Nephrogenic Diabetes Insipidus Research Articles

Incidence of nephrogenic diabetes insipidus during prolonged sevoflurane sedation in the intensive care unit: a retrospective analysis and predictive model

Incidence of nephrogenic diabetes insipidus during prolonged sevoflurane sedation in the intensive care unit: a retrospective analysis and predictive model

Low exposition to lithium prevents nephrogenic diabetes insipidus but not microcystic dilations of the collecting ducts in long-term rat model.

Lithium induces nephrogenic diabetes insipidus (NDI) and microcystic chronic kidney disease (CKD). As previous clinical studies suggest that NDI is dose-dependent and CKD is time-dependent, we investigated the effect of low exposition to lithium in a long-term experimental rat model. Rats were fed with a normal diet (control group),with the addition of lithium (Li+ group), or with lithium and amiloride (Li+/Ami group) for 6 months, allowing obtaining low plasma lithium concentrations (0.25 ± 0.06 and 0.43 ± 0.16 mmol/L, respectively). Exposition to low concentrations of plasma lithium levels prevented NDI but not microcystic dilations of kidney tubules, which were identified as collecting ducts (CDs) on immunofluorescent staining. Both hypertrophy, characterized by an increase in the ratio of nuclei per tubular area, and microcystic dilations were observed. The ratio between principal cells and intercalated cells was higher in microcystic than in hypertrophied tubules. There was no correlation between AQP2 messenger RNA levels and cellular remodeling of the CD. Additional amiloride treatment in the Li+/Ami group did not allow consistent morphometric and cellular composition changes compared to the Li+ group. Low exposition to lithium prevented overt NDI but not microcystic dilations of the CD, with differential cellular composition in hypertrophied and microcystic CDs, suggesting different underlying cellular mechanisms.

Arginine vasopressin deficiency: diagnosis, management and the relevance of oxytocin deficiency.

Polyuria-polydipsia syndrome can be caused by central diabetes insipidus, nephrogenic diabetes insipidus or primary polydipsia. To avoid confusion with diabetes mellitus, the name 'central diabetes insipidus' was changed in 2022 to arginine vasopressin (AVP) deficiency and 'nephrogenic diabetes insipidus' was renamed as AVP resistance. To differentiate the three entities, various osmotic and non-osmotic copeptin-based stimulation tests have been introduced in the past decade. The hypertonic saline test plus plasma copeptin measurement emerged as the test with highest diagnostic accuracy, replacing the water deprivation test as the gold standard in differential diagnosis of the polyuria-polydipsia syndrome. The mainstay of treatment for AVP deficiency is AVP replacement with desmopressin, a synthetic analogue of AVP specific forAVP receptor 2 (AVPR2), which usually leads to rapid improvements in polyuria and polydipsia. The main adverse effect of desmopressin is dilutional hyponatraemia, which can be reduced by regularly performing the so-called desmopressin escape method. Evidence from the past few years suggests an additional oxytocin deficiency in patients with AVP deficiency. This potential deficiency should be further evaluated in future studies, including feasible provocation tests for clinical practice and interventional trials with oxytocin substitution.

MANAGEMENT OF DIABETES INSIPIDUS AFTER SUBLABIAL TRANSSPHENOIDAL HYPOPHYSECTOMY SURGERY

MANAGEMENT OF DIABETES INSIPIDUS AFTER SUBLABIAL TRANSSPHENOIDAL HYPOPHYSECTOMY SURGERY

Cannabinoid Receptor Type 1 Activation Causes a Water Diuresis by Inducing an Acute Central Diabetes Insipidus in Mice.

