The Role Of Keto/ Amino

Acid analaogue in the management of

Chronic Kidney Disease
UNTUNG SURAPATI 1
INTRODUCTION

• Indonesian Renal Registry data (IRR, 2018) : the incidence of CKD in dialysis
around 499/one million population.
• “The mortality rate is also high”
• ESRD is the second largest in spending the funds for catastrophic disease by
the “BPJS”
• BPJS (2019) : Hemodialysis pocedures cost 4.9 trillion /year
• “The only way to reduce the country’s economic burden due to kidney disease
2
is to prevent as early possible
• Prevent the incidence of End Stage Renal Disease (ESRD)
DEFINITION OF CKD

3
4
 5

DALLAS NEPHROLOGY
ASSOCIATES, 2021
 6

KDIGO, 2020
RISK FACTOR OF CKD

7
COMPLICATION OF CKD

• PROGRESSIVITY OF CKD

8
PREVENTION OF CKD

Ameh OI, Ekrikpo UE, Kengne AP. Preventing CKD in low- and middle-income countries:
a call for urgent action. Kidney Int Rep. 2020;5(3):255–262.
 PROTEIN NUTRITION IN
RESTRICTION CKD

10

KDOQI,2020
11
PATHWAYS RESTRICTION DIET & RAAS BLOCKERS IN CKD
PROGRESSION

12

Koppe, L, & Fouque, D (2018). The Role for Restriction in

Addition to RAAS Inhibitors in the Management of CKD. AJKD
THE ROLE OF LPD IN MANAGEMENT OF CKD

13

Dietary protein intake and chronic kidney disease.

Ko GJ1, Obi Y, Tortorici AR, Kalantar-Zadeh K.Dietary protein intake and chronic kidney disease. Curr Opin Clin Nutr Metab. 2018
14
PROTEIN INTAKE

15

KDOQI, Clinical nutrition practise guideline for nutrition in CKD, 2020

SCHEMATIC OF THE PROTEIN INTAKE GUIDELINES

Non
Dialysis
Dialysis

Without Without
With DM With DM
DM DM
16
Low-protein diet: 0.55 to 0.60 g
PRO/kg BW/day 0.6-0.8 g PRO/kg BW/day 1.0-1.2 g PRO/kg BW/day 1.0-,1.2 g PRO/kg BW/day

Very low-protein diet: 0.28 to

0.43 g PRO/kg BW/day with keto High risk Hypo/hyper
acid/amino acid analogs (KAA) glycaemia--- high level of
dietary protein intake

KDOQI, Clinical nutrition practise guideline for nutrition in CKD, 2020

 Keto Acid Therapy in Predialysis Chronic
Kidney Disease Patients : Final Consensus

17

Aparicio M, et al. Keto Acid Therapy in Predialysis Chronic Kidney Disease Patients:
Final Consensus Journal of Renal Nutrition, Vol 22, No 2S (March), 2012: pp S22-S24.
 Goals of Nutritional Therapy

1. To diminish the accumulation of nitrogenous waste

products and the metabolic disturbances of uremia

2. To ensure that the diet will prevent malnutrition

3. To slow the progression of renal failure

18
 TURNOVER OF PROTEINS in a normal 70 kg man

Oral protein intake

70 g/day (1 g protein/kg bw/day)
Cell proteins
5.8 kg
0.3 3.7-4.7
g/kg/day g/kg/day Ribosomes
Plasma Total free
proteins amino acid pool
0.5 kg ca. 62 g Amino
Proteins
acids

19
Proteasome
Nitrogen excretion
11.2 g/day

MITCH and GOLDBERG (1996): Mechanisms of muscle wasting. N.Engl. J. Med., 335, 1807-1905
Non-Essential and Essential Amino Acids

Non-Essential Essential
Amino Acids Amino Acids
Alanine Histidine (EAA)
Asparagine
Isoleucine (KA)
Aspartic acid
Cysteine Leucine (KA)
Glutamic acid Lysine (EAA)
Ornithine Methionine (KA)
Glycine Phenylalanine (KA)
Proline Threonine (EAA)
Serine Tryptophan (EAA)
Arginine Valine (KA) 20
Tyrosine*

* Tyrosine normally can be build from Phenylalanine. In patients with a

CRF this transformation is impaired
 PROTEINS
Exclusive or mainly build out of Amino Acids
20 Amino Acids are commonly in biological materials

General formular of a Amino Acid:

Carboxyl group
COOH
21
H - C - NH2
R Amino group
 DEGRADATION OF AMINO ACIDS

ornithine-
arginine-
cycle urea
NH3

COOH Glucose

H - C - NH2 + 1/2 O2
citric-
COOH pyruvic acid-
R acid cycle
(amino acid) C=O
22
R FADH + H+
HMG-CoA
( - NADH + H+
ketoacid)
ketone bodies
 PROTEIN METABOLISM

NH2

FOOD
PROTEIN
(S)EAA
NH2 EAA

BODY
PROTEIN
23
+
Unused
Amino Acids
 METABOLISM OF UNUSED AMINO ACIDS

unused
amino acids

carbon
skeletons
are burned
+ 24

Nitrogen is
excreted
as urea
 LOW PROTEIN DIET + ESSENTIAL AMINO ACIDS

FOOD NH2
PROTEIN
+
EAA (S)EAA

BODY
PROTEIN

+ 25

Unused
Amino Acids
 LOW PROTEIN DIET + KETOACIDS

FOOD
PROTEIN
+
KETO ACIDS

BODY
PROTEIN
26
+
Unused
Keto Acids
What is the benefit of Ketoanalogue ?

