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http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/index.htm

How many Americans have a Kidney KO?

Partial KO=Chronic Kidney DiseaseComplete KO=End Stage Renal Disease

Definition of CKD

5. Hyperglycemia6. Proteinuria

Definition of ESRD

5. Hyperglycemia6. Proteinuria

Time for CKD=>ESRD

Footnote: Difficulties in Measuring GFRΔ’s in CKD.

Good News• Throughout the long course of CKD, the

kidney demonstrates adaptive mechanisms, so that patients with a Cr=4 are generally symptom free (except for HTN) E ti t ith C 10HTN). Even some patients with Cr=10 are symptom free because they can still excrete excess Na, H20, and can conserve Na, H20 if the deficit is not so severe.

• No one should die from loosing renal function per se because of the availability of renal replacement therapies.

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Volume, Na handling in CKD

THE KIDNEY MAINTAINS STEADY STATEResponse of the Kidney to Changes in Diet

In Deficit and In Excess

N E

XCR

ETE

This

muc

h

This little Na THE KIDNEY CAN EXCRETE This much Na

This

littl

e H

2O

THE

KID

NEY

CA

NH

2O

CKDCKD

Deficit and Excesses of Volume in CKD• Remain in balance because our environmental perturbations

are limited and our diets fall in a narrow range.• Flexibility is lost to excrete large amounts of Na and water or to

conserve Na and water. • If losses to the environment increase (febrile illness, exposure) or

dietary intake is reduced, then conservation mechanisms by the kidney are found to be inadequate and hypovolemia, hypernatremia may be seen. O th th h d di t hi h ld b th i

CKD

• On the other hand, dietary excess which would be otherwise tolerated by normals results in hypoosmolarity and voume overload in CKD.

• Excesses or deficits are cumulative (ie day 5 in the ICU).• The imbalance worsens with progressive disease: Single nephron

drop out (glomerulonephritis) is less problematic than global dysfunction (tubulointerstitial disease) which interrupts the relationship of the nephron to the vasa recta.

.

Maintaining Volume, Na Balance in CKD

5. Filter 28,000mEq NaCl…..Excrete 140mEq (0.5%)Filter 2,800 mEq NaCl……Excrete 140mEq (5%)

How is the New Balance Achieved?

ANF………………… AII

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GFR

GFRΔP

πGC πGC

ΔP

mm

Hg

3030

Hormonal Regulation of Hormonal Regulation of ΔP, Δπ by ANFGFR=Kf x (ΔP - πGC)

GFR

πGC

ΔP

Distance Along Glomerular Capillary

Control ANP1010

A E A E

1- Dilates afferent arteriole2- This Increases ΔPGC by transmiting systemic pressures and it reduces ΔπGC by delivering fresh blood ie increases RBF, so that the Pequilibrium is not reached.3- This increases GFR

Angiotensin IIA E A E

ANF Receptor KO in mice=HTN

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Water handling in CKD

Maintaining Water Balance in CKD

Maintaining Water Balance in CKD

Separation of Tubule from PeriTububular Capillary in Interstitial Diseas

A-Mild Interstitial Fibrosis

B-Severe Interstitial Fibrosis results in a loss of concentrating ability ie can nomaximally absorb water. The patient will have an obligate loss of water, meaningurine flow is greater than appropriate. This results in nocturia, the patient has tofrom sleep, whereas normal kidneys (under the influence of ADH) would conserwater

K/Acid/Base Handling in CKD

1. 15% increase in the radial size of the tubules,

2. 35% increase in the length,

3. Increases in basolateral infolding

K excretion/ nephron is increased maintaining a normal K excretion

Increased ammoniagenesis, compensatory until a Creatinine=4

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Summary

• Natiuresis, ANF• Urine dilution intact, limited by GFR• Urine concentration disturbed, fibrosis• K excretion intact due to hypertrophy• NH3 excretion intact due to hypertrophy

Deficit and Excesses of Volume in CKD• Remain in balance because our environmental perturbations

are limited and our diets fall in a narrow range.• Flexibility is lost to excrete large amounts of Na and water or to

conserve Na and water. • If losses to the environment increase (febrile illness, exposure)

or dietary intake is reduced, then conservation mechanisms by the kidney are found to be inadequate and hypovolemia, hypernatremia may be seen. O th th h d di t hi h ld b th i

CKD

• On the other hand, dietary excess which would be otherwise tolerated by normals results in hypoosmolarity and voume overload in CKD.

• Excesses or deficits are cumulative (ie day 5 in the ICU).• The imbalance worsens with progressive disease: Single

nephron drop out (glomerulonephritis) is less problematic than global dysfunction (tubulointerstitial disease) which interrupts the relationship of the nephron to the vasa recta.

Progression of CKD: Glomerular HTN

Need for dialysis

5. Hyperglycemia6. Proteinuria

Protein Restriction

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Progression of CKD: Vitamin D

Ca PO4 and the Kidney

• Vitamin D production occurs in the kidney• Vitamin D production is sensitive to PO4

and Ca levels. Vit i D d ti i i hibit d b• Vitamin D production is inhibited by acidemia

• PO4 s normally excreted by filtration• Hyper-phosphatemia inhibits Vitamin D

production

Loss of Vitamin D3 Production and Hyperphosphatemia Results in Hyperparathyroidism

Sequelae of Hyper PTH

Sequelae of Hyper PTH

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Fall of Serum Calcium in CKD

Fall of Serum Calcium in CKD

Kidney Calcinosis

Summary

• Loss of PO4 excretion• Ca PO4 precipitation, further organ

damageD i f 1 25 Vit D• Depression of 1,25 Vit D

• Rise in PTH• Bone wasting

Therapy for Elevated PTH

Progression of CKD to ESRD

Progressive Failure Should be Linear, But Often it Isn’t Late in Disease Course

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Uremia

Anemia is a Major Component of Uremia

Anemia is Due to Loss of Erythropoeitin

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Summary

Diet Control is One of the Most Important Therapies for CKD

CKD=> ESRD

Afghanistan (1) Algeria (4) Andorra (1)

Angola (1) Anguilla (St Maarten) (1) Antigua and Barbuda (1)

Argentina (33) Armenia (1) Aruba (3)

Australia (127) Austria (82) Azerbaijan (1)

Bahamas (5) Bahrain (1) Bangladesh (11)

Barbados (6) Belgium (86) Belize (1)

Bermuda (1) Bolivia (1) Brazil (75)

CKD=> ESRD

Bermuda (1) Bolivia (1) Brazil (75)

Brunei (1) Bulgaria (5) Cameroon (1)

Canada (114) Cayman Islands (1) Chile (119)

China (12) Colombia (55) Costa Rica (4)

Croatia (Hrvatska) (39) Cuba (2) Cyprus (6)

Czech Republic (102) Denmark (20) Dominican Republic (8)

Ecuador (4) Egypt (78) El Salvador (5)

Finland (46) France (879) French Guiana (4)

French Polynesia (1) Germany (1351) Ghana (1)

From www. “Holiday Dialysis”