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CKD for the internist

 . CKD for the internist. July 2014. Alison Landrey MD Charlie MacLean, MD and Virginia Hood, MD. Learning Objectives. Identify and categorize CKD Perform an appropriate evaluation for underlying causes of CKD Identify and modify risk factors for progression of CKD

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CKD for the internist

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  1.  CKD for the internist July 2014 Alison Landrey MD Charlie MacLean, MD and Virginia Hood, MD

  2. Learning Objectives • Identify and categorize CKD • Perform an appropriate evaluation for underlying causes of CKD • Identify and modify risk factors for progression of CKD • Understand and monitor for metabolic and hematological complications of CKD • Renally dose medications • Know when to refer to nephrology • Be able to explain CKD to patients

  3. Definitions! • CKD: • either kidney damage OR GFR <60 mL/min/1.73m2 for >3 mo • Kidney damage: • abnormal pathology, imaging, U/A • Proteinuria: • “microalbuminuria”: • 30-300 mg/g • Nephrotic range proteinuria: • >3 g/day (>3000 mg/g spot protein/creat) • If protein on dip – this is abnormal. Repeat up to 2-3 times to see if transient/benign etiology. If persistent get a spot protein/creatinine • Note dip picks up mostly albumin • eGFR: • MDRD equation: Age, serum cr, gender, race (black or non-black) • If serum creatinine is in normal range eGFR is less accurate for an individual : 24 hour urine collection for creatinine clearance measurement help with accuracy in limited circumstances. • Note: a complete 24 h urine collection should contain creatinine amount of • 15-20 mg/kg/day women; 20-25 mg/kg/day men

  4. Who should be screened?What constitutes screening? Screening: yearly serum Cr AND urine prot or alb/creat • Metabolic syndromes • Diabetes • Obesity • Cardiovascular disease • Hypertension • Hyperlipidemia • Smoking • Infections • Human immunodeficiency virus (HIV) • Hepatitis C virus infection • Malignancy • Family history of kidney disease (e.g. PKD) • Nephrotoxic drugs • History of AKI (!)

  5. 2002 Staging

  6. 2012 staging with prognostication

  7. Examples • Cr 1.6 GFR 40, urine protein/cr= 300 mg/g • Stage 3b A2 • Cr 0.9 GFR 65, urine protein/cr =100 mg/g • Stage 2 A2 • Cr 3.3 GFR 29, urine protein/cr =1g/g • Stage 4 A3 • Cr 1.2 GFR 55, urine protein/cr 500 mg/g • Stage 3a, A3 • Cr 1.4 GFR 50, urine protein/cr 20 mg/g • Stage 3a A1

  8. MKSAP 30 A 25 yo W with no PMH comes in for an evaluation before undergoing nephrectomy for a living related donor kidney transplant to her brother. PE: normal temperature, BP 116/68, P 72, RR 18 weight 135 lb, BMI 23 Serum creatinine 0.8 mg/dl Urine cr 47 mg/dL-> Creatinine clearance 26 mL/min 24 hr urine volume 650 mL/24 hr Protein 50 mg/24 hrcr 475 mg/24 hr CT abdomen normal Which is the next most appropriate step? • Measure cystatin C • Reject as a potential donor • Repeat timed urine collection • Use the MDRD equation

  9. MKSAP 30 A 25 yo W with no PMH comes in for an evaluation before undergoing nephrectomy for a living related donor kidney transplant to her brother. PE: normal temperature, BP 116/68, P 72, RR 18 weight 135 lb, BMI 23 Serum creatinine 0.8 mg/dl Urine cr 47 mg/dL-> Creatinine clearance 26 mL/min 24 hr urine volume 650 mL/24 hr Protein 50 mg/24 hrcr 475 mg/24 hr CT abdomen normal Which is the next most appropriate step? • Measure cystatin C • Reject as a potential donor • Repeat timed urine collection • Use the MDRD equation

