1. IgA nephropathy haiying liu department of nephrology
the second hospital of shandong university

2. 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

3. 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

4. IgA Deposition is Common
IgA deposition in other forms of glomerulonephritis
thin basement membrane nephropathy
lupus nephritis
minimal change disease
diabetic nephropathy

5. 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

6. IgA Nephropathy demonstrating large, globular mesangial IgA deposits
IgA nephropathy is established only by kidney biopsy
Immunofluorescence microscopy
demonstrating large, globular mesangial IgA deposits
IgA often accompanied by C3 and IgG in the mesangium

7. IgA Nephropathy EM
electron dense deposits that are limited to the mesangial regions

8. IgA Nephropathy
mesangial glomerulonephritis showing segmental areas of increased mesangial matrix and cellularity

9. Conditions associated with IgA nephropathy
Idiopathic (most cases)
Hepatic cirrhosis
Gluten enteropathy
HIV infection
Minimal change disease
Membranous GN
Wegener’s granulomatosis
ankylosing spondylitis
Small cell carcinoma
Disseminated tuberculosis

10. 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.

11. Increased Plasma IgA Levels
Not alone is 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

12. 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

13. 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

14. 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

15. 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
Heavy proteinuria
Elevated Cr >2-2.5

16. 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)

17. Ig A Nephropathy Outcomes
Ace inhibitors
Effectively reduce proteinuria
ACE-I preserve GFR in Ig A
Questionable addititive effect with ARBS

18. 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
Established use for transplant
Not that much improvement for Ig A

19. Ig A Treatment Summary If Uprot <0.5 g/d and CrCl >70
Observe and consider ACEI or ARB
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
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

20. Transplant Recipients
high recurrence rate in renal transplant recipients who have IgA nephropathy
25-60%
disappearance of the deposits from donor kidneys with IgA nephropathy when transplanted into donors without the disease

21. Case Presentation 44-year-old white male with complaints of hematuria
had associated abdominal pain
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

22. Case Presentation
recent upper respiratory infection 2 weeks ago with fevers and chills
foamy urine
denies any recent known UTI, over-the-counter NSAIDs, history of nephrolithiasis, contrasted procedure, physical exercise

23. Case Presentation Positive signs : Recent URI two weeks ago
10 pound weight gain with edema
Hematuria
Foamy urine
Abdominal pain

24. Case Presentation : Labs
CCa 9.6 Alb 1.6
No Phos or Mg
UA is cloudy with positive nitrite, 10 grams protein, too numerous to count red cells, trace bacteria, 1-5 white cells

25. 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

26. Case Presentation : Labs
All negative
Complements
ANA, dsDNA
Hepatitis profile
Anti GBM
P and C ANCA’s
HIV
ASO

27. 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 2.0mg/dl
10 grams proteinuria
Hyperlipidemia

28. Red Blood Cell Casts Glomerular hematuria Dysmorphic rbc’s
glomerular damage
rule out urologic causes

29. Differential Diagnosis: Glomerulonephritis
Postinfectious GN
IgA nephropathy
Thin basement membrane
Mesangial proliferative GN
SLE
Goodpasture’s syndrome
Vasculitis
Cryoglobulinemia
HIV
Membranoproliferative glomerulonephritis
Rapidly progressive GN
Focal glomerulosclerosis
Membranous nephropathy
Amyloidosis
Multiple Myeloma DM
HUS

30. Renal Biopsy : Ig A Nephropathy
Light microscopy - Mesangial hypercellularity
IgA is predominantly polymeric IgA1
mainly derived from the mucosal immune system

31. 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

32. 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

33. 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

34. Question 2
You are seeing a 30yr Asian woman with 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

35. 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