Ignite Creation Date:
2024-05-06 @ 3:34 PM
Last Modification Date:
2024-10-26 @ 1:52 PM
Study NCT ID:
NCT04674397
Status:
COMPLETED
Last Update Posted:
2021-12-07
First Post:
2020-03-16
Brief Title:
BOne Dysfunction in Donor NEphrectomieS
Sponsor:
Manchester University NHS Foundation Trust
Organization:
Manchester University NHS Foundation Trust
Study Overview
Official Title:
Effect of Donor Nephrectomy on Markers of Bone Function in Living Kidney Donors
Status:
COMPLETED
Status Verified Date:
2021-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BONES
Brief Summary:
Most dialysis patients die from vascular disease which is statistically associated with changes related to chronic kidney disease associated mineral bone disorder CKD-MBD3-9 Understanding the mechanisms behind this high death rate is crucial to improving the length and quality of life for patients with all grades of kidney disease including those on dialysis This is a priority for patients and clinicians alike
Most humans with early CKD are asymptomatic and unaware that they have a problem with their kidneys Therefore they are unlikely to consult a doctor and early CKD is often unrecognised Patients who are aware of early CKD often have other co-morbidities including diabetes hypertension and vascular disease which in the setting of a clinical study complicate the identification of changes solely resulting from CKD However over the past decade living kidney donation has become increasingly common and is now the source of organs for more than 120 patients annually at Manchesters renal transplant centre Prospective donors are carefully examined and known to have normal kidney function without other co-morbidities They then undergo a planned unilateral nephrectomy and lose approximately 50 of their kidney mass creating an immediate state of moderate CKD Over subsequent months the remaining kidney will hypertrophy and partially correct this although the mechanisms are unknown In the immediate post-operative period donors are inpatients on the kidney transplant ward and have regular blood and urine tests meaning that careful study of metabolic processes during their recovery is relatively easy by analysis of serial plasma and urine samples Sequential changes in the plasma and urine levels of different bone turnover markers and metabolites can be analysed and will provide valuable new information to increase our understanding of the initial stage of CKD-MBD development
Most humans with early CKD are asymptomatic and unaware that they have a problem with their kidneys Therefore they are unlikely to consult a doctor and early CKD is often unrecognised Patients who are aware of early CKD often have other co-morbidities including diabetes hypertension and vascular disease which in the setting of a clinical study complicate the identification of changes solely resulting from CKD However over the past decade living kidney donation has become increasingly common and is now the source of organs for more than 120 patients annually at Manchesters renal transplant centre Prospective donors are carefully examined and known to have normal kidney function without other co-morbidities They then undergo a planned unilateral nephrectomy and lose approximately 50 of their kidney mass creating an immediate state of moderate CKD Over subsequent months the remaining kidney will hypertrophy and partially correct this although the mechanisms are unknown In the immediate post-operative period donors are inpatients on the kidney transplant ward and have regular blood and urine tests meaning that careful study of metabolic processes during their recovery is relatively easy by analysis of serial plasma and urine samples Sequential changes in the plasma and urine levels of different bone turnover markers and metabolites can be analysed and will provide valuable new information to increase our understanding of the initial stage of CKD-MBD development
Detailed Description:
The likelihood of five year survival for a 60 year old dialysis patient 50 is significantly worse than for breast 88 prostate 90 or colon cancer sufferers 561 but robust information about the contributory risk-factors to inform clinician-patient discussions is lacking2 Most dialysis patients die from vascular disease which is statistically associated with changes related to chronic kidney disease associated mineral bone disorder CKD-MBD3-9 Understanding the mechanisms behind this high death rate is crucial to improving the length and quality of life for patients with all grades of kidney disease including those on dialysis This is a priority for patients and clinicians alike
A recent Kidney Disease Improving Global Outcomes KDIGO statement highlighted the poor level of understanding of the mechanisms of CKD-MBD in early and late kidney disease which inhibits the development of targeted therapies to either halt the process or at least improve outcomes10-12
