1. Treatment of Metabolic Acidosis in CKD Presented by Pharmacist: Ola Mohammad Elkersh PharmD student 2008-2009

2. Metabolic acidosis is a characteristic feature of moderate to severe renal insufficiency. Patients with stable uncomplicated renal insufficiency ( Serum Creatinine= 2-4 mg/dl) show an average decrease in serum total CO2 level to 22 mmol/L ( normal: 23-30 mEq/L ).

3. However, even patients with advanced renal insufficiency (Serum Cr. = 12 mg/dl) when stable and uncomplicated are characterized by only moderate degree of metabolic acidosis. (HCO3 in plasma > 12 meq/L).

4. More severe degrees of metabolic acidosis may also occur due to a defective response to an augmented acid load caused by catabolic stress such as sepsis, postoperative state or change in dietary intake and diarrhea (loss of HCO3).

5. An overt acidosis is present when the estimated GFR is below 30 mL/min/1.73 m² in a large proportion of patients, and it progresses such that most patients on maintenance dialysis have an acidosis.

6. Pathophysiology The major acidification defect in the acidosis of chronic renal insufficiency is due to impaired acid excretion. Net Acid Excretion << Endogenous acid production Reduced reabsorption of bicarbonate is of lesser pathogenetic significance.

7. Treatment The utility of treating the metabolic acidosis of chronic renal insufficiency in ADULT patients remains undefined. Although mild and usually asymptomatic, chronic metabolic acidosis should be adequately corrected.

8. CHRONIC METABOLIC ACIDOSIS Increased oxidation of branched Chain amino acids Increased oxidation of branched Chain amino acids Increased protein degradation Increased protein degradation Decreased albumin synthesis Decreased albumin synthesis Reduced bone density

9. In contrast to adults, treatment of metabolic acidosis is imperative in children with chronic renal insufficiency in view of the fact that the imposed adverse effects on bone can retard growth strikingly.

10. Metabolic acidosis In Children reduces pulsatile pituitary secretion of GH reduces pulsatile pituitary secretion of GH reduces IGF-I expression in chondrocytes of the growth plate of the long bone reduces IGF-I expression in chondrocytes of the growth plate of the long bone

11. RECOMMENDATIONS

12. The decision to give bicarbonate should be based upon the clinical state of the patient and the degree of acidosis. Treatment with bicarbonate is unnecessary, except in extreme cases of acidosis when the pH is less than 7.1-7.2 and the plasma bicarbonate concentration falls below 22mEq/L.

13. 1- Regular follow up of pH & serum bicarbonate level to maintain plasma level of bicarbonate near normal level (20- 23 meq/L) especially for stages 3,4 &5. This level can be achieved by: increasing fruit intake ( citrate is converted to bicarbonate) minimizing acid load. restriction of the use of phosphate binders to a GFR < 10-20 ml/min. (phosphate is the main titratable acid excreted in urine).

14. 2- If the above mentioned level can not be achieved, we may provide 2 to 4 g/day or 25 to 50 mEq daily as oral Sodium bicarbonate or Sodium citrate which were shown to be more tolerable than sodium chloride. However, great caution should be taken to avoid volume overload and increase in blood pressure by corresponding restriction of dietary sodium chloride. The amount of sodium bicarbonate required for correction of metabolic acidosis may be calculated from the equation: Mmol of sodium bicarbonate required = (mmol/L plasma bicarbonate desired - mmol/L observed) x (0.5-0.8) x body weight (Kg) Half correction may also be a useful tool and is done by : mmol of sodium bicarbonate = base deficit x 0.3 x body weight

15. Caution should be taken with bicarbonate therapy because of its potential complications, including the following: Volume overload Hypernatraemia Hypokalemia Hypocalcemia CNS acidosis because HCO3 − does not diffuse across cell membranes, intracellular acidosis is not corrected and may paradoxically worsen because some of the added HCO3 − is converted to CO2, which does cross into the cell and is hydrolyzed to H+ and HCO3 −. Hypercapnia Overshoot alkalosis

16. 3- For patients on dialysis, increasing the bicarbonate concentration in the dialysate fluid to (> 38 mmol/L).

17. THANK YOU