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TUTOR - Physiology
  • Test Id: 1957668cfed488b2d0
  • QId: 165263
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A 19-year-old woman, African American descent, comes to clinic for follow up visit. She has been found to have type 1 diabetes mellitus since the age of 12 years of age. She has been using insulin pump for the last 5 years. She reports no hypoglycemic symptoms and has been monitoring blood sugar using flash glucose monitor. She reports infrequent hypoglycemic episodes all being self-managed. She met with an ophthalmologist for eye screening and has no retinopathy. She exercises regularly for 30 mins. Her vitals recording shows BP of 127/66 mmHg. Her BMI is 22.2.  Systemic  examination is unremarkable. 

Her laboratory investigation is as follows.


Characteristic

value

Hemoglobin

13.2 gm/L 

WBC count

7.8 X 103/cubic mm

Platelet count

241 X 103/cubic mm

Segmented Neutrophils 

Lymphocytes

Monocytes

Band neutrophils 

Eosinophils

Basophils

60%

36%

2%

0%

2%

0%

Sr. Sodium

136 mEq/L

Sr. Potassium

4.2 mEq/L

Sr. Creatinine

0.6 mg/dL

eGFR using CKD-EPI

153.1 ml/min/1.73m2

Sr. Bicarbonate

24 mEq/L

Sr. Chloride

101 mEq/L

Total Bilirubin

1.0 mg /dL

AST

16 U/L

ALT

18 U/L

Sr. Albumin

4.0 g/dL

HBA1C

8.2%

Sr. Calcium

10 mg/dL

Urine dipstick

pH- 5.4

Albumin-nil

 no blood

 no WBCs

24-hour urinary protein 

86 milligrams/day

 

What is the MOST LIKELY False statement regarding renal hyper filtration stage of Diabetic Kidney Disease in this patient?

A. Renal hyper filtration is attenuated by SGLT2 inhibition.
B. Renal hyper filtration occurs in both type 1 and type 2 diabetes mellitus.
C. Obesity can also lead to single-nephron hyper filtration.
D. Incretins like GLP-1 and GIP are neutral in terms of altering renal hemodynamics unlike SGLT2 blockers.

The Correct Answer is Option D : Incretins like GLP-1 and GIP are neutral in terms of altering renal hemodynamics unlike SGLT2 blockers.


Supra-physiologic elevation in GFR is observed early in the natural history of type 1 and type 2 diabetes mellitus which is due to glomerular hyperfiltration. Pathogenesis of hyper filtration in diabetes is complex with a prominent role for hyperglycemia and distorted insulin levels especially in early diabetes and pre-diabetes.Dilatation of the afferent (pre-capillary) glomerular arteriole plays an important role in the hyper-filtration response, by raising both the intra-glomerular pressure and renal blood flow.

 

The effect of incretins can be demonstrated by experiment using GLP-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase (DPP)–4 inhibitors which are associated with renal hemodynamic effects, potentially beyond glycemic control. These observations have been attributed to a GLP-1–mediated inhibition of NHE3 (which assembles with DPP-4 in the proximal tubular brush border), thereby reducing proximal sodium reabsorption and GFR through activation of TGF (tubuloglomerular feedback).


Option A :  In an 8-week study, empagliflozin in T1DM patients with whole-kidney hyper filtration (mean GFR 172±23 ml/min per 1.73 m2) demonstrated a glucose-independent 19%decrease in GFR, which was associated with a decline in ERPF (estimated renal plasma flow) and estimated glomerular pressure and increase in afferent arteriolar resistance, as assessed by the Gomez equations. SGLT2 inhibition could reduce (single-nephron) hyperfiltration in diabetes by restoring sodium-chloride concentration at the macula densa and subsequent TGF mediated afferent arteriolar vasoconstriction.

 

Option B : Reported prevalence of hyper filtration at the whole-kidney level vary greatly: between 10% and 67% in type 1 diabetes mellitus (T1DM) (with GFR values up to 162 ml/min per 1.73 m2), and 6%–73% in patients with type 2 diabetes (T2DM) (up to 166 ml/min per 1.73 sq. m. 


Option C: Independent of diabetes and glucose levels, body weight also augments GFR (by about 15% in obese to about 56% in severely obese non-diabetic subjects).

