1. Approach to the Patient of Glomerular Disease 신장내과 R4 조주희

2. Clinical Syndromes of glomerular injury 1.Acute nephritic syndrome 2.Nephrotic syndrome 3.Basement membrane syndrome 4.Glomerular-vascular syndrome 5.Infectious disease-associated syndrome

3. Clinical Syndromes – 1. Acute nephritic syndrome 1–2 g/24 h of proteinuria Hematuria with red blood cell casts Pyuria Hypertension Fluid retention Rise in serum creatinine associated with a reduction in glomerular filtration  If glomerular inflammation develops slowly, the serum creatinine will rise gradually over many weeks, but if the serum creatinine rises quickly, particularly over a few days, acute nephritis is called rapidly progressive glomerulonephritis (RPGN) - histopathologic term crescentic glomerulonephritis is the pathologic equivalent of the clinical presentation of RPGN

4. 0. Normal Glomerulus 1. Infiltration of many cells 2. Rupture of Glomerular capillary & Proteinaceous materials in bowman’s space 3. Cellular crescent 4. Fibrocellular crescent 5. Fibrous crescent and globalsclerosis

6. Type 1 : Anti-GBM Ab : 2-20% Goodpatures syndrome Type 2 : Immune complex : 15-40% idiopathic PIGN, SLE, HSP, IgAN Type 3 : Pauci-Immune, ANCA : 40-80% Granulomatosis with polyangitis (GPA) Microscopic polyangiitis (MPA) Churg-Strauss syndrome Renal limited, idiopathic Type 4 : Type 1 + Type 3 : Double antibody Disease Types of Crescentic GN

7. Relative Frequency of Immunopathologic Categories of Crescentic Glomerulonephritis in Different Age Groups Categories of CGNAge in Years 1–20 (n = 73) 21–60 (n = 303) >60 (n = 256) Anti-GBM GN 12%15% Immune complex GN 45%35%6% Pauci-immune GN 42%48%79% Other 0%3%0% Brenner The Kidney 8 th edition, p1036

8. Differential Diagnosis of Crescentic GN

9. Clinical Syndromes- 2. Nephrotic syndrome Heavy proteinuria (>3.0 g/24 h) Hypertension Hypercholesterolemia Hypoalbuminemia Edema/anasarca Microscopic hematuria  Glomerular filtration rate (GFR) in these patients may initially be normal or, rarely, higher than normal, but with persistent hyperfiltration and continued nephron loss, it typically declines over months to years.

10. Differential diagnosis of glomerular disease Acute renal failure in NS Concurrent ATN in MCD Tubular injury in collapsing FSGS MCD with acute interstitial nephritis induced by NSAID Crescentic GN superimposed upon MN Nephrotic syndrome secondary to monoclonal immunoglobulin deposition disease Superimposed thrombotic microangiopathy Severe volume depletion in an acutely developing hypoalbuminemia associated with MCD

11. Clinical Syndromes 3.Basement membrane syndrome microscopic hematuria mild to heavy proteinuria hypertension variable elevations in serum creatinine 4.Glomerular-vascular syndrome hematuria moderate proteinuria

12. Clinical Syndromes- 5. Infectious disease associated syndrome These infectious diseases produce a variety of inflammatory reactions in glomerular capillaries, ranging from nephrotic syndrome to acute nephritic injury, and urinalyses that de monstrate a combination of hematuria and proteinuria

13. IgA Nephropathy

14. Introduction  most common cause of primary glomerulonephritis throughout most developed countries  Japan and Korea - highest recorded incidences : 50% of new cases of GN and 40% of ESRD in Japan are due to IgAN  peak incidence in the second and third decades of life  50% of patients reaching ESRD after 20~25 yrs (20~25% over 10yrs ) N Engl J Med 2002; 347:738-748 Am J Kidney Dis. 1991;18(1):12

15. Pathology  pathognomonic finding on immunofluorescence microscopy - globular deposits of IgA (often accompanied by C3 and IgG) in the mesangium and, along the glomerular capillary wall  Light microscopy - focal or more often diffuse mesangial proliferation and matrix expansion - Segmental crescents are relatively common  Electron microscopy - electron-dense deposits that are primarily limited to the mesangium (may also occur in the subendothelial and subepithelial spaces)

