selected aspects of acid base physiology- acidosis in ckd norbert lameire, md, phd em prof of...

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