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 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 Disease Objectives
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
kidney function or more of the adult level of normal 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 variable equation
for estimating GFR using the
4-
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 24-hour urine
than measured creatinine clearance from 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
of 70 yrs, obese or edematous pts after age
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 untimed
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 Disease Diabetic Nephropathy
Diabetic Kidney Disease Glomerulosclerosis 5-7 yr after dx Hypertrophy and hyperfiltration in glomerulus Strict glycemic control ACEi ARB
Chronic Kidney Disease Diabetic 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 Disease Diabetic 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 Disease Diabetic 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 Disease Hypertensive 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 Disease Hypertensive 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 Disease Hypertensive 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 Disease Hypertensive 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 Disease Complications
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 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
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
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
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
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
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 Disease Diet
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
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
decreased of oral meds can be increased or 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
Nephrotoxicity.
Dose reduction
(bactrim). 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
recommended and follow hr and blood pressure are
Chronic Kidney Disease & Medications
Diuretics
Thiazide
are recommended in those with
gfr >30
Loop
are recommended in those with
gfr <30
Potassium-sparing caution
should be in those with gfr < 30
used with
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.