ABIM Qbank Demo

A 25 year-old female is referred by her primary care provider for evaluation of hypertension and hypokalemia. The primary care provider has already started her on oral potassium, despite therapy her Potassium being 2.8 meq/L. Her blood pressure despite treatment with amlodipine and Lisinopril 154/96 mm of Hg. There is no renal bruit. Systemic and fundus examinations are normal. Her mother was also diagnosed with hypertension at an early age. Her brother died of a cerebrovascular accident 2 years ago. Laboratory findings are as follows:

Na 140

Potassium 2.8

Chloride 100

HCO3 26

BUN 15

Creatinine 0.8

Glucose 110

TSH and Cortisol are normal

ACTH elevated

Renin 0.7 (Low)

Aldosterone 48 (elevated)

Urinalysis:

Sodium 240 mEq/D

Potassium 98 mEq/D

Urinary 18-OH Cortisol and 18-oxocortisol are elevated.

The most appropriate treatment for this patient is:

		A. Steroids
		B. Spironolactone
		C. Steroids + Spironolactone
		D. Amiloride

Cyclosporine nephrotoxicity in a renal transplant recipient is associated with all the below renal biopsy findings EXCEPT:

(THIS PICTURE BELOW IN LOW POWER SHOWS ONE OF THE CLASSICAL FINDINGS IN CSA TOXICITY)

		A. Interstitial Fibrosis
		B. Tubular atrophy
		C. Endothelial cell swelling
		D. Glomerular thrombin deposits
		E. Glomerular basement membrane thickening
		E. Double contours of the GB

Explanation:

The correct answer is D

Glomerular thrombin deposits

Explanation:

In a patient with suspected cyclosporine nephrotoxicity, the renal biopsy reveals an obliterative arteriolopathy (which is classically seen in afferent renal arterioles) suggesting primary endothelial damage and subsequently endothelial cell swelling which may persist for months in a patient with elevated cyclosporine blood levels. This is also associated with thickened glomerular basement membrane and double contour pattern. In fact according to BANF thickened glomerular basement membrane and double contour pattern is most suggestive of chronic allograft nephropathy (CAN) also called as TRANSPLANT GLOMERULOPATHY.

The other renal biopsy findings of cyclosporine nephrotoxicity include ischemic collapse or scarring of the glomeruli, vacuolization of the tubules, FSGS, and focal areas of tubular atrophy and interstitial fibrosis (producing a picture of “ZEBRA” or "STRIPED" fibrosis) These changes are seen with both low-dose and higher-dose cyclosporine therapy, although they seem to co-relate earlier with higher doses.

(THE ABOVE PICTURE IN THE UPPER HALF SHOWS TUBULAR ATROPHY APPEARING DARK AND REDDISH ALTERNATING WITH LIGHT BLUE AREAS OF INTERSTITIAL FIBROSIS GIVING A "STRIPED" OR "ZEBRA" APPEARANCE)

THE PICTURE BELOW SHOWS TUBULAR ATROPHY, VACUOLIZATION OF THE TUBULES AND ISCHEMIC CHANGES:

Mild arteriolar hyalinosis at six months appears to be associated with high doses of cyclosporine and was reversible. However, after more than a year irreversible severe arteriolar hyalinosis and glomerulosclerosis were observed, despite decreased doses and trough levels of cyclosporine.

Glomerular thrombin deposits are typically seen in patients with Lupus, anti phospholipid syndromes and other vasculitides. It is typically not seen in cyclosporine nephrotoxicity.

Copyright © ABIM Exam World
Created On: 09/14/2017
Last Modified: 08/06/2018

A 36 year-old female was diagnosed as having membranous nephropathy secondary to SLE. Her 24 hour protein excretion was 7.5 gms/day. Her serum creatinine was 0.9mg/dl. She was started on 500 mg of cyclophosphamide IV every 15 days (Euro-Lupus) and prednisolone 1 mg/kg orally per day. After 3 months of therapy, she presented with decreased urine output, puffiness of face, and oedema feet. On physical examination, her temperature is 37 C, blood pressure is 160/100 mm Hg, pulse is 90/min, and respiration rate is 20/min. She is anemic and there is puffiness of the face and oedema of the feet. On systemic examination air entry was decreased in the bases of both the lung fields and heart sounds are distant and feeble. Chest X-Ray reveals bilateral pleural effusions. Echocardiogram reveals mild to moderate pericardial effusion. Laboratory examination is as follows:

Hemoglobin 10.0 g/dL

Hematocrit 34%

Platelet Count 150,000 mm3

WBC 8,000 mm3

Differential count P 80% L 12% E 6% M 2%

ESR 50.8 mm/h

Urinalysis:

Protein 1450 mg/24 h

Glucose None

RBCs 70-80/HPF dysmorphic

WBCs 5-8/HPF

Leukocyte Esterase Negative

Nitrites Negative

BUN 35 mg/dL

Creatinine 3.9 mg/dL

Sodium 140 mEq/L

Potassium 5.2 mEq/L

Bicarbonate 15.5 mEq/L

Calcium 9.2 mEq/L

Phosphorus 5.6 mg/dL

Glucose 100 mg/dL

Uric Acid 5.3 mg/dL

C3 & C4 decreased

ANA positive

dsDNA positive

Repeat biopsy shows:

Which of the following is the most appropriate therapy for her current condition?

