Selected aspects of acid base physiology- acidosis in CKD Norbert Lameire, MD, PhD Em Prof of Medicine University 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

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

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 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 Figure 3. Kaplan-Meier analysis to assess the probability of reaching ESRD for the two groups. De Brito-Ashurst et al, JASN, 20, 2075-2084, 2009

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