Presentation on theme: "Chronic Kidney Disease"— Presentation transcript:
1 Chronic Kidney Disease Identification and ManagementAmy L. Hazel, CNPKidney & Hypertension Consultants
2 Chronic Kidney Disease One in 10 Americans have Chronic Kidney Disease
3 Chronic Kidney Disease Chronic Kidney Disease is most common in those > 70 years old
4 Chronic Kidney Disease Incidence of Chronic Kidney Disease is increasing most rapidly in people 65 years and older
5 Chronic Kidney Disease Kidney disease is the 8TH leading cause of death in the United States
6 Chronic Kidney Disease People with Chronic Kidney Disease are times more likely to die than reach End-Stage Renal Disease
7 Chronic Kidney Disease The 1-year mortality for heart attack patients without identified Chronic Kidney Disease is 36% , compared with 51% for patients with stage 3 to 5 CKD
8 Chronic Kidney Disease Early detection and education can help prevent the progression of kidney disease to kidney failure
9 Chronic Kidney Disease Objectives Define Chronic Kidney DiseaseClassify the disease by Glomerulofiltration rate, and amount of proteinuriaDiscuss stages of disease and its risk factorsTreatment in hypertensive and diabetic renal diseaseConsequences of diseaseMedications in ckd patientWe will NOT be discussingRenal Replacement therapies including transplantAcute Kidney Injury
10 Chronic Kidney Disease KDOQI (Kidney Disease Outcomes Quality Initiative)2002 National Kidney Foundation classification systemStages of Chronic Kidney DiseaseKDIGO (Kidney Disease: Improving Global Outcomes)Updated, more clearly defined (2004)Classified based on cause, GFR category and albuminuria category (2012)
11 Chronic Kidney Disease DefinedAbnormalities in structure or function > 3 months with implications for healtheGFR < 60 ml/min/1.73mA loss of half or more of the adult level of normal kidney functionalbuminuria or proteinuriaCasts or blood in urineStructuralHydronephrosis, small kidneys, congenital kidneys, polycystic kidney diseaseHistory of kidney transplant
12 Chronic Kidney Disease What is GFR?GFR (glomerular filtration rate) is equal to the total of the filtration rates of the functioning nephrons in the kidney.In young adults it is approximately mL/min/1.73 m2 and declines with age.
13 Chronic Kidney Disease MDRD (Modification of Diet in Renal Disease)Preferred method for estimating GFR using the 4-variable equation based on Serum Creatinine, age, gender, and ethnicity.Includes body surface areaeGFRs per 1.73m2May be the best estimate for eGFR in older populationCurrent gold standardMore accurate than measured creatinine clearance from 24-hour urine collections or estimated by the Cockroft-Gault formula
14 Chronic Kidney Disease Stages of diseaseLimitations of CRAge < 18 or >70Gfr > 60Extreme body sizeSevere malnutritionParaplegia or quadriplegiaDoes not adjust for Hispanic or Asian populationsTends to overestimate gfrUrinary creatinine excretion is lower in ckd, therefore overestimating gfr from serum creatinine.
15 Chronic Kidney Disease Cockroft-Gault FormulaDoes not includes body weight, reflecting muscle mass….main determinant of creatinine generation.May overestimate individuals having ckd after age of 70 yrs, obese or edematous ptsLess accurate than mdrd and ckd-epi
16 Chronic Kidney Disease CKD-Epidemiology Collaboration (CKD-EPI)Uses the 4 variables found in MDRD equation, with addition of serum cystatin C to provide more accurate eGFR than MDRD in gfr >60May raise the number of older individuals with ckdCKD-EPI and MDRD Study equations can therefore be applied to determine level of kidney function, regardless of a patient’s size.
17 Chronic Kidney Disease To use the free GFR calculator on the NKF web site: Go toTo download NKF’s new GFR calculator to your smartphone: Go to
19 Chronic Kidney Disease Because of greater cardiovascular disease risk and risk of disease progression at lower eGFRs, CKD Stage 3 is sub-divided into Stages 3A (45–59 mL/min/1.73 m2) and 3B (30–44 mL/min/1.73 m2).
20 Chronic Kidney Disease Proteinuria Proteinuria (most important marker of disease progression)Ratio of the concentrations of urine albumin (mg/dl) to that of urine creatnine (g/dl) on a spot untimed specimen (or early morning?????)Mg albumin/g creatinine (UACR)Normal <30 mg albumin/g creatinineMicroalbuminemia > mg albumin /g creatinineMacroalbuminemia > 300 albumin/ g creatinineCkd if 2 of 3 tests are abnormal
21 Chronic Kidney Disease Proteinuria AlbuminuriaPresence of excessive amounts of the protein albumin in urineMicroalbuminuriaUACR mg/mmol in menUACR mg/mmol in womenMacroalbuminuriaUACR > 25mg/mmol in menUACR > 35mg/mmol in women(Urinary creatinine excretion is influenced by muscle mass, urinary creatinine excretion higher in men, on average, than women)The preferred method: urinary albumin-to-creatinine ratio (UACR) in first void. Spot urine is acceptable if first void not practical.
22 Chronic Kidney Disease Proteinuria Presence of excessive amounts of proteins in urineIncludes: albumin, low-molecular weight immunoglobulin's, lysozyme, insulin and microglobinTotal protein (mg/dl) to creatinine (g/dl) on a spot urine sampleNormal < 200 mg/gUrine pr mg/dl 200Urine cr mg/dl 100Ratio 200/100 = 2gm protein/24hoursIncreased excretion of protein leads to progression of ckd and increases cvd risksAlbuminuria and proteinuria are related, but not interchangeable.
26 Chronic Kidney Disease Stage 1 and 2 new guidelines American College of Physicians 2013Do not recommend screening for ckd in asymptomatic adults without risk factors for ckdFalse positive test results, disease labelingNo benefit of early treatmentTreat hypertension in stage 1-3 ckd with acei or arbNo need to test urine for protein in adults with or without diabetes if currently taking acei or arbManage elevated LDL in pt with stage 1-3 ckd
27 Chronic Kidney Disease Risk Factors Diabetes44% of new cases of ckdHypertension28% of new cases of ckdCardiovascular diseaseObesityHigh cholesterolLupusFamily history of CKDUTI/urinary stonesSystemic infectionsRecovery from Acute Kidney Injury (AKI)Exposure to certain drugsSocio-demographic groupsElderlyminority populationAfrican American, Native American, Hispanic, and Asian.Low income/education
28 Chronic Kidney Disease Diabetic Nephropathy Diabetic Kidney DiseaseGlomerulosclerosis 5-7 yr after dxHypertrophy and hyperfiltration in glomerulusStrict glycemic controlACEiARB
29 Chronic Kidney Disease Diabetic Nephropathy Blood pressure controlGoalDiabetic or Non diabetic with Albumin-to-creatinine ratio > 30 mg/g <130/80Diabetic or Non diabetic with albumin-to-creatinine ratio < 30gm/g <140/90Protein restriction, individualizeSmoking cessation
30 Chronic Kidney Disease Diabetic Nephropathy Hypoglycemics AgentsSulfonylureas, biguanides, DPP-4 inhibitors, GLP-1 agonists, and insulin require dose adjustmentsAll second generation sulfonylureas can be used in ckd ptsGlyburide not recommended with crcl < 50%Glipizide, no adjustment
31 Chronic Kidney Disease Diabetic Nephropathy Hypoglycemic AgentsMetforminLactic AcidosisAvoid in gfr < 30 ml/min/1.73m2InsulinThiazolidinedionesDecreased renal glucogenesisDecreased renal clearance of sulfonylureas
32 Chronic Kidney Disease Hypertensive Nephropathy Hypertensive Kidney DiseaseBoth a cause and consequence of the diseasePrimarily: Inappropriate sodium reabsorptionActivation of RAASErythropoietin administrationRASExtracellular fluidCalcified arterial treeCardiovascular diseaseAntiplatelet agents are recommendedBNP in gfr <60, interpret with caution
33 Chronic Kidney Disease Hypertensive Nephropathy ManagementRAAS blockadeReduce proteinuriaLowers systemic BP and intraglomerular pressureMore difficult d/t increase in vascular resistance and increased blood volumeLow sodium diet (DASH diet not recommended in CKD stage 3-5)Combination of ace/arb significantly slowed disease progression, greater reduction in proteinuriaUse of non-dihydropyridine CCB have shown to decrease proteinuria (if failed ace/arb)
34 Chronic Kidney Disease Hypertensive Nephropathy GoalsDiabetic or Non-diabetic with Albumin-to-creatinine ratio > 30 mg/g <130/80Diabetic or Non-diabetic with albumin-to-creatinine ratio < 30gm/g <140/90Delay progression of diseaseReduce cardiovascular risk
35 Chronic Kidney Disease Hypertensive Nephropathy DiureticsEnhances antihypertensive therapyDecreasing tubular sodium reabsorption, increasing sodium excretion, reversing ECF volume expansion and lowering bp.Thiazides (qd) for gfr > 30 (stage 1-3)Loops (qd-bid) for gfr < 30 (stages 4 & 5)Potassium sparing diureticsRisk of hyperkalemia, esp with ACEI/ARB
37 Chronic Kidney Disease Complications Chronic Kidney Disease-Metabolic Bone Disorder (CKD-MBD)Systemic disorderRenal osteodystrophyExtraskeletal (vascular) calcificationIncreases in morbidity and mortality of ckd ptsAbnormalities inCalciumPhosphorusParathyroid HormoneVitamin D25(OH)D1,25(OH)2DOsteoporosis (ckd 1-3) versus renal osteodystrophy (later stages)
38 Chronic Kidney Disease Complications GFR fallsRise in phosphorus decrease in calciumdecreased production of calcitriolTriggers increase in Parathyroid hormone (PTH) productionIncreased absorption of Phosphorus in kidneysNormalize phosphorus with high PTH
44 Chronic Kidney Disease Complications Treat complicationsHigh phosphorusLow Phosphorus dietPhosphorus BindersCorrect low Vitamin D levelsErgocalciferol/cholecalciferolWatch for high CalciumActive Vitamin D to suppress PTHSeen more in late stages of disease
45 Chronic Kidney Disease Complications Anemia (hgb < 13g/dL in males, < 12g/dL in females)A decline in production of erythropoietin (EPO)Not measured, assumedCheck red cell indices, absolute reticulocyte count, vitamin B12 and folate levels, and iron panelGoalHemoglobin???Serum transferrin saturation (TSAT) > 30%Serum ferritin <500ng/mlAcute phase reactant, elevated with infection/inflammation
46 Chronic Kidney Disease Complications Anemia TreatmentIron therapyMost common cause of anemia in ckdOral vs IVErythropoiesis-stimulating Agents (ESA)Prevent need for transfusionsImprove QOL?Based on weightNot recommended in hgb > 10g/dLTreat <10g/dL on individual basis
47 Chronic Kidney Disease Complications Metabolic acidosisResult of decreased production of ammonia by the kidneySeen in stages 3-5Treatment: supplement BicarbonateComplicationsBone lossAnorexiaHypoalbuminemiaInsulin resistanceMuscle wasting
48 Chronic Kidney Disease Diet SodiumRestriction reduces blood pressure and may reduce albuminuriaDash diet, not rec. for ckd stage 3-5High sodium diet limits effectiveness of ACEi/ARBsPotassiumLow: loop diureticsHigh: Common in stage 4/5 & aldactone/ACEi/ARB/BB/NSAIDSDiet? Salt substitutes?ConstipationTreatmentKayexlateeducation
49 Chronic Kidney Disease Diet PhosphorusHigh levels contribute to vascular calcificationHigh phosphorus is risk factor for cvdhigh phosphorus leads to a more rapid decline in kidney functionPhosphate salts added to processed foods in form of additives and preservativesThese are > 90% absorbed versus 40-60% absorption from organic phosphorus (ie: beans, peas, nuts)Beverages (clear)Nutrition labelingTreatment: Low phosphorus diet, phosphorus binders with meals
50 Chronic Kidney Disease Diet ProteinRestriction should not be used in severe ckdRestriction among selected patientsRestriction, controversialg/kg per dayProvide a small reduction in rate of decline of gfrFollow body weight, serum albumin, pre-albumin in advanced ckdMonitored by dietician
52 Chronic Kidney Disease & Medications PharmacokineticsBioavailability of oral meds can be increased or decreasedChanges in gastric pHIncreases in metabolismDecreases in absorption
53 Chronic Kidney Disease & Medications PharmacokineticsDistribution affected by hypoalbuminemia, uremia and alterations in protein binding sitesPossibility leading to toxicity of unbound drug
54 Chronic Kidney Disease & Medications PharmacokineticsMetabolism of drugs may be increased, decreased or unchanged.Reduced activity of cytochrome P-450
55 Chronic Kidney Disease & Medications PharmacokineticsElimination of drugs may cause accumulation of drug and prolong its action, active metabolites may have toxic effects
56 Chronic Kidney Disease & Medications Diabetic medsSulfonylureas metabolized by liver, however GLYBURIDE AND GLIMEPIRIDE produce active metabolites and may contribute to hypoglycemia. Glyburide not recommended. Glipizide, no decrease needed.Biguinides, metformin eliminated unchanged by kidney. Contraindicated risk of lactic acidosis. Hold in women cr >1.4 men 1.5mg/dl per package insertInctretins are eliminated by kidney, so not recommended in crcl < 30ml/minInsulin, with 40-50% elimination by kidneys, dose reductions are recommended
57 Chronic Kidney Disease & Medications StatinsMetabolized by liver, however, active metabolites renally eliminated.Not atorvastatin (lipitor)Inc risk of myopathy with inc doses and declining gfr
58 Chronic Kidney Disease & Medications Antibiotics (ATN)Most penicillins, cephalosporins, and all fluroquinolones except moxifloxacin are eliminated by kidneys. Require reductionAminoglycosides (gent, tobra) can cause nephrotoxicity especially when used with vancomycinNitrofurantoin (macrobid). Excreted by kidneys. contraindicated in crcl <60Sulfamethoxazole-trimethoprim (bactrim). Nephrotoxicity. Dose reduction of ½ in CrCl and avoid in < 15.
59 Chronic Kidney Disease & Medications Analgesics (prerenal)NSAIDSInhibit the synthesis of prostaglandin leading to vasoconstriction and reduced renal blood flow to kidneysCause a decline in gfr and impaired sodium, water, potassium and hydrogen excretionCOX-2 inhibitors work similarly to NSAIDS in that they inhibit synthesis of prostaglandin production
60 Chronic Kidney Disease & Medications AntihypertensivesAll ACEi have some renal elimination. Use lower doses. High risk for high k+, increase in serum creatinine and hypotensionAll ARBs are metabolized by liver, however, watch k+, serum creatinine and blood pressure in ckdBetaBlockersMany eliminated by kidney. Dose adjustments are recommended and follow hr and blood pressure
61 Chronic Kidney Disease & Medications DiureticsThiazide are recommended in those with gfr >30Loop are recommended in those with gfr <30Potassium-sparing should be used with caution in those with gfr < 30
62 Chronic Kidney Disease & Medications Gabapentin (neurontin). Primarily removed by the kidneys. Use with caution.Stage in two divided dosesStage once dailyStage once dailyGout medicationsCKD patient at increased risk for hypersensitivity reactions from drug. Use of low dose colchicine or xanthine oxidase inhibitors (uloric, allopurinol)Inject glucocorticoids for flareAvoid NSAIDs
63 Chronic Kidney Disease & Medications Cancer therapies (ATN)Toxicity, impaired gfrImmunosuppressive agents (ATN)AntithromboticsMany not studied in renal populationDiagnostic agents (ATN)Use of low osmolar contrast (but still problem with high risk pts) less nephrotoxicHold potentially nephrotoxic agents before and after procedureAdequately hydrate with saline before, during and after procedureAvoid gadolinium-containing contrast in gfr < 15
66 ReferencesWillems, J.M, et al Performance of Cockroft-Gault, MDRD, and CKD-EPI in estimating prevalence of renal function and predicting survival in the oldest old. BioMed Central 2013National Kidney and Urologic Diseases Information ClearinghouseMatzke, G. R, et al. Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney International 2011Qassem, A. Screening, Monitoring, and Treatment of Stage 1 to 3 Chronic Kidney Disease: A clinical practice guideline from the clinical guidelines committee of the American College of Physicians. American College of Physicians. 2013Perazella, M. A. Core Curriculum in Nephrology. Toxic Nephropathies: Core Curriculum American Journal of Kidney Disease. Feb 2010Zuber, K., et al. Medication dosing in patients with chronic kidney disease. Journal of the American Academy of Physician Assistants. 2013Liles, A. M., Medication considerations for patients with chronic kidney disease who are not yet on dialysis. Nephrology Nursing Journal, May-June 2011Johnson, D. W., Chronic kidney disease and measurement of albuminuria or proteinuria: a position statement. Medical Journal of Australia, August 2012Eknoyan, G, et al. Proteinuria and other markers of chronic kidney disease: A position statement of the National Kidney Foundation (NKF) and the National Institute of Diabetes and Kidney Diseases (NIDDK)Bakris, G. L., Slowing Nephropathy Progression: Focus on Proteinuria Reduction. American Society of Nephrology, 2008James, P. A., 2014 Evidence-Based Guidelines for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eight Joint National Committee (JNC 8). Journal of American Medical Association, 2013National Kidney Foundation: Kidney Disease Outcomes Quality Initiative GuidelinesSummary of Recommendation Statements. Kidney Disease International Supplement, 2012Ferrari, P. Serum iron markers are inadequate for guiding iron repletion in chronic kidney disease. American Society of Nephrology, 2011Kopple, J. D., Risks of chronic metabolic acidosis in patients with chronic kidney disease. Kidney International, Supplement, 2005.