		A. Mycophenolate and steroid
		B. Mycophenolate, tacrolimus and steroids
		C. Rituximab
		D. I.V Immunoglobulins
		E. Plasma exchange

Explanation:

The correct answer is B

Mycophenolate, tacrolimus and steroids

Explanation:

This patient had membranous lupus being treated with Euro-Lupus regime. Activity in the urine with a positive ANA and dsDNA and low C3, C4 suggests activity of the disease. The biopsy is showing active lupus nephritis combined with features of class IV & V diffuse proliferative GN. Patients with both DPGN and membranous lesions are more likely to be resistant to standard induction regimens with cyclophosphamide or MMF with steroids. In these patients, combined treatment with MMF and tacrolimus is recommended. This was suggested by Bao H. et al in a small, short term prospective trial in which 40 patients with diffuse proliferative plus membranous lupus nephritis were randomly assigned to induction therapy with MMF (0.75g to 1g/d) and tacrolimus (3-4 mg/d) or intravenous cyclophosphamide alone .All patients received steroids. At nine months there was significantly higher rate of complete remission in patients treated with MMF and tacrolimus as compared to cyclophosphamide (65% versus 15%).

(Choice A) Mycophenolate and steroids can be used in patients who have received cyclophosphamide and are resistant to it.

(Choice C and D) Rituximab and I.V. Immunoglobulins can be used in patients with lupus nephritis who have failed to respond to cyclophosphamide, MMF and steroids.

(Choice E) Plasma exchange is recommended in patients with SLE and (TTP).

KDIGO Clinical Practice Guidelines for Glomerulonephritis recommends the following treatment for resistant lupus nephritis:

Treatment of resistant disease 12.9.1: In patients with worsening S. Cr and/or proteinuria after completing one of the initial treatment regimens, consider performing a repeat kidney biopsy to distinguish active LN from scarring. (Not Graded) 12.9.2: Treat patients with worsening S. Cr and/or proteinuria who continue to have active LN on biopsy with one of the alternative initial treatment regimens. If patient has received cyclophosphamide use MMF and if patient has received MMF use cyclophosphamide (Not Graded) 12.9.3

KDIGO suggests that non -responders who have failed more than one of the recommended initial regimens (cyclophosphamide, MMF or CNI) may be considered for treatment with rituximab, IV Immunoglobulins, or CNIs. (2D).

Copyright © ABIM Exam World
Created On: 09/20/2017
Last Modified: 08/06/2018

A 25 year-old male comes to the physician complaining of flank pain and hematuria. He says the pain is constant and dull. There is no frequency, urgency or dysuria. He has a history of mental retardation and seizures. On physical exam his blood pressure is 140/90 mm Hg, and his pulse is 80 bpm. He has multiple yellow papules across his nose and cheeks and numerous areas of blanched skin spots on his face. A 2-3 cm hypopigmented macule is noted on the right arm. CT scan of the head was done as patient presented with seizures. CT head was reported normal. CT scan of the abdomen shows bilateral hypodense fat containing renal masses and cysts.

What is the MOST likely diagnosis associated with these findings?

		A. Von Hippel Lindau
		B. Sturge Weber Syndrome
		C. Tuberous Sclerosis
		D. Osler Weber Rendu
		E. Neurofibromatosis type 2

Explanation:

The correct answer is C

Tuberous Sclerosis

Explanation:

This patient’s skin lesions are consistent with sebaceous adenomas. The findings of mental retardation, sebaceous adenomas and seizures are most consistent with tuberous sclerosis. Tuberous sclerosis is associated with renal angiomyolipomas and renal cysts. Abdominal CT can diagnose these tumors as the density of fat is less than that of water. In patients with flank pain and hematuria there is an increased likely of co-existing renal cysts. Based on presentation and findings this is tuberous sclerosis, the other choices are less likely as explained below.

(Choice A) Bilateral renal cell carcinoma is associated with Von Hippel Lindau disease. Imaging is not suggestive of renal cell cancer.

(Choice B) Leptomeningeal Angiomas are cerebral malformations commonly found in Sturge-Weber Syndrome. CT head is normal in this patient.

(Choice D) Osler Weber Rendu is an autosomal dominant disease associated with telangectasias of the mucosal surfaces as well as AVM’s in the brain, GI tract and lung. Again clinical presentation and imaging is not suggestive of this diagnosis.

(Choice E) Neurofibromatosis type 2 is an autosomal dominant condition associated with acoustic neuromas, gliomas and ependymomas. Skin shows neurifibromas but other associations favor the diagnosis of tuberous sclerosis.

