A

B

100

Different scope: Many R3 insights are valuable but pertain to escalation/advanced management rather than “what can I safely close now.”

On a peripheral-blood smear, the red cells are normochromic and normocytic.

Which one of the following management strategies is the most appropriate next step for this patient?

Option a:

Repeat hemoglobin level in one month with no other intervention at this time

Answer rate9%

Option b:

Initiate treatment with folate and vitamin C

Answer rate1%

Option c:

Transfuse packed red cells

Answer rate3%

Option d:

Start intravenous iron

Answer rate9%

Option e:

Start an erythropoiesis-stimulating agent

Answer rate78%

Anemia is a common feature in patients with chronic kidney disease. Although other nonrenal causes should be excluded, in a patient with advanced chronic kidney disease who has normocytic, normochromic anemia and normal iron stores, the anemia is likely related to the reduced production of erythropoietin by the kidney. Erythropoiesis-stimulating agents (ESAs), which stimulate bone marrow to produce red cells, are the standard of care for treating anemia in this setting.

When to Start an ESA

The partial correction of anemia with ESAs can improve clinical symptoms and quality of life and can often obviate the need for red-cell transfusions in hemodialysis patients.

In most patients on hemodialysis, ESAs are started when the hemoglobin level falls below 9–10 g/dL, to avoid having the hemoglobin concentration fall below 9 g/dL. However, these agents should be avoided or used with caution in patients with active malignancy or a history of stroke. In addition, there is growing evidence that ESAs confer little benefit — and may increase risk — when used to maintain hemoglobin levels greater than 13 g/dL. For this reason, most clinicians recommend a target hemoglobin level no higher than 11.5 g/dL.

When to Give Iron Before an ESA

Patients with CKD and anemia should receive iron supplementation before starting an ESA if their iron stores are reduced, as indicated by a transferrin saturation ≤30% or a ferritin level ≤ 500 ng/mL. For patients on hemodialysis, the iron should be administered intravenously. For those not on hemodialysis, oral therapy is generally tried first; if the patient cannot tolerate or does not respond to the oral therapy, then intravenous iron may be tried. In this case, the patient’s transferrin saturation and ferritin levels are high enough that the ESA can be started without providing iron supplementation first.

Key learning point: The most appropriate treatment strategy in patients on hemodialysis with anemia secondary to chronic kidney disease is to start an erythropoiesis-stimulating agent.

300

A 45-year-old man presents for evaluation after his serum creatinine level was found to be elevated during a routine primary care visit. He reports no acute concerns. He recalls that years ago, he was told he had cysts in both kidneys.

There is a family history of polycystic kidney disease in the patient’s father and paternal uncle. The father receives dialysis three times weekly. There is no family history of intracranial bleeding, stroke, or unexplained sudden death.

On physical examination, the patient has a blood pressure of 142/81 mm Hg, a heart rate of 83 beats per minute, a temperature of 37˚C, and an oxygen saturation of 99% while he breathes ambient air. Both kidneys are palpable on examination. The rest of the examination is unremarkable.

Laboratory results are notable for a serum creatinine level of 1.5 mg/dL (reference range, 0.8–1.3). The rest of the basic metabolic panel is normal, as are the urinalysis and urine protein-to-creatinine ratio.

Which one of the following tests is most appropriate to conduct at this time to evaluate for extrarenal manifestations of this patient’s condition?

Option a:

CT of the head

Option b:

Magnetic resonance venography of the head and neck

Option c:

Complete ultrasound of the abdomen

Option d:

MRI of the pelvis

Option e:

Transthoracic echocardiography

Magnetic resonance venography of the head and neck

Magnetic resonance venography would image the venous system, which is not affected in this condition and thus would not be indicated for ICA screening.

500

A young man, 19 years of age, is evaluated for hyponatremia 7 days after transsphenoidal surgery for a suprasellar mass. Before his surgery, he had presented with fatigue, weight gain, cold intolerance, and double vision on lateral gaze. Endocrine testing revealed a low morning- cortisol level, central hypothyroidism, and secondary hypogonadism. Cerebral imaging revealed a 1.5-cm by 1.5-cm suprasellar mass that contained calcifications and displaced the optic chiasm anteriorly.

Preoperatively, he was treated with hydrocortisone 20 mg in the morning and 10 mg in the evening, as well as levothyroxine 100 μg daily.

His endocrine medications were continued postoperatively. On postoperative day 2, his urine output was 350 mL/hour, and he noted increased thirst. His serum sodium level rose to 148 mEq/L (reference range, 135–145) before normalizing. Now, 7 days postoperatively, his serum sodium level is 128 mEq/L.

Which one of the following diagnoses is the most likely cause of hyponatremia in this case?

