Peritoneal Ultrafiltration for Chronic Kidney Failure

(IPUF-HD Trial)

Overseen By Patricia Jarosz, MMASc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Disqualifiers: Uncontrolled diabetes, Active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 3 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

Sodium accumulates in the tissues of patients with kidney disease and impairs survival. Three-times weekly, standard hemodialysis alone cannot remove excess sodium efficiently. A sample of 10 chronic hemodialysis patients will undergo a 5-week, pilot, interventional study to test the efficacy of additional sodium removal in-between hemodialysis sessions, twice per week, for three weeks. Tissue sodium removal will be achieved with peritoneal dialysis after the surgical insertion of a peritoneal dialysis catheter. Tissue sodium removal will be assessed at the beginning and at the end of the study with sodium magnetic resonance imaging of a peripheral limb (leg). Patients will also undergo monitoring for symptoms and blood pressure throughout the study to assess the safety of this procedure.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Interdialytic Peritoneal UltraFiltration for chronic kidney failure?

Research shows that peritoneal dialysis, a similar treatment, can effectively manage fluid overload in patients with treatment-resistant congestive heart failure, improving their quality of life and reducing hospitalizations. This suggests that Interdialytic Peritoneal UltraFiltration might also help manage fluid balance in chronic kidney failure. ^{1 2 3 4 5}

Is peritoneal ultrafiltration safe for humans?

The research indicates that ultrafiltration failure is a significant complication in peritoneal dialysis, which can lead to serious issues like increased mortality and the need to switch to other treatments. However, these studies focus on complications rather than direct safety concerns, so it's important to consult with a healthcare provider for personalized advice. ^{2 6 7 8 9}

How is peritoneal ultrafiltration different from other treatments for chronic kidney failure?

Peritoneal ultrafiltration is unique because it uses the peritoneum (a membrane in the abdomen) to remove excess fluid and waste from the body through osmosis and diffusion, unlike hemodialysis which filters blood outside the body. This method can be used at home and is less invasive than a kidney transplant. ^{2 5 6 10 11}

Research Team

Christopher W. McIntyre, MD, PhD

Principal Investigator

Lawson Research Institute

Eligibility Criteria

This trial is for adults over 18 who are on hemodialysis up to three times a week for chronic kidney failure but can't reach their prescribed dry weight. They should gain at least 4% of their dry weight between sessions and be able to consent. It's not for those with conditions that rule out peritoneal dialysis or MRI, uncontrolled diabetes, active infections, non-compliance with hemodialysis, or very low sodium levels.

Inclusion Criteria

I can't reach my target weight with my current treatment.

I undergo hemodialysis up to three times a week.

I need more dialysis sessions to reach my target weight.

Exclusion Criteria

I cannot undergo peritoneal dialysis due to health reasons.

I cannot have an MRI due to certain health reasons.

My diabetes is not well-controlled.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Assessment of residual renal function, volume, hemodynamic and cardiac status during HD

1 week

Treatment

Participants receive interdialytic peritoneal ultrafiltration with a 10% dextrose solution, twice a week for three consecutive weeks

3 weeks

2 visits per week (in-center)

Wash-out

Monitoring of potential residual effects of the iPUF intervention

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Interdialytic Peritoneal UltraFiltration

Trial Overview The study tests if extra peritoneal dialysis using a dextrose solution can better remove excess sodium from tissues in-between regular hemodialysis sessions. Ten patients will have this additional treatment twice weekly for three weeks and undergo leg MRIs to measure tissue sodium before and after the study.

Participant Groups

Group I: Interdialytic peritoneal ultrafiltration Experimental Treatment 1 Intervention

Will receive incremental interdialytic peritoneal ultrafiltration with a 10% dextrose solution, twice a week for three consecutive weeks

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Sequana Medical N.V.

Industry Sponsor

Trials

16

Recruited

820+

Findings from Research

Extracorporeal ultrafiltration (UF) is effective for short-term management of patients with congestive heart failure (CHF) who have severe fluid overload, leading to significant improvements in symptoms and quality of life.

Peritoneal dialysis (PD) may be more suitable for long-term treatment of CHF, but further research is needed to determine if these therapies can improve survival rates in patients with refractory CHF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of peritoneal dialysis in the management of treatment-resistant congestive heart failure: A European perspective. Khalifeh, N., Vychytil, A., Hörl, WH.[2019]

In a study of nine peritoneal dialysis patients with poor ultrafiltration, using two icodextrin exchanges per day led to an average body weight reduction of 2.9 kg in six patients, indicating potential efficacy in managing fluid retention.

The treatment appeared safe, with stable HbA1c levels in diabetic patients and a slight decrease in serum sodium, suggesting that further long-term studies are needed to evaluate the overall impact and safety of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two icodextrin exchanges per day in peritoneal dialysis patients with ultrafiltration failure: one center's experience and review of the literature. Dousdampanis, P., Trigka, K., Chu, M., et al.[2021]

A study of 1,203 patients undergoing peritoneal dialysis (PD) from 1990 to 2019 showed significant improvements in patient survival rates, with 5-year survival increasing from 64% in the 1990-1999 cohort to 93% in the 2010-2019 cohort.

The rate of peritonitis, a common complication in PD, decreased significantly over time, from 0.278 episodes per patient-year to 0.162, indicating enhanced treatment protocols and care quality in the PD center.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving outcomes of peritoneal dialysis: secular trends at a single large center over three decades. Kang, M., Kim, YL., Kang, E., et al.[2021]

In a study of five infants with acute kidney injury, continuous flow peritoneal dialysis (CFPD) significantly improved ultrafiltration rates compared to conventional peritoneal dialysis, achieving a median ultrafiltration rate of 6.7 mg/kg/h versus 1.7 mg/kg/h (p=0.042).

