WEEK 7

KIDNEY DISEASE

Sierra Parker, RD, LDN, CNSC, MBA

Agenda
1 Overview of Kidney Disease and Causes 3

2 Types of Dialysis 7

3 AKI and Chronic Kidney Disease I-V Nutrition Recommendations 11

4 Bone Mineral Disorder 14

5 Labs, Medications and Food/Drug Interactions 16

6 Dietary Restrictions and Recommendations: Sodium, Potassium, Phosphorus, Calcium, Fluid, and More 23

7 Microbiota and Kidney Disease 27

8 Journal Articles 29

9 Resources 34
1 Overview of Kidney Disease and Causes
Kidney Basics
•Excretory Functions: Removes excess fluid and
waste products including urea, vitamins and
minerals
•Acid-Base Balance: Buffer system through filtration
and reabsorption using bicarb and citrate
•Endocrine Function: Calcitriol (1,25-dihydroxy-
vitamin D3) is produced by the kidney to enhance
calcium absorption and erythropoietin (EPO) is
produced to increase production of red blood cells
•Fluid and Electrolyte Balance: Antidiuretic
hormone (ADH) regulates reabsorption of water,
renin-angiotensin-aldosterone system will increase
blood pressure if extracellular volume decreases to
maintain adequate tissue perfusion
•Degradation: hormones, drugs, insulin, glucagon,
PTH, prolactin, growth hormones, etc.
Causes of Failure
• Diabetes – one quarter of all diabetics will have kidney disease
• Produces excessive reactive oxygen species, which damages the kidney's glomeruli resulting in albumin in the urine.
• Progresses and glomerular filtration barrier (GFB) is increasingly damaged. Now allows proteins in the blood to leak through, leading to
proteinuria. Deposition of abnormally large amounts of mesangial matrix causes periodic-acid schiff positive nodules called Kimmelstiel–
Wilson nodules. High blood sugar, which leads to formation of advanced glycation end products; and cytokines have also been implicated as
mechanisms for the development of diabetic nephropathy.
• High Blood Pressure - 1 in 2 U.S. adults have high blood pressure
• High blood pressure can constrict and narrow the blood vessels, which eventually damages and weakens them throughout the body, further
reducing blood flow and harming the kidneys.
• Glomerular Kidney Diseases
• Nephrotic syndrome- only proteins such as albumin, antithrombin or the immunoglobulins pass through the cell membrane and appear in
urine.
• Nephritis syndrome- small pores in the podocytes of the glomerulus, large enough to permit proteins and red blood cells to pass into the
urine (yielding proteinuria and hematuria)
• Polycystic Kidney Disease (and other genetic disease)
• Autosomal dominant PKD (ADPKD), which is usually diagnosed in adulthood - 1 in every 400 to 1,000 people in the world
• Autosomal recessive PKD (ARPKD), which can be diagnosed in the womb or shortly after a baby is born - 1 in 20,000 children
• Kidney-Related Birth Defects
• Autoimmune Kidney Diseases
• Idiopathic (unknown cause)
Types of Kidney Failure
Acute Kidney Injury (AKI) Chronic Kidney Disease (CKD)
• Prerenal AKI –decreased renal perfusion • CKD Stage 1 (GFR <90)
(with treatment can be quickly reversed) – DELAY PROGRESSION
• Renal AKI – underlying structural or • CKD Stage 2 (GFR 60-89)
functional changes – DELAY PROGRESSION
• Postrenal AKI – ex: obstructive uropathy
(remove cause of obstruction) • CKD Stage 3 (GFR 30-59)
– DELAY PROGRESSION
• MNT:
• Energy: RRT 20-30 kcal/kg EDW, • CKD Stage 4 (GR 15-29)
• Protein: 1-1.5 g/kg (up to 1.7 if on CRRT – DELAY PROGRESSION!
and/or hypercatabolic) • CKD Stage 5 (GFR <15)
• Fluid restriction if anuric/oliguric (not CRRT) – AKA Kidney Failure or ESRD
• Vitamin/mineral losses in CRRT (replace)
New Insight into Iron Supplementation and
CKD
Iron Deficiency Anemia
• Cause:
• Damaged kidneys produce less erythropoietin, which is a hormone
that signals your bone marrow to make red blood cells.
• Increased hepcidin due to decreased renal clearance and elevated IL-
6 results in iron sequestration in macrophages and resistance to EPO
• Inability to absorb iron in the gastrointestinal tract
• Diagnosis:
• TSAT is ≤20% +
• Serum ferritin concentration is ≤100 ng/mL 
• Hb <13 g/dL (M) and Hb <12 g/dL (W), according to WHO criteria for
those with GFR <60ml/min/1.73m²
• Treatment:
• KDOQI: oral iron trial followed by IV iron
• PIVOTAL trial showed that high-dose iron was noninferior to low-dose
IV iron
• Risks:
• Excess iron supplementation may result in intestinal permeability and
contribute to dysbiosis
2 Types of Dialysis
Type of Dialysis Location Duration Frequency • Continuous Ambulatory Peritoneal
Conventional In-Center 3-5 hr 3x/wk Dialysis (CAPD)
Home Nocturnal Home 7-10 hr 5-7x/wk
• Automated Peritoneal Dialysis (APD)
Home Short Daily Home 2-3 hr 5-7x/wk
• Continuous cyclic PD (CCPD)
In-Center Daily In-Center 2-3 hr 5-6x/wk • Nocturnal intermittent PD (NIPD)
In-Center In-Center 7-8 hr 3x/wk
Nocturnal
Starting HD
• Access placed (if emergent, might start with catheter)
• First choice is AV fistula, then graft, then catheter.
• MD will create prescription with bath, time and blood flow rate
• As patient starts and gets used to the procedure (get weighed, wash
access, be in chair, hold sites, take post weight), the interdisciplinary
team will meet with them
Starting PD

