Chronic Kidney Disease

Question 1

Chronic kidney disease (CKD) definition

Answer 1

• permanent reduction in GFR
• divided into 5 stages
• ==> end stage renal disease (ESRD) = CKD progressed to point where renal replacement therapy (dialysis, transplant) needed

Question 2

Stages of CKD (Description, GFR, Action)

Answer 2

• Stage 1 = kidney damage, normal GFR
  
  • GFR > 90
  • Dx & Tx
• Stage 2 = kidney damage, mild GFR decrease
  
  • GFR = 60-89
  • Estimate progression
• Stage 3 = moderate GFR decrease
  
  • GFR = 30-59
  • Tx complication
• Stage 4 = severe GFR decrease
  
  • GFR = 15-29
  • Prepare for renal replacement
• Stage 5 = kidney failure
  
  • GFR < 15 or dialysis
  • Dialysis or transplant

Question 3

Most common causes of CKD

Answer 3

• Diabetic nephropathy**
• Hypertensive nephrosclerosis & Renal vascular disease
• Glomerulonephritis
• Polcystic kidney disease
• Interstitial nephritis
• Obstruction

Question 4

Renal adaptation that maintain solutes despite renal insufficiency

Answer 4

• Intact nephron hypothesis: fxning nephrons compensate/balance filtration & net excretion
• Magnification phenomenon: altered solute handling to maintain balance
• Individual solute control systems
• Trade-off hypothesis: mechanisms that maintain individual solutes => negative effects on other systems => contribute to uremia

Question 5

Creatine and Urea balance in CKD

Answer 5

• rate of filtration is maintained @ expense of elevated plasma concentration
• excretion rates are constant despite diminished clearance

Question 6

Water balance in CKD

Answer 6

• faction of water reabsorbed must decrease
• progressive CKD => compromised ability to excrete water => hypoosmolality (hyponatremia)
• fixed urine concentrating => dehydration = water deficiency (hypernatremia)

Question 7

Sodium balance in CKD

Answer 7

• fraction of sodium reabsorbed must be decreased/excreted must increase
• increased natriuretic peptide => increased excretion
• unable to respond to sudden changes in sodium intake or extrarenal loss

Question 8

Potassium balance in CKD

Answer 8

• increased tubular secretion of potassium helps maintain balance until severe CKD
• then fecal excretion of potassium increases

Question 9

Hydrogen ion balance in CKD

Answer 9

• fxning nephrons produce mroe NH₄⁺ to compensate/maintain acid balance
• @ GFR < 20-25ml/min => retention of hydrogen ions + bicarb => non-anion gap metabolic acidosis

Question 10

Uremia definition

Answer 10

• “urine in blood”
• clinical syndrome from retention of substances normally ecreted into urine
• substances accumulate ==> toxicity

Question 11

Main components in pathogenesis of uremia

Answer 11

• retained metabolic products
  
  • e.g. urea, nitrogenous waste
• overproduction of counter-regulatory hormones
  
  • overproduction of PTH in response to hypocalcemia
  • overproduction of natriuretic hormone in response to volume overload
• underproduction of renal hormones
  
  • decreased EPO => anemia
  • decreased 1-hydroxylation of vitamin D => bone disease & 2^o hyperparathyroidism

Question 12

Clinical features/organ systems affected by uremia

Answer 12

• Neurological Disorders:
• Hematological Disorders
• Cardiovascular Disorders
• Pulmonary Disorders:
• Gastrointestinal Disorders
• Metabolic-Endocrine Disorders:
• Bone, Calcium, Phosphorus Disorders:
• Skin Disorders:
• Psychological Disorders:
• Fluid and Electrolyte Disorders:

Question 13

Characteristics of Anemia in CKD

Answer 13

• occurs @ GFR < 25 ml/min; may occur @ mild CKD
• EPO production/response is depressed
• Red cell survival decreased
• blood loss due to decreased platelet fxn
• marrow space fibrosis <==osteitis fibrosa of 2^o hyperPTHism

Question 14

Characteristics of HTN in CKD

Answer 14

• occurs @ 80-90% of CKD pts
• expansion of ECG <== reduced sodium excretion ability
• increased RAS
• dysfxn of ANS: insensitive barorecptors ==> increased sympathetic tone
• diminished vasodilaors

Question 15

Characteristics of Mineral Bone Disease in CKD

Answer 15

1. trade-off:
   
   1. phosphorous retained => low Ca²⁺ => PTH release
   2. prolonged elevated PTH => no further response @ renal tubules => hyperphosphatemia + hypocalcemia
   3. high PTH => bone disease + osteitis fibrosa
2. PTH regulation
   
   1. Ca²⁺ receptor: binding to receptor => downregulation of PTH
   2. 1,25 vitamin D: downregulates PTH
   3. FGF-23 downregulates 1,25 vitamin D => decreased calcium/phosphorous absorption @ gut + increased PTH activity

Question 16

Pathophysiology of progression of CKD

Answer 16

• compensatory events + loss of nephrons ==> accelerate rate of destruction
• @ slowly progressive phase: loss of kidney fxn occurs at constant rate
• glomerular HTN = compensatory mechanism to attempt to maintain GFR ==> glomerular destruction over time

Question 17

Tx of CKD

Answer 17

• aggressive tx of HTN w/ACE-I & ARBs
• maintain serum phosphorous w/in normal using dietary counseling and phosphate binders
• @ uremic syndrome: hemodialysis, peritoneal dialysis, renal transplantation