16. N Engl J Med 2002; 347:738-748

17. Kidney International (2009) 76, 534–545  A consensus on pathologic classification of IgA nephropathy by the International IgA nephropathy Network in collaboration with the Renal Pathology Society  265 patients who were followed for a median of five years  following variables correlated with renal outcomes: Oxford classification of IgA nephropathy  not include crescents or necrotizing lesions

18.  Crescent (+) IgA 신증의 조직학적 특성과 임상양상 : 고혈압, 단백뇨의 정도가 심하고 말기신부전으로의 진행이 빠르다. James et al. Seminars in Nephrology 2004 Boyce et al. AJKD 1986  가속성 고혈압을 보이는 IgA 신증 환자의 70% 에서 crescent (+) 또는 endocapillary proliferation 이 관찰되었다. Subias et al. Clin Nephol 1987 crescent(-)(n=164)crescent(+)RPGN(-)(n=15)crescent(+)RPGN(+)(n=8) 신기능 감소 (%) 67.7%78.5%66.6%

19. Clinical feature  40~50% : one or recurrent episodes of visible hematuria, usually following an upper respiratory infection for a few years at most  'synpharyngitic hematuria‘  30 ~ 40 % : microscopic hematuria and usually mild proteinuria - incidentally detected on a routine examination  <10 % : present with either nephrotic syndrome or acute rapidly progressive glomerulonephritis picture  Rarely,present with malignant hypertension  Rarely, acute kidney injury with or without oliguria may be due to crescentic IgA nephropathy, or to heavy glomerular hematuria leading to tubular occlusion and/or damage by red cell

21. Renal prognosis  Reduced GFR  Hypertension SCrcumulative incidence of ESRD ≤1.25 mg/dL2.5 % 1.26 to 1.67 mg/dL26% >1.68 mg/dL71% - cumulative incidence of dialysis or death was much higher in patients with hypertension (>140/90 mmHg) at disease discovery compared with those without hypertension : 15% vs 3% and 41% vs 6 % at 10 and 20 years, respectively Nephrol Dial Transplant. 2006;21(10):2800 J Am Soc Nephrol. 2011;22(4):752

22. Renal prognosis  Protein excretion above 1 g/day : rate of progression is very low among patients excreting less than 1g/day and is greatest among those excreting more than 3.0 to 3.5 g/day  Acute onset of nephrotic syndrome : adverse predictor of prognosis  Hematuria without proteinuria recurrent episodes of gross hematuria without proteinuria are at low risk for progressive kidney disease compared with who have persistent microscopic hematuria and proteinuria Am J Kidney Dis. 1992;20(4):315  Oxford histologic classification  Hypertension J Am Soc Nephrol. 2011;22(4):752

23. Renal prognosis  Absolute renal risk score incidence of death or dialysis at 10 and 20 years for specific ARR scores : score of 0 – 2 and 4 % score of 1 – 2 and 9 % score of 2 – 7 and 18 % score of 3 – 29 and 64 %

24. Treatment 1. isolated hematuria, no or minimal proteinuria (less than 500 to 1000 mg/day), and a normal glomerular filtration rate - periodically monitored at 6 to 12 month intervals to assess for progression 2. persistent proteinuria greater than 1000 mg/day - angiotensin inhibition with an ACE inhibitor or ARB with a goal below 1000 mg/day 3. angiotensin inhibition elevated or increasing serum creatinine and/or protein excretion above 1.0 to 1.5 g/day despite maximum antiproteinuric therapy - immunosuppressive therapy with glucocorticoids 4. severe disease at baseline (initial serum creatinine >1.5 mg/dL ) or progressive disease (eg, increasing serum creatinine and/or protein excretion) with glucocorticoids alone who do not have significant chronic damage on kidney biopsy - oral prednisone and cyclophosphamide 5. crescentic glomerulonephritis and a rapidly progressive clinical course - intravenous pulse glucocorticoids and cyclophosphamide 6. acute onset of nephrotic syndrome - glucocorticoid therapy as in other patients with minimal change disease