Cannabis and synthetic cannabinoid consumption is increasing worldwide. Cannabis contains numerous phytocannabinoids that act on the G-protein-coupled cannabinoid receptors type 1 (CB1R) and type 2 (CB2R) expressed throughout the body, including the kidney. Essentially every organ, including the kidney, produces endocannabinoids (ECs), endogenous ligands to these receptors. Cannabinoids acutely increase urine output in rodents and humans, thus potentially influencing total-body water and electrolyte homeostasis. As the kidney collecting duct (CD) regulates total body water, acid/base, and electrolyte balance through specific functions of principal cells (PCs) and intercalated cells (ICs), we examined the cell-specific immunolocalization of CB1R in the mouse CD. Antibodies against either the C-terminus or N-terminus of CB1R consistently labeled AQP2(-) cells in the cortical and medullary CD, and thus presumably ICs. Given the well-established role of ICs in urinary acidification, we utilized a clearance approach in mice that were acid-loaded with 280 mM NH4Cl for 7d and non-acid-loaded mice treated with the cannabinoid receptor agonist, WIN55,212-2 (WIN), or a vehicle control. While WIN had no effect on urinary acidification, these WIN-treated mice had less apical+subapical AQP2 expression in PCs compared to controls and developed an acute diabetes insipidus (DI) associated with the excretion of large volumes of dilute urine. Mice maximally concentrated their urine when WIN + 1-desamino-8-d-arginine-vasopressin (desmopressin, DDAVP) were co-administered, consistent with central rather than nephrogenic DI. Although ICs express CB1R, the physiologic role of CB1R in this cell type remains to be determined.

Genetic analysis of nephrogenic diabetes insipidus patients: A study on the Iranian population.

Nephrogenic diabetes insipidus (NDI) is a rare genetic disease that causes water imbalance. The kidneys play a crucial role in regulating body fluids by controlling water balance through urine excretion. This highlights their essential function in managing the body's water levels, but individuals with NDI may have excess urine production (polyuria), that leads to excessive thirst (polydipsia). Untreated affected individuals may exhibit poor feeding and failure to thrive. This disease is caused by mutations in the AVPR2 and the AQP2 genes which have the X-linked and autosomal recessive/dominant inheritance, respectively. Both of these genes are expressed in the kidney. Twelve Iranian patients from 10 consanguineous families were studied in this project. DNA was extracted from the whole blood samples of the patients and their parents. All coding exons and exon-intron boundaries of the AVPR2 and AQP2 genes were sequenced in the affected individuals, and the identified variants were investigated in the parents. All variants were analyzed according to the ACMG (American College of Medical Genetics and Genomics) guidelines. In this study, 6 different mutations were identified in the patients, including 5 in the AQP2 gene (c.439G>A, c.538G>A, c.140C>T, c.450T>A, and the novel c.668T>C) and 1 in the AVPR2 gene (c.337C>T) in the present study. As expected, all the detected mutations in this study were missense. According to the ACMG guideline, the identified mutations were categorized as pathogenic or likely pathogenic. Unlike previous studies which showed more than 90% of mutations were in the AVPR2 gene, and only less than 10% of the mutations were in the AQP2 gene, it was found that more than 90% of our identified mutations located in the AQP2 gene, and only one mutation was observed in the AVPR2 gene, which seems it may be a result of the high rate of consanguineous marriages in the Iranian population. We observed genotype-phenotype correlation in some of our affected individuals, and some of the mutations were observed in unrelated families from same ethnicity which could be suggestive of a founder mutation.

149 Severe Hypokalemia from Heavy Coffee/Cola Consumption Complicated by Rhabdomyolysis, Nephrogenic Diabetes Insipidus and Polyuria-Induced Hydronephrosis

149 Severe Hypokalemia from Heavy Coffee/Cola Consumption Complicated by Rhabdomyolysis, Nephrogenic Diabetes Insipidus and Polyuria-Induced Hydronephrosis

98 A Tale of Two Sodiums: Concurrent Primary Polydipsia and Nephrogenic Diabetes Insipidus

98 A Tale of Two Sodiums: Concurrent Primary Polydipsia and Nephrogenic Diabetes Insipidus

The β3-AR agonist BRL37344 ameliorates the main symptoms of X-linked nephrogenic diabetes insipidus in the mouse model of the disease.

