The Practicality and Utility of Measured vs Estimated GFR in adCKD

The eligible study population includes all adults under the care of nephrology at Manchester Foundation Trust with advanced chronic kidney disease approaching end stage renal failure and those established on haemodialysis who still produce urine. This pilot study aims to collect 50 measurements in each of three groups of participants (total 150): (1) those with advanced kidney disease not yet on dialysis; (2) those undergoing peritoneal dialysis and (3) those undergoing haemodialysis who still have residual kidney function. Those who have not yet started dialysis will have repeat measurements when they become symptomatic with renal failure and a third time after they are established on dialysis (either peritoneal or haemo-) to assess for a threshold of renal function at which individuals need to start dialysis, and consistency of the measurements whether undergoing dialysis or not. This will mean a maximum of 150 participants would be required.

Screening and recruitment will take place in advanced kidney care clinics, peritoneal dialysis clinics and dialysis units managed by Manchester University NHS Foundation Trust. Potential participants will be given information about the study by their usual care provided and, if agreeable, contacted later by the research team for further discussion and formal recruitment to the study.

Study methods:

======== Participants will have up to three sets of tests taken as part of the study depending at what stage they are recruited.

Each set of tests is done over one planned visit to hospital, except for those on haemodialysis where samples are taken from two consecutive visits. All study visits coincide with routine care with no study specific hospital visits.

For those not yet started on dialysis, at the participant's next kidney clinic they will have a brief assessment by the research team and confirmation of their medical background. They will be given a demonstration and provided with information about how to perform finger prick tests at home. Instead of having their usual bloods taken for clinic, a small cannula will be inserted and bloods for the study will be taken at the same time as any bloods requested by their doctor. 5ml of iohexol will be injected and the cannula removed. This should take approximately 15 minutes in total. They will be asked to stay on site for 30 minutes for observation. Urine samples collection is required for analysis although this is part of routine care. Participants will be provided with equipment and asked to take 4 finger prick blood samples at home over the next 24 hours. These should be as close as possible to 3, 6, 10 and 24 hours after the injection but will be flexible to fit around lifestyle and planned times for samples agreed with the participant. The research team will contact them within an hour before the first and last sample as a reminder. These samples can be posted back in a prepaid and addressed envelope at the participant's convenience.

Participants will also be given a brief questionnaire to complete about the experience and return along with the finger prick samples.

Participants will be followed up remotely at each subsequent clinic visit. Once their medical team identifies them as needing to start dialysis, participants will be approached again by the research team (either at the same or their subsequent clinic visit). The same process will be applied for brief clinical assessment, blood \& urine sampling, injection of iohexol, finger prick technique demonstration and finger prick sampling. Participants will not be given a second questionnaire. Participants may be waiting to start dialysis at the time of recruitment to the study - in this circumstance they will not have this second set of study tests prior to starting dialysis.

Participants will continue to be followed up remotely and once established on dialysis for at least a week will be approached for a third time by the research team at one of their dialysis visits.

In those who are undergoing peritoneal dialysis, the next study visit will coincide with their next clinic where 24-hour urine collection is planned (done as routine care). The process for assessment and sample collection will be be the same as in the predialysis setting. The results from the 24 hour urine collection are of interest to the study but are not study specific. Participants already on peritoneal dialysis can be directly recruited at this stage. Participants will be given a questionnaire only if they have not already completed one. Participants will have completed their time in the study after this.

In those established on haemodialsyis, the next study visit will coincide with the next dialysis visit where interdialytic urinary collection is planned (done as routine care). Participants will undergo a brief clinical assessment given a demonstration of finger prick sampling and asked to provide a urine sample as in the predialsyis setting. Blood samples for study purposes will be taken at the start of their dialysis session from their usual dialysis access at the same time as routine bloods. Additional blood samples will be taken at the end of dialysis as part of routine care. 5ml iohexol will be injected via their usual dialysis access after the dialysis session is completed but before they are disconnected. They will then be disconnected as per usual care but asked to remain on site for 30 minutes. As above, participants will be asked to collect 4 finger prick blood samples over the following 24 hours. These samples will be brought back to their next dialysis session. Further blood samples will be taken at the start and end of the subsequent dialysis session from their usual dialysis access at the same time as routine bloods. Participants already on haemodialsyis can be recruited to the study directly at this stage. Participants will be given a questionnaire only if they have not already completed one. Participants will have completed their time in the study after this.

Rationale for methodology:

The study design has been chosen in this way to minimise impact on the participant. Study visits will coincide with planned hospital visits to minimise any additional time and travel burden. Blood tests specific for the study will all be done simultaneously with routine blood sampling. No additional venepuncture is therefore required. For those on dialsyis, study visits will coincide specifically with visits where urine collection is planned as routine. This will avoid the need for additional samples and associated burden to participants.

The design is also chosen to coincide with routine hospital visits in this way to emulate how the test might be done in routine clinical care.

Convenience sampling for participant recruitment will be used. In the predialysis and peritoneal dialysis cohort, recruitment through clinic only will allow all interactions and blood sampling to coincide with planned hospital visits. In the dialysis cohort, recruitment will be clustered by dialysis unit initially recruiting from those units that send their routine blood samples to Manchester Royal Infirmary's laboratories, then according to unit size. By doing this participants can be tested simultaneously and sample handling costs minimised. The specific dialysis unit that a patient attends is based on geographical proximity to their home. The investigators expect very little clinical variation between different units and would not expect this methodology to impact results.

• Patient acceptability of performing measured GFR as assessed by participant questionnaire [Срок оценки: 24 hours. The questionnaire should take no more than 5 minutes but requires completion of the participant's first 24 hour mGFR testing to be done.]
• Number of iohexol finger prick samples correctly returned [Срок оценки: Assessed at each study visit through study completion, up to 6 months.]
• Single sample iohexol measured GFR [Срок оценки: Assessed at each study visit through study completion, up to 6 months.]
• eGFR calculated by novel markers [Срок оценки: Assessed at each study visit through study completion, up to 6 months.]
• Presence of uraemic syndrome [Срок оценки: Assessed at each study visit through study completion, up to 6 months.]
• Concentrations of markers of renal tubular function [Срок оценки: Assessed at each study visit through study completion, up to 6 months.]