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TUTOR - Glomerulonephritis
  • Test Id: 19509677652d57a277
  • QId: 167274
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A 35 year-old Caucasian male presents with persistent swelling of both legs associated with dark colored urine for two months. He went to an emergency room 2 months ago for these complaints and was told that he has some protein and blood in the urine. He was treated with 3 days of levofloxacin. There is no other past medical history. No history of skin rash or joint swelling. On examination the blood pressure was 130/85 mm Hg and there was bilateral 1+ pedal edema. Rest of the physical examination was normal. Urine analysis showed 3+ proteinuria, 10-15 RBCs per high-power field, and occasional RBC cast. The BUN was 10 mg/dL, serum creatinine was 0.9 mg/dL. Antistreptolysin was negative, C3 level is decreased and C4 level is normal. Antinuclear antibodies, ANCA, hepatitis B and C serology were negative. 24-hour urine collection showed 2 g proteinuria and a kidney biopsy was performed. On light microscopy, kidney biopsy showed increase in the mesangial matrix and cellularity and glomerular basement membrane appeared irregularly thickened. Silver stain revealed duplication of glomerular basement membrane in multiple glomeruli. Immunofluorescence showed positive staining for C3, but negative for IgG, IgM and IgA. Electron microscopy revealed electron-dense deposits in the mesangium and sub-endothelial area. 

What is the most likely diagnosis?

A. Acute poststreptococcal glomerular nephritis
B. Diffuse proliferative lupus nephritis 
C. Dense deposit disease 
D. C3 glomerulopathy 
E.
The correct answer is D
C3 glomerulopathy

Explanation:

This patient has proteinuria, microscopic hematuria, hypertension and edema suggestive of acute nephritis of 2 months duration. The classic prototype of acute nephritis is acute post streptococcal glomerulonephritis. Typically in the acute post infective glomerular nephritis, complement levels normalize in 6 weeks and generally proteinuria and microhematuria resolve in approximately 6 weeks. Hence (Choice A) is wrong. This patient has hypocomplementemia and features of acute nephritis for 2 months suggesting that we should look for other causes of acute nephritis. 

Acute nephritis with low complement levels:
Post-infectious glomerulonephritis
Lupus nephritis
Membranoproliferative glomerular nephritis
Mixed cryoglobulinemia
C3 Nephropathy

Acute nephritis with normal complement levels:
IgA nephropathy
Thin basement membrane disease
Hereditary nephritis
HSP
Mesangial proliferative glomerulonephritis
Lupus nephritis
Membranoproliferative glomerular nephritis
Mixed cryoglobulinemia
Dense deposit disease

This patient is a male and ANA is negative. Lupus is mainly a disease affecting young women in third and fourth decade and most of them are ANA positive. A variety of glomerular pathologies are described, but immunofluorescence typically shows ‘full house’ pattern with positive IgG, IgM, IgA and C3. ANA negativity and not having the IF picture showing full house to suggest lupus nephritis makes lupus nephritis (Choice B) unlikely.

Dense deposit disease is type II MPGN and it mainly affects children and young adults. In the majority of patients there is circulating C3 nephritic factor. Immunofluorescence microscopy demonstrates C3 deposits, and EM shows characteristic sausage-shaped, wavy deposits along the glomerular basement membranes (GBM) and mesangium. Lack of typical EM appearance makes dense deposit disease (Choice C) unlikely.

C3 Glomerulopathy is a morphologic variant of MPGN type I. In “C3 glomerulopathy”, different light microscopy pathologies such as mesangioproliferative, membranoproliferative glomerulonephritis, diffuse proliferative glomerulonephritis, crescentic GN and Sclerosing GN has been described. C3 level is usually low and C4 level is normal. In Sclerosing disease, C3 level can also be normal. The distinct feature of this is that IF shows exclusively C3 deposits, without any immunoglobulins. EM does not show sausage shaped intra-membranous deposits. Hence, the  correct choice is (Choice D).

C3 glomerulopathy can present with varying degrees of proteinuria, azotemia and can advance to ESRD. It can recur after transplantation.

Educational Objective:
C3 glomerulopathy can present with varying degrees of proteinuria, azotemia and can advance to ESRD. It can recur after transplantation.
C3 glomerulopathy is a morphologic variant of MPGN type I. The distinct feature of this is that IF shows exclusively C3 deposits, without any immunoglobulins. EM does not show sausage shaped intra-membranous deposits.

IMPORTANT BOARD EXAM ADVICE:

1. Differentiate between DDD and C3GN
2. Know the glomerulonephritis with low and normal complement levels.
3. BOARD QUESTIONS will be asked on DDD and C3GN, so know it well.

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  • Test Id: 19509677652d57a277
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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 - Glomerulonephritis
  • Test Id: 19509677652d57a277
  • 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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TUTOR - Hypertension
  • Test Id: 19509677652d57a277
  • 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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TUTOR - Hypertension
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  • QId: 165233
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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 
The correct answer is C

Steroids + Spironolactone

Explanation:

This patient has (GRA) – Glucocorticoid Remediable Aldosteronism. These are typically young patients presenting with hypertension and hypokalemia. There is strong family history of early onset hypertension along with a history of fatal CVA or hemorrhagic strokes. These patients typically have low Renin and high Aldosterone mimicking a state of primary hyperaldosteronism. Because of this they have high urinary potassium losses as manifested in this patient. (Urinary potassium of more than 40mEq/D is considered increased losses). Increased ACTH and 18-OH cortisol further support the diagnosis of GRA.

Steroids alone are used in the treatment of Pregnancy associated mineralocorticoid excess and congenital adrenal hyperplasia. Steroids alone in this patient will suppress ACTH but this patient also needs an aldosterone antagonist for the hyperldosterone state and to reduce urinary potassium losses. Hence, the right answer is steroids plus spironolactone.

Spironolactone alone is not sufficient, as steroids are needed to suppress the increased ACTH state. 

Amiloride blocks the EnaC channel in Liddle’s syndrome.

PLEASE NOTE THAT "GRA" IS A FREQUENTLY ASKED QUESTION IN NEPHROLOGY BOARD EXAMS

PLEASE REVIEW GLUCOCORTICOID REMEDIABLE ALDOSTERONISM WELL. 

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  • Test Id: 19509677652d57a277
  • QId: 167274
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A 35 year-old Caucasian male presents with persistent swelling of both legs associated with dark colored urine for two months. He went to an emergency room 2 months ago for these complaints and was told that he has some protein and blood in the urine. He was treated with 3 days of levofloxacin. There is no other past medical history. No history of skin rash or joint swelling. On examination the blood pressure was 130/85 mm Hg and there was bilateral 1+ pedal edema. Rest of the physical examination was normal. Urine analysis showed 3+ proteinuria, 10-15 RBCs per high-power field, and occasional RBC cast. The BUN was 10 mg/dL, serum creatinine was 0.9 mg/dL. Antistreptolysin was negative, C3 level is decreased and C4 level is normal. Antinuclear antibodies, ANCA, hepatitis B and C serology were negative. 24-hour urine collection showed 2 g proteinuria and a kidney biopsy was performed. On light microscopy, kidney biopsy showed increase in the mesangial matrix and cellularity and glomerular basement membrane appeared irregularly thickened. Silver stain revealed duplication of glomerular basement membrane in multiple glomeruli. Immunofluorescence showed positive staining for C3, but negative for IgG, IgM and IgA. Electron microscopy revealed electron-dense deposits in the mesangium and sub-endothelial area. 

What is the most likely diagnosis?

A. Acute poststreptococcal glomerular nephritis
B. Diffuse proliferative lupus nephritis 
C. Dense deposit disease 
D. C3 glomerulopathy 
E.
The correct answer is D
C3 glomerulopathy

Explanation:

This patient has proteinuria, microscopic hematuria, hypertension and edema suggestive of acute nephritis of 2 months duration. The classic prototype of acute nephritis is acute post streptococcal glomerulonephritis. Typically in the acute post infective glomerular nephritis, complement levels normalize in 6 weeks and generally proteinuria and microhematuria resolve in approximately 6 weeks. Hence (Choice A) is wrong. This patient has hypocomplementemia and features of acute nephritis for 2 months suggesting that we should look for other causes of acute nephritis. 

Acute nephritis with low complement levels:
Post-infectious glomerulonephritis
Lupus nephritis
Membranoproliferative glomerular nephritis
Mixed cryoglobulinemia
C3 Nephropathy

Acute nephritis with normal complement levels:
IgA nephropathy
Thin basement membrane disease
Hereditary nephritis
HSP
Mesangial proliferative glomerulonephritis
Lupus nephritis
Membranoproliferative glomerular nephritis
Mixed cryoglobulinemia
Dense deposit disease

This patient is a male and ANA is negative. Lupus is mainly a disease affecting young women in third and fourth decade and most of them are ANA positive. A variety of glomerular pathologies are described, but immunofluorescence typically shows ‘full house’ pattern with positive IgG, IgM, IgA and C3. ANA negativity and not having the IF picture showing full house to suggest lupus nephritis makes lupus nephritis (Choice B) unlikely.

Dense deposit disease is type II MPGN and it mainly affects children and young adults. In the majority of patients there is circulating C3 nephritic factor. Immunofluorescence microscopy demonstrates C3 deposits, and EM shows characteristic sausage-shaped, wavy deposits along the glomerular basement membranes (GBM) and mesangium. Lack of typical EM appearance makes dense deposit disease (Choice C) unlikely.

C3 Glomerulopathy is a morphologic variant of MPGN type I. In “C3 glomerulopathy”, different light microscopy pathologies such as mesangioproliferative, membranoproliferative glomerulonephritis, diffuse proliferative glomerulonephritis, crescentic GN and Sclerosing GN has been described. C3 level is usually low and C4 level is normal. In Sclerosing disease, C3 level can also be normal. The distinct feature of this is that IF shows exclusively C3 deposits, without any immunoglobulins. EM does not show sausage shaped intra-membranous deposits. Hence, the  correct choice is (Choice D).

C3 glomerulopathy can present with varying degrees of proteinuria, azotemia and can advance to ESRD. It can recur after transplantation.

Educational Objective:
C3 glomerulopathy can present with varying degrees of proteinuria, azotemia and can advance to ESRD. It can recur after transplantation.
C3 glomerulopathy is a morphologic variant of MPGN type I. The distinct feature of this is that IF shows exclusively C3 deposits, without any immunoglobulins. EM does not show sausage shaped intra-membranous deposits.

IMPORTANT BOARD EXAM ADVICE:

1. Differentiate between DDD and C3GN
2. Know the glomerulonephritis with low and normal complement levels.
3. BOARD QUESTIONS will be asked on DDD and C3GN, so know it well.

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Last Modified: 03/07/2021

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  • Test Id: 19509677652d57a277
  • 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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  • 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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  • Test Id: 19509677652d57a277
  • 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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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 
The correct answer is C

Steroids + Spironolactone

Explanation:

This patient has (GRA) – Glucocorticoid Remediable Aldosteronism. These are typically young patients presenting with hypertension and hypokalemia. There is strong family history of early onset hypertension along with a history of fatal CVA or hemorrhagic strokes. These patients typically have low Renin and high Aldosterone mimicking a state of primary hyperaldosteronism. Because of this they have high urinary potassium losses as manifested in this patient. (Urinary potassium of more than 40mEq/D is considered increased losses). Increased ACTH and 18-OH cortisol further support the diagnosis of GRA.

Steroids alone are used in the treatment of Pregnancy associated mineralocorticoid excess and congenital adrenal hyperplasia. Steroids alone in this patient will suppress ACTH but this patient also needs an aldosterone antagonist for the hyperldosterone state and to reduce urinary potassium losses. Hence, the right answer is steroids plus spironolactone.

Spironolactone alone is not sufficient, as steroids are needed to suppress the increased ACTH state. 

Amiloride blocks the EnaC channel in Liddle’s syndrome.

PLEASE NOTE THAT "GRA" IS A FREQUENTLY ASKED QUESTION IN NEPHROLOGY BOARD EXAMS

PLEASE REVIEW GLUCOCORTICOID REMEDIABLE ALDOSTERONISM WELL. 

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

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