Under Pressure
A 68-year-old woman is admitted to the medical intensive care unit with respiratory distress of sudden onset. She has been exposed to Covid-19 by a family member. She has received two Covid mRNA vaccines and a booster. She also has a history of well-controlled hypertension and heart failure. Medications include lisinopril 20 mg daily, aspirin 81 mg daily, carvedilol 12.5 mg twice daily, and furosemide 20 mg daily. She uses bilevel positive airway pressure. Her BP is 148/78 mm Hg, heart rate 88 bpm, chest sounds rhonchi bilaterally systolic ejection murmur present, no edema. Family is concerned that patient may require intubation and want the physicians to stop the lisinopril because they are afraid this will worsen her Covid-19 symptoms.
Which ONE of the following is the MOST appropriate next step in management?
A. Stop lisinopril and switch to losartan 100 mg daily
B. Stop lisinopril and switch to amlodipine 10 mg daily
C. Continue current medications
D. Stop lisinopril because upregulation of ACE2 by lisinopril will exacerbate Covid-19 symptoms
What is (c)?
Answer options A, B, and D are incorrect because no data suggest that ACEIs are harmful in the setting of COVID infection. Despite theoretic concerns that use of RAS blockade could potentially worsen Covid-19 symptoms, ACEIs/ARBs do not seem to predispose to SARS-CoV-2 infection, nor do they appear to worsen symptoms in patients with COVID-19, whether the infection is mild, moderate, or severe.
A 40-year-old woman with a medical history of
schizophrenia presents to the emergency department with tonic-clonic seizures. She is intubated on arrival. On examination, BP is 179/88 mm Hg, and heart rate 137 beats/min.
Laboratory evaluation shows serum sodium 183mmol/L, serum osmolality 363 mOsm/kg, potassium 3.6 mmol/L, chloride 128 mmol/L, blood glucose 115 mg/dl, BUN 22 mg/dl, creatinine 1.0 mg/dl. The patient’s family reports that she might have ingested 500 ml of triple-strength Japanese seasoning soy sauce 3 to 4 hours before seizure onset.
Which of the following statements regarding the management of an acute salt intoxication is correct?
A. Goal serum sodium correction should not exceed more than 10 mmol/L in 24 hours or 0.5 mmol/L per hour to avoid the development of cerebral edema
B. Cerebral edema is unlikely to occur in this setting of acute hypernatremia, and rapid correction of serum Na to baseline should be undertaken
C. Acute hypernatremia allows for the formation of idiogenic osmoles counterbalancing the osmotic gradient between extracellular and intracellular compartments
D. Administration of free water at high rates is sufficient to treat salt intoxication, and extracorporeal removal can cause too rapid a decrease in the serum sodium concentration
What is (B)?
It has to be recognized that salt intoxication in contrast to other forms of hypernatremia is not due to the loss of water but rather due to a massive salt ingestion.
Unlike chronic hypernatremia, the acute change in serum tonicity does not allow time for the
formation of idiogenic osmoles to counterbalance the osmotic gradient (answer C is incorrect). Therefore, the risk of cerebral edema is low in the setting of early recognized salt intoxication and rapid correction (answer B is correct). Rapid lowering of the serum sodium concentration with substantial free water administration is paramount and the rate should
certainly exceed 10 mmol/L in 24 hours or 0.5 mmol/L/hour per hour (answers A is incorrect).
In fact, acute hypernatremia in the setting of a massive salt ingestion as outlined above is often fatal and extracorporeal removal is often indicated as the rate of correction needs to be fast (answer D is incorrect).
A 34-year-old woman is referred to your clinic for evaluation and management of microscopic hematuria and occasional flank pain. She does not have hypertension, headaches, urinary tract infection, or kidney stones. The patient’s mother and maternal aunt have ADPKD and are currently receiving hemodialysis. On physical examination, her BP is normal, and her kidneys are not palpable. Laboratory studies show hemoglobin of 14 g/dl,
normal serum electrolytes, and SCr of 0.9 mg/dl.
Urinalysis shows specific gravity of 1.025, pH 5,
3+ blood, and negative protein. A microscopic
examination shows >100 monomorphic erythrocytes
per high-power field.