CKD confers certain atypical risk factors for mortality most notably a state of disordered mineral metabolism which is implicated in the development of hyperphosphataemia hyperparathyroidism and vascular calcification Despite the variety of biological malfunctions attributed to CKD-MBD the pathophysiology is not understood partly because there is no animal model of progressive CKD Rodent models do not survive long enough for the all changes of CKD-MBD to develop Therefore current therapy is inadequate and usually deployed late in the course of CKD when the patient has progressed to end-stage renal disease Furthermore there is no reliable evidence that current therapies improve patient outcome in terms of length or quality of life The progression of CKD is not always linear and less than 5 of patients proceed to end-stage renal disease While aetiology of renal impairment determines progression to some extent there is no reliable means of determining who will progress and who will not so that targeted study of early CKD-MBD pathogenesis is not possible
Most humans with early CKD are asymptomatic and unaware that they have a problem with their kidneys Therefore they are unlikely to consult a doctor and early CKD is often unrecognised Patients who are aware of early CKD often have other co-morbidities including diabetes hypertension and vascular disease which in the setting of a clinical study complicate the identification of changes solely resulting from CKD However over the past decade living kidney donation has become increasingly common and is now the source of organs for more than 120 patients annually at Manchesters renal transplant centre Prospective donors are carefully examined and known to have normal kidney function without other co-morbidities They then undergo a planned unilateral nephrectomy and lose approximately 50 of their kidney mass creating an immediate state of moderate CKD Over subsequent months the remaining kidney will hypertrophy and partially correct this although the mechanisms are unknown In the immediate post-operative period donors are inpatients on the kidney transplant ward and have regular blood and urine tests meaning that careful study of metabolic processes during their recovery is relatively easy by analysis of serial plasma and urine samples Sequential changes in the plasma and urine levels of different bone turnover markers and metabolites can be analysed and will provide valuable new information to increase our understanding of the initial stage of CKD-MBD development
A recent Kidney Disease Improving Global Outcomes KDIGO statement highlighted the poor level of understanding of the mechanisms of CKD-MBD in early and late kidney disease which inhibits the development of targeted therapies to either halt the process or at least improve outcomes10-12
CKD confers certain atypical risk factors for mortality most notably a state of disordered mineral metabolism which is implicated in the development of hyperphosphataemia hyperparathyroidism and vascular calcification Despite the variety of biological malfunctions attributed to CKD-MBD the pathophysiology is not understood partly because there is no animal model of progressive CKD Rodent models do not survive long enough for the all changes of CKD-MBD to develop Therefore current therapy is inadequate and usually deployed late in the course of CKD when the patient has progressed to end-stage renal disease Furthermore there is no reliable evidence that current therapies improve patient outcome in terms of length or quality of life The progression of CKD is not always linear and less than 5 of patients proceed to end-stage renal disease While aetiology of renal impairment determines progression to some extent there is no reliable means of determining who will progress and who will not so that targeted study of early CKD-MBD pathogenesis is not possible
Most humans with early CKD are asymptomatic and unaware that they have a problem with their kidneys Therefore they are unlikely to consult a doctor and early CKD is often unrecognised Patients who are aware of early CKD often have other co-morbidities including diabetes hypertension and vascular disease which in the setting of a clinical study complicate the identification of changes solely resulting from CKD However over the past decade living kidney donation has become increasingly common and is now the source of organs for more than 120 patients annually at Manchesters renal transplant centre Prospective donors are carefully examined and known to have normal kidney function without other co-morbidities They then undergo a planned unilateral nephrectomy and lose approximately 50 of their kidney mass creating an immediate state of moderate CKD Over subsequent months the remaining kidney will hypertrophy and partially correct this although the mechanisms are unknown In the immediate post-operative period donors are inpatients on the kidney transplant ward and have regular blood and urine tests meaning that careful study of metabolic processes during their recovery is relatively easy by analysis of serial plasma and urine samples Sequential changes in the plasma and urine levels of different bone turnover markers and metabolites can be analysed and will provide valuable new information to increase our understanding of the initial stage of CKD-MBD development
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None