Brian Stith, DOPGY-3

Via Christi Family Medicine Residency

Definition Screening Initial Evaluation Labs to follow Medications Diet Overview When to refer

20 million Americans have CKD (1 out of 9 persons)

Higher morbidity and mortality on dialysis 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

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

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 Transplant

$24,952/year $75,000-l50,000 for actual transplant and 3

months of follow-up

Evidence of structural or functional renal abnormalities that persists for at least 3 months With or without a decrease in GFR Most common manifestation of CKD is albuminuria

Or 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 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

GFR – # of functioning nephrons Assessment of GFR

1. Serum Creatinine Concentration2. Creatinine Clearance (24 hr urine sample)3. Estimation Equations based on serum

creatinine MDRD, Cockroft-Gault

www.mdrd.com Accounts for some variables – age, gender, race,

body size Best overall measurement of renal function

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

Normal GFR is 100-125 mL/minute until age 40 After age 40, normal GFR loss is 0.5-0.75

mL/min/year 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

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

Diabetes mellitus (45%) Most common cause of ESRD in all

racial/ethnic groups Hypertension (27%) Polycystic kidney disease Glomerulonephritis Vesico-ureteral reflux Nephrolithiasis

Renovascular disease (very common) Glomenrulonephritis

Wegeners, Goodpastures, Lupus Membranous nephropathy

Hepatitis B & C, Cancer Renal papillary necrosis (rare) Autonomic neuropathy of the bladder Urinary tact infection Pyelonephritis Contrast Nephropathy

Annually Hypertension Diabetes mellitus Cardiovascular disease Family history of renal disease

Consider annual testing Persistent hematuria (after exclusion of other

causes) Recurrent UTI’s Systemic illnesses that can affect the kidney (i.e.

SLE, Hyperuricemia, Multiple myeloma)

History and Physical History of comorbid conditions and length

of disease 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

Review Meds – causing/contributing to CKD *NSAIDs Diuretics Lithium Cyclosporine Tacromilus Antivirals Chemotherapeutic medications Dietary or Herbal supplements

Physical Exam Vitals Volume Status

Serial weights, JVD, Edema BMI Assess for abdominal or femoral bruit

May indicate renal artery stenosis Cardiac rub – present in advanced CKD

(uremia)

Renal sonogram – structural examination Normal size indicates amenable to medical

treatment Large kidneys (>13cm)

Seen with DM, amyloid, infiltrative disease, HIV nephropathy

Small kidneys – suggests irreversible disease Asymmetry

Suggests renovascular disease or ureteral obstruction May be a congenital abnormality

Labs CMP (K+, Na+, Ca2+, HCO3

-, BUN, Cr, Glucose) Phosphorous UA with microurinalysis CBC UA

Add protein-to-creatinine ration of 1+ or more Random urine albumin-to-creatinine ratio

(those with DM) Lipid panel

Anemia – Erythropoietin deficiency Hypocalcemia – Secondary to low Vitamin D Acidosis – Bone will act as buffer & dump

calcium Osteomalacia/osteopenia/osteoporosis Secondary hyperparathyroidism Malnutrition

Albumin <3.8 increases mortality in ESRD due to low immunoglobulin production

Fluid control

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

Phosphorous Goal – 2.7-4.6 mg/dL For CKD stage 5, goal is 3.5-5.5 mg/dL

Total calcium Goal – use lab reference range For CKD stage 5, goal is 8.4-9.5 mg/dL

Causes of anemia in CKD Reduced erythropoietin production Shortened RBC survival Iron Deficiency

Treatment Replace Iron if deficient Recombinant human erythropoietin

Initially at 80-100 units/kg/week SQ and titrate Treatment goal of Hgb 11-13

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 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

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

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

CKD patients have a decreased ability to excrete uric acid

Theorized that hyperuricemia may contribute to CKD progression Thus, treatment with allopurinol may slow

disease

General goal is a uric acid <5.0 Levels >5.2 have been correlated

greatly with CKD disease progression

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 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)