Which ONE of the following is the next MOST
appropriate diagnostic study?
A. Renal ultrasonography
B. Computed tomography (CT) of the kidneys
C. MRI of the kidneys
D. Genetic testing for PKD1 and PKD2
mutations
What is (A) Renal ultrasonography?
Screening for the diagnosis of ADPKD in an individual at risk with a positive family history usually relies upon imaging of the kidney. Among at-risk individuals, ultrasonography of the kidneys is the preferred initial imaging modality for screening and diagnosis. Kidney ultrasonography is usually used for screening because it is safe,effective, and relatively inexpensive; choice A is correct. CT and MRI (choices B and C) are more sensitive than ultrasonography, but are more expensive. Moreover, CT scans result in needless exposure to radiation and contrast exposure (CT). Among patients with equivocal ultrasound results and/or when a definite diagnosis is required (such as in a potential living donor), contrasted CT or uncontrasted MR imaging and/or genetic testing (choice D) may be required, but would not be the initial most appropriate diagnostic study.
A 55-year old Caucasian, obese man with hypertension and hypercholesterolemia is referred for elevated serum creatinine. His eGFR is 22 ml/min per 1.73 m2, consistent with stage 4 CKD. Among his several medications, he is treated with a statin. His current total cholesterol and LDL and HDL cholesterol are well controlled, but the patient has occasional “aches” in his left calf when walking.
Which ONE of the following statements is correct concerning statin treatment in CKD?
A. His statin treatment will reduce his risk for cardiovascular morbidity.
B. The statin should be discontinued because of myopathy.
C. His statin therapy will likely lead to an improvement in his GFR.
D. He should be switched to treatment with a fibrate.
What is (A)?
There has been much discussion of the German Diabetes and Dialysis Study, often referred to as the 4D Study.
This study was a randomized controlled trial that compared atorvastatin and placebo in hemodialysis patients with diabetes. Although LDL cholesterol was reduced 42% in the atorvastatin group, there was no benefit in terms of a composite endpoint composed primarily of cardiovascular events. Although this study involved hemodialysis patients, it raised questions about the value of statin therapy in later CKD stages. Strippoli et al. recently performed a meta-analysis of studies of statin use in CKD to evaluate the efficacy and safety of treatment. A total of 50 trials involving 30,144 patients were analyzed. Compared with placebo, statins significantly reduced total cholesterol, LDL cholesterol, and urinary protein excretion. There was, however, no improvement in GFR (choice C). Although there was no effect on all-cause mortality, both fatal and nonfatal cardiovascular events were reduced with statin treatment (choice A). Importantly, the stage of kidney disease did not seem to be an important predictor of response. The authors concluded that statins have cardiovascular benefits in CKD, but cautioned that any renoprotective effects should be interpreted with caution due to reporting bias. The patient’s aches in his left calf when walking could represent claudication. However, they are not definitively attributable to statin-induced myopathy (choice B). Although fibrate therapy has a clear place in the treatment of certain types of hyperlipidemia, there is no indication to switch therapy in this patient (choice D).
A 38-year-old man with hypertension and hyperlipidemia has issues with compliance and forgets to take his medications on occasion. His BP control has been variable. He has no other health issues. He is complaint with lifestyle modifications. He is currently taking losartan 50 mg daily, hydrochlorothiazide 12.5 mg daily, and amlodipine 2.5 mg at night. His BP in office is 148/86 mm Hg. His BMI is 28. The results of physical examination are otherwise normal. Which ONE of the following is the MOST appropriate next step in management?
A. Switch to triple combination therapy to improve BP control and compliance
B. Increase amlodipine to 5 mg daily and continue other medications
C. Add spironolactone 12.5 mg daily
D. Add carvedilol 12.5 mg twice daily
E. No change in therapy
What is (A)?
