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Source: Hudson JQ, Wazny LD. Chronic kidney disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. Accessed January 2, 2017.




  • 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).

    • Categories 1–5, each increasing number indicating more advanced stage of disease, as defined by declining GFR.

    • This classification system from the Kidney Disease: Improving Global Outcomes (KDIGO) 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/1.73 m2 (<0.14 mL/s/m2) and either chronic dialysis or kidney transplantation is needed to sustain life.

      • CKD 5D indicates a patient with ESRD who requires dialysis (hemodialysis or peritoneal dialysis).




  • Susceptibility factors increase risk for kidney disease but do not directly cause kidney damage, including.

    • Advanced age.

    • US ethnic minority: African American, American Indian, Hispanic, Asian, or Pacific Islander.

    • Exposure to certain chemical and environmental conditions.

    • Low income/education.

  • Initiation factors are conditions that directly result in kidney damage and can be modified by drug therapy, including.

    • Diabetes mellitus.

    • Hypertension.

    • Obesity.

    • Autoimmune diseases.

    • Systemic infections.

    • Urinary tract infections.

    • Urinary stones.

    • Lower urinary tract obstruction.

    • Neoplasia.

    • Family history of CKD

    • Recovery from acute kidney injury.

    • Reduction in kidney mass.

    • Exposure to certain drugs.

    • Low birth weight.

  • Progression factors hasten decline in kidney function after initiation of kidney damage, including.

    • Glycemia in diabetics.

    • Hypertension.

    • Proteinuria.

    • Obesity.

    • Smoking.




  • Most progressive nephropathies share final common pathway to irreversible renal parenchymal damage and ESRD (Fig. 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 a result of direct cellular damage.


Proposed mechanisms for progression of renal disease. Reprinted with permission from Wells BG, DiPiro JT, Schwinghammer TL, et al. Pharmacotherapy Handbook. 10th ed. New York, NY: McGraw-Hill; 2017.

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  • Four most common causes of stage 5 CKD in the United States:

    • Diabetes mellitus.

    • Hypertension.

    • Glomerulonephritis.

    • Polycystic kidney disease.




  • See Etiology.




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


  • Symptoms associated with stages 4 or 5

    • Fatigue.

    • Weakness.

    • Shortness of breath.

    • Mental confusion.

    • Nausea/vomiting.

    • Bleeding.

    • Loss of appetite.

    • Itching.

    • Cold intolerance.

    • Peripheral neuropathies.


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