Resident Conference 2004 Katy Moran MD July 13, 2004.
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Transcript of Resident Conference 2004 Katy Moran MD July 13, 2004.
Resident Conference 2004
Katy Moran MD
July 13, 2004
Case Presentationadapted from Singh AK, Colvin RB. Case 36-2003: A 68 year old woman with impaired renal function. N Engl J Med
2003; 349;2055-63.
• HPI: 68 yo WF c/o dyspnea, subj fever one month agonebulizers given sx improved
• 14 d ago malaise, diffuse myalgias tx with ibuprofen sx minimally improve
• 10 d agodeveloped pruritis, temp 100.0prescribed cetirizine (Zyrtec)
• 6 d ago UA ++ protein, WBC 50, mod tubular cells, BUN 20 mg/dL, Cr 1.5 mg/dL (baseline 0.8)d/c ibuprofen
• Admission emesis, malaise, fatigue, oliguria but no dyspnea, fever, chills, CP, abd pain, diarrhea, dysuria, arthralgia, rash
• Meds: HCTZ, Estrogen, Asprin, MVI, ibuprofen• NKDA• PMH
– HTN – Endometrial carcinoma s/p TAH – Appy
• SH: remote tobacco use, 1 glass wine/day, married with several children
• FH: NC
• T 99.0, BP 110/75, P 66• Physical exam remarkable only for trace
peripheral edema, otherwise normal• Labs
– UA: +++ protein, tr ketones, 0-2 RBCs and WBCs, 0-2 hyaline casts, 3-5 granular casts, 0-2 waxy casts, SG 1.030
– CBC: WBC 14,700 - N66L11Band4M4E14, plts 208,000, Hg 12.1, Hct 37.2
– Coags nl
• Serum chemistries – T Prot 7.4, Alb 2.0, Globulin 5.4, BUN 40, Cr
3.7, Ca 7.1, Phos 6.3, Mg nl, AST nl, ALT nl– Na 125, K 3.0, Cl 95, CO2 24, Anion gap 6
– Studies: CT abd/pelvis-overall unremarkable, specifically no hydronephrosis
• Hospital course– Plan: d/c HCTZ and NSAIDs, observe– Day 2 - pruritis and nausea resolve, oliguria persists,
results of 24 hour urine 3.4 g protein– Day 3 - steroids initiated– Days 4-5 - oliguria persists, BUN and Cr continue to
rise, 98 mg/dL and 7.6 mg/dL respectively
• Day 5 – Diagnostic procedure: renal biopsy• What results would you predict?
Objectives
• Examine the differential diagnosis of intrinsic renal failure in the context of a clinical case
• Review the pathophysiology of interstitial nephritis
• Briefly review the role of NSAIDs in renal failure
• Examine the role of the nephrotic syndrome with AIN and ARF
Clinical problem: Acute renal failure
• Acute renal failure– Prerenal - reduction of blood flow to kidneys
• No history of hypotension, heart failure, sepsis or other factors that make cause renal hypoperfusion
– Intrinsic – process within the kidneys• Most likely given lack of evidence of other etiology
– Post Renal – obstruction of urine flow• No evidence of hydronephrosis on imaging
Intrinsic Renal Failure
• Differential Diagnosis– Acute Glomerulonephritis– Acute Interstitial Nephritis– Tubular disease– Vascular disease
Acute Glomerulonephritis
• Presentation– HTN– Edema– Renal failure– Hematuria– RBC casts– May have mild proteinuria
• Quick review: so what are these RBC casts, anyway?
