ABIM Qbank Demo

A 56 year-old male was brought to the emergency room with drowsiness and lethargy. He has been experiencing these for the last 2 days. He complains of a recent history of anorexia, nausea, and vomiting, He has diabetes mellitus and is on glimepiride 1 mg daily for the last 4 years. One week ago he had decreased vision with redness in his right eye. He was treated by his ophthalmologist with drops which seem to have resolved the problem. He currently takes cholecalciferol weekly for osteoporosis. On physical examination his pulse is 80/min, blood pressure is 140/90 mm Hg, respiratory rate is 20/min, and temperature is 97.7 F. The patient appears drowsy but shows no focal neurological deficits. Review of systems is otherwise unremarkable. Urinalysis is positive for glucose and negative for proteinuria, WBCs and RBC casts. A 24 hour urinary protein collection is significant for proteinuria of 3.5 g/day. Further labs reveal:

Hemoglobin 8 gm%

Hct 24%

MCV 85

WBC 7800/ml

PMN 80%

Lymphocytes 20%

ESR 80 mm/hr

Na 145 mEq/L

BUN 80 mg/dL

Cr 1.8 mg/dL

CL 115 mEq/L

HCO3 25 mEq/L

Uric acid 5.8 mg/dL

Ca 14 mg/dl

PO4 2.8 mg/dL

Total Protein 7.8 gm/dL

Albumin 3.5 mg/dL.

Vitamin D 40 ng/ml

PTH 10 pg/ml

Which of the following is most likely the cause of his hypercalcemia?

		A. Vitamin D toxicity
		B. Primary hyperparathyroidism
		C. Multiple myeloma.
		D. Sarcoidosis

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.

Explanation:

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.

Copyright © ABIM Exam World
Created On: 09/12/2017
Last Modified: 03/07/2021

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.

Explanation:

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).

Copyright © ABIM Exam World
Created On: 10/31/2018
Last Modified: 10/23/2020

An 18 year-old male is brought to the renal clinic for evaluation of hypertension. There is no history of edema of the feet, puffiness of the face, hematuria, oliguria ,or recurrent urinary tract infections. He is an active football player, but lately he complains of weakness and muscle cramps. His blood pressure for the last 3-4 years has always been borderline high and during this visit was as noted below.

Physical examination shows: Pulse 100/min, all peripheral pulsations are well felt. BP 150/100 mm Hg, Temp. 37.4 degrees C. He is pale. His growth is stunted. His cognitive function is normal and no focal neurological deficits are noted. Other systems are unremarkable. Laboratory examination is as follows:

Hemoglobin 13.5 g/dL

Hematocrit 42%

Platelet Count 150,000 mm3

White Blood Cells 8,000 mm3

Urinalysis:

Protein 100 mg/24 h

Glucose None

Red Blood Cells None

White Blood Cells None

Leukocyte Esterase Negative

Nitrites Negative

Chemistry:

BUN 13.5 mg/dL

Creatinine 0.9 mg/dL

Sodium 140 mEq/L

Potassium 5.8 mEq/L

Bicarbonate 18.5 mEq/L

Chloride 112 mEq/l

Calcium 9.2 mEq/L

Phosphorus 3.2 mg/dL

Aldosterone 5 ng/mL

PRA <1.0ng/dl/hr

Glucose 100 mg/dL

HbA1C 5.30%

S. Osmolality 282 mOsmol

Uric Acid 5.3 mg/dL

ESR 9.8 mm/h

ABG:

pH 7.25

PCO2 32 mm Hg

HCO3 16 mEq/L

PO2 90 mm Hg

USG Normal size kidneys, no hydronephrosis

Considering the history and the laboratory findings, which of the following is most likely the cause of hypertension in this patient?

