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
  • See more

• Nephritic Syndrome
  • See more

• 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/