Session 1

Q: Process of anemia and ESRD- why do they have it? 

Those with CKD/ESRD have kidneys that are diseased or damaged. Therefore, they have decreased EPO production which often becomes clinically significant during stage 3 CKD. As a result of this, the bone marrow makes fewer red blood cells, resulting in anemia.  This also means fewer red blood cells are available for carrying oxygen through your body.

CKD is also associated with high hepcidin levels, which blocks GI iron absorption and mobilization of iron from body stores; this results in a functional iron deficiency—the so-called “anemia of chronic disease.”

Other common causes of anemia in people with kidney disease include blood loss from hemodialysis and low levels of the following nutrients found in food:

• Iron
  • (Certain iron-rich foods like red meats and beans may be limited in a dialysis diet)
  • After a hemodialysis session, a small amount of blood is often left in the dialyzer (dialysis machine). Over time, this amount lost will build up and could lead to not having enough iron.
• vitamin B12
• folic acid

These nutrients are necessary for red blood cells to make hemoglobin, the main oxygen-carrying protein in the red blood cells.

 

Sources:

https://www.niddk.nih.gov/health-information/kidney-disease/anemia

https://www.kidneyfund.org/anemia/anemia-in-esrd/#causes_of_anemia_in_kidney_failure

Dirkx TC, Woodell T. Chronic Kidney Disease. In: Papadakis MA, McPhee SJ, Rabow MW. eds. Current Medical Diagnosis and Treatment 2020 New York, NY: McGraw-Hill; . http://accessmedicine.mhmedical.com.york.ezproxy.cuny.edu/content.aspx?bookid=2683&sectionid=225130730. Accessed April 22, 2020.

 

 

Session 2

Assignment: Insulin in ESRD and gluconeogenesis in Liver failure and ESRD 

Patients with diabetes and progressively declining kidney function are at increased risk for hypoglycemia. Diabetes treatment options for patients with advanced CKD therefore may be limited due to safety and tolerability concerns. Because the risk of adverse events related to hypoglycemia may be greater in patients with reduced kidney function, attention increasingly is being given to the risks of hypoglycemia (glucose , 70 mg/dL) in patients with diabetes and CKD.
The pathogenesis of hypoglycemia in patients with diabetic CKD is complex, particularly because there are other derangements in glucose metabolism in kidney failure. Consistent glycemic control is difficult to achieve in patients with ESRD because of altered glucose metabolism related to insulin resistance, impaired insulin secretion, and decreased insulin degradation, as well as effects on drug metabolism, adding further complexity to glycemic management. Diminished renal insulin clearance, as GFR decreases to 15-20 mL/min/1.73 m2 , prolongs the action of insulin. Aside from the liver, the kidneys represent the main site for insulin degradation, and as kidney function declines, so does the ability to remove insulin. Therefore, the risk of hypoglycemia is increased in CKD and one study suggested an insulin dose reduction of ~50% in these patients.
Reductions in kidney mass and diminished kidney function lead to decreased renal gluconeogenesis, a major source of glucose production from precursor molecules during starvation. Preliminary findings hint that the risk of hypoglycemia is particularly high in patients with diabetic ESRD who have more glycemic variability.

Hemodialysis Aspect:
Glycemic control is a tedious task in patients undergoing hemodialysis. Hemodialysis improves insulin sensitivity and insulin clearance. This compounds the insulin requirement estimation in patients with ESRD undergoing maintenance hemodialysis. Insulin resistance is a representative feature of type 2 diabetes. As mentioned before, insulin resistance and reduced clearance of insulin are factors that lead to changes in glycemic levels. Some patients on dialysis therapy may require different doses on different days due to the effect of dialysis on insulin sensitivity. If administered insulin is not altered, these patients are at greater risk of acute metabolic complications. Diabetic patients on hemodialysis may need lesser doses of insulin after dialysis treatments than they do on days when they do not have dialysis. If they continue to take the same dose of insulin after dialysis, they could have a greater chance of hypoglycemia.

Gluconeogenesis in Liver Failure
The mechanism of hypoglycemia in chronic kidney disease is less clear. It likely involves impaired gluconeogenesis, reduced renal clearance of insulin, and reduced renal glucose production. In severe liver failure, gluconeogenesis is also impaired.

Sources:

https://www.ajkd.org/article/S0272-6386(13)01432-7/pdf

https://www.uptodate.com/contents/carbohydrate-and-insulin-metabolism-in-chronic-kidney-disease?topicRef=1857&source=see_link#H8

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320826/