Chronic Kidney Disease

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Basics

Chronic kidney disease (CKD) is defined as structural or functional abnormalities of the kidney for ≥3 months, as determined by either pathologic abnormalities or markers of damage—including abnormalities in blood or urine tests, histology, imaging studies, or history of kidney transplant—or a GFR <60 mL/min/1.73 m2 for ≥3 months.

Description

  • In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) classified CKD in six categories by GFR estimation (in mL/min/1.73 m2):
    • G1: kidney damage with normal or increased GFR ≥90
    • G2: mild ↓ GFR 60 to 89
    • G3a: mild to moderate ↓ GFR 45 to 59
    • G3b: moderate to severe ↓ GFR 30 to 44
    • G4: severe ↓ GFR 15 to 29
    • G5: kidney failure: GFR <15 or dialysis
  • CKD per albumin-to-creatinine ratio (ACR) category:
    • A1: normal to mildly increased: <30 mg/g or <3 mg/mmol
    • A2: moderately increased: 30 to 300 mg/g or 3 to 30 mg/mmol
    • A3: severely increased: >300 mg/g or >30 mg/mmol
  • Risk of progression depends on comorbid conditions.
  • System(s) affected: renal/urinary, cardiovascular, skeletal, endocrine, metabolic, hematologic, lymphatic, immune, neurologic
  • Synonym(s): chronic renal failure; chronic renal insufficiency

Geriatric Considerations
GFR normally decreases with age, despite normal creatinine (Cr). Adjust renally cleared drugs for GFR in the elderly.

Pediatric Considerations
CKD definition is not applicable for children <2 years because of lower GFR even when corrected for body surface area. Calculated GFR based on serum Cr is used in this age group.

Pregnancy Considerations
Renal function in CKD may deteriorate during pregnancy. Cr >1.5 and hypertension (HTN) are major risk factors for worsening renal function.
  • Increased risk of premature labor, preeclampsia
  • ACE inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are contraindicated due to teratogenicity. Use diuretics with caution.

Epidemiology

  • African Americans are 3.6 times more likely to develop CKD than Caucasians.
  • Predominant sex: similar in both sexes; however, incidence rate of end-stage renal disease (ESRD) is 1.6 times higher in males than females.

Incidence
Estimated annual incidence of 1,700/1 million population

Prevalence
Overall prevalence of CKD is 14.2%. Unadjusted prevalence/incidence rates of ESRD (stage 5) are 1,752 and 362.4/1 million, respectively. Numbers do not reflect the burden of earlier stages of CKD (stages 1 to 4), which are estimated to affect 13.1% of the population nationwide or 26.3 million in the United States.

Etiology and Pathophysiology

Progressive destruction of kidney nephrons; GFR will drop gradually, and plasma Cr values will approximately double, with 50% reduction in GFR and 75% loss of functioning nephrons mass. Hyperkalemia usually develops when GFR falls to <20 to 25 mL/min. Anemia develops from decreased renal synthesis of erythropoietin.

  • Renal parenchymal/glomerular
    • Nephritic: hematuria, RBC casts, HTN, variable proteinuria
      • Focal proliferative: IgA nephropathy, systemic lupus erythematosus (SLE), Henoch-Schönlein purpura, Alport syndrome, proliferative glomerulonephritis, crescenteric glomerulonephritis
      • Diffuse proliferative: membranoproliferative glomerulonephritis, SLE, cryoglobulinemia, rapidly progressive glomerulonephritis (RPGN), Goodpasture syndrome
    • Nephrotic: proteinuria (>3.5 g/day), hypoalbuminemia, hyperlipidemia, and edema
      • Minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis
      • Amyloidosis, diabetic nephropathy
  • Vascular: HTN, thrombotic microangiopathies, vasculitis (Wegener), scleroderma
  • Interstitial tubular: infections, obstruction, toxins, allergic interstitial nephritis, multiple myeloma, connective tissue disease, cystic disease
  • Postrenal: obstruction (benign prostatic hyperplasia [BPH]), neoplasm, neurogenic bladder
Genetics
  • Alport syndrome, Fabry disease, sickle cell anemia, SLE, and autosomal dominant polycystic kidney disease can lead to CKD.
  • Polymorphisms in gene that encodes for podocyte nonmuscle myosin IIA are more common in African Americans than Caucasians and appear to increase risk for nondiabetic ESRD.

Risk Factors

  • Type 1 or 2 diabetes mellitus (DM); most common
  • Age >60 years
  • Cardiovascular disease (CVD) (e.g., HTN [common], renal artery stenosis, atheroemboli)
  • Previous kidney transplant
  • Urinary tract obstruction (e.g., BPH)
  • Autoimmune disease, vasculitis/connective tissue disorder
  • Family history of CKD
  • Nephrotoxic drugs (lithium, salicylate, high-dose or chronic NSAIDs, sulfonamide)
  • Congenital anomalies, obstructive uropathy, renal aplasia/hypoplasia/dysplasia, reflux nephropathy
  • Hyperlipidemia
  • Low income/education/ethnic minority status
  • Obesity/smoking/heroin use
  • Chronic infection (hepatitis B, hepatitis C, HIV)

General Prevention

  • Treat reversible causes: hypovolemia, infections, diuretics, drugs (NSAIDs, aminoglycosides, IV contrast).
  • Treat risk factors: DM, HTN, hyperlipidemia, smoking, and obesity; adjust medication doses to prevent renal toxicity.

Commonly Associated Conditions

HTN, DM, CVD

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