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Chronic kidney disease. Dr. Gerrard Uy. Chronic kidney disease. Encompasses a spectrum of different pathophysiologic process associated with abnormal kidney function and progressive decline in glomerular filtration rate. Chronic renal failure.
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Chronic kidney disease Dr. Gerrard Uy
Chronic kidney disease • Encompasses a spectrum of different pathophysiologic process associated with abnormal kidney function and progressive decline in glomerular filtration rate
Chronic renal failure • Process of continuing significant irreversible reduction in nephron number • Corresponds to CKD stages 3-5 • Regardless of the cause: Decreased: GFR, tubular function & tubular reabsorption capabilities. Dysfunction fluids & electrolytes, acid base disturbances, & systemic problems develops
End Stage Renal Risease (ESRD) • Represents a stage of CKD where the accumulation of toxins, fluid, and electrolytes normally excreted by the kidneys result in uremic syndrome • Corresponds to CKD stage 5
Pathophysiology of CKD • 2 mechanisms: • Initiating mechanisms specific to the underlying etiology (immune complex, toxins, etc) • Progressive mechanisms involving hyperfiltration and hypertrophy of the remaining viable nephrons
Risk Factors • hypertension, • diabetes mellitus, • autoimmune disease, • older age, • African ancestry, • a family history of renal disease, a previous episode of acute renal failure • presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract
Stages Of CKD • Normal annual decline in GFR with age from peak GFR (120 ml/min) attained during the 3rd decade of life is ~ 1ml/min per year • Mean GFR is lower in women than in men • Measurement in albuminuria is helpful in monitoring nephron injury • > 17 mg of albumin per gram of creatinine in males and > 25 mg of albumin per gram of creatinine in females signifies chronic renal damage
Stages Of CKD • Stage 1 and stage 2 CKD are usually asymptomatic • Stages 3 and 4 will show prominent clinical and laboratory complications of CKD • Stage 5, toxins accumulate and patients experience a marked disturbance in their activities
Etiology • Diabetic nephropathy – the most frequent cause of CKD • Hypertensive nephropathy – common cause of CKD in the elderly
Clinical and Laboratory Manifestations of CKD and Uremia • Fluid, Electrolyte and Acid Base Disorders • Cardiovascular abnormalities • Hematologic abnormalities • Abnormal Hemostasis • Neuromuscular abnormalites • Gastrointestinal and Nutritional abnormalities • Endocrine abnormalities • Dermatologic abnormalities
Fluid, Electrolyte, and Acid Base Disorders • Sodium and Water Homeostasis • Total body content of sodium and water is modestly increased • Potassium Homeostasis • Potassium secretion diminishes as the GFR declines • Metabolic Acidosis • Disorders of Ca and Phosphate metabolism • Declining GFR leads to reduced excretion of phosphate • Decreased levels of ionized calcium 2 to decreased calcitriol production
Cardiovascular Abnormalities • Leading cause of morbidity and mortality in patients at every stage of CKD • Presence of any stage of CKD is a major risk factor for ischemic cardiovascular disease • Inflammatory state associated with CKD accelerates vascular occlusive disease • LVH and microvascular disease augment myocardial ischemia • Diminished availability of nitric oxide • Hemodialysis with episodes of hypotension and hypovolemia may further aggravate coronary ischemia
Cardiovascular Abnormalities • Increased permeability of alveolar capillary membranes as a manifestation of the uremic state • Hypertension – most common complication of CKD • LVH and dilated cardiomyopathy are among the strongest risk factors for cardiovascular morbidity and mortality
Hematologic Abnormalities • Normocytic, normochromic anemia is observed as early as stage 3 CKD • Universal by stage 4 • Primary cause is insufficient production of EPO • Other causes: iron deficiency and chronic inflammation
Abnormal Hemostasis • Prolonged bleeding time • Decreased activity of platelet factor III • Abnormal platelet aggregation • Impaired prothrombin consumption • Clinical manifestations: • Increased tendency of bleeding • Prolonged bleeding from surgical procedures • Menorrhagia • Spontaneous GI bleeding • Greater susceptibility to thromboembolism
Neuromuscular Abnormalities • CNS, peripheral, and autonomic neuropathy • Due to retained nitrogenous metabolites and middle molecules including PTH • Clinical manifestations of uremic neuromuscular disease usually become evident at stage 3 CKD • Symptoms: • Disturbances in memory and concentration • Sleep disturbance • Hiccups, cramps and fasciculations
Neuromuscular Abnormalities • Peripheral neuropahty becomes evident at stage 4 CKD • Sensory nerves are involved more than motor • Lower extremity > upper extremity • “restless leg syndrome” • Evidence of peripheral neuropathy without another cause (e.g DM) is a firm indication for starting renal replacement therapy
Gastrointestinal Abnormalities • Uremic fetor – urine like odor on the breath • Gastritis and peptic ulcer disease • Prone to constipation • Retention of uremic toxins also lead to anorexia, nausea, and vomiting • Protein – energy malnutrition common in advanced CKD and is an indication for starting renal replacement therapy • Assessment of PEM should begin in stage 3 CKD
