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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. 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.

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  • Chronic renal insufficiency
  • Progressive kidney disease

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  • 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.

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  • 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:

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  • 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

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Figure 1.
Graphic Jump Location

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.

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

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  • 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.

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

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Signs and Symptoms

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  • 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 and muscle ...

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