iga-nephropathy
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Transcript iga-nephropathy
Case Presentation
Staci Smith DO
GVH Nephrology
Case Presentation
44-year-old white right-handed
male that presented to GVH with complaints of
hematuria
had associated abdominal
pain and took a Zantac for it
no history of known CKD and has not
actually seen a doctor in 25 years
no history of other hematuria,prostate trouble,
dysuria, nocturia,incontinence
not on any outpatient anticoagulation
20 years of tobacco abuse
Case Presentation
recent upper respiratory
infection 2 weeks ago with fevers and chills
foamy urine
denies any recent known UTI, over-thecounter NSAIDs, history
of nephrolithiasis, contrasted procedure,
physical exercise
Case Presentation
PAST MEDICAL HISTORY:
OA
Tobacco abuse
URI 2 weeks ago
MEDS:
SOCIAL HISTORY:
PAST SURGICAL HISTORY:
ALLERGIES:
Right knee scope
None
FAMILY HISTORY:
Htn
No medical renal dz
None
Cleans gutters / construction
work
Positive tobacco 1-2 ppd x 20 yrs
Social EtOh only
Case Presentation
Positive ROS :
Recent URI two weeks ago
10 pound weight gain with LE edema
Hematuria
Foamy urine
Abdominal pain - Zantac
Case Presentation : Physical Exam
VS:126/87- 97.9 F (T-max 99.2)- HR 84- RR 20- 96%sat
GEN-Awake, alert and oriented x3. Family is at bedside and updated. No
acute distress.
HEENT: Poor dentition. Atraumatic, normocephalic. Extraocular muscles
intact. Sclerae are anicteric. Mucous membranes are now moist
CHEST: Respirations clear to auscultation bilaterally. No wheezing, rhonchi
or crackles
ABDOMEN: Soft, nontender, nondistended. Positive bowel sounds. No
perotoneal signs or Foley
EXTREMITIES: No clubbing, cyanosis. Plus 2 pitting edema. There
is no asterixis
SKIN: There is no rash or cellulitis
NEUROLOGIC: Cranial nerves II-XII grossly intact.
Case Presentation : Labs
133 109 13
5
22 2.0
122
CCa 9.6 Alb 1.6
No Phos or Mg
UA is cloudy with
positive nitrite, large blood, 300 protein, too numerous to count red
cells, trace bacteria, 1-5 white cells
Case Presentation : Labs
CT of the abdomen and pelvis was negative
for any stone, multiple loops of fluid-filled nondilated
small bowel without obstruction or contracted GB
Urine Pr/ Cr ratio- 10
CPK was negative at 148.
LFTs normal. Amylase and lipase are normal.
TSH is 3.03
Total cholesterol 277
total triglycerides 264, HDL 26, LDL 198
7.8 11.3 165 S 79-L 11-M 8 – E 2
33.6
Case Presentation : Labs
All negative
Complements
ANA, dsDNA
Hepatitis profile
SPEP/ UPEP with IFE
Rheumatoid factor/ Anti CCP
Anti GBM
P and C ANCA’s
HIV
ASO
Differential Diagnosis
Back to our case
44 yo with hematura, proteinuria, and lower
extremity edema two weeks after an URI
No previous know CKD or AKI
Cr now 2.0
10 grams proteinuria
Hyperlipidemia
Differential Diagnosis
hematuria
proteinuria
red blood cell casts
glomerulonephritis
Red Blood Cell Casts
Glomerular hematuria
Dysmorphic rbc’s
glomerular damage
rule out urologic causes
Nephritic syndrome
HTN
RBC casts
Proteinuria
Edema
