Active clinical trials for "Diabetes Insipidus, Nephrogenic"

Lithium (Li) is the leading treatment for BD, protecting against both maniac and depressive relapse, and reducing the risk of suicide and mortality. However, despite this major clinical efficacy, the use of lithium is limited by its narrow therapeutic index and by its side effects. Li induces a vasopressin-resistant urinary concentration defect, with resulting nephrogenic diabetes insipidus (NDI) in 12-50 % of patients. This feature is more frequent after 5 years of treatment with lithium. Polyuria and subsequent thirst might affect patients' quality of life, but also cause potentially life-threatening hypernatremia if free access to water is impaired. Thus, we aim at evaluating the efficacy of amiloride on urine concentrating ability in patients with nephrogenic diabetes insipidus due to chronic lithium treatment.

The purpose of this research is to study the effectiveness and safety of the medication PB in slowing the frequent urination related to tolvaptan as long-term treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD), or frequent urination related to inherited nephrogenic diabetes insipidus as an inherited condition or as an acquired condition from prior treatment with lithium.

Newborn screening (NBS) is a global initiative of systematic testing at birth to identify babies with pre-defined severe but treatable conditions. With a simple blood test, rare genetic conditions can be easily detected, and the early start of transformative treatment will help avoid severe disabilities and increase the quality of life. Baby Detect Project is an innovative NBS program using a panel of target sequencing that aims to identify 126 treatable severe early onset genetic diseases at birth caused by 361 genes. The list of diseases has been established in close collaboration with the Paediatricians of the University Hospital in Liege. The investigators use dedicated dried blood spots collected between the first day and 28 days of life of babies, after a consent sign by parents.

The goal of this National Registry is to is to collect information from patients with rare kidney diseases, so that it that can be used for research. The purpose of this research is to: Develop Clinical Guidelines for specific rare kidney diseases. These are written recommendations on how to diagnose and treat a medical condition. Audit treatments and outcomes. An audit makes checks to see if what should be done is being done and asks if it could be done better. Further the development of future treatments. Participants will be invited to participate on clinical trials and other studies. The registry has the capacity to feedback relevant information to patients and in conjunction with Patient Knows Best (Home - Patients Know Best), allows patients to provide information themselves, including their own reported quality of life and outcome measures.

The purpose of this study is to determine whether metformin can increase urine concentration (osmolality) and decrease the amount of urine in patients with congenital nephrogenic diabetes insipidus (NDI).

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.

The purpose of this research study is to determine if two investigational medications will be more effective in decreasing urine output than the currently available and routinely used medications in patients with congenital nephrogenic diabetes insipidus (NDI).

Lithium remains the gold-standard treatment for bipolar disorder, with 30-40% of patients with responding preferentially to this medication. Additionally, lithium is commonly used in treatment-resistant depression, and other psychiatric disorders (e.g. schizoaffective disorder). Lithium is especially valuable considering the great difficulty in achieving and maintaining symptomatic remission, the high rates of disability, as well as tremendous personal, family, and societal costs associated with bipolar disorder and treatment-resistant depression. Despite this, clinicians are increasingly avoiding lithium, largely due to fear of irreversible chronic kidney disease (CKD), particularly in North America. It is well known that lithium exposure, even when dosed safely (<1.0mmol/L in adults 11 and <0.8mmol/L in geriatric patients 12,13), can increase the risk of CKD by 3 times, in large part through Nephrogenic Diabetes Insipidus (NDI) 14-19. NDI itself has also been associated with acute kidney injury 20, and life-threatening hypernatremia, which is an electrolyte imbalance characterized by high levels of blood sodium. Aside from hypertension, diabetes mellitus, aging, and other nonspecific CKD risk factors. NDI is characterized by excessive thirst (polydipsia) due to increased production of dilute urine (polyuria). In NDI, lithium is believed to interact with the inositol monophosphate and protein kinase C pathways, thereby affecting calcium-related intracellular signaling, cyclic AMP (cAMP), inhibition of Glycogen Synthase Kinase-3 Beta (GSK3Beta), activation of MAP Kinase and many other pathways. NDI occurs commonly in lithium users: 50% of chronic lithium users have urinary concentrating difficulties, with 12-19% have decreased urine osmolality (UOsm) <300mOsm/Kg). To date, amiloride (5-20mg/day) is the only medication with prior evidence of therapeutic effectiveness in NDI from randomized clinical trials. However as a potassium-sparing diuretic 31, amiloride can lead to lithium-level elevations, and can thereby theoretically increase the risk of lithium-associated CNS and acute renal toxicity. There is a need for novel, well-tolerated agents for the treatment of lithium-induced NDI. We recently demonstrated that statins, which are well-tolerated and commonly used medications, are associated with low lithium-induced NDI risk in the first and only previous cross-sectional study examining statins and NDI in humans (n=71) 33. In this study we examined current lithium users aged 20-95, who had a mean lithium duration and serum lithium level of 10.6 years and 0.62mmol/L, respectively. Patients were assessed for UOsm following 10-hour water-restriction, a reliable measure of NDI. We found that 0% (0/17) of statin users compared to 20.4% (11/54) on non-users had UOsm <300mOsm/Kg following 10-hour water-restriction (Fisher's Exact p=0.055). The main statin prescribed in our previous study was atorvastatin 10-40mg/day (n=10) 33, which is the most widely used statin for cardiovascular disease. Atorvastatin and other statins are well-tolerated and have not been found to have adverse effects on mood, cognition, or renal function. The mechanism by which statins may treat NDI is not yet known, but two independent mice studies have demonstrated the effectiveness of statins in treating genetic forms of NDI. In those mice models of genetic NDI, prostaglandin and intracellular cytoskeleton proteins pathways were thought to explain statins' activity on NDI. In preparation for this project, our co-investigators Drs. Trepiccione and Christensen have initiated a pilot study in mice to investigate whether atorvastatin treatment could improve the lithium-induced NDI. NDI was induced in 10 mice by feeding mice with a LiCl-enriched diet for 15 days. After induction of NDI, a group of mice received intraperitoneal injection of atorvastatin (n=5) and a control group received vehicle (n=5) for additional 5 days in parallel with continued lithium treatment. Although our small statistical sample do not allow us to reach significance, (n=5 per group), the mice receiving atorvastatin showed a tendency to reduce polyuria. In line with this research, our present research protocol aims at conducting a randomized controlled trial investigating a statin, such as atorvastatin, in the treatment of lithium-induced NDI.

The investigators aim to retrospectively explore the electronic medical records of all patients who were admitted to the Intensive Care Unit (ICU) of the UZ Brussels in the last 10 years (March 1st 2011- March 1st 2021) and who received prolonged sedation (>24h) with sevoflurane.

OBJECTIVES: I. Determine the relationship between genotype variations and clinical phenotype in patients with congenital nephrogenic diabetes insipidus.