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Created On: 10/31/2018
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TUTOR - Glomerulonephritis
  • Test Id: 1957668cfed488b2d0
  • QId: 165246
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A 32 year-old male is brought to renal clinic with history of hematuria, oedema feet, and puffiness of face. He gives a history of fever and sore throat a week ago. He also complains of breathlessness on exertion and oliguria. Physical examination shows: Pulse 100/min, BP 150/100 mm Hg, and Temp. 37.4 C. He is pale. He has puffiness of face and oedema feet. Systemic examination-unremarkable. Laboratory examination is as follows:

Hb   10.5 g/d

Hct   34%

Platelet 250,000 mm3

WBC  8,000 mm3

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

ESR  9.8 mm/h


Urinalysis:

Protein   3000 mg/24 h

Glucose   None

RBC   50-60/hpf Dysmorphic

WBC   occasional

Leukocyte Esterase Negative

Nitrites   Negati

BUN   40 mg/dL

Creatinine  3.9 mg/dL

Sodium   140 mEq/L

Potassium  4.2 mEq/L

Bicarbonate  25.5 mEq/L

S. protein  5.5 g/dl

S. Albumin  2.5 g/dl

Calcium   9.2 mEq/L

Phosphorus  3.2 mg/dL

Glucose   100 mg/dL

Uric Acid   5.3 mg/dL

C 3    Low

C4     normal

HBsAg /HIV   Neg

ANA    Neg

Kidney Biopsy: Shows enlarged Glomeruli, lobular accentuation, mesangial hypercellularity, endo-capillary proliferation and double contour along the capillary wall. IF shows bright C3 in mesangium and capillary wall with absent immunoglobulin staining. 

Electron Microscopy: Suggestive of dense deposits.

What is the BEST treatment option for this patient?


A. Plasma exchange + Rituximab 
B. Rituximab 
C. Eculuzimab
D. Cyclophosphamide + Steroids 
The correct answer is C

Eculuzimab

Explanation:

This patient has nephritic-nephrotic picture with low C3. The Kidney biopsy along with clinical presentation is suggestive of MPGN. Negative Immunoglobulins along with positive C3 staining narrows it down to DDD (DENSE DEPOSIT DISEASE) or C3-GN (C3-GN GLOMERULONEPHRITIS)

DDD or Dense deposit disease is best treated with Eculuzimab. 
Rituximab has not been found to be useful in DDD or C3-GN. 

ECULUZIMAB : has been shown to be useful in:
1. DDD
2. Atypical HUS – used along with plasma exchange. If using Eculuzimab give meningococcal vaccine or give penicillin till the vaccine becomes effective.

However, (additional information not pertaining to this question)

RITUXIMAB : has been shown to be useful in:
1. ANCA vasculitis (can be used in induction or relapse – RAVE TRIAL)
2. Wegeners
3. HCV cryoglobulinemia
TTP

***** TREATMENT OPTIONS IN GLOMERULONEPHRITIS WITH RITUXIMAB AND ECULUZIMAB ARE FREQUENTLY TESTED CONCEPTS IN NEPHROLOGY BOARD EXAMS. PLEASE REVIEW THESE IN DETAIL.*****


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Created On: 09/20/2017
Last Modified: 08/06/2018

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TUTOR - CKD / ESRD / MBD
  • Test Id: 1957668cfed488b2d0
  • QId: 165264
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A 68-year-old gentleman, Caucasian descent, comes to clinic for follow up visit. He is known to have type 2 diabetes mellitus for the past 18 years. His father had diabetes from 40 years of age and developed kidney disease requiring dialysis after 15 years of diabetes. He reports no symptoms. He has been having hypertension and coronary artery disease with history of  PCI 2 years ago. He has non-proliferative diabetic retinopathy. His medications are sitagliptin, gliclazide and metformin in addition to losartan and hydrochlorothiazide. He has been monitoring blood sugar at home and reports no hypoglycemia. He exercises at least at least 30 minutes per day. His vitals recording shows BP of 168/66 mm Hg. His BMI is 29.2.  Systemic  examination is unremarkable.

His laboratory investigation is reported as follows.

