Participants will be able to
Discuss the markers of malnutrition in CKD
Identify causes of malnutrition in CKD
Discuss current recommendations for treatment of malnutrition in CKD
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Combating malnutrition in ckd
1. Combating Malnutrition in Chronic
Kidney Disease
Vishal Bagchi MBA RD LD
Director of Medical and Scientific Affairs
Patient Care America
3/2/2020 1
2. Disclosure
• Vishal Bagchi is an employee of Patient Care
America
• Slides are scientific and based on information and
research evidence available during the time of the
lecture
• Examples of products used are for educational and
demonstration purpose and not for defamation of a
company or product.
3/2/2020 2
3. Objectives
• Participants will be able to
Discuss the markers of malnutrition in CKD
Identify causes of malnutrition in CKD
Discuss current recommendations for treatment
of malnutrition in CKD
3/2/2020 3
4. Why RD’s are so important!
• A person with chronic kidney disease
should always eat a diet that has low-
protein content. Too much protein
makes the kidney problem to get
worse. The diet should also contain
low amounts of potassium and
sodium. For some patients, it is also
important for fluid restrictions to be
imposed.
• Some people suffer from both
diabetes and chronic kidney disease.
In this case, a diet that is low on
carbohydrates is recommended
3/2/2020 4
5. The Pre-Dialysis Diet
• Low protein or no restriction??
• Self restriction
• Keto acids with low protein
• Recently released USRDS report found that only about 25%
of patients starting dialysis in 2009 had > 12 months of a
Nephrologists care prior to starting dialysis.
• Only 10.5% of the patients beginning dialysis in 2005 had
received dietary counsel before starting ESRD therapy.
3/2/2020 5
6. Consensus Statement – JRN 9/2009
• Keto acid/ Amino acid-supplemented protein restricted diets should
be considered for diabetic and non diabetic patients with
CKD
– 0.3-0.6 g protein per kg body weight per day depending on stage
– Keto acid/ amino acid supplementation of one tablet/5 kg body weight
per day (0.1 gm/ kg)
– Energy at 30-35 kcal body weight per day
– Phosphate at 5-7 mg/kg body weight per day (>800 mg)
– Sodium at <2 g/day
– Vitamins and trace elements (iron)
3/2/2020 6
8. 1850 calories, 37gm protein
• Breakfast: 1 orange, 1 egg or egg substitute, 1/2 cup rice or creamed cereal, 1 slice
whole wheat bread (toasted), 1/2 tablespoon margarine or butter, 1/2 cup whole
milk, hot, non-caloric beverage, 1 tablespoon sugar (optional).
• Lunch: 1 ounce sliced turkey breast, 1/2 cup steamed broccoli, 1 slice whole wheat
bread, 1/2 tablespoon margarine or butter, 1 apple, 1/2 cup gelatin dessert, 1 cup
grape juice, hot, non-caloric beverage, 1 tablespoon sugar (optional).
• Mid-Afternoon Snack: 6 squares salt-free soda crackers, 1/2 tablespoon margarine
or butter, 1 to 2 tablespoons jelly, 1/2 cup apple juice.
• Dinner: 1/2 cup tomato juice, 1 ounce beef, 1 baked potato, 1 teaspoon margarine
or butter (optional), 1/2 cup steamed spinach, 1 slice whole wheat bread, 1/3 cup
sherbet, 4 apricot halves, hot, non-caloric beverage.
