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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. 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. 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:

  • 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

Figure 1.

Proposed mechanisms for progression of renal disease. Reprinted with permission from Wells BG, DiPiro JT, Schwinghammer TL, et al. Pharmacotherapy Handbook. 8th ed. New York: McGraw-Hill, 2012.

  • 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.

  • 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
    • Cramping ...

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