Various studies have shown that use of combination therapy improves compliance and therefore improves BP control. When patients likely forget to take all their medications, switching to a single tablet to be taken once daily will likely improve compliance (answer option A is correct). Increasing medication dosages or adding additional medications is unlikely to improve BP control (answer options B, C, and D are incorrect). A recent study from Australia—the QUARTET trial—used quadruple ultra-low-dose treatment for hypertension, a combination of a quarter of the standard dose of four antihypertensive agents: irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg taken once daily (“quadpill”), compared with irbesartan 150 mg daily. In the quadpill group, the office BP was significantly lower, which persisted for a year in the extended follow-up phase. Side effects and laboratory findings were very similar between the two groups. Additional therapy was used in 15% of the quadpill group and 40% of the control group.
A 22-year old woman is referred for hypokalemia. The patient’s history indicates progressive weakness over the past 3 weeks and weight gain despite exercise and following a healthy balanced diet. The patient does not describe having diarrhea or vomiting, and she does not have a history of using over-the-counter (OTC) medications or herbal supplements. Her body/m2, mass index (BMI) is 19 kg and BP is 120/80 mmHg. The results of physical examination are unremarkable.
Laboratory evaluation shows plasma sodium 133mEq/L, plasma potassium 2.7 mEq/L, plasma chloride 83 mEq/L, plasma bicarbonate 34 mEq/L, plasma BUN 6 mg/dl, plasma creatinine 0.6 mg/dl, arterial blood gases pH 7.46 and PCO2 44 mm Hg, urine electrolytes (mEq/L) [Na1] 70, urine [K1] 35, urine [Cl2],15, urine pH 8.
What is the most likely cause of this patient’s
hypokalemia?
A. Early (“continuous”) vomiting
B. Magnesium deficienc
C. Long-term laxative use
D. Remote diuretic use
What is (A)?
Early vomiting causes hypochloremic hypokalemic metabolic alkalosis with a normal/low BP and an inappropriately elevated urine potassium indicating a renal etiology of the K+ loss that is due to bicarbonaturia (1). In the absence of vomiting, the H+ normally secreted by the gastric parietal cell apical H+, K+-ATPase leaves behind HCO3- at the basolateral cell membrane that is absorbed into the venous circulation and represents retention of HCO3-. However, with vomiting there is a loss of gastric HCl, thus eliminating the entry of acid into the duodenum, which is the stimulus for secretion of HCO3- by the pancreas. Therefore, with vomiting there is net gain of [HCO3-] from the unopposed loss of gastric H+ secretion. With metabolic alkalosis the increase in the filtered load of HCO3- beyond the tubular transport maximum (Tm) for HCO3- in the proximal tubule (PCT), causes an increase in distal HCO3- delivery. Volume depletion and enhanced NaHCO3 delivery distally increases K+ secretion. Furthermore, once hypokalemia occurs, it maintains the metabolic alkalosis by: (a) increasing the activity of the H+, K+-ATPases in the cortical CD and outer medullary collecting duct (OMCD), and (b) the direct effect of hypokalemia to enhance ammoniagenesis and increase net acid excretion that, therefore, causes new bicarbonate to be produced by the kidney and returned to the systemic circulation.
A 25-year-old man is referred to you for further
evaluation of asymmetric kidney size and an elevated serum creatinine (SCr) level. He has develop mental delay, retinitis pigmentosa, hypogonadism,and obesity. He has no family history of kidney disease. On physical examination, the body mass index is 32 kg/m2. There is gynecomastia. His phallus is small, and the testicular volume is approximately 8 ml bilaterally. There is a paucity of axillary and genital hair. His cognitive function is impaired. Laboratory evaluation shows a SCr of 1.5 mg/dl. The urinalysis is unremarkable.
Kidney ultrasound shows a left kidney of 11 cm in size. The right kidney is 9.2 cm in size with four cortical cysts, the largest of which is 0.8 cm in diameter. A dimercaptosuccinic acid (DMSA) scan reveals that 25% of the total kidney function is derived from the right kidney.
Which ONE of the following is the MOST likely diagnosis?
A. Autosomal dominant interstitial kidney disease
B. Autosomal dominant polycystic kidney disease (ADPKD)
C. Multicystic dysplastic kidney
D. Bardet–Biedl Syndrome
E. Senior–Løken Syndrome
What is (D) Bardet-Biedl syndrome?
The constellation of symptoms described includes 4 of the 5 major criteria needed to diagnose Bardet-Biedl syndrome. The diagnostic criteria require the presence of 4 major criteria or 3 major criteria and 2 minor criteria. The major criteria include polydactyly, learning difficulties, hypogonadism, retinitis pigmentosa, obesity and renal involvement. Minor criteria include diabetes mellitus, congenital heart defects, hearing loss, hepatic fibrosis, hypertelorism, dental crowding and anosmia. The renal involvement of Bardet-Biedl can be more heterogeneous than what is observed in nephronophthisis and may include asymmetric kidney sizes. Autosomal dominant interstitial kidney disease (ADIKD), choice A, is incorrect because a family history of kidney disease would be expected. CKD is usually apparent in ADIKD by age 40, but may be detected as early as the teenage years. Asymmetry in kidney size is not a typical feature of ADIKD, and extra-renal features may include hyperuricemia and early onset gout (usually during teenage years) in individuals with uromodulin and renin gene mutations. Early onset gout, however, is not a feature of ADIKD and mucin gene mutations. Autosomal dominant polycystic kidney disease (ADPKD), choice B, is incorrect because this condition is also inherited in an autosomal dominant fashion. The absence of a compatible family history and the presence of other features characteristic of Bardet-Biedl make the diagnosis of ADPKD less likely. Multicystic dysplastic kidneys are typically non-functional (minimal to no GFR).
Senior-Løken syndrome does include retinitis pigmentosa, but not the other clinical features noted in this man. Asymmetry in kidney size is not a feature of Senior-Løken syndrome. Kidney involvement in this syndrome mirrors that of nephronophthisis.
A 22-year old woman with type I diabetes diagnosed at age 13 years comes to you for advice to prevent diabetic complications. During college, she did not receive regular medical care. She denies current complications, although she reports frequent hypoglycemia. Her current medications are neutral protamine Hagedorn insulin and regular insulin twice per day and birth control pills. On examination, she has a BP of 125/75 mmHg, no retinopathy, and a normal neurologic examination. Her laboratory results show normal electrolytes, an albumin/
creatinine ratio of 7 mg/g, and the following measurements: creatinine, 0.6 mg/dl; LDL cholesterol, 100 mg/dl;
HDL cholesterol, 55 mg/dl; triglycerides, 150 mg/dl; and hemoglobin A1C, 7.9%.
Which ONE of the following is the MOST effective treatment to decrease the risk of kidney disease?
A. Start an angiotensin-converting enzyme inhibitor (ACEI).
B. Change to an insulin pump.
C. Stop the birth control pills.
D. Start a hepatic hydroxymethyl glutaryl–CoA reductase inhibitor.
E. Start treatment with 81 mg of aspirin.
What is (B) Change to insulin pump?
Although ACEIs or ARBs can decrease progression to renal diseases in patients with type I or type II diabetes, they do not prevent mesangial expansion or worsening albuminuria in those with normoalbuminuria (answer A). Stopping birth control pills, using a statin, or using aspirin has not been shown to be effective. In the Diabetes Control and Complications Trial, use of insulin regimens that produce tight control has been shown to prevent progression.
A 58-year-old woman with longstanding hypertension returns to see you. Her BP is 155/95 mm Hg despite maximal doses of amlodipine, candesartan, and chlorthalidone. Her kidney function remains normal. Evaluation for secondary causes of hypertension has been unrevealing, and she appears to be compliant with her medications and your lifestyle recommendations. You would like to add an additional antihypertensive medication to help control her BP. Which ONE antihypertensive medication would be BEST to add-on to her current regimen?
A. Doxazosin
B. Hydralazine
C. Labetalol
D. Spironolactone
What is (D) Spironolactone?
Spironolactone is the preferred fourth-line agent to be added to her current antihypertensive regimen. The PATHWAY-2 study found greater BP reduction with spironolactone as fourth-line add-on therapy compared with bisoprolol, doxazosin, and placebo. A subsequent mechanistic subanalysis of PATHWAY-2 found that autonomous aldosterone secretion (often below the thresholds defining primary aldosteronism) is highly prevalent in the resistant hypertension population, which likely explains why spironolactone was found to be more effective than its comparator medications (answer option D is correct).
A 79-year-old woman with ESKD routinely presents on Tuesday mornings with predialysis potassium 6.8 mEq/L. She undergoes dialysis three times weekly for 4 hours via a fistula. Her Kt/V is 1.7.
Which of the following is most likely to be an evidence-based approach to her hyperkalemia?
A. Sodium zirconium cyclosilicate should not be chosen as it is effective in reducing potassium in non dialysis CKD patients but not in dialysis patients
B. Sodium zirconium cyclosilicate should be chosen
for this patient rather than patiromer as it is less
likely to cause edema
C. Sodium zirconium cyclosilicate also removes
hydrogen ions and may increase serum bicarbonate
D. Sodium zirconium cyclosilicate works quickly and has been shown to provide added benefit to insulin and glucose in the treatment of acute severe hyperkalemia
What is (C)?
Data from three placebo-controlled trials demonstrated a dose-dependent increase in mean serum bicarbonate of 0.3 to 1.5 mM within 48 h of treatment with sodium zirconium cyclosilicate. These changes were maintained over 29 days. With highest sodium zirconium cyclosilicate maintenance doses, the percentage of patients with serum bicarbonate <22 mM declined from 39% at baseline to 4.9% at 29 days.
Which ONE of the following is correct regarding the use of tolvaptan in ADPKD?
A. Tolvaptan inhibits cyst progression by blocking
mammalian target of rapamycin
B. Tolvaptan does not reduce the rate of progression
of kidney disease in early ADPKD
C. Tolvaptan is approved by the Food and
Drug Administration for use in ADPKD
D. Dizziness is the most common side effect
of tolvaptan
E. Transaminitis may occur in patients with
ADPKD on tolvaptan and requires regular
monitoring of liver function tests.
What is (E)?
Approximately 1% of participants enrolled in the TEMPO trial were found to have increased liver enzymes compared to about half that in the placebo group. Therefore, choice E is correct and choice C is incorrect. Tolvaptan is believed to inhibit cyst growth by lowering renal epithelial cyclic AMP levels; therefore, choice A is
incorrect. Tolvaptan reduced the annual rate of decline in GFR (choice B is incorrect). The FDA has not approved tolvaptan for use in ADPKD because of the potential for irreversible liver injury (choice C is incorrect). Increased thirst and polyuria resulting from an aquaresis are the most common side effects of the drug, occurring in 55.3%, (20.5% with placebo) and 38.3% (17.2% with placebo) of participants, respectively. Dizziness was less common, and occurred in 11.3% of participants compared with 8.7% in controls; therefore, choice D is incorrect.
You are teaching a group of medical residents about the management of hyperphosphatemia in CKD. After discussing traditional phosphate binders, you move on to discuss newer agents and explain that there are multiple routes of phosphate absorption in the small intestine that can serve as targets for the treatment of hyperphosphatemia. Which ONE of the following hyperphosphatemia treatments primarily targets intestinal paracellular phosphate absorption?
A. Tenapanor
B. Modified-release nicotinamide
C. EOS789
D. Ferric iron oxide adipate
What is (A) Tenapanor?
The two mechanisms of intestinal phosphate transport are transcellular (active transport across cell membranes) or paracellular (passive transport between cells).
Tenapanor is an example of a drug that uses inhibition of the intestinal sodium-hydrogen
exchanger 3 (NHE3) to decrease paracellular phosphate permeability (answer option A is correct). Nicotinamide formulations primarily act by inhibiting NaPi-IIb expression (an important transcellular transporter), while EOS789 is a novel broad-spectrum inhibitor of transcellular transport by acting on NaPi-IIb, PiT-1, and PiT-2 transcellular transporters (answer options B and C are incorrect). Ferric iron oxide adipate is an iron-based phosphate binder that complexes to free phosphate in the intestinal lumen to inhibit its availability (answer option D is incorrect).
