Bracketology

www.AJKDBlog.org

March 1-31, 2025

Slides Prepared by the

NephMadness Executive Committee

• Matthew Sparks
• Anna Burgner
• Anna Vinnikova
• Elena Cervantes
• Jeffrey Kott
• Ana Catalina Alvarez-Elías
• Dia Waguespack
• Krithika Mohan

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What to do

• Review the Regions & Teams on AJKDBlog

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• Submit your picks by March 31, 2025, on Tourneytopia

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• Discuss on social media using #NephMadness

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• Claim CME/MOC credit through NKF PERC

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The BRP Has Chosen the Winning Bracket

To win, predict what the BRP thinks will bring the most practice change to nephrology!

• Roger Rodby
• Deidra Crew
• Kirk Campbell
• Samira Farouk
• Tom Oates
• Meredith Atkinson
• Linnys Alcántara Quiroga
• Clodagh Sweeney
• David Rush

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Resistant Hypertension

Writer:

Stephanie Torres Rodriguez

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Expert:

Jordana Cohen

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Region Execs:

Matthew Sparks

Elena Cervantes

Novel Drugs for Hypertension

Novel Drugs for Hypertension

Definition​

• Blood pressure remains above goal despite concurrent use of ≥3 anti-hypertensive agents of different classes​
• If tolerated – one of the agents should be a diuretic
• All agents should be prescribed at maximum recommended (or maximally tolerated) anti-hypertensive doses​

OR​

• Blood pressure controlled with ≥4 medications – also is considered resistant​

Evaluate for other contributors to hypertension

• Untreated obstructive sleep apnea​
• Hormone dysregulation​
• Hyperaldosteronism​
• Thyroid disease (hypo/hyperthyroidism)​
• Pheochromocytoma / paraganglioma​
• Hypercortisolism (Cushing syndrome)​
• Apparent mineralocorticoid excess​
• Volume overload​
• Aortic coarctation​
• Renal artery stenosis​
• Fibromuscular muscular dysplasia – 10-25% of RAS​
• Atherosclerotic disease

• Dual endothelin receptor antagonist: aprocitentan

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• Aldosterone synthase (CYP11B2) inhibitor: baxdrostat & lorundrostat

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• Small interfering RNA (siRNA) for angiotensinogen: zilebesiran

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• Glucagon-like peptide-1 receptor agonist (GLP-1 RA): semaglutide

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~4 mmHg

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~10 mmHg

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~4 mmHg

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~5 mmHg anti-HTN meds

BP

Effect

Adverse effects

BP

Effect

Adverse effects

BP

Effect

Adverse effects

BP

Effect

Adverse effects

Novel Drugs for Hypertension

~10-15% fluid retention

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~2% hyperkalemia

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~6-7% hyperkalemia

~10% injection site reaction

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~30% nausea

~10% diarrhea

PO Daily

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PO Daily

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SQ q 6 months

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SQ q week

Route

FDA Approved

FDA Approved

Renal Denervation

EFFLUENT EIGHT ROUND

Pick Your Champion for the Resistant Hypertension Region

Renal Denervation

vs

Novel Rx for HTN

Disaster Nephrology

Writer:

Rasha Raslan

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Expert:

Mehmet S Sever

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Region Execs:

Anna Vinnikova

Ana Catalina Alvarez-Elías

Kidney Care In Natural Disasters

Disaster Nephrology and Crush-AKI

World War II saw the introduction of the artificial kidney by Kolff and the first ever HD treatment.

Disaster Nephrology is a specialized field focused on coordination of care of kidney patients during a disaster. The term evolved from the earlier “Seismo-Nephrology” dedicated to managing Crush-AKI.

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AKI from crush injury was first recognized during World War 1.

