Commentarycase

BYPROF DR /FAWZY MEGAHED

ASST LEC/ RAFAAT SAIED

• 79-year-old woman presented to the Hospital from a rehabilitation facility with worsening dyspnea, nonproductive cough, and fever.

• she was hospitalized at an outside hospital for 1 month for evaluation of fever, chills, and malaise.

• During that hospitalization, she aspirated stomach contents, and pneumonia subsequently developed, which was treated with a 7-day course of intravenous antibiotic

• Her hospitalization was further complicated by acute kidney injury after contrast computed tomography.

• Bilateral lower extremity deep venous thrombosis developed and was being treated with enoxaparin.

• A peripherally inserted central venous catheter and urinary catheter were placed during the hospitalization and removed before discharge

• Three days after admission to the rehabilitation facility, the patient experienced dyspnea, a nonproductive cough, chest discomfort, and fever. The family reported that she was urinating several times daily

• On admission to our hospital, the patient was afebrile and had a pulse rate of 89 beats/ min, respiratory rate of 24 breaths/min, blood pressure of 152/81 mm Hg, and oxygen saturation of 96% while receiving 15 L of oxygen via nonrebreather mask.

• She appeared frail and in moderate respiratory distress.

• Examination revealed 2-cm jugular venous distention above the sternal notch.

• She had decreased breath sounds in the right lower lobe, bibasilar crackles, and bronchial breath sounds in the upper airways.

• There was a 3/6 holosystolic murmur at the apex that radiated to the left axilla

• bilateral pitting oedema.

• There was no lymphadenopathy

Laboratory studies

• hemoglobin, 12.1 g/dL (12.0-15.5 g/dL)• mean corpuscular volume, 84.1 fL (81.6-98.fL); • leukocytes, 15.8 109/L (3.5-10.5 109/L); • platelet count, 343 109/L (150-450 109/L);• potassium, 3.7 mmol/L (3.6-5.2 mmol/L)• bicarbonate, 23 mmol/L (22-29 mmol/L);

• creatinine, 3.2 mg/ dL (0.6-1.1 mg/dL);• blood urea nitrogen,43 mg/dL (6-21 mg/dL);• aspartate aminotransferase, 18 U/L (8-4U/L); • alanine aminotransferase, 14 U/L (7-45 U/L);• total bilirubin, 0.5 mg/dL (1.2 mg/dL);• alkaline phosphatase, 142 U/L (55-142 U/L);

• prothrombin time, 15.1 seconds;• International normalized ratio, 1.1. • Arterial blood gas a pH of 7.38, PaCO2 of 43.4 mm Hg (35-45

mm Hg), and PaO2 of 192.4 mm Hg (80.0-100.0 mm Hg) while the patient received 15 L/min of oxygen via nasal cannula.

• Chest radiography revealed bilateral diffuse fibrotic changes, pulmonary infiltrates, and bilateral pleural effusions.

1. Which one of the following would be the most appropriate next step in management of this patient?

a. Computed tomographic angiography of the chest b. Continue enoxaparin c. Urinalysis d. Antimicrobial therapy for treatment of

community-acquired pneumonia e. Temporary dialysis catheter placement and dialysis

A-Computed tomographic angiography of the chest should not be performed because of the patient’s impaired renal function.

B- Enoxaparin should be discontinued because it is cleared renally and increases the risk of bleeding in patients with renal failure.

• Unfractionated heparin is preferred in this situation

C-The most appropriate step for the patient at this time is urinalysis

• Urinalysis with microscopy is crucial in differentiating causes of acute renal failure.

D-The patient’s presentation could represent pneumonia. However, she was hospitalized more than 48 hours within the past 90 days, so she meets criteria for health care-associated pneumonia, not community-acquired pneumonia

E-At this point, the patient does not require dialysis. Her serum potassium level is normal, and she is not uremic or anuric.

• Urinalysis revealed grade 2 proteinuria, trace leukocyte esterase, and notable occult blood with more than 182 RBCs per high power field, WBCs per high-power field, and bacteria and yeast present.

• Gram stainyielded negative results

• Urine microscopy showed RBC and hyaline casts. A 24-hour urinary protein measurement was ordered

• Noncontrast chest computed tomography revealed bilateral interstitial thickening with mixed airspace and interstitial opacities predominantly in the upper lobes and right middle lobe

• Enoxaparin was discontinued, and unfractionated heparin was administered to maintain a partial thromboplastin time of 60 to 90 seconds.

• Antimicrobial therapy consisting of vancomycin, cefepime, and levofloxacin was initiated for health care-associated pneumonia.

• Furosemide, 40 mg, was administered intravenously, and 800 mL of urine output followed.