CFPD also enhanced clearance rates for urea and creatinine, with clearances of 19 mL/min/1.73 m² and 41 mL/min/1.73 m² respectively, compared to 6.89 mL/min/1.73 m² and 7.46 mL/min/1.73 m² with conventional PD (both p=0.043).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous flow peritoneal dialysis (CFPD) improves ultrafiltration in children with acute kidney injury on conventional PD using a 4.25 % dextrose solution. Nourse, P., Sinclair, G., Gajjar, P., et al.[2018]

Ultrafiltration failure is a growing concern in patients on peritoneal dialysis, leading to increased cardiovascular risks and often resulting in the discontinuation of this treatment method.

This review highlights various strategies for preventing and treating ultrafiltration failure, emphasizing the importance of ongoing research to improve clinical outcomes for the increasing number of patients requiring renal replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective measures against ultrafiltration failure in peritoneal dialysis patients. Aguirre, AR., Abensur, H.[2022]

Ultrafiltration failure in peritoneal dialysis, defined as not achieving at least 400 ml of net ultrafiltration during a 4-hour dwell with 4.25% dextrose, is a major reason for patients needing to switch to hemodialysis.

Understanding the four main causes of ultrafiltration failure—high peritoneal transport state, low osmotic conductance to glucose, low effective peritoneal surface area, and high total peritoneal fluid loss—can help in diagnosing and managing this condition effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrafiltration failure in peritoneal dialysis: a pathophysiologic approach. Teitelbaum, I.[2022]

In a study of 90 long-term peritoneal dialysis patients, 19 experienced ultrafiltration failure (UFF), with 8 showing early UFF linked to a higher prevalence of diabetes and a rapid decline in residual renal function during the third year.

Patients with early UFF required significantly higher concentrations of dialysate glucose to maintain adequate ultrafiltration, suggesting that glucose levels on both sides of the peritoneal membrane may contribute to UFF, although the exact mechanisms remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors responsible for ultrafiltration failure in early stages of peritoneal dialysis. Selgas, R., Bajo, MA., Castro, MJ., et al.[2020]

In patients undergoing continuous ambulatory peritoneal dialysis (CAPD), the accumulation of advanced glycation end products (AGEs) in the peritoneum is linked to severe interstitial fibrosis and microvascular sclerosis, which can lead to ultra-filtration failure.

The study found that the extent of AGE accumulation correlates with the progression of fibrosis and sclerosis, indicating that targeting AGEs may be a potential strategy to improve peritoneal ultra-filtration capacity in CAPD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accumulation of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration. Honda, K., Nitta, K., Horita, S., et al.[2019]

In a study of 177 patients on automated peritoneal dialysis, those with daily ultrafiltration (UF) below 750 mL at baseline had increased mortality over 2 years, indicating that poor UF is a significant risk factor for survival.

The study found no clear differences in comorbidities or nutritional status between patients with low and adequate UF, suggesting that the link between poor UF and increased mortality may be due to factors like membrane function rather than just health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the link between poor ultrafiltration and increased mortality in anuric patients on automated peritoneal dialysis? Analysis of data from EAPOS. Davies, SJ., Brown, EA., Reigel, W., et al.[2020]

In a study comparing uraemic rats to healthy controls over 6 weeks of peritoneal dialysis (PD) fluid exposure, uraemic rats showed significant increases in serum urea and creatinine levels, indicating renal failure, along with changes in peritoneal tissue such as new blood vessel formation and elevated angiogenic factors.

While both uraemia and PD fluid exposure caused harmful changes to the peritoneum, the study found that uraemia did not significantly worsen the effects of PD fluid, suggesting that the damage from PD fluid is substantial on its own.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunopathological changes in a uraemic rat model for peritoneal dialysis. Zareie, M., De Vriese, AS., Hekking, LH., et al.[2017]

Peritoneal dialysis is an effective treatment for end-stage chronic kidney failure, utilizing the peritoneum's vascularization to remove waste from the body, but it can lead to complications such as catheter dysfunction and infections.

Early recognition and management of complications are crucial for patient safety, as they can significantly impact treatment success and may necessitate a switch to haemodialysis if not addressed promptly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Complications after placement of peritoneal catheter]. Mirković, TD., Popov, M., Korica, M., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

The role of peritoneal dialysis in the management of treatment-resistant congestive heart failure: A European perspective. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Two icodextrin exchanges per day in peritoneal dialysis patients with ultrafiltration failure: one center's experience and review of the literature. [2021]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Evolving outcomes of peritoneal dialysis: secular trends at a single large center over three decades. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Continuous flow peritoneal dialysis (CFPD) improves ultrafiltration in children with acute kidney injury on conventional PD using a 4.25 % dextrose solution. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Protective measures against ultrafiltration failure in peritoneal dialysis patients. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Ultrafiltration failure in peritoneal dialysis: a pathophysiologic approach. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Risk factors responsible for ultrafiltration failure in early stages of peritoneal dialysis. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Accumulation of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

What is the link between poor ultrafiltration and increased mortality in anuric patients on automated peritoneal dialysis? Analysis of data from EAPOS. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Immunopathological changes in a uraemic rat model for peritoneal dialysis. [2017]

11. Serbia pubmed.ncbi.nlm.nih.gov

[Complications after placement of peritoneal catheter]. [2019]