• Evening Snack: 1 banana.425 kcal, 10gm protein each
3/2/2020 8
9. Benefits of low protein
• Decreases cytokines and CRP
• Improved fasting glucose, hyperglycemia, insulin
resistance
• Decreased retention of waste products
• Improved acid/base, Calcium and PO4 metabolism
• 49% slower rate of decline in eGFR compared to pts on
traditional mixed LPD
3/2/2020 9
10. Protein restricted
• Very specific patients
• CLOSE medical
monitoring by MD and
RD
• Patient should be VERY
motivated
3/2/2020 10
11. Starting RRT
• One study found that patients entering the ESRD
program (Fresenius) in 2004 and 2005, the mean
serum albumin was 3.1 g/dL
• ~50% of pts who started 2005-2009 had low
albumins
• MDRD - mean albumin 4.2 mg/dL, after 9
months
• GFR
3/2/2020 11
12. Pre dialysis
diet for 90KG
man – 0.6gm
Protein per
Kg
Hemo
dialysis diet
for 90 Kg
man – 1.2
gm
protein/ Kg
3/2/2020 12
13. Obesity – Good or Bad ?
• An independent risk
factor for CKD
• In dialysis there is an
inverse relationship
between BMI and
mortality
3/2/2020 13
15. Anorexia
• A metabolic effect of inflammation
• Animal studies have shown that cytokines have a direct
effect on the satiety center
• Animal studies have also shown an increase in skeletal
muscle breakdown in response to TNF- administration
• Diminished appetite (anorexia) is associated with higher
concentration of proinflammatory cytokines, higher levels
of EPO hyporesponisveness and poor clinical outcome.
3/2/2020 15
18. Protein energy wasting
• PEW is found in 20-50% of patients with
advanced kidney disease
• PEW sharply increases mortality risk and
frequency of hospitalizations
• One study found that in the first 48 hours of
hospitalization pts met only 7% of protein
needs and 14% of calorie needs
3/2/2020 18
19. CRP
• Studies have shown an inverse
relationship between serum
albumin and CRP levels in
hemodialysis patients.
• CRP has been found to be
elevated in PD patients with
chronic infection
• CRP values become
significantly elevated during
peritonitis
3/2/2020 19
20. Hemodialysis
• Borah et al – study on nitrogen balance
High (1.44) and low protein diets (0.5)
Low always negative nitrogen balance
High in negative nitrogen balance on dialysis days
only
• The process of dialysis increases CRP and IL-6
3/2/2020 20
21. 90 kg Male eating 1.44
gms protein/ kg BW =
18 oz daily or 6 three oz
servings.
Recommendation for
PD is 1.2-1.3 gm/kg BW
= 15oz daily or 5 3oz
servings
3/2/2020 21
22. Peritoneal dialysis
• Protein loss in dialysate
• Feeling of fullness due
to PDF
• Uremia associated
cachexia
• Protein energy wasting
3/2/2020 22
24. High is….. GOOD????
Shouldn’t everything be low?
Low PTH
Low weight
Low cholesterol
Poor nutrition status
3/2/2020 24
25. Albumin management and ESA use
• There is an inverse relationship between ESA
dose and appetite
– (Locatelli et al. Nutritional inflammation status and resistance to erythropoietin therapy in
hemodialysis patients; Nephrol Dial Transplant 21: 991-998, 2006)
• Increase in serum albumin concentration is
associated with rapid improvement in anemia.
Such a rate of anemia correction can only be
realized by tripling the dose of ESAs
– (Agarwal R, Davis J, Smith L, Serum albumin is strongly associated with erythropoietin
sensitivity in hemodialysis patients; Clin J Am Soc Nephrol 3:98-104, 2008)
3/2/2020 25
29. Projections for the US ESRD population regarding potential
cost savings from an intervention that improves nutritional
status in patients with serum albumin < 3.5 g/dL
Improvement in Alb from
<3.5 g/dL
25% 50% 75%
+ 0.1 g/dL $ 14,469,231 $ 28,938,462 $ 43,400,769
+ 0.2 g/dL $ 18,166,154 $ 36,325,385 $ 54,491,538
+ 0.3 g/dL $ 29,229,231 $ 58,465,385 $ 87,694,615
Adapted from; Lascon et al. Potential Impact of Nutritional Intervention on End Stage Renal Disease Hospitalization, Death
and Treatment costs. Journal of Renal Nutrition; 2007; 17(6) 363-3713/2/2020 29
30. Carnitine
• Plays a critical role in energy
balance across cell
membranes
• Plasma carnitine levels can
drop by 60% during
hemodialysis
• IV L-Carnitine
– Muscle myopathies
– Impaired exercise capacity
– Intradialytic hypotension
– EPO resistant anemia
3/2/2020 30
31. More carnitine benefits
• Carnitine promotes
positive protein balance
• Reduces insulin resistance
• Reduces inflammation
• However:
– Studies are limited in
subject number and all
have been “open labeled”
3/2/2020 31
32. Zinc
• Zinc deficiency is common in HD
and associated with uremia
– Anorexia
– Hypogeusia
– Disorders in sexual and
immunologic functions
• Zinc supplementation can correct
zinc deficiency in HD and may
help to decrease CRP levels
• Exact daily requirement for HD is
unknown
• MVI with Zinc
3/2/2020 32
33. Vitamin D
• Studiesin mice have shown that vitamin D may delay
the progressionof CKD
• Vitamin D receptor knockoutmice have an activated
renin-angiotensin system, are more hypertensive,and
have increased cardiac hypertrophy
• End stage kidney disease patients on active vitamin D
have a 26% reduction in mortality
• Nutritional D
Wolf M, Thadhani R: Vitamin D in Patients with Kidney Disease: Cautiously Optimistic. Adv Chronic Kidney Dis 2007,
14:22-26.
