CKD Overview

1. CKD Overview Dr. Shaun Joshi North Idaho Nephrology Associates, Inc. Hayden, Idaho 208-762-7760

2. WHICH PATIENTS ARE AT INCREASED RISK FOR CKD? • Risk factors • Diabetes • Hypertension • Autoimmune diseases • Recurrent urinary tract infections (UTIs) (> 3 in 1 year) • Nephrolithiasis • Lower urinary-tract obstruction • Hyperuricemia • Prev acute kidney injury • Family history of chronic kidney disease • >55 yrs. • Black race 3.5*, Asian 1.5*, Hispanic 1.5* • NSAIDs • Tobacco • Obesity

3. CKD PREVALENCE Who? • Over 20 million adults estimated prevalence • 1:3 with diabetes and 1:5 with hypertension

6. Tests For Screening Screen individuals at increased risk for CKD -those older than 55 years, black race, htn, DM, obesity Screening: estimate GFR and test for kidney damage markers -serum creatinine to estimate GFR -urinalysis for leukocytes and red blood cells -qualitative test for urine albumin (or protein) with dipstick; if positive, measure amount to calculate an albumin-to-creatinine (or a protein-to-creatinine) ratio -caveat for myeloma proteins

7. URINE ALBUMIN & PROTEIN TO CREATININE RATIO Albumin-to-creatinine ratio • Normal to mildly increased <30 mg/g • Moderately increased 30-300 mg/g • Severely increased >300 mg/g Protein-to-creatinine ratio • Normal to mildly increased <150 mg/g • Moderately increased 150-500 mg/g • Severely increased >500 mg/g Type 2 diabetes: screen for albuminuria q6 mo. or annually -positive when >30 mg/g creatinine in a spot urine sample

8. ARE PREVENTIVE MEASURES USEFUL FOR PATIENTS AT INCREASED RISK FOR CKD? Diabetes - ?? -hyperglycemia is associated with development and progression of diabetic nephropathy -good glycemic control reduces CKD risk -maintain hemoglobin A1c ~7% with dietary interventions, oral hypoglycemic medications, and insulin Hypertension -treatment reduces CV risks but not CKD risk -hastens renal function decline -maintain blood pressure <140/90 (?130/80) mm Hg with lifestyle modification and antihypertensive drug therapy

9. WHAT IS THE DEFINITION OF CKD? • Kidney damage or GFR <60 mL/min / 1.73 m2 for >3 mo • Kidney damage can be either functional or structural • Functional abnormalities • Proteinuria, albuminuria • albumin/creatinine ratio >30 on two occasions over 90 days apart • Abnormalities of urinary sediment (dysmorphic red cells) • Structural abnormalities • On ultrasound scanning or other radiological tests • Polycystic kidney disease, reflux nephropathy, or other abnormalities

11. Cystatin C -Low molecular weight basic protein, freely filtered -Creat filtered and secreted, released by muscle -Produced at constant amount by all nucleated cells -Not affected by inflammatory conditions -Less influenced by age, gender, weight, and muscle mass

14. STAGE OF CHRONIC KIDNEY DISEASE BY GFR AND ALBUMINURIA

15. Cases, is CKD present? Patient 1: Age 75, creat 0.9, UA neg, female. MDRD=63 ml/min No CKD Patient 2: Age 85, creat 0.9, UA neg, female. MDRD=58 ml/min G3aA1 Patient 3: Age 35, creat 0.7, male, alb/cr=4, MDRD=122ml/min G1A3 Patient 4: Age 40, creat 4, male, alb/cr=4, MDRD=18 ml/min G3A3

16. WHAT LABORATORY TESTS AND IMAGING SHOULD CLINICIANS USE TO EVALUATE CKD? • Serum creatinine (to estimate GFR) • Serum electrolytes • CBC and lipid profile • Urinalysis (specific gravity, pH, red cells, leukocytes) • Urine P/Cr, Alb/Cr • If GFR <60 mL/min per 1.73 m2 • Serum calcium, phosphorus, parathyroid hormone, albumin   Renal ultrasound -for hydronephrosis, cysts, and stones -to assess echogenicity, size, kidney symmetry

17. If indicated by findings • Antinuclear antibody to evaluate for lupus/other CTD • C3C4 • Serologies for HBV, HCV, and HIV • ANCA, GBM for vasculitis • Serum and urine protein immunoelectrophoresis for multiple myeloma • Antiphospholipase A2 receptor antibody • Stages 4 and 5 CKD: test for hyperkalemia, acidosis, hypocalcemia, hyperphosphatemia

18. CKD SCREENING TOOL

19. CLINICAL BOTTOM LINE: DIAGNOSIS... • CKD is defined as kidney damage or a GFR <60 mL/min per 1.73 m2 for > 3 months • Classify • Diabetic nephropathy • Hypertensive nephropathy • Nondiabetic, non hypertensive kidney disease • Then, into groups based on levels of GFR and albuminuria • History and physical exam often point to a cause • Definitive diagnosis requires: • Diagnostic tests • Renal ultrasound • Sometimes renal biopsy

20. WHAT NON-DRUG THERAPIES SHOULD CLINICIANS RECOMMEND? • Quit smoking, and exercise 30 min/d on most days • Limit alcohol intake • Maintain BMI within normal range • Eat a diet high in fruits, vegetables, and whole grains • DASH diet recommended if GFR >60 mL/min per 1.73 m2 and high normal blood pressure or stage 1 hypertension • If hypertension present: restrict salt intake <2.0 g/d • Most patients with CKD should avoid high-protein diets • Stage 4 or 5: consider low-protein diet (0.6 g/kg/d)