Spot Urine Protein/Creatinine ratio

24 hr urine protein

Lab Method Advantages

• Strong correlation with 24 hr urine protein•Patient convenience•Rapid Results

More accurate quantification of proteinuria

Disadvantages

Less accurate for proteinura >4g/day and <500mg/day

•Poor patient compliance•Time consuming•Delay in obtaining results

Urine Ratios Albumin to Creatinine Ratio

More precise at lower concentrations More expensive Use for screening in patients at increased risk of CKD

Diabetes mellitus, Hypertension

Protein to Creatinine Ratio 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

Monitoring proteinuria in CKD patients should be done with quantitative measurements

Urine Protein-to-Creatinine Ratio Normal

< 150 mg/24 hour sample < 0.2 g/g (> 200 mg protein/mg creatinine)

Nephrotic Range > 3g /24 hours > 3.5 mg /mg

Low Phosphorous Studies have shown significant decrease in

PTH and improvements in bone histology in mild CKD

Low Protein 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

No NSAIDs Use Tylenol or narcotic pain medications

When GFR <30 Save non-dominant arm from IV, PICC lines,

needles Saves veins for future grafting of AV fistula

Discuss options of fistula/graft/peritoneal dialysis

Transplant evaluation – able to get if GFR <20 Dialysis at GFR <15

ACE-I/ARBs Slows progression independent of BP

effect Monitor Cr and K+ 1-2 weeks after

initiation Should be continued in most patients

unless: Acute decline in GFR by >30% within 2

weeks of starting the medicine K+ > 6, despite appropriate treatment

ACE-I/ARBs Insufficient evidence to recommend

combo of ACE-I and ARB to slow disease progression

Only benefit seen in non-diabetic CKD patients with concomitant IgA nephropathy (Berger’s disease)

Lowers systemic BP Lowers glomerular pressure Increase renal blood flow

Reduces proteinuria Even if BP is controlled and patient is

normotensive, doses of ACE-I/ARBs should be raised even greater than recommended

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

Diuretics Use in patients with volume overload May be useful to also control potassium

levels HCTZ not useful in patients with GFR is

<30 Not able to get to the distal tubule at that

low of GFR Use Loops + Metalazone

Allopurinol Titrate to uric acid <5.0 There is no risk of causing further renal

failure Max dose is 900 mg/day

Uloric (Febuxostat) Another option for hyperuricemia Up to 80 mg/day More expensive

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

Phosphate Binders Indicated with patients with elevated

PTH and increased phosphate, despite phosphate restriction for 2-4 weeks

Calcium containing – preferred Calcium carbonate

Do not use H2 blockers/PPI Needs acid to become active

Calcium acetate

Phosphate Binders Non-calcium containing

Sevelamer Lanthanum

Aluminum hydroxide – former med of choice, but out of favor due to aluminum toxicity

Vitamin D Cholecalciferol (Vitamin D3) – preferred Ergocalciferol (Vitamin D2)

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)

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 Lowers PTH Lowers Calcium Lowers Phosphorus

Prevents bone disease related to CKD

Be alert that other diseases can develop in addition to diabetic nephropathy

Hypertensive nephrosclerosis is common Renal artery stenosis can occur anytime

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 Arteriograms, heart catherization, CT scan, IVP's

Goal Blood Pressure <130/80 mm Hg Reduce proteinuria with ACE-I/ARBs

Goal <1g/day Control phosphate – diet, binders Maintain Vitamin D25 >30 ng/mL Prevent hyperparathyroidism

Correct Vitamin D, Phosphorus, Calcium

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

HgA1c goal <7.0 (6.5 even better)

Underlying cause is unclear after basic work-up Renal biopsy is indicated eGFR < 30 mL/min/1.73m2

Facilitate education, planning of dialysis/transplant Rapid progression of CKD

GFR decline 50% in less than 6 months with no obvious cause

Superimposed acute renal failure Metabolic complications

Anemia, Secondary hyperparathyroidism Management is beyond your comfort level

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.