X-linked nephrogenic diabetes insipidus (X-NDI) is a rare congenital disease caused by inactivating mutations of the vasopressin type-2 receptor (AVPR2), characterized by impaired renal concentrating ability, dramatic polyuria, polydipsia and risk of dehydration. The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP-intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the β3-adrenergic receptor could be such an ideal candidate. We evaluated the effect of continuous 24 h stimulation of the β3-AR with the agonist BRL37344 and assessed the effects on urine output, urine osmolarity, water intake and the abundance and activation of the key renal water and electrolyte transporters, in the mouse model of X-NDI. Here we demonstrate that the β3-AR agonism exhibits a potent antidiuretic effect. The strong improvement in symptoms of X-NDI produced by a single i.p. injection of BRL37344 (1 mg/kg) was limited to 3 h but repeated administrations in the 24 h, mimicking the effect of a slow-release preparation, promoted a sustained antidiuretic effect, reducing the 24 h urine output by 27%, increasing urine osmolarity by 25% and reducing the water intake by 20%. At the molecular level, we show that BRL37344 acted by increasing the phosphorylation of NKCC2, NCC and AQP2 in the renal cell membrane, thereby increasing electrolytes and water reabsorption in the kidney tubule of X-NDI mice. Taken together, these data suggest that human β3-AR agonists might represent an effective possible treatment strategy for X-NDI.

A case of pregnancy with severe polyhydramnios related to long-term use of lithium.

Severe polyhydramnios during pregnancy may be associated with long-term lithium use and presents considerable challenges. This complication, which has been linked to induced nephrogenic diabetes insipidus (NDI), underscores the necessity for cautious management of pregnant women with bipolar disorder. This case report aims to elucidate the relationship between long-term lithium use, pregnancy, and the development of severe polyhydramnios, emphasizing the importance of diagnosing NDI in order to prevent obstetric and neonatal complications. We present the case of a 42-year-old primigravida undergoing long-term lithium treatment for bipolar disorder type I, who developed severe polyhydramnios at 34 weeks of gestation. Clinical data including obstetric monitoring and neonatal outcomes were analyzed. This case emphasizes the need for heightened awareness and proactive measures to mitigate the risk associated with lithium treatment during pregnancy. Close monitoring and timely interventions are essential to ensure optimal outcomes for both mother and fetus. Our article puts forth the hypothesis that there is a link between lithium use during pregnancy and the occurrence of polyhydramnios and Nephrogenic Diabetes Insipidus (NDI), which may lead to severe obstetric and neonatal complications. This case report contributes to the limited literature on the subject and gives doctors practical advice that may help them make a better risk-benefit analysis. Further research is warranted in order to refine risk assessment protocols and management strategies in this complex clinical scenario.

Retracted: A Novel Missense Mutation of Arginine Vasopressin Receptor 2 in a Chinese Family with Congenital Nephrogenic Diabetes Insipidus: X-Chromosome Inactivation in Female CNDI Patients with Heterozygote 814A>G Mutation.

[This retracts the article DOI: 10.1155/2022/7073158.].

Remission of nephrogenic diabetes insipidus (arginine vasopressin resistance): description of a rare clinical case

Nephrogenic diabetes insipidus is a heterogeneous disease in the etiopathogenesis of which are involved acquired and congenital factors. In this case, the kidneys do not respond to vasopressin and continue to produce large concentrated volumes of urine. Distinctive features in the pathology of central genesis are the fact of trauma, brain tumor with involvement of pituitary gland, response to intranasal vasopressin in the form of decreased diuresis.For diagnosis it is important to perform a series of differential diagnostic tests.In this article we present a unique clinical case of a patient with a long-term course of diabetes insipidus with the development a spectrum of comorbid conditions, metabolic disorders, required kidney transplantation.

