Nephritic syndrome

1. Nephritic syndrome

2. Definition : • Injury to or inflammation of the glomeruli (with damage involving the basement membrane ,capillary endothelium , and mesangium) that enables passage of proteins ,erythrocytes , and leukocytes into the renal tubule , along with decreased GFR , and abnormal blood pressure regulation .

3. Manifestations : • Azotemia • Decreased GFR • Hematuria ( with RBC casts ), proteinuria ( non-nephrotic range ) , and pyuria • Hypertension

4. Causes • Either primary or secondary • Can also be classified as immune complex mediated vs Pauci-immune

6. IgA nephropathy ( Berger's Disease ) • The MOST COMMON primary glomerulonephritis in adult population. • Is also the most common cause of recurrent gross hematuria . • Typically causes hematuria 2 days post URTI . • IgA antigen-antibody complexes are deposited within the mesangium. • Could primarily affect the kidney or could be a part of a wider spectrum of diseases including HIV , celiac disease , alcoholic liver disease and IBD . • It is the renal manifestation of Henoch-Schonlein purpura . • Has predilection for males , especially of Asian or white descents .

7. Diagnosis • Kidney biopsy reveals mesangioprolifrative glomerulonephritis on light microscopy , and IgA –Dominant mesangial immune deposits on immunofluorescence .

8. Treatment • Patients who have IgA nephropathy with a low risk of progressive disease should be treated with ACE-I to maintain a goal 24 hour urine protein excretion of less than 1 g /24 hours , and a blood pressure of less than 130 / 80 . • Immunosuppressive therapy must be considered for: 1- patients with persistent proteinuria ( more than 1g/24 hours) , 2-progressive kidney dysfunction, 3-or histological findings indicative of a more aggressive disease ( like crescents ) This includes pulse corticosteroids and cyclophosphamide followed by azathioprine with ACE-I .

9. Post- infectious GN • Glomerulonephritis secondary to bacterial infection most commonly the nephritogenic strains of streptococcus ( group A beta hemolytic streptococci ),causing a type III hypersensitivity reaction . • Typically affects children 2 weeks post throat infection or 6 weeks post skin infection ( impetigo ) .

10. Reminder

13. Clinical manifestations

16. Management • Supportive with management of high blood pressure and fluid overload , spontaneous resolution is expected .

17. Membranoproliferative glomerulonephritis • Also called mesangiocapillary GN. • Immune complex formation secondary to chronic antigen stimulation. • Common causes are : • Chronic indolent infections including hepatitis C, syphilis , mastoiditis …etc. . • Autoimmune such as Sjogren , lupus …etc. • Essential cryoglobulinemia ( types I and II ) ,what is this , and what is the Meltzer triad ???? • Malignancies such as carcinomas , sarcomas , lymphomas and leukemias . • Partial lipodystrophy ( type 2 memranoprolifrative )

18. immune-complex and/or complement protein deposition in the mesangium and sub endothelium of the capillaries • this results in proliferation of the mesangial and remodeling of the capillary wall

20. TREATMENT and PROGNOSIS • Corticosteroids • Immunosuppressive agents • Antiplatelets More than 50 % progress to advanced CKD .

21. Anti- Glomerular Basement Membrane Antibody Disease • Antibodies develop against the GBM ( type IV collagen ) , deposited in a linear pattern , • Leading to influx of inflammatory cells and mediators , resulting in a necrotizing rapidly progressive glomerulonephritis . Which should be treated urgently . • Younger patients are more likely to manifest Goodpasture Syndrome with diffuse pulmonary hemorrhage associated with RPGN .

23. Treatment • Plasmapheresis using albumin replacement for 1-2 weeks ,followed by corticosteroids and cyclophosphamide for 3-6 months , • Maintenance with azathioprine for 1-2 years .

24. Other causes • Include lupus nephritis , cryoglobulinemic vasculitis , Wegner Granulomatosis , and Churg Straus syndrome ) which were covered in rheumatology lectures ) .

25. Question 1 • A 9-year-old Caucasian girl presents to your office with hematuria. An electron micrograph of her renal biopsy is shown below in Figure A. Which of the following is the most likely composition of the structures marked by the white arrows?

26. 1Albumin • 2Non-enzymatic glycosylation • 3IgA • 4IgG • 5IgG, IgM, C3

27. Question 2 • A 62-year-old man presents to his primary care doctor complaining of recent-onset hemoptysis. He has not had any fevers, night sweats, or weight loss. He recently traveled to Italy with his wife. He has a 5 pack-year smoking history. On review of systems, he reports that his urine has been “red-tinged” for several months. Urinalysis reveals the findings shown in Figure A. He is referred to a nephrologist and undergoes a renal biopsy. Immunofluorescence staining of the biopsy is shown in Figure B. Which of the following is the most likely underlying pathogenesis of his disease?

29. 1Type III hypersensitivity reaction • 2Antibodies to collagen type IV • 3Presence of C-ANCA • 4Mycobacterial infection • 5Metastatic malignancy

30. Question 3 • A 21-year-old male presents to your office with hematuria 3 days after the onset of a productive cough and fever. Following renal biopsy, immunofluorescence shows granular IgA deposits in the glomerular mesangium. Which of the following do you suspect in this patient? • 1Lipoid nephrosis • 2Berger’s disease • 3Poststreptococcal glomerulonephritis • 4Systemic lupus erythematosus • 5HIV infection

31. Question 4 • Multiple patients present to your office with hematuria following an outbreak of Group A Streptococcus. Biopsy reveals that all of the patients have the same disease, characterized by large, hypercellular glomeruli with neutrophil infiltration. Which patient has the best prognosis? • 65-year-old nulliparous woman • 50-year-old man with a history of strep infection • 8-year-old boy who undergoes no treatment • 38-year-old man with sickle cell trait • 18-year-old man treated with corticosteroids

32. Question 5 • A 37-year-old man presents with significant hematuria and hemoptysis. The results of the immunofluorescence are shown in Figure A. What pathologic changes would be expected under light microscopy?

33. 1"Wire looping" of the capillaries • 2Hypercellular glomeruli • 3Crescentic glomerulonephritis • 4Focal proliferative glomerulonephritis • 5Normal glomeruli

34. Question 6 • A 25-year-old male visits his primary care physician with complaints of hemoptysis and dysuria. Serum blood urea nitrogen and creatinine are elevated, blood pressure is 160/100 mm Hg, and urinalysis shows hematuria and RBC casts. A 24-hour urine excretion yields 1 gm/day protein. A kidney biopsy is obtained, and immunofluorescence shows linear IgG staining in the glomeruli. Which of the following antibodies is likely pathogenic for this patient’s disease?

35. 1Anti-DNA antibody • 2Anti-neutrophil cytoplasmic antibody (C-ANCA) • 3Anti-neutrophil perinuclear antibody (P-ANCA) • 4Anti-glomerular basement membrane antibody (Anti-GBM) • 5Anti-phospholipid antibody

36. Question 7 • Three weeks after recovering from pharyngitis, a nine-year-old girl presents with periorbital edema and dark brown urine. An image of the kidney biopsy is shown in Figure A. What is responsible for these changes?

37. Thank you