3/2/2020 33
36. Diet Counseling
• Participants in the HEMO
study had average daily
intakes of 23 Kcal per Kg of
body weight
• Complicated diet, needs
constant reinforcement
• Intensive dietary counseling
increased albumin while
ONS decreased
• Eating on dialysis
3/2/2020 36
37. Steroids and appetite stimulants
• Megace
• Original use
• Side effects
• Weight gain
• Marinol
• Derivative of??
• Side effects
• Effectiveness
• Use in dialysis
• Corticosteroids
• Dexamethasone (Decadron)
• Comparable to Megace
• Side effects
3/2/2020 37
38. Megace and elderly dialysis patients
• 24 week, randomized, double blind placebo controlled pilot
study
• Pts also received weight resistant physical therapy for 40
minutes, 2x per week prior to dialysis
• 9 patients – 6 completed, 3 withdrew
• Significant improvements in weight, fat mass and ability to
exercise
• Improved quality of life and decrease in CRP
• No significant lean muscle gain or improvement in ADL’s
3/2/2020 38
39. Megace study
• Hs CRP decreased in both groups with progressive
resistance exercise training
• Megace may “blunt” the effects of training equaling less
muscle strength and decreased performance
3/2/2020 39
40. Unsaturated Fat!
• Hypothesis: Adding fat
to the diet would
increase energy intake,
improve nutrition status
and lower CRP
• A caloric increase of 380
kcal in MUFA and PUFA
3/2/2020 40
41. Results
• Results: Only 14
completed the study
– 5 – adverse effects
– 2- refused to take
• No significant difference
in blood lipids
• Dry body weight higher
• CRP lower
3/2/2020 41
42. Brazil Nuts
• Study found that when dialysis patients eat one
Brazil Nut daily levels of selenium improve
• 81 pts, for 3 months
• Before supplementation plasma levels were 18.8
mcg/L
• After supplementation levels were 104 mcg/L
• Erythrocytes and GSH-Px increased as well
3/2/2020 42
44. Statins and inflammation
Recent study by Lundberg et al. measured the effect of
statins on patients with IgA Nephropathy.
Results showed that free radical production can be
decreased with statin therapy
Previous studies have established that statins exert anti
inflammatory effects that may slow the progression of CKD
by improving inflammatory cell signaling pathways as well
as improving lipid profiles
Statins also protect against the oxidation of LDL and as a
result reduce oxidative stress
Lundberg, S. et al. Atorvastatin-induced modulation of monocyte respiratory burst in vivo in patients with IgA
nephropathy: a chronic inflammatory kidney disease. Clinical Nephrology, Vol 73-No. 3/2010 (221-8).3/2/2020 44
45. However,
• Statins have not produced the same results in
maintenance hemodialysis patients
• No difference was found in the control vs.
treatment group
• The recent AURORA trial found that a high
phosphate level was one of the strongest risk
factors for the occurrence of cardiovascular
endpoints in their study
Venkata Narla, Michael J Blaha, Roger S Blumenthal, and Erin D Michos. The JUPITER and AURORA clinical trials for
rosuvastatin in special primary prevention populations: perspectives, outcomes, and consequences. Vasc Health
Risk Manag. 2009; 5: 1033–1042. Published online 2009 December 29.3/2/2020 45
47. Omega 3 Fish Oil
• EPA and DHA
• Fish intake and
albuminuria
• Cost
• # of pills
3/2/2020 47
48. Implications
• Increase Fat?
• More nuts?
• Olives?
• Supplements?