Kidney Impact in Natural Disasters

ACUTE KIDNEY INJURY

TRANSPLANT

CKD AND ESKD

• Prerenal AKI in entrapped or bleeding victims

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• ATN from prolonged shock, sepsis, and transfusion reactions

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• Rhabdomyolysis and crush syndrome in crush victims

• Loss of access to medications

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• Emergency disconnects from HD

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• Complications from missed dialysis treatments

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• Power and water outages

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• Issues with supplies delivery

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• Disruption of transplant activities
• Loss of access to medications

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• Increased infectious complications

BEFORE

DURING

AFTER

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Patients:

• Practice HD emergency disconnect procedures, PD manual exchanges
• Emergency kits
• Stockpile medications and supplies for 1-2 weeks

Dialysis facility:

• Develop disaster protocols
• Contracts for generators and water tankers
• Disaster preparedness training
• Tabletop drills

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• Follow protocols

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• Rapid triage and evacuations

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• Telemedicine

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• Arrange generators, water tankers as needed

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• Communication with disaster relief authorities

• Re-establish care of neglected conditions

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• Mental healthcare for patients and staff

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• Evaluate disaster response, debrief, lessons learned

Kidney Care in Natural Disasters

Kidney Care In Conflicts

ACUTE KIDNEY INJURY

CHRONIC KIDNEY DISEASE

TRANSPLANT

• High AKI burden (hard to quantify)

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• Pre-renal is the most common due to dehydration or hemorrhagic shock

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• Nephrotoxic exposure to noxious gases and toxic agents

• Limited evaluation

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• Difficulty with dietary and medication adherence

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• Poor access to treatment and supplies

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• Degradation of specialized care

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• Inability to create longer term vascular access like fistulas

• Poor functionality of transplant facilities or access to specialist

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• Increased risk of rejection due to poor access to medications

Kidney Impact in Conflicts

BEFORE

DURING

AFTER

• Training patients and staff on self-security issues

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• Training on best practices in resource-limited setting

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• Medication stockpiling

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• Training patients on emergency dietary restrictions

• Field hospitals

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• Evacuations

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• Telemedicine

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• Rotating schedule for staff

• Restoration of services

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• Address mental health

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• Debriefing

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Kidney Care in Conflicts

EFFLUENT EIGHT ROUND

Pick Your Champion for the Disaster Nephrology Region

In Conflicts

vs

In Natural Disasters

Genetics

Writer:

Matthew Gross

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Expert:

Jordan Nestor

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Region Execs:

Elena Cervantes

Matthew Sparks

Genetics in FSGS

Genetics in FSGS

The following are the most common genes with mutations known to cause genetic FSGS:

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Genetic Counseling

Genetic Counseling

• Purpose of Genetic Testing: It helps diagnose genetic kidney disease, assess risks in kidney donors, inform at-risk family members, and guide personalized treatments (i.e. post hoc analysis of the DUPLEX trial showed more proteinuria reduction with sparsentan vs irbesartan in genetic FSGS).

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• Testing Modalities: There are several, but curated gene panels/targeted next-generation sequencing (NGS) - which assesses for specific sets of genes- is our go-to tool in clinical practice! Whole exome sequencing (WES) analyzes the entire exome and is used in research or in patients from whom NGS was non-diagnostic.

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• Informed Consent Considerations: Patients should understand potential test implications, such as:

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�

• Kidney Donation and Genetic Testing: Genetic screening can be considered in living kidney donors- testing in ADPKD can be high yield while identifying APOL1 variants remains a complex issue.�
• Genetic Counselors: They assist in interpreting results, managing emotional and social impacts,�and guiding cascade testing for at-risk family members.

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EFFLUENT EIGHT ROUND

Pick Your Champion for the Genetics Region

Genetic Counseling

vs

Genetics in FSGS

CAR-T for Kidney Disease

Writer:

Yara Mouawad

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Expert:

Jeffrey Sparks

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Region Execs:

Dia Waguespack

Anna Burgner

CAR-T for Autoimmune Disease

From Idea to Impact: The CAR-T Cell Journey

CAR-T Cell Therapy for Autoimmune Diseases

• Autoantibodies are directly pathogenic in select autoimmune diseases.
• Targeting B-cells has proven effective.
• However, persistent B-cell infiltrates in tissue.
• Based on success in cancer therapies, use expanded to autoimmune disease.
• Murine model of lupus:
• Effective depletion of CD19 B-cells in inflamed tissue → decreased Ab targeting dsDNA, decreased proteinuria, and increased survival.

NEJM 2024: Case series, 15 patients with refractory autoimmune dz (8 with SLE). Followed ~15 months. Demonstrated rapid expansion of CAR T cells and effective B cell depletion, most with B cell reconstitution at 100 days. Remained in remission off immunosuppression

*Limitations: open label, single arm small number of patients, no kidney biopsies

• T-cells are collected from patients through apheresis.
• CD19 CAR T-cells are generated through lentiviral transduction of the CAR encoding vector.
• Cells expanded using cytokine cocktail.
• Patient receive lymphodepleting chemotherapy:
• Cyclophosphamide and fludarabine
• More targeted strategies (e.g. Treg in development).