Differential Diagnosis: Glomerulonephritis
Postinfectious GN
IgA nephropathy
Thin basement membrane
Henoch-Schönlein purpura
Mesangial proliferative GN
SLE
Goodpasture’s dz
Vasculitis
Wegener’s, Churg-Strauss
Cryoglobulinemia
HIV
Membranoproliferative
glomerulonephritis
Rapidly progressive GN
Fibrillary glomerulonephritis
Focal glomerulosclerosis
Membranous nephropathy
Amyloidosis
Multiple Myeloma
DM
HUS
Differential Diagnosis: Glomerulonephritis
UA with C and S
Cbc with differential
Renal panel
Urine Pr/Cr
Renal US
Renal Duplex
Cystography
Urine eosinophils
SPEP / UPEP with IFE
Differential Diagnosis: Glomerulonephritis
ANA, dsDNA
Anti-GBM dz
Goodpasture’s
ANCA’s
c-ANCA: Wegener’s
p-ANCA: PAN, Churg
Strauss, MPA
Complements
Cryoglobulinemia, HCV
Anti-GBM
SLE
Cryoglobulins, RF
ASO
MPGN
HIV
Post Strept GN
Hepatitis profile
C3, C4, CH50
HIV, FSGS
Renal Biopsy
Renal Biopsy : Ig A Nephropathy
Light microscopy - Mesangial
hypercellularity
IgA is predominantly polymeric IgA1
mainly derived from the mucosal
immune system
IgA Nephropathy : Berger’s Disease
the most common lesion found to cause
primary glomerulonephritis
peak incidence in the second and third
decades of life
2:1 male to female
greatest frequency in Asians and Caucasians
relatively rare in blacks
IgA Nephropathy
large undiagnosed "latent" IgA nephropathy
in the general population
the process of mesangial IgA deposition is
likely to be separate from the induction of
glomerular injury
IgA deposition does not necessarily need to be
followed by nephritis
IgA Deposition is Common
IgA deposition in other forms of
glomerulonephritis
thin basement membrane nephropathy
lupus nephritis
minimal change disease
diabetic nephropathy
IgA Nephropathy
Many patients are detected on routine urine
screening
asymptomatic hematuria and/or proteinuria
higher prevalence
active urine testing program
low threshold for renal biopsy
IgA Nephropathy
IgA nephropathy is established only
by kidney biopsy
Immunofluorescence microscopy
demonstrating large, globular
mesangial IgA deposits
also seen with HSP
IgA often accompanied by C3
and IgG in the mesangium
IgA Nephropathy
EM
electron dense deposits that are limited to the
mesangial regions
IgA Nephropathy
mesangial glomerulonephritis showing segmental areas of
increased mesangial matrix and cellularity
Conditions associated with IgA nephropathy
Idiopathic (most cases)
Hepatic cirrhosis
Gluten enteropathy
HIV infection
Minimal change
disease
Membranous GN
Wegener’s
granulomatosis
Dermatitis herpetiformis
Seronegative arthritis eg, ankylosing
spondylitis
Small cell carcinoma
Disseminated
tuberculosis
Mycosis fungoides
IgA Nephropathy
Initiating event in the pathogenesis is the
mesangial deposition of IgA
Codeposits of IgG and complement
commonly seen
may contribute to disease severity
Between episodes of gross hematuria
persistent microhematuria, proteinuria, or both.
Gross hematuria has also followed
tonsillectomy, vaccinations, strenuous physical
exercise, and trauma.
