Kidney Diseases with Proteinuria

Question 1

1. Describe (derangement of) normal glomerular physiology.

Answer 1

nephrotic syndrome can present with loss of normal interdigitation of podocytes or altered capillary permeability

disturbing the interaction between podocytes and BM can alter slit diaphragm (permeability) as well as causing foot detachment

Question 2

2. Describe the pathophysiology of diseases presenting with the nephrotic syndrome. Define nephrotic disease including signs.

Answer 2

nephrotic syndrome is caused by a derangement in glomerular capillary walls, resulting in increased permeability to plasma proteins with the following signs

nephrotic range proteinuria (>3.5 g/d)
hypoalbuminemia
edema
hyperlipidemia (increased production by liver)
lipiduria

Question 3

3,4 . Describe the morphology and corresponding clinical presentation of Minimal Change Disease

Answer 3

young patients presenting with 
massive proteinuria (>3.5g/d), hypoalbuminemia, generalized edema, hyperlipidemia and lipiduria

only microscopic abnormality will be loss effaced podocyte foot processes on EM

unknown etiology, usually cured with prednisone

Question 4

3,4 . Describe the morphology and corresponding clinical presentation of Focal Segmental Glomerular Sclerosis.

Answer 4

nephrotic syndrome (massive proteinuria (>3.5g/d), hypoalbuminemia, generalized edema, hyperlipidemia and lipiduria)

LM shows focal segmental glomerular
sclerosis (capillary loops appear collapsed, urinary space larger), EM shows foot process effacement

primary RSGS etiology is unknown, circulating factor may be a factor; poorly responsive to steroids (can progress to ESRF)

Question 5

5. Describe clinical disease entities presenting with nephrotic syndrome.

Answer 5

minimal change nephrotic syndrome (children)
focal segmental glomerulosclerosis (idiopathic or secondary)
membranous nephropathy (idiopathic o secondary)
diabetic nephropathy
amyloidosis

Question 6

5. Describe clinical disease entities presenting with nephrotic syndrome- secondary causes of FSGS.

Answer 6

since podocyte injury is central the following can contribute to damage:
HIV/AIDS
sickle cell disease
obesity (BMI to kidney perfusion low)
vesico-ureteral reflux
reduction in renal mass (unilateral renal agenesis)

Question 7

Describe the proteins linking of podocytes in the slit diaphragm

Answer 7

nephrine molecules have cysteine loops that help to link the processes from two cell together

Question 8

3,4 . Describe the morphology and corresponding clinical presentation of Congentital nephrotic syndrome (Finnish type).

Answer 8

nephrin mutations cause the development of renal failure in infancy due to podocytes inability to form and link

Question 9

3,4 . Describe the morphology and corresponding clinical presentation of Membranous nephropathy.

Answer 9

patients of all ages see damage due to immune complexes, antigen is in/of the podocyte, complexes can build up sub epithelial or with/in BM

silver stain on EM shows vertical spikes and granular pattern on Immunoflorescence due to deposition of C3 and IgG along peripheral capillary walls

etiology: autoantibodies to M-type phospholiase A2 receptor; outcomes vary and treatment includes ACEI, prednisone and immunosuppressive agents

Question 10

5. Describe clinical disease entities presenting with nephrotic syndrome- secondary causes of membranous glomerular nephropathy.

Answer 10

infectious organisms: hep B, malaria, syphilis
Drugs: catopril, NSAIDs, penicillamine, probenecid
Metals
Tumors (lymphomas and carcinomas

Question 11

5. Describe clinical disease entities presenting with nephrotic syndrome- systemic diseases.

Answer 11

diabetic nephropathy: directly related to duration of DM 1 or 2; characteristically acellular nodule pathologic lesion (Kimmelstiel-Wilson) due to reaction of amino groups of BM proteins to produce advanced glycation end products (AGEs), expansion of messangium with increases in fluid filtration

amylodosis: abnormal deposition of proteins with a fibrillar organization; primary (plasma cell neoplasia AL amyloid) and secondary (chronic inflammation-AA amyloid; highlighted with congo red stain and polarized light; EM shows fibrillar nature of protein deposited