Nephrology Lecture #2

Tuft resides in the _____________.

Bowman's capsule

Cluster of capillaries that make up the glomerulus is called ____________.

tuft

tuft + capsule =

renal corpuscle

Describe the pathway of blood in the glomerulus.

Afferent arteriole and exits via efferent arteriole

What is interstitial nephritis and why does it happen?

Interstitial inflammatory response with edema. Can involve the glomerulus, tubules, or interstitial renal tissue.

What causes acute interstitial nephritis?

Drugs

Infectious disease

Autoimmune disorders

A 48-year-old man presents to the clinic with fever, a diffuse maculopapular rash, and joint pains. He started taking amoxicillin-clavulanate 10 days ago for sinusitis. He denies hematuria or flank pain. Vitals are stable. Physical exam reveals a low-grade fever and a non-blanching rash on the trunk and extremities.

Lab results:

BUN: 42 mg/dL

Creatinine: 3.1 mg/dL (baseline: 0.9 mg/dL)

Urinalysis: WBCs, WBC casts, and mild proteinuria

CBC: Eosinophils elevated at 9% (normal: <5%)

What is likely the diagnosis?

How do you definitively diagnose this condition?

What caused this condition?

How do you treat it?

1.) Acute interstitial nephritis

2.) Kidney biopsy

3.) augementin (penicillin)

4.) Supportive care, remove inciting agent

Which protein is most abundant protein species in blood and urine?

Albumin

Patient has 2 grams of albumin in her urine, what does this mean?

She has greater then 1-2 grams of protein in urine per day. This is an underlying glomerular kidney disease

Describe glomerular proteinuria.

Damage to glomeruli leads to increased permeability

What is the difference between nephritic syndrome and nephrotic syndrome?

Nephritic syndrome - Symptoms that occur with some disorders that cause swelling and inflammation of the glomeruli in the kidney, also called glomerulonephritis. Acute nephritic syndrome is caused by an immune response triggered by an infection or other disease.

Nephrotic syndrome - Kidney disease characterized by edema and loss of more then 3 grams/day of protein from the plasma into the urine due to increased glomerular permeability.

Cola-colored urine

Hematuria found in nephritic syndrome

Red blood cell casts is associated with ___________ syndrome.

Nephritic

Low serum albumin is associated with __________________ syndrome.

nephrotic

Raised blood pressure and jugular venous pressure is associated with __________________ syndrome.

Nephritic

Edema is found in both nephrotic and nephritic syndrome, but which one is it more prominent in?

Nephrotic syndrome

A 9-year-old boy is brought to the pediatrician by his mother because of facial puffiness and dark-colored urine for the past two days. He recently recovered from a sore throat about two weeks ago. On examination, his blood pressure is 138/90 mmHg. Periorbital edema is noted. Urinalysis reveals:

+3 blood

+1 protein

Red blood cell casts on microscopy

No nitrites or leukocyte esterase

Serum labs:

BUN: 34 mg/dL

Creatinine: 1.2 mg/dL

Low complement C3 levels

What is most likely the diagnosis?

Nephritic syndrome.

Note that it classically presents with

1.) Hypertension

2.) Hematuria

3.) RBC casts

4.) Dependent Edema

5.) Mild to moderate proteinuria

A 28-year-old man presents to the clinic with brown-colored urine, mild facial swelling, and fatigue. He reports having a sore throat 2 weeks ago that resolved without treatment. His blood pressure is 150/92 mmHg. Physical exam reveals mild periorbital edema.

Which of the following is the most likely diagnosis?

A. Acute tubular necrosis

B. Nephrolithiasis

C. Post-streptococcal glomerulonephritis

D. Minimal change disease

What labs would you order for this condition?

How do you confirm diagnosis?

C. Post-streptococcal glomerulonephritis

Serum creatine

Dipstick - Hematuria and sub nephrotic proteinuria would be present.

Kidney biopsy is needed to confirm

Red cell casts

Glomerulonephritis

What is immune complex deposition and when does it occur?

Occurs with moderate overproduction of antigen compared to antibody production.

What is immune complex deposition?

Immune complex deposition results from moderate overproduction of antigens compared to antibody production.

It gets trapped in the kidney and triggers glomerular inflammation resulting in immune complex glomerulonephritis.

This is different from ant-GBM GN where there is a direct antibody attack on the basement membrane. This is also different from pauci-immune GN where there is little to no immune deposits.

What are some causes of glomerulonephritis secondary to immune complex deposition?

- IgA nephropathy

- Infection-related glomerulonephritis

- lupus nephritis

- Cryoglobulinemic glomerulonephritis

What is the most common primary glomerulonephritis in the world?

IgA nephropathy (Berger Disease)

How does Berger disease occur?

IgA immune complex deposits in the glomerular mesangium (space between capillary loops) and capillary wall

A 19-year-old college student presents to urgent care with dark-colored urine that began 1 day ago. He denies pain with urination or fever. He reports having a sore throat and congestion about 3 days ago, which has mostly resolved. He feels otherwise well. Vital signs are normal.

Serum creatinine - 1.0mg/dL (normal)

Hematuria

Proteinuria

Which of the following is the most likely diagnosis?

A. Post-streptococcal glomerulonephritis

B. IgA nephropathy

C. Minimal change disease

D. Urolithiasis

What is the gold standard for diagnosing this condition?

How do you treat this?

What can you give if the patient has persistent proteinuria?

B. IgA nephropathy

Classic presentation: intermittent hematuria following an upper respiratory infection in a young, otherwise healthy patient

1.) Kidney biopsy

2.) ACEI/ARB - Control BP and reduce protein in urine

3.) Corticosteroids

IgA Vasculitis classic triad

1.) Purpura

2.) Arthritis

3.) Abdominal Pain

How does IgA vasculitis occur?

IgA deposition in small vessels. This can lead to glomerulonephritis.

A 6-year-old boy is brought to the pediatrician with a rash on his legs and complaints of joint pain and abdominal cramps. The rash started 2 days ago and has not been itchy. On examination, he has palpable purpura on his lower extremities and mild swelling in both knees. His parents report that he had a mild cold about a week ago. He has no fever.

Urinalysis shows:

+2 blood

Microscopy: RBCs and mild proteinuria

What is most likely the diagnosis?

How do you diagnose this?

How can you treat it?

1.) IgA vasculitis

2.) Clinical diagnosis

3.) Self limiting

Who is IgA vasculitis more common in?

Males then females.

What is the most common type of post-infectious glomerulonephritis?

Post-streptococcal glomerulonephritis

A 7-year-old boy is brought to the pediatrician with facial swelling and dark brown urine. His mother reports he had a sore throat about 10 days ago that resolved on its own. On exam, he has mild periorbital edema and elevated blood pressure.

Labs show:

Urinalysis: +3 blood, +1 protein, RBC casts

Serum creatinine: 1.3 mg/dL (elevated for age)

Complement C3: Low

ASO titer: Elevated

What is the most likely diagnosis?

A. IgA nephropathy

B. Post-infectious glomerulonephritis

C. Minimal change disease

D. Alport syndrome

How do you treat this?

B. Post-infectious glomerulonephritis

Note that it is not IgA nephropathy. IgA nephropathy: typically occurs within 1-2 days of URI, not 1-2 weeks later

1.) Hospitalization to manage acute nephritic syndrome

- Pencillin prophylaxis to family members

A 6-year-old boy presents with facial swelling, reduced urine output, and dark-colored urine. His mother reports that he had a skin infection around his mouth and nose about a month ago, diagnosed as impetigo and treated with topical antibiotics.

On exam:

Periorbital edema

BP: 128/82 mmHg

No fever

Urinalysis:

+3 blood

+1 protein

Microscopy: RBC casts

Labs:

Creatinine: 1.4 mg/dL (elevated for age)

Low C3 complement

ASO titer: normal

Anti-DNase B antibody: elevated

What is the most likely diagnosis?

Post infectious glomerulonephritis secondary to impetigo

What workup would you do for post-streptococcal glomerulonephritis secondary throat infections?

In addition to urinalysis and microscopic urinalysis you would do ASO titers - Positive

What workup would you do for post-streptococcal glomerulonephritis secondary to impetigo?

In addition to urinalysis and microscopic urinalysis you would find anti-DNase B - Positive

What is pauci-immune glomerulonephritis (PIG)?

Necrotizing glomerulonephritis in which there are few or no immune deposits by immunofluorescence or electron microscopy

Pauci is Latin word meaning few/little - compared to IgA Nephritis, there is no direct immune complex deposition or antibody binding

How does pauci-immune glomerulonephritis occur?

It is a cell mediated process in which ANCA (anti-neutrophil cytoplasmic antibodies) activate neutrophils in the blood stream which then damage small vessels including the glomerular capillaries. This causes necrotizing glomerulonephritis.

In other words in ANCA-GN - Immune cells go crazy and attack vessels directly.

A 55-year-old man presents with fatigue, weight loss, hematuria, and shortness of breath with occasional blood-tinged sputum. He reports a 2-week history of low-grade fever and sinus congestion. Physical examination reveals purpuric lesions on his lower extremities and decreased sensation in his right foot.

What is likely the diagnosis?

What labs would you order and what would you find?

What is the gold standard diagnosis?

How do you treat it?

1.) PIG - Pauci Immune glomerulonephritis

2.) ANCA serologic testing

3.) Renal biopsy is gold standard

4.) Prompt initiation of treatment is essential

- Induction therapy

--> High dose corticosteroids + cyclophosphamide OR rituximab

- Maintenance Therapy

---> Long term rituximab

What is another word for anti-GBM glomerulonephritis?

Goodpasture disease

Describe anti-GBM glomerulonephritis or Goodpasture syndrome

Autoimmune disease where the immune system makes antibodies against your own glomerular basement membrane.

What are some risk factors for goodpasture syndrome?

Men in third decade

Men or women in 6-7 decade

Pulmonary infection

Tobacco use

Hydrocarbon solvent exposure

Alemtuzumab

HLA-DR2 and HLA-B7 Antigens

A 35-year-old man presents to the emergency department with shortness of breath, fatigue, and blood in his sputum for the past 2 days. He also reports decreased urine output and dark-colored urine. One week ago, he had symptoms of an upper respiratory infection. He denies recent travel or sick contacts.

Lab findings:

Hemoglobin: 9.2 g/dL

BUN: 38 mg/dL

Creatinine: 4.1 mg/dL

Urinalysis: +3 blood, +1 protein, RBC casts

Chest X-ray: bilateral patchy infiltrates

Anti-GBM antibodies: positive

What is the diagnosis?

You order a kidney biopsy, what do you find?

How do you treat this?

1.) Anti GBM/Goodpasture

2.) Cresent formation, IgG staining along glomerular basement membrane

3.) Plasma exchange daily for 2 weeks, can also treat with corticosteroids and cyclophosphamide to prevent new antibodies

Solve the riddle

I am a chronic autoimmune disease, but no one knows what causes me. I can attack any organ of the body but I like the kidneys most. I produce antinuclear antibodies (ANA). I can cause mild joint pain and skin involvement to life threatening kidney, CNS, or hematologic problems. What am I?

SLE

How does lupus nephritis occur?

In those with SLE it often occurs when immune complexes deposit into the glomeruli and this triggers inflammation and damage to the glomerular basement membrane.

A 24-year-old woman with a known history of systemic lupus erythematosus (SLE) presents to clinic with complaints of facial puffiness, foamy urine, and joint stiffness in the mornings. She denies fever, cough, or hemoptysis. On exam, she has periorbital edema and mild pedal swelling. A renal biopsy is performed and shows immune complex deposition with "full-house immunofluorescence"

What other tests can you order?

What is the diagnosis?

How do you treat it?

1.) Screening urinalysis, 24 hour urine, serologic testing (ANA, anti-DNA, antiphospholipid antibodies

2.) lupus nephritis

3.) Level of severity helps determine treatment of choice. Corticosteroid if significant renal disease, immunosuppressive agents

Glomerulonephritis that presents with hemoptysis

Goodpasture syndrome

Glomerulonephritis that has no evidence of immunoglobulin or complement deposition.

Pauci Immune glomerulonephritis