Hypokalemia Induced Partial Nephrogenic Diabetes Insipidus: A Case Report

Diabetes insipidus is a condition characterised by a large volume of diluted urine production andincreased thirst. In this case report, a 49-year-old gentleman presented with 3 months of polyuria andpolydipsia. He had a repeated history of hypokalemia. On the evaluation of polyuria and polydipsia,he was diagnosed with partial nephrogenic diabetes insipidus based on his inability to concentrateurine after a water deprivation test and his less than 50% response to exogenous desmopressin.On the evaluation of recurrent hypokalemia, the investigation reports met biochemical criteria forthe diagnosis of Gitelman syndrome. He was encouraged to increase his fluid intake as required,and potassium chloride supplementation relieved his symptoms. This case report demonstrates thereversibility of nephrogenic diabetes insipidus with a correction of hyperkalemia.

Diabetes Insipidus can Increase Patient Security: A Review

Diabetes insipidus (DI) is a condition marked by polydipsia (drinking more than three liters of fluid per day) and a high hypotonic urine production (greater than 50 milliliters per kilogram of body weight per 24 hours). The hypothalamus or pituitary gland's insufficient production of arginine vasopressin (AVP) and its consequent inadequate secretion cause central DI. In addition to central DI, different primary forms (of renal origin) or secondary forms of polyuria may be the cause of additional underlying etiologies of DI. These variations are all part of the Polyuria Polydipsia Syndrome. This is crucial since different treatment plans have different effects, and using the incorrect one can be harmful. Since its discovery in 1942, diabetes insipidus has been linked to pregnancy complications in at least 4 out of every 100,000 patients.The regulatory mechanisms behind CDI and NDI are then discussed, with an emphasis on the water channel molecule aquaporin 2 (AQP2) and the vasopressin receptor 2 (V2R) regulatory axis. (DI) is a complicated pregnancy condition that can affect about 1 in 30,000 pregnancies. It is a heterogeneous illness that most commonly manifests as polyuria and polydipsia. The pathophysiology of DI during pregnancy determines the course of treatment; DI without AVP can be managed with desmopressin (DDAVP); DI with AVP resistance necessitates investigation of the underlying reasons. Previously known as diabetes insipidus (DI), arginase vasopressin disorder is a disease condition that causes electrolyte imbalances by either reducing the secretion of antidiuretic hormone (ADH, also known as vasopressin or AVP) or by reducing the body's response to ADH. Both arginine vasopressin deficiency (AVP-D; formerly known as central DI) and arginine vasopressin resistance (AVP-R; formerly known as nephrogenic DI) are forms of arginine vasopressin disease, with both congenital and acquired origins. Lithium increased the amount of lipid peroxidation (LPO) and reactive oxygen species (ROS) in the kidney.

Targeted long-read sequencing identified a causal structural variant in X-linked nephrogenic diabetes insipidus.

X-linked nephrogenic diabetes insipidus (NDI) is a rare genetic renal disease caused by pathogenic variants in the AVPR2 gene. Single nucleotide variants and small insertions/deletions in AVPR2 are reliably detected by routine clinical sequencing. Nevertheless, structural variants involving AVPR2 are challenging to identify accurately by conventional genetic testing. Here, we report a novel deletion of AVPR2 in a Czech family identified for the first time by targeted long-read sequencing (T-LRS). A male proband with X-linked NDI underwent clinical sequencing of the AVPR2 gene that failed and thus indicated possible whole-gene deletion. Therefore, PCR mapping and subsequent targeted long-read sequencing (T-LRS) using a Pacific Biosciences sequencer were applied to search for the suspected deletion. To validate the deletion breakpoints and prove variant segregation in the family with X-linked NDI, Sanger sequencing of the deletion junction was performed. Quantitative real-time PCR was further carried out to confirm the carrier status of heterozygous females. By T-LRS, a novel 7.5 kb deletion of AVPR2 causing X-linked NDI in the proband was precisely identified. Sanger sequencing of the deletion junction confirmed the variant breakpoints and detected the deletion in the probands´ mother, maternal aunt, and maternal cousin with X-linked NDI. The carrier status in heterozygous females was further validated by quantitative real-time PCR. Identifying the 7.5 kb deletion gave a precise molecular diagnosis for the proband, enabled genetic counselling and genetic testing for the family, and further expanded the spectrum of structural variants causing X-linked NDI. Our results also show that T-LRS has significant potential for accurately identifying putative structural variants.

