kidney disease. Kidney International,
Supplement, 2005.