• Use olive oil and canola
oil
• Low K, low PO4 and low
Na++ foods that are high
in unsaturated fatty acids
3/2/2020 48
50. PO Supplements
• Initial intervention
• Readily available and
convenient
• Adherence to oral
supplements is variable
and low
• Peridialytic use
– Provided to patient
– At no cost
3/2/2020 50
51. PO Supplements
• Recent study found
maintenance of KDOQL
score
• Increased albumin
• Non treatment group had
decreased albumin
• Some participants
consumed 40%, others
200%, average was 84%
• Drawbacks: Staff missing
or patients refusing 30%
of the time
3/2/2020 51
52. IPN/ IDPN
• Non invasive
• Compliance
• Studies have shown safety
• IKizler et al showed that IDPN promoted a 96%
increase whole body protein synthesis and a 50%
decrease in whole body proteolysis compared
with controls
• Cost
3/2/2020 52
53. Figure 3 Effect of nutritional therapy modality on forearm muscle homeostasis
Kalantar-Zadeh, K. et al. Diets and enteral supplements for improving outcomes in chronic kidney disease Nat. Rev.
Nephrol. doi:10.1038/nrneph.2011.60
Data obtained from Pupim, L. B., Majchrzak, K. M., Flakoll, P. J. & Ikizler, T. A.3/2/2020 53
54. Projections
• IKizler, “Nutrition Support for the Chronically Wasted or
Acutely Catabolic Chronic Kidney Disease Patient” Dec 2009
• An increase in albumin of 0.2 in 50% of the US dialysis
population
• Approximately 1,400 lives saved
• Approximately 6,000 hospitalizations averted
• Approximately $36 Million in Medicare cost savings resulting
from a reduction of approximately 20,000 hospital days over 1
year.
3/2/2020 54
55. The bottom line in nutrition
• 30-75% of dialysis patients are malnourished
• Inflammation and malnutrition are multifactorial and virtually inevitable in CKD
and Dialysis
• Adequate calories from all sources as well as essential and conditionally essential
vitamins and minerals
• Calories can be administered enterally or parenterally
• There are new approaches being studied constantly
• Considerations
• Compliance/ adherence
• Ability to understand importance
• Quality of life
• Bundling
– Improved nutrition/ improved inflammation = better EPO responsiveness
3/2/2020 55
56. Thank You
Vishal Bagchi MBA RD LD
Director of Medical and Scientific Affairs
Patient Care America
214-736-7969
vbagchi@pcacorp.com
www.pcacorp.com
3/2/2020 56
57. FINE Study
• Best designed study to date
• There was no non treatment group
• Patients on CHD with PEW
• Compared the effects of the route of
supplementation on morbidity and mortality
• Found that the route was not a factor
• The important thing was to deliver the nutrients
3/2/2020 57
58. Ghrelin
• TNF- administration in rats decreased plasma acyl ghrelin levels
and reduced food intake in mice
• Injections of Des Acyl ghrelin in mice decreased food intake,
induces negative energy balance and delays gastric emptying
• There is a strong inverse relationship between CRP and acyl ghrelin
levels
• Higher acyl ghrelin levels are found in pts without inflammation
compared to pts with inflammation
• SubQ Ghrelin increases appetite in dialysis short-term
• In PD it doubled intake
3/2/2020 58
60. Speaker-Vishal Bagchi
• UT Southwestern Medical Center School of Allied
Health- Clinical Nutrition
• University of Dallas MBA- Healthcare and Marketing
• UT Southwestern – Critical Care and Acute Dialysis
• Fresenius 2007-2013- Home Therapies, Peritoneal
Dialysis, Nocturnal, Conventional HD
• NKF-CRN Dallas Chair
3/2/2020 60
Notes de l'éditeur
Keto acids with low protein intake is better at reducing the rate of CKD progression and delaying the start of dialysis, also improves clinical and metabolic consequences.
Keto acids are the nitrogen-free analogues of amino acids and are transaminated to form the respective amino acid in the body. This improves the nitrogen balance at a lower nitrogen intake because essential amino acid requirements are met with a lower nitrogen intake with reduced waste product formation and relief of the symptoms of uremia while maintaining good nutrition.