ASSOCIATED FINDINGS IN TUBEROUS SCLEROSIS --

(This patient has majority of these as bolded below)

o Bilateral renal angiomyolipomas (Fat containing renal masses on CT scan)

o Renal Cysts

o Astrocytomas

o Cortical tubers

o Ash-leaf spots on skin

o Sebaceous adenomas on face

o Seizures

o Mental retardation

IMPORTANT TOPIC FROM RENAL BOARD POINT OF VIEW

You are rounding on your patients in the dialysis unit and seeing a 65-year-old gentleman with ESRD due to chronic interstitial disease. He also has a history of diet-controlled diabetes mellitus and hypertension. His other past medical history is significant for dyslipidemia, coronary artery disease, hypothyroidism, gout and depression. He has been hospitalized in the recent past for swelling and pain of his right great toe. He was seen by the foot doctor, a scan was done and eventually the great toe had to be amputated. He has been on hemodialysis 3 times a week. His weekly Kt/V is 1.9. You are conducting the monthly blood work review for this patient. You note that his hemoglobin has been persistently low for past few monthly blood draws. He is currently on 100 mcg of Darbepoetin weekly on dialysis. On enquiry there is no history of blood loss in the form of hematemesis, melena, hematochezia or hemoptysis. His active medication list includes Losartan, Atorvastatin, Calcitriol, multivitamin supplements, paroxetine, allopurinol, aspirin.

His pertinent blood work is as follows:

Test	Result
WBC	4500 cells /cumm
Hemoglobin	8.2 g/dL
Platelet count	450 thousand /cumm
Reticulocyte count	Normal
Iron	55 (range 50-150)
Total iron binding capacity	250 g/dl (range 250-310)
Transferrin saturation	20%
Ferritin	1400 ng/ml (range 20-235)
Haptoglobin	400 mg/dl (range 83-267)
Lactate dehydrogenase	240 U/L (range 80-225)
Total bilirubin	1.0 mg/dl
Folate	7 ng/ml (range 1.8-9.0)
B12	500 pg/ml (range 200-800)
Peripheral blood smear.	Normal RBC morphology, few burr cells.

Which of the following is true about this patient’s anemia?

	Erythropoietin deficiency. Check EPO levels.
	ESRD patients tend to have low Hepcidin production due to renal failure. This contributes to anemia.
	This patient has chronically inflamed state and this is contributing to his anemia.
	Patient has developed pure red cell aplasia.
	Patient is under dialysed. Start daily dialysis to overcome EPO resistance.

Explanation:

Correct Answer: Option C: This patient has chronically inflamed state which is contributing to his anemia.

Explanation:

10-15% of patients who have been receiving erythrocyte estimating agents (ESA) develop resistance. There are multiple reasons why ESRD patients develop resistance.

ESA resistance occurs due to the following reasons:

Iron deficiency.
Chronic inflammation.
Under-dialysis.
Hemolysis.
Folate and B12 deficiency.
Chronic blood loss.
Anti EPO antibodies.
Pure red cell aplasia.
Failed chronic renal allograft.
ACEI/ARB.
Aluminum overload.
Hyperparathyroidism.
Hematological disorders or malignancy.

Option A: Incorrect option. ESRD is associated with erythropoietin deficiency. Patient has been initiated on ESA already. There is no point in measuring EPO levels. There is no evidence of measuring EPO levels in management of anemia in CKD.

Option B: Incorrect option. ESRD is an inflamed state. In inflammatory milieu there is increased production of Hepcidin. The hepatic iron-regulatory hormone Hepcidin and its receptor, the cellular iron exporter Ferroportin, constitute a feedback-regulated mechanism that maintains adequate plasma concentrations of iron-transferrin for erythropoiesis and other functions, ensures sufficient iron stores, and avoids iron toxicity. In chronic kidney disease, inflammation and impaired renal clearance increases plasma hepcidin, inhibiting duodenal iron absorption and sequestering iron in macrophages. These effects of hepcidin can cause systemic iron deficiency, decreased availability of iron for erythropoiesis, and resistance to endogenous and exogenous erythropoietin.

Choice C: Correct option. Refer explanation for option B. He had pain, swelling of his right great toe, a foot doctor sees him, a bone scan is done and subsequently the amputation. All suggestive of an infective etiology probably osteomyelitis.There is a temporal relationship between patients’ anemia and underlying chronic inflammatory state.

The high ferritin is also suggestive of inflamed state.

Choice D: Incorrect option. Pure red cell aplasia, a form of severe ESA hypo-responsiveness mediated by anti-erythropoietin antibodies, was first reported with certain formulations of Epoetin alfa but has now been reported with all commercially available forms of ESA. This syndrome presents with rapid onset of severe anemia (hemoglobin <7 g/dl), severe reticulocytopenia (reticulocyte count <10,000/?l) and marked elevations in serum ferritin level (>1000 ng/ml) and transferrin saturation (>70%) resulting from low iron utilization. Pure red cell aplasia is unlikely given the absence of characteristic laboratory findings. Moreover, the patient did not receive Epoetin alfa.

Choice E: Incorrect option. Under-dialysis leads to anemia due the same mechanism mentioned earlier in option B. Under-dialysis worsens the uremic milieu which in turn leads to inflammatory state. This leads to anemia. Patient in this clinical vignette has been dialysed appropriately. His weekly Kt/V is 1.9, which is above the target goal of 1.7