• Access placed – peritoneal catheter

• PD RN performs in-home and clinic training with the patient, works
them on everything from storing supplies, hand hygiene, and PD
initiation/completion

Transporter Waste Removal Water Removal Best type of PD

PET Test
High or Fast Fast Poor Frequent exchanges, short dwells
Average Fair Fair CAPD or APD
Slow or Low Slow Good CAPD, 5 evenly spaced exchanges and 1 exchange at
night using a small machine
 AKI and Chronic Kidney Disease I-V Nutrition
3
Recommendations
Chronic Kidney Disease Management
Protein
• Modification of Diet in Renal Disease
(MDRD) study (800 pts with CKD) -
beneficial effect from protein
restriction (delays dialysis).
• Consuming plant proteins may have
less effect on GFR
• Stage 1 and 2: 0.8-1.4 g/kg/d
• Stage 3 and 4: 0.55-0.8 g/kg/d
• Stage 5 Pre-dialysis: 0.6 g/kg/d (to
alleviate uremic symptoms)
• Dialysis Patients: 1-1.2 or 1.3g/kg
Energy
• 23-35 kcal/kg (like healthy controls) for CKD
• Dialysis Patients: 30-35 kcal/kg
• Unfortunately, energy intake often decreases as
disease progresses (as GFR drops below
60mL/min/1.73m2 both calorie and protein
intake decrease)
• Higher BMI is associated with lower mortality
(ideal range is 22-25.5)
• Protein-energy wasting (PEW) at start of dialysis
is associated with increased mortality
• Actual body weight is often used to determine
needs in both under- and overweight individuals
unless clinical judgment indicts otherwise.
4 Bone Mineral Disorder
 Calcium, Phosphorus, PTH, Calcitriol

