Download Nephrology Case Presentation IgA Nephropathy

Nephrology Case
Presentation
Douglas Stahura D.O.
Grandview Hospital
November 20, 2001
Case Presentation
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24 y/o AAF referred by PCP c/o fatigue,
periorbital edema, lower extremity edema,
hematuria, proteinuria
 Pt relates a 5 year history of intermittent
gross hematuria usually associated with
“colds”
 Over past four months has noticed increasing
fatigue, swelling “around my eyes, especially
in the morning” and swelling in the ankles and
legs
Case Presentation
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PMH – one pregnancy, uncomplicated
PSH – none
Allergy – none
Meds – Lasix 40 mg QD
Social – married, nursing student,
nonsmoker, EtOH socially, caffeine-2 cpd
Family – Father deceased age 50 MVA,
Mother DM2 age 56
Case Presentation
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ROS
– Fatigue, Weight gain 10#, No energy, poor
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appetite,
Swelling in feet/ankles, worse at end of the
day, legs “feel heavy”
Denies CP/PALP/DOE,
Cough/Sputum/SOB
Denies N/V/D, +/-Constipation
No recent UTI, hematuria
Case Presentation
Exam: BP 135/85, T-98.6, P-80, R-14
 Wt-146, Ht-5’3”
 NAD, pleasant, cooperative
 CV,RESP,GI,MS, LYMPH – WNL
 SKIN – warm/dry, 3+ pitting up to knees
B/L, no rash/purpura,
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Case Presentation
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Lab data:
– Na-133, K-4.1, Cl-103, HCO3-25
– BUN-8, Cr-0.8
– CBC normal
– AST-18, ALT-22, ALP-80, ALB-0.6
– UA SG-1.020, pH-5, BLO-2+, PRO-4+,
GLU-neg, Ketones-Neg
– CXR-normal
Differential Diagnosis
Hematuria, gross
 Proteinuria
 Hypoalbuminuria
 Nephrotic Syndrome
 Nephritic Syndrome
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Clinical Investigation
Imaging: Renal Ultrasound
 Lab:
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ANA, dsDNA
ASO titer, ANCA, anti-GBM Ab
Serum/Urine Electropheresis
HBV, HCV, HIV, C3, C4, CH50
24 hour Urine: Protein, Creatinine
Renal Biopsy
Clinical Investigation
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24 hour urine
– 18 grams protein/24 hours
– Creatinine Clearance 120 ml/min
00:00
IgA Nephropathy
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Mesangial proliferative glomerulonephritis
characterized by diffuse mesangial deposition
of IgA
 Described by Berger in Paris 1968
 Common clinical presentation is gross
hematuria provoked by mucosal infection
 Diagnosis is made by Immunoflorescence
IgA Nephropathy
Pathogenesis
IgA preferentially deposits in glomerulus
 Abnormality of host IgA immune system
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– No consistent evidence for a specific
antigen
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Bacterial, viral, food
– Possibly autoimmune against mesangium
– Antigen-independent mechanism – IgA
glycosylation
IgA Nephropathy
Pathogenesis
IgA most abundant Ig in the body and
provides mucosal defence
 Two subclasses: IgA1, IgA2
 Mucosal Ag challenge provokes pIgA by
plasma cells in MALT
 Bone marrow derived mIgA1
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IgA Nephropathy
Pathogenesis
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In IgA nephropathy
– pIgA1 is deposited in mesangium
– pIgA1 is downregulated in mucosa and
upregulated in the marrow
– Tonsillar pIgA1 is increased
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Mesangial proliferation is a result of
cytokines and growth factors (PDGF,
TGF-beta)
IgA Nephropathy
Clinical Presentation
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Macroscopic Hematuria in 2nd & 3rd decades
of life (40-50%)
“Synpharingitic” hematuria
Microscopic hematuria +- proteinuria
Nephrotic Syndrome w/ hematuria(5%)
Acute Renal Failure (rare)
– Cresentic or tubular occlusion by hematuria
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Chronic Renal Failure w/HTN
IgA Nephropathy
Clinical Associations
IgA Nephropathy
Prognosis
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Clinical
– POOR
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Increasing Age
Duration of symptoms
Severity of proteinuria
Hypertension
Renal impairment
– NO IMPACT
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Gender
Serum IgA level
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Histopathologic
– POOR
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Glomerular sclerosis
Tubule atrophy
Interstitial fibrosis
Vascular wall
thickening
Capillary loop wall IgA
deposits
IgA Nephropathy
Therapy
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Reduce IgA production
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Tonsillectomy
Gluten free diet – neither reduce incidence of
renal failure
Altering Immune and Inflammation
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In cresentic IgAN – plasmapheresis, steroids,
and cyclophosphamide – poor long term results
Steroids – alternate day regimen x 2 years
Cyclophosphamide only – no good data
IgA Nephropathy
Therapy
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Altering Immune and Inflammation
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Dipyridimole and warfarin – no benefit
Cyclosporine – hemodynamic effect only
Slowly Progressive
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Hypertension – Use of ACE-Inhibitor to target
125/75 will reduce proteinuria
Fish Oil – 4-8 grams/day provided renal
protection from progressive disease, but did not
lower proteinuria
My Patient
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Daily Prednisone, then to alternate day
therapy – Failed, no decrement of renal
function, but no improvement of proteinuria
 Fish Oil – unable to comply and quit therapy
after 3-4 months
 Cytoxan/Methyprednisolone monthly IV
pulses x 6 (Lupus Nephritis regimen)
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Albumin =4.1
clinical Nephrotic syndrome resolved
References
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Comprehensive Clinical Nephrology, RJ Johnson/J
Feehally, Harcourt, 2000
The Kidney, Brenner and Rector, 6th Ed, Saunders,
2000
The long term Outcome of Patients with IgA
Nephropathy Treated with Fish Oil in a Controlled
Trial, Donadio et al., JASN:10;1772-1777, 1999