  10. Learning Objectives • Identify and categorize CKD ✔ • Perform an appropriate evaluation for underlying causes of CKD • Identify and modify risk factors for progression of CKD • Understand, monitor for and if possible modify risk for cardiovascular, metabolic and hematological complications of CKD • Renally dose medications • Know when to refer to nephrology • Be able to explain CKD to patients

  11. Major Causes of Severe Chronic Kidney Disease • Diabetes mellitus 44.9 % • Type 1 3.9 • Type 2 41.0 • Hypertension 27.2 % • Glomerulonephritis 8.2 % • Chronic interstitial nephritis or obstruction 3.6 % • Hereditary or cystic disease 3.1 % • Secondary glomerulonephritis or vasculitis 2.1 % • Neoplasms or plasma-cell dyscrasias 2.1 % • Miscellaneous conditions 4.6 % • Uncertain or unrecorded cause 5.2%

  12. once CKD is established, is any Further Testing indicated? • Urinalysiswith microscopic sediment analysis • If abnormal sediment -> referral for biopsy may be indicated • if hematuria and/or proteinuria consider • ANA/C3/C4, ANCA • HIV, Hep C/hep b • SPEP, serum free light chains, urine immunofix • Kidney Ultrasound • Kidney size can be helpful in diagnosis of etiology • Cystic kidney disease • Hydronephrosis • Diabetic kidney disease: special considerations • Typically with proteinuria and larger kidneys • Typically accompanied by retinopathy, but not always • Consider other causes if the degree of kidney disease does not fit with the diabetes clinical picture

  13. MKSAP 1 A 35 yo W with a history of type 1 diabetes x 10 years is evaluated for 1 mo of progressive b/l LE edema. 4 months ago her urine albumin-creatinine ratio was 100 mg/g. Medications are enalapril, glargine, aspart and ASA. On PE BP is 162/90 CV lung and fundoscopic exam normal 3+ pitting edema b/l to the thighs A1C 7.1% Albumin 3 g/dL Serum cr 1.1 mg/dL U/A 3+ protein, 2+ blood, 8-10 dysmorphic erythrocytes Urine protein-cr ratio: 5.2 mg/mg Kidney US: 12.2 cm/12.7 cm kidneys What is the next most appropriate step in management? • Cystoscopy • Kidney biopsy • Spiral CT A/P • Observation

  14. MKSAP 1 A 35 yo W with a history of type 1 diabetes x 10 years is evaluated for 1 mo of progressive b/l LE edema. 4 months ago her urine albumin-creatinine ratio was 100 mg/g. Medications are enalapril, glargine, aspart and ASA. On PE BP is 162/90 CV lung and fundoscopic exam normal 3+ pitting edema b/l to the thighs A1C 7.1% Albumin 3 g/dL Serum cr 1/1 mg/dL U/A 3+ protein, 2+ blood, 8-10 dysmorphic erythrocytes Urine protein-cr ratio: 5.2 mg/mg Kidney US: 12.2 cm/12.7 cm kidneys What is the next most appropriate step in mgmt? • Cystoscopy • Kidney biopsy • Sprial CT A/P • Observation

  15. MKSAP 40 A 59 yo W with CAD HTN and HLD comes for a routine evaluation. Meds are clopidogrel, metoprolol, simvastatin and ASA. On PE BP is 135/82 BM 32 Fasting glucose 98 TC 190 HDL 45 LDL 100 TG 225 sCR 1.4 U/A normal Which of the following studies should be performed next? • 24 hr urine collection for protein • Kidney US • Spot urine albumin-creatinine ratio • No further studies

  16. MKSAP 40 A 59 yo W with CAD HTN and HLD comes for a routine evaluation. Meds are clopidogrel, metoprolol, simvastatin and ASA. On PE BP is 135/82 BM 32 Fasting glucose 98 TC 190 HDL 45 LDL 100 TG 225 sCR 1.4 U/A normal Which of the following studies should be performed next? • 24 hr urine collection for creatinine clearance • Kidney US • Spot urine albumin-creatinine ratio • No further studies

