Chronic%20Kidney%20Disease

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Chronic Kidney Disease

• Identification and Management
• Amy L. Hazel, CNP
• Kidney Hypertension Consultants

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Chronic Kidney Disease

• One in 10 Americans have Chronic Kidney Disease

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Chronic Kidney Disease

• Chronic Kidney Disease is most common in those gt
  70 years old

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Chronic Kidney Disease

• Incidence of Chronic Kidney Disease is
  increasing most rapidly in people 65 years and
  older

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Chronic Kidney Disease

• Kidney disease is the 8TH leading cause of death
  in the United States

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Chronic Kidney Disease

• People with Chronic Kidney Disease are 16-40
  times more likely to die than reach End-Stage
  Renal Disease

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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

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Chronic Kidney Disease

• Early detection and education can help prevent
  the progression of kidney disease to kidney
  failure

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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

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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)

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Chronic Kidney Disease

• Defined
• Abnormalities in structure or function gt 3 months
  with implications for health
• eGFR lt 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

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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.

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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

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Chronic Kidney Disease

• Stages of disease
• Limitations of CR
• Age lt 18 or gt70
• Gfr gt 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.

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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

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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 gt60
• 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 patients size.

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Chronic Kidney Disease

• To use the free GFR calculator on the NKF web
  site Go to www.kidney.org/gfr
• To download NKFs new GFR calculator to your
  smartphone Go to www.kidney.org/apps

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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 (4559
  mL/min/1.73 m2) and 3B (3044 mL/min/1.73 m2).

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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 lt30 mg albumin/g creatinine
• Microalbuminemia gt 30-300 mg albumin /g
  creatinine
• Macroalbuminemia gt 300 albumin/ g creatinine
• Ckd if 2 of 3 tests are abnormal

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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 gt 25mg/mmol in men
• UACR gt 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-creatinin
  e ratio (UACR) in first void. Spot urine is
  acceptable if first void not practical.

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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 lt 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.

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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)

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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

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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

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Chronic Kidney DiseaseDiabetic Nephropathy

• Diabetic Kidney Disease
• Glomerulosclerosis 5-7 yr after dx
• Hypertrophy and hyperfiltration in glomerulus
• Strict glycemic control
• ACEi
• ARB

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Chronic Kidney DiseaseDiabetic Nephropathy

• Blood pressure control
• Goal
• Diabetic or Non diabetic with Albumin-to-creatinin
  e ratio gt 30 mg/g lt130/80
• Diabetic or Non diabetic with albumin-to-creatinin
  e ratio lt 30gm/g lt140/90
• Protein restriction, individualize
• Smoking cessation

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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 lt 50
• Glipizide, no adjustment

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Chronic Kidney DiseaseDiabetic Nephropathy

• Hypoglycemic Agents
• Metformin
• Lactic Acidosis
• Avoid in gfr lt 30 ml/min/1.73m2
• Insulin
• Thiazolidinediones
• Decreased renal glucogenesis
• Decreased renal clearance of sulfonylureas

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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 lt60, interpret with caution

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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)

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Chronic Kidney DiseaseHypertensive Nephropathy

• Goals
• Diabetic or Non-diabetic with Albumin-to-creatinin
  e ratio gt 30 mg/g lt130/80
• Diabetic or Non-diabetic with albumin-to-creatinin
  e ratio lt 30gm/g lt140/90
• Delay progression of disease
• Reduce cardiovascular risk

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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 gt 30 (stage 1-3)
• Loops (qd-bid) for gfr lt 30 (stages 4 5)
• Potassium sparing diuretics
• Risk of hyperkalemia, esp with ACEI/ARB

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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)

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Chronic Kidney DiseaseComplications

• 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

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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

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Chronic Kidney DiseaseComplications

• Anemia (hgb lt 13g/dL in males, lt 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) gt 30
• Serum ferritin lt500ng/ml
• Acute phase reactant, elevated with
  infection/inflammation

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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 gt 10g/dL
• Treat lt10g/dL on individual basis

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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

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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

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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 gt 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

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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

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Chronic Kidney Disease Medications

• Pharmacokinetics
• Bioavailability of oral meds can be increased or
  decreased
• Changes in gastric pH
• Increases in metabolism
• Decreases in absorption

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Chronic Kidney Disease Medications

• Pharmacokinetics
• Distribution affected by hypoalbuminemia, uremia
  and alterations in protein binding sites
• Possibility leading to toxicity of unbound drug

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Chronic Kidney Disease Medications

• Pharmacokinetics
• Metabolism of drugs may be increased, decreased
  or unchanged.
• Reduced activity of cytochrome P-450

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Chronic Kidney Disease Medications

• Pharmacokinetics
• Elimination of drugs may cause accumulation of
  drug and prolong its action, active metabolites
  may have toxic effects

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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 gt1.4 men 1.5mg/dl per package
  insert
• Inctretins are eliminated by kidney, so not
  recommended in crcl lt 30ml/min
• Insulin, with 40-50 elimination by kidneys, dose
  reductions are recommended

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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

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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 lt60
• Sulfamethoxazole-trimethoprim (bactrim).
  Nephrotoxicity. Dose reduction of ½ in CrCl 15-30
  and avoid in lt 15.

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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

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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

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Chronic Kidney Disease Medications

• Diuretics
• Thiazide are recommended in those with gfr gt30
• Loop are recommended in those with gfr lt30
• Potassium-sparing should be used with caution in
  those with gfr lt 30

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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

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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 lt 15

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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

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• Questions?
• Thank You!

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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.