Transcript Longitudinal Management of Chronic Kidney Disease

Outpatient Management of
Chronic Kidney Disease
Brian Stith, DO
PGY-3
Via Christi Family Medicine Residency
Goals and Objectives
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Definition
Screening
Initial Evaluation
Labs to follow
Medications
Diet
Overview
When to refer
Disease Burden
20 million Americans have CKD (1 out of 9
persons)
 Higher morbidity and mortality on dialysis
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Diabetic life expectancy is 2 years (25% death rate/year)
Non-diabetic is 5 years
Renal Failure – 9th leading cause of death
 Medicare can't support the cost – and it is
getting worse
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CKD – USRDS report
Total of 512,502 CKD patients in 2006
 Total of 355,000 ESRD and l51,502 transplant
patients
 CKD – 6.6% of Medicare population, but19.4%
of the cost
 Total cost of the ESRD program in the US was
approximately $39.46 billion in 2008
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CKD – USRDS report
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ESRD
1.2% of Medicare population, but 8.2% of the cost
 $ 71,889/year for those on Hemodialysis
 $53,327/year for those on Peritoneald Dialysis
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Transplant
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$24,952/year
$75,000-l50,000 for actual transplant and 3 months of
follow-up
CKD - Definition
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Evidence of structural or functional renal abnormalities
that persists for at least 3 months
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With or without a decrease in GFR
Most common manifestation of CKD is albuminuria
Or
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GFR persistently below 60 mL/minute/1.73 m2, which
is below the level of kidney function expected to occur
with aging
 No clear relationship between eGFR and CKD
clinical manifestations, but they tend to occur at
lower eGFR levels
CKD - Definition
CKD refers to the many clinical abnormalities
that progressively worsen as kidney function
declines
 Results from a large number of systemic
diseases damaging the kidney or from
disorders that are intrinsic to the kidney
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Glomerular Filtration Rate
GFR – # of functioning nephrons
 Assessment of GFR
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Serum Creatinine Concentration
Creatinine Clearance (24 hr urine sample)
Estimation Equations based on serum creatinine
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MDRD, Cockroft-Gault
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www.mdrd.com
Accounts for some variables – age, gender, race, body size
 Best overall measurement of renal function
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CKD by GFR
Normal GFR 100-125 ml/min
 Stage l - GFR > 90 m/min with proteinuria
 Stage 2 - GFR: 60-89 m/min
 Stage 3 - GFR: 30-59 m/min
 Stage 4 - GFR: 15-29 m/min
 Stage 5 - GFR < 15 m/min or dialysis
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Loss of GFR
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Normal GFR is 100-125 mL/minute until age 40
After age 40, normal GFR loss is 0.5-0.75 mL/min/year
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Example: For an 80 year old patient:
(80 - 40 years) X 0.5-0.75 mL/min/year = 20-30 mL/min
Normal GFR for this patient should be
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100-l25 mL/min – 20-30 mL/min = 70-95 mL/min
This is CKD level 2 even with normal aging
Diabetic Nephropathy – May lose 2-20 mL/min/year
GFR below 60 represents loss of ½ or more of the adult
normal renal function
Causes of CKD/ESRD
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Diabetes mellitus (45%)
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Most common cause of ESRD in all racial/ethnic
groups
Hypertension (27%)
 Polycystic kidney disease
 Glomerulonephritis
 Vesico-ureteral reflux
 Nephrolithiasis
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Other renal diseases causing ESRD
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Renovascular disease (very common)
Glomenrulonephritis
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Membranous nephropathy
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Wegeners, Goodpastures, Lupus
Hepatitis B & C, Cancer
Renal papillary necrosis (rare)
Autonomic neuropathy of the bladder
Urinary tact infection
Pyelonephritis
Contrast Nephropathy
Screening for CKD – UA, GFR
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Annually
Hypertension
 Diabetes mellitus
 Cardiovascular disease
 Family history of renal disease
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Consider annual testing
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Persistent hematuria (after exclusion of other causes)
Recurrent UTI’s
Systemic illnesses that can affect the kidney (i.e. SLE,
Hyperuricemia, Multiple myeloma)
Initial Evaluation
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History and Physical
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History of comorbid conditions and length of disease