  17. Learning Objectives • Identify and categorize CKD ✔ • Perform an appropriate evaluation for underlying causes of CKD ✔ • Identify and modify risk factors for progression of CKD • Understand, monitor for and if possible modify risk for cardiovascular, metabolic and hematological complications of CKD • Renally dose medications • Know when to refer to nephrology • Be able to explain CKD to patients

  18. Modify risk of progression of CKD • Most important modifiable risk factors for progression: • HTN, higher amount of proteinuria • Proteinuria • Should be on an ACE/ARB regardless of BP • Goal <300-500 mg/g • DM • Goal A1C: as close to 7 as possible if this can be achieved without causing hypoglycemia – not proven to slow progression • dietary protein restriction to 0.5-0.7 g/day if more advanced CKD: delay progression to uremia and small trials show delay progression of CKD • Bicarb if metabolic acidosis (more later)

  19. Hypertension treatment effect mirrors observational risk effect Observational risk effect Treatment effect Lewington et al, Lancet 2002 High blood pressure is the most modifiable risk factor for reducing stroke and preventing progression of kidney & cardiovascular disease

  20. HyperTeNsion MGMT • CKD patients with HTN often require two agents: • Tip from Dr. Hood: many patients do better on two drugs at lower doses rather than one at higher dose • ACE-I/ARB 1st choice • Proven to slow progression of CKD in patients with proteinuria • Has not been shown to slow progression of CKD in patients with proteinuria <500 mg/day BUT RAAS inhibition may have CV benefits too • Studies have not shown benefit to combination of ACE-I/ARB • Diuretics, esp if e/o fluid overload (edema e.g.) • Thiazide if GFR >30 • Loop if GFR <30 – DON’T BE AFRAID of furosemide in CKD • *Remember to advise on salt restriction as well* • Other agents to consider if needed • BB esp if CAD/angina • CCBs: nondihydropyridines (diltiazem, verapamil) also have an antiproteinuric effect but dihydropyridines better for BP control • Ok to add spironolactone if GFR >30 and K low enough • Hydralazine, alpha blocker, clonidine if need 4-5 drugs

  21. More on ACE-I/ARB ARBs appear to be as beneficial as ACE-I in CKD but have less data Trials showing benefit excluded hypovolemic pts and pts with RAS

  22. Blood Pressure goals • Goal BP <140/90 according to JNC8 for all CKD • ? Goal <130/80 for CKD with albuminuria >30 mg/day or proteinuria >500-1000 mg/day • MDRD study: 3 year f/u • <1 g/day proteinuria: no benefit to aggressive BP control (target 125/75) vs. target 140/90 • Evidence for delayed progression with tighter BP control if proteinuria/albuminuria • ACE-I used in both groups (about ½ of all enrolled) • Consider more relaxed goals <150/90 if elderly (>60? >80?)

  23. MKSAP 72 A 70 yo W comes for routine f/u for recently diagnosed CKD and HTN. She is asymptomatic. Her only med is lisinopril, which was titrated up to the maximal dose over the last 3 months. She is adherent to this and a sodium restricted diet. On PE VS show BP 160/90 and she has trace b/l pedal edema K 5.0, sCr 1.3, Urine protein-cr ratio 2.1 mg/mg Which of the following is the most appropriate treatment for this patient? A) Hydrochlorothiazide B) Losartan C) Metoprolol D) Verapamil

  24. MKSAP 72 A 70 yo W comes for routine f/u for recently diagnosed CKD and HTN. She is asymptomatic. Her only med is lisinopril, which was titrated up to the maximal dose over the last 3 months. She is adherent to this and a sodium restricted diet. On PE VS show BP 160/90 and she has trace b/l pedal edema K 5.0, sCr 1.3, Urine protein-cr ratio 2.1 mg/mg Which of the following is the most appropriate treatment for this patient? A) Hydrochlorothiazide B) Losartan C) Metoprolol D) Verapamil

  25. Learning Objectives • Identify and categorize CKD ✔ • Perform an appropriate evaluation for underlying causes of CKD ✔ • Identify and modify risk factors for progression of CKD✔ • Understand, monitor for and if possible modify risk for cardiovascular, metabolic and hematological complications of CKD • Renally dose medications • Know when to refer to nephrology • Be able to explain CKD to patients