Why?

How?

CAR-T Side Effects

CAR-T Cell Therapy - Side Effects and Potential Limitations

Short Term Side Effects

Long Term Side Effects

• Cytokine release syndrome (CRS):
• Result of T-cell activation and cytokine release
• Severity of reaction varies.
• Symptoms: fever, respiratory failure, hypotension, possible progression to multiorgan failure, death
• Immune cell associated neurotoxicity syndrome (ICANS):
• Mechanism not understood.
• Severity of reaction varies.
• Symptoms: confusion, aphasia, seizure, coma
• Supportive treatment with steroids

• Cytopenias
• Hypogammaglobulinemia
• Infections
• Potentially impaired response to vaccinations
• Malignancies
• Due to insertional mutagenesis
• Risk of T-cell malignancies appears to be lower than those undergoing traditional chemotherapy.
• Require lifelong monitoring.

Accessibility is limited by cost, limited treatment centers, eligibility restrictions and logistical challenges.

The small number of patients treated with CAR T-Cells for autoimmune dz, severe toxicities have thus far been rare.

Kidney Related Considerations

EFFLUENT EIGHT ROUND

Pick Your Champion for the CAR-T for Kidney Dz Region

CAR-T Side Effects

vs

CAR-T for Autoimmune Dz

Hemodialysis

Writer:

Mansi Bapat

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Expert:

Mariana Murea

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Region Execs:

Jeffrey Kott

Anna Burgner

Hemodiafiltration

• Hemodiafiltration (HDF) combines diffusive with convective clearance to improve clearance of larger molecular weight molecules including certain proteins/uremic toxins (i.e. FGF-23, Advanced Glycation Endproducts) that contribute to increased cardiovascular (CV) mortality and impaired immune function in patients undergoing chronic dialysis.

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• HDF not only uses dialysate but replacement fluid which is infused into the patient to replace the large volume of plasma water removed through ultrafiltration.

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• 5 Randomized Controlled Trials have been been completed with varying results with respect to all-cause, cardiovascular, or infection related mortality
• Peters et. al., a meta-analysis of 4 RCTs (not including the Convince Trial) demonstrated a 14% reduction in all-cause mortality and a 23% reduction in CV mortality compared to HD, especially those who received higher convections volumes
• Long term follow up of the patients from 4 RCTs demonstrated stable Left Ventricular Mass and Ejection Fraction in the groups that received HDF compared to Hemodialysis
• There may be some evidence that HDF is cost effective, however the Quality-Adjusted Life Year (QALY), a measurement of patient’s quality and quantity of life is limited, and further research is needed.
• In addition to cost effectiveness, there are several questions that remain to be answered regarding HDF
• While preliminary data has demonstrated higher convection volumes may be beneficial, no direct head-to-head trial has compared the two approaches.
• No studies have focused on individuals that have not yet started Kidney Replacement Therapy. The ideal convective volume remains unclear in this population.

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Hemodiafiltration

Incremental Dialysis

• Incremental Hemodialysis (HD) involves adjusting the frequency or duration of a patient’s hemodialysis prescription based on their biology and symptoms and is a patient centered approach to HD compared to the traditional 3x weekly HD.
• That is in contrast with Peritoneal dialysis, where residual kidney function (RKF) is factored into a patients ”dose” (Kt/V), HD prescriptions usually target a Kt/V of 1.2, not taking RKF into account.

What challenges exist? And how can we overcome them?

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• Uncertainty regarding patient adherence and expectations related to incremental changes in HD prescriptions.
• Repeated Patient Education
• Increased workload for nephrologists and dialysis staff, who must monitor patient parameters more frequently and closely.
• Automating RKF measurement and substitution of additional care typically dedicated to HD to monitoring of RKF
• Potential for reduced financial margins for dialysis stakeholders due to fewer overall HD treatments and lower financial reimbursements.
• Potentially longer patient lifespans could ultimately lead to more dialysis treatments.

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Feasibility Trials have demonstrated incremental dialysis is both feasible and safe, however larger scale, randomized trials are needed

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• The decline in RKF differs based on the individual, and incremental dialysis would take into account the need for a higher dose of dialysis.