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HTN, Diabetes mellitus, CV disease, Lower urinary tract
symptoms, Hepatitis B and C, HIV, Nephrolithiasis
Chronic pain syndrome? – concern for long term NSAID use
No symptoms are specific or diagnostic for CKD
Assess for Family History of renal diseases
Initial Evaluation
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Review Meds – causing/contributing to CKD
*NSAIDs
 Diuretics
 Lithium
 Cyclosporine
 Tacromilus
 Antivirals
 Chemotherapeutic medications
 Dietary or Herbal supplements
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Initial Evaluation
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Physical Exam
Vitals
 Volume Status
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Serial weights, JVD, Edema
BMI
 Assess for abdominal or femoral bruit
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May indicate renal artery stenosis
Cardiac rub – present in advanced CKD (uremia)
Initial Evaluation
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Renal sonogram – structural examination
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Normal size indicates amenable to medical treatment
Large kidneys (>13cm)
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Seen with DM, amyloid, infiltrative disease, HIV nephropathy
Small kidneys – suggests irreversible disease
Asymmetry
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Suggests renovascular disease or ureteral obstruction
May be a congenital abnormality
Initial Evaluation
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Labs
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CMP (K+, Na+, Ca2+, HCO3-, BUN, Cr, Glucose)
Phosphorous
UA with microurinalysis
CBC
UA
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Add protein-to-creatinine ration of 1+ or more
Random urine albumin-to-creatinine ratio (those with
DM)
Lipid panel
Complications of CrCl < 30 mg/min
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Anemia – Erythropoietin deficiency
Hypocalcemia – Secondary to low Vitamin D
Acidosis – Bone will act as buffer & dump calcium
Osteomalacia/osteopenia/osteoporosis
Secondary hyperparathyroidism
Malnutrition
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Albumin <3.8 increases mortality in ESRD due to low
immunoglobulin production
Fluid control
Labs to follow with CKD
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When CKD stage 3, 4, or 5
CMP
 CBC
 Fasting Lipid panel
 PTH intact
 UA with micro
 25-OH Vitamin D levels
 Uric acid
 Urine Protein-to-Creatinine Ratio
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CMP
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Phosphorous
Goal – 2.7-4.6 mg/dL
 For CKD stage 5, goal is 3.5-5.5 mg/dL
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Total calcium
Goal – use lab reference range
 For CKD stage 5, goal is 8.4-9.5 mg/dL
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CBC
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Causes of anemia in CKD
Reduced erythropoietin production
 Shortened RBC survival
 Iron Deficiency
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Treatment
Replace Iron if deficient
 Recombinant human erythropoietin
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Initially at 80-100 units/kg/week SQ and titrate
 Treatment goal of Hgb 11-13
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PTH intact
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Causes of secondary hyperparathyroidism in CKD
 Phosphate retention
 Decreased free calcium
 Decreased Vitamin D1,25
Kidney function is required to convert Vitamin D25 to
Vitamin D1,25
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Reaction stimulated to PTH
Patients with CKD have low circulating Vitamin D1,25,
low Vitamin D25, and increased PTH, even before
demonstratable hyperphosphatemia and hypocalcemia
PTH intact
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Goal PTH intact level – to control secondary
hyperparthyroidism
35-70 pg/mL with eGFR 30-59 (state III)
 70-110 pg/mL with eGFR 15-29 (stage IV)
 150-300 pg/mL for dialysis pts or eGFR <15
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Vitamin D
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The kidney is the location of 1-hydroxylation to
make the active form of vitamin D (calcitriol)
Deficiency is associated with secondary
hyperparathyroidism
 Treatment helps regulate PTH levels via vitamin D
receptors on the parathyroid
Deficiency associated with increased albuminuria
Goal level is for Vitamin D25 is > 30 ng/mL
Uric Acid
CKD patients have a decreased ability to
excrete uric acid
 Theorized that hyperuricemia may contribute
to CKD progression
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Thus, treatment with allopurinol may slow disease
General goal is a uric acid <5.0
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Levels >5.2 have been correlated greatly with
CKD disease progression
Proteinuria
Marker of renal damage
 Two classes of proteins – Albumin, Globulins
 Potent independent risk factor for
progression of renal disease and an
independent cardiovascular risk factor
