Chronic Kidney Disease Thomas W. Ozbirn Jr. Nephrology Associates, PC

Introduction CKD is a worldwide public health problem -Rising incidence and prevalence -In 2003, 100,499 patients entered ESRD programs and 82,000 died -Disproportionate share of healthcare resources

Introduction - Survival probability at 1,5,10 years is 80,40 and 18% -Growth due to changes in demographics -Difference in disease burden between racial groups -Under recognition of early stages

Prevalence Presence of markers of kidney damage for > 3 months Presence of GFR < 60 ml/min for 3 months Elevated serum creatinine -0.8 to 1.3 in men -0.6 to 1.0 in women  Decreased GFR -Cockcroft-Gault -MDRD

Stages of CKD Stage 1- Albuminuria, normal GFR Stage 2- Albuminuria, GFR Stage 3- GFR Stage 4- GFR Stage 5- GFR < 15 or ESRD

Racial Variations Racial and ethnic differences in ESRD 256 per million population in whites 982 per million population in African Americans 344 per million in Asian Americans 514 per million in Native Americans Age/gender ratio (AA/white) 6 to 1

Microalbuminuria Normal < 20 mg/day mg defines microalbuminuria > 300 mg/day Albuminuria -Earliest finding of diabetic nephropathy -Risk factor for cardiovascular disease (CVD)

Impact of CKD on Morbidity HTN, DM, CVD and PVD present in far greater proportion 3x increase in hospital days Older age, gender, race, cardiac disease and PVD are risk factors for hospitalization

Under Recognition of CKD Low awareness of CKD -41,29,22 and 45% recognition in stages 1,2,3 and 4 -African Americans, men and those with hypertension least likely to know -Extends to physicians

Screening for CKD Detect in earlier stages Various therapeutic interventions slow progression Laboratory database screening NKF-K/DOQI guidelines

Management Adaptive hyperfiltration -Initially beneficial -Progressive renal insufficiency -Uremia -ACEi may slow progression -Rate of progression varies

Case 1 47 y/o white male with CKD, creatinine 1.9, BP 144/84, on lisinopril 10 mg q day, and urine protein 1.5 grams/24 hour. Which is best choice for management? No change in therapy (optimal) Add ARB Increase ACEi, add ARB, BP goal < 130/80, and urine protein goal < 500 mg/day Increase ACEi, BP goal < 130/80, and urine protein goal <500 mg/day

Case 1 47 y/o white male with CKD, creatinine 1.9, BP 144/84, on lisinopril 10 mg q day, and urine protein 1.5 grams/24 hour. Which is best choice for management? No change in therapy (optimal) Add ARB Increase ACEi, add ARB, BP goal < 130/80, and urine protein goal < 500 mg/day Increase ACEi, BP goal < 130/80, and urine protein goal <500 mg/day

Association with CVD CKD is a risk factor for CVD Risk of death from CVD greater than the risk of ESRD Phosphate binders may increase Coronary Atherosclerosis

Reversible Causes of Renal Dysfunction Decreased renal perfusion -Hypovolemia -Hypotension -Infection/sepsis -Drugs

Reversible Causes of Kidney Failure  Nephrotoxic drugs -Aminoglycosides -NSAIDs -Iodinated contrast -? Gadolinium -Cimetidine,Tmp,Cefoxitin  Urinary Tract Obstruction

Progression of CKD Intraglomerular HTN Glomerular hypertrophy Hyperlipidemia Metabolic Acidosis Tubulointerstitial disease Secondary FSGS

Progression of CKD ACEi/ARB Antihypertensive therapy given for renal and cardiac protection Reduced proteinuria Goal systolic BP 130 Therapy more effective in earlier stages

Progression of CKD Hyperlipidemia Metabolic Acidosis Protein restriction Smoking cessation JNC 8/ K/DOQI guidelines

Treatment of Complications Volume overload -Homeostatic mechanisms until GFR<15 -Less able to respond to rapid infusions of sodium -Sodium restriction -Diuretics

Case 2 50 y/o female with CKD III, DM II, HTN, and CHF with creatinine 1.6, serum potassium mEq/L and she takes losartan. She is very compliant with a low potassium diet. Which is the next best step? Add thiazide diuretic Add insulin Hemodialysis Sodium polystyrene sulfonate

Case 2 50 y/o female with CKD III, DM II, HTN, and CHF with creatinine 1.6, serum potassium mEq/L and she takes losartan. She is very compliant with a low potassium diet. Which is the next best step? Add thiazide diuretic Add insulin Hemodialysis Sodium polystyrene sulfonate

Treatment of Complications Hyperkalemia -Aldosterone secretion and distal flow -Oliguric, increase K+ diet, increased tissue breakdown  Metabolic Acidosis -Hydrogen ion retention -Serum bicarbonate rarely <10

Treatment of Complications Hyperphosphatemia -Reduce filtered phosphate load -Secondary Hyperparathyroidism -Dietary phosphate restriction -Protein restriction -Phosphate binders -CaxPO4 <55

Treatment of Complications Renal Osteodystrophy -Osteitis Fibrosa -Osteomalacia -Adynamic Bone Disease

Treatment of Complications Hypertension % of patients with CKD -Diuretics -Loop vs. Thiazides (less effective if GFR < 20)  Sexual Dysfuntion -Amenorrhea common -50% of men with ED

Treatment of Complications Anemia -Normocytic and Normochromic -Reduced production of Erythropoetin -Shortened RBC survival -Untreated, Hct stabilizes at 25 -TREAT trial -Address iron/ESA issues

Normal Hematocrit Trial Study halted due to increasing difference in event-free survival between the two groups Normal group need more IV iron Low group needed more transfusions Conclusion In patients with CHF or ischemic heart disease who are receiving hemodialysis, administration of EPO to raise the hematocrit to 42% is not recommended.

TREAT Trial Increase risk of CV and renal events in patients with CKD and DM II. Can increased hemoglobin levels effect clinical outcomes? Anemia with hemoglobin 15% Two groups Darbepoetin alfa Placebo Primary end points: death or CV event Secondary end points: time to death, quality of life, and rate of decline of GFR

Treatment of Complications Dyslipidemia -C ommon, especially hypertriglyceridemia -Limited data suggests lipid lowering may slow progression  Malnutrition -Strong correlation between PCM and death -Decreased intestinal absorption -Renal diet

Treatment of Complications Uremic bleeding -Prolonged bleeding time secondary to impaired platelet function -ddAVP, estrogen, dialysis  Pericarditis  Uremic Neuropathy  Thyroid Dysfunction

Predictors of Accelerated Progression Greater Proteinuria Higher BP Black race Lower HDL Lower Transferrin

Predictors of Accelerated Progression Metabolic Syndrome Analgesics Obesity Smoking DM

Targeted Therapies Phosphate retention -Contributes to progression of CKD -Calcium phosphate precipitation in the renal interstitium  Aldosterone -Excess mineralocorticoid receptor stimulation -Spironolactone- Aldosterone antagonist

Targeted Therapies Hyperuricemia -Decreased urinary excretion -Contributes to progression by stimulation of afferent vascular smooth muscle cell proliferation -Uric acid lowering may delay progression

Indications for Initiation of Dialysis Pericarditis Progressive Uremic Encephalopathy Bleeding diathesis Fluid overload refractory to diuretics Hypertension poorly responsive to meds Persistent metabolic disturbances Persistent nausea and vomiting

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