Characteristic

value

Hemoglobin

12.2 gm/L

WBC count

6.8 X 103/cubic mm

Platelet count

241 X 103/cubic mm

Segmented Neutrophils

Lymphocytes

Monocytes

Band neutrophils

Eosinophils

Basophils

60%

36%

2%

0%

2%

0%

Sr. Sodium

139 mEq/L

Sr. Potassium

4.9 mEq/L

Sr. Creatinine

1.2 mg/dL

Sr. Bicarbonate

22 mEq/L

Sr. Chloride

101 mEq/L

Total Bilirubin

1.0 mg /dL

AST

16 U/L

ALT

18 U/L

Sr. Albumin

4.0 g/dL

HBA1C

7.8%

Sr. Calcium

10 mg/dL

Urine dipstick

pH- 5.4

Albumin-trace

 no blood

 no WBCs

24-hour urinary albumin

200 milligrams/day


What is the MOST LIKELY correct statement regarding clinical diagnosis of Diabetic Kidney Disease in this patient ?

A. Diabetic Kidney Disease previously called as diabetic nephropathy can be diagnosed clinically with renal biopsy only.  
B. Presence of microalbuminuria is adequate for clinical diagnosis of Diabetic Kidney Disease. 
C. Presence of hematuria without non-diabetic kidney disease is impossible in Diabetic Kidney Disease as diabetic kidney disease is a non-proliferative glomerular disease. 
D. Family history of Diabetic Kidney Disease is associated with renal involvement in Diabetes.

The Correct Answer is Option D: Family history of Diabetic Kidney Disease is associated with renal involvement in Diabetes.

 Explanation:

Familial studies have demonstrated clustering of diabetic nephropathy. Patients with DM with a first-degree relative with T1/T2DM and diabetic nephropathy have more risk for developing diabetic nephropathy than those without an affected relative. This familial clustering has also been well documented in the Pima Indian population. The candidate genes identified are glucose transporter 2(GLUT2), transforming growth factor beta (TGF- ?), and endothelial nitric oxide synthase (eNOS). 

Option A:  Diabetic nephropathy is a clinical syndrome characterized by the following:

·         Persistent albuminuria (>300 mg/d) that is confirmed on at least 2 occasions 3-6 months apart

·         Progressive decline in the glomerular filtration rate (GFR)

·         Elevated arterial blood pressure 

 Hence kidney biopsy is not a mandatory investigation to diagnose diabetic kidney disease.

 Option B:  If the amount of urine albumin exceeds 30 mg/d and is less than 300 mg/d it is called microalbuminuria, and if it is greater than 300 mg/d it is called macro albuminuria or overt albuminuria. Microalbuminuria is present in 5-7% of normal individuals and is associated with cardiovascular mortality and morbidity. It is marker of endothelial dysfunction in type 2 diabetes mellitus. Presence of microalbuminuria alone with diabetes cannot be clinically diagnostic of diabetic kidney disease.

Option C:  Micro hematuria has been demonstrated in biopsy studies with isolated diabetic nephropathy. Red blood cell casts have also been described in patients with diabetic nephropathy. However, it is important to rule out other glomerular and extra-glomerular causes of hematuria.

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TUTOR - PHARMACOLOGY
  • Test Id: 1957668cfed488b2d0
  • QId: 16521
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As per the JNC VIII committee recommendation, for individuals that are part of the African American population, including those with diabetes, the initial treatment should include a thiazide type diuretic or calcium channel blocker (CCB).  

Which of the following thiazide type diuretic is preferred as the initial antihypertensive therapy?

 

A. Hydrochlorthiazide 
B. Chlorthalidone 
C. Indapamide 
D. Metalazone 
E. Polythiazide 
The correct answer is B 
Chlothalidone

Explanation:

• Chlorthalidone at the same dose is approximately 1.5 to 2 times as potent as hydrochlorothiazide.

• Chlothalidone has a longer duration action than hydrochlorothiazide.

• There are No randomized clinical trials that directly compare outcomes in hypertensive patients treated with hydrochlorothiazide versus chlorthalidone. A multiple treatment (network) meta-analysis of nine trials including 50,946 patients was conducted in which hydrochlorothiazide and chlorthalidone were indirectly compared by evaluating their efficacy against common comparative drugs (ACE inhibitors were compared with hydrochlorothiazide in ANBP2 trial and with chlorthalidone in ALLHAT trial). The major findings of this meta-analysis showed that chlorthalidone significantly reduced the risk of cardiovascular events compared to hydrochlorothiazide (relative risk 0.79, 95% CI 0.72 to 0.88) and heart failure (relative risk 0.77, 95% CI 0.61 to 0.98). The authors calculated that 27 patients would need to be treated with chlorthalidone instead of hydrochlorothiazide over five years to prevent one cardiovascular event. Chlorthalidone remained superior to hydrochlorothiazide even after the meta-analysis was controlled for achieved office systolic blood pressure (relative risk for cardiovascular events 0.82, 95% CI 0.70 to 0.97). This finding may reflect the longer duration of action and lower nocturnal blood pressure associated with chlorthalidone.