NH
3 27
Structure

NH 2

CH 3- CH - CH - COOH Essensial Amino Acid

OH
( Threonine )

O
(CH - CH - CH - C - COO) Ca 28
3 3 2
Ketoanalogue
CH
3
alpha - Keto analogue of Leucine
THE ROLE AND BENEFIT OF KETOANALOGUE
 Decreased uremic symptom
 Slow progression of CKD
 Prevention of protein degradation
 Decreased daily protein loss
 Normalization carbohydrate metabolism
 Improvement the disturbance of calcium and
phosphate metabolism, secondary 29

hyperparathyroid and renal osteodystrophy

 Improvement the disturbance of lipid profile
 COMPARATION OF CREATININE SERUM LEVEL
BETWEEN KETOANALOG AND EAA
IN UREMIC PATIENTS WITH LOW PROTEIN DIET

Creatinine serum (mg/100 ml)

0.4 g protein/BW+ EAA

0.4 g protein/BW + Ketoanalog

30

Month

SCHMICKER et al. (1986): Influence of LPD supplemented with AA and KA on the progression of CRF.
Contr. Nephrol., 53, 121-127
Keto acid supplemented LPD
Delays the onset of dialysis

31
 Effect Of Dietary Management On The Progression
Of CRF VLPD + KA/AA Versus VLPD + AA

VLPD + VLPD + AA
KA/AA
Teschan et al. (1998)
20
Walser et al. (1992) 20 Teschan et al. (1998)
Aparicio et al. (1990) Walser et al. (1993)

Change in GFR (ml/min)

Change in GFR (ml/min)

Combe et al. (1993)

15 15
Walser et al. (1992)

10 10

5 5

0 0
0 1 2 3 4 5 0 1 2 3 4 5
Years Years
32
Calculated delays (in years) up to the postulated start of dialysis (5 ml/min):
VLPD + KA VLPD + AA
Teschan et al. (1998) Ø 3.0 years Ø 1,6 years
Walser et al. (1992) Ø 2.8 years Ø 1.5 years
Aparicio et al. (1990) Ø 4.6 years -
Walser et al. (1993) - Ø 1.4 years
 The Effect of Low Protein Diet
on “Kidney Death”

33

Kidney Death: Need for dialysis, transplantation or death during the study

Cochrane Database Systematic Reviews 2006

In conclusion, this prospective study represents the
first evidence that in moderate to advanced CKD, the VLPD diet
supplemented with ketoanalogs, as compared to either
standard LPD or unrestricted diet, allows a marked and 34
sustained improvement of BP control which is associated with
a significant decrement in the extent of proteinuria.

Kidney International (2007) 71, 245–251

 Keto acid supplemented LPD
Effect on proteinuria
8
Study begin
7
Study end
Proteinuria (g/24h)

6
5
4
3
2
1
0
Barsotti et al. Aparicio et al. Combe et al. Barsotti et al. Aparicio et al. Teplan et al. 35
(1987) (1988) (1993) (1998) (2000) (2003)

No of patients 8 15 27 32 41 63
diabetics non-diabetics non-diabetics diabetics non-diabetics non-diabetics
Diet/Medication VLPD/KA VLPD/KA VLPD/KA VLPD/KA VLPD/KA LPD/KA/EPO
Duration (months) 15.6 3 23.0 ±10.6 44.4 ± 37.2 29.6 ± 25.1 36
 Keto acid supplemented LPD
Effects on serum albumin levels
60 Study begin
Study end
50
Serum Albumin (g/l)

40

30

20

10
36
0
Aparicio et Vetter et al. Walser et Barsotti et Teplan et Di Iorio et Prakash et
al. (1988) (1990) al. (1993) al. (1998) al. (2000) al. (2003) al. (2004)

No of patients 16 37 5 21 20 10 18
Duration (months) 6 12 4 6 12 18 9
 37

Journal of Renal Nutrition, Vol 30, No 3 (may), 2020: 189-199

 38

Journal of Renal Nutrition, Vol 30, No 3 (may), 2020: 189-199

 39

Journal of Renal Nutrition, Vol 30, No 3 (may), 2020: 189-199

 40
KETO ACID

Journal of Renal Nutrition, Vol 30, No 3 (may), 2020: 189-199

 41

KETO ACID

Journal of Renal Nutrition, Vol 30, No 3 (may), 2020: 189-199

VERY LOW PROTEIN DIET (VLPD)+KETOANALOG

1.For CKD stage 4 & 5

2.Collaboration with nutritionist
3.Enough calories and metabolically stable
4.Ketoacid dose 1 tab /5 kg BW/day
5.Evaluation of Nutritional Status every month 42
THE ROLE OF KETO ACID/AMINO ACID ANALOGS IN
CKD PROGRESSION

43

Nutrients 2019,11,2071; doi:10.3390/nu11092071

CONCLUSION
 Protein Restriction (LPD/VLPD) can preserve kidney function
 Ketoanalogue has the role and benefit of reducing uremic symptomps, slowing the
progression of CKD, preventing protein degradation, decreasing daily protein loss,
normalizing carbohydrate metabolism, improving Ca and P metabolism, and lipid
profile
 A study combining HD, LPD, EAA and ketoanalogue has been proven to be
effective in reducing waste metabolites, and thus less dialysis sessions, and
resulting in better quality of life
 In individuals supplementing the very low-protein diet with KAAs, clinical supervision and
44
monitoring is recommended
45