This is a diet I found on the internet, it is not renal specific but it gives an idea of how much food people have to eat to hit the calorie recommendations – and they would still need to add a low protein supplement like Suplena to complete the calorie requirements
Independent risk factor is mediated by obesity related glomularopathy and enhanced by glomular blood pressure , DM, HTN, high TG and high LDL
In dialysis an inverse relationship between BMI and mortality, even at overweight and obesity range
Often our patients start like this – the majority did not get here by being compliant with diets or following a healthy lifestyle. So when they need the protein and they need to eat, but not too much of course – inflammation is just one of the factors that contribute to this
Increases in CRP, IL-6 and fibrinogen synthetic rate
Comparison of survival predictability of baseline serum albumin level in the unmatched cohort of patients treated using peritoneal dialysis (PD) and hemodialysis (HD). Reference group: HD patients with serum albumin level of 4.00-4.19 g/dL. Abbreviation: MICS, malnutrition-inflammation complex syndrome.
Modeled relationship of Hgb trajectories, epo dose, and serum albumin concentration. No epo use is associated with Hgb decline (slope A). An average of 24,000 units in a patient with average and stable albumin is required to maintain Hgb (slope B). When serum albumin concentration is 1 SD below average, anemia is likely. Increase in serum albumin to SD above average is associated with rapid Hgb response (slope C). This slope is similar to that achieved by tripling the dose in the average patient (slope D).
We feel like this a lot, it is almost fighting a loosing battle with CKD and inflammation
BUT, I offer you this guy – he is 80 yrs old, his goal for he 80th birthday was to be able to walk up the down elevator in a department store near his home in England. He accomplished his mission, he trained for it when the store was not busy and on his birthday he climbed up the stairs without stopping. They subsequently banned him from the store for going up the elevator the wrong way and scaring the lingerie sales girl when he got to the top because he was all red faced and breathing hard. He was interviewed later and said it was worth it, even though he was banned from the store.
Slow replacement from muscle stores, are often depleted after multiple dialysis sessions
IV L-carnitine can replenish lost carnitine and decrease muscle myopathies and impaired exercise capacity. Myopathy is a term used to describe muscle disease generally secondary to inflamation
Intradialytic hypotension and helping with EPO resistant anemia
An open-label trial or open trial is a type of clinical trial in which both the researchers and participants know which treatment is being administered.
Zinc and CRP – 60 subjects, given 220mg zinc sulfate for 42 days
UL for zinc is 40mg
Zinc toxicity = nausea, vomiting, loss of appetite, abdominal cramps, diarrhea, and headaches
This is independent of other cardiovascular risks, PTH and bone mineral markers
The key findings of this pilot double-blind, randomized, controlled trial are that short-term exposure to paricalcitol results in the following: (1) no significant improvement in endothelial function; (2) an anti-inflammatory effect; (3) 50% reduction in albuminuria; and (4) that these changes are not attributable to changes in BP, GFR, or PTH concentrations. Thus, the anti-inflammatory and antialbuminuric effects appear to be mediated by nonhemodynamic, non-PTH mechanisms.
26 patients with GFR 30
KDOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease
Shows the importance of on going counseling to increase protein intake
Original use was for treatment of metastatic breast cancer, also found to have significant anti inflammatory prosperities
One study found long term use caused headaches, dizziness, confusion, diarrhea and hyperglycemia. It is well established that Megace can cause uterine bleeding, peripheral edema and adrenal insufficiency
Testing in dialysis is limited. Megace is excreted in the urine and dializability has not been determined
Weight gain with Megace is due to an increase in fat mass, not muscle mass, and is also related to edema. Dry weight increases have been fat mass. Compliance is an issue. Pts are likely to reduce dose on their own
New formulation Magace ES has lower volume for higher doses and has shown promise with reduced occurrence of side effects and better occurrence of weight gain in HIV patients
Dronabinol –
Does not work as well as megace – studied in cancer patients
Side effects – impaired cognition, also tachycardia, hypotension, delayed gastric emptying, and decreased muscle strength
Study in JRN in 1995 : At the end of the 16 weeks of intervention, weight and body mass index increased by 9%, body fat proportion by 31%, and triceps skinfold by 40% (P < .01). Serum albumin increased from 3.0 to 3.3 g/dL and continued to increase significantly to 3.6 g/dL after 3 months post intervention (P = .03). Serum leptin increased from 5.2 to 10.7 ng/mL (P = .09). Daily protein and energy intake increased progressively up to 27% to 42% by the end of the trial (P ≤ .01). In 8 patients without acute infection, serum C-reactive protein declined from 1.24 to 0.78 mg/L (P = .06). QoL and appetite were reported to be improved. No major side effects were observed, and all 10 patients completed the 16 weeks of daily intake of megestrol acetate without interruption.
