MANAGEMENT OF CHRONIC KIDNEY DISEASE: THE UNIQUE EFFECT OF KETOACID

ON PROGRESSION IN CKD.

Haidar Alatas

PertemuanIlmiahTahunan I
PerhimpunanDokterSpesialisPenyakitDalam Indonesia
Cabangpurwokerto
Minggu, 27 April 2014

Abstract
The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice
Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD)
serves to update the 2002 KDOQI Clinical Practice Guidelines for Chronic Kidney
Disease: Evaluation, Classification, and Stratification following a decade of focused
research and clinical practice in CKD.

The document aims to provide state-of-the-art guidance on the evaluation,

management and treatment for all patients with CKD. Specifically, the guideline
retains the definition of CKD but presents an enhanced classification framework for
CKD; elaborates on the identification and prognosis of CKD; discusses the
management of progression and complications of CKD; and expands on the
continuum of CKD care: timing of specialist referral, ongoing management of people
with progressive CKD, timing of the initiation of dialysis, and finally the
implementation of a treatment program which includes comprehensive conservative
management. The development of the guideline followed an explicit process of
evidence review and appraisal. Treatment approaches are addressed in each chapter
and guideline recommendations are based on systematic reviews of relevant trials.

Keywords: Albuminuria; Chronic kidney disease; Classification; Clinical practice

guideline; Evidence-based recommendation; GFR; Glomerular filtration rate;
KDIGO; Proteinuria; Systematic review.
Consensus Keto Acid Therapy in CKD Patients :
Well plannedketo/amino acid-supplemented protein restricted diet therapy as part of a
treatment program:
is safe, does not induce malnutrition and can improve metabolic
abnormalities associated with renal insufficiency.
may slow progression and will delay the time until dialysis is required to
treat uremic symptoms.
Team approach between all disciplines involved (doctors/dieticians/nutritionists) is
needed keto/amino acid supplemented protein restricted dietis a cost-effective
treatment therapy, and can improvethe quality of life of patients in predialysis
stage. Specific international guidelines and recommendations for keto/amino acid-
supplemented protein-restricteddiets are specified:
. the daily protein intake at a low-protein diet supplemented with keto
acids should not exceed 0.6 g/kg b.w./day, optimal protein intake is 0.30.4
g/kg b.w./ day
. the recommended dosage of keto/amino acids is 0.1 g/kg b.w./day
. a daily energy intake of 35 kcal/kg b.w./day should be
recommended
. a low-protein diet (0.6 g protein/kg b.w./day) is indicated at a

creatinine clearance of 50 ml/min/1.73 m2, a ketodiet at a creatinine clearance

of 2025 ml/min/1.73 m2 (however, these recommendations can be impracti-

cal in countries with different guidelines)
. in the first 3 months after the beginning of a (very) low-protein diet
supplemented with keto/amino acids the control examinations should be
recommended monthly, afterwards the intervals between the control
examinations could be 23 months.
. the following parameters should be measured at the control
examinations: 24-hour urea nitrogen, body weight, electrolytes, calcium,
phosphate, PTH, serum creatinine, creatinine clearance, acid-base balance
(Atrup), bicarbonate, blood counts, hemoglobin, lipids, glycaemia, transferrin
(only at the beginning).
. vitaminsandironareimportantsupplementsofa low protein diet
. the phosphorus intake should be 57 mg/kg b.w./day (500 to not
 more than 800 mg/day)
. the daily salt intake should be in the range of 100 mmol sodium
chloride, especially in patients with hypertension or other signs of
extracellular volume overload

In diabetic nephropathy patients, a properimplementation of Keto Acid Therapy:

Does not induce malnutrition or even improve nutritional status (e.g. albumin, BMI)
Can improve metabolic abnormalities associated with renal insufficiency (e.g.
bicarbonate, phosphorus, calcium)
Can improve/correct diabetes associated metabolic disturbances in type II (good
glycemic control, improvement of insulin sensitivity, reduction of hyperinsulinemia)
Enables a good glycemic control in type I diabetes mellitus
May slow progression of renal insufficiency and will delay the time until dialysis is
required to treat uremic symptoms.

Specific international guidelines andrecommendations for Keto Acid Therapy

Low protein diet (0.60.7 g protein/kg b.w./day) is indicated at a creatinine clearance

of 50 ml/min/ 1.73 m2, Keto Acid Therapy is indicated at a creatinine clearance of

2025 ml/min/1.73 m2
Daily protein intake at a low protein diet supplemented with keto acids should not
exceed 0.6 g/kg b.w./day, opti- mal protein intake is 0.40.6 g/kg b.w./day
Recommended dosage of keto acids is 0.1 g/kg b.d./day
Daily energy intake of 35 kcal/kg b.w./day should be recommended
Protein calories must be replaced by complex carbohydrate calories not by lipids.

Crucial aspects for the efficacy of Keto Acid Therapy indiabetic nephropathy
patients:
Patients have to be properly selected in respect to motivation and ability to follow a
protein restricted diet. In order to reap the benefits for diabetic nephropathy
patients, it is absolutely necessary that all disciplines involved in the treatment
(nephrologists/physicians/dieticians/nutritionists) act as a highly motivated team.
Support for increasing patients compliance is needed: recipes, dietary computer
program.
Development of guidelines as well as convincing Diabetes Associations /
Diabetologists about the efficacy and safety of Keto Acid Therapy is regarded as a
major issue for increasing the awareness of Keto Acid Therapy.

Consensus
Keto Acid Supplementation in Patients Being Treated by Dialysis
It is estimated that 3050% of dialysis patients suffer from protein-energy
malnutrition. Nutritional status is an important predictor of clinical outcome in
chronic hemodialysis patients, as uremic malnutrition is strongly associated with an
increased risk of death and hospitalization events. Abnormalities in nutritional
markers are common and include decreased serum protein/albumin, lower body mass
as assessed by anthropometric measurements and subjective global assessment, and
decreased nutrient intake. In this context, a decreased muscle mass is the most
significant predictor of morbidity and mortality in these patients.
Oral supplementation of keto/amino acids in dialysis
patients may have beneficial effects in:
Compensation of essential amino acids being lost into the dialysate
Normalization of low plasma levels of amino acids, especially branched-chain amino
acids
Improvement overall nutritional status (albumin, SGA, body weight) in malnourished
dialysis patients
Supporting the normalization of calcium-phosphate disorders (increasing serum
calcium and reducing phosphate levels)
Recommendations for protein and energy intake and keto/amino acid supplementation
in patients being treated by dialysis:
Dietary protein intake: 1.2 g/kg b.w./day
Dietary energy intake: 35 kcal/kg b.w./day: <60 years,
3035 kcal/kg b.w./day: >60 years
Recommended dosage of ketoacids :1 tablet/58 kg b.w./day
Central needs in order to judge the efficacy of keto/ amino acid supplementation in
patients being treated by dialysis are studies. In case keto/amino acids could induce
lean body mass (e.g. measured by DEXA or other equivalent measures), it would be a
real alternative for nutritional repletion in malnourished patients.
References:

Kidney International Supplements. Improving Global Outcomes (KDIGO) 2012

Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney
Disease (CKD), Vol 3, 1, 2013.

Kidney International Supplements (2013) 3, 4; doi:10.1038/kisup.2012.76

Kidney International Supplements (2013) 3, 514; doi:10.1038/kisup.2012.77
Am J Nephrol 2005;25(suppl 1):128.