• MCC of CKD: Diabetes Mellitus
• MCC of death in CKD: cardiovascular disease (34.7%)
  • malignant neoplasms are the 2nd MCC (31.8%)

"Half-and-half" nails (Lindsay nails)

• Chronic renal failure is associated with "half-and-half" nails (Lindsay nails), a sharply demarcated transverse leukonychia.  The mechanism remains unknown but is unlikely to be related to azotemia because the transition line disappears after renal transplantation but not with hemodialysis.
• Complication of ESRD: hyperkalemia
• Patients with chronic kidney disease (CKD) can develop hyperphosphatemia due to decreased filtration of phosphate.  Fibroblast growth factor 23 (FGF23) is secreted in response to hyperphosphatemia and lowers plasma phosphate by reducing intestinal absorption and renal reabsorption of phosphate.  FGF23 levels are useful as an early marker of abnormal phosphate metabolism in patients with CKD.
• Dietary phosphorus restriction is recommended for patients with CKD.  However, oral phosphate binders are usually needed if dietary restriction is not sufficient to lower phosphate levels.  Phosphate binders can be calcium containing (eg, calcium carbonate/acetate) or non–calcium containing (eg, sevelamer, lanthanum).  Sevelamer is a nonabsorbable anion-exchange resin that binds intestinal phosphate to reduce systemic absorption.  The resulting complex is eliminated in the feces.

• indications for dialysis: AEIOU

  • Acidosis
  • Electrolyte imbalances (hyperK > 6.5)
  • Intoxication → overdose of a dialyzable substance (mnemonic: SLIME)
  • Overload of fluid → CHF
  • Uremic symptoms

  note: dialyzable substances → SLIME: Salicylates (ASA), Lithium, Isopropyl alcohol, Magnesium laxatives, Ethylene glycol

• Medications contraindicated in renal impairment and hyperkalemia → ACEi, spironolactone

  • For anticoagulation, unfractionated heparin is preferred over low-molecular-weight heparin, fondaparinux, and rivaroxaban in patients with severe renal insufficiency (estimated glomerular filtration rate <30 mL/min/1.73 m2) as reduced renal clearance increases anti-Xa activity levels and bleeding risk.

• Patients with chronic kidney disease have inflammatory damage to renal EPO-producing cells and often develop normocytic anemia due to insufficient EPO.
  • In adults, approximately 80% of EPO is generated in the kidney; the remainder is largely generated in the liver by hepatocytes and Ito perisinusoidal cells.

Patients with chronic kidney disease (CKD) often develop symptomatic anemia (eg, fatigue, exertional dyspnea) as the glomerular filtration rate declines.  Most cases are due to the inadequate secretion of erythropoietin (EPO), a glycoprotein hormone produced by peritubular fibroblasts in the renal cortex in response to tissue hypoxia (as is seen with anemia).  EPO acts on erythrocyte precursor cells (erythroid colony–forming unit cells) in the bone marrow to stimulate red blood cell differentiation and survival.

• These individuals are often treated with synthetic EPO agents (eg, epoetin, darbepoetin) to stimulate erythrocyte production.  As iron is rapidly consumed to make red blood cells, individuals treated with EPO agents are often also given iron supplementation to prevent the development of iron deficiency anemia.
• Chronic kidney disease increases the risk for platelet dysfunction, which is thought to be due to inappropriately upregulated nitric oxide, causing decreased platelet adhesion, activation, and aggregation. Coagulation studies and platelet count are typically normal.

<aside> 🩸 Gastrointestinal bleeding in a patient with CKD and uremia is most likely secondary to uremic platelet dysfunction.

• Abnormal platelet adhesion and platelet aggregation in individuals with uremia are multifactorial and most likely occur because of the presence of platelet function inhibitors, uremic toxins, and glycoprotein IIb/IIIa dysfunction. Abnormalities in von Willebrand factor and thrombocytopenia may also play a role in increased bleeding tendency in patients with CKD.
• In CKD, platelet function is thought to be disrupted due to inappropriate upregulation of nitric oxide.  Patients with CKD have elevated urea, the end product of ammonia breakdown, which is derived from arginine.  As urea levels rise, arginine and its precursors are shunted to a different pathway, instead producing guanidinosuccinic acid (GSA), a precursor to nitric oxide.  Inappropriately high nitric oxide levels in CKD inhibit primary hemostasis via the following mechanisms:
  • Decreased platelet adhesion: Nitric oxide downregulates vWF secretion by endothelial cells.
  • Decreased activation and aggregation: Nitric oxide leads to reduced levels of ADP and thromboxane A2. In addition, it inhibits activation of the glycoprotein IIb/IIIa receptor.
• Anemia in CKD (due to reduced erythropoietin production) can also contribute to platelet dysfunction by reducing platelet marginalization along the endothelial surface.
• Laboratory findings that suggest dysfunctional platelet aggregation may include increased bleeding time and normocytic anemia. PT and aPTT are usually normal unless there is concomitant coagulopathy.
• Treatment includes renal replacement therapy by hemodialysis, peritoneal dialysis, or kidney transplantation. </aside>

CKD notes.pdf