Intern Report 6.8

Case Presentation by Dr. Alexandra Weissman

Chief Complaint:

I’m coughing up blood.

History of Presenting Illness:

The patient is a 22 y/o M with no previous medical problems who has been experiencing lightheadedness, headaches, occasional nausea and vomiting, fatigue, cough, anorexia, and 10 pound weight loss for the past 2 months. The patient was taking Motrin daily for headache.  In October, the patient presented to his PCP’s office initially with these complaints and was found to have nephrotic range pronteinuria of 4.8 on 24 hour urine collection, as well as hypertension of 180s/100s. At this time he was told to follow up with a Nephrologist, however he decided to rest at home and felt somewhat better. However, over the past month the patient has had progressive fatigue and a chronic cough, and in the past two weeks the patient developed hemoptysis, exertional shortness of breath, paroxysmal nocturnal dyspnea, bilateral flank pain, night sweats, fever/chills, nausea and emesis with black clots, anorexia, and non-bloody/non-mucoid diarrhea. The patient also noted intermittent periorbital edema. The patient denies any recent travel, rashes, joint pain, known sick contacts, hematuria, dysuria, or polyuria. The patient has continued to take Motrin multiple times daily for pain. Two weeks ago, the patient presented to the ED with the above complaints and was diagnosed with atypical pneumonia and discharged home with azithromycin. The patient did not improve and returned on 12/24/12 with the same complaints.  The patient denies recent travel inside or outside the country or known sick contacts.

Family Medical History:  HTN

Social History:

Positive for tobacco use and occasional marijuana use, denies other illicit drug use or alcohol use.



Review of Systems:

Constitutional:  Fever, Chills, Sweats, Weakness, Decreased activity.

Eye:  Negative.

Ear/Nose/Mouth/Throat:  Negative.

Respiratory:  Shortness of breath, Cough, Sputum production, Hemoptysis, Wheezing.

Cardiovascular:  Tachycardia, No peripheral edema, No syncope. Bilateral pleuritic chest pain.

Gastrointestinal:  Nausea, Vomiting, Diarrhea.  Abdominal pain: Right, The pain is mild.

Genitourinary:  No dysuria, No hematuria, No change in urine stream, No urethral discharge, No lesions.

Hematology/Lymphatics:  No bruising tendency, No bleeding tendency, No swollen lymph nodes.

Endocrine:  No excessive thirst, No polyuria, No excessive hunger.

Immunologic:  Recurrent fevers, Recurrent infections.

Musculoskeletal:  Back, hands and legs cramp up. No back pain, No neck pain, No joint pain.

Integumentary:  No rash, No breakdown, No skin lesion.

Neurologic:  Negative, No confusion, No numbness, No tingling, No headache.

Psychiatric:  Negative.

Physical Exam:

Vital Signs: Blood pressure 154/101, pulse 103, respiratory rate 22, temperature 35.9, and pulse ox 97% on room air.

General:  Alert and oriented, Mild distress, Rigors, Restless.

Eye:  Pupils are equal, round and reactive to light, Extraocular movements are intact.

HENT:  Normocephalic, Atraumatic, Oral mucosa is moist, No sinus tenderness, No nasal discharge, No oral ulcers .

Respiratory:  Breath sounds are equal, Using accessory muscles, RR calculated to be around 40. Auscultation revealed minimal crackles in the lung bases, no wheezes. Dullness to percussion bilateral lower lung fields, left greater than right. Egophony bilaterally at the bases. Crackles heard in the dependent left lung when patient is in the lateral decubitus position, no crackles when patient upright.

Cardiovascular:  Regular rhythm, S1 auscultated, S2 auscultated, No rub, No murmur, Good pulses equal in all extremities, No edema, Tachycardic.

Gastrointestinal:  Soft, Non-distended, Normal bowel sounds, Mild tenderness in the abdomen, mostly in the right middle abdomen. No rebound, No guarding. Positive bowel sounds. No masses appreciated.

Genitourinary:  CVA tenderness bilaterally.

Lymphatics:  No lymphadenopathy.

Musculoskeletal: No tenderness.  No swelling.  No deformity.

Integumentary:  Warm, Intact, No rash.

Neurologic:  Alert, Oriented, No focal defects.

Psychiatric:  Cooperative, Appropriate mood & affect.


Electrolytes: 138/3.9|101/17|92/11 anion gap is 20, calcium < 5, phosphorus 7.4

CBC: 10.5/9.2/27.7/349.

INR is 0.97. PTT is 30.8. PT 10.1

Urinalysis: SG 1.025, pH 6, Glucose/Ketones/Leuk Est/Nitrites/Bili/Urobili are negative, 2+ blood, 2+ protein, 2-5 RBC, < 5 WBC, < 5 Epithelial Cells, No casts/crystals/mucus/bacteria/sperm/Trich

12-lead ECG: normal sinus rhythm with a rate of 101 beats per minute.  The axis is normal.  The PR, QRS, and QT intervals are normal.  R-wave progression is normal.  There is no ST elevation or depression.  There are inverted T waves in the lateral precordial leads.  Voltage consistent with LVH, otherwise this is a normal ECG.




