Chapter 21.2 (Consequence)

Progenitor cells

What cells of the kidney produce 90% of the hormone EPO, which stimulates red blood cell (RBC) production?

EPO

Reduction in the number of functioning nephrons decreases renal production of —, which is the primary cause of anemia in patients with CKD

• cardiac output (CO)

• left ventricular hypertrophy (LVH)

The development of anemia of CKD results in decreased oxygen delivery and utilization, leading to increased — and —, which increase the cardiovascular risk and mortality in patients with CKD

• 13 g/dL (130 g/L or 8.07 mmol/L)

• 12 g/dL (120 g/L or 7.45 mmol/L)

Current KDIGO guidelines define anemia as an Hgb level as

• less than — in males

• less than — in females.

Anemia

A number of factors contribute to the development of — including deficiencies in vitamin B12 or folate, hemolysis, bleeding, or bone marrow resistance to EPO.

True

True or false

• The prevalence of anemia correlates with the degree of kidney dysfunction.

False

True or false

• The primary cause of anemia in patients with CKD is a increase in EPO production.

• As the number of functioning nephrons increase, EPO production also decreases.

True

True or false

• With normal kidney function, as Hgb, hematocrit (Hct), and tissue oxygenation decrease, the plasma concentration of EPO increases exponentially

• as Hgb, Hct, and tissue oxygenation decrease in patients with CKD, plasma EPO levels remain constant within the normal range but low relative to the degree of hypoxia present

normochromic, normocytic anemia.

• as Hgb, Hct, and tissue oxygenation decrease in patients with CKD, plasma EPO levels remain constant within the normal range but low relative to the degree of hypoxia present. The result is —

Uremia

—, the accumulation of toxins that results from declining kidney function, decreases the lifespan of RBCs from a normal of 120 days to as low as 60 days in patients with CKD G5

• 60 mL/min (1.0 mL/s)

• 2 mg/dL (177 μmol/L)

Patients with CKD should be evaluated for anemia when the:

• GFR falls below —

• the SCr rises above —

erythropoiesis-stimulating agents (ESAs)

Abnormalities found during the anemia workup should be corrected before initiating —, particularly iron deficiency, because iron is an essential component of RBC production.

10 g/dL (100 g/L or 6.21 mmol/L)

If Hgb is below — when all other causes of anemia have been corrected, EPO deficiency should be assumed.

True

True or false

• EPO levels are not routinely measured and have little clinical significance in monitoring progression and treatment of anemia in patients with CKD.

RBC transfusions

Approximately 1 to 2 mg of iron is absorbed daily from the diet. This small amount is generally not adequate to preserve adequate iron stores to promote RBC production in patients with CKD-related anemia.

• — have been used in the past as the primary means to maintain Hgb and Hct levels in patients with anemia of CKD.

erythropoiesis-stimulating agents (ESAs)

When iron supplementation alone is not sufficient to increase Hgb levels, — are necessary to replace EPO. They are synthetic formulations of EPO produced by recombinant human DNA technology

erythropoiesis-stimulating agents (ESAs)

Use of — increases the iron demand for RBC production and iron deficiency is common, requiring iron supplementation to correct and maintain adequate iron stores

• 500 ng/mL (mcg/L; 1124 pmol/L)

• 30% (0.30)

Use of ESAs can lead to iron deficiency if iron stores are not adequately maintained. According to the KDIGO guidelines, iron supplementation should be considered when:

• Serum ferritin levels less than —

• Transferrin saturation (TSat): less than —

Serum ferritin

— is an acute phase reactant that may become elevated with inflammation and infection. Thus when serum ferritin is normal or elevated in conjunction with TSat levels less than 30% (0.30), treatment should be based on the clinical picture of the patient

200 mg

When administering iron by the oral route, how much of elemental iron should be delivered daily in divided doses to increase iron stores?

False

True or false

• When oral iron is not effective to increase iron stores or for patients receiving HD, IV iron should not be administered

1 g

Patients receiving HD have ongoing blood losses with each HD session, which can lead to iron losses of 1 to 2 g per year. For HD, IV iron may be administered episodically based on routine surveillance of iron stores as a total of how many g of IV iron, administered in small sequential doses to replete iron stores?

iron dextran

Anaphylaxis may occur with all IV preparations, but most notably with —, which can also cause delayed reactions, such as arthralgias and myalgias. A test dose of 25 mg should be administered 30 minutes before the full dose to monitor for potential anaphylactic reactions

• Sodium ferric gluconate

• Iron sucrose

• Ferric carboxymaltose

These iron preparations are associated with fewer severe reactions and a much lower risk of anaphylaxis and do not require a test dose, making them the preferred agents in CKD

• Serum ferritin

• TSat

After administering a 1-g course of IV iron, iron status should be monitored to determine the effectiveness of the treatment.