		A. Liddle's Syndrome
		B. Gordon's Syndrome
		C. Congenital adrenal hyperplasia
		D. Glucocorticoid-remediable aldosteronism
		E. Mineralocorticoid receptor activating mutation

Explanation:

The correct answer is B

Gordon’s syndrome

Explanation:

Gordon’s syndrome - Young male with hypertension, hyperkalemia, hyperchloremic metabolic acidosis, normal renal function, low rennin, and low aldosterone is highly characteristic of Gordon’s syndrome. This syndrome is also known as pseudohypoaldosteronism type II. Recently it has been reported that Gordon’s syndrome is linked to chromosomes 1, 12, and 17. Hyperkalemia and hypertension in Gordon’s syndrome are caused by abnormalities in WNK kinases, proteins that are localized to the distal nephron and affect the thiazide-sensitive Na-Cl Cotransporter. Mutations affecting either WNK4 or WNK1 result in increased chloride reabsorption in the distal nephron, thereby reducing lumen electronegativity and lowering the force for potassium secretion. These mutations also result in decreased expression of the potassium channels through which potassium enters the collecting duct. Thus, mutant WNK4 increases sodium chloride reabsorption in the distal tubule and decreases potassium secretion in the collecting tubule resulting in sodium retention and decreased potassium excretion resulting in hypertension, hyperkalemia, and metabolic acidosis. The volume expansion leads to suppression of rennin and aldosterone.

(Choice A) Liddle’s syndrome presents as hypertension in childhood. It is usually resistant to standard antihypertensive drugs. This is due to gain of function mutation at chromosome 16 affecting the beta or gamma subunit of ENaC channel in collecting duct of the nephron. This results in sodium retention and volume expansion causing hypertension and hypokalemia. The volume expansion leads to suppression of rennin and aldosterone. These patients will have hypertension, hypokalemia, metabolic alkalosis, low rennin and low aldosterone.

(Choice C) Congenital adrenal hyperplasia presents in childhood with hypertension and virilization in girls and precocious puberty in boys. The other features include primary amenorrhea, delayed sexual maturation, ambiguous genitalia, with clitoral enlargement in girls. The 11 beta hyroxylase (CYP11B1) and (17 alpha hydroxylase (CYP17) deficiencies lead to excess deoxycoticosterone which leads to hypertension through a mineralocorticoid action. Biochemically it is characterized by metabolic alkalosis, low rennin and low aldosterone.

(Choice D) Glucocorticoid-remediable aldosteronism (GRA) is also known as familial hyperaldosteronism type I. In this disorder there is a chimeric gene formed from portions of the 11-beta-hydroxylase gene (CYP11B2) and the aldosterone synthase gene (CYP11B2). Patients with GRA have ectopic aldosterone synthesis occurring in the zona - fasciculata under the direct influence of ACTH rather than the renin. GRA presents with hypertension, hypokalemia, metabolic alkalosis, low rennin and high aldosterone. GRA resembles a primary hyperladosterone state with excessive urinary potassium loss. Look for a clue of family history of CVA or brain haemorrhage in the stem of the question.

(Choice E) Mineralocorticoid receptor activating mutation is a very rare autosomal dominant disorder. The mutation lies in the mineralocorticoid receptor, which causes it to be activated by steroid lacing 21 –hyroxyl groups, such as progesterone and spironolactone. Both normally antagonize the receptor but have opposite effect on this mutant receptor. It usually present as early onset hypertension in females. It may get accelerated during pregnancy due to elevated levels of progesterone. Biochemically it is characterized by hypokalemia, metabolic alkalosis low renin and low aldosterone.

Educational objective:

IF YOU KNOW THESE 5 POINTS FOR THESE 5-6 SYNDROMES YOU CAN ANSWER ALL NEPHROLOGY BOARD QUESTIONS ASKED ON THESE SYNDROMES:

Blood pressure - Normotension or hypertension

Potassium - Hyperkalemia or hypokalemia

Acid-Base - Acidosis or alkalosis

Renin - Low or High

Aldosterone - Low or High

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