• When a glomerular lesion is present, RBCs are extravasated through the glomerulus into the tubular lumen
• Proteins secreted from tubules (Tamm Horsfall glycoproteins) remain in the lumen for an extended period of time
• These proteins take the shape of the lumen, forming a “cast” and trap the nearby RBCs in their matrix
• Glomerular disease usually means urinary stasis, i.e. more time for proteins to become trapped in the lumen
RBC casts
Acute Glomerulonephritis
• Case analysis– Urine prior to admission lacking rbcs or rbc
casts– Urine on admission with few red cell casts,
few WBC casts but + granular casts – History of HTN in the past medical history but
this was well controlled, BP on admission normotensive
Interstitial Nephritis
• Presentation– May be asymptomatic or have nonspecific
nausea, vomiting, malaise– Allergic symptoms can be a clue – rash, fever,
eosinophilia or eosinophiluria– Urine sediment: WBCs, RBCs, white cell
casts– Usually nl or minimal protein in urine
Pathology of acute interstitial nephritis
• The hallmark is the infiltration of inflammatory cells into the interstitial compartment with sparing of glomeruli and interstitial edema
• Infiltrating cell population is comprised mainly of T cells (often CD4+) and monocytes. Plasma cells, neutrophils, and eosinophils may be seen
• In nearly all cases, the tubular epithelium involved in the inflammatory process will aberrantly express MHC class II antigens and adhesion molecules like ICAM, important for the engagement of T cells
• Together with interstitial edema, this infiltrate causes the tubules to be pushed away from one another, rather than lying closely together
• Most forms of acute interstitial nephritis do not have immune deposits present
Picture of AIN and Normal Interstitial inflammation and
unremarkable glomerulus
Normal glomerulus, normal interstitium
Types of Interstitial Nephritis
Singh, A. K. et al. N Engl J Med 2003;349:2055-2063
Interstitial Nephritis
• Case analysis– Symptoms of low grade fever, pruritis on
admission– Urinary sediment prior to admission +WBCs– Eosiniphilia – Possible etiologies
• NSAIDs ibuprofen• HCTZ
– However, urine on admit few WBCs and heavy proteinuria
Tubular Disease
• Definition– Acute tubular necrosis
• Ischemia, progression of prerenal cause• Toxin• Drugs (AG, amphotericin, cisplatin)• Contrast• Pigments (myoglobin, Hb), crystals (uric acid) or protein (Ig
light chains)
• UA: muddy brown, pigmented granular and epithelial cell casts and free epithelial cells – Ischemic or toxic injury to the tubular epithelial cells
cell sloughing into the tubular lumen
• Case analysis– UA on admit with granular casts, not
diagnostic of ATN but would be consistent with ATN
– SG on high end of nl so concentrating ability preserved, less consistent with ATN
– Predisposing factors?• No ischemia, toxin, contrast, crystal• Protein - Globulin high at 5.4, SPEP/UPEP non
revealing
Vascular Causes of ARF
• Differential Diagnosis– Renal artery stenosis
• Especially bilateral stenosis plus an ACE-inhibitor
– HTN crisis– Scleroderma renal crisis– Cholesterol emboli– HUS/TTP
• Case analysis– Not consistent with clinical picture
Renal Biopsy
• Why biopsy?– Uncertainty about diagnosis– Degree and severity of renal failure – Lack of recovery after discontinuation of likely
offending agent
• Performed on Day 5
Renal-Biopsy Specimen Showing Interstitial Nephritis (Hematoxylin and Eosin)
Singh, A. K. et al. N Engl J Med 2003;349:2055-2063
NSAIDs and Acute interstitial nephritis
• Compared with “classic” AIN, disease due to NSAIDs is:– Less likely to present with hematuria,
eosinophilia, or fever– More likely to cause renal dysfunction,
requiring dialysis in 33% of cases– More likely to coincide with nephrotic
syndrome
AIN and Nephrotic syndome• Nephrotic syndrome
– Clinical features• Heavy proteinuria (>3.5 g/d), hypoalbuminemia, edema,
hyperlipidemia, lipiduria• Case analysis: Proteinuria, low albumin compatible,
however lipids were normal
• Frequently accompanies NSAID induced AIN, especially pts >50 yo
• Mechanism – Unknown– Hypothesis: NSAID metabolite may induce
inflammation and recruit and activate T cells
The Role of NSAIDS
• NSAID and electrolytes– Renal prostaglandins also play a role in water
balance• Antagonize the role of ADH causing water
retention disproportionate to sodium retention• Inhibit active chloride transport by thick ascending
limb of loop of Henle• Regulate medullary blood flow
• Case analysis – hyponatriemia on admission may be related to NSAID effect
