Nephrotic syndrome

1. Nephrotic syndrome

2. Figure 1. Nephrotic edema.

3. Figure 2. Nephrotic edema.

4. Clinical Syndrome • 肾脏及泌尿系疾病经常会引起一些临床症状、 体征和实验室表现相似的综合征。识别患者属于哪一种综合征对诊断很有帮助，因为导致每个综合征的病因较之其包含的个别临床症状和体征的致病原因要少，故识别患者属于哪一种综合征对诊断有帮助。

5. The most common syndrome of kidney disease 肾脏疾病常见综合征 • Nephrotic syndrome • Nephritic syndrome • Asymptomatic urinary abnormalities • Acute renal failure or Rapidly progressive renal failure • Chronic kidney disease(Table 1) • (一)肾病综合征 • (二)肾炎综合征 • (三)无症状性尿检异常 • (四)急性及急进性肾衰竭综合征 • (五)慢性肾脏病(表1)

6. Table 1. STAGES OF CHRONIC KIDNEY DISEASE* * Chronic kidney disease is defined as either kidney damage or GFR < 60mL/min/1.73m2 for ≥ 3months. Kidney damage is defined as pathologic abnormalities or markers of damage, including abnormalities in blood or urine tests or image studies.

7. Nephrotic syndrome This is characterized by proteinuria (Typically > 3.5g/24h), hypoalbuminemia ( less than 30g/dL ) and edema. Hyperlipidaemia is also present. Primary and secondary causes are summarized in Table 2, 3 In practice, many clinicians refer to “nephrotic range” proteinuria regardless of whether their patients have the other manifestations of the full syndrome because the latter are consequences of the proteinuria.

8. NEPHROTIC SYNDROME • Pathophysiology • Proteinuria • Hypoalbuminemia • Edema • Hyperlipidemia • Cause (diagnosis and differential diagnosis) • Systemic renal disease hepatitis B associated glomerulonephritis, Henoch-Schonleinpurpura, systemic lupus erythematosus, diatetes mellitus, amyloidosis • Idiopathic nephrotic syndrome • Complications • Infection • Coagulation disorders • Protein malnutrition and dyslipidemia • Acute renal failure

9. Pathophysiology

10. Proteinuria • Proteinuria can be caused by systemic overproduction, tubular dysfunction, or glomerular dysfunction. It is important to identify patients in whom the proteinuria is a manifestation of substantial glomerular disease as opposed to those patients who have benign transient or postural (orthostatic) proteinuria.

11. Heavy proteinuria (albuminuria) Figure 3.

12. Hypoalbuminemia • Hypoalbuminemia is in part a consequences of urinary protein loss. It is also due to the catabolism of filtered albumin by the proximal tubule as well as to redistribution of albumin within the body. This in part accounts for the inexact relationship between urinary protein loss, the level of the serum albumin, and other secondary consequences of heavy albuminuria .

13. Edema The salt and volume retention in the NS may occur through at least two different major mechanisms. • In the classic theory, proteinuria leads to hypoalbuminemia, a low plasma oncotic pressure, and intravascular volume depletion. Subequent underperfusion of the kidney stimulates the priming of sodium-retentive hormonal systems such as the RAS axis, causing increased renal sodium and volume retention, In the peripheral capillaries with normal hydrostatic pressures and decreased oncotic pressure, the Starling forces lead to transcapillary fluid leakage and edema .

14. Edema • In some patients, however, the intravascular volume has been measured and found to be increased along with suppression of the RAS axis. An animal model of unilateral proteinuria shows evidence of primary renal sodium retention at a distal nephron site, perhaps due to altered responsiveness to hormones such as atrial natriuretic factor. Here only the proteinuric kidney retains sodium and volume and at a time when the animal is not yet hypoalbuminemic. Thus, local factors within the kidney may account for the volume retention of the nephrotic patient as well.

15. Figure 4.

16. Hyperlipidemia • Most nephrotic patients have elevated levels of total and low-density lipoprotein (LDL) cholesterol with low or normal high-density lipoprotein (HDL) cholesterol . Lipoprotein (a) [Lp(a)] levels are elevated as well and return to normal with remission of the nephrotic syndrome. Nephrotic patients often have a hypercoagulable state and are predisposed to deep vein thrombophlebitis, pulmonary emboli, and renal vein thrombosis.