Conclusions
Megestrol acetate oral solution in half of its conventional dose is safe and improves the nutritional state, inflammation, and anorexia in maintenance dialysis patients. Larger-scale placebo-controlled randomized studies are needed to confirm the beneficial effects of 400 mg/day of megestrol acetate in dialysis patients.
Decadron
Only appetite stimulant comparable to Megace but long term side effects include myopathy, gastric/ duodenal irritation with long term use
Reasons for withdrawl: two placebo – one due to bad taste and one due to decreased sexual drive
One MA group – acute diverticulitis
Also – 16 were excluded – 12 due to high CRP of >10, indicative of infection, 2 compliance
METHODS:
A total of 81 patients on hemodialysis (52.0±15.2 y old, average time on dialysis 82.3±91.4 mo, body mass index 24.9±4.4 kg/m(2)) from the RenalCor and RenalVida Clinics in Rio de Janeiro, Brazil, were studied. All patients received one nut (around 5 g, averaging 58.1 μg Se/g) a day for 3 mo. The Se concentrations in the nuts and in plasma and erythrocytes were determined by atomic absorption spectrophotometry with hydride generation (Hitachi, Z-500). GSH-Px levels were measured using Randox commercial kits.
RESULTS:
Plasma Se (18.8±17.4 μg/L) and erythrocyte (72.4±37.9 μg/L) levels were below the normal range before nut supplementation. After supplementation, the plasma level increased to 104.0±65.0 μg/L and erythrocytes to 244.1±119.5 μg/L (P<0.0001). The activity of GSH-Px also increased after supplementation, from 46.6±14.9 to 55.9±23.6 U/g of hemoglobin (P<0.0001). Before supplementation, 11% of patients had GSH-Px activity below the normal range (27.5-73.6 U/g of hemoglobin). After supplementation, all patients showed GSH-Px activity within the normal range.
CONCLUSION:
The data revealed that the investigated patients presented Se deficiency and that the consumption of only one Brazil nut a day (5 g) during 3 mo was effective to increase the Se concentration and GSH-Px activity in these patients, thus improving their antioxidant status
1 nut = 290
Two new and interesting studies have shown that there are ways other than pill supplementation to increase selenium concentrations and glutathione peroxidase activity. The first was by an Italian group, which examined the impact of statins on selenium status in hemodialysis (HD) patients. The study, by Taccone-Gallucci et al (J Trace Elem Med Biol. 2010;24:27-30), enrolled 103 HD patients and 69 healthy controls. Results showed that the patients receiving statins had serum selenium higher than both the healthy controls and the HD patients not receiving the medication (111.83 vs. 96.47 vs. 81.65 μg/L, respectively). Normal ranges for serum selenium are 60-120 μg/L. The authors suggest that statins have antioxidant properties which spare selenium reserves. This study was the first of its kind and certainly of interest.
Study found nepro was well accepted, and successfully maintained alb and select QOL measures
Change in albumin – non treatment group went down, treatment group went up
Granted the studies have not been perfect due to cost and time BUT many have shown a benefit be it anecdotal or numerical - improvements in quality of life, albumin, etc
List serve debate
Compliance – cases of nepro coming back after death, but pt states they were taking it. Pt is 80 and straight out does not want to be told what and how to eat.
Ability to understand – If in NH does staff understand and can pt comprehend
Quality of life – If you had to drink 5 cans of Nepro because the RD was telling you to, how would your quality of life be?
PEG tube? How many agree to it
Patients were randomized to oral or parenteral nutrition with the goal of meeting KDOQI guideline for protein and energy intake
IKizler calculated a 15% improvement in overall mortality in supplemented pts
A recent study published in the Journal of renal nutrition found high leptin and des acyl ghrelin levels in patients undergoing HD. Levels of acyl ghrelin were reduced and negatively linked with C Reactive protein Patients with elevated des acyl ghrelin to acyl ghrelin ratios presented low protein intakes and serum creatinine levels
one potential role of mild inflammation in the ghrelin system. They found a strong inverse relationship between CRP and acyl ghrelin and the des acyl ghrelin to acyl ghrelin ratio
Another study found that TNF Alpha administration in rats decreased plasma ghrelin levels and reduced food intake in mice