Board Review PracticeMust Know Clinical

Images for the Boards 2021

Ajay K. Singh, MBBS, FRCPRenal Attending, Brigham and Women’s Hospital

Senior Associate Dean for Postgraduate Medical Education Harvard Medical School

Ajay K. Singh Bio▪Attending Nephrologist, Brigham

and Women’s Hospital

▪Senior Associate Dean for Postgraduate Medical Education, Harvard Medical School

▪Research interests: Anemia of CKD and CKDu

▪Clinical interests: managing patients with CKD

Disclosures

▪ Stock: Gilead

▪ Consulting: GSK

A 64-year-old man admitted with fever, dyspnea, and acute kidney injury.

Presents with a 4-day h/o fever (≈39oC) and shaking chills. No chest pain, orthopnea, or leg swelling. No recent travel. Works as a bus driver but no known contact with anyone with confirmed SARS-CoV-2 infection.

History of diabetes, hypertension, CAD, and obesity.

Exam: T 37.90C, BP 122/80 mm Hg (non-orthostatic), HR 105 bpm, RR 42/min, O2 sat 94% on RA. BMI 38. NL skin turgor. No edema

Labs: BUN/Cr 30/1.8, 1-year earlier Scr 0.8 mg/dL.

Chem: K 4.6 mEq/L, Phos 2.6

CBC: WNL. INR 1.2, CK 22

COVID PCR pending

UA: No hematuria, trace prot. USED muddy brown casts

Renal Ultrasound: no hydronephrosis

CASE 1

SOURCE: https://tidsskriftet.no/en/2020/05/kronikk/diagnostic-imaging-covid-19-

patients

This patient has COVID-19 and AKI. The most likely cause for the AKI is:

A.) Volume depletion

B) ATN related to COVID-19

C) Collapsing glomerulopathy from COVID-19

D.) COVID-19 related microangiopathy

E.) Acute obstruction

SOURCE: https://tidsskriftet.no/en/2020/05/kronikk/diagnostic-imaging-covid-19-

patients

This patient has COVID-19 and AKI. The most likely cause for the AKI is:

A.) Volume depletion

✓B) ATN related to COVID-19

C) Collapsing glomerulopathy from COVID-19

D.) COVID-19 related microangiopathy

E.) Acute obstruction

SOURCE: Nadim, M.K., Forni, L.G., Mehta, R.L. et al. COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup. Nat Rev Nephrol 16, 747–764 (2020). https://doi.org/10.1038/s41581-020-00356-5

• Nadim, M.K., Forni, L.G., Mehta, R.L. et al. COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup. Nat Rev Nephrol 16, 747–764 (2020). https://doi.org/10.1038/s41581-020-00356-5

A 69 year old woman

with 3 months onset of

malaise and weakness

presents anemia (Hb 8.9

g/dL), diffuse achiness

in her bones and on

work-up a Scr of 3.8

mg/dL. A renal biopsy is

performed. What’s the

diagnosis?

A. Light chain

deposition disease

B. Phosphate

nephropathy

C. Uric acid nephropathy

D. Cast nephropathy

E. Fibillary

glomerulonephritis

CASE 2

A 69 year old woman with

3 months onset of

malaise and weakness

presents anemia (Hb 8.9

g/dL), diffuse achiness in

her bones and on work-

up a Scr of 3.8 mg/dL. A

renal biopsy is

performed. What’s the

diagnosis?

A. Light chain deposition

disease

B. Phosphate

nephropathy

C. Uric acid nephropathy

✓ D. Cast nephropathy

E. Fibillary

glomerulonephritis

CASE 2

D. Cast nephropathy

•Multiple myeloma is the malignant proliferation of plasma cells involving >10

percent of the bone marrow

• Bone pain related to multiple lytic lesions is the most common clinical

presentation. Upto 30 percent of patients are diagnosed incidentally while

being evaluated for unrelated problems

•1/3rd of patients are diagnosed after a pathologic fracture, commonly of the

axial skeleton.

•Overproduction of light chains → tubular capacity for reabsorption is

exceeded. Filtered light chains & immunoglobulins then bind Tamm-Horsfall

glycoprotein (secreted in the medullary TAL of the loop of Henle).

