KETOANALOGUES AND

THEIR ROLE IN CKD

PROGRESSION
AMAL EL-ROWMEIM

QC DIETETIC INTERN

11/10/18
KETOANALOGUES

• Ketoanalogues (KA) are a nitrogen free analogue of essential amino acids.

• KAs are transaminated to form the amino acids.
• KAs allow the essential amino acids requirements to be met with a lower protein intake and
with reduced formation of nitrogenous wastes.
• Contains calcium.
• Phosphate Binder.
• Tablet form; ketosteril
UREMIA & PROTEINURIA

• Uremia: Buildup of urea and other nitrogenous waste compounds in the blood.
• Amino acids not utilized in protein synthesis are metabolized into ammonia which is further
metabolized into urea.
• Complications:
• Metabolic acidosis
• Uremic sarcopenia
• Muscle atrophy/breakdown
• Altered mental status etc

• Proteinuria: abnormal amounts of protein in the urine.

EVIDENCE ANALYSIS LIBRARY GUIDELINES

• Chronic Kidney Disease (CKD) pre-dialysis patients with glomerular filtration rate (GFR) <50:
• Protein intake w/o diabetes: 0.6-0.8 g/kg (rating: strong)
• Protein intake with diabetes: 0.8-0.9 g/kg (rating: strong)
• CKD pre-dialysis patients with GFR<20:
• Very low protein diet (VLPD) of 0.3-0.5 g/kg with addition of keto acids (rating: strong)
• CKD patients energy needs:
• 23-35 kcals/kg (rating: fair)
PARTICIPANTS

• Stage 4 or greater
• Stable renal function for at least 12 weeks
• Good nutritional status
• Excluded: uncontrolled blood pressure (BP >145/85), diabetes, heart failure, hepatic disease,
malabsorptive diseases, pericarditis, polyneuropathy, poor energy intake
• Good compliance with low protein diet (LPD)
• 3 month run in phase in which compliance to a 0.6 gm/kg protein and 30 kcals/kg energy intake
was assessed. If within +/- range of 10% accepted into study
• 1413 assessed for eligibility and only 207 met the criteria.
STUDY DESIGN

• Randomized, controlled trial over 18 months

• First 3 months run in phase; intensive nutritional counseling
• Next 15 months intervention phase
• Participants regularly assessed to determine compliance to diet, compliance to KA, and
any adverse effects.
• Protein intake evaluated via urinary urea nitrogen excretion and energy intake with 3 day food
diary
• BP, cholesterol, iron, mineral abnormalities and metabolic acidosis monitored and
corrected as needed.
STUDY DESIGN

• LPD: 0.6 g/kg • VLPD (0.3g/kg)

• 30 kcals/kg ideal dry body weight • 30 kcals/kg ideal dry body weight
• Mixed protein sources • + KA supplements (0.125g/kg ideal dry
body weight)
• Vegetarian protein sources
STUDY DESIGN

• At baseline no significant differences in either group in:

• Age (55.2 yrs in KD and 53.6 in LPD)
• Sex (63% male in KD and 59% in LPD)
• GFR (18 in KD and 17.9 in LPD)
• BMI (23.6 in KD and 23.2 in LPD)
RESULTS

• 55 subjects or 28% of study cohort reached the primary end point (Needed dialysis or >50%
reduction in initial GFR): (significant difference)
• 13% of KD group
• 42% of LPD group
• Probability of reaching end point within 1 year: (significant difference)
• 12% in KD group
• 39% in LPD group
• Dialysis initiation: (significant difference)
• 11% in KD group
• 30% in LPD group
RESULTS

• GFR: no significant difference in median GFR reductions

• KD: from 18.7 to 17.4
• LPD: from 18 to 15

• Significantly lower urea, uric acid in KD group

• Serum bicarbonate increased in KD
• Calcium phosphorous metabolism improved in KD group
DISCUSSION

• Factors that may affect results:

• Differences in protein intake 0.3 g/kg vs 0.6 g/kg
• Differences in quality of protein: vegetarian vs mixed
• Vegetable proteins:
• Base producing vs acid producing animal products,
• Lower in phosphorous

• Participants were all white, non-diabetic, fairly young, no severe proteinuria, good BP
control, good nutritional status, and compliant with diet.
CONCLUSION

• KD diet may slow CKD progression by:

• Improve nitrogen balance
• Reduce metabolic acidosis/uremia
• Reduce mineral disturbances
• Reduce inflammation.

• Requires further research!

QUESTION?

How would you change the design of the study

to produce more accurate results?
REFERENCES

• Garneata, L., et al. “Ketoanalogue-Supplemented Vegetarian Very Low-Protein Diet and CKD
Progression.” Journal of the American Society of Nephrology, vol. 27, no. 7, 2016, pp. 2164–2176.,
doi:10.1681/asn.2015040369.
• Alper, Brent. “Uremia.” Emedicine.medscape, 5 Feb. 2016,
emedicine.medscape.com/article/245296-overview#showall.
• “CKD: Protein Intake 2010.” EAL,
www.andeal.org/template.cfm?template=guide_summary&key=2409.
• “CKD: Energy Intake 2010.” EAL,
www.andeal.org/template.cfm?template=guide_summary&key=2410.