Increased Plasma IgA Levels
Not alone is not sufficient to produce
mesangial IgA deposits
Found in 50% of cases
IgA is probably accumulated and deposited
because of a systemic abnormality rather
than a defect intrinsic to the kidney
IgA Nephropathy
Two common presentations
episodic gross hematuria
40-50%
upper respiratory tract infection, or, less often,
gastroenteritis
persistent microscopic hematuria
30-40%
asymptomatic, with erythrocytes (RBCs), RBC casts,
and proteinuria discovered on urinalysis
IgA Nephropathy
Nephrotic range proteinuria is uncommon
occurring in only 5% of patients
Indicates more advanced disease
Approximately 1-2% of all patients with IgA nephropathy
develop ESRD each year
Hypertension seldom occurs at the time of initial
presentation
Ig A Pathophysiology
Platelet Derived Growth
Factors
Made by mesangial cells
Increased PDGG
receceptors in glomerular
dz
Infusion of glomerular
transfection with PDGF
leads to mesangial
proliferation
TGF- beta
Made by mesangial cells
Pro fibrotic
Antiinflammatory and
immunosuppresive
Morbidity and Mortality
follow a benign course in most cases
at risk for slow progression to ESRD
approximately 15% of patients by 10 years
20% by 20 years
Ig A Nephropathy Outcomes
20-30% progress to ESRD over 20 years
1-2% per year
Clinical predictors of poor renal outcome
Absence of gross hematuria
Male
Older onset age
HTN
Heavy proteinuria
Elevated Cr >2-2.5
Ig A Nephropathy Outcomes
Therapy remains to be defined
Antibiotics
Tonsillectomy
Cyclophosphamide, dipyridamole
High dose immunoglobulin therapy
Statins
Fish Oils
Ace inhibition
Cellcept (mycophenolate mofetil)
Ig A Nephropathy Outcomes
Ace inhibitors
Effectively reduce proteinuria in glomerular dz
ACE-I better than other anti – HTN meds to
preserve GFR in Ig A
Questionable addititive effect with ARBS
Ig A Nephropathy Outcomes
Fish Oil
Meta analysis concluded there may be a minor
benefit in heavy proteinuria
Dillon 1997 JASN
Low does omega 3 fatty acids as effective as high
dose
Cellcept
Inhibits de novo guanosine nucleotide synthesis
Established use for transplant
Not that much improvement for Ig A
Ig A Treatment Summary
If Uprot <0.5 g/d and CrCl >70
If Uprot > 0.5 g/d and Cr Cl > 70
ACEI/ARB for target bp 125/75
If Uprot 1-3 g/d with Cr Cl >70
Observe and consider ACEI or ARB
Maximal ACEI/ ARB
Consider 6 months of high dose steroids and taper for 6 mo
If Uprot >3 g/d and CrCl <70 or declining
Steroids plus Cytotoxics
Possible maintenance with AZA or MMF
Transplant Recipients
high recurrence rate in renal transplant
recipients who have IgA nephropathy
25-60%
Increased risk of allograft loss in living related
donor
disappearance of the deposits from donor
kidneys with IgA nephropathy when
transplanted into donors without the disease
Patient Progression
Cr continued to worsen with disease progression
March Cr: 2.0
April Cr: 3.09 – 4.2
Initiation of Cytoxan and Steroids ( 2 cycles)
ACEI caused hyperkalemia
Fish Oil, BB, Lasix , Zaroxolyn, Statin, PPI, Oscal
May Cr :5.2
June 18th: 8.76
ESRD with hemodialysis initiation
Uncontrollable edema and pulmonary edema despite
diuretics
Question 1
Which of the following is the most predictive
for progression of Ig A
A- elevated levels of IgA
B- elevated Cr at baseline diagnosis
C- male gender
D- absence of gross hematuria
Question 1
Which of the following is the most predictive
for progression of Ig A
A- elevated levels of IgA
B- elevated Cr at baseline diagnosis
C- male gender
D- absence of gross hematuria
Question 2
You are seeing a 30yr Asian woman with bx proven
Ig A. Her Uprotein is 3.5g/d despite maximal ACEI,
Bp is 100/70, Cr stable at 1.6 for the past year.
Diffuse foot process effacement is seen on EM.
What is the next step for management?
A- Add ARB
B- Add MMF
C- Add steroids
D- Add fish oils
E-Tonsillectomy
Question 2
You are seeing a 30yr Asian woman with bx proven
Ig A. Her Uprotein is 3.5g/d despite maximal ACEI,
Bp is 100/70, Cr stable at 1.6 for the past year.
Diffuse foot process effacement is seen on EM.
What is the next step for management?
A- Add ARB
B- Add MMF
C- Add steroids
D- Add fish oils
E-Tonsillectomy