  26. Cardiovascular risk • 17 fold higher risk of CV events in CKD vs. non-CKD patients (Should CKD be considered a CAD risk equivalent?) • Most randomized trials of CV disease have excluded patients with CKD IV and V • Lifestyle recommendations remain key • Smoking cessation • Exercise • Diet • Remember again: low sodium • Aspirin? • Assess risks and benefits and use SDM • E.g. if CV risk estimated to be >10% and no excess bleeding risk, consider adding 81 mg ASA daily

  27. Statin therapy? • Lancet 2011: CKD 3-5: risk reduction from 13.4% to 11.3% over 5 years for all major CV events. Does not modify risk of progression of CKD • Still take into account all risk factors (e.g. CV/framingham risk)

  28. Prevalence of chemical and metabolic consequences of CKD increase with decreasing GFR, notably < 60 ml/min JASN 20: 164–171, 2009

  29. Metabolic complications/Mineral and Bone disorders • Hyperkalemia • esp with ACE/ARB, K-sparing diuretic • Metabolic Acidosis • Treat with sodium bicarb if serum bicarb <22 • Shown to slow progression of kidney disease • Dr. Hood recommends baking soda (1/2 tsp/day) • Metabolic Bone disease - complex • For CKD 3 and above: check PTH, Vitamin D-25, calcium and phosphorus • In general: refer to nephrology if PTH or phosphorus high

  30. Moe, SM et al. ACKD: 3-12, 2007

  31. A refresher on secondary hyperparathyroidism in cKD

  32. More on PTH/phos/ca physiology • In CKD 2-3, increased PTH helps maintain normal serum Ca • Stage 4-5: sustained hyperphosphatemia leads to: • Even higher levels of PTH which further suppresses 1,25 Vit D production and can lead to hypocalcemia • Increased cal-phos product -> increased vascular calcification: may contribute to CV mortality • Maintaining optimal balance between treating vitamin D deficiency and preventing extraosseous calcification is challenging • Achieving target phos and cal levels priority over PTH level

  33. Calcium and Phosphorus Management in CKD stage 3, 4 and 5 • goals: serum Ca 8.4 - 9.5 mg/dl serum P 2.7 - 4.5 mg/dl intact PTH ? 35 - 70 pg/ml - stage 3 ? 70 - 110 pg/ml - stage 4 ? 150 - 300 pg/ml – stage 5 • Strategies to maintain normal • reduce dietary phosphorus intake < 1 g/d • use phosphate binders with meals to keep P at goal (Ca CO3, calcium acetate, sevelamer CO3, lanthanum CO3) • Avoid calcium based phos binders if ca-phos product high and/or PTH too low • Replace low Vit D-25 with cholecalciferol • give 1,25 D3 (calcitriol) 0.25-0.5 mcg/d if PTH high (? >2x N) but avoid oversuppression also

  34. Prevalence of types of bone disease as determined by bone biopsy in patients with CKD-MBD AD, adynamic bone; OF, osteitis fibrosa; OM, osteomalacia.

  35. BONE DISEASE DISEASE IN CKD/”RENAL OSTEODYSTROPHY”: MANY FLAVORS • Adynamic bone disease • Low bone turnover/low PTH: common in CKD 5 • Functional hypoparathyroidism may contribute (PTH<100) • E.g. Oversupplementation of vitamin D/calcium • Osteitis fibrosa cystica • High turnover bone disease/high PTH: Subperiosteal bone reabsorption • Asymptomatic if early, bone pain, fractures if advanced • Brown tumors: erosive osteolytic lesions • Tx: vit d analogs, lower serum phos • Osteomalacia • Low bone turnover: hypocalcemia, hypophosphatemia, aluminum toxicity • Osteoporosis • DXA inaccurate in CKD 3 + because of other bone abnormalities – may be present if fractures plus hx of steroids, vit d deficiency, etc. • Bone biopsy if high suspicion is required prior to starting any therapy • Bisphosphonates may contribute to adynamic bone disease in CKD 4/5

