L5. Kidney in Systemic disease

Question 1

LUPUS NEPHRITIS

Age:

Presentation:

ARA criteria:

Lab:

Pathology

Pathogenesis:

Answer 1

Age: Early age onset, nephritis w/i 3 yrs after diagnosis

Presentation: Hematuria, nephritic syndrom not uncommon, prominent proteinuria

ARA criteria: 4 of 11ARA criteria –> 96% sensitivity and specificity for SLE

Lab: : “telescoped” urine, Serum ANAs (anti-ds-DNA Ab). Serum C3 and C4 decreased

Pathology: ISN/RPS classification

Pathogenesis: Immune complex disease

Question 2

American College of Rheumatology criteria for diagnosis of lupus

Answer 2

Question 3

Name and Define Class I- VI of the ISN/RPS classification of lupus nephritis

Answer 3

ISN/RPS Classification of Lupus Nephritis

Class I Minimal mesangial lupus nephritis
(normal glomeruli by LM but mesangial deposits by IF)

Class II Mesangial proliferative lupus nephritis
(mesangial hypercellularity by LM and mesangial
deposits by IF)

Class III Focal lupus nephritis (< 50% of glomeruli)
(endo- or extracapillary glomerulonephritis, typically
with subendothelial deposits and mesangial deposits)

Class IV Diffuse lupus nephritis (> 50% of glomeruli)
(endo- or extracapillary glomerulonephritis, typically
with subendothelial deposits and mesangial deposits)

Class V Membranous lupus nephritis

Class VI Advanced sclerosing lupus nephritis (> 90%)

Question 4

Focal lupus nephritis subtypes

Answer 4

III (A): active lesions
III (A/C): active and chronic lesions
III (C): chronic lesions

Question 5

Diffuse lupus nephritis subtypes

Answer 5

Diffuse segmental (IV-S) or global (IV-G) LN
IV (A): active lesions
IV (A/C): active and chronic lesions
IV (C): chronic lesions

Question 6

Describe pathogenesis of SLE

Answer 6

Multiple etiologic factors act on the immune system. The generation of auto-antibodies, immune complexes, T cells and inflammatory cytokines initiate damage to various organs.

Question 7

Explain the different mechanism of immune complexe deposition on lupus nephritis

Answer 7

1. Classic –> Preformed Ag-Ab complexes get trapped in glomerulus
2. Ab bind to intrinsic glomerular Ag (membranous lupus)
3. Ab bind to extrinsic Ag that become trapped in glomeruli
4. Pauci-immune pattern w/o ANCAs or immune complexes –> necrotizing lupus nephritis

Question 8

What is the most common cause of ESRD

Answer 8

Diabetic nephropathy

Question 9

Describe the pathology behind Diabetic nephropathy

Answer 9

glomerular enlargement,

GBM thickening,

diffuse increase in mesangial matrix and with progression,

prominent mesangial nodules (Kimmelstiel-Wilson lesions) form;

hyalinosis of Bowman’s capsule (“capsular drops”)

severe hyaline arteriolosclerosis (of both afferent and efferent hilar arterioles).

Question 10

Pathogenesis of Diabetic nephritis

Answer 10

Multifactorial

• Advance glycation end products (AGEs)
• Protein kinase C activation
• Polyol pathway

Question 11

Explain diabetic retinopathy and its relation w/ diabetic nephritis

Answer 11

Arborization of blood vessels under the influence of VEGF + microaneurism formation –> Reflects what is going on at the vascular level in the kidneys

Question 12

Explain the process of Advance glycation end products (AGEs)

Answer 12

AGEs accumulate

(1) directly cross-link matrix proteins
(2) interact with receptors (ex. RAGE) leading to nuclear factor Kb activation, which results in growth factor-mediated synthesis of matrix proteins.