Dynamic Measurement of Renal Functional Reserve as a Predictor of Long-Term Renal Function

Study Overview
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Brief Summary
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The number of people with kidney disease is constantly rising and renal failure represents one of the major health care burdens globally. An accurate measurement of kidney function is urgently needed to better understand and treat loss of renal function. Kidneys have an intrinsic reserve capacity to respond to a higher work load by increasing filtration in their nephrons. The number of nephrons and their reserve capacity define how well kidneys can adapt to an increased demand and disease. The degree of renal reserve capacity becomes particularly important when the number of functioning nephrons is significantly reduced either due to surgical removal of one kidney as in living kidney donation or in tumor nephrectomy or due to progressive injury as in autosomal dominant polycystic kidney disease (ADPKD). A reduced functional reserve likely reflects an impaired adaptive capacity and increased risk of accelerated loss of function in the remaining single kidney or in kidneys exposed to a disease. Despite the importance of accurately measuring baseline and reserve capacity renal function, due to the time- and laborintensive procedure, in clinical routine this testing is rarely done. Investigators aim to measure renal functional reserve (RFR) and loss of function in patients undergoing nephrectomy (living kidney donors and renal tumor patients) as well as in patients with ADPKD. The results should provide evidence whether renal functional reserve indeed predicts adaptive capacity and functional loss after removal of a healthy kidney (living donors), of a tumor kidney (cancer patients) or in progressive kidney disorders (ADPKD patients). Investigators are confident that the proposed project will enhance the understanding of progressive kidney disease and with this improve donor safety, planning of tumor nephrectomy, and prediction of renal functional loss as well as provide a strong argument that dynamic renal function testing, i.e. accurate measurement of baseline and reserve capacity, is necessary in certain disease entities.

Detailed Description
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The measurement of RFR will be performed by dynamic testing of the changes in baseline glomerular filtration rate (GFR) induced by an oral protein load. Sinistrin (a polyfructosan with identical clearance characteristics to inulin) will be used to measure GFR.

Official Title
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Dynamic Measurement of Renal Functional Reserve as a Predictor of Long-Term Renal Function

Conditions
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Adult Polycystic Kidney Disease, Kidney Neoplasms, Kidney Dysfunction

Intervention / Treatment
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* Diagnostic Test: sinistrin clearance dynamic measurement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Potential living kidney donor Patients with diagnosed ADPKD Patients with primary kidney tumor requiring nephrectomy Female and male patients over 18 years of age Exclusion Criteria: Bilateral kidney tumor Kidney metastases of a tumor of other origin Renal failure that requires dialysis Pregnant patient Incomplete medical records Patients with diabetes mellitus Patients who cannot tolerate iv fluids Hypersensitivity to the active substance (sinistrin) or to any of the excipients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Living donors<br>sinistrin clearance dynamic measurement | Diagnostic Test: sinistrin clearance dynamic measurement<br>* sinistrin clearance measurements will be performed before and 90 min after oral protein load<br>|
| Active Comparator: ADPKD patients<br>sinistrin clearance dynamic measurement | Diagnostic Test: sinistrin clearance dynamic measurement<br>* sinistrin clearance measurements will be performed before and 90 min after oral protein load<br>|
| Active Comparator: Patients with primary renal tumor<br>sinistrin clearance dynamic measurement | Diagnostic Test: sinistrin clearance dynamic measurement<br>* sinistrin clearance measurements will be performed before and 90 min after oral protein load<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RFR predicts renal functional decline | Sinistrin levels in plasma before and after oral protein load. Participants with impaired RFR are expected to have higher sinitrin levels in plasma. | up to 8 months |