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Nutrition in Solitary Kidney Care and Kidney Transplantation

“Opportunity to mitigate poor outcomes in individuals who give and persons who take”

Ekamol Tantisattamo, MD, FASN, FASTTransplant nephrologist

Assistant Clinical Professor of Medicine

Division of Nephrology, Hypertension and Kidney Transplantation

Department of Medicine

University of California Irvine School of Medicine

Nutritional and Dietary Management of Kidney Disease:

A Patient Care Approach

Saturday, February 29th, 2020 1

Disclosure

• None

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Outline• Solitary kidney

– Epidemiology

– Etiology

• Living kidney donor– Complications

– Nutritional management

• Kidney transplant recipient– Outcomes

– Food security

– Nutrition management3

Why only 1 kidney?

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Epidemiology of adult non-transplant solitary kidney

1McClung et al. J Trauma Acute Care Surg. 1262 2013;75:602–606. 2Hart et al. Kidney. Am J Transplant. 2019;19 Suppl 2:19-123.

3Shuch et al. Cancer. 2013;119:2981–2989. 5

Acquired solitary kidney

Renal traumaKidney

donationRenal cancer

• 126 / y 1 • 5,650 / y 2 • 269 / y 3

Average nephrectomy / year

• 31 y/o M • 35 – 45 y/o F • >60 y/o

Options for ESRD patients

Courtesy from Dr. John Friedewald, Comprehensive Transplant Center Northwestern University 6

End‐stage renal disease

Conservative Dialysis

Hemodialysis

Peritoneal dialysis

Kidney transplant

Living donor

Deceased (Cadaveric) 

donor

Tolerance

Artificial kidney

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Living kidney donor

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“Dedicated to true heroes

Those who give without wanting

Those who receive without forgetting”

UCSF Transplant Center

Care for living kidney donors

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• Cardiovascular• Psycho‐social• Hypertension• Obesity

• Cardiovascular• Psycho‐social• Hypertension• Obesity

Pre‐donationPre‐donation

• Hypertension• Obesity• CKD (proteinuria), 

ESRD• Psycho‐social

• Hypertension• Obesity• CKD (proteinuria), 

ESRD• Psycho‐social

Post‐donationPost‐donation

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Unilateral native nephrectomy

Renal hemodynamic change Glomerular structural change

⇧ effective renal plasma flow

⇧single nephron GFR

Glomerular hyperfiltration

Glomerular hypertrophy⇧ Intraglomerular pressure

Podocyte injury

ProteinuriaGlomerulosclerosis

Pathways of cell regulation e.g.

• mTOR• IL-10• TGF-β

Secondary FSGS

Tantisattamo E, Dafoe DC, Reddy UG, Ichii H, Rhee CM, Streja E, Landman J, Kalantar-Zadeh K. Current Management of Acquired Solitary Kidney.

Kidney Int Rep: In Press

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Unilateral nephrectomy

↓ Nephron mass

New GFR =

65 – 70% of pre-donation GFR

Compensatory mechanism

Delanaye et al. Nephrol Dial Transplant. 2012;27:41–50. DO NOT

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Medical complications from Living kidney donation

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Chronic kidney disease (Proteinuria)

Hypertension

ESRD

Living donation VS. Proteinuria

Garg et al. Kidney Int. 2006;70(10):1801-10.

24‐h protein

Microalbumin

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Ref. ESRD(Living kidney donor vs. Controls)

Ibrahim et al., 2009 1 180 cases/million/year vs.

268 cases/million/year

Mjoen et al., 2014 2 Living donor had higher risk of ESRD (HR 11.38 (95% CI 4.37–29.6))

Muzaale et al, 2014 3 30.8 per 10,000 (95% CI, 24.3-38.5) vs.

