Chronic Kidney Disease

Stages (1)

Stage I: GFR ≥ 90 mL/min

Stage II: GFR 60-89 mL/min

Stage IIIa: GFR 45-59 mL/min

Stage IIIb: GFR 30-44 mL/min

Stage IV: GFR 15-29 mL/min

Stage V: GFR <15 mL/min

Common Causes

  • Diabetes mellitus
  • Hypertension

Rarer Causes

  • Inherited Disorders
    • Polycystic Kidney Disease
    • Tubulointerstitial Disease
  • Decreased Renal Mass
    • Renal Agenesis
    • Nephrectomy
  • Severe or Recurrent Acute Disease States
    • Severe/prolonged AKI
    • Recurrent/Complicated UTI
  • Nephrotic Syndrome
  • Nephritic Syndrome
  • Chronic Disease States
    • Heart Failure
    • Cirrhosis
    • Renovascular Disease
  • Cancer
    • Multiple Myeloma
    • Renal Cell Carcinoma
  • Medications/Toxins
    • Chemotherapy (cisplatin (2), ifosfamide (3) are big culprits)
    • NSAIDs
    • Lithium
    • Lead exposure

Management

  • Blood pressure and diabetes control
  • Treat underlying condition and remove offending agents
  • Slow the progression of proteinuria
    • ACE-Inhibitors
    • Angiotensin-Receptor Blockers
    • SGLT-2 Inhibitors (generally only in patients with concomitant diabetes, but more recently have been shown to be efficacious in patients without diabetes as well (4))
  • Treat complications as below

Complications

  • Acidemia
    • From retained anions and inability to excrete acid as renal function deteriorates
    • KDIGO recommends bicarbonate therapy if serum bicarbonate is chronically <22, which has been shown to slow the progression of renal disease
  • Anemia
    • From decreased amount of EPO production (see Anemia)
    • First, replete iron stores if deficient, then can supplement with EPO if anemia persists
  • Volume overload and hypertension
    • Patients with CKD and hypertension generally require a diuretic for blood pressure and volume control
  • Hyponatremia, hyperkalemia
    • Loop diuretics may serve as treatment
  • Hypocalcemia
    • As a result of decreased hydroxylation of 25-OH-Vitamin D into its active form (1,25-OH-Vitamin D) by renally-located enzyme 1-α-hydroxylase
    • Treatment: supplementation with cholecalciferol (Vitamin D3), as well as calcium supplementation to prevent secondary hyperparathyroidism as below. Though this vitamin still needs to be activated by 1-α-hydroxylase, it has been shown to have benefit in patients with CKD, who tend to have low 25-OH-Vitamin D levels (5)
  • Secondary Hyperparathyroidism (6)
    • Triggers
      • Hypocalcemia
      • Low Vitamin D levels
      • Hyperphosphatemia (from reduced GFR in CKD leading to increased phosphate reabsorption)
    • Pathophysiology
      • The above triggers cause an appropriately-increased PTH secretion, which in turn leads to increased bone turnover
    • Treatment (7)
      • Low phosphate diet
      • Phosphate binders (sevelamer)
      • Vitamin D
      • Calcimimetic agents (cinacalcet)
        • Activate CaSR -> decrease PTH production
  • Tertiary Hyperparathyroidism (8)
    • Progression of secondary hyperparathyroidism to the point of autonomous proliferation of the parathyroid gland so that excessive PTH secretion occurs regardless of calcium or vitamin D levels
    • Will typically see elevated calcium levels, decreased phosphate levels
    • Treatment: Parathyroidectomy
  • Dyslipidemia
    • Elevated triglycerides and low HDL
    • Pathophysiology involves complex biochemical pathways including decreased catabolism of triglyceride-rich lipoproteins, decreased apolipoprotein availability for HDL synthesis, and impairment of lecithin-cholesterol acyltransferase (the enzyme responsible for converting cholesterol into a cholesteryl ester that can be packaged into HDL) (9)
  • Uremia
    • Platelet dysfunction
    • Pericarditis
    • Encephalopathy

References:

  1. Estimated glomerular filtration rate (egfr). (2020, September 14). Retrieved March 10, 2021, from https://www.kidney.org/atoz/content/gfr
  2. Shi M;McMillan KL;Wu J;Gillings N;Flores B;Moe OW;Hu MC;. (n.d.). Cisplatin nephrotoxicity as a model of chronic kidney disease. Retrieved March 11, 2021, from https://pubmed.ncbi.nlm.nih.gov/29858580/
  3. KD;, A. (n.d.). Chronic Ifosfamide TOXICITY: Kidney pathology And pathophysiology. Retrieved March 11, 2021, from https://pubmed.ncbi.nlm.nih.gov/24518127/
  4. Heerspink, H., Al., E., For the DAPA-CKD Trial Committees and Investigators*, & Author AffiliationsFrom the Department Clinical Pharmacy and Pharmacology. (2021, January 28). Dapagliflozin in patients with chronic KIDNEY DISEASE: NEJM. Retrieved March 11, 2021, from https://www.nejm.org/doi/full/10.1056/NEJMoa2024816
  5. Jean, G., Souberbielle, J., & Chazot, C. (2017, March 25). Vitamin d in chronic kidney disease and dialysis patients. Retrieved March 11, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409667/
  6. Muppidi, V. (2021, January 06). Secondary hyperparathyroidism. Retrieved March 11, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK557822/
  7. Cozzolino, M., Galassi, A., Conte, F., Mangano, M., Lullo, L., & Bellasi, A. (2017, June 01). [Full TEXT] treatment of secondary HYPERPARATHYROIDISM: The clinical utility Of et: TCRM. Retrieved March 11, 2021, from https://www.dovepress.com/treatment-of-secondary-hyperparathyroidism-the-clinical-utility-of-ete-peer-reviewed-fulltext-article-TCRM
  8. Electron Kebebew, M. (2004, September 01). Tertiary hyperparathyroidism. Retrieved March 11, 2021, from https://jamanetwork.com/journals/jamasurgery/fullarticle/397336
  9. Mikolasevic, I., Žutelija, M., Mavrinac, V., & Orlic, L. (2017, February 7). Dyslipidemia in patients with chronic kidney DISEASE: Etiology and management. Retrieved March 11, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304971/

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: