SeanWu25/NEJM-AI_Benchmarking_Medical_Language_Models huggingface dataset:
Subject: Primary and Secondary Glomerular Diseases

A 59-year-old man with no known history of kidney disease experiences AKI, with a serum creatinine of 2.7 mg/dL and eGFR of 24 mL/min per 1.73m2. He has a urine protein/creatinine ratio of 2.2 g/g. He has no hematuria. A serologic workup is performed and includes a negative antibody testing for HIV, hepatitis C, hepatitis B, and serum anti-PLA2R. Serum protein electrophoresis, serum immunoﬁxation, serum kappa-lambda free light chain assay, urine protein electrophoresis. and urine immunoﬁxation tests are pending. He undergoes kidney biopsy, which shows membranoproliferative glomerulonephritis on light microscopy and immunoﬂuorescence microscopy showing staining for IgG (3+), kappa (2+), lambda (2+). and C3 (3+). Electron microscopy is pending, but an immunohistochemical stain for DnaJ homolog subfamily B member 9 (DNAJB9) is positive..
Question: Which of the following statements is true about DNAJB9-positive ﬁbrillary glomerulonephritis?
1. The majority of patients with DNAJB9-positive ﬁbrillary glomerulonephritis have an underlying lymphoproliferative disorder
2. All kidney biopsy specimens should undergo pronase digestion of paraﬃn-embedded tissue in order to evaluate for the presence of “masked” immunoglobulin deposits
3. Congo red staining is required to rule out AL (light chain) amyloidosis
4. DNAJB9 positive ﬁbrillary glomerulonephritis is not an monoclonal gammopathy of renal signiﬁcance (MGRS)-associated lesion, and therefore no hematologic workup is recommended
Answer: D
Subject: Primary and Secondary Glomerular Diseases

A 73-year-old man with no known history of kidney disease presents to the hospital with abdominal fullness, a new rash, and decreased urine output. On examination, he is found to have nonblanching palpable purpura on his upper and lower extremities and new lower extremity edema. He also exhibits splenomegaly and has palpable bilateral cervical lymphadenopathy on examination. He reports occasional fevers and night sweats. His serum creatinine on admission labs is 3.4 mg/dL (eGFR 17 mL/min/1.73 per m2).His urinalysis results are signiﬁcant for 3+ protein and 3+ blood, with 20 to 50 red blood cells per high powered ﬁeld on urine microscopy, including the presence of dysmorphic red blood cells. Antinuclear antibody, anti-myeloperoxidase and anti–serine proteinase 3 antibody test results are negative, as are antibodies for HIV, hepatitis B, and hepatitis C. He undergoes kidney biopsy..
Question: What is the most likely diagnosis?
1. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID-Ig)
2. Pauci-immune, necrotizing, and crescentic glomerulonephritis
3. Type I cryoglobulinemic glomerulonephritis
4. Type II cryoglobulinemic glomerulonephritis
Answer: C
Subject: Primary and Secondary Glomerular Diseases

A 67-year-old man with metastatic melanoma was recently prescribed treatment with nivolumab. Two months after initiation of therapy, he experienced an acute rise in serum creatinine from 1 mg/dL to 2.8 mg/dL. Renal biopsy revealed severe tubulointerstitial nephritis that was attributed to the immune checkpoint inhibitor..
Question: What is the best management strategy?
1. Continue nivolumab and initiate glucocorticoids
2. Hold nivolumab and monitor kidney function
3. Hold nivolumab and initiate glucocorticoids
4. Change nivolumab to ipilimumab
5. Immune checkpoint inhibitors should be permanently discontinued
Answer: C
Subject: Primary and Secondary Glomerular Diseases

A 64-year-old-woman is prescribed the tyrosine kinase inhibitor sunitinib for renal cell cancer. Three months after initiation of treatment, she is noted to be newly hypertensive with a BP of 160/92 mmHg. Urinalysis reveals 3+ proteinuria, and a sub-sequent 24-hour urine collection yielded 3.7 g protein. A urinalysis from 4 months prior was unremarkable. Her serum creatinine has increased from 0. 9 mg/dL at baseline to 1.3 mg/dL, and her serum albumin is 3.1 g/dL. She undergoes renal biopsy for diagnostic evaluation..
Question: What is the most likely ﬁnding?
1. Thrombotic microangiopathy
2. Collapsing FSGS
3. Membranous nephropathy
4. AA amyloidosis
Answer: B
Subject: Primary and Secondary Glomerular Diseases

A 76-year-old man receives a diagnosis of multiple myeloma and painful osteolytic bone lesions. His eGFR is 25 mL/min. He is prescribed pamidronate and subsequently experiences nephrotic-range proteinuria. The proteinuria improves after holding further pamidronate..
Question: What is the next best step in the management of his bone disease?
1. Initiate zoledronate
2. Initiate denosumab
3. Rechallenge patient with pamidronate
4. Antiresorptive therapy should be permanently discontinued
Answer: B
Subject: Primary and Secondary Glomerular Diseases

A 34-year-old woman presents to the emergency room with necrotic skin ulcers on her nose and ears, arthralgias, and myalgias. Initial laboratory results are notable for neutropenia and hematuria. A serologic evaluation reveals she has positive titers for both PR3-ANCA and MPO-ANCA..
Question: Double-positive MPO and PR3-ANCA is associated with which of the following?
1. Progression to end-stage renal disease
2. Development of pulmonary hemorrhage
3. Increased risk of mortality
4. Drug-induced AAV
Answer: D
Subject: Primary and Secondary Glomerular Diseases

A 35-year-old man with hypertension is referred for evaluation of decreased GFR. He has one healthy brother; his father has diabetes, hypercholesterolemia, and coronary artery disease; and his mother was treated for breast cancer. His maternal uncle experienced end-stage kidney disease at age 40. His maternal grandmother at age 76 years has a history of mild hearing loss and stage 3a CKD. There is no history of consanguinity. His only medication is hydrochlorothiazide. On examination his BP is 145/88 mmHg, his pulse rate is 70/min, and his body mass index is 29 kg/m2. There is no peripheral edema, and there are no actively inﬂamed joints. Laboratory studies show creatinine 2.0 mg/dL, BUN 55 mg/dL, sodium 140 meq/L, potassium of 5.0 meq/L, total CO2 21 meq/L, hemoglobin 126 g/L, leukocytes 7.8 e9/L, platelets 292 e9/L, hemoglobin A1C 6.5%. His ANA, HIV, ANCA and hepatitis serology, and complement levels are all normal or negative. Urinalysis has 2+ blood, negative protein, and negative nitrites. Urinary albumin/creatinine ratio was 160 mg/g. His creatinine 1 year ago was 1.8 mg/dL..
Question: What is the MOST likely mode of inheritance of this condition?
1. Autosomal dominant
2. Autosomal recessive
3. X-linked recessive
4. De novo somatic mutation
Answer: C
Subject: Primary and Secondary Glomerular Diseases

A 27-year-old man presents with persistent subnephrotic proteinuria without hematuria or reduced GFR. Marked podocyte deposition of globotriaosylceramide (GB3) is observed..
Question: Which model best demonstrates a pathophysiologic pathway of Fabry disease?
1. GLA mutation, α-galactosidase A deﬁciency, GB3 accumulation
2. GLA mutation, β-galactosidase A deﬁciency, GB3 accumulation
3. GLA mutation, α-galactosidase A deﬁciency, lyso-GB3 accumulation
4. GLA mutation, β-galactosidase A deﬁciency, lyso-GB3 accumulation
5. Silencing of X-linked genes, Gb3 accumulation, podocyturia
Answer: C
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

A 46-year-old woman presents with fatigue, weakness, and dyspnea in the setting of viral illness for 2 weeks. Her medical history is remarkable for longstanding Raynaud syndrome and migraine headaches. Medications include topiramate and ibuprofen. Her serum phosphate is 0.3 mmol/L (1 mg/d). Other laboratory values are notable for serum bicarbonate of 16 mEq/L..
Question: What is the next best test to evaluate the role of renal phosphate wasting in this patient’s hypophosphatemia?
1. Serum parathyroid hormone (PTH) and ﬁbroblast growth factor-23 (FGF23) concentrations
2. Serum protein electrophoresis and light chains
3. Fractional excretion of phosphate
4. Tubular maximal reabsorption of phosphate/GFR in a second morning urine after an overnight fast
Answer: D
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

You are following a 54-year-old woman with polycystic kidney disease and eGFR 15 mL/min per 1.73m2. Her son is a potential kidney donor but is a soldier currently deployed in Afghanistan. Your patient does not want him to donate a kidney until his active service is over because she is afraid his remaining kidney will be injured. Both the patient and her son wish to avoid dialysis at all costs. Her creatinine is 3.9 mg/dL. Her serum phosphate is 5.9 mg/dL. She is not on any phosphate binders. She asks you to explain the science behind dietary phosphate restriction so she can adjust her diet..
Question: Which of the following is true regarding intestinal phosphate absorption?
1. It does not matter whether the source of phosphate is processed food, dairy products or vegetables as long as the total amount of phosphate is the same.
2. Unlike processed foods, the bioavailability of phosphate in whole grains is very high.
3. When dietary phosphate is high, the passive paracellular route of phosphate absorption is less important in determining the serum phosphate concentration than the closely regulated transport-mediated transcellular pathway.
4. The expression of the sodium driven phosphate transporter NaPi-IIb increases when dietary phosphate is low.
Answer: D
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

You are asked to evaluate hypophosphatemia in a 39-year-old woman who has ESRD due to IgA nephropathy, and recently received a deceased donor kidney allograft. Anti-rejection medications include prednisone, mycophenolate and tacrolimus. She is also on trimethoprim/sulfamethoxazole and omeprazole..
Question: Which of the following statement is true regarding this patient’s phosphate balance?
1. Her medications have no eﬀect on phosphate balance
2. Her hypophosphatemia is most likely unrelated to her kidney disease or transplant status
3. Her phosphate concentration is maintained by intestinal absorption, internal shifts and renal excretion
4. A phosphate sensing molecule has been identiﬁed in humans and underlies post-transplantation hypophosphatemia
Answer: C
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

A 70-year-old diabetic man is evaluated in the emergency department because of 2 days of paresthesia and muscle cramps. His medical history is notable for adenocarcinoma of the prostate since 2017, treated initially with docetaxel chemotherapy, androgen deprivation therapy, and cholecalciferol followed by denosumab because of tumor progression and bone metastatic disease; denosumab 120 mg subcutaneously every 4 weeks was started earlier. Two weeks before his presentation to the emergency department, he was hospitalized with urinary tract infection and AKI secondary to obstruction. He was treated with parenteral ceftriaxone for 7 days and discharged with a long-term urinary indwelling catheter after receiving denosumab. Laboratory data at the time of the discharge showed hemoglobin of 10.0 g/dl, serum sodium of 138 mEq/L, potassium of 4.0 mEq/L, glucose of 80 mg/dl, albumin of 3.4 g/dl, BUN of 60 mg/dl, creatinine of 2.1 mg/dl, serum calcium of 7.0 mg/dL, phosphorus of 2.4 mg/dl, PTH of 90 pg/ml (reference range 12–72 pg/ml), and 25-hydroxyvitamin D level of 12 ng/ml (reference range 20–100 ng/ml)..
Question: What is the most likely diagnosis?
1. Denosumab-induced hypocalcemia
2. Denosumab-induced worsening of kidney function
3. Denosumab-induced hyperphosphatemia
4. Ceftriaxone-induced interstitial nephritis with consequent worsening of kidney function
Answer: A
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

A 27-year-old man presents for evaluation of recurrent nephrolithiasis. He has had four stones since he was 17 years old, requiring lithotripsy twice. His father and brother also have kidney stones. A 24-hour urine demonstrates a volume of 3.2 L and abnormally high urine calcium..
Question: Which of the following proteins regulate calcium excretion and have been associated with increased stone risk?
1. Polycystin 2
2. Claudin
3. Klotho
4. FGF23
Answer: B
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

A 6-year-old girl was referred to a renal pediatric service because of polydipsia, polyuria, and the ﬁnding of nephrocalcinosis on abdominal ultrasonography. Laboratory ﬁndings were notable for eGFR of 55 ml/min per 1.73 m2, hypomagnesemia (1.25 mg/dl; reference range, 1.6–2.6 mg/dl), elevated fractional excretion of magnesium (Fe Mg, 11%; reference range, < 4%), hypercalciuria (13 mg/kg per day; reference range, < 4 mg/kg per day), hypocitraturia (95 mg/day; reference range, 300–600 mg/day), and elevated serum PTH in serum (120 pg/ml; reference range, 10–65 pg/ml). She had received a diagnosis of myopia magna and macular coloboma at the age of 4 years. Her parents were cousins, and her 20-year-old brother had recently received a diagnosis of advanced chronic kidney disease (CKD)..
Question: Which ONE of the following genetic abnormalities best explains this clinical condition?
1. A loss of function mutation in the calcium-sensing receptor gene
2. A gain of function mutation in the calcium-sensing receptor gene
3. A loss of function mutation in the CLDN19 gene
4. A loss of function mutation in the CLDN16 gene
Answer: C
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

A 40 year-old man with a history of well-controlled HIV infection presented to his routine evaluation with a 2-month history of irritability and polyuria. He had no history of opportunistic infection, his viral load was undetectable, and his CD4+ T cell count was 600 (reference range, 410–1590 × 106/L). His medications were abacavir/lamivudine/dolutegravir. Laboratory workup disclosed creatinine of 2.5 mg/dl and albumin-corrected serum calcium of 15.1 mg/dl (conﬁrmed twice). He denied use of illicit drugs, vitamin supplements, calcium, or diuretics. Computed tomography of the chest, abdomen, and pelvis showed nodular soft tissue densities in both buttocks. The patient conﬁrmed a history of cosmetic injections with polymethylmethacrylate for HIV lipodystrophy 3 months before the onset of symptoms. Serum PTH was 5 pg/ml (reference range, 12–72 pg/ml)..
Question: At this point, which ONE of the following would you recommend next?
1. Measuring PTH-related protein
2. Measuring 1,25 dihydroxyvitamin D
3. Measuring serum and urine protein electrophoreses with immunoﬁxation
4. Measuring 25 dihydroxyvitamin D
Answer: B
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

A 45-year-old man with ESKD who had been using maintenance hemodialysis for 10 years received a diagnosis of severe and refractory hyperparathyroidism and was referred to your service for a parathyroidectomy. Laboratory values were calcium 11 mg/dl, phosphorus 7.5 mg/dl, PTH 1300 pg/ml (reference range, 12–72 pg/ml), and alkaline phosphatase 450 U/ml (reference range, 36–92 U/ml), serum albumin 3.2 g/dl. Six hours after surgery, his serum calcium dropped to 7.2 mg/dl..
Question: Which ONE of the following is most likely a risk factor for his hypocalcemia?
1. Hyperphosphatemia
2. Hypoalbuminemia
3. Hypercalcemia
4. High serum alkaline phosphatase
Answer: D
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

A 46-year-old woman is being evaluated in clinic for stage 4 CKD and is found to have mild hyperphosphatemia with a phosphorus of 4.5 mg/dl..
Question: On the basis of results from the COMBINE trial, which ONE of the following statements is correct?
1. Addition of nicotinamide to lanthanum carbonate is more eﬀective than lanthanum carbonate alone for lowering se-rum PTH in patients with stage 4 CKD
2. Lanthanum carbonate therapy can be expected to lower serum FGF23 concentrations by at least 30% in patients with stage 4 CKD
3. Lanthanum carbonate plus nicotinamide should be considered as a ﬁrst-line therapy for reducing serum phosphorus in patients with stage 4 CKD
4. Treatment with lanthanum carbonate either alone or in combination with nicotinamide has little eﬀect on serum PTH in patients with stage 4 CKD
Answer: D
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

A 62-year-old man with a history of hypertension, peripheral vascular disease, and ESKD requiring long-term maintenance hemodialysis therapy is seen during routine dialysis rounds. His medication regimen includes cinacalcet 30 mg, calcium acetate 2001 mg with meals, and paricalcitol 4 µg three times per week. Recent laboratory results show a serum calcium of 10.8 mg/dl, serum phosphorus of 5.0 mg/dl, and serum PTH of 475 pg/ml..
Question: Which ONE of the following medication changes would be MOST appropriate at this time?
1. Change calcium acetate to sevelamer carbonate
2. Increase paricalcitol dose to 6 µg thrice weekly
3. Reduce calcium acetate to 1334 mg with meals
4. Increase cinacalcet dose to 60 mg daily
Answer: A
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

It has been demonstrated that vitamin D, phosphate, and calcium are all important regulators of parathyroid gland biology..
Question: Which ONE of the following statements is correct?
1. Paricalcitol lowers PTH production by enhancing the binding of calcium to the calcium-sensing receptor
2. Cinacalcet blocks the binding of PTH to its receptors in bone
3. Cinacalcet stimulates the degradation of circulating PTH
4. Phosphate increases PTH production by reducing binding of calcium to the calcium-sensing receptor
Answer: D
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