 Initially assess with Urine Dip
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First morning sample preferred, random is acceptable
+1 reached at excretion of 300-500 mg/day (upper
limit of normal for proteinuria is 150mg/day)
Proteinuria
Lab Method
Advantages
Disadvantages
Spot Urine
Protein/Creatinine ratio
• Strong correlation with
24 hr urine protein
•Patient convenience
•Rapid Results
Less accurate for
proteinura >4g/day and
<500mg/day
24 hr urine protein
More accurate
quantification of
proteinuria
•Poor patient
compliance
•Time consuming
•Delay in obtaining
results
Proteinuria
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Urine Ratios
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Albumin to Creatinine Ratio
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More precise at lower concentrations
More expensive
Use for screening in patients at increased risk of CKD
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Diabetes mellitus, Hypertension
Protein to Creatinine Ratio
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Many of the studies on treatment of CKD stratified patients
based on this value
Recommended due to cost benefit
Closely correlates to 24 hour urine protein sample
Used to trend proteinuria, if albumin/creatinine ratio is high
Proteinuria
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Monitoring proteinuria in CKD patients should be
done with quantitative measurements
Urine Protein-to-Creatinine Ratio
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Normal
< 150 mg/24 hour sample
 < 0.2 g/g (> 200 mg protein/mg creatinine)
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Nephrotic Range
> 3g /24 hours
 > 3.5 mg /mg
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Diet – Dietician referral may be needed
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Low Phosphorous
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Low Protein
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Studies have shown significant decrease in PTH
and improvements in bone histology in mild CKD
Insufficient evidence to use for disease progression
May delay onset of uremic symptoms in those close to
needing dialysis
Patient needs at least 0.6-0.8 g/kg/day
Low Potassium – prevents hyperkalemia
Counseling Guidelines
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No NSAIDs
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Use Tylenol or narcotic pain medications
When GFR <30
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Save non-dominant arm from IV, PICC lines,
needles
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Saves veins for future grafting of AV fistula
Discuss options of fistula/graft/peritoneal dialysis
 Transplant evaluation – able to get if GFR <20
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Dialysis at GFR <15
Medications
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ACE-I/ARBs
Slows progression independent of BP effect
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 Monitor Cr and K 1-2 weeks after initiation
 Should be continued in most patients unless:
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Acute decline in GFR by >30% within 2 weeks of
starting the medicine
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 K > 6, despite appropriate treatment
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Medications
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ACE-I/ARBs
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Insufficient evidence to recommend combo of
ACE-I and ARB to slow disease progression
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Only benefit seen in non-diabetic CKD patients with
concomitant IgA nephropathy (Berger’s disease)
Renoprotective Effect of ACE-I
Lowers systemic BP
 Lowers glomerular pressure
 Increase renal blood flow
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Renoprotective Effect of ACE-I
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Reduces proteinuria
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Even if BP is controlled and patient is normotensive, doses
of ACE-I/ARBs should be raised even greater than
recommended
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To reduce protein excretion to levels <500mg (level most optimal
to protect the kidney)
Natriuretic (salt excretion)
Decrease in Aldosterone production
Inhibits Angiotensin II, cytokines, growth factors, and
macrophages
Medications
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Diuretics
Use in patients with volume overload
 May be useful to also control potassium levels
 HCTZ not useful in patients with GFR is <30
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Not able to get to the distal tubule at that low of GFR
Use Loops + Metalazone
Medications
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Allopurinol
Titrate to uric acid <5.0
 There is no risk of causing further renal failure
 Max dose is 900 mg/day
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Uloric (Febuxostat)
Another option for hyperuricemia
 Up to 80 mg/day
 More expensive
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Medications