•Cast formation & obstruction in the distal nephron

A 52-year-old-female underwent thoracoabdominal resection of a right

adrenal cancer, right periadrenal lymph node dissection, and resection of

the inferior vena cava. Baseline Scr 0.9 mg/dL. 10 days after surgery,

presents with R flank pain, foul smelling brownish drainage (from her

drain that had been in place from the time of surgery). BP140/82 mmHg, T

1000 F. WBC 17.89 1000/, hematocrit 22.9% Scr 1.6 mg/dL. This syndrome

is:A.) Alagille syndrome

B.) Page Kidney

C.) Benjamin Syndrome

D.) Brodie Abscess

CASE 3

A 52-year-old-female underwent thoracoabdominal resection of a right

adrenal cancer, right periadrenal lymph node dissection, and resection of

the inferior vena cava. Baseline Scr 0.9 mg/dL. 10 days after surgery,

presents with R flank pain, foul smelling brownish drainage (from her

drain that had been in place from the time of surgery). BP140/82 mmHg, T

1000 F. WBC 17.89 1000/, hematocrit 22.9% Scr 1.6 mg/dL. This syndrome

is:A.) Alagille syndrome

✓ B.) Page Kidney

C.) Benjamin Syndrome

D.) Brodie Abscess

CASE 3

B. Page Kidney

•In 1955, Engel and Page reported a case of hypertension associated with a

renal subcapsular hematoma in a football player who had sustained blunt

trauma to the flank. This was the first clinical correlate to Page’s 1939 study

of hypertension induced in dogs by wrapping one or both kidneys with

cellophane.

•Any external compression of the kidney can cause renal hypoperfusion

and ischemia. Causes include bleeding secondary to trauma, surgery, a cyst

or tumor.

•CT of the abdomen is the preferred imaging modality because renal

ultrasound may not be sufficiently sensitive to detect a small compressive

subcapsular hematoma.

•In the case presented here, Tc-99m MAG3 renal scan was used to assess

the differential (split) renal function.

Alagille syndrome is a genetic disorder that affects the liver, heart,

kidney, and other systems of the body. Problems associated with

the disorder generally become evident in infancy or early

childhood. The disorder is inherited in an autosomal dominant

pattern,

Benjamin Syndrome (or Benjamin anemia) is a type of multiple

congenital anomaly/mental retardation (MCA/MR) syndrome. It is

characterized by hypochromic anemia with mental deficiency and

various craniofacial and other anomalies.[1] It can also include

heart murmur, dental caries and splenic tumors.[2]

A Brodie abscess is a subacuteosteomyelitis, which may persist

for years before converting to a frank osteomyelitis. Classically,

this may present after conversion as a draining abscess extending

from the tibia out through the shin.

A 58-year old patient with a 12-year history

of T2DM HbA1C of 8.2, HTN and

hyperlipidemia is referred for management of

a Scr of 1.4 mg/dL and UACR of 3.8 g/g cr.

Already being treated with lisinopril 40 mg/d,

amlodipine 10 mg/day, and furosemide 40

mg/d. A renal biopsy performed 1 year back

is shown. On exam: BP 132/60 mmHg, HR 70

bpm. Trace to 1+ edema. What is the next

best step?

A.) Tell the patient that other than better

control of his diabetes he is on all the

right treatments

B.) Tell the patient that an SGLT2

inhibitor and a MRA should be

considered

C.) Tell the patient that a referral for

kidney transplant evaluation

D.) Perform another kidney biopsy to

confirm the diagnosis

E.) Consider adding an angiotensin

receptor antagonist to his treatment

regimen

CASE 4

A 58-year old patient with a 12-year history

of T2DM HbA1C of 8.2, HTN and

hyperlipidemia is referred for management of

a Scr of 1.4 mg/dL and UACR of 3.8 g/g cr.

Already being treated with lisinopril 40 mg/d,

amlodipine 10 mg/day, and furosemide 40

mg/d. A renal biopsy performed 1 year back

is shown. On exam: BP 132/60 mmHg, HR 70

bpm. Trace to 1+ edema. What is the next

best step?

A.) Tell the patient that other than better

control of his diabetes he is on all the

right treatments

✓ B.) Tell the patient that an SGLT2

inhibitor and a MRA should be

considered

C.) Tell the patient that a referral for

kidney transplant evaluation

D.) Perform another kidney biopsy to

confirm the diagnosis

E.) Consider adding an angiotensin

receptor antagonist to his treatment

regimen

CASE 4

▪ Diabetic nephropathy

▪ Renal amyloidosis

▪ Monoclonal immunoglobulin deposition disease

▪ Cryoglobulinemia glomerulosclerosis

▪ Fibrillary glomerulonephritis

▪ Immunotactoid glomerulonephritis

▪ Idiopathic nodular glomerulosclerosis

Differential Diagnosis of Nodular Changes

▪ ACEI/ARB

▪ Treat BP – goal BP <130/80, multiple agents will be needed

▪ SGLT2 inhibitor (T2D and non-diabetic patients)

▪ MRA – Finerenone

▪ Manage diabetes

▪ Consider other interventions: low protein diet, statin

Keys to Managing CKD with T2DM

ACEi and ARBs

• ACEi and ARB have similar antiproteinuric effects

• Combination of ACEi and ARB: 20% reduction in albuminuria –over and above either agent alone

• Dual blockade not recommended

Newer therapy for renal progression in T2 Diabetics: YES… SGLT2 inhibitors

• Reduction in

HbA1c ≈0.5-1.5%

without inducing

hypoglycaemia

•Weight loss of ≈

2-3kg, (calorie loss

via renal glucose

excretion (loss of

80-85g glucose per

day) at around 6

months

•Decrease SBP ≈2-

5 mmHg

• Double blind RCT, N=4401

• T2D with CKD, eGFR 30-90, UACR 0.3 to 5 g alb/g cr

• Canagliflozin, (SGLT2 inhibitor), at a dose of 100 mg daily vs. placebo

• Median F/U 2.62 years

• Primary Outcome: Reduction ≈ 30% in RR of composite of ESRD

(dialysis, transplantation, or a sustained estimated GFR of <15 ml per

minute per 1.73 m2), a doubling Scr, or death from renal or CVD causes

• Components of Primary endpoint reduction ≈ 30%

• CVD and HF benefits

June 13, 2019

CREDENCE: SGLT2 and T2DM

Percovic V et al N Engl J Med 2019; 380:2295-2306

Both diabetics and non-diabetics benefit from SGLT2 inhibition

Oct 8, 2020

• RCT, N= 4304

• eGFR of 25 to 75 ml/min/1.73 m2, UACR 200 to 5000 mg/d, T2DM

and nonT2DM

• Dapagliflozin (10 mg once daily) vs. placebo.

• Primary outcome: composite of a sustained decline eGFR >50%,

ESRD, or death from renal or cardiovascular causes

• Median FU 2.4 years,

• Fewer primary outcomes in dapa (197 of 2152 participants

(9.2%)) vs. placebo (312 of 2152 participants (14.5%)) (hazard ratio,

0.61; 95% CI 0.51 to 0.72; P <0.001

• Number needed to treat to prevent primary=19

Effect of non-steroidal mineralocorticoid receptor antagonist in CKD and T2DM

• Double blind RCT, N= 5734

• CKD and type 2 diabetes

• Primary composite outcome: kidney failure, sustained decrease of >40% in

the eGFR from baseline, or death from renal causes.

• Median follow-up of 2.6 years

• Fewer primary outcome event in finerenone (504 of 2833 (17.8%)) vs.

Placebo (600 of 2841 patients (21.1%)) HR 0.82; 95% CI0.73 to 0.93;

P=0.001

• Hyperkalemia-related discontinuation of the trial regimen was higher with

finerenone than with placebo (2.3% and 0.9%, respectively)

Dec 3, 2020

A 39-year-old homeless man presented to the emergency department with

anorexia, nausea, vomiting, and oliguria. Five months earlier, he had stopped

attending his regular hemodialysis sessions. On exam, BP167/80 mm Hg,

lethargic, slowed speech and LE edema; breath had urine-like odor.

What is the diagnosis?

A. Retention keratosis

B. Uremic frost

C. Eczema

D. Post-inflammatory desquamation

Q

:

CASE 5

SOURCE: Martins JM et al N Engl J Med 2018; 379:669

DOI: 10.1056/NEJMicm1716367

A 39-year-old homeless man presented to the emergency department with

anorexia, nausea, vomiting, and oliguria. Five months earlier, he had stopped

attending his regular hemodialysis sessions. On exam, BP167/80 mm Hg,

lethargic, slowed speech and LE edema; breath had urine-like odor.

What is the diagnosis?

A. Retention keratosis

✓ Uremic frost

A. Eczema

B. Post-inflammatory desquamation

Q

:

CASE 5

SOURCE: Martins JM et al N Engl J Med 2018; 379:669

DOI: 10.1056/NEJMicm1716367

B. Uremic Frost

• Uremic frost was first described by Hirschsprung in 1865.

• Rarely seen today because of early dialytic intervention.

• Exact incidence is not known.

• Concentration of urea in sweat increases greatly when the blood

urea nitrogen level is high. Evaporation of sweat with high urea

concentration causes urea to crystallize and deposit on the skin.

• To verify that the crystals are composed of urea or nitrogenous

waste, scrapings of the frost can be diluted in normal saline, which

can then be tested for elevated urea nitrogen levels comparable to

blood levels.

Martins JM et al N Engl J Med 2018; 379:669 DOI: 10.1056/NEJMicm1716367 Mohan D et al KI 81, 11 1153: June 1 2002https://www.kidney-

international.org/article/S0085-2538(15)55234-4/

A 22-year old woman

presents with joint and

abdominal pain and a rash.

Rectal exam is positive for

occult blood. Urine shows

hematuria. What is the most

likely diagnosis?

A. Renal cell cancer

B. Renal infarction

C. Kidney stone

D. Goodpasture’s syndrome

E. Henoch-Schonlein

purpura

CASE 7

A 22-year old woman

presents with joint and

abdominal pain and a rash.

Rectal exam is positive for

occult blood. Urine shows

hematuria. What is the most

likely diagnosis?

A. Renal cell cancer

B. Renal infarction

C. Kidney stone

D. Goodpasture’s syndrome

✓ E. Henoch-Schonlein

purpura

CASE 7

D. Henoch-Schonlein purpura

The patient has palpable purpura

and hematuria.

RBCs appear crenated --

dysmorphic red cells.

HSP is an IgA-mediated, small-

vessel vasculitis that

predominantly affects children but

also is seen in adults.

HSP is a subset of necrotizing

vasculitis characterized by

fibrinoid destruction of blood

vessels and leukocytoclastic

vasculitis

Pathology of IgAN/HSP nephritis

HSP nephritisClinical Features

Dermal

Purple, nonblanching,

urticarial, purpuric papules

may become confluent

Bx: leukocytoclastic vasculitis

GI

Abd pain (2/3rds of cases)

may precede rash

Vomiting

Diarrhea

Periumbilical pain

Major complications (5%)

intussusception

bowel ischemia necrosis

Joints

Arthralgias and periarticular edema

(2/3) knees, ankles, elbows, wrists

Renal

33% children, 63% adults

Hematuria

Proteinuria

Azotemia

What is the most likely

diagnosis?

A. Renal tubular acidosis

B. Primary

hypoparathyroidism

C. Familial hypocalciuric

hypercalcemia

D. Salicylate overdose

E. Paget's disease

Q

:

Source Serrano A et al , N Engl J Med 2008; 359:e1July 3, 2008DOI: 10.1056/NEJMicm072776

CASE 8

What is the most likely

diagnosis?

✓ A. Renal tubular acidosis

B. Primary

hypoparathyroidism

C. Familial hypocalciuric

hypercalcemia

D. Salicylate overdose

E. Paget's disease

Q

:

Source Serrano A et al , N Engl J Med 2008; 359:e1July 3, 2008DOI: 10.1056/NEJMicm072776

CASE 8

Answer:

A. Renal tubular acidosis

The film reveals bilateral

symmetric calcification of the

renal parenchyma, sparing only

the renal pelvis.

This patient had been diagnosed

with renal tubular acidosis at 9

years of age, but did not

undergo medical follow-up for 20

years.

The other listed choices are not

common causes of

nephrocalcinosis.

Distal RTA

1. Classical form of RTA (described first)

2. Failure of alfa intercalated cells to secrete H+ and K+

3. Hypokalemia, hypocalecemia, hyperchloremia

4. Urinary stone formation (related to alkaline urine, hypercalciuria and

low urine citrate)

5. Nephrocalcinosis

6. Bone demineralization (rickets in children, osteomalacia in adults)

The most likely diagnosis is

A.) Idiopathic focal segmental glomerulosclerosis

B.) Diabetic nephropathy

C.) Membranoproliferative glomerulonephritis

D.) Microscopic polyangiitis

E.) Anti-GBM nephritis

CASE 9

The most likely diagnosis is

A.) Idiopathic focal segmental glomerulosclerosis

B.) Diabetic nephropathy

C.) Membranoproliferative glomerulonephritis

D.) Microscopic polyangiitis

✓ E.) Anti-GBM nephritis

CASE 9

E. Anti-GBM nephritis

•1919 - Dr. Ernest Goodpasture, resident of the MGH Path department, moonlighting at

the Chelsea Naval Hospital, reported autopsy findings in young sailors (Am J Med Sci,

1919)

•1958- Stanton and Tange used the term Goodpasture’s syndrome: hemorrhage and

glomerulonephritis (Aust Ann Med, 1958)

•1964 -Scheer and Grossman reported linear staining on IF (Ann Intern Med, 1964)

• Uncommon: incidence 0.1 cases/million population, 1-2% of renal biopsy specimens

• 50-75% have upper respiratory prodrome, plus fever, rash, myalgias, malaise,

headache, weight loss

• Renal presentation with RPGN

• US - normal size kidneys

• Renal function declines rapidly

CXR Findings in Goodpasture’s

SOURCE: Bolton WK. Goodpasture's syndrome. Kidney Int. 1996 Nov;50(5):1753-66. doi: 10.1038/ki.1996.495.

Rx of Pulmonary Renal Syndromes

SOURCE: Bolton WK. Goodpasture's syndrome. Kidney Int. 1996 Nov;50(5):1753-66. doi: 10.1038/ki.1996.495.

Goodpasture’s Syndrome

Treatment

• Protocol

– Pulse methyl prednisone (solumedrol) 1 g QD x 3 d, 1-1.5

mg/Kg prednisone

– Cyclophosphamide 3 mg/Kg/d (reduced dose in older patients,

or if GFR < 10) > 2 months

– Plasma exchange daily 4 L with albumin replacement (or FFP

if pulmonary hemorrhage present) x 14 d or until antibody titer

close to zero

This 64-year old patient with ESRD

on HD presents with an ulcerative

painful lesion. She says it started off

as a reddish rash and then evolves

into an ulcer over a few weeks.

The most likely way to reach a

definitive diagnosis would be:

A. Surgical exploration of wound

B. C diff toxin assay

C. Skin biopsy

D. PT and INR

E. Lupus serologies

CASE 10

This 64-year old patient with ESRD

on HD presents with an ulcerative

painful lesion. She says it started off

as a reddish rash and then evolves

into an ulcer over a few weeks.

The most likely way to reach a

definitive diagnosis would be:

A. Surgical exploration of wound

B. C diff toxin assay

✓ C. Skin biopsy

D. PT and INR

E. Lupus serologies

CASE 10

C. Skin biopsy

Calcific uremic arteriolopathy (CUA) better

term for this process in ESRD patients

• 1% to 4.5% of patients in dialysis

• Classical clinical picture is that of an

initial skin lesion, livedo reticularis-like

on the lower limbs, which progress to

violaceous, painful, plaque or

subcutaneous nodules, followed by

ischemic/necrotic ulcers of reticular

pattern.

• DDX: Necrotizing fasciitis, Pyoderma

gangrenosum, Coumadin necrosis, SLE

• Severe pain, non healing ulcerations,

recurrent hospitalizations. Most common

in 50s, women 2:1 over men, more

common in white patients

• 1-year mortality 40-80%

• Skin biopsy confirms arteriolar

calcificaton and mural thrombosis

associated with septal panniculitis.

Marques SM et al An Bras Dermatol. 2013 Nov-Dec; 88(6 Suppl 1): 44–47. Beitz J https://www.o-

wm.com/content/calciphylaxis-a-case-study-with-differential-diagnosis

Treatment

▪ Local wound care and metabolic control

▪ Avoiding tissue trauma or excessive manipulation

▪ Prescribing systemic antibiotics as needed

▪ Surgical debridement controversial due to increased risk of sepsis and worsening pain

▪ Correct the Ca and Phos (CaxPhos <55)

▪ Normalization of PTH ?parathyroidectomy

▪ Sodium thiosulfate • Dissolve the insoluble calcium salts embedded in tissue

• Doses 5 g - 25 g given IV over 1 h post HD

• ? Bisphosphonates