Chronic Kidney Disease Identification and Management Amy L. Hazel, CNP Kidney & Hypertension Consultants

Chronic Kidney Disease

Identification and Management

Amy L. Hazel, CNP

Kidney & Hypertension Consultants


One in 10 Americans have Chronic Kidney Disease


Chronic Kidney Disease is most common in those > 70 years old


Incidence of Chronic Kidney Disease is increasing most rapidly in people 65 years

and older


Kidney disease is the 8TH leading cause of death in the United States


People with Chronic Kidney Disease are 16-40 times more likely to die than reach End-

Stage Renal 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


Early detection and education can help prevent the progression of kidney disease to

kidney failure

Chronic Kidney DiseaseObjectives

Define Chronic Kidney Disease

Classify the disease by Glomerulofiltration rate, and amount of proteinuria

Discuss stages of disease and its risk factors

Treatment in hypertensive and diabetic renal disease

Consequences of disease Medications in ckd patient

We will NOT be discussing Renal Replacement

therapies including transplant

Acute Kidney Injury


KDOQI (Kidney Disease Outcomes Quality Initiative) 2002 National Kidney Foundation classification

system Stages of Chronic Kidney Disease

KDIGO (Kidney Disease: Improving Global Outcomes) Updated, more clearly defined (2004) Classified based on cause, GFR category and

albuminuria category (2012)

Chronic Kidney Disease Defined

Abnormalities in structure or function > 3 months with implications for health eGFR < 60 ml/min/1.73m

A loss of half or more of the adult level of normal kidney function

albuminuria or proteinuria Casts or blood in urine Structural

Hydronephrosis, small kidneys, congenital kidneys, polycystic kidney disease

History of kidney transplant


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 120-130 mL/min/1.73 m2 and declines with age.


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 area eGFRs per 1.73m2

May be the best estimate for eGFR in older population Current gold standard

More accurate than measured creatinine clearance from 24-hour urine collections or estimated by the Cockroft-Gault formula


Stages of disease Limitations of CR

Age < 18 or >70 Gfr > 60 Extreme body size Severe malnutrition

Paraplegia or quadriplegia

Does not adjust for Hispanic or Asian populations

Tends to overestimate gfr Urinary creatinine

excretion is lower in ckd, therefore overestimating gfr from serum creatinine.


Cockroft-Gault Formula Does 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 pts Less accurate than mdrd and ckd-epi


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 >60

May raise the number of older individuals with ckd CKD-EPI and MDRD Study equations can therefore

be applied to determine level of kidney function, regardless of a patient’s size.


To use the free GFR calculator on the NKF web site: Go to www.kidney.org/gfr

To download NKF’s new GFR calculator to your smartphone: Go to www.kidney.org/apps


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).

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 untimedspot untimed specimen (or early morning?????)specimen (or early morning?????) Mg albumin/g creatinine (UACR)

Normal <30 mg albumin/g creatinine Microalbuminemia > 30-300 mg albumin /g creatinine Macroalbuminemia > 300 albumin/ g creatinine

Ckd if 2 of 3 tests are abnormal


Albuminuria Presence of excessive amounts of the protein albumin in urine

Microalbuminuria UACR 2.5-25mg/mmol in men UACR 3.5-35mg/mmol in women

Macroalbuminuria UACR > 25mg/mmol in men UACR > 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.


Proteinuria Presence of excessive amounts of proteins in urine

Includes: albumin, low-molecular weight immunoglobulin's, lysozyme, insulin and microglobin

Total protein (mg/dl) to creatinine (g/dl) on a spot urine sample Normal < 200 mg/g

Urine pr mg/dl 200 Urine cr mg/dl 100 Ratio 200/100 = 2gm protein/24hours

Increased excretion of protein leads to progression of ckd and increases cvd risks

Albuminuria and proteinuria are related, but not interchangeable.


Persistant microalbuminemia: Tx lipid disorders and /or htn Retest in 6mo

Affect urinary albumin excretion UTI High protein diet Acute febrile illness Heavy exercise within 24 hrs Menstruation Drugs (NSAIDS, ACEI, ARB)


Stage 1 and 2 new guidelines American College of Physicians 2013 Do not recommend screening for ckd in asymptomatic

adults without risk factors for ckd False positive test results, disease labeling No benefit of early treatment

Treat hypertension in stage 1-3 ckd with acei or arb No need to test urine for protein in adults with or

without diabetes if currently taking acei or arb Manage elevated LDL in pt with stage 1-3 ckd

Chronic Kidney Disease Risk Factors

Diabetes 44% of new cases of

ckd Hypertension

28% of new cases of ckd

Cardiovascular disease Obesity High cholesterol Lupus Family history of CKD UTI/urinary stones

Systemic infections Recovery from Acute

Kidney Injury (AKI) Exposure to certain

drugs Socio-demographic

groups Elderly minority population

African American, Native American, Hispanic, and Asian.