• Thoracentesis was performed. Pleural fluid analysis yielded the following results:

• hazy yellow color; WBCs, 459/mL; segmented neutrophils, 8.0%; tissue cells, 4.0%; lymphocytes, 30.0%; mononuclear cells, 58.0%; eosinophils and basophils, 0.0%;

• pH, 8.0; glucose, 95 mg/dL; total protein, 2.2 g/dL; albumin, 1.1 g/dL; amylase, 22 U/L;

• lactate dehydrogenase (LDH), 124 U/L; and cholesterol, 29 mg/ dL.

• Serum studies revealed the following: albumin, 2.5 g/dL (3.5-5.0 g/dL); glucose, 92 mg/dL (70-140 mg/dL), LDH, 222 U/L (122-222 U/L); and total protein, 5.9 g/dL (6.3-7.9 g/dL). Gram stain results were negative.

2. Based on the results of pleural fluid analysis in this patient, which one of the following is the best next step?

a. Pleurodesisb. Echocardiographyc. Serum rheumatoid factor measurementd. Administration of somatostatin analogues and

diet modificatione. Tube thoracostomy for empyema drainage

A-Pleurodesis is required for recurrent effusions, so at this point, it should not be performed.

Based on Light’s criteria, the pleural fluid was transudative, representing an imbalance between hydrostatic and oncotic pressures as seen in congestive heart failure and cirrhosis.

• It would be exudative if any of the following criteria were met:

(1) pleural fluid protein to serum protein ratio greater than 0.5;

(2) pleural fluid LDH to serum LDH ratio greater than 0.6;

(3) pleural fluid LDH more than two-thirds the upper limit of normal serum LDH.

• Exudative effusions typically represent local factors causing fluid accumulation and inflammation

• as in pneumonia/infection or malignancy. • Pulmonaryemboli can cause either exudative

or transudative effusions.

B-Because congestive heart failure is part of the differential diagnosis, echocardiography would aid in determining if systolic and/or diastolic dysfunction is present.

C- Rheumatoid effusions are typically exudative, so rheumatoid factor measurement is not helpful in the setting of a transudate and no clinical findings suggestive of rheumatoid arthritis

D-Somatostatin analogues and a diet restricting medium-chain fatty acids are used in the treatment of a chylous effusion, which is exudative.

E-Similarly,an effusion associated with empyema is exudative and often associated with a pH of less than 7.2. Therefore, tube thoracostomy for empyema drainage would not be appropriate inthis patient

• Based on pleural fluid results, antimicrobial therapy was discontinued.

• Echocardiography revealed a left ventricular ejection fraction of 75% and mild diastolic dysfunction.

• Consequently, the effusion was believed to be secondary to hypoalbuminemia and possibly

intravenous fluid hydration during the previous hospitalization.

• Additionally, a 24-hour urinary protein measurement was 50 mg (27-93 mg/24 h).

• Although the patient continued to have satisfactory urinary output, on hospital day her serum creatinine level increased to 3.6 mg/ dL. Despite attempts to optimize intravascular volume, the serum creatinine level increased to 4.4 mg/dL.

• Renal ultrasonography revealed bilateral increased cortical echogenicity without hydronephrosis. Her gas exchange values remained stable while she received 4 L/min of oxygen via nasal cannula.

3. Based on the work-up, which one of the following is the most likely etiology of the patient’s renal failure?

a. Glomerulonephritisb. Contrast-induced nephropathyc. Catheter-associated urinary tract infectiond. Acute interstitial nephritis (AIN)e. Nephrolithiasis

A-Red blood cell casts are pathologic and indicate glomerular inflammation, which is the likely cause of this patient’s renal failure. Therefore, glomerulonephritis is the most likely etiology.

B-The patient was believed to have contrast-induced nephropathy. Urine microscopy findings may be consistent with acute tubular necrosis, such as muddy brown granular casts. Therefore, contrast-induced nephropathy is not the cause of this patient’s renal failure.

C-The patient had a urinary catheter placed during her previous hospitalization, which puts her at risk for a catheter-associated urinary tract infection.

• Urinalysis revealed WBCs and trace leukocyte esterase; nevertheless, Gram stain yielded negative results.

D-In addition to infection, WBCs or WBC casts may suggest AIN; however, in AIN, the sediment is not active, and therefore AIN is not causing our patient’s renal failure.

E-Although hematuria is common in nephrolithiasis, our patient’s hematuria is most likely related to a glomerular process in the setting of an active urinary sediment.

• Serum was tested for antineutrophil cytoplasmic antibodies (ANCAs) and antieglomerular basement membrane (GBM) antibodies to exclude an immune-mediated process and pulmonary renal syndrome.

• Hepatitis serologies and cryoglobulin measurements were also ordered.

• Results were positive for anti-GBM antibodies and myeloperoxidase (MPO)-ANCA

• Renal biopsy was scheduled for the following day. The patient continued to hav satisfactory urinary output.