• What levels should be monitored no sooner than 1 week after the last dose of IV iron?

• 500 ng/mL (mcg/L; 1124 pmol/L)

• 30% (0.30)

If Hgb does not increase after a course of IV iron or serum ferritin is not greater than — and TSat greater than —, an additional 1 g of IV iron may be administered, based on the clinical situation

erythropoiesis-stimulating agents (ESAs)

This drug may be considered if Hgb levels remain persistently low to improve symptoms of anemia. In patients not receiving dialysis, the decision to initiate this drug should be based on the rate of Hgb decline, prior response to anemia treatment, risks associated with this drug and the patient’s symptoms.

True

True or false

• However, the target for Hgb is unclear because use of ESAs to increase Hgb levels beyond 12 g/dL (120 g/L or 7.45 mmol/L) is associated with increased mortality.

Methoxy PEG-epoetin beta

— has the addition of an amide bond that produces a longer half-life than the other ESAs and is referred to as a continuous erythropoietin receptor activator (CERA).

erythropoiesis-stimulating agents (ESAs)

The most common adverse effect seen with ESAs is increased blood pressure, which may require antihypertensive agents to control blood pressure.

> 180/100 mm Hg

Caution should be used when initiating an ESA in patients with very high blood pressures (—). If blood pressures are refractory to antihypertensive agents, ESAs may need to be withheld.

erythropoiesis-stimulating agents (ESAs)

Seizures and pure red cell aplasia have also been reported in patients initiating — therapy, and have been reported more with the CERA product.

Subcutaneous (SC)

What administration of ESA is the preferred route of administration for all agents because it produces a more predictable and sustained response than IV administration, and lower doses of ESAs are generally needed?

False

True or false

• When prescribing ESAs, clinicians should attempt to target “normal” Hgb levels

11 g/dL (110 g/L or 6.83 mmol/L)

Nonetheless, based on these findings, the US FDA recommended addition of a black box warning to the product information for all ESAs indicating the maximum target Hgb should not exceed —

• HgB

• Iron status

• Need for blood transfusions

The outcomes to monitor for anemia of CKD include:

3 months

Hemoglobin should be monitored every — in patients with CKD not on dialysis or receiving PD and monthly in patients receiving HD.

11.5 g/dL (115 g/L or 7.14 mmol/L).

Evaluate Hgb monthly when ESA therapy is initiated or the dose is adjusted to ensure Hgb does not exceed —

3 months

The ESA dose can increase monthly if Hgb is below goal. Once a stable Hgb is attained, evaluate Hgb every — thereafter

PTH

The actions of — on bone turnover lead to CKD-mineral and bone disorders (CKD-MBD). The majority of patients with CKD G3-G5 have CKD-MBD.

Phosphorus

As kidney function declines in patients with CKD, decreased — excretion disrupts the balance of calcium and phosphorus homeostasis.

vitamin D

Decreased — activation in the kidney also decreases calcium absorption from the gastrointestinal (GI) tract.

Fibroblast growth factor 23 (FGF-23)

— is a hormone produced by osteocytes and osteoblasts that is stimulated by increased phosphate and calcitriol. In CKD, elevated phosphate concentrations increase expression of this, which promotes phosphorus excretion and downregulates vitamin D activation in the kidney.

• Calcium

• Phosphorus

The parathyroid glands release PTH in response to decreased serum — and increased serum — levels.

Calcitriol

• Although the activity of — also increases phosphorus absorption in the GI tract and mobilization from the bone, which can worsen hyperphosphatemia.

• — also decreases PTH levels through a negative feedback loop.

Secondary Hyperparathyroidism

As kidney function continues to decline and the GFR falls less than 30 mL/min/1.73 m2 (0.29 mL/s/m2), phosphorus excretion continues to decrease and calcitriol production decreases, causing PTH levels to begin to rise significantly, leading to —.

Secondary Hyperparathyroidism

The excessive production of PTH leads to hyperplasia of the parathyroid glands, which decreases the sensitivity of the parathyroid glands to serum calcium levels and calcitriol feedback, further promoting —

renal osteodystrophy (ROD)

The most dramatic consequences of sHPT are vascular calcifications and alterations in bone turnover, which lead to —

• Calcium

• Phosphorus

• Intact PTH

Diagnosis and management of bone disease in CKD is based on corrected serum levels of:

True

True or false

• KDIGO guidelines recommend that hypercalcemia should be avoided in patients with CKD.

• Phosphorus and PTH levels should be maintained as close to normal as possible.

• vitamin D

• cinacalcet

Management of sHPT often requires treatment with — analogs or — in addition to phosphorus management

800 to 1000 mg/day

The first-line treatment for the management of hyperphosphatemia is dietary phosphorus restriction to what levels in patients with CKD G3 or higher who have phosphorus levels at the upper limit of the normal range or elevated iPTH levels.