A 50-year-old otherwise healthy woman is referred to you for hypertension (170/100 mm Hg) plus spontaneous hypokalemia (3.1 mmol/L). Plasma renin activity is ,1 ng/ml per hour, and plasma aldosterone concentration is 35 ng/dl. Dynamic confirmatory testing via oral sodium loading confirms the diagnosis of primary aldosteronism. A CT scan of the adrenal gland shows a left adrenal nodule. What is best next step in the treatment of this patient?
A. Order an adrenal MRI
B. Order adrenal vein sampling
C. Treat with lifelong spironolactone
D. Proceed with surgical adrenalectomy
What is (B)?
The best next step in the diagnostic evaluation for this patient with primary aldosteronism is to perform adrenal vein sampling. A key branch point in the evaluation of primary aldosteronism is to determine whether the source of autonomous aldosterone secretion arises from one or both adrenal glands (i.e., disease lateralization). This distinction is necessary to determine whether to recommend surgical adrenalectomy versus lifelong mineralocortoid receptor antagonist therapy as the preferred treatment. Determination of disease lateralization is a two-step process, which first involves adrenal CT or MRI to assess for a nodule, followed in the majority of cases by adrenal vein sampling.
A 74-year-old man with type II diabetes mellitus and heart failure with reduced ejection fraction presents to the emergency department with a 1-week history of fatigue, vomiting, headache, and abdominal pain. He is found to have AKI, with creatinine increased to 2.3 mg/dl from baseline 1.2 mg/dl. Other laboratory results show Na 134mEq/L, K 4.0mEq/L, Cl 98mEq/L, HCO3 15mmol/L, BUN 68mmol/L, glucose 196mmol/L. Lactate is 1.5 mEq/L. On examination, he is in hemodynamically stable condition, with a mildly tender abdomen, but the results of physical examination are otherwise unremarkable. For his diabetes, he takes insulin and another oral antidiabetic medication that he cannot recall the name of. He reports that his blood sugars have been very well controlled, such that his insulin was recently reduced by 50%.
In considering this case, which of the following statements is most accurate?
A. Metformin is the most likely culprit agent for acidosis in this case
B. The recent reduction in insulin dosing may be the precipitant for this clinical presentation
C. The patient’s near-normal blood glucose excludes ketoacidosis as a cause of this presentation
D. This patient should be given an intravenous infusion of isotonic bicarbonate
What is (B)?
This clinical presentation is most in keeping with euglycemic ketoacidosis induced by SGLT2 inhibitor. SGLT2 inhibitors reduce the insulin-to-glucagon ratio, promoting a switch to lipolysis, and increase hepatic ketoacid production. Excessive reductions in insulin dosage can precipitate ketoacidosis, while urinary glucose losses help to maintain normal serum glucose (B is correct). Patients with euglycemic ketoacidosis frequently present with vague symptoms such as abdominal pain, nausea and fatigue. Although the AG is significantly elevated,
diagnosis may be delayed due to the absence of significant hyperglycemia (C is incorrect).
Recommended treatment is for SGLT2 inhibitor induced euglycemic ketoacidosis similar to hyperglycemic DKA, although the degree of volume depletion is significantly less due to the absence of hyperglycemia. Intravenous bicarbonate is generally recommended for patients with severe acidosis, and in this case may precipitate hypokalemia. Restarting an appropriate dose of insulin, in collaboration with advice from colleagues in endocrinology is an initial
management step (D is incorrect).
Important risk factors for euglycemic ketoacidosis include female gender, excessive reduction or discontinuation of insulin, major surgery/trauma, intercurrent illnesses that limit the ability to eat/drink, alcohol consumption, and low carbohydrate intake.
Which features are MOST useful in differentiating autosomal dominant interstitial kidney
disease from juvenile nephronophthisis?
A. The pattern of inheritance
B. The pathologic findings on kidney biopsy
C. The kidney size, cortical echogenicity, and
presence and distribution of renal cysts
D. The presence of polyuria
What is (A)?
Auosomal dominant interstitial kidney disease (ADIKD; also called medullary cystic kidney disease) and nephronophthisis are similar in their histology (choice B), ultrasound presentation (choice C) and renal manifestations (choice D; polyuria and concentrating defect). They differ, however, in the mode of inheritance (autosomal dominant for ADIKD and autosomal recessive for nephronophthisis). Individuals with UMOD and REN gene mutations causing ADIKD develop early onset gout and hyperuricemia, whereas individuals with nephronophthisis may have cerebellar, retinal, and musculoskeletal manifestations. Therefore, choice A is correct.