Option a:

Pseudohyponatremia

Answer rate6%

Option b:

Inappropriate release of antidiuretic hormone

Answer rate60%

Option c:

Adrenal insufficiency

Answer rate11%

Option d:

Growth-hormone deficiency

Answer rate— %

Option e:

Diabetes insipidus

Inappropriate release of antidiuretic hormone

Answer rate60%

Hyponatremia is typically caused by water retention rather than loss of sodium. Water retention is typically mediated by an elevation in antidiuretic hormone (ADH) levels, often as a result of volume depletion, decreased effective arterial blood volume, postoperative pain, nausea, and spinal injury. The diagnosis of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) requires clinical euvolemia, which under normal circumstances would not be associated with increased ADH release. SIADH is caused by the nonosmotic release of ADH. After transsphenoidal surgery, there is often a triphasic response, with an initial polyuric phase (24 hours to 5 days after surgery) that reflects postoperative inhibition of ADH release, followed by SIADH that results from the release of stored ADH (6 to 12 days after surgery) from damaged neurons; a third phase may result in permanent diabetes insipidus, which can indicate permanent damage to the hypothalamus.

Key learning point: The triphasic water and sodium abnormalities that follow transsphenoidal surgery consist of the phases of transient central diabetes insipidus, followed by a phase of inappropriate release of antidiuretic hormone, and then (potentially) permanent diabetes insipidus.

A

100

A 25-year-old man with bipolar disorder who is being treated in the outpatient setting has been taking lithium 300 mg twice daily. However, his serum drug level is below the therapeutic range, prompting you to increase the dose to 300 mg three times daily. You wish to measure the serum drug level again to ensure that levels are therapeutic and not toxic, and you read that the half-life of lithium is 24 hours.

How long after the dose increase would a serum measurement give a useful and safe reading of the steady-state serum level of lithium?

Option a:

36 hours after the dose change

Option b:

5 days after the dose change

Option c:

3 days after the dose change

Option d:

14 days after the dose change

Option e:

10 days after the dose change

Lithium has an elimination half-life of approximately 24 hours, and drugs typically reach steady-state concentrations at four to five half-lives. Therefore, 36 hours after a dose change would not be sufficient time for lithium to reach steady-state concentrations. BB

300

A 29-year-old man with a history of Crohn disease is found to have nephrolithiasis. He has had an ileocecal resection, and his disease remains intermittently active on medical therapy.

Which one of the following dietary recommendations is most appropriate to reduce this patient’s risk for future kidney-stone formation?

Option a:

Increase animal protein intake

Option b:

Increase calcium intake

Option c:

Increase fat intake

Option d:

Increase oxalate intake

Option e:

Increase vitamin C intake

Increase oxalate intake

Reducing intake of fat, oxalate, and animal protein may reduce the risk for calcium oxalate stones.

500

A

Add dapagliflozin

Answer rate85%

In patients with chronic kidney disease (CKD) and proteinuria who are already taking an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB), the addition of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor has been shown to reduce the incidence of both CKD progression and all-cause mortality, regardless of the presence or absence of type 2 diabetes. SGLT-2 inhibitors have been shown to be safe and effective in patients with CKD who have an estimated glomerular filtration rate >25 mL/min/1.73 m2 and a urine albumin-to-creatinine ratio of 200 to 5000 mg/g. This patient meets these criteria and should have an SGLT-2 inhibitor added to his regimen.

Key learning point: The most appropriate next step for a patient with chronic kidney disease and type 2 diabetes who has persistent proteinuria while taking an angiotensin-converting-enzyme inhibitor or angiotensin-receptor blocker is to start a sodium-glucose cotransporter-2 inhibitor.

H

100

A 62-year-old woman is evaluated for hypotension, pneumonia, acute kidney injury, and hyperkalemia. Her total urine output during the past 6 hours is 75 mL. She is treated with intravenous antibiotics and normal saline. Her blood pressure improves from 82/50 mm Hg to 112/62 mm Hg.

Laboratory testing reveals a creatinine level of 4.2 mg/dL (reference range, 0.6–1.1) and a potassium level of 6.6 mEq/liter (3.5–5.0). An electrocardiogram shows a heart rate of 92 beats per minute and peaked T waves.

Which one of the following therapies is the most appropriate initial treatment for this patient?

Option a:

Intravenous furosemide

Answer rate1%

Option b:

Intravenous calcium gluconate

Answer rate89%

Option c:

Intravenous sodium bicarbonate

Answer rate1%

Option d:

Rectal sodium polystyrene sulfate resin

Answer rate— %

Option e:

Intravenous regular insulin and dextrose

Intravenous calcium gluconate

Answer rate89%

This patient has hyperkalemia that is severe enough that effects on myocardial excitability are a concern. Hyperkalemia may cause nonspecific repolarization abnormalities, and an electrocardiogram (ECG) will show peaked T waves and QRS widening. The rhythm may progress to an unstable arrhythmia. Therefore, patients with a serum potassium level >6.5 mEq/liter or with abnormal ECG findings should be treated immediately with intravenous calcium. Intravenous calcium raises the threshold resting membrane potential and makes the cardiac cells less excitable. Calcium is usually provided in the form of calcium gluconate, which can be given via a peripheral intravenous line, as opposed to calcium chloride, which is not given through a peripheral intravenous line because it can cause local tissue necrosis if there is tissue extravasation.

