LOGICAL DRUG THERAPY IN CHRONIC KIDNEY DISEASE Dr S.Raeisi Nephrologist, MD

GENERAL MANAGEMENT OF CHRONIC KIDNEY DISEASE Treatment of reversible causes of renal dysfunction Preventing or slowing the progression of renal disease Treatment of the complications of renal dysfunction Identification and adequate preparation of the patient in whom renal replacement therapy will be required

preventing Minimizing further renal injury Can be treated SECONDARY FACTORS

GENERAL MANAGEMENT OF CHRONIC KIDNEY DISEASE Strict glycemic control in diabetics with CKD Strict control lf hypertension Correction of anemia Control of serum phosphorus, vitamin D, and parathyroid hormone Lipid-lowering therapy Hyperkalemia, Metabolic acidosis, Uremic bleeding Volume overload Beta-blockers and aspirin: Cardioprotective effects Supplements

K/DOQI classification for the 5 stages of CKD

DRUG DOSE ADJUSTMENTS IN CRF Estimate GFR MDRD formula: GFR (mL/min/1.73 m2)= × (PCr)−1.154 × (age)−0.203 × (if female) × 1.21 (if black), where PCr = plasma creatinine concentration in mg/dL (to convert from μmol/L to mg/dL, divide by 88.4).

case A 68 yr old man with DM and Scr=2 mg/dl and BW=60 kg came for check up what is her eGFR? = (140-68) × 60 / 72 × 2 = 72 × 60 / 72 × 2 = 60 / 2 = 30 ml/min

Lipid-lowering therapy Elevated levels of low-density lipoprotein cholesterol (LDL-C) and other lipid marker molecules are a traditional risk factor for cardiovascular disease Also, data in animals suggest that high lipid levels and cholesterol loading may augment glomerular injury. Thus, treatment of CKD patients with statins to reduce lipids may both prevent progression and lower cardiovascular risk. LDL-C goal of <100 mg/dL is recommended. Drug therapy is recommended when LDL-C levels are >130 mg/dL and is optional when LDL-C levels are between 100 and 130 mg/dL

Dose adjustment for renal insufficiency Statins as a class have been associated with rhabdomyolysis, and dose reduction in severe renal impairment is recommended for some statins (e.g., rosuvastatin) or when statins are used in combination with fibrates

Volume overload Thiazide diuretics are the diuretic of choice for mild CKD, when SCr is <1.8 mg/dL. When SCr is >1.8 mg/dL, a loop diuretic (twice-a-day dosing regimen) is recommended, due to presumed reduced efficacy of thiazides.

Hyperkalemia In selected patients, low dose Kayexalate (5 grams with each meal) can be used to lower the serum potassium concentration without the side effects associated with larger doses g QID for sever hyperkalemia.

Acidosis Given that chronic metabolic acidosis results in increased resorption of bone, the use of sodium bicarbonate is recommended to maintain the serum bicarbonate level at 22 mmol/L. The usual amount of sodium bicarbonate to give is mmol/L/kg per day

Uremic bleeding An increased tendency to bleeding is present in both acute and chronic kidney disease. The administration of: 1.Desmopressin (dDAVP), 2.Cryoprecipitate, 3.Estrogen,

Beta-blockers and aspirin: Cardioprotective effects The cardioprotective effects of beta-blockers are not diminished in CKD patients. Aspirin and beta-blocker cardioprotection after myocardial infarction is similar in CKD patients and in patients with normal renal function. Because most CKD patients, especially in stage 3 and higher, tend to have cardiac disease, a case can be made for routinely treating such patients with both aspirin and beta-blockers, although this is not widely practiced at all centers. Aspirin has been associated with GI bleeding in end-stage renal disease (ESRD) patients. Whether an increased risk is present in stage 1 to 4 CKD patients is not well known.

When to initiate dialysis The uremic syndrome consists of symptoms and signs that result from toxic effects of elevated levels of nitrogenous and other wastes in the blood. Symptoms. Uremic patients commonly become nauseated and often vomit soon after awakening. They may lose their appetite such that the mere thought of eating makes them feel ill. They often feel fatigued, weak, and/or cold. Their mental status is altered; at first, only subtle changes in personality may appear, but eventually, the patients become confused and, ultimately, comatose.

When to initiate dialysis Signs. The classic uremic physical findings of a sallow coloration of the skin due to accumulation of urochrome pigment (the pigment that gives urine its yellow color) and of an ammonia- like or urine-like odor to the breath are rarely seen unless the degree of uremia is severe. A pericardial friction rub or evidence of pericardial effusion with or without tamponade reflects uremic pericarditis, a condition that urgently requires dialysis treatment. Foot- or wrist-drop may be evidence of uremic motor neuropathy, a condition that also responds to dialysis. Tremor, asterixis, multifocal myoclonus, or seizures are signs of uremic encephalopathy. Prolongation of the bleeding time occurs and can be a problem in the patient requiring surgery.

Indications for dialysis in the chronic setting Usually dialysis is initiated in adult patients when the eGFR decreases to about 10 mL per minute per 1.73 m2. However, evaluation of the need for dialysis should begin at a higher eGFR level, probably somewhere around mL per minute per 1.73 m2.

Complications that may prompt initiation of kidney replacement therapy Intractable extracellular volume overload and/or hypertension Hyperkalemia refractory to dietary restriction and pharmacologic treatment Metabolic acidosis refractory to bicarbonate treatment Hyperphosphatemia refractory to dietary counseling and to treatment with phosphorus binders Anemia refractory to erythropoietin and iron treatment Otherwise unexplained decline in functioning or well-being Recent weight loss or deterioration of nutritional status, especially if accompanied by nausea, vomiting, or other evidence of gastroduodenitis

Urgent Indications Neurologic dysfunction (e.g., neuropathy, encephalopathy, psychiatric disturbance) Pulmonary edema Sever hyperkalemia or sever acidosis resistant to therapy Pleuritis or pericarditis without other explanation Bleeding diathesis manifested by prolonged bleeding time

Questions A 68 yr old woman with DM and HTN came to your office with a lab paper, her cr=2.0 mg/dl Hb=12, K=5, Na=137, LDL=139 she is 50 kg and her drugs are: metformin 1000 mg/d, furosemide 40mg/d, losartan 50 mg/d, cefixime 400mg/d? 1. How much is her eGFR? 2. Which drug must be discontinued? 3. Which drug must be dose adjusted? 4. Is there any drug that must be added to her list?

Questions