In a recent large epidemiologic study that analyzed data collected from patients with CKD over several decades, the association between serum PTH and several key clinical outcomes was studied..
Question: Which ONE of the following best describes the observed associations with high concentrations of PTH in univariate and multivariate analyses?
1. Increased risk of fracture, no increased risk of all-cause mortality
2. Increased risk of fracture, increased risk of vascular events, increased risk of mortality
3. No increased risk of fracture, increased risk of vascular events, no increased risk of all-cause mortality
4. No increased risk of fracture, increased risk of vascular events, increased risk of all-cause mortality
Answer: B
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis
Question: Question 5756
For which ONE of these dialysis patients would a bone biopsy be most likely to help make a correct diagnosis?
1. A 58-year-old woman with pruritis and recent distal radius fracture, PTH level of 750 ng/ml, serum phosphate level of 5.9 mg/dL, serum calcium level of 10.3 mg/dL.
2. A 40-year-old man who had noticed pain in his thigh when he stands and had previously been treated with aluminum hydroxide for severe hyperphosphatemia. Radiographs of the hands show subperiosteal resorption. PTH is 290 ng/L; serum phosphate is 5.4 mg/dl.
3. A 64-year-old woman with diabetes who underwent a parathyroidectomy 3 years ago and who fractured her hip after a fall when she tripped over a root Her serum calcium is 8.9 mg/dl, phosphate is 4.1 mg/dL, PTH is 56 pg/ml, and bone alkaline phosphatase is low (15 µg/L).
4. A 50-year-old man with a stress fracture of his femoral neck. He has a history of obesity and underwent a gastric bypass procedure 10 years ago. His laboratory studies show PTH of 450 ng/L, calcium of 7.1 mg/dl, phosphate of 3.5 mg/dl, 25-hydroxy-vitamin D level of 12 ng/ml, and alkaline phosphatase of 300 IU/L.
Answer: B
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

A 53-year-old woman with stage 4 CKD is diagnosed with osteoporosis after a radial fracture. She is already taking phosphate binders and is taking calcitriol for treatment of secondary hyperparathyroidism. Her primary care physician suggests that she start taking a bisphosphonate, and when she comes to see you, she asks about the eﬀect of these agents on bone formation..
Question: In patients treated with bisphosphonates, which of the following is correct?
1. The bone formation rate does not change because bisphosphonates decrease the bone resorption rate
2. The bone formation rate decreases to levels that are average for normal people
3. The bone formation rate gradually decreases over approximately 6 months and then remains at a rate that is below normal
4. The bone formation rate increases because of stimulation of PTH
Answer: C
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

Low levels of klotho have been associated with cardiovascular disease in CKD, and treatment with klotho is being investigated in preclinical models of cardiovascular disease..
Question: What action of soluble klotho raises the concern that supplementation could have a negative eﬀect on bone?
1. Klotho can act as a coreceptor for FGF23 on the parathyroid cells and reduce PTH
2. In early stages of CKD, klotho could act as a coreceptor for FGF23 on renal tubular cells to increase the excretion of phosphate
3. Klotho decreases calcium reabsorption in the distal tubule, causing high urine calcium
4. Klotho inhibits Wnt signaling by blocking the frizzled receptor, and this reduces the number of osteoblasts
Answer: D
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

The term “bone turnover” can be expressed as the bone formation rate if there is coupling between resorption and formation..
Question: In which of these clinical situations is it most likely that the bone formation rate and the bone resorption rate will be approximately the same?
1. A patient with high PTH and increased calcium and alkaline phosphatase
2. A patient who has been treated with glucocorticoids, who has some metabolic acidosis and weight loss
3. A patient who has experienced multiple myeloma and has evidence of skeletal lesions on magnetic resonance imaging
4. A patient who received a bisphosphonate injection 3 weeks before the biopsy
Answer: A
Subject: Disorders of Divalent Ions, Renal Bone Disease and Nephrolithiasis

A 49-year-old biophysicist with polycystic kidney disease has been receiving hemodialysis for 4 years while awaiting trans-plantation. He has an abdominal plain radiograph during an emergency department evaluation for abdominal pain. The abdominal pain turns out to be related to constipation, and he is discharged from the emergency department..
Question: He reads the radiology report online, which notes “extensive calciﬁcation observed in the tunica media of the aorta.” He asks you, “What caused this problem?”
Which of the following statements is most accurate regarding the development of vascular calciﬁcation?
1. Secondary calciprotein particles (CPP-II) form as kidney function declines and as result of decreases in expression of fetuin-A and ƴ-linolenic acid—rich protein, and induce osteoblast diﬀerentiation of vascular smooth muscle cells.
2. The removal of extracellular vesicles from serum increases the calciﬁcation of vascular smooth muscle cells in both uremic and nonuremic individuals.
3. Increased phosphate concentration is necessary and suﬃcient for vascular calciﬁcation.
4. Patients receiving hemodialysis invariably experience vascular calciﬁcation.
Answer: A