After calcium administration, the next step in management of hyperkalemia is to administer medications that shift potassium into cells. Intravenous insulin and dextrose shifts potassium intracellularly within 3 to 5 minutes after administration, reducing the serum potassium level by 0.6 to 1.0 mEq/liter after 30 minutes. Nebulized albuterol can also shift potassium intracellularly. The effective dose of albuterol to treat hyperkalemia, however, is much higher than that used for bronchospasm (10 to 20 mg instead of 2.5 mg). Many clinicians have reservations about using high-dose albuterol in patients with hyperkalemia for fear of producing a tachyarrhythmia.

Key learning point: The most appropriate initial treatment in severe hyperkalemia is intravenous administration of calcium.

300

A 35-year-old woman is evaluated for polyuria one day after transsphenoidal pituitary surgery to resect a nonfunctional pituitary adenoma (2 cm in diameter). She has had a urine output of approximately 400 or 500 mL/hour for the past 4 hours and is very thirsty. Physical examination reveals dry mucous membranes and normal visual fields.

Laboratory testing shows a serum sodium level of 147 mEq/L (reference range, 136–145), a blood glucose level of 105 mg/dL (70–100), and a urine specific gravity of 1.001 (1.001–1.035).

What treatment is indicated for this patient?

Option a:

Hypertonic saline (3%)

Answer rate1%

Option b:

Fludrocortisone

Answer rate2%

Option c:

Demeclocycline

Answer rate11%

Option d:

Hydrocortisone

Answer rate4%

Option e:

Vasopressin

Vasopressin

Answer rate82%

Patients who undergo transsphenoidal pituitary surgery are at risk for central diabetes insipidus. Surgery can disrupt the hypothalamus, stalk, and posterior pituitary, leading to a block in the release of vasopressin. The symptoms of diabetes insipidus tend to develop within the first 48 hours after surgery.

In diabetes insipidus, the inability to appropriately concentrate urine results in polyuria (urinary excretion >2.5 mL/kg/hour). In addition to polyuria, diabetes insipidus is diagnosed by a combination of symptoms and laboratory findings including dilute urine, polydipsia, dehydration, a high serum sodium level, low urine osmolality, and high serum osmolality.

Patients with diabetes insipidus should be treated with vasopressin. Vasopressin acts on receptors in the kidney to modulate water reabsorption.

Key learning point: The most appropriate treatment for a patient who has low urine osmolality, hypernatremia, and high serum osmolality one day after pituitary surgery is vasopressin.

500

A 64-year-old man with an 8-year history of type 2 diabetes is brought to the emergency department after an episode of hypoglycemia at home during which he was tremulous, diaphoretic, and confused. His glucose level on fingerstick testing is 44 mg/dL (reference range, 70–100).

The patient’s diabetes is managed with glyburide 10 mg daily. He also has hypertension, controlled with labetalol 200 mg twice daily. Three months ago, he underwent unilateral nephrectomy for localized renal-cell carcinoma. His most recent estimated glomerular filtration rate was 55 mL/min/1.73 m2 (reference range, ≥60).

Which one of the following mechanisms is most likely to have contributed to this patient's episode of hypoglycemia?

Option a:

Increased glucagon-like peptide-1 levels

Answer rate13%

Option b:

Impaired adrenergic response

Answer rate27%

Option c:

Increased glucagon production

Answer rate9%

Option d:

Impaired gluconeogenesis

Answer rate48%

Option e:

Impaired ketogenesis

Impaired gluconeogenesis

Answer rate48%

Sulfonylureas, such as glyburide, act on the pancreatic beta-cells to increase the secretion of insulin. These medications therefore lead to an uncoupling of blood glucose and insulin secretion; insulin secretion can continue even in the absence of hyperglycemia. This puts patients taking sulfonylureas at high risk for developing hypoglycemia.

Counterregulatory mechanisms are critical in preventing and correcting hypoglycemia. One of the counterregulatory mechanisms is an increase in gluconeogenesis (production and release of glucose) by the liver and kidneys. However, this process is inhibited by the presence of insulin. Therefore, the insulin produced by the pancreas in patients treated with sulfonylureas inhibits gluconeogenesis, further delaying the recovery from the hypoglycemic episode. In this patient, the unilateral nephrectomy may be an additional contributor. Renal gluconeogenesis accounts for approximately 20% of glucose production. A patient with chronic renal failure or who has undergone nephrectomy would, therefore, be at increased risk for hypoglycemia when taking sulfonylureas. In addition, glyburide is best avoided in patients whose glomerular filtration rate is <60 mL/min/1.73 m2, because decreased medication clearance also poses a risk for hypoglycemia.

Key learning point: Counterregulatory mechanisms allowing for glucose release in the postabsorptive state include gluconeogenesis from both the liver and kidneys.