21. ACC/AHA HIGH BLOOD PRESSURE GUIDELINES  Blood pressure categories in the new guideline are: • Normal: Less than 120/80 mm Hg; • Prehypertension: Systolic between 120-129 and diastolic less than 80; • Stage 1: Systolic between 130-139 or diastolic between 80-89; • Stage 2: Systolic at least 140 or diastolic at least 90 mm Hg; • Hypertensive urgency: Systolic over 180 and/or diastolic over 120, no sx or evidence of end-organ damage • Hypertensive emergency: Systolic over 180 and/or diastolic over 120, evidence of end-organ damage • -immediate medical attention

22. WHAT IS THE ROLE OF BLOOD PRESSURE MANAGEMENT? To reduce CVD risk, treat to <140/90 mm Hg • If proteinuria is significant or urine albumin-to-creatinine ratio >30mg/g: treat to <130/80 mm Hg • Use ACE inhibitors and ARBs (improve kidney outcomes) Combination therapy often needed • Diuretics reduce extracellular fluid volume, lower BP, and reduce risk for CVD • Diuretics also potentiate effects of antihypertensives • Thiazide-type diuretic if GFR ≥30 mL/min per 1.73 m2 • Loop diuretic if GFR <30 mL/min per 1.73 m2

23. WHEN SHOULD CLINICIANS PRESCRIBE ACE INHIBITORS VERSUS ARBS? • Prescribe either for reducing progression of diabetic nephropathy • Prescribe either in hypertension or in diabetes when urine albumin excretion >30mg / 24h • Prescribe either in non-diabetic proteinuria • Do not combine an ACE inhibitor with an ARB • Monitor patients closely for side effects and adjust dose as needed • *Safe to continue medication if GFR declines < 30% over 4 mos and serum potassium <5.5 mEq/L

24. HTN/CKD

31. Metabolic acidosis • Seldom significant until GFR <30 mL/min per 1.73 m2 • Contributes to CKD progression, insulin resistance, decreased cardiorespiratory fitness, altered bone metabolism • Consider when HC03 < 22 • Use alkali therapy with serum bicarbonate <22 mmol/L to maintain serum bicarbonate levels within normal range -Sodium bicarbonate 650 mg = 8 MeQ bicarb -Baking soda 1 tsp. = 25 MeQ bicarb, 500 mg sodium

32. HOW SHOULD CLINICIANS MANAGE PATIENTS WITH ANEMIA? • Measure hemoglobin and hematocrit, RBC indices, reticulocyte count, serum iron, percent transferrin saturation, vitamin B12 and folate levels, serum ferritin • Identify potential sources of bleeding  • Treat with erythropoietin when hemoglobin drops below 9-10 g/dL • Prescribe oral / IV iron as needed to maintain iron stores • Maintain hemoglobin levels 10-11 g/dL • Use caution with active malignancy

33. WHAT ARE THE INDICATIONS FOR RENAL REPLACEMENT THERAPY? • Volume overload unresponsive to diuretics • Pericarditis • Uremic encephalopathy • Major bleeding secondary to uremic platelets • Hypertension that does not respond to treatment • Hyperkalemia and metabolic acidosis that cannot be managed medically • Progressive “uremic” symptoms, which include fatigue; anorexia, nausea or vomiting; malnutrition; and insomnia • GFR <10 ml/min – no evidence to support early start

36. The Cost • More than 650,000 (75% Dialysis, 25% Txp) in the United States, 2 million patients worldwide are affected by end stage renal disease (ESRD). • ESRD is increasing in the United States by 5% per year. • Those who live with ESRD are 1% of the U.S. Medicare population but account for 7% of the Medicare budget. • More than 100,000 patients in the United States are on the kidney transplant list, but each year there are less than 20,000 available donor kidneys. • The need for donor kidneys in the United States is rising at 8% per year. • ESRD $89000/yr (32 billion/yr), Transplant $25000-32000/yr

37. Elderly Starts for RRT USRDS database (age years) -70-74: 3.6 vs 12.2 -75-79: 3.1 vs 9.2 -75-80: 2 vs 3.5 Mayo Clinic, those 75 and older -26% 6 mo. ICU start -23% 1 year ICU start -88% 6 mo. non ICU -56% 1 year

38. Nursing Home, October 15, 2009 New England Journal of Medicine, Chertow et al. -4% of new ESRD starting -By 1 yr, only 42% alive -13% at 1 yr still functioned at the same level as they did before beginning dialysis -Study lacked control arm

39. Take Home -All takers, 35% 5 yr survival -Transplant 3% 5 yr survival ->65 evaluate functional status ->75 live longer but QOL is poor, functionality drops -PD/Home cheaper by 1/3 -Nothing new concrete in the pipeline -Kidney Project UCSF -1/15/19“Wearable PD Device Granted Breakthrough Device Designation” -Stem cells to grow a kidney

40. CLINICAL BOTTOM LINE: TREATMENT... • The goals are to slow progression of CKD and prevent complications from cardiovascular disease • Maintain normal blood pressure in patients with hypertension • Include an ACE inhibitor or an ARB when treating hypertension • Diuretics cornerstone • Control glycemia in patients with diabetes • Manage electrolyte disturbances, anemia, secondary hyperparathyroidism, and malnutrition • Refer to a nephrologist as CKD progresses

41. METFORMIN

42. METFORMIN

43. METFORMIN

44. INSULIN

45. INSULIN

46. INSULIN

47. A1C

48. DM MEDS

50. LIPIDS CKD