1. Selected aspects of acid base physiology- acidosis in CKD
Norbert Lameire, MD, PhD
Em Prof of Medicine
University Hospital
Gent, Belgium
Tbilisi, October 2015

2. Normal Blood pH:

3. The Organim Faces Daily Acid Stress

4. The Regulation of Blood pH

5. Buffer Systems (I)

6. Buffer Systems (II)

7. Acid Stress: The Respiratory Response

8. Acid Stress: The Renal Response

9. Bicarbonate Reabsorption in Proximal Tubule

10. In Summary….

11. Clinical manifestations of acidemia
Kalantar-Zadeh et al, N Engl J Med 2013;369:

12. ANION GAP

13. The anion gap High AG acidosis Normal AG acidosis Normal AG AG AG HC03
Cl-
Na+
Cl-
Na+
Cl-
Na+
The anion gap

14. Normal values of serum anion gap in the literature
Kraut, Nagami, Clin J Am Soc Nephrol 8: 2018–2024, 2013

15. Classification of metabolic acidosis
Chloride-rich solutions

16. The metabolic acidosis of chronic kidney disease

17. Relationship between plasma bicarbonate and GFR in patients with CKD of various causes
Elkinton JR Ann Int Med 57: , 1962

18. Evolution of the electrolyte pattern of metabolic acidosis in CKD
Widmer et al, Arch Int Med 139: ,1979
In the phase of early renal dysfunction, the prevailing mild hypobicarbonatemia is entirley offset by an increase in serum chloride with the unmeasured anions remaining normal. At more advanced CKD (< 25% of normal) the graded decrements in bicarbonate are associated with equivalent increments in unmeasured anions, but the element of yperchloremia established earlier persists.

19. Association of serum bicarbonate levels with mortality in patients with non-dialysis-dependent CKD
Kovesdy et al, Nephrol Dial Transplant (2009) 24: 1232–1237

20. Cardiovascular and renal outcomes in CKD 2/4 related to serum bicarbonate quartiles
Renal outcome: ESRD (start of dialysis or kidney Tx or 50% reduction in eGFR)
Dobre et al, Am J Kidney Dis. 62(4): ,2013

21. Effect of bicarbonate treatment on progression of CKD
Yeong et al, Electrolyte Blood Press 12:80-87, 2014

22. Changes of renal function during treatment with oral bicarbonateNS
P <0.05
Yeong et al, Electrolyte Blood Press 12:80-87, 2014

23. Bicarbonate substitution refrains progression of CKD
Figure 3. Kaplan-Meier analysis to assess the probability of reaching ESRD for the two groups.
De Brito-Ashurst et al, JASN, 20, , 2009

24. Bicarbonate substitution improves dietary protein intake
De Brito-Ashurst et al, JASN, 20, , 2009

25. Beneficial effects on GFR decline of bicarbonate treatment of acidosis in CKD
Susantitaphong et al, Am J Nephrol 2012;35:540–547

26. CONCLUSIONS (1)
Acid-base homeostasis is regulated by a complex set of mechanisms inclusing intestine, lungs and kidneys (tubular system)
Acidemia disturbs many physiological functions
The type of acidemia is defined by the anion gap
High anion gap (normochloremic) is characterized by retention of extra anions (acids)
Normal anion gap (hyperchloremic) is characterized by loss of bicarbonate, compensated by chloride retention

27. CONCLUSIONS (2)
Acidosis of CKD is a mixed type (partly anion retention, partly bicarbonate loss)
Acidosis in CKD is a factor enhancing morbidity and mortality (J-shaped curve!)
Correction of acidosis in CKD may positively influence mortality and progression of kidney disease