  36. MKSAP 19 A 59 yo W is evaluated for a 2 wk hx of right hip pain. She has CKD treated with peritoneal dialysis. Meds are epoetin alfa, calcium acetate, calcitriol, and a MVI. PE: VS wnl, tender over right lateral trochanter, rotation at the hip elicits pain Labs: phos 5.6, ca 10.2 ALP 86 PTH 21 1,25 OH D =52 25-OH D =15 Plain radiograph of R hip shows diffuse osteopenia. An area of lucency is seen along the medial aspect of the femoral neck consistent with a stress fracture. Which is the most likely cause of this patient’s bone disease? • Adynamic bone disease • B2-microglobulin-associated amyoidosis • Osteitis fibrosa cystica • Osteomalacia

  37. MKSAP 19 A 59 yo W is evaluated for a 2 wk hx of right hip pain. She has CKD treated with peritoneal dialysis. Meds are epoetin alfa, calcium acetate, calcitriol, and a MVI. PE: VS wnl, tender over right lateral trochanter, rotation at the hip elicits pain Labs: phos 5.6, ca 10.2 ALP 86 PTH 21 1,25 OH D =52 25-OH D =15 Plain radiograph of R hip shows diffuse osteopenia. An area of lucency is seen along the medial aspect of the femoral neck consistent with a stress fracture. Which is the most likely cause of this patient’s bone disease? • Adynamic bone disease • B2-microglobulin-associated amyoidosis • Osteitis fibrosa cystica • Osteomalacia

  38. Anemia in Renal Disease • Secondary to: • deceased erythropoietin production by kidney • Anemia of kidney disease is usually apparent by CKD 4 • Diagnosis of exclusion • iron deficiency, B12 deficiency, hemolysis • Epo levels NOT recommended

  39. Iron Replacement in CKD • Monitor: serum ferritin, iron saturation (TSAT) • Goal: serum ferritin 100-600 ng/ml, TSAT 20-50% • Oral ferrous sulfate 325 mg 1-3 times/day • – often poorly tolerated or ineffective • intravenous preparations: ferric gluconate • Safety concerns: • infusion reactionsconcurrent active infection

  40. What is the target HGB in Anemia of renal disease? 9-11 g/dL • CHOIR 2006: RCT to Hb 11.3 v 13.5 in 1432 with GFR 15-50 Adverse CV outcomes in 13.5% (Hb 11.3) v 17.5% (Hb 12.6) No change in QOL measures • CREATE 2006: RCT to Hb 10.5-11.5 v 13-15 in 603, GFR 15-35 No difference in time to first CV event (but underpowered) Better QOL (vitality score SF36)in high Hb group • TREAT 2010: RCT in 4000 CKD (GFR 20-60), DM2 , Hb < 11; Intervention: darbepoietin v placebo; Goal: Hb 13 g/dl or rescue if < 9 g/dl; Outcome: all cause mortality, CV morbidity no different but higher rate of stroke and thrombolic events

  41. Erythropoietin (ESAs) use in CKD 3-5 • prior to initiating treatment: control BP (< 160/90 mmHg) ensure adequate B12, Fe (% saturation > 20) • check for treatable inflammation • during ongoing treatment: monitor Hb or HCT every 2-4 weeks monitor Fe saturation, ferritin every 3 months maintain Fe sat 20-50%, ferritin < ? 600 ng/ml keep BP well controlled

  42. MKSAP 43 A 35 yo W with a history of stage 4 CKD and HTN 2/2 FSGS is evaluated for a 2 month hx of fatigue. She has no SOB, melena or menorrhagia. Meds include lisinopril, ASA, sevelamer, and furosemide. Family hx negative for anemia. On PE she has pallor, stool negative for occult blood. Labs: Hgb 8.6 WBC 5600 MCV 82 Retic 0.5% Ferritin 25, Transferrin saturation 10%, B12 600 Folate 14 Which is the next most appropriate step? • Begin epoalfa • Begin iron • Measure serum erthropoietin • Schedule bone marrow examination