A 72-year-old man has CKD stage 4 related to renovascular disease. He has coronary artery disease and is s/p ST elevation myocardial infarction, and s/p multiple angioplasties. He has peripheral vascular disease and severe chronic obstructive pulmonary disease. He has been taking glucocorticoids for years for chronic obstructive pulmonary disease. He has had a number of fractures, related to falls, and also has a nontraumatic vertebral fracture. He has been taking calcitriol for many years, but this was stopped when his PTH was noted to be ,100 pg/ml. Follow-up labs after stopping vitamin D receptor activator (VDRA) show a low bone-specific alkaline phosphatase and PTH 120 pg/ml. Vitamin D levels are normal. Phosphorus is normal, and he is not taking phosphate binders. Calcium is normal at 9.8 mg/dl. Of the following, which is the best agent for his osteoporosis?
A. Pamidronate
B. Denosumab
C. Teriparetide
D. Romosozumab
What is (C) Teriparetide?
Teriparatide is a recombinant peptide encoded by the first 34 amino acid residues of human PTH. It has been shown to reduce fracture risk in patients with age-related and glucocorticoid induced osteoporosis. Recent studies have suggested that teriparatide is safe and effective in patients with advanced CKD and low turnover bone disease. This patient’s low PTH level after years of calcitriol and low BSAP suggest that he could have low turnover bone disease (answer option C is correct). Answer options A and B are incorrect because both bisphosphonates (pamidronate) and denosumab are antiresorptive agents that inhibit bone turnover and thus should NOT be used in patients with low bone turnover. In addition,
bisphosphonates are not recommended in patients with eGFR <30 ml/min per 1.73 m2 (stage 4).
Although romosozumib may be of benefit among patients with low turnover disease, it has been
associated with a higher rate of cardiovascular events, which this patient is at risk for (answer
option D is incorrect).
A 41-year-old woman is noted to be hypertensive at her first prenatal appointment at 12 weeks. She describes being mildly hypertensive during her prior pregnancy 6 years ago, but she has not been followed up by a physician since then. She states that both her parents have hypertension. She further notes that she has measured her BP at home using her mother’s BP cuff, and it runs 139/92 mm Hg. Her BMI is 33, and her examination results are otherwise unremarkable. Laboratory investigation results, including urinalysis, protein-to-creatinine ratio, and serum creatinine, are normal.
What is the MOST likely diagnosis?
A. Essential hypertension
B. Gestational hypertension
C. Preeclampsia
D. White-coat hypertension
What is (A) Essential Hypertension?
The patient has risk factors for essential hypertension, including family history and increased body mass index, and had consistently elevated BP before pregnancy (answer option A is the best choice). Answer options B and C are incorrect because both gestational hypertension and preeclampsia present in later stages of pregnancy (at after 20 weeks’ gestation). Answer D is incorrect because white-coat hypertension, defined by elevated BP in the clinic setting and normal BP at home, is excluded by her home BP readings.
A 66-year-old woman with a history of hypertension,
CKD stage IV, and dyslipidemia is seen at renal clinic.
On review of her laboratory results, total CO2
has decreased to 20 mEq/L. You advise her to increase her intake of alkali-generating fruits and vegetables, but she is reluctant to make dietary changes. As an alternative, you suggest that she start oral bicarbonate therapy.
Regarding the benefits of alkali therapy in CKD,
which of the following is correct?
A. In patients with CKD stage III to stage V, treatment of metabolic acidosis has been associated
with reduction in progression to ESKD
B. Bicarbonate therapy has not been associated with
improvements in mortality in randomized controlled
trials (RCTs)
C. Patients with uncontrolled hypertension and
advanced heart failure have been enrolled in RCTs
investigating the use of NaHCO3 in CKD
D. In an RCT, treatment with veverimer was associated with improved [HCO3] but no significant improvement in physical function scores
What is (A)?
