Chronic Kidney Disease (CKD)

Source: Derebail VK, Kshirsagar AV, Joy MS. Chronic Kidney Disease: Progression-Modifying Therapies. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th edition. http://www.accesspharmacy.com/content.aspx?aid=7981349 and Hudson JQ. Chronic Kidney Disease: Management of Complications. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th edition. http://www.accesspharmacy.com/content.aspx?aid=7981679. Accessed August 13, 2012.

• Chronic renal insufficiency
• Progressive kidney disease

• Progressive loss of function over several months to years, characterized by gradual replacement of normal kidney architecture with parenchymal fibrosis.
• Chronic kidney disease (CKD) categorized by level of kidney function:
  • Based on glomerular filtration rate (GFR)
  • Stages 1–5, each increasing number indicating more advanced stage of disease, as defined by declining GFR.
  • This classification system from the National Kidney Foundation’s Kidney Dialysis Outcomes and Quality Initiative (K/DOQI) also accounts for structural evidence of kidney damage.
  • CKD stage 5, previously referred to as end-stage renal disease (ESRD):
    • Occurs with GFR <15 mL/min/1.73m2 (<0.14 mL/s/m2) or in patients receiving renal replacement therapy (RRT).
    • For our purposes, ESRD refers specifically to patients receiving chronic dialysis.

• Susceptibility factors increase risk for kidney disease but do not directly cause kidney damage, including:
  • Advanced age
  • Reduced kidney mass and low birth weight
  • Racial or ethnic minority
  • Family history
  • Low income or education
  • Systemic inflammation
  • Dyslipidemia
• Initiation factors are conditions that directly result in kidney damage and can be modified by drug therapy, including:
  • Diabetes mellitus
  • Hypertension
  • Autoimmune diseases
  • Polycystic kidney disease
  • Systemic infections
  • Urinary tract infections
  • Urinary stones
  • Nephrotoxicity
• Progression factors hasten decline in kidney function after initiation of kidney damage, including:
  • Glycemia in diabetics
  • Hypertension
  • Proteinuria
  • Hyperlipidemia
  • Obesity
  • Smoking

• Most progressive nephropathies share final common pathway to irreversible renal parenchymal damage and ESRD (Figure 1).
• Key pathway elements:
  • Loss of nephron mass resulting from exposure to any of initiation risk factors
  • Glomerular capillary hypertension resulting from compensatory hypertrophy
  • Proteinuria as result of direct cellular damage

• Four most common causes of stage 5 CKD in United States:
  • Diabetes mellitus
  • Hypertension
  • Glomerulonephritis
  • Polycystic kidney disease

• Screening studies should be done in older individuals and those with family history of kidney disease.
  • Serum creatinine
  • GFR measurement
  • Urinalysis
  • Imaging studies of the kidney
• Screen for presence of cardiovascular risk factors.

• See Etiology.

• CKD development and progression are insidious; early stages often undetected.

Signs and Symptoms

• General symptoms associated with stages 1–4 (generally absent in stages 1 and 2; minimal in stages 3 and 4):
  • Edema
  • Cold intolerance
  • Shortness of breath
  • Palpitations
  ...