• Biopsy Results– With standard staining glomeruli were normal– No thickening of capillary wall, scarring,
immunoglobulin deposition, complement, fibrinogen
• Electron microscopy– Effacement of foot processes and villous
hypertrophy of podocytes
Renal-Biopsy Specimen Showing Minimal-Change Glomerular Disease
Singh, A. K. et al. N Engl J Med 2003;349:2055-2063
Summary of case
• Clinical picture compatible with acute interstitial nephritis with nephrotic syndrome
• Biopsy with AIN with tubular injury and minimal change disease
• Case follow-up:– Pt required 3 dialysis treatments during hospitalization
and was treated with steroids– Kidney function gradually improved with Cr 1.2 mg/dL
fifteen days after admission
Board Review Questions
• A 73 yo WF with rheumatic heart disease is being treated with ampicillin and gentamicin for endocarditis. One week into the course she develops a morbilliform rash and fever. Her creatinine and BUN have doubled from baseline, and the UA is positive for blood, protein, WBCs. Ultrasound shows bilaterally enlarged kidneys. Most likely cause:– A) Tubular necrosis caused by AG– B) Membranous nephropathy resulting from endocarditis– C) Enterococcal pyelonephritis– D) Cystitis– E) Hypersensitivity reaction to ampicillin
• The answer is (E) hypersensitivity rxn to ampicillin– Learning point: Acute interstitial nephritis may
be caused by a number of drugs. Classic features include:
• Hematuria• Fever• Skin rash • UA protein, WBCs, maybe eosinophils• Ultrasound: enlarged kidneys
• A 50 yo man is hospitalized for treatment of enterococcal endocarditis. He has been receiving ampicillin and gentamicin for the past 2 weeks but is persistently febrile. Labs: Na 145, K 5.0, Cl 110, HCO3 20, BUN 14, Cr 3.5, Urine Na 20, Urine Cr 3000. Most likely cause of ARF?– (A) Tubular necrosis– (B) Insensible skin losses– (C) Renal artery embolism– (D) Cardiac failure– (E) Nausea and vomiting
• The answer is (A) tubular necrosis• Learning point: Calculation of FENa
– U Na x P Cr / P Na x U Cr x100
• In this case FENa 1.4 impaired Na reabsorption, more likely intrinsic renal failure– Prerenal azotemia = avid Na reabsorption– Intrinsic renal dysfunction = impaired Na
reabsorption
• Which of the following patients is most likely to develop destruction of renal papillae with tubulointerstitial damage?– (A) A middle aged man who has consumed
“moonshine alcohol” distilled in an automobile radiator– (B) An older man with early stage prostate CA– (C) A young adult woman with B-thalassemia– (D) An older woman who uses analgesics for chronic
headaches– (E) Middle aged woman with her first UTI that is
responding to antibiotics
• The answer is (D) an older woman on chronic analgesics– Learning point: Renal papillary necrosis is classically
associated with long term analgesic abuse. Other causes include sickle cell anemia, diabetic nephropathy, acute obstructive nephropathy.
– NOT associated with prostate CA, a single UTI. – Lead can cause tubular atrophy and fibrosis of small
renal arteries.
• Objectives revisited:– Differential diagnosis of intrinisic renal failure– Pathology of acute interstitial nephritis– NSAIDs and renal failure– Nephrotic syndrome and interstitial nephritis
Questions?
Resources• Singh AK, Ucci A, Madias NE. Predominant tubulointerstitial lupus nephritis. Am J Kidney Dis
1996;27:273-278 • Singh AK, Colvin RB. Case 36-2003: A 68 year old woman with impaired renal function. N Engl
J Med 2003; 349;2055-63.• Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal anti-inflammatory drugs. N
Engl J Med 1984;310:563-572. • Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal anti-inflammatory drugs. N
Engl J Med 1984;310:563-572. • Tam VK, Green J, Schwieger J, Cohen AH. Nephrotic syndrome and renal insufficiency
associated with lithium therapy. Am J Kidney Dis 1996;27:715-720. • Chen CY, Pang VF, Chen CS. Pathological and biochemical modifications of renal function in
ibuprofen-induced interstitial nephritis. Ren Fail 1996;18:31-40. • Michel, DM, Kelly, CJ. Acute interstitial nephritis. J Am Soc Nephrol 1998; 9:506. • Rennke HG, Roos PC, Wall SG. Drug-induced interstitial nephritis with heavy glomerular
proteinuria. N Engl J Med 1980;302:691-692.• Rossert, J. Drug-induced acute interstitial nephritis. Kidney Int 2001; 60:804. • Up to date• Hricik, Sedor, Ganz. Nephrology Clinical Secrets. • Sabatine, Mark. Pocket Medicine. • Stone, Richard. Harrison’s Principles of Internal Medicine Self Assessment and Board Review.• MD Consult