• Multiple Risk Factor Intervention Trial (MRFIT) - Men Hypertensive 2392 were treated with chlorthalidone and 4049 were treated with hydrochlorothiazide. During six years of follow-up, cardiovascular events (defined as myocardial infarction, stroke, coronary artery bypass surgery, heart failure, left ventricular hypertrophy, peripheral artery disease, or angina) were significantly less common with chlorthalidone compared with hydrochlorothiazide (hazard ratio 0.79, 95% CI 0.68 to 0.92). Through the course of the study, systolic blood pressure and LDL cholesterol levels were also lower with chlorthalidone compared with hydrochlorothiazide. 

• Indapamide - is a thiazide like diuretic and has a half-life of 14-16 hours. This drug has been used in HYVET trial alone or in combination with perindropril in treatment of hypertension in patients more than 80 years old. Study showed 30% reduction in stroke, 39% reduction in the rate of death .21%in death from any cause, 23%reduction in CV death and 64%reduction in the rate of heart failure. The trial has shown careful BP lowering in very elderly is beneficial. Indapamide is not preferred over chlorthalidone.

• Metalazone - There are many studies with metalazone available. An important additional property is its effectiveness as a diuretic at lower GFR value. The duration of action is about 24 hours.
It is not preferred over chlorthalidone.

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Last Modified: 10/28/2024

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TUTOR - Tubular / Cystic / Miscellaneous
  • Test Id: 1957668cfed488b2d0
  • QId: 167320
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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
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

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Created On: 09/13/2017
Last Modified: 12/30/2017

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TUTOR - Hypertension
  • Test Id: 1957668cfed488b2d0
  • QId: 165212
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The ACCOMPLISH trial is the first major trial addressing the issue of combination therapy in 11,506 patients who were at high cardiovascular risk. The goal blood pressure was less than 130/80 mm Hg in the patients with diabetes or impaired renal function, and less than 140/90 mm Hg in the patients with prior cardiovascular disease.

Which of the following combinations of blood pressure medications was the best in reducing cardiovascular events and slowing the progression of nephropathy in patients with hypertension who were at high risk for such events?

A. ACEI + Diuretics
B. ACEI + CCB 
C. ACEI + Beta-blocker 
D. CCB + Beta-blocker 
The correct answer is B
ACEI + CCB

Explanation:

• The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension  - (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality.

• ACCOMPLISH ACCOMPLISH was a double-blind, randomized trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals.

• The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization.

• The benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events.

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Last Modified: 01/25/2021

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TUTOR - Glomerulonephritis
  • Test Id: 1957668cfed488b2d0
  • QId: 165242
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A 60 year-old with recently diagnosed colon cancer and diabetes presents with bilateral pedal edema, BP is 120/80 mm Hg, Urinalysis showed  4+ protein, no RBCs or WBCs, and 8-10 Hyaline casts. His BUN is 20, Creatinine is 1 mg/dL, and albumin is 2 grams/dL. 24 hour urine collection showed 10 grams protein. The patient undergoes kidney biopsy. The EM is shown below :


What is the most likely diagnosis?

A.  Crescentic GN
B.  IgA nephropathy
C.  Minimal change disease
D.  Focal segmental glomeruloscerosis
E.  Membranous nephropathy
E. Diabetic nephropathy

The correct answer is E

Membranous Nephropathy.

The Electron microscopy shows subepithelial electron dense deposit as classically seen in membranous nephropathy. If in the question there is a suggestion of colon, breast, or lung cancer, then the glomerulopathy is usually membranous. After that look for other findings on histopathology which will confirm the diagnosis. Subepithelial electron dense deposits.

Explanation:

BOARD POINT - FAMILIARIZE YOURSELF WITH THESE ASSOCIATIONS :

1. Solid cancers (colon, breast, lung, renal) plus proteinuria = Membranous nephropathy

2. Hodgkins lymphoma plus proteinuria = Minimal change disease

3. HIV plus proteinuria = Focal segment glomerulosclerosis FSGS

4. Pamidronate plus protenuria = FSGS (rare)

5. Myeloma, no albuminuria on dipstix, but proteinuria on protein/creatinine ratio or 24 hrs urine: Light chain nephropathy

6. Myeloma with non specific proteinuria (on dipstix, urine protein/creatinine ratio and 24 hrs urine): Light chain nephropathy or amyloidosis.


