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  • Chronic kidney disease (CKD) is defined as abnormalities in kidney structure or function, present for 3 months or longer.

  • CKD is classified by glomerular filtration rate (GFR) and urinary albumin-to-creatinine ratio (uACR) based on the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for evaluation and management of CKD. The KDIGO classification system is referred to as CGA staging (cause, GFR, albuminuria).

  • A patient is classified with end-stage renal disease (ESRD) when their GFR is below 15 mL/min/1.73 m2 (0.14 mL/sec/m2) and either chronic dialysis or kidney transplantation is needed to sustain life. KDIGO classification will be used in this chapter; the term CKD 5D indicates a patient with ESRD requiring dialysis as either hemodialysis (CKD 5HD) or peritoneal dialysis (CKD 5PD).

  • Prognosis of CKD depends on cause of kidney disease, GFR at time of diagnosis, degree of albuminuria measured by uACR, and presence of other comorbid conditions. Please refer to Pharmacotherapy: A Pathophysiologic Approach, 11th ed., Chapter 61, Figure 61-1: KDIGO GFR and albuminuria categories and prognosis of CKD by category.


  • Clinical and sociodemographic risk factors for susceptibility to and initiation of CKD are useful for identifying individuals at risk of developing CKD. Clinical factors include, but aren’t limited to, diabetes, hypertension, obesity, autoimmune diseases, systemic infections, family history of CKD, reduction in kidney mass, and low birth weight. Sociodemographic factors include older age, US ethnic minority status, low income or education, and exposure to certain chemical and environmental conditions.

  • KDIGO recommends that prognosis be considered to help guide testing and treatment decisions. Validated estimating equations such as the kidney failure risk equation (KFRE) provide an accurate 2- and 5-year risk of progression to kidney failure for individuals with stage 3–5 CKD.

  • Progression risk factors are associated with further decline in kidney function. Persistence of the underlying initiation factors (eg, diabetes mellitus, hypertension, glomerulonephritis) appears to be the most important predictor of progressive CKD.

  • Most progressive nephropathies share a final common pathway to irreversible renal parenchymal damage and ESRD (Figure 75-1). Key elements of the pathway to ESRD include loss of nephron mass, glomerular capillary hypertension, and proteinuria.


Proposed mechanisms for progression of kidney disease.


  • Progression of CKD from category 1 to 5 occurs over decades in the majority of people who are asymptomatic until they reach CKD 4 or 5. Signs and symptoms seen with stages 4–5 include fatigue, weakness, shortness of breath, mental confusion, nausea, vomiting, bleeding, anorexia, itching, cold intolerance, peripheral neuropathies, edema, weight gain, changes in urine output, and “foaming” of urine.


General Approach

  • Goals of Treatment: The goal is to delay or prevent the progression ...

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