Chronic Kidney Disease (CKD) Lecture Notes PDF

Chronic Kidney Disease: Progression Modifying therapy References Kidney Disease: Improving Global Outcomes (KDIGO) http://www.kdigo.org/  Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chron...

Chronic Kidney Disease: Progression Modifying therapy References Kidney Disease: Improving Global Outcomes (KDIGO) http://www.kdigo.org/  Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney inter., Suppl. 2013; 3: 1-150.  Pharmacotherapy principles and practice Objectives  Define the stages of chronic kidney disease based on glomerular filtration rate (GFR) and pathologic findings.  Identify populations at risk and causes for developing CKD.  Describe the pathologic mechanisms that contribute to the progression of kidney disease.  Determine appropriate nonpharmacologic and pharmacotherapeutic regimens for patients with CKD to address comorbid conditions and secondary complications.  Discuss the effects of pharmacologic and nonpharmacologic interventions on the rate of progression. Kidney Structure & Function Kidney Functions  pharmacist membership FREE Urine 6 Kidney Functions Excretory Function Maintains body Homeostasis Regulation of electrolyte Blood volume. Blood pressure Endocrine Function Hormone secretion ◦ Erythropoietin (EPO). ◦ Activation of vitamin D. RAAS SYSTEM CKD Definition & Classification Definition of Chronic Kidney Disease  Kidney damage for ≥ 3 months, as defined by structural or functional abnormalities of the kidney, using histology, imaging or laboratory assessments, with or without decreased GFR OR  GFR < 60 mL/min/1.73 m2 for ≥ 3 months, with or without kidney damage Stages of Chronic Kidney Disease  Classification of CKD Patients are classified as: G1-G5-----based on eGFR A1-A3 -------based on ACR (albumin:creatinine Classification of CKD Pathophysiology of Progressive Kidney Disease  With reduced nephron mass (resulting from DM, HTN, glomerulonephritis, etc.) vasodilatation of the afferent arteriole (mediated primarily by prostaglandins PGI2 & PGE2) and constriction of the efferent arteriole (mediated primarily by Angiotensin II) occur to compensate. This leads to an increase in blood flow, single nephron intra-glomerular capillary filtration pressure, and hyper-filtration (increased single nephron GFR). Sustained increases in plasma flow and hydrostatic pressure lead to hyper-filtration injury and glomerular sclerosis → continued loss of nephron function Pathophysiology: Auto- regulation…….  Diagnostic Criteria: Progressive Kidney Disease Classification of CKD Diagnostic Criteria: Progressive Kidney Disease  Progressive increase in serum creatinine: consider factors that may alter serum creatinine such as decreased muscle mass & nutritional status  Decreased GFR  In stage 1 and stage 2 CKD, reduced GFR alone not enough for diagnosis, as the it may be normal or borderline normal.  In such cases, the presence of one or more of the following markers of kidney damage can establish the diagnosis:  Albuminuria (albumin excretion >30 mg/24 hr or albumin:creatinine ratio >30 mg/g [>3 mg/mmol])  Urine sediment abnormalities  Electrolyte and other abnormalities due to tubular disorders  Structural abnormalities detected by imaging NKF advised that GFR and albuminuria levels should be used together, to evaluate risks for AKI, ESRD, and progressive CKD. CLINICAL PRESENTATION OF CHRONIC KIDNEY CKD is often DISEASE ASYMPTOMATI C until CKD4 OR CKD5  Because the early stages of CKD are often undetected, the diagnosis requires a high level of suspicion in patients with chronic conditions such as HTN or DM Clinical Presentation (signs & (Particularly with more severe kidney disease, symptoms) stages 4-5) Fatigue Edema Weakness Weight