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Statins
Lipid lowering is important in CKD, especially in
nephrotic range CKD
 Studies suggest that high lipid levels contribute to
CKD disease progression
 Hyperlipidemia experimentally activates mesangial
cells and increases production of macrophage
chemotactic factors, fibronectin, type IV collagen,
plasminogen activator-1, reactive O2 species
 If diabetic, remember goal LDL is <70
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Medications
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Phosphate Binders
Indicated with patients with elevated PTH and
increased phosphate, despite phosphate
restriction for 2-4 weeks
 Calcium containing – preferred
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Calcium carbonate
 Do not use H2 blockers/PPI
 Needs acid to become active
 Calcium acetate
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Medications
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Phosphate Binders
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Non-calcium containing
Sevelamer
 Lanthanum
Aluminum hydroxide – former med of choice, but out of
favor due to aluminum toxicity
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Medications
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Vitamin D
Cholecalciferol (Vitamin D3) – preferred
 Ergocalciferol (Vitamin D2)
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Vitamin D analogues - not routinely used
Use – when PTH is still high, despite correcting
Phosphorus and Calcium to <9.5 mg/dL
 Calcidiol (25-hydroxyvitamin)
 Calcitriol (1,25-dihydroxyvitamin D)
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Medications
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Sensipar (Cinacalcet)
Treatment of secondary hyperparathyroidism in
patients not on dialysis
 Not currently approved for this use
 Increases sensitivity of calcium sensing receptor
on parathyroid gland
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Lowers PTH
 Lowers Calcium
 Lowers Phosphorus
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Prevents bone disease related to CKD
To think about…
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Be alert that other diseases can develop in addition to
diabetic nephropathy
Hypertensive nephrosclerosis is common
Renal artery stenosis can occur anytime
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Suggested if creatinine rises > 0.2-0.3 mg/dl and high
potassium after starting an ACE-I
Suggested is >1cm size difference in renal ultrasound
Diabetics are at higher risk of contrast nephropathy
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Arteriograms, heart catherization, CT scan, IVP's
Overview of recommendations
Goal Blood Pressure <130/80 mm Hg
 Reduce proteinuria with ACE-I/ARBs
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Goal <1g/day
Control phosphate – diet, binders
 Maintain Vitamin D25 >30 ng/mL
 Prevent hyperparathyroidism
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Correct Vitamin D, Phosphorus, Calcium
Overview of recommendations
Correct Anemia – goal Hgb 11-13 mg/dL
 Give diuretics for volume overload
 Control K+ - diet restriction, diuretics
 Protein intake at least 0.6-0.8 g/kg/day
 Control metabolic acidosis with oral sodium
citrate
 Tight diabetes mellitus control
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HgA1c goal <7.0 (6.5 even better)
Indications for Referral in CKD
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Underlying cause is unclear after basic work-up
Renal biopsy is indicated
eGFR < 30 mL/min/1.73m2
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Rapid progression of CKD
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GFR decline 50% in less than 6 months with no obvious cause
Superimposed acute renal failure
Metabolic complications
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Facilitate education, planning of dialysis/transplant
Anemia, Secondary hyperparathyroidism
Management is beyond your comfort level
References
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Epidemiology and risk factors for chronic kidney disease. McClellan WM – Med Clin
North Am – 01-MAY-2005; 89(3): 419-45
Cecil, R. L., Goldman, L., & Schafer, A. I. (2012).Goldman's Cecil medicine. Philadelphia:
Elsevier/Saunders.
National Kidney Foundation – Am J Kidney Dis – 01-FEB-2002; 39(2 Suppl 1): S1-266
Chronic Kidney Disease Working Group. (2008). VA/DoD clinical practice guideline for
the management of chronic kidney disease in primary care.Version 2.0. Washington, DC:
Veterans Health Administration and Department of Defense.
Outpatient management of chronic kidney disease: proteinuria, anemia and bone
disease as therapeutic targets. Lam A – Dis Mon – 01-APR-2010; 56(4): 215-32
Bope, E. T., Rakel, R. E., Kellerman, R. D., & Conn, H. F. (2011). Conn's current therapy
2011. Philadelphia, Pa: Saunders/Elsevier.
Rose, Burton D MD. Evaluation of isolated proteinuria in adults. In: UpToDate,
Basow, DS (Ed),UpToDate, Waltham, MA, 2011.
Post, Theodore W MD. Overview of the management of chronic kidney disease in
adults. In: UpToDate, Basow, DS (Ed),UpToDate, Waltham, MA, 2011.