• Her volume status was closely monitored with the goal of euvolemia. Her creatinine level remained stable at 4.4 mg/ dL, and her serum potassium level was 3.9 mmol/L.

4. While awaiting renal biopsy, which one of the following would be the most appropriate therapy?

a. Enalaprilb. Methotrexatec. Plasma exchanged. Intravenous immunoglobuline. Methylprednisolone

A-Angiotensin-converting enzyme inhibitors are contraindicated in acute renal failure; therefore, enalapril is not appropriate in this patient’s management.

B-Methotrexate is not used in the treatment of anti-GBM disease.

C-Therapeutic plasma exchange removes circulating anti-GBM antibodies but should be performed with biopsy confirmation of the disease when possible.

D-Intravenous immunoglobulin may be given to patients with anti- GBM disease and other diseases who have development of a severe infection while undergoing plasma exchange, but there is no indication for its use in our patient at this time

E-Methylprednisolone minimizes new antibody formation and may be given before biopsy and therefore is the best option for our patient.

• Serologic studies were positive for anti- GBM antibodies, and the patient was treated empirically with methylprednisolone

• Renal biopsy confirmed anti-GBM disease. Light microscopy revealed crescentic glomerulonephritis, and immunofluorescence microscopy documented linear deposition of IgG along glomerular capillaries.

5. Which one of the following statements is correct regarding this patient’s diagnosis of anti-GBM disease?

a. The disease process is slow and unlikely to progress to end-stage renal failure

b. She requires treatment only with prednisone because she does not have pulmonary hemorrhage

c. Serum creatinine at the time of diagnosis affects prognosis

d. Bronchoscopy should be performed to confirm alveolar involvement

e. Myeloperoxidase-ANCA positivity decrease sher likelihood of renal response to therapy

A-Anti-GBM disease is a form of a rapidly progressive glomerulonephritis.Without treatment, this disorder rapidly progresses to end-stage renal failure.

B-Anti-GBM disease, regardless of pulmonary involvement, is treated with therapeutic plasma exchange, cyclophosphamide, and prednisone.

• Conversely, in patients with anti-GBM disease who have pulmonary involvement, including hemorrhage, treatment is required regardless of the degree of renal involvement

C-Serum creatinine concentration at the time of diagnosis correlates with the percentage of crescentic glomeruli.

• Patients with creatinine levels over 4 mg/dL generally dopoorly despite therapy, and there is a low likelihoodof response in patients who are dialysisdependent.

D-Bronchoscopy will not affect treatment and is not necessary to confirm pulmonary involvement.

E- Myloperoxidase-ANCA positivity does not adversely affect prognosis. In fact, patients who are dialysis dependent and MPOANCA positive have a higher likelihood of renal response.

• The patient was treated with therapeutic plasma exchange and methylprednisolone, 1000 mg intravenously daily for 3 days, followed by oral prednisone and cyclophosphamide.

• She also received prophylactic trimethopri sulfamethoxazole for Pneumocystis pneumonia and nystatin for oropharyngeal fungal infections .

• One month later, the patient’s renal function improved with a serum creatinine level of 1.6 mg/dL, despite a hospitalization complicated by rectal bleeding and cytomegalovirus colitis.

DISCUSSION

• Anti-GBM disease is frequently a missed or delayed diagnosis. There should be a high clinical suspicion for anti-GBM disease in any patient with acute renal failure or rapid progression of glomerulonephritis and/or pulmonary findings including hemorrhage.

• Anti-GBM disease is a rare autoimmune disease and small-vessel vasculitis involving the lungs and kidneys and often presents as pulmonary-renal syndrome. The term anti- GBM disease is now preferred to the previously used term Goodpasture disease.

• anti-GBM antibodies develop against the alpha3 chains of type IV collagen, located primarily in the basement membranes of the renal glomeruli or pulmonary alveoli.

• Autoreactive T cells enhance B-cell function and antibody production and cause rapidly progressive (crescentic) glomerulonephritis and pulmonary hemorrhage

• Anti-GBM disease presents with acute renal failure, nonnephrotic proteinuria, and nephritic sediment with dysmorphic RBCs and RBC or granular casts.

• Pulmonary involvement may present with alveolar hemorrhage, dyspnea, cough, hemoptysis, increased diffusing capacity of lung for carbon monoxide, and infiltrates on chest imaging.

• Pulmonary involvement occurs in approximately 30% of patients and is more likely in those with previous pulmonary disease including fibrosis and pulmonary injury due to infection and cigarette smoking.

• Cases of possible lung injury or prior pneumonia triggering anti-GBM disease have also been reported

• A renal biopsy is definitive for diagnosis and treatment monitoring, while serology may vary in accuracy with sensitivity ranging from 63% to 100%.

• The preferred treatment for anti-GBM disease is a combined regimen of therapeutic plasma exchange, prednisone, and cyclophosphamide.

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