Diabetes Insipidus: Types, Diagnosis and Management

Diabetes insipidus (DI) is an acquired or hereditary water imbalance disorder characterized by polydipsia and polyuria. It is a condition that involves the excretion of dilute urine in large volumes. The illness can strike at any age, with males and females have identical rates of occurrence of the disease. The two main mechanisms responsible for diabetes insipidus are either insufficient release or production of ADH (antidiuretic hormone) from the hypothalamus (central diabetes insipidus) or ADH resistance in which the kidneys are unable to respond to ADH (nephrogenic diabetes insipidus). Another form of DI is transient diabetes insipidus commonly known as gestational diabetes insipidus that occurs in the second/third trimester of pregnancy due to increased levels of placental vasopressinase that occurs progressively during pregnancy and increases metabolic clearance of vasopressin. The fourth type of DI is primary polydipsia, characterized by elevated levels of water intake that physiologically lower vasopressin and may be psychogenic, iatrogenic or dipsogenic. Signs and symptoms of DI often include water electrolyte-imbalance, excessive or severe thirst, frequent and excessive urination, fatigue, dehydration, and weight loss. Diabetes insipidus (DI) should be distinguished from primary polydipsia, and whether it is caused by a central, nephrogenic, or gestational cause. This distinction is critical since incorrect treatment can result in serious repercussions. Diagnosis of DI includes measurement of plasma sodium and osmolality, baseline copeptin, hypertonic saline stimulation and arginine stimulation test. The treatment for DI includes the use of drugs such as desmopressin, thiazide diuretics, indomethacin and amiloride.

Angiotensin receptor blocker induced fetopathy: two case reports and literature review

The administration of angiotensin type 2 receptor blockers (ARBs) during pregnancy is known to cause ARB fetopathy, including renal insufficiency. We aimed to analyze the outcomes of two patients who survived ARB fetopathy and perform an accompanying literature review. Case 1 was exposed antenatally from a gestational age of 30 weeks to valsartan because of maternal pregnancy-induced hypertension. The patient presented with oliguria immediately after birth, and renal replacement therapy was administered for 24 days. Seven years after birth, renal function was indicative of stage 2 chronic kidney disease (CKD) with impaired urinary concentration. Case 2 had a maternal history of hypertension and transient ischemic attack and was treated with olmesartan until 30 weeks of pregnancy. Renal replacement therapy was performed for 4 days since birth. After 8 years, the patient is with CKD stage 2, with intact tubular function. Recent reports suggest that ARB fetopathy might manifest as renal tubular dysgenesis and nephrogenic diabetes insipidus, in contrast to mild alterations of glomerular filtration. Tubular dysfunction may induce CKD progression and growth retardation. Patients with ARB fetopathy should be monitored until adulthood. The ARB exposure period might be a critical factor in determining the severity and manifestations of fetopathy.

Lithium precipitated acute kidney injury: A rare case report

Lithium is known to cause nephrogenic diabetes insipidus, chronic tubule-interstitial nephropathy, and partial distal renal tubular acidosis. We are describing a rare instance of lithium precipitating acute renal injury within a week in a patient receiving long-term nonsteroidal anti-inflammatory drugs (NSAIDs) for medically unexplained symptoms. The patient presented with fluctuating orientation, cerebellar signs, and brisk deep tendon reflexes. Citing associated lithium toxicity discontinuation of lithium and NSAIDs brought back kidney function test to normal. Lithium toxicity was treated with intravascular fluids. We conclude that lithium may precipitate severe but reversible renal failure.

Metabolic Reprogramming of Renal Epithelial Cells Contributes to Lithium-Induced Nephrogenic Diabetes Insipidus

Metabolic Reprogramming of Renal Epithelial Cells Contributes to Lithium-Induced Nephrogenic Diabetes Insipidus

A Novel Renal Collecting Duct Model to Study