BOARD POINT - FAMILIARIZE YOURSELF WITH THESE HISTOPATHOLOGY ASSOCIATIONS FOR VARIOUS GLOMERULAR DISEASES



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Last Modified: 08/29/2018

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TUTOR - CKD / ESRD / MBD
  • Test Id: 1957668cfed488b2d0
  • QId: 167339
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All of the following are helpful in predicting AV Graft stenosis EXCEPT:

A. Hyperpulsatility of the AV Graft
B. Ruduced pulse augmentation
C. Increased bleeding and clots 
D. Decreased KT/V
E. Decreased Blood Flow rate
E. Surveillance of the graft
The correct answer is F

Surveillance of the graft

Explanation:

Intra-graft or venous outflow stenosis – A strong pulse in the AV graft - HYPERPULSATILITY suggests an increase in resistance as occurs with a venous stenotic lesion. The intensity of this pulse is directly proportional to the severity of the stenosis. For this reason, in an AV graft Hyperpulsatility can be considered as an indicator of impending AV graft stenosis.

Arterial stenosis – REDUCED PULSE AUGMENTATION suggests inflow stenosis due to stenosis of the arterial anastomosis or of the feeding artery. Although pulse augmentation is commonly performed, it is less sensitive for the detection of inflow stenosis in AV grafts compared with AV fistulas.

INCREASED BLOOD CLOTS, DECREASED KT/V, and DECREASED BLOOD FLOW RATE are all suggestive of impending AV graft stenosis. Often patients are seen with dilated, collateral veins over the arm and chest wall (very important to examine your hemodialysis patients after taking off their shirts) suggestive of central venous stenosis - The classic physical finding in a patient with a significant central venous stenosis is diffuse upper extremity edema. Subcutaneous collateral veins are frequently evident over the chest. Swelling and collateral veins are caused by generalized venous hypertension of the extremity, which occurs in central, but is rare with peripheral lesions. 

SURVEILLANCE  does not predict AV Graft stenosis. It is not a sensitive or specific modality to detect the same accurately.

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Last Modified: 08/06/2018

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TUTOR - CKD / ESRD / MBD
  • Test Id: 1957668cfed488b2d0
  • QId: 1673177
  • 9 of 10
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All of the following are helpful in predicting AV Graft stenosis EXCEPT:

A. Hyperpulsatility of the AV Graft
B. Reduced pulse augmentation
C. Increased bleeding and clots 
D. Decreased KT/V
E. Decreased Blood Flow rate
E. Surveillance of the graft
The correct answer is F
Surveillance of the graft

Explanation:

Intra-graft or venous outflow stenosis – A strong pulse in the AV graft - HYPERPULSATILITY suggests an increase in resistance as occurs with a venous stenotic lesion. The intensity of this pulse is directly proportional to the severity of the stenosis. For this reason, in an AV graft Hyperpulsatility can be considered as an indicator of impending AV graft stenosis.

Arterial stenosis – REDUCED PULSE AUGMENTATION suggests inflow stenosis due to stenosis of the arterial anastomosis or of the feeding artery. Although pulse augmentation is commonly performed, it is less sensitive for the detection of inflow stenosis in AV grafts compared with AV fistulas.

INCREASED BLOOD CLOTS, DECREASED KT/V, and DECREASED BLOOD FLOW RATE are all suggestive of impending AV graft stenosis. Often patients are seen with dilated, collateral veins over the arm and chest wall (very important to examine your hemodialysis patients after taking off their shirts) suggestive of central venous stenosis - The classic physical finding in a patient with a significant central venous stenosis is diffuse upper extremity edema. Subcutaneous collateral veins are frequently evident over the chest. Swelling and collateral veins are caused by generalized venous hypertension of the extremity, which occurs in central, but is rare with peripheral lesions. 

SURVEILLANCE  does not predict AV Graft stenosis. It is not a sensitive or specific modality to detect the same accurately.

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TUTOR - Kidney Transplantation
  • Test Id: 1957668cfed488b2d0
  • QId: 167345
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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 
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.

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Created On: 09/14/2017
Last Modified: 08/06/2018

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