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Selected aspects of acid base physiology-
acidosis in CKDNorbert Lameire, MD, PhD
Em Prof of MedicineUniversity Hospital
Gent, Belgium
Tbilisi, October 2015
Normal Blood pH: 7.37-7.43
The Organim Faces Daily Acid Stress
The Regulation of Blood pH
Buffer Systems (I)
Buffer Systems (II)
Acid Stress: The Respiratory Response
Acid Stress: The Renal Response
Bicarbonate Reabsorption in Proximal Tubule
In Summary….
Clinical manifestations of acidemia
Kalantar-Zadeh et al, N Engl J Med 2013;369:374-82.
ANION GAP
Na+ Cl-
HC03
Cl-
HC03
Na+ Cl-
AGAG AG HC03
NormalHigh AGacidosis
Normal AGacidosis
Na+
The anion gap
Normal values of serum anion gap in the literature
Kraut, Nagami, Clin J Am Soc Nephrol 8: 2018–2024, 2013
Classification of metabolic acidosis
Chloride-rich solutions
The metabolic acidosis of chronic kidney disease
Relationship between plasma bicarbonate and GFR in patients with CKD of various causes
Elkinton JR Ann Int Med 57:660-684, 1962
Evolution of the electrolyte pattern of metabolic acidosis in CKD
Widmer et al, Arch Int Med 139:1099-1102,1979
Association of serum bicarbonate levels with mortality in patients with non-dialysis-dependent CKD
Kovesdy et al, Nephrol Dial Transplant (2009) 24: 1232–1237
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):670-678,2013
Effect of bicarbonate treatment on progression of CKD
CKD- 5 CKD-4
Yeong et al, Electrolyte Blood Press 12:80-87, 2014
Changes of renal function during treatment with oral bicarbonate
NS P <0.05
Yeong et al, Electrolyte Blood Press 12:80-87, 2014
Bicarbonate substitution refrains progression of CKD
De Brito-Ashurst et al, JASN, 20, 2075-2084, 2009
Figure 3. Kaplan-Meier analysis to assess the probability of reaching ESRD for the two groups.
Bicarbonate substitution improves dietary protein intake
De Brito-Ashurst et al, JASN, 20, 2075-2084, 2009
Beneficial effects on GFR decline of bicarbonate treatment of acidosis in CKD
Susantitaphong et al, Am J Nephrol 2012;35:540–547
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
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