The Effects of Calcitriol on Biomarkers in Diabetic Kidney Disease Patients

Study Overview
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Brief Summary
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Diabetic Kidney Disease (DKD) is a complication that occurs due to poor glycemic control over a long period. The decrease or loss of podocytes is an important index in determining the degree of glomerular damage. Previous studies in patients with DKD reported that vitamin D administration can improve their renal function through several mechanisms. However, there is still little evidence available regarding the effects of calcitriol on biomarkers of DKD. This trial is a double-blind randomized controlled trial to assess the effect of calcitriol in DKD patients through several biomarkers which reflect pathomechanism in DKD. Those biomarkers include urinary podocin, urinary nephrin, urinary KIM-1, urinary IL-6, plasma renin, and albuminuria. The primary outcome is any improvement on podocyte markers, tubular markers, kidney inflammation parameters, plasma renin, and albuminuria between calcitriol and placebo groups. Secondary outcomes include the relation between each marker and the side effects of intervention therapy.

Detailed Description
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Diabetic Kidney Disease (DKD) is a complication that occurs due to poor glycemic control over a long period. The decrease or loss of podocytes is an important index in determining the degree of glomerular damage. Albuminuria and estimated glomerular filtration rate (eGFR) are currently used as the marker of DKD. However, these markers may not directly measure renal tissue injury. Thus, investigating novel biomarkers, particularly podocyte-associated biomarkers, is needed to predict DKD. Previous studies in patients with DKD reported that vitamin D administration can improve their renal function. of the various types of vitamin D, there is still little evidence available regarding the effects of calcitriol on biomarkers of DKD. Therefore, this study aimed to determine the effect of calcitriol on podocyte damage markers, tubular injury markers, kidney inflammation parameter, plasma renin, dan albuminuria in DKD patients. This study is a double-blind randomized controlled clinical trial to assess the effect of calcitriol in DKD patients through several markers including albuminuria. Podocyte damage is characterized by urinary podocin and urinary nephrin, tubular marker injury is characterized by urinary KIM-1, kidney inflammation is represented by urinary IL-6, hemodynamic is represented by plasma renin. The primary outcome is any improvement on those markers between calcitriol and placebo groups. And the secondary outcomes include the relation between each marker and the side effects of intervention therapy.

Official Title
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Effects of Calcitriol on Podocytes in Diabetic Kidney Disease Patients: Assessment of Urine Podocin, Urine Nephrin, Urine Interleukin-6, Urine KIM-1, Plasma Renin, and Albuminuria

Conditions
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Diabetic Kidney Disease

Intervention / Treatment
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* Drug: Calcitriol capsules
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Controlled type 2 diabetes mellitus with HbA1C at least <8% and albuminuria (UACR>30 mg/mmol) Estimated Glomerular Filtration Rate (eGFR) >45 ml/min/1.73 m2 Agree to participate in the research Exclusion Criteria: Uncontrolled hypertension with routine Angiotensin-converting-enzyme inhibitors (ACEi) or Angiotensin II receptor blockers (ARBs) treatment Hypercalcemia (total serum Ca level >10/5 mg/dL) Hyperphosphatemia (total serum phosphate level >5 mg/dL) Hypersensitivity to calcitriol Suffering from other diseases that cause proteinuria Acute diseases Smoker or previous smoking history Taking medications or suplements that can affect calcitriol metabolism (thiazide, digoxin, anti-convulsant)

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group<br>Drug: Calcitriol The intervention group will be given calcitriol at a dose of 0.25 mcg/day for six months in the form of capsules that have been marked and numbered. The drugs will be taken through the RSCM pharmacy once a month during visit and the allocation will be given using drug labels that are sealed and packaged identically. | Drug: Calcitriol capsules<br>* Calcitriol under the name of Oscal, 0.25 mcg/day (minimum dose) will be given for 6 months, starting at the day of the time when inclusion criteria have been met.<br>* Other names: Oscal;|
| Active Comparator: Placebo Group<br>Drug: Placebo oral The placebo drug will be given for six months in the form of capsules that have been marked and numbered. The drugs will be taken through the RSCM pharmacy once a month during visit and the allocation will be given using drug labels that are sealed and packaged identically. | Drug: Placebo<br>* One placebo capsule matching the active drug will be given per day for 6 months, starting at the day of the time when inclusion criteria have been met<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary podocin | Marker of podocyte injury, will be measured before, during, and after treatment | 6 months | 
| Urinary nephrin | Marker of podocyte injury, will be measured before, during, and after treatment | 6 months | 
| Urinary KIM-1 | Marker of tubular injury, will be measured before, during, and after treatment | 6 months | 
| Urinary IL-6 | Marker of kidney inflammation, will be measured before, during, and after treatment | 6 months | 
| Plasma renin | Marker of hemodynamic pathway, will be measured before, during, and after treatment | 6 months | 
| Albuminuria | Marker of glomerular damage, will be measured before, during, and after treatment | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calcium level | Will be measured monthly | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Kidney Disease, Podocin, Nephrin, Calcitriol, Tubular injury, Podocyte injury