Incremental Dialysis

EFFLUENT EIGHT ROUND

Pick Your Champion for the Hemodialysis Region

Incremental Dialysis

vs

Hemodiafiltration

Green House

Writers:

Ethan Downes

Rachel Kahn

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Expert:

Linda Awdishu

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Region Execs:

Anna Vinnikova

Elena Cervantes

Tubular Toxins

Tubular Toxins

• 80% of patients in the world use herbal medicines (HMs).
• 8% of patients with CKD use HMs on NKF “avoid in CKD” list.
• HMs are not regulated or assessed for safety and efficacy.
• FDA can remove supplements only if there’s proof of harm/deceptive labeling.

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HMs can hurt kidneys:

• Nephrotoxicity
• Contamination
• Adulteration
• Misidentification
• Drug interactions (i.e. with immunosuppressants)

Kidneys are ‘terrific’ toxin targets

• Major site of drug excretion
• Large volume of blood processed
• Renal tubular epithelium has broad surface area and high metabolic activity relative to blood supply

Why?

How?

• proximal tubular dysfunction
• rapidly progressive CKD-> ESKD
• severe anemia
• shrunken kidneys with fibrosis on biopsy

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• glycyrrhyzic acid blocks 11-β-HSD allowing cortisol to
• activate MR receptors

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• Originally used in slimming regimens
• Currently banned
• Causes aristolochic acid nephropathy (AAN)

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• Urothelial carcinoma

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• Widely used in sweets
• Alternative medicinal use as expectorant, gastroprotective and hepatoprotective agent
• Causes hypertension and hypokalemia

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• AKI sec to hypokalemic rhabdomyolysis or tubular toxicity

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Aristolochia

Licorice

Famous Tubular Toxins

Oxalate Offenders

Oxalate Offenders

• Oxalate is an organic acid produced by plants for protection against

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• Oxalate is an anti-nutrient (reduces absorption of Ca, Mg, Fe)

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• Famous Oxalate Offenders: star fruit, cranberries, nuts + see the VA

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• Oxalate Nephropathy:

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ATN -> reabsorbed crystals initiate inflammation via NLRP3 inflammasome -> TIN ->

interstitial fibrosis

1. Intratubular and interstitial deposition of translucent crystals (H&E)
2. Crystals are birefringent under polarized light

• hard ions in groundwater
• infections
• herbivores

Oxalate Offenders

Management of dietary hyperoxaluria

(extrapolated from Primary Hyperoxaluria)

• Decrease enteric oxalate absorption

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• Binders

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• Removal/excretion

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• Metabolism

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Low oxalate diet

Adequate dietary Ca

High fluid intake

Citrate to alkalinize urine

Lanthanum

Hemodialysis

Oxalobacter formigenes

Oxalate decarboxylase

Magnesium

EFFLUENT EIGHT ROUND

Pick Your Champion for the Green House Region

Oxalate Offenders

vs

Tubular Toxins

Obesity in Kidney Transplant

Writers:

Alissa Ice

Trevor Stevens

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Experts:

Swee-Ling Levea

Babak Orandi

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Region Execs:

Jeffrey Kott

Obesity in Kidney Transplant Donors

• >90,000 individuals on the kidney transplant waiting list in the U.S.
• We need to find ways to expand donor pool!
• No standard BMI threshold for ability to donate
• About ⅔ of donors in the U.S. have a BMI > 30 kg/m²
• Obesity in kidney transplant donors increases the risk of development of ESRD 1.9 fold above non-obese donors
• Treatment of obesity should be multi-modal
• Past data shows potential donors rarely are able to lose the weight
• Donors frequently (re)gain weight post donation
• Therapies to promote health are essential both pre and post donation!