Rapidly progressing central interstitial pattern.  The differential diagnosis includes atypical pneumonia, atypical pulmonary edema, viral pneumonia, TB, Goodpasture’s disease, lupus vasculitis, Wegener’s granulomatosis, or microscopic polyangiitis.


Ultrasound – Renals – Complete


1.  Mildly echogenic kidneys raise suspicion for medical renal disease.

2.  No hydronephrosis or renal calculus.

3.  Small left pleural effusion.

ED Course:

Initially, given history and physical examination, it was suspected that the patient had HTN and bronchitis refractory to outpatient therapy. However, upon examination of the labs and imaging studies, the differential widened to renal failure of unknown duration with bronchitis vs. nephrotic syndrome vs. pulmonary-renal syndrome (Goodpasture vs. Wegener). The patient was initially admitted to the internal medicine service for renal failure and bronchitis, however he went into respiratory failure requiring intubation while still in the ED. ICU was consulted regarding the patient, and a bronchoscopy was performed in the ED that did not demonstrate an active source of bleeding or tracheobronchal abnormality. Fluid obtained during bronchoscopy was sent for cytology and culture.


1. Which of the following drugs is not known to cause Acute Interstitial Nephritis?

a) Acetaminophen

b) Cephalosporins


d) Penicillins

2. What dangerous complication should you think of in a person presenting with nephrotic syndrome?

a) Myocardial infarction

b) Pulmonary embolism

c) Pneumonia

d) All of the above

3. From and emergency medicine perspective, what is the mainstay of treatment for nephrotic syndrome in an otherwise stable patient?

a) Cyclophosphamide

b) Corticosteroids

c) High-protein diet and follow up with a Nephrologist

d) Oral anticoagulation and supportive treatment



Differential Diagnoses (diseases paired with the lab tests that are classically diagnostic)

NSAID-induced AIN – +/- urine eosinophils

Tuberculosis – 3 AFB sputum cultures, Quantiferon gold test

Pneumonia – urine Streptococcal antigen, sputum culture

Legionella – Legionella urine antigen

HIV – ELISA HIV test and Western blot

Goodpasture Syndrome – anti-glomerular basement membrane antibody

Wegener Granulomatosis – ANCA, anti-myeloperoxidase antibody, anti-serine protease 3 antibody

Microscopic Polyangiitis – ANCA, RBC urinary casts, normal C3 and C4

SLE – ANA, dsDNA, anti-Sm, anti-RNP

Sjogren’s syndrome – anti-Ro, anti-La

Scleroderma – Scl-70, anti-Ro, anti-La, anti-RNP

Mixed Connective Tissue Disorders – anti-Ro, anti-La, anti-RNP

Rheumatoid Arthritis – RF, anti-CCP

Churg-Strauss – pANCA (anti-MPO Ab), eosinophilia, RBC urinary casts, RF

Heroin or HIV induced FSGS

Hepatitis B or C induced nephrotic syndrome


Hospital Course:

The patient was admitted to the ICU for a total stay of 20 days before being stabilized for transfer to the general medical floor. A thorough workup for autoimmune etiologies, infectious etiologies, and toxic etiologies was performed. UDS and SDS were negative.  Urinalysis demonstrated no dysmorphic RBC or RBC casts, with few WBC and WBC casts, and rare tubular cells – these results pointed away from a glomerulonephritis and toward a nephrotic syndrome. Testing for urine eosinophils was negative, however this does not rule out NSAID-induced AIN. All serologic testing for autoimmune disorders was negative including cANCA, pANCA, ENA profile (ANA, dsDNA, anti-Ro, anti-La, anti-RNP, anti-Sm, Scl-70, anti-Jo-1), RF, anti-myeloperoxidase Ab, anti-serine proteinase-3 Ab, C3, C4, IgG and IgG subtypes 1-4, and immunofluroescence assay. ESR and CRP were elevated, however these are nonspecific markers for inflammation. There was initially concern for Tuberculosis since the patient had hemoptysis, weight loss, chronic cough, and sweats, however 3 AFB sputum cultures and Quantiferon Gold testing was negative for Tuberculosis. There was also concern for new-onset HIV, however the patient was found to be HIV negative.  Urine Legionella antigen, urine Streptococcal antigen were negative and ASO were negative. Sputum cultures and BAL cultures with gram stain were negative bacteria, fungi, HSV 1 and 2, Influenza A and B, Parainfluenza 1/2/3, Herpes Zoster, Adenovirus, RSV, Pneumocystis jiroveci, or Chlamydia. Hepatitis B and C were negative as well. TTE did not demonstrate vegetations and blood cultures were negative, therefore endocarditis was highly unlikely.

