Kidney Remnant Model. Brown. 2013. JVECC

Question 1

How is removal of tissue generally accomplished in the kidney remnant model?

Answer 1

surgery:

• surgical removal typically involved unilateral nephrectomy
• other study sharp dissection

infarction

• ligation of a variable number of interlobular arteries > loss of viability of the infarcted area

Question 2

What does graded reduction of renal mass entail?

Answer 2

unilateral nephrectomy combined with contralateral infarction

• can express the degree of renal mass reduction as a fraction of total renal mass, e.g., 3/4, 15/16

Question 3

What is the goal of renal remnant model studies?

Answer 3

the remaining kidney mass is used to study the changes occuring in nephrones of patients with reduced renal function irrespective of the primary kidney disease

i.e., how do the left over nephrons adapt

Question 4

Describe the “intact nephron hypothesis”

Answer 4

hypothesis that surviving nephrons of the diseased kidney retain functional integrity and that these nephrons undergo adaptions that are the same regardless of the inciting cause of CKD

Question 5

What is “Bright’s disease”?

Answer 5

a historical, general term for end-stage human renal disease

characterized by proteinuria, uremia, and histologic appearance of severe interstitial fibrosis

indicates a final common pathway of progressive CKD, not a specific kidney disease

Question 6

How is compensation of the remaining nephrons demonstrated on postmortem dissections of kidneys of people with Bright’s disease?

Answer 6

surviving or remnant nephrons were dramatically enlarged, confirming the presence of renal compensatory hypertrophy

i.e., shrunken fibrotic kidneys are populated by enlarged, structurally intact nephrons

Question 7

What is the veterinary equivalent of Bright’s disease?

Answer 7

chronic interstitial nephritis

Question 8

What is the hyperfiltration theory?

Answer 8

“hyperfiltration theory” = adaptive glomerular hyperperfusion, hyperfiltration, hypertension ==> progressive loss of nephrons, decrements of GFR, ==> progressive nature of CKD

hemodynamic changes in remnant nephrons

• adaptive increases in glomerular pressures and flows in remnant nephrons ==> short term beneficial increase in GFR ==> but ultimate nephron destruction

Question 9

what are the main maladaptions leading to inherent progression of CKD?

Answer 9

• glomerular hyperperfusion
• hyperfiltration
• hypertension

Question 11

what dietary changes have shown to reduce progression in CKD and how does this support the hyperfiltration theory?

Answer 11

single nephron hyperfiltration is linked to alterations in renal eicosanoid metabolism:

• changing dietary polyunsaturated fatty acid composition ==> alters renal eicosanoid metabolism ==> blunts these adaptions ==> slows progression of CKD

Question 12

name a marker of glomerular hypertension

Answer 12

proteinuria

changes in proteinuria mirror changes in intraglomerular pressure

important predictor of future progression

Question 13

what type of damage does the nephron sustain in the face of arterial hypertension and what is its protective mechanism?

How is this altered in CKD?

Answer 13

renal autoregulation

critical in protecting the renal microcirculation from barotrauma and shear stress

studies showed that renal autoregulation was impaired in the face of azotemia, impairment was directly related to the severity of renal dysfunction

Question 14

What are the trade-off of re-establishing the phosphate balance in CKD?

Answer 14

effects of:

• adverse effects of hyperphosphatemia
• renal secondary hyperparathyroidism