3.9 per 10,000 (95% CI, 0.8-8.9)

Grams et al., 2016 4 3.5 to 5.3 times greater in living kidney donors compared to age-matched nondonors

1Ibrahim et al. N Engl J Med. 2009;360:459–469; 2Mjoen et al. Kidney Int. 2014;86:162–167. 1238

3Muzaale et al. JAMA. 1240 2014;311:579–586. 1241; 4Grams et al. N Engl J Med. 1243 2016;374:411–421

Risk of end-stage renal disease after kidney donation

Living donation VS. Hypertension

Boudville et al. Ann Intern Med. 2006;145(3):185-96.

SBP

DBP

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What is the top asked questions

from potential living kidney donors?

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Diet in living kidney donor

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Protein

Sodium

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Dietary protein intake

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Amount of protein

Sources of protein

GFR vs. Dietary protein intake

18Cirillo et al. Nephrol Dial Transplant. 2015;30(7):1156-62.DO NOT

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High dietary protein intake in living kidney donor

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Kidney donationKidney donation High protein dietHigh protein diet

Glomerular hyperfiltrationGlomerular hyperfiltration

↑ Intraglomerular pressure↑ Intraglomerular pressure

Kidney injuryKidney injury

CKDCKD

Ko GJ, Obi Y, Tortorici AR, Kalantar-Zadeh K. Curr Opin Clin Nutr Metab Care. 2017;20(1):77-85.

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How low is low protein?

CKD

• eGFR <45 ml/min per 1.73 m2 or proteinuria >0.3 g/day

• Protein intake 0.6 –0.8 g/kg/day

Living kidney donor

• ???

• Protein intake ≤ 1 g/kg/day

Kalantar-Zadeh K, Fouque D. N Engl J Med. 2017;377(18):1765-76.DO NOT

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Sources of protein VS. CKD progression

21Haring et al. J Ren Nutr. 2017;27(4):233-42.

Animal protein Plant-based protein

Na diet VS. CKD

22Yoon et al. Kidney Int. 2018;93(4):921-31.

Na 2.93 to 4.03 g/d

<2.08 g/d

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Daily Na intake ≤ 4 g/day

??? >2 g/day

23Kalantar-Zadeh K, Fouque D. N Engl J Med. 2017;377(18):1765-76.

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Trends of 10-year all-cause and cause-specific mortality among KTx recipients.

Awan et al. Am J Nephrol. 2018;48(6):472-481. DO NOT

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Mortality in living donor KTx recipients

Hart et al. OPTN/SRTR 2018 Annual Data Report: Kidney. Am J Transplant 2020;20 Suppl s1:20-130.

Risk factors for CVD in KTx recipients

Traditional • Age• Gender• DM• HTN• Smoking• Dyslipidemia• Renal function• Proteinuria

Nontraditional• Metabolic syndrome• Oxidative stress,

inflammation• Hyperparthyroidism• Anemia• Endothelial dysfunction• Hypoalbuminemia

CKD

KTx

Immunosuppression

Single kidney

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Advanced CKD or ESRDAdvanced CKD or ESRD Post-KTxPost-KTx

Diet Pre- vs. Post-KT

Food (in)security

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13,863.

(February 25, 2020)

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Food security in KTx recipientsFood security in KTx recipients

“All people, at all times, have access to sufficient, safe, nutritious food to maintain a healthy and active life”

World Food Summit, 1996

“All people, at all times, have access to sufficient, safe, nutritious food to maintain a healthy and active life”

World Food Summit, 1996

World Food Summit, 1996 Limb et al. NKF 2018 Spring Clinical Meetings Abstracts #188. AJKD Vol 71 | Iss 4 | April 2018 p562

24‐hour diet recall interview and analyzed using the USDA Supertracker

24‐hour diet recall interview and analyzed using the USDA Supertracker

Living farther from the grocery store Living farther from the grocery store

If food cost influenced food

choices

If food cost influenced food

choices

• ↓ Na, protein, PO4• ↓ Fast food• ↑Carb• ↑Others preparing meal• Not related to calorie, BMI

• ↓ Na, protein, PO4• ↓ Fast food• ↑Carb• ↑Others preparing meal• Not related to calorie, BMI

• ↑Prepared food• ↑ Stress• ↓ Vit D

• ↑Prepared food• ↑ Stress• ↓ Vit D

Nutrition in KTx

Macronutrients

• Fat

• Protein

• Carbohydrate

Micronutrients

• Sodium

• Phosphorus

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Fat and Obesity

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How come I cannot stop eating after KTx?

• 52 y/o White man

• eGFR >60

• BMI 37

https://www.google.com/search?tbm=isch&source=hp&biw=1264&bih=749&ei=Bj23W7TeIrjH0PEPw6-

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Pre- vs. Post-KTx

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Pre-KTx Post-KTx

MortalityCardiovascular

Nutritional status • Sarcopenia• Malnutrition

• Weight gain- Overweight- Obese

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Potential contributing factors for post-transplant weight gain and obesity

Tantisattamo E.  Adv Obes Weight Manag Control. 2017;7(2):276‒279. DO NOT

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Causes of dyslipidemia post-KTxMedications

• Steroids

• Calcineurin inhibitors

• mTori

Other secondary causes

• Nephrotic syndrome

• Hypothyroidism

• Diabetes mellitus

• Excessive alcohol intake

• Obesity

• Chronic liver disease

• Genetic predisposition

• Low daily exercise

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Diet recommendation for hyperlipidemic KTx patient

• 6-mo of moderate calorie-restricted AHA step 1 in hyperlipidemic pt with BMI >27

• Mediterranean diet rich in olive oil and polyunsaturated fatty acids

• Soy protein (rich in mono and polyunsaturated fatty acids and protoestrogens) -> ↓ total cholesterol and LDL

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Fish oil vs. placeboHDL in KT recipient

Lim et al. Cochrane Database Syst Rev. 2016 Aug 18;(8):CD005282.

Total 15 RTC: 5 studies, 178 participants. Mean diff 0.12 mmol/L (95% CI 0.03 to 0.21)↑HDL, ↓Serum Cr (fish oild > 6 mo), ↓DBP

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Negative nitrogen balance during immediate post-KTx

↑ Hepatic gluconeogenesis

2/2 high dose steroids

↑ Hepatic gluconeogenesis

2/2 high dose steroids

Surgery-induced stress

Surgery-induced stress

Wound healingWound healing

Negativenitrogen balance

Negativenitrogen balance

Goral S, Bleicher MB. Handbook of Nutrition and the Kidney. Philadelphia, PA: Lippincott Williams and Wilkins (2010).

Nolte Fong JV and Moore LW. Front Med (Lausanne) 2018;5:302.

Guideline for post-KTx dietary protein intake

Post-KTx conditions Recommendation

Immediate post-KTx • ≥1.4 g/kg/day1

• 1.3-1.52

• 1.3-23

Regular review by a dietitian

Long-term (>4 mo post-KTx) • Female 0.75 g/kg/day1

• Male. 0.84 g/kg/day1

• <1 g/kg/day2

Treatment with high doses of prednisone e.g. acute rejection

• Same as immediate post-KTx1

Chronic renal allograft dysfunction • ? but >0.55 g/kg/day)1

1Chadban et al. Nephrology (Carlton) 2010;15 Suppl 1:S68-71. 2Goral S, Bleicher MB. Handbook of Nutrition and the Kidney. Philadelphia, PA: Lippincott Williams and Wilkins (2010). 3Nolte Fong JV and Moore LW. Front Med (Lausanne) 2018;5:302.DO N

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Carbohydrate &

Diabetes

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Transplant-associated hyperglycemia (TAH)

Goral S, Bleicher MB. Handbook of Nutrition and the Kidney. Philadelphia, PA: Lippincott Williams and Wilkins (2010).

Insufficient insulin secretionInsufficient insulin secretion ↑Insulin metabolism(Possible unmasked pre‐KTx DM)

↑Insulin metabolism(Possible unmasked pre‐KTx DM)

TAHTAH

↑Insulin resistance↑Insulin resistance

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Risk factors E.g.

Non-modifiable • Advanced age• Male• Non-White• Family history

Modifiable • Obesity• Physical inactivity• Weight gain• HCV• Immunosuppressive medications

Risk factors for TAH

Goral S, Bleicher MB. Handbook of Nutrition and the Kidney. Philadelphia, PA: Lippincott Williams and Wilkins (2010).

Diet recommendation for TAH

• Daily CHO 130– 180 g/day

• 1,800 – 2,000 Kcal/day

• Complete avoidance of concentrated sweets

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Nutrition in KTx

Macronutrients

• Fat

• Protein

• Carbohydrate

Micronutrients

• Sodium

• Phosphorus

• Magnesium

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Sodium48DO N

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Daily Na intake and on post-KTx HTN

Soypacaci et al. DTransplant Proc 2013;45:940-943.

Dietary Na suggestion• 2,000 mg of Na per day esp. h/o HTN

• Choose fresh, frozen, or canned food items without added salt.

• Limit the amount of salty snacks.

• Avoid adding salt when cooking or at the dinner table.

• Select unsalted or reduced sodium versions of broth, soups, and other processed foods.

• Spices and herbs in place of salt when cooking.

Phillips S and DeMello S. J Ren Nutr 2014;24:e15-17.DO NOT

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Phosphorus

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Should I drink more Coca Cola after KTx?

• 60 y/o Hispanic man

• eGFR >60

• Serum PO4 2

• On K-PO4-Neutral

kreg.steppe via http://www.flickr.com/photos/spyndle/5047889128/ Creative Commons

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Post-KTx hypophosphatemia

KTx

TacrolimusFGF23 remains

elevatedPTH remains elevated

Hypophosphatemia

• ↑Renal Pi excretion• ↓Intestinal Pi absorption• ↓1-alpha hydroxylation

• ↑Renal Pi excretion• ↓NaPi2a• ↑Renal Pi excretion

Blaine et al. Clin J Am Soc Nephrol 2015;10:1257-1272.

Nolte Fong JV and Moore LW. Front Med (Lausanne) 2018;5:302.

Post-KTx hypophosphathemiaDiet modification

• 3 sources of phosphorus• Organic phosphorus in plant foods

• Organic phosphorus in animal protein

• Inorganic phosphorus

• Phosphate rich foods e.g. whole grains, eggs, poultry, fish, and dairy products

• When good graft functionWickham E. J Ren Nutr 2014;24:pp e1-e4.

Watanabe et al. Clin Nutr ESPEN. 2016 Aug;14:37-41.

Pochineni V and Rondon-Berrios H. Front Med (Lausanne) 2018;5:261.DO NOT

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55Gomes-Neto et al. Clin J Am Soc Nephrol. 2020 Feb 7;15(2):238-246.

Food security in KTx recipients

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Environment &

Place to live

Environment &

Place to live

Food costPolicy

Regulations

Food costPolicy

Regulations

• Protein, CHO, fat• Na, K, PO4• Protein, CHO, fat• Na, K, PO4

• ↑ Stress• ↓ Vit D• ↑ Stress• ↓ Vit D

Food choicesFood choices

Social & Family support

Social & Family support

• ?Calorie• ?BMI• ?Calorie• ?BMI

• Prepared food• Fast food• Prepared food• Fast food

Education from providers

Education from providers

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Conclusions

• Living kidney donation is the most common cause of acquired solitary kidney in adults.

• Secondary FSGS is pathophysiologic change after unilateral nephrectomy.

• Long-term complications include CKD / ESRD, HTN, and proteinuria.

Conclusions

• Nutrition management should be one of the main strategies for the care after nephrectomy; although, there is a lack of evidence.

• Post-KTx immunological and non-immunological factors leads to complex nutrition-related conditions but provide opportunities to intervene and improve post-KTx outcomes.

• While waiting for evidences of nutritional management in KTxrecipients, secure food with education from all of us should help to mitigate poor renal and patient outcomes.

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Acknowledgements

• Dr. Kalantar for his advice of his mentorship and preparation for this talk.

