Primary Nephrotic Syndrome

1. Primary Nephrotic Syndrome Mao Jianhua, Department of Nephrology, The Children’s Hospital of Zhejiang University School of Medicine

2. Introduction Nephrotic syndrome is a group of symptoms including proteins in the urine (more than 50 mg/kg/day), low blood albumin levels, high cholesterol levels, and swelling.

3. Secondary NS This condition can also occur as a result of infections, use of certain drugs, cancer, genetic disorders, immune disorders, or diseases that affect multiple body systems including diabetes, HBV infections, systemic lupus erythematosus, Henoch Schonlein purpura, etc.

4. Congenital NS Finnish type of congenital nephrotic syndrome Diffuse Mesangial Sclerosis Familial FSGS …

5. Primary NS in children ■Minimal change disease: 80% ■ FSGS: 10% ■Mesangioproliferative glomerulonephritis: 5% ■Membranous glomerulopathy ■ Membranoproliferative glomerulonephritis

6. Nephrotic syndrome is characterized by • Proteinuria：>50 mg/kg/24hr • Hypoalbuminemia：<25~30 g/L • Hyperlipidemia：Cholesterol>5.72 mmol/L • Edema: the most common symptom in NS

7. Heavy proteinuria---reasons and results ? • Injured glomerular filtration barrier. • Prolonged glomerular leakage of protein leads to hypoalbuminaemia that is associated with loss of fluid into the extracellular space, manifested as edema. Reduction in circulating volume stimulates renal retention of salt and water.

10. Plasma Oncotic pressure Interstitial pressure Interstitial pressure Interstitial oncotic pressure Interstitial oncotic pressure Blood pressure

11. （A）Proteinuria is the essential alteration in pathogenesis of nephrotic syndrome

12. The syndrome results from a major alteration in glomerular permeability due to structural damage of the glomerular capillary wall or loss of its negative charges.

13. （B）Hypoalbuminemia is the major manifestation

14. （C）Edema may be the only clinical manifestation in some patients

15. 1、Decrease in plasma oncotic pressure 2、Fluid volume excess

16. （D）Hyperlipidemia is one of the sentinel features of NS

17. Hyperlipidemia occurs as a enhanced hepatic synthesis and defective peripheral utilization of lipids.

18. CLASSIFICATION

19. ETIOLOGY • Primary (idiopathic)： • Secondary：HSP，SLE，Hepatitis B Virus associated nephritis, et al. • Congenital：3~6 months

20. MANIFESTATION • 单纯型：只具有上述四大特征 • 肾炎型：还具有以下四项之一或多项者 ① 两周内3次尿沉渣红细胞>10个/HP ② 反复出现或持续高血压，学龄儿童 >130/90mmHg，学龄前儿童> 120/80mmHg，排除激素影响 ③ 持续性氮质血症，排除少尿因素 ④ 血总补体活性或C3反复降低

21. When the renal biopsy is appropriate?

22. 1. Once there are clinical features suggesting a diagnosis other than MCD. 2. If the onset of Nephrotic syndrome begins in the first year of life or after 6 years of age. 3. When there is failure to respond to a 28-day course of prednisone, particularly if there have been changes in the clinical course during this period of time.

24. Renal Anatomy Minor calyx Medullary pyramid Minor calyx Renal column (of Bertin) Renal column (of Bertin) Major calyx Renal Pelvis Cortex Papilla Papilla

25. Minimal ChangeGlomerulonephritis

27. 正常肾小球，用PAS染色以突出基底膜。肾小球血管袢薄而清晰。正常肾小球，用PAS染色以突出基底膜。肾小球血管袢薄而清晰。

28. normal glomerulus

29. a much higher magnification electron micrograph. The urinary space and the foot processes are at the top

31. only background staining in minimal nephrotic syndrome patients

32. MCD

40. IgA nephropathy: IgA deposits in mesangial area.

41. FSGS

43. a silver-stained section with collapsing variant of FSGS

44. 电镜下膜增生性肾小球肾炎II型，基底膜有电子致密物沉积。这些基底膜内的暗色的电子致密物沉积常融合成肋骨样。电镜下膜增生性肾小球肾炎II型，基底膜有电子致密物沉积。这些基底膜内的暗色的电子致密物沉积常融合成肋骨样。

46. 肾小球的银染突出了呈黑色的蛋白基底膜。可见膜性肾小球肾炎时黑色的基底膜物质突出于毛细血管袢周围，呈特征性的“火焰”状。肾小球的银染突出了呈黑色的蛋白基底膜。可见膜性肾小球肾炎时黑色的基底膜物质突出于毛细血管袢周围，呈特征性的“火焰”状。

47. COMPLICATIONS

48. Infection：bacteria, virus or fungus

49. Electrolyte imbalance

50. Hypercoagulable status and Thrombosis