In a randomized controlled trial of 740 patients from Italy with CKD stage 3 to 5, randomized to either standard care or NaHCO3 treatment with a three-year follow up period, those treated with NaHCO3 had lower incidence of doubling of serum creatinine (6.6% versus 17%) and significantly lower rates of development of ESKD (6.9% versus 12.3%) and death (3.1% versus 6.8%) (A is correct; B is incorrect).
This study and the BASE study excluded patients with heart failure NYHA III and IV and those
with BP >50/90 mm Hg; thus, the safety of NaHCO3 in such patients is unclear (C is incorrect).
In a phase III randomized controlled, multicenter trial, 217 patients with CKD eGFR 20–40 mL/min per 1·73 m² and serum [HCO3 –] 12–20 mmol/L, were randomly assigned to veverimer (6 g/day) or placebo and followed for 12 weeks. During this study and the 40-week extension period, veverimer treatment was associated with significantly higher rates of normalization of [HCO3 –] and a significant increase in physical function scores compared to control (D is incorrect)
You have recently received the results of genetic
testing for an 8-year-old boy who you have been
following for a suspected diagnosis of nephronophthisis.
The results indicate that he has a homozygous
deletion at the nephronophthisis 1 (NPHP1)
locus. Neither of his parents have kidney disease.
His parents are now considering the possibility of
having another child. They are interested in learning
the potential risk for nephronophthisis with
future pregnancies.
Which ONE of the following is the probability
of future offspring developing
nephronophthisis?
A. 100%
B. 50%
C. 25%
D. 0%
What is (C) 25%?
Nephronophthisis is a fully penetrant autosomal recessive kidney disease. Since the child has a deletion on both of the alleles at the NPHP1 locus, it can be inferred that he received one copy of the homozygous deletion at the NPHP1 locus from each parent. Since his parents do not have nephronophthisis, they are each heterozygous for
the deletion at the NPHP1 locus and are carriers. Each parent has a 50% chance of passing the NPHP1 deletion to future offspring. A child would have to receive the NPHP1 deletion from both parents for disease expression to occur (0.5 chance of deletion from father x 0.5 chance of deletion from mother = 0.25 chance of inheriting two deletions). Therefore, there is a 25% chance that each future child would inherit the pathogenic allele from both parents; choice C is correct.
A 62-year-old woman receives a diagnosis of HCV infection after routine screening by her primary care doctor. She was referred to you because CKD screening performed as part of her HCV evaluation demonstrated creatinine 1.4 mg/dl, 21 proteinuria, and 21 hematuria. When evaluated in your office, she has normal vital signs; her repeat laboratory studies confirm a creatinine of 1.4, and 24-hour proteinuria collection demonstrates 2.9 g of proteinuria. Her cryocrit level is 2%. She undergoes a kidney biopsy showing membranoproliferative GN with histologic activity but no crescents. She feels well and is asymptomatic. She has not yet been prescribed any therapy.
Which of the following statements is MOST accurate?
A. A direct-acting antiviral (DAA) regimen, such as sofosbuvir and velpatasvir, and rituximab should be started concurrently because she has an active GN
B. She should be treated with a nonhepatically metabolized DAA regimen because of her kidney disease
C. She should be treated with rituximab first followed by any DAA
D. She should undergo plasmapheresis, rituximab, corticosteroids, and DAA therapy
E. She should be treated with a pangenotypic DAA, and rituximab should not be used, at least initially
What is (E)?
She should be treated with a pangenotypic DAA (including sofosbuvir/velpatasvir or glecaprevir/pibrentasvir); neither of these DAAs need renal adjustment. Given her stable presentation, rituximab should not be used, at least initially, as many patients will achieve remission of glomerulonephritis with cure of HCV alone. Rituximab is indicated for patients who do not respond to DAA (answer option E is correct). The recommended treatment for HCV-associated glomerular disease that is not rapidly progressive is to begin with DAAs alone. Upfront immunosuppression with steroids and rituximab is reserved for patients with aggressive presentation (rapidly progressive glomerulonephritis, pulmonary hemorrhage, symptomatic nephrotic syndrome) (answer option A is incorrect).