Decline in Renal Concentration Ability in Lithium Treated Patients

Study Overview
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Brief Summary
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Lithium therapy is cornerstone in therapy of bipolar disorders. A well known side-effect of lithium therapy is a urinary concentration defect which manifests in it's most severe form as nephrogenic diabetes insipidus. The development of urinary concentration defects and its progression to nephrogenic diabetes insipidus in the population of lithium treated patients is unknown and therefore this study aims to evaluate the decline of urinary concentration defects in a Dutch population of lithium treated patients. In this prospective cohort study, 51 participants treated with lithium at Canisius Wilhelmina Hospital, Nijmegen and included in the previous study in 2012 will be approached to undergo a follow-up dDAVP-test.

Official Title
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Decline in Renal Concentration Ability in Lithium Treated Patients

Conditions
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Lithium Toxicities, Bipolar Disorder, Concentration Ability Impaired, Nephrogenic Diabetes Insipidus, Lithium - Induced Nephropathy

Intervention / Treatment
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* Diagnostic Test: Deamino Arginine Vasopressin (dDAVP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: included in the previous study men and women age ≥ 18 years Exclusion Criteria: General contra-indications for participation in a trial: inability to give informed consent pregnancy unstable psychiatric condition Alternative causes of (nephrogenic) diabetes insipidus: hypokalemia (plasma potassium < 3.0 mmol/l) severe hypercalcemia (albumin-corrected plasma calcium > 2.80 mmol/l) hyperglycemia (plasma glucose > 10.0 mmol/l) history of amyloidosis, Sjögren's syndrome or Sickle cell anemia previous treatment with ifosfamide established primary polydipsia or central diabetes insipidus Contra-indications for dDAVP administration: inability to comply with water restriction renal insufficiency (GFR < 45 ml/min/1.73 m2) hyponatremia (plasma sodium < 130 mmol/l) instable angina pectoris decompensated cardial insufficiency Other: concomitant treatment with desmopressin or democlocycline

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 2012-cohort<br> | Diagnostic Test: Deamino Arginine Vasopressin (dDAVP)<br>* After voiding, 40 μg 1-desamino-8-D arginine vasopressin (dDAVP) will be administered intranasally. Throughout the day, urine volume and maximal renal concentrating ability will be determined by measuring osmolality in urine collected at 4 and 6 hours after administration of dDAVP. In addition, water intake, body weight, blood pressure and heart rate will be determined at baseline and 6 hours after administration of dDAVP.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decline renal concentration ability | To explore the decline in renal concentration ability (RCA) in a Dutch population of lithium treated patient. The primary endpoint is the percentual change in maximal urine osmolality. | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relation between changes in kidney function and renal concentration ability | To determine the correlation between changes in kidney function and renal concentration ability | 10 years | 
| Relation between history of lithium-use and renal concentration ability | To determine the relationship between renal concentration ability and clinical parameters (duration of lithium therapy, plasma lithium concentration, baseline plasma creatinine, sodium and potassium concentration and baseline urinary osmolality) of lithium treated patients. | 10 years | 
| Chronic kidney disease | To determine the number of patients with chronic kidney disease at follow-up. | 10 years | 
| Decline in kidney-function | To explore the decline in kidneyfunction (expressed as eGFR, estimated by the CKD-EPI equation). | 10 years |