Nephrology Case Presentation IgA Nephropathy
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Transcript Nephrology Case Presentation IgA Nephropathy
Nephrology Case
Presentation
Douglas Stahura D.O.
Grandview Hospital
November 20, 2001
Case Presentation
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
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
ROS
– Fatigue, Weight gain 10#, No energy, poor
–
–
–
–
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,
Case Presentation
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
Clinical Investigation
Imaging: Renal Ultrasound
Lab:
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–
–
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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
24 hour urine
– 18 grams protein/24 hours
– Creatinine Clearance 120 ml/min
00:00
IgA Nephropathy
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
– No consistent evidence for a specific
antigen
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
IgA Nephropathy
Pathogenesis
In IgA nephropathy
– pIgA1 is deposited in mesangium
– pIgA1 is downregulated in mucosa and
upregulated in the marrow
– Tonsillar pIgA1 is increased
Mesangial proliferation is a result of
cytokines and growth factors (PDGF,
TGF-beta)
IgA Nephropathy
Clinical Presentation
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
Chronic Renal Failure w/HTN
IgA Nephropathy
Clinical Associations
IgA Nephropathy
Prognosis
Clinical
– POOR
Increasing Age
Duration of symptoms
Severity of proteinuria
Hypertension
Renal impairment
– NO IMPACT
Gender
Serum IgA level
Histopathologic
– POOR
Glomerular sclerosis
Tubule atrophy
Interstitial fibrosis
Vascular wall
thickening
Capillary loop wall IgA
deposits
IgA Nephropathy
Therapy
Reduce IgA production
Tonsillectomy
Gluten free diet – neither reduce incidence of
renal failure
Altering Immune and Inflammation
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
Altering Immune and Inflammation
Dipyridimole and warfarin – no benefit
Cyclosporine – hemodynamic effect only
Slowly Progressive
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
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)
Albumin =4.1
clinical Nephrotic syndrome resolved
References
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