True

True or false

• Many foods high in phosphorus are also high in protein, which can make it difficult to restrict phosphorus intake while maintaining adequate protein intake to avoid malnutrition

False

True or false

• Onset of sHPT and ROD is not subtle and may be associated with symptoms.

• CKD G4

• CKD G5

parathyroidectomy. Chronic ingestion of aluminum-containing antacids and other aluminum-containing products should be avoided in patients with CKD — and — (GFR less than 30 mL/min/1.73 m2 [0.29 mL/s/m2]) because of the risk of aluminum toxicity

Parathyroidectomy

— is a treatment of last resort for sHPT, but should be considered in patients with:

• persistently elevated iPTH levels above 800 pg/mL (ng/L; 85.6 pmol/L) that is refractory to medical therapy to lower serum calcium and/or phosphorus levels

phosphate-binding agents

When serum phosphorus levels cannot be controlled by restriction of dietary intake, what agents are used to bind dietary phosphate in the GI tract to form an insoluble complex that is excreted in the feces.

False

True or false

• Although phosphate binders are not FDA approved for patients with CKD who are not receiving dialysis, they are not used clinically when phosphorus levels are elevated, regardless of the GFR category.

• Sevelamer

• Lanthanum

These phosphate binders do not contain calcium, iron, or aluminum. These agents are particularly useful in patients with hyperphosphatemia who have elevated serum calcium levels or who have vascular or soft tissue calcifications.

Sevelamer

It is a cationic polymer that is not systemically absorbed and binds to phosphate in the GI tract, and it prevents absorption and promotes excretion of phosphate through the GI tract via the feces. It has an added benefit of reducing LDL-C by up to 30% and increasing HDL-C levels.

• Sucroferric oxyhydroxide

• Ferric citrate

These are iron-based phosphate binders that lower phosphate levels.

• Levothyroxine

• Doxycycline and Alendronate

Sucroferric oxyhydroxide cannot be taken with — and must be taken 1 hour after — and —.

True

True or false

• CCPBs, including calcium carbonate and calcium acetate, are effective in decreasing serum phosphate levels, as well as in increasing serum calcium levels.

Calcium carbonate

What CCPB can also aid in the correction of metabolic acidosis, another complication of kidney failure

Calcium citrate

What CCPB is usually not used as a phosphatebinding agent because the citrate salt can increase aluminum absorption.

CCPBs

In general, these should not be used if corrected serum calcium levels are near or above the upper end of the normal range or if arterial calcifications are present

• Constipation

• Hypercalcemia

The most common adverse effects of CCPBs are —

• Encephalopathy

• Bone disease

• Anemia

Aluminum-containing phosphate-binding agents are not recommended for chronic use in patients with CKD to avoid aluminum accumulation, leading to —, —, and —

vitamin D

It regulates many processes in the body, including calcium and phosphorus absorption from the GI tract and kidney, PTH secretion, maintaining muscle, cardiovascular, immune and brain function, and glucose control.

• Liver

• Kidney

What are the primary sites of Vit D activation

• Calcitriol

• 25-dihydroxyvitamin D

Vit D:

• Activated form —

• Precursor —

vitamin D

Exogenous — compounds that mimic the activity of calcitriol act directly on the parathyroid gland to decrease PTH secretion by upregulation of the vitamin D receptor in the parathyroid gland, which decreases parathyroid gland hyperplasia and PTH synthesis and secretion.

• Cholecalciferol

• Ergocalciferol

• Calcifediol

Vitamin D supplements can be used to lower serum PTH levels in patients with CKD.

• What Vit D Supplements have been shown to be effective in lowering PTH secretion in patients with CKD G3, and are useful in later stages of CKD to maintain adequate 25-hydroxyvitamin D levels for extrarenal functions

• Cinacalcaet

• Etelcalcetide

These are calcimimetics that increase the sensitivity of receptors on the parathyroid gland to serum calcium levels to reduce PTH secretion, but have no effect on intestinal absorption of calcium or phosphorus, and lower serum calcium levels

Calcimimetics

What class of drugs should be used with caution in patients with seizure disorders because low serum calcium levels can lower the seizure threshold

Cinacalcet

It is an oral calcimimetic that is most widely used for sHPT. GI side effects, including nausea and vomiting, can decrease tolerability of cinacalcet for some patients.

Etelcalcetide

It is an injectable agent that was recently developed to reduce GI side effects. It is administered as an IV three times a week after HD, which may improve adherence.

• Calcium

• Phosphorus

• PTH

KDIGO guidelines recommend monitoring what serum levels early in CKD, with increasing frequency as renal function declines.