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Outpatient Management of Chronic Kidney Disease Brian Stith, DO PGY-3 Via Christi Family Medicine Residency Goals and Objectives 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 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 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 CKD – USRDS report 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 CKD - Definition 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 - 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 Glomerular Filtration Rate GFR – # of functioning nephrons Assessment of GFR 1. 2. 3. Serum Creatinine Concentration Creatinine Clearance (24 hr urine sample) 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 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 Loss of GFR 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 Causes of CKD/ESRD Diabetes mellitus (45%) Most common cause of ESRD in all racial/ethnic groups Hypertension (27%) Polycystic kidney disease Glomerulonephritis Vesico-ureteral reflux Nephrolithiasis Other renal diseases causing ESRD Renovascular disease (very common) Glomenrulonephritis Membranous nephropathy 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 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) Initial Evaluation 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 Initial Evaluation Review Meds – causing/contributing to CKD *NSAIDs Diuretics Lithium Cyclosporine Tacromilus Antivirals Chemotherapeutic medications Dietary or Herbal supplements Initial Evaluation 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) Initial Evaluation 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 Initial Evaluation 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 Complications of CrCl < 30 mg/min 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 Labs to follow with CKD 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 CMP 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 CBC 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 PTH intact 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 PTH intact 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 Vitamin D 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 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 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 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 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 Proteinuria 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 Diet – Dietician referral may be needed Low Phosphorous Low Protein 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 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 Medications 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 Medications 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) Renoprotective Effect of ACE-I Lowers systemic BP Lowers glomerular pressure Increase renal blood flow Renoprotective Effect of ACE-I 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 Medications 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 Medications 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 Medications 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 Medications 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 Medications Phosphate Binders Non-calcium containing Sevelamer Lanthanum Aluminum hydroxide – former med of choice, but out of favor due to aluminum toxicity Medications 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) Medications 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 To think about… 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 Overview of recommendations 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 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 HgA1c goal <7.0 (6.5 even better) Indications for Referral in CKD Underlying cause is unclear after basic work-up Renal biopsy is indicated eGFR < 30 mL/min/1.73m2 Rapid progression of CKD GFR decline 50% in less than 6 months with no obvious cause Superimposed acute renal failure Metabolic complications Facilitate education, planning of dialysis/transplant Anemia, Secondary hyperparathyroidism Management is beyond your comfort level References 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.