gain Shortness of Changes in urine output (volume and breath consistency), Mental “foaming” of urine confusion (indicative of Nausea and proteinuria), vomiting Bleeding Loss of appetite Itching Clinical Presentation (Particularly with more severe kidney disease, (Laboratory stages 4-5) test) ↓eGFR ↑ Serum ↓ bicarbonate creatinine (metabolic acidosis) ↑ BUN ↑ potassium, ↓Hb/hematocrit (Hct) (TSat)phosphorus ↓Transferrin saturation (anemia) and/or ↑ ↑ ACR ferritin (IDA; increased due to PTH note: ferritin may be inflammatory ↑BP conditions) ↑ ↓Vitamin D levels, glucose albumin ↑ LDL & ↓Glucose (decreased insulin degradation ↑Calcium (in (malnutrition) early TG kidney function or stages of CKD). with impaired poor oral intake) ↓Calcium (more likely in CKD 5).  Chronic Kidney Disease: Progression Modifying therapy  Goals of CKD Management  Prevent or slow the progression of kidney disease  Evaluate and manage comorbid conditions  Review medication regimen regularly to make appropriate adjustments based on degree of kidney dysfunction  Prevent and treat cardiovascular disease  Prevent and treat secondary complications of decreased kidney function  Prepare for kidney failure and kidney replacement therapy as needed Replace kidney function with dialysis OR transplantation, if signs and symptoms of TREATMENT of CKD General Approach to Patient Care for Chronic Kidney Disease Recommendations for Individuals with Chronic Kidney Disease/ Non- pharmacologic  Exercise 30 minutes five times / week to achieve a BMI 2mg/dl: Avoid Avoid A- Glucosidas e inhibitors Miglitol SCr > 2 mg/dl: Avoid Avoid Drug Therapy for Patient with Moderately to Severe CKD CKD CLASS DRUG Stage 3-5 DIALYSIS COMPLICATION Contraindicated: Biguanide Metformin Male: SCr > 1.5mg/dl Avoid Lactic Acidosis Female: SCr > 1.4mg/dl No dose Piolitazone No dose adjustment adjustment Volume retention TZDs No dose Rosiglitazone No dose adjustment adjustment Volume retention Repaglinide No dose adjustment Avoid Meglitinides Nateglinide Initial Low dose: 60mg Avoid Hypoglycemia No dose Incretin mimetic Exenatide No dose adjustment adjustment No dose adjustment Amylin Analog Pramlintide GFR < 20ml/min/1.73m2: Unknown Unknown Dipeptidyl- GFR 30-50 ml/min 1.73 m2 ↓25% peptidase IV Sitagliptin GFR < 30ml/min/1.73 m2 ↓50% ↓ 50% Hypoglycemia inhibitor  Hyperlipidemia Hypertension Dietary restriction of Lifestyle modification cholesterol per JNC VIII Weight reduction Exercise Reduced blood pressure ≤ 130/80 Pharmacologic lipid-lowering agents Diabetes Dietary protein restriction 0.6g/kg/day Poor metabolic control Proteinuria Intensify glycemic Screen for UAE once a year control (Goal: normal fasting blood glucose 70- 120 mg/dL) Microalbuminuria x 2 Albuminuria x 1 (30-300 mg/day) (>300 mg/day) Multiple daily OR Continuous SC insulin insulin injections infusion by pump Initiate ACEI (or ARB) therapy Titrate therapy to achieve maximal effect on UAE Minimize hypoglycemia Monitor blood glucose Monitor serum K+, Cr, and UAE up to 4 times per day DiPiro Hand Book Chapter 76 Correction of Hyperlipidemia ↑ cholesterol (particularly LDL) associated with rate of decline in kidney function ↑ triglycerides prevalent in patients with chronic kidney disease Correction of Hyperlipidemia No evidence that treating dyslipidemia prevents the progression of CKD or diabetic nephropathy, but evidence does support treatment to prevent cardiovascular events. A Panel III guidelines and recommend LDL and cholesterol levels 15 1-3 months 1-3 months 1-3 months Monitor CBC, Na, K, Cl, bicarbonate, urea, creatinine, and eGFR. If DKD, add HbA1C. Fasting lipid profile at least yearly. At CKD category 3b or later: also add albumin, calcium, phosphorus, PTH, serum iron, TIBC, and ferritin. Case