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

MANAGEMENTDecrease fluid 1000ml/dayDecrease protein (.5-1kg body weight)Decrease sodium (1-4gm variable)Decrease potassiumDecrease phosphorous (<1000mg/day)Dialysis (peritoneal, hemodialysis)RBC, Vitamin D (calcitrol replacement) etc

DIALYSISDr. 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

HEMO ADVANTAGES & DISADVANTAGES

Rapid fluid removalRapid removal of urea

& creatinineEffective K+ removalLess protein lossLower triglyceridesHome dialysis possibleTemporary access at

the bedside

Vascular access problems

Dietary & fluid restrictions

HeparinizationExtensive equipmentHypotensionAdded blood lostTrained specialist

Advantages Disadvantages

PD ADVANTAGES AND DISADVANTAGES

Immediate initiationLess complicatedPortable (CAPD)Fewer dietary

restrictionsShort training timeLess cardio stressChoice for diabetics

Bacterial/chemical periotonitis

Protein lossExit site of catheterSelf imageHyperglycemiaSurgical placement of

catheterMultiple abdominal

surgery

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