Obesity in Kidney Transplant Donors

Obesity in Kidney Transplant Recipients

• ~30% of patients are obese at the time of kidney transplant

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• Weight gain is common post kidney transplant

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• Obesity increases short and long term risks post kidney transplant
• Delayed graft function
• Poor wound healing
• Cardiovascular disease
• Posttransplant diabetes mellitus

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• Fear of movement and low self-efficacy are common in transplant recipients

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• There is limited data of pharmaceutical agents in this population
• Limited data of GLP-1s, DPP4 inhibitors, and metformin suggest safety in carefully selected patients

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• Bariatric surgery has been shown to be effective in kidney transplant recipients.
• Higher doses of tacrolimus needed due to decreased absorption

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• Even with increased risks of kidney transplant in obese patients, obese kidney transplant patients still perform better than obese ESKD patients who remain on the waiting list

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Post-Transplant Obesity

EFFLUENT EIGHT ROUND

Pick Your Champion for the Obesity in Kidney Transplant Region

Obesity in Recipients

vs

Obesity in Donors

Minimal Change Disease

Writers:

Mallory Downie

Robert Myette

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Expert:

Susan Samuel

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Region Execs:

Ana Catalina Alvarez-Elías

Matthew Sparks

Minimal Change Disease Diagnosis & Pathogenesis

Minimal Change Disease Pathophysiology

Minimal Change Disease (MCD) is a histopathological diagnosis characterized by foot effacement of the podocytes which are part of the glomerular filtration barrier. The clinical presentation in adult and pediatric population is massive proteinuria, hypoalbuminemia and edema (nephrotic syndrome)

Diagnosis through a kidney biopsy

Diagnosis through clinical response to corticosteroid therapy. Traditionally assumed in Steroid Sensitive Nephrotic Syndrome (SSNS)

A d u l t s

• T cell mediated
• Permeable circulating factor
• Genetics

Physiopathology remains UNKNOWN!

PREVIOUS THEORIES

• B cells mediated
• Anti-Nephrin antibodies
• Atypical B cells
• Genetics

Childhood nephrotic syndrome (NS)

according to steroid response (KDIGO Guidelines)

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• Steroid sensitive NS (SSNS): Complete remission after 4 weeks of treatment with recommended dose of steroids.
• Frequent relapsing NS (FRNS): More than 2 relapses within 6 months or more than 4 relapses within 12 months
• Steroid dependent NS (SDNS): Two relapses while in steroid therapy or within 14 days of discontinuing steroid therapy
• Steroid resistant NS (SRNS): Fail to achieve remission after 4 weeks of recommended steroid

treatment

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NEW THEORIES

C h I l d r e n

1-12 years

(could be older)

Minimal Change Disease Relapse

Minimal Change Disease Relapse

Initial treatment

Prednisone or prednisolone:

• 60 mg/m²/day or 2 mg/kg/day (maximum 60 mg/day) until the child remits completely for more than ≥3 days.
• After achieving complete remission, reduce dose to 40 mg/m² or 1.5 mg/kg (maximum 50 mg) on alternate days for ≥ 4 weeks. [KDIGO Guidelines]

Relapse treatment

Prednisone or prednisolone:

• 60 mg/m²/day or 2 mg/kg/day for 4-6 weeks (with a maximum dose of 60 mg/day) and
• 40 mg/m²/ every other day or 1.5 mg/kg/ every other day for 4-6 weeks, for a total duration of 8-12 weeks for initial treatment [KDIGO Guidelines]

Steroid-sparing drugs for childhood nephrotic syndrome

• Calcineurin Inhibitors:

Tacrolimus or cyclosporine

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• Antiproliferative:

Mycophenolate Mofetil or Mycophenolic

Acid

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• Alkylating agents:

Cyclophosphamide

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• Antiparasitic:

Levamisole (not available in USA or

Canada)

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• Anti-CD20:

Rituximab, Ofatumumab and Obinutuzumab

The steroid-sparing drug of use depends on center practices, patient’s preference, availability and cost. No strong evidence about a specific drug being more effective.

EFFLUENT EIGHT ROUND

Pick Your Champion for the Minimal Change Disease Region

MCD Relapse

vs

MCD Dx & Pathogenesis

From your Effluent 8,

pick your Filtered 4

From your Filtered 4,

pick your Left and Right Kidneys

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Crown your

NephMadness 2024

CHAMPION:

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• Submit brackets by March 31, 2025 on Tourneytopia

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• Claim CME and MOC credit through NKF PERC

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• Discuss on social media using #NephMadness

Thanks for playing and good luck!

Important Dates:

March 1, Saturday (7:00 am Eastern): Bracket entry opens

March 31, Monday (11:59 pm Eastern): Deadline for entering contest

April 2, Wednesday:  Effluent 8 results

April 4, Friday: Filtered 4 results

April 7, Monday: Left & Right Kidney results 

April 8, Tuesday: NephMadness Champion crowned