• Faculty and staff, Division of Nephrology, Hypertension and Kidney transplantation

• UCI Medical Center and School of Medicine

• Our patient (both give and take) to motive our learning to improve our patient care

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References

1: Hart A, Smith JM, Skeans MA, Gustafson SK, Wilk AR, Castro S, Foutz J,Wainright JL, Snyder JJ, Kasiske BL, Israni AK. OPTN/SRTR 2018 Annual Data Report: Kidney. Am J Transplant. 2020 Jan;20 Suppl s1:20-130. doi: 10.1111/ajt.15672. PubMed PMID: 31898417.

2: Gomes-Neto AW, Osté MCJ, Sotomayor CG, van den Berg E, Geleijnse JM, Berger SP, Gans ROB, Bakker SJL, Navis GJ. Mediterranean Style Diet and Kidney Function Loss in Kidney Transplant Recipients. Clin J Am Soc Nephrol. 2020 Feb 7;15(2):238-246. doi: 10.2215/CJN.06710619. Epub 2020 Jan 2. PubMed PMID: 31896540.

3: Awan AA, Niu J, Pan JS, Erickson KF, Mandayam S, Winkelmayer WC, NavaneethanSD, Ramanathan V. Trends in the Causes of Death among Kidney Transplant Recipients in the United States (1996-2014). Am J Nephrol. 2018;48(6):472-481.doi: 10.1159/000495081. Epub 2018 Nov 23. PubMed PMID: 30472701; PubMed Central PMCID: PMC6347016.

4: Nolte Fong JV, Moore LW. Nutrition Trends in Kidney Transplant Recipients: the Importance of Dietary Monitoring and Need for Evidence-Based Recommendations. Front Med (Lausanne). 2018 Oct 31;5:302. doi: 10.3389/fmed.2018.00302. eCollection 2018. Review. PubMed PMID: 30430111; PubMed Central PMCID: PMC6220714.

5: Pochineni V, Rondon-Berrios H. Electrolyte and Acid-Base Disorders in the Renal Transplant Recipient. Front Med (Lausanne). 2018 Oct 2;5:261. doi: 10.3389/fmed.2018.00261. eCollection 2018. Review. PubMed PMID: 30333977; PubMed Central PMCID: PMC6176109.

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References

6: Merhi B, Shireman T, Carpenter MA, Kusek JW, Jacques P, Pfeffer M, Rao M, Foster MC, Kim SJ, Pesavento TE, Smith SR, Kew CE, House AA, Gohh R, Weiner DE, Levey AS, Ix JH, Bostom A. Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort. Am J Kidney Dis. 2017 Sep;70(3):377-385. doi: 10.1053/j.ajkd.2017.04.014. Epub 2017 Jun 2. PubMed PMID: 28579423; PubMed Central PMCID: PMC5704919.

7: Watanabe MT, Araujo RM, Vogt BP, Barretti P, Caramori JCT. Most consumed processed foods by patients on hemodialysis: Alert for phosphate-containing additives and the phosphate-to-protein ratio. Clin Nutr ESPEN. 2016 Aug;14:37-41. doi: 10.1016/j.clnesp.2016.05.001. Epub 2016 Jun 1. PubMed PMID: 28531397.

8: Pranger IG, Gruppen EG, van den Berg E, Soedamah-Muthu SS, Navis G, Gans RO, Muskiet FA, Kema IP, Joosten MM, Bakker SJ. Intake of n-3 fatty acids and long-term outcome in renal transplant recipients: a post hoc analysis of a prospective cohort study. Br J Nutr. 2016 Dec;116(12):2066-2073. doi: 10.1017/S0007114516004207. Epub 2016 Dec 20. PubMed PMID: 27993180.

9: Lim AK, Manley KJ, Roberts MA, Fraenkel MB. Fish oil for kidney transplant recipients. Cochrane Database Syst Rev. 2016 Aug 18;(8):CD005282. doi: 10.1002/14651858.CD005282.pub3. Review. PubMed PMID: 27535773.

