chronic kidney disease identification and management amy l. hazel, cnp kidney & hypertension...
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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 End-
Stage 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 DiseaseObjectives
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
We will NOT be discussing Renal Replacement
therapies including transplant
Acute Kidney Injury
Chronic Kidney Disease
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 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
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
MDRD (Modification of Diet in Renal Disease) Preferred method for estimating GFR using the 4-
variable 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 Cockroft-Gault formula
Chronic Kidney Disease
Stages of disease Limitations of CR
Age < 18 or >70 Gfr > 60 Extreme body size Severe malnutrition
Paraplegia or quadriplegia
Does not adjust for Hispanic or Asian populations
Tends to overestimate gfr Urinary creatinine
excretion is lower in ckd, therefore overestimating gfr from serum creatinine.
Chronic Kidney Disease
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
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
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 untimedspot untimed specimen (or early morning?????)specimen (or early morning?????) Mg albumin/g creatinine (UACR)
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
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
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
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
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
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
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 DiseaseDiabetic Nephropathy
Diabetic Kidney Disease Glomerulosclerosis 5-7 yr after dx Hypertrophy and hyperfiltration in glomerulus
Strict glycemic control ACEi ARB
Chronic Kidney DiseaseDiabetic Nephropathy
Blood pressure control Goal
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
Protein restriction, individualize Smoking cessation
Chronic Kidney DiseaseDiabetic Nephropathy
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 DiseaseDiabetic Nephropathy
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 DiseaseHypertensive Nephropathy 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 DiseaseHypertensive Nephropathy 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 DiseaseHypertensive Nephropathy
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 DiseaseHypertensive Nephropathy
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 DiseaseComplications Chronic Kidney Disease-Metabolic Bone Disorder (CKD-MBD)
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 DiseaseComplications
GFR falls
Rise in phosphorus decrease in calciumdecreased production of calcitriol
Triggers increase in Parathyroid hormone (PTH) production
Increased absorption of Phosphorus in kidneys
Normalize phosphorus with high PTH
Chronic Kidney DiseaseComplications
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 DiseaseComplications 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 DiseaseComplications
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 DiseaseComplications
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 DiseaseDiet
Sodium 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
Potassium Low: loop diuretics High: Common in
stage 4/5 & aldactone/ACEi/ARB/BB/NSAIDS
Diet? Salt substitutes? Constipation Treatment
Kayexlate education
Chronic Kidney DiseaseDiet
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 DiseaseDiet
Protein Restriction should not be used in severe ckd Restriction among selected patients Restriction, controversial 0.6-0.8g/kg per day
Provide a small reduction in rate of decline of gfr Follow body weight, serum albumin, pre-albumin in
advanced ckd Monitored by dietician
Chronic Kidney Disease& Medications
Pharmacokinetics
Bioavailability of oral meds can be increased or decreased Changes in gastric pH Increases in metabolism Decreases in absorption
Chronic Kidney Disease& Medications
Pharmacokinetics
Distribution affected by hypoalbuminemia, uremia and alterations in protein binding sites Possibility leading to toxicity of unbound drug
Chronic Kidney Disease& Medications
Pharmacokinetics
Metabolism of drugs may be increased, decreased or unchanged. Reduced activity of cytochrome P-450
Chronic Kidney Disease& Medications
Pharmacokinetics
Elimination of drugs may cause accumulation of drug and prolong its action, active metabolites may have toxic effects
Chronic Kidney Disease& Medications
Diabetic meds 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
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
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) 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
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
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
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
Cancer therapies (ATN) Toxicity, impaired gfr
Immunosuppressive agents (ATN)
Antithrombotics Many not studied in
renal population
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 gadolinium-containing contrast in gfr < 15
Chronic Kidney Disease& Medications
Over-the-counter Medications
Pseudoephedrine Nsaids Magnesium Bismuth Phosphorus-containing
enemas
Sodium bicarbonate PPI Zantac Calcium-based reflux
meds Salt substitutes Herbal remedies and
dietary supplements
Questions?Thank You!
References 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.