& Serum Phos

Serum Phos

Serum Phos

Increases both Ca
and Phos
absorption,
decreases PTH
production

(Calcitriol)
Kidney failure inhibits vitamin
D activation
5 Labs, Medications and Food/Drug Interactions
 Labs
Frequent Lab Test ESRD Typical Goal Values Causes
Albumin >3.5, best to see >4.0 Low: Fluid overload, hepatic disease, weight loss, poor appetite,
medication side effects, hospitalization/infection, comorbidities
Aluminum <60 High: Medication side effect (old aluminum binders, stomach med)
Calcium (Adjusted) 8.4-10.2 Low: low vitamin D due to renal failure, high phosphorus, hungry bone
High: calcium excess (dietary/binder), active Vitamin D excess
Ca x Phos Product <55 High calcium and/or high phosphorus (see other labs)
Carbon dioxide >22 Low: acidosis
Glucose <200 Low: too much insulin, poor nutrition
High: too little insulin, diet
Kt/V >1.2 Low: inadequate dialysis
Magnesium 1.5-2.4 Low: Diuretics, acidosis, poor nutrition, malabsoprtion
High: Meds (antacids/laxatives), thiazide diuretics, D3

Jessica Krefting MS, RD, LDN

Frequent Lab Test ESRD Typical Goal Values Causes
PCR/PNA >0.8 Low: protein deficit, anabolism
>1.4 (considered high) High: excessive intake/excessive LBV protein, catabolism
Phosphorus 2.5-5.5 Low: Malnutrition, GI losses, excessive binder dosage
High: Excessive dietary intake, binder nonadherence/inadequate rx,
constipation/gut motility, enema use, catabolism, severe BMD

Potassium 2.5-5.5 Low: Medication side effect, malnutrition, chronic diarrhea/GI loss
High: Excessive dietary intake, underdialyzed or access issue,
medication side effect, acidosis, constipation, hyperglycemia
PTH Around 150-600 Low: adynamic bone disease, too much activated vit D
High: hyperparathyroidism
Sodium 135-144 Low: Fluid overload
High: Dehydration
URR >65 Low: Inadequate dialysis

Vitamin D >30 Low: Renal function

Jessica Krefting MS, RD, LDN

 Medications At Dialysis
Medication Purpose Nutrition Effect and Implications
ESAs (erythropoietin Promote red blood cell production (kidney normally Increased appetite
stimulating agents) produces EPO) Increased blood pressure
May lead to iron deficiency, low folate and B12 stores

IV or Oral Iron Iron-deficiency anemia treatment Constipation/GI upset (oral)

Calcitriol Activated vitamin D Mobilizes minerals from bones, shuts off PTH production,
enhances gut absorption of calcium and phosphorus
Hectoral Vitamin D analog (vitamin D2 prohormone) Lowers PTH with a low rate of hypercalcemia and
hyperphosphatemia

Jessica Krefting MS, RD, LDN

Dialysis Baths: 1K, 2K, 3K
• Rapid rise and decline of serum K may cause cardiac arrhythmias
• K fluctuation with intermittent HD
• Patients are particularly vulnerable during first dialysis of the week
due to rapid K loss
• Lower dialysate K baths and higher serum K/Higher dialysate K baths
and lower serum K  risk of rapid fall or rise of serum K
Potassium Binders
• Newer agents: Patiromer
• A non-absorbed, cation exchange binder
• Works by binding free K in the colon and releasing Ca for exchange
• Distal colon has highest concentration of free K, hence binding of K
results in significant fecal K excretion
• Not taken with other oral drugs due
to binding or drug-drug interactions

• Kayexelate (sodium polysyrene sulfate resin)

• Causes diarrhea, exchanges sodium ions for potassium
 Bone Mineral Disorder Medications
Medication Method of Administration Amount of Phos Bound Nutrition Effect and Implications
Calcium carbonate (Tums) Tablet– chewable 39 mg phos/g Hypercalcemia (absorb more calcium than
with calcium acetate)