10: Rathi M, Rajkumar V, Rao N, Sharma A, Kumar S, Ramachandran R, Kumar V, Kohli HS, Gupta KL, Sakhuja V. Conversion from tacrolimus to cyclosporine in patients with new-onset diabetes after renal transplant: an open-label randomized prospectivepilot study. Transplant Proc. 2015 May;47(4):1158-61. doi: 10.1016/j.transproceed.2014.12.050. PubMed PMID: 26036543.

References

11: Pirsch JD, Henning AK, First MR, Fitzsimmons W, Gaber AO, Reisfield R, Shihab F, Woodle ES. New-Onset Diabetes After Transplantation: Results From a Double-Blind Early Corticosteroid Withdrawal Trial. Am J Transplant. 2015 Jul;15(7):1982-90. doi: 10.1111/ajt.13247. Epub 2015 Apr 16. PubMed PMID: 25881802.

12: Blaine J, Chonchol M, Levi M. Renal control of calcium, phosphate, and magnesium homeostasis. Clin J Am Soc Nephrol. 2015 Jul 7;10(7):1257-72. doi: 10.2215/CJN.09750913. Epub 2014 Oct 6. Review. Erratum in: Clin J Am Soc Nephrol. 2015 Oct 7;10(10):1886-7. PubMed PMID: 25287933; PubMed Central PMCID: PMC4491294.

13: Phillips S, DeMello S. Nutrition and the kidney donor. J Ren Nutr. 2014 Mar;24(2):e15-7. doi: 10.1053/j.jrn.2013.12.001. PubMed PMID: 24559894.

14: McKane CK, Marmarelis M, Mendu ML, Moromizato T, Gibbons FK, Christopher KB. Diabetes mellitus and community-acquired bloodstream infections in the critically ill. J Crit Care. 2014 Feb;29(1):70-6. doi: 10.1016/j.jcrc.2013.08.019. Epub 2013 Oct 3. PubMed PMID: 24090695.

15: Soypacaci Z, Sengul S, Yıldız EA, Keven K, Kutlay S, Erturk S, Erbay B. Effect of daily sodium intake on post-transplant hypertension in kidney allograft recipients. Transplant Proc. 2013 Apr;45(3):940-3. doi: 10.1016/j.transproceed.2013.02.050. PubMed PMID: 23622593.

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References

16: Pascual J, Royuela A, Galeano C, Crespo M, Zamora J. Very early steroid withdrawal or complete avoidance for kidney transplant recipients: a systematic review. Nephrol Dial Transplant. 2012 Feb;27(2):825-32. doi: 10.1093/ndt/gfr374. Epub 2011 Jul 22. Review. PubMed PMID: 21785040.

17: Chadban S, Chan M, Fry K, Patwardhan A, Ryan C, Trevillian P, Westgarth F, CARI. The CARI guidelines. Protein requirement in adult kidney transplant recipients. Nephrology (Carlton). 2010 Apr;15 Suppl 1:S68-71. doi: 10.1111/j.1440-1797.2010.01238.x. PubMed PMID: 20591048.

18: Woodle ES, First MR, Pirsch J, Shihab F, Gaber AO, Van Veldhuisen P; Astellas Corticosteroid Withdrawal Study Group. A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy. Ann Surg. 2008 Oct;248(4):564-77. doi: 10.1097/SLA.0b013e318187d1da. PubMed PMID: 18936569.

19: Rettkowski O, Wienke A, Hamza A, Osten B, Fornara P. Low body mass index in kidney transplant recipients: risk or advantage for long-term graft function? Transplant Proc. 2007 Jun;39(5):1416-20. PubMed PMID: 17580151.

20: Vincent AM, Russell JW, Low P, Feldman EL. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr Rev. 2004 Aug;25(4):612-28. Review. PubMed PMID: 15294884.

References

21: Hasse JM. Nutrition assessment and support of organ transplant recipients. JPEN J Parenter Enteral Nutr. 2001 May-Jun;25(3):120-31. Review. PubMed PMID: 11334061.

22: Terranova A. The effects of diabetes mellitus on wound healing. Plast Surg Nurs. 1991 Spring;11(1):20-5. PubMed PMID: 2034714.

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