  43. MKSAP 43 A 35 yo W with a history of stage 4 CKD and HTN 2/2 FSGS is evaluated for a 2 month hx of fatigue. She has no SOB, melena or menorrhagia. Meds include lisinopril, ASA, sevelamer, and furosemide. Family hx negative for anemia. On PE she has pallor, stool negative for occult blood. Labs: Hgb 8.6 WBC 5600 MCV 82 Retic 0.5% Ferritin 25 B12 600 Folate 14 Which is the next most appropiratestep? • Begin epialfa • Begin iron • Measure serum erthropoietin • Schedule bone marrow examination

  44. Learning Objectives • Identify and categorize CKD ✔ • Perform an appropriate evaluation for underlying causes of CKD ✔ • Identify and modify risk factors for progression of CKD✔ • Understand, monitor for and if possible modify risk for cardiovascular, metabolic and hematological complications of CKD✔ • Renally dose medications • Know when to refer to nephrology • Be able to explain CKD to patients

  45. Avoid nephrotoxic Agents! • NSAIDs and Cox-2 inhibitors • Iodinated Contrast • Magnesium and phosphate containing cathartics • Milk of mag, mag citrate • Discontinue: • Metformin if GFR <50 • Risk of lactic acidosis • Bisphosphonates if GFR <50 • Risk of adynamic bone disease

  46. Other meds May require adjustment • For those with or at risk for CKD: • Avoid glyburide, especially in the elderly (longer half life, more hypoglycemia) • Benadryl has a longer half life, as it is renaly excreted • In gout, treat to a target uric acid level rather than a specific dose reduction of allopurinol – lower uric acid level may also slow risk of progression of CKD, studies underway • Colchicine also renally dosed – relevant if avoiding NSAIDs and prednisone for acute gout tx • Antibiotics, antiepileptics often require renal dosing

  47. MKSAP 36 A 55 yo M comes for a new patient evaluation. He was diagnosed with type 2 DM 15 years ago. He also has HTN and a 1-year hx of R knee OA that is well controlled with maximal-dose ibuprofen. He has not been evaluated by a physician in 3 yeas and has been out of his HCTZ, losartan, metformin and pravastatin for 2 years. BP 146/92, BMI 31, cardiopulmonary exam normal, b/l pedal edema to mid shin Labs: glucose 230 nonfasting Potassium 5.7 sCr 2.5 urine protein-creatinine ratio 0.46 mg/mg U/A 3+ protein, 2+ glucose In addition to initiating furosemide, which of the following is the most appropriate initial step in managing his CKD? • Begin HCTZ • Begin losartan • Begin spironolactone • Discontinue ibuprofen

  48. MKSAP 36 A 55 yo M comes for a new patient evaluation. He was diagnosed with type 2 DM 15 years ago. He also has HTN and a 1-year hx of R knee OA that is well controlled with maximal-dose ibuprofen. He has not been evaluated by a physician in 3 yeas and has been out of his HCTZ, losartan, metformin and pravastatin for 2 years. BP 146/92, BMI 31, cardiopulmonary exam normal, b/l pedal edema to mid shin Labs: glucose 230 nonfasting Potassium 5.7 sCr 2.5 urine protein-creatinine ratio 0.46 mg/mg U/A 3+ protein, 2+ glucose In addition to initiating furosemide, which of the following is the most appropriate initial step in managing his CKD? • Begin HCTZ • Begin losartan • Begin spironolactone • Discontinue ibuprofen

  49. Learning Objectives • Identify and categorize CKD ✔ • Perform an appropriate evaluation for underlying causes of CKD ✔ • Identify and modify risk factors for progression of CKD✔ • Understand, monitor for and if possible modify risk for cardiovascular, metabolic and hematological complications of CKD✔ • Renally dose medications✔ • Know when to refer to nephrology • Be able to explain CKD to patients

  50. Help! When to enlist our nephrology friends • If etiology unclear and/or may need biopsy • Any CKD 4 – need to start discussion of planning for RRT at this point • ?CKD 3b if challenging management issues • BP difficult to control • Hyperphosphatemia and/or PTH> 150? • Metabolic acidosis?

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