Calcium Acetate (PhosLo, Gelcap – swallow only (no cut/crush) 45 mg phos/g

PhosLyra) Powder – mix with fluid & swallow, GI tube
Sevelamer carbonate Tablet – swallow only (no cut/crush) 21 mg phos/g
(Renvela) or HCL (Renagel) Powder – mix with fluid & swallow, GI tube
Lanthanum carbonate Tablet - chewable 115mg/tab Taste issues
(Fosrenol)
Sucroferric oxyhydroxide Tablet – chewable 130 mg/phos/tab
(Velphoro)
Ferric citrate (Auryxia) Tablet – swallow only 46 mg phos/g Can also impact iron levels if concern of
anemia, but be aware of iron impact on
microbiome
Sensipar (Cinacalcet) Tablet – swallow only N/A Acts on parathyroid For treatment of secondary HPT – does not
calcium-sensing receptor increase calcium or phosphorus (in fact can
and reduce PTH secretion lower), nausea and vomiting side effects
 Dietary Restrictions and Recommendations:
6 Sodium, Potassium, Phosphorus, Calcium, Fluid,
and More
HD and PD Sodium and Potassium
Recommendations
Sodium Potassium
• Individualized for fluid status, blood • Depending on urine output, 2-4g of
pressure, interdialytic weight gain (IDWG) potassium can be allowed (generally
and residual renal function. closer to 2g)
• Restrict sodium to <2g – adherence is
the issue
• Individual allowance between 40-
• Very little residual renal function (500
50 mg/kg of ideal body weight
mL/d) can have up to 1,500 mL • Management with dialysis removal
• <5% of IDWG is goal for between (bath), diet, medications
treatments • More liberalized in PD
• IDWG >5.7% of dry weight is associated
with a 35% increase in mortality
HD and PD Dietary Recommendations &
Restrictions
Phosphorus
• 800-1000 mg/d (<17mg/kg body weight)
• May be more restricted in PD depending on
dietary patterns and oral nutritional
supplements due to poor clearance
• Management is based on a combination of
dialysis removal, intestinal binding and
dietary restrictions
• HD phosphorus clearance ranges from 500-
1000mg per treatment (more in first 1-2 hours)
• High phos can lead to uremic pruritus when
excessive calcium and phosphorus precipitate in
the skin
Calcium
• 1000-2000 mg/d in diet,
supplements, and medications
• Management is through
bone/intestinal absorption and
renal excretion, diet,
supplements, medication, and
dialysis bath
• Explore limiting calcium to 500
mg/d if calcium based binders
HD and PD Dietary Recommendations &
Restrictions
• Water soluble vitamins
supplementation should be used to
replace what is lost during dialysis
• Vitamin A is often increased in HD
patients and supplementation is not
recommended
• Vitamin E supplementation
evidence is inconclusive
• Vitamin K has been shown to be low
to normal so it may be useful.
• Active vs. inactive vitamin D
Vegetarian Diet and CKD
7 Microbiota and Kidney Disease
Gut Microbiota and Renal Disease Kidney Dysfunction
and Changes in the Gastrointestinal Tract
• The most widely studied uremic retention solutes derived of microbial metabolism are indoxyl sulfate,
p-cresyl sulfate, and Trimethylamine N-oxide (TMAO).
• Indoxyl sulfate is 40-fold higer in dialysis patients. It can lead to increased oxidative stress through the activation of
NADPH oxidases, enhanced inflammatory state through the activation of NF-kB via STAT3, activation of the renin-
angiotensin-aldosterone system, enhanced aortic calcification, and mineral and bone disorder.
• P-cresyl sulfate has been associated with increased inflammation, reduced antioxidant capacity, activation of renin-
angiotensin-aldosterone system, increased insulin resistance, cardiovascular risk, and all-cause and cardiovascular
mortalities.
• TMAO also caused progressive kidney fibrosis experimentally and clinically was associated with progression of CKD,
cardiovascular disease, mineral and bone disorder and mortality.

• Vaziri et al. reported that individuals with ESKD undergoing hemodialysis treatment had a higher
relative abundance of Actinobacteria, Firmicutes, and Gammaproteobacteria, whereas individuals
without CKD had a higher relative abundance of Lactobacillaceae, Sutterellaceae, and Bacteroidaceae
families.
• Crespo-Salgado et al. showed that fecal microbiota of pediatric peritoneal dialysis and post-transplant
patients had lower bacterial species richness compared with patients on hemodialysis and healthy
controls.
• In a targeted quantitative real-time PCR analysis, Wang et al observed that adult patients undergoing
peritoneal dialysis had decreased relative abundances of Bifidobacterium and Lactobacillus spp.
including B. catenulatum, B. longum, B. bifidum, L. plantarum, and L. paracasei.
• Therefore, somewhat consistently, it has been observed that in patients with CKD, the relative
abundance of symbiotic bacteria is reduced, whereas some potential pathobionts are increased.
 Prebiotic, Probiotic, and Synbiotic Supplementation in
Chronic Kidney Disease
Discussion:
• 16 studies
• 645 adults
• Prebiotic, probiotic, and synbiotic supplementation
may have led to little or no difference in serum urea
(p = 0.76), indoxyl sulfate (p = 0.61), and p-cresyl
sulfate (p = 0.35,). Prebiotic supplementation may
have slightly reduced serum urea concentration (p =
0.006).
• Of the 2 studies investigating microbiota changes,
synbiotic interventions significantly increased
Bifidobacterium.
• Supplement effects on clinical outcomes were
uncertain.
8 Journal Articles
IHOPE

Methods Results
• 5 HD centers • No significant effect on shuttle walk test results
• Randomized Control Trial between the 3 groups.
• Inclusion Criteria: Patients receiving HD treatment >3 days/week; dialysis
vintage >3 months; age 30–80 years; and not currently receiving intradialytic • 6 months, performance on the sit-to-stand (STS)
ONS or participating in intradialytic exercise. 138 met inclusion criteria. and timed up-and-go (TUG) improved by 15% (P =
• Control (CON) patients received 150g of a non-nutritive beverage (Crystal 0.018) and 6% (P = 0.003) in the PRO EX group but
Light, Kraft Foods Group, Inc., Chicago, IL) during each dialysis session. did not change in the CON or PRO groups.
• Protein supplementation (PRO) patients received a 30-g whey protein
supplement (True Protein Inc., Vista, CA) at each dialysis session, mixed into • Gait speed improved at 6 months by 11%–12% in
4–6 ounces of water and consumed at the beginning of the session. both the PRO and PRO EX groups, but only 7% in
• Protein exercise training (PRO EX) patients received the 30-g whey protein the CON group (P = < 0.05 for all).
supplement and underwent supervised exercise for up to 45 minutes on
cycle ergometers (Rehab trainer 881E, Monark Inc., Langley, WA) during
each dialysis session.
• High dropout rate in our exercise group (27% at 6
• The training started with patients cycling at a tolerable pace for 5–10
months, and 41% by 12 months).
minutes/session, increasing progressively until able to cycle
continuously for up to 45 minutes/session at a rating of perceived
exertion of 12–14 (“some what hard”).
• Follow-up at baseline, 6 months, and 12 months with a shuttle walk test.
IHOPE
Discussion
• The objective of the study was to see if protein and
exercise supplementation for hemodialysis patients
could indeed improve the quality of life of CKD patients.
• Most studies have not showed added benefits of protein
supplementation, exercise or the two together over a
long period of time or have consistent results.
• Conclusion: 12 months of intradialytic OPS, with or
without intradialytic exercise training, had limited
benefits on physical function, body composition, markers
of CVD risk, and QOL in HD patients.
• Confirmed that there is need for additional studies to
assess exercise and protein consumption for dialysis
patients, but as well as the importance of tailored
nutrition recommendations.
Further Points
• High-drop out rate
• There was no “exercise only” group
• Only collected patients from 5 HD centers all within
the same geographic area
• Did not assess alternative protein supplements or
sources
• Did not assess hand-grip strength and used SWT,
which has not been verified in HD patients.
• The protein consumption on dialysis days was closer
to dietary guidelines, which makes you question if
the protein requirements are appropriate for dialysis
patients. However, there is no comment in the study
about dietary recall data.
Efficacy of Prebiotics…
Methods
• Any HD or PD patient over 18 years of age
• Patient taking any prebiotic, probiotic, or synbiotic oral
supplement
• Primary outcome measure: circulatory endotoxin,
indoxyl-sulphate, and p-cresyl sulfate
• Reviewed any study that had a parallel-group randomized
controlled trial (allocation at individual or cluster level or
using a quasi-randomized method) or crossover
randomized controlled trial
Results
• Twenty-one trials (1152 randomized participants)
• Probiotic and synbiotic supplementation
significantly reduced circulating levels of endotoxin
(p= 0.004)
• Prebiotic, probiotic, and synbiotic supplementation
showed a decrease in indoxyl-sulphate (p = 0.02)
• Prebiotic only studies did not show any approval in
indoxyl-sulphate levels
• Prebiotic, probiotic, and symbiotic
supplementation indicated a significant reduction
in circulating p-cresyl sulfate (p= 0.01)
Efficacy of Prebiotics…

Discussion
• Demonstration that prebiotics, probiotics and
synbiotics do improve circulatory endotoxin,
indoxyl-sulphate, and p-cresyl sulfate levels

Further Points
• Concern of study bias
• Reviewed small trials
• Minimal blinding
9 Resources
Byham-Gray, L, Stover, J, and Wiesen, K. (2013). A Clinical Guide to Nutrition Care in Kidney Disease.
Davita Inc., Dietitian Manual. Revised: September 2010.
Gafter-Gvili, A, Schecter, A, and Rozen-Zvi, B. (2019). Iron Deficiency Anemia in Chronic Kidney Disease. Acta Haematologica, 142, 44-50.
Ikizler, T. A, et al. (2020). KDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update. American Journal of Kidney Disease, 76(3), S1-S107.
Jeong, J, H, et al. (2019). Results from the randomized controlled IHOPE trial suggest no effects of oral protein supplementation and exercise training on
physical function in hemodialysis patients. Kidney International, 96, 777-786.
Kim, M, Yang, J, Jo, S. (2021). Intestinal microbiota and kidney diseases. Kidney Research and Clinical Practice, 40(3), 335–34
https://www.niddk.nih.gov/health-information/kidney-disease/polycystic-kidney-disease/what-is-pkd
https://www.niddk.nih.gov/health-information/kidney-disease/high-blood-pressure
Lambert, K, et al. (2021). Commentary on the 2020 update of the KDOQI clinicalpractice guideline for nutrition in chronic kidney disease. Nephrology, 1-4.
March, D, S, et al. (2020). The Efficacy of Prebiotic, Probiotic, and Synbiotic Supplementation in Modulating Gut-Derived Circulatory Particles Associated With
Cardiovascular Disease in Individuals Receiving Dialysis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Journal of Renal Nutrition,
30(4), 347-359.
McCann, L. (2015) Pocket Guide to Nutrition Assessment of the Patient with Kidney Disease. A Concise, Practical Resource for Comprehensive Nutrition Care
in Kidney Disease. National Kidney Foundation, 5.
McFarlane, C, et al. (2019). Prebiotic, Probiotic, and Synbiotic Supplementation in Chronic Kidney Disease: A Systematic Review and Meta-analysis. Journal of
Renal Nutrition, 29(3), 209-220.
Pourafshar, S, Scialla, J, J. (2021). Reconsidering Plant-Based Diets in Patients Receiving Maintenance Hemodialysis. American Journal of Kidney Disease,
78(5), 624-626.
Ramezani, A, Raj, D, S. (2014). The Gut Microbiome, Kidney Disease, and Targeted Interventions. Journal of the American Society of Nephrology, 25(4), 657-
670.
Ribeiro, M, Fonseca, L, S. Anjos, J, et al. (2022). Oral iron supplementation in patients with chronic kidney disease: can it be harmful to the gut microbiota?
Nutrition Clinical Practice, 37, 81-93.
Snelson, M, Biruete, A, McFarlan, C, and Campbell, K. (2019). A Renal Clinician’s Guide to the Gut Microbiota. Journal of Renal Nutrition, 11(002), 1-12.
Vaziri N, D, Yuan, J, Norris, K (2013). Role of urea in intestinal barrier dysfunction and disruption of epithelial tight junction in chronic kidney disease.
American Journal of Nephrology, 37, 1-6.