The patient had at least a 3 month history of elevated creatinine, hypertension, and regular NSAID use. Nephrology concluded that the most likely cause of the patient’s nephrotic syndrome was interstitial nephritis from NSAID use. A renal biopsy was not performed since the patient was considered to have chronic renal disease at the time of presentation and Nephrology stated that renal biopsy would only reveal nonspecific histological findings of focal segmental glomerulosclerolsis at this time. The patient was placed on high dose IV steroids, which he responded to well. The chronic cough likely resulted from pulmonary congestion secondary to hypoalbuminemia and renal failure. Although the initial physical exams did not demonstrate edema, periorbital edema is a common finding in nephrotic syndrome, and in children is often one of the first signs of the disease. Low oncotic pressure in the intravascular space secondary to hypoalbuminemia creates a gradient for water to move to the extravascular space, resulting in peripheral edema. Chronic edema affects the gastrointestinal tract as well, causing defective absorption and often resulting in diarrhea and chronic malnutrition.


1. A – Acetaminophen is not known to cause AIN. Many drugs are implicated in the development of AIN, most commonly NSAIDS, penicillins, diuretics, cephalosporins, rifampin, anticoagulants, and proton-pump inhibitors. AIN can also result from infection with HIV, tuberculosis, bacterial, fungal, protozoan, and rickettsial infections as well as in association with autimmune states such as SLE, Scleroderma, Sjogren’s Syndrome, sarcoidosis, and essential cryoglobinemia. The pathophysiology of drug-induced AIN involves both the humoral and cellular immune systems. Antibodies directed at the drug can be found on the tubular basement membrane, and biopsy reveals a mixture of T cells, eosinophils, plasma cells, and monocytes. Effacement of the podocyte processes is a common histological finding in NSAID-induced AIN.

2. D – Nephrotic syndrome is associated with venous thromboembolism including pulmonary embolism and deep venous thrombosis, myocardial infarction, and pneumonia. In nephrotic syndrome, a prothrombotic state emerges due to to the loss of antithrombin III and plasminogen secondary to renal losses of these proteins. At the same time, the liver is induced to make more proteins, including clotting factors, in response to hypoalbuminemia from renal losses of albumin. As for myocardial infarction, the increased hepatic synthesis of proteins also results in increased synthesis of lipoproteins, which results in accelerated atherosclerosis and hyperlipidemia. The increased synthesis of lipids results in lipiduria, which is why oval fat bodies and fatty casts are typical urine sediment findings in nephrotic syndrome. Lastly, it is hypothesized that the increased renal losses of proteins including immune globulins combined with the malnourished low protein state predisposes the body to infection in nephrotic syndrome.

3. B – In addition to treating the underlying infection or removing the offending drug, corticosteroids are the mainstay of treatment for nephrotic syndrome of autoimmune, infectious, drug-induced, or idiopathic etiology. Corticosteroids reduce the inflammatory response via inhibition of inflammatory mediator gene transcription and thus also diminish proteinuria. They are particularly effective for Minimal Change Disease in children. However, there are steroid resistant forms of nephrotic syndrome that do require more cytotoxic agents such as cyclophosphamide or cyclosporine.  Other medications given for supportive therapy are diuretics for associated edema, ACE-inhibitors for their anti-hypertensive and renal protective benefits, low salt and 1-2g/kg protein diet.

5 Responses

  1. 1-

    2- …However, encapsulated organisms like strep pneumo can cause infection in this syndrome but peritonitis is a more common complication than pneumonia. Also this syndrome can cause hyperlipidemia which can lead to MI in those already at high risk but thromboembolism is a direct complication of this syndrome.


  2. 1.


    3. –After a lit review, I don’t even see what most people think to be the right answer to this, high dose diuretics and salt restricted diet, on here. Corticosteroids are given a lot without any real evidence to support, so if this is the answer, it’s wrong.

  3. 1) 2) , nephrotic syndrome increases risk of thromboembolic events and decreases levels of Ig all of which can be dangerous 3)

  4. 1. Couldn’t any cause AIN? Maybe least common is APAP, but my understanding is that it can cause AIN too

    • Some reports of acetaminophen causing AIN:

      Fruchter LL, Alexopoulou I, Lau KK. Acute interstitial nephritis with acetaminophen and alcohol intoxication. Ital J Pediatr. 2011 Apr 15;37:17. doi: 10.1186/1824-7288-37-17.

      Trinn C, Szöke B, Tóth T, Nagy J. Paracetamol induced acute interstitial nephritis superimposed on mesangiocapillary glomerulonephritis. Acta Physiol Hung. 1996;84(4):469-70.

      Paller MS. Drug-induced nephropathies. Med Clin North Am. 1990 Jul;74(4):909-17.

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