17. Cause

18. Table 2 CAUSES OF THE NEPHROTIC SYNDROME

19. Table 3a NEPHROTIC SYNDROME ASSOCIATED WITH SPECIFIC CAUSES (“SECONDARY” NEPHROTIC SYNDROME)

20. Table 3b NEPHROTIC SYNDROME ASSOCIATED WITH SPECIFIC CAUSES (“SECONDARY” NEPHROTIC SYNDROME)

21. Pathology patterns and clinical presentations of idiopathic nephrotic syndome

22. Renal biopsy • In adults, the nephrotic syndrome is a common condition leading to renal biopsy. In many studies, patients with heavy proteinuria and the nephrotic syndromes have been a group highly likely to benefit from renal biopsy in terms of a change in specific diagnosis, prognosis, and therapy. • Selected adult nephrotic patients such as the elderly have a slightly different spectrum of disease, but again the renal biopsy is the best guide to treatment and prognosis (Table 2, 3).

23. PRIMARY NEPHROTIC SYNDROME • Minimal Change Disease • Focal Segmental Glomerulosclerosis • Membranous Nephropathy • Membranoproliferative Glomerulonephritis (MPGN)

24. Figure 5a. Pathology of glomerular disease. Light microscopy. (a) Normal glomerulus; minimal change disease.

25. Table 4

26. PRIMARY NEPHROTIC SYNDROME • Minimal Change Disease • Focal Segmental Glomerulosclerosis • Membranous Nephropathy • Membranoproliferative Glomerulonephritis(MPGN)

27. Figure 5b. Segmental sclerosis; focal segmental glomerulosclerosis.

28. Figure 6. Light microscopic appearances in focal segmental glomerulosclerosis. Segmental scars with capsular adhesions in otherwise normal glomeruli.

29. Table 5

30. PRIMARY NEPHROTIC SYNDROME • Minimal Change Disease • Focal Segmental Glomerulosclerosis • Membranous Nephropathy • Membranoproliferative Glomerulonephritis(MPGN)

31. Figure 7a. Early MN: a glomerulus from a patient with severe nephrotic syndrome and early MN, exhibiting normal architecture and peripheral capillary basement membranes of normal thickness (Silver–methenamine ×400).

32. Figure 7b morphologically advanced MN

33. Figure 7c. Morphologically more advanced MN (same patient as in (b))

34. Table 6

35. PRIMARY NEPHROTIC SYNDROME • Minimal Change Disease • Focal Segmental Glomerulosclerosis • Membranous Nephropathy • Membranoproliferative Glomerulonephritis(MPGN)

36. Figure 8. Pathology of membranoproliferative glomerulonephritis type I. (a) Light microscopy shows a hypercellular glomerulus with accentuated lobular architecture and a small cellular crescent (methenamine silver).

37. Table 7

38. Diagnosis and Differential diagnosis

39. Initial evaluation of the nephrotic patient includes laboratory tests to define whether the patient has primary, idiopathic nephrotic syndrome or a secondary cause related to a systemic disease.

40. Common screening tests include the fasting blood sugar and glycosylated hemoglobin tests for diabetes, and antinuclear antibody test for rheumatoid disease, and the serum complement, which screen for many immune complex-mediated disease (Table 3), In selected patients, cryoglobulins, hepatitis B and C serology, anti-neutrophil cytoplasmic antibodies (ANCAS), anti GBM antibodies, and other tests may be useful. Once secondary causes have been excluded, treating the adult nephrotic patient often requires a renal biopsy to define the pattern of glomerular involvement.

41. Complications • Infection • Coagulation disorders • Protein malnutrition and dyslipidemia • Acute renal failure • It leads to a multitude of other consequences , such as predisposition to infection and hypercoagulability. In general, the diseases associated with NS cause chronic kidney dysfunction, but rarely they can cause ARF. ARE may be seen with minimal change disease, and bilateral renal vein thrombosis.

42. Treatment 治疗 1. General treatment 2. Symptomatic treatment (e.g.diuresis to relieve edema, treating dyslipidemias, anticoagulate treatment, etc.) 3. Immunosupressive treatment 一、一般治疗 二、利尿消肿 三、免疫抑制治疗 四、调脂药物 五、抗凝治疗

43. Thank you