Endocrine Metabolic Disturbances • Impaired glucose metabolism • Increased postprandial glucose, normal fasting glucose • In women with CKD, estrogen levels are low • Presence of menstrual abnormalities and infertility • GFR < 40 ml/min, associated with spontaneous abortions • In men, testosterone levels are low leading to sexual dysfunction and oligospermia
Dermatologic Abnormalities • Pruritus is common • Hyperpigmentation – due to deposition of retained pigment molecules, urochromes • First line of management is to rule out scabies and control phosphate concentrations
Approach to Patient • Identify if it is ACUTE RENAL FAILURE or CHRONIC. • Identify co-morbidities such as hypertension, diabetes mellitus, cardiovascular disease, etc • Evaluate uremic syndrome • Findings that suggest chronic kidney disease include anemia, evidence of renal osteodystrophy (radiologic or laboratory), and small scarred kidneys
Approach to Patient • Most useful imaging study is renal ultrasound – presence of bilaterally small kidney (<8.5 cm) supports diagnosis of CKD • Hypophosphatemia, hypocalcemia, and elevated PTH and ALP suggests chronicity • Normochromic, normocytic anemia
Management • Slowing the progression of CKD • ECFV depletion, uncontrolled hypertension, urinary tract infection, obstructive uropathy, exposure to nephrotoxic agents • Protein restriction – slow the rate of renal decline at earlier stages of renal disease • Daily protein intake of 0.6 – 0.75 gm/kg/day • At least 50% = high biologic value protein • Sufficient energy intake, 35 kcal/kg • Reducing intraglomerular hypertension and proteinuria • Control of systemic and glomerular hypertension
Management • Slowing the progression of diabetic renal disease • Prognosis of diabetic patients on dialysis is poor with survival comparable to many forms of cancer • Recommended preprandial glucose <90-130 mg/dl • Hba1c <7% • Testing for microalbumin is recommended in all diabetic patients at least annually
Management Decrease fluid 1000ml/day Decrease protein (.5-1kg body weight) Decrease sodium (1-4gm variable) Decrease potassium Decrease phosphorous (<1000mg/day) Dialysis (peritoneal, hemodialysis) RBC, Vitamin D (calcitrol replacement) etc
Dialysis Dr. Gerrard Uy
Dialysis • Leading cause of ESRD: • Diabetes mellitus • hypertension • Other causes of ESRD: • Glomerulonephritis • Polycystic kidney disease • Obstructive uropathy • 2 types of dialysis • Hemodialysis • Peritoneal Dialysis
Criteria for Initiating Dialysis • Presence of uremic symptoms • Hyperkalemia unresponsive to conservative measures • Persistent extracellular volume expansion despite diuretic therapy • Acidosis unresponsive to medical therapy • Bleeding diasthesis • Creatinine clearance or estimated GFR <10ml/min
General Principle • Movement of fluid and molecules across a semi permeable membrane from one compartment to another Hemodialysis – Move substances from blood through a semi permeable membrane and into a dialysis solution (dialysate –bath) (synethetic membrane) Peritoneal – Peritoneal membrane is the semi permeable membrane
Goals of Dialysis • To remove both low and high molecular weight solutes • Majority of patients with ESRD require 9-12 hrs of dialysis each week, usually divided into 3 equal sessions
Complications during Hemodialysis • Hypotension – most common acute complication • Muscle cramps • Anaphylactoid reactions • Type A reactions – IgE mediated hypersensitivity reaction • Type B reaction – nonspecific chest and back pain
Complications of Peritoneal Dialysis • Peritonitis • Elevated peritoneal fluid leukocyte • Typical presentation: pain and cloudy dialysate • Most common etiology: gram positive cocci • Catheter associated nonperitonitis infections • Weight gain • Residual uremia • hyperglycemia
Disequalibrium Syndrome Fluid removal and decrease in BUN during hemodilaysis which cause changes in blood osmolarity.These changes trigger a fluid shift from the vascular compartment into the cells. In the brain, this can cause cerebral edema, resulting in increase intracranial pressure and visible signs of decreasing level of consciousness. Symptoms: Sudden onset of headache, nausea and vomiting, nervousness, muscle twitching, palpitation, disorientation and seizures Treatment: Hypertonic saline, Normal saline
Rapid fluid removal Rapid removal of urea & creatinine Effective K+ removal Less protein loss Lower triglycerides Home dialysis possible Temporary access at the bedside Vascular access problems Dietary & fluid restrictions Heparinization Extensive equipment Hypotension Added blood lost Trained specialist Hemo Advantages & Disadvantages Advantages Disadvantages
Immediate initiation Less complicated Portable (CAPD) Fewer dietary restrictions Short training time Less cardio stress Choice for diabetics Bacterial/chemical periotonitis Protein loss Exit site of catheter Self image Hyperglycemia Surgical placement of catheter Multiple abdominal surgery PD Advantages and Disadvantages Advantages Disadvantages
Transplantation • Treatment of choice for advanced chronic renal failure • Mortality rates after transplantation are highest in the first year and are age related • 2% for 18-34 yrs • 3% for 35-49 yrs • 6.8% for > 50 yrs
Common problems in Transplantation • Infections • Tissue Rejection • Malignancy (skin and lip carcinoma, lymphomas, cervical carcinoma) • Hypercalcemia • Hypertension • Chronic hepatitis • anemia