Low income/education

Chronic Kidney DiseaseDiabetic Nephropathy

Diabetic Kidney Disease Glomerulosclerosis 5-7 yr after dx Hypertrophy and hyperfiltration in glomerulus

Strict glycemic control ACEi ARB


Blood pressure control Goal

Diabetic or Non diabetic with Albumin-to-creatinine ratio > 30 mg/g <130/80

Diabetic or Non diabetic with albumin-to-creatinine ratio < 30gm/g <140/90

Protein restriction, individualize Smoking cessation


Hypoglycemics Agents Sulfonylureas, biguanides, DPP-4 inhibitors, GLP-1

agonists, and insulin require dose adjustments All second generation sulfonylureas can be used in

ckd pts Glyburide not recommended with crcl < 50% Glipizide, no adjustment


Hypoglycemic Agents Metformin

Lactic Acidosis Avoid in gfr < 30 ml/min/1.73m2

Insulin Thiazolidinediones

Decreased renal glucogenesis Decreased renal clearance of sulfonylureas

Chronic Kidney DiseaseHypertensive Nephropathy Hypertensive Kidney Disease

Both a cause and consequence of the disease Primarily: Inappropriate sodium reabsorption Activation of RAAS Erythropoietin administration RAS Extracellular fluid Calcified arterial tree

Cardiovascular disease Antiplatelet agents are recommended BNP in gfr <60, interpret with caution

Chronic Kidney DiseaseHypertensive Nephropathy Management

RAAS blockade Reduce proteinuria Lowers systemic BP and intraglomerular pressure

More difficult d/t increase in vascular resistance and increased blood volume

Low sodium diet (DASH diet not recommended in CKD stage 3-5)

Combination of ace/arb significantly slowed disease progression, greater reduction in proteinuria

Use of non-dihydropyridine CCB have shown to decrease proteinuria (if failed ace/arb)

Chronic Kidney DiseaseHypertensive Nephropathy

Goals Diabetic or Non-diabetic with Albumin-to-creatinine

ratio > 30 mg/g <130/80 Diabetic or Non-diabetic with albumin-to-creatinine

ratio < 30gm/g <140/90 Delay progression of disease Reduce cardiovascular risk

Chronic Kidney DiseaseHypertensive Nephropathy

Diuretics Enhances antihypertensive therapy Decreasing 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 diuretics

Risk of hyperkalemia, esp with ACEI/ARB

Chronic Kidney DiseaseComplications Chronic Kidney Disease-Metabolic Bone Disorder (CKD-MBD)

Systemic disorder Renal osteodystrophy Extraskeletal (vascular) calcification Increases in morbidity and mortality of ckd pts Abnormalities in

Calcium Phosphorus Parathyroid Hormone Vitamin D

25(OH)D 1,25(OH)2D

Osteoporosis (ckd 1-3) versus renal osteodystrophy (later stages)

Chronic Kidney DiseaseComplications

GFR falls

Rise in phosphorus decrease in calciumdecreased production of calcitriol

Triggers increase in Parathyroid hormone (PTH) production

Increased absorption of Phosphorus in kidneys

Normalize phosphorus with high PTH


Treat complications High phosphorus

Low Phosphorus diet Phosphorus Binders

Correct low Vitamin D levels Ergocalciferol/cholecalciferol Watch for high Calcium

Active Vitamin D to suppress PTH Seen more in late stages of disease

Chronic Kidney DiseaseComplications Anemia (hgb < 13g/dL in males, < 12g/dL in females)

A decline in production of erythropoietin (EPO) Not measured, assumed

Check red cell indices, absolute reticulocyte count, vitamin B12 and folate levels, and iron panel

Goal Hemoglobin??? Serum transferrin saturation (TSAT) > 30% Serum ferritin <500ng/ml

Acute phase reactant, elevated with infection/inflammation


Anemia Treatment Iron therapy

Most common cause of anemia in ckd Oral vs IV

Erythropoiesis-stimulating Agents (ESA) Prevent need for transfusions Improve QOL? Based on weight Not recommended in hgb > 10g/dL Treat <10g/dL on individual basis


Metabolic acidosis Result of decreased production of ammonia by the kidney Seen in stages 3-5 Treatment: supplement Bicarbonate Complications

Bone loss Anorexia Hypoalbuminemia Insulin resistance Muscle wasting

Chronic Kidney DiseaseDiet

Sodium Restriction reduces

blood pressure and may reduce albuminuria

Dash diet, not rec. for ckd stage 3-5

High sodium diet limits effectiveness of ACEi/ARBs

Potassium Low: loop diuretics High: Common in

stage 4/5 & aldactone/ACEi/ARB/BB/NSAIDS

Diet? Salt substitutes? Constipation Treatment

Kayexlate education


Phosphorus High levels contribute to vascular calcification

High phosphorus is risk factor for cvd high phosphorus leads to a more rapid decline in kidney

function Phosphate salts added to processed foods in form of additives

and preservatives These are > 90% absorbed versus 40-60% absorption from

organic phosphorus (ie: beans, peas, nuts) Beverages (clear) Nutrition labeling Treatment: Low phosphorus diet, phosphorus binders with

meals


Protein Restriction should not be used in severe ckd Restriction among selected patients Restriction, controversial 0.6-0.8g/kg per day

Provide a small reduction in rate of decline of gfr Follow body weight, serum albumin, pre-albumin in

advanced ckd Monitored by dietician

Chronic Kidney Disease& Medications

Pharmacokinetics

Bioavailability of oral meds can be increased or decreased Changes in gastric pH Increases in metabolism Decreases in absorption


Pharmacokinetics

Distribution affected by hypoalbuminemia, uremia and alterations in protein binding sites Possibility leading to toxicity of unbound drug


Pharmacokinetics

Metabolism of drugs may be increased, decreased or unchanged. Reduced activity of cytochrome P-450


Pharmacokinetics

Elimination of drugs may cause accumulation of drug and prolong its action, active metabolites may have toxic effects


Diabetic meds Sulfonylureas 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 insert

Inctretins are eliminated by kidney, so not recommended in crcl < 30ml/min

Insulin, with 40-50% elimination by kidneys, dose reductions are recommended


Statins

Metabolized by liver, however, active metabolites renally eliminated. Not atorvastatin (lipitor) Inc risk of myopathy with inc doses and

declining gfr


Antibiotics (ATN) Most penicillins, cephalosporins, and all

fluroquinolones except moxifloxacin are eliminated by kidneys. Require reduction

Aminoglycosides (gent, tobra) can cause nephrotoxicity especially when used with vancomycin

Nitrofurantoin (macrobid). Excreted by kidneys. contraindicated in crcl <60

Sulfamethoxazole-trimethoprim (bactrim). Nephrotoxicity. Dose reduction of ½ in CrCl 15-30 and avoid in < 15.


Analgesics (prerenal) NSAIDS

Inhibit the synthesis of prostaglandin leading to vasoconstriction and reduced renal blood flow to kidneys

Cause a decline in gfr and impaired sodium, water, potassium and hydrogen excretion

COX-2 inhibitors work similarly to NSAIDS in that they inhibit synthesis of prostaglandin production


Antihypertensives

All ACEi have some renal elimination. Use lower doses. High risk for high k+, increase in serum creatinine and hypotension

All ARBs are metabolized by liver, however, watch k+, serum creatinine and blood pressure in ckd

BetaBlockers Many eliminated by kidney. Dose adjustments are

recommended and follow hr and blood pressure


Diuretics Thiazide are recommended in those with gfr >30 Loop are recommended in those with gfr <30 Potassium-sparing should be used with

caution in those with gfr < 30


Gabapentin (neurontin). Primarily removed by the kidneys. Use with caution. Stage 3 400-1400 in two divided doses Stage 4 200-700 once daily Stage 5 100-300 once daily

Gout medications CKD patient at increased risk for hypersensitivity

reactions from drug. Use of low dose colchicine or xanthine oxidase inhibitors (uloric, allopurinol)

Inject glucocorticoids for flare Avoid NSAIDs


Cancer therapies (ATN) Toxicity, impaired gfr

Immunosuppressive agents (ATN)

Antithrombotics Many not studied in

renal population

Diagnostic agents (ATN) Use of low osmolar

contrast (but still problem with high risk pts) less nephrotoxic

Hold potentially nephrotoxic agents before and after procedure

Adequately hydrate with saline before, during and after procedure

Avoid gadolinium-containing contrast in gfr < 15


Over-the-counter Medications

Pseudoephedrine Nsaids Magnesium Bismuth Phosphorus-containing

enemas

Sodium bicarbonate PPI Zantac Calcium-based reflux

meds Salt substitutes Herbal remedies and

dietary supplements

Questions?Thank You!

References Willems, 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 2013 National Kidney and Urologic Diseases Information Clearinghouse Matzke, 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 2011 Qassem, 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. 2013 Perazella, M. A. Core Curriculum in Nephrology. Toxic Nephropathies: Core Curriculum 2010. American Journal of Kidney

Disease. Feb 2010 Zuber, K., et al. Medication dosing in patients with chronic kidney disease. Journal of the American Academy of Physician

Assistants. 2013 Liles, A. M., Medication considerations for patients with chronic kidney disease who are not yet on dialysis. Nephrology

Nursing Journal, May-June 2011 Johnson, D. W., Chronic kidney disease and measurement of albuminuria or proteinuria: a position statement. Medical

Journal of Australia, August 2012 Eknoyan, 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, 2008 James, 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, 2013 National Kidney Foundation: Kidney Disease Outcomes Quality Initiative Guidelines Summary of Recommendation Statements. Kidney Disease International Supplement, 2012 Ferrari, P. Serum iron markers are inadequate for guiding iron repletion in chronic kidney disease. American Society of

Nephrology, 2011 Kopple, J. D., Risks of chronic metabolic acidosis in patients with chronic kidney disease. Kidney International,

Supplement, 2005.

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Chronic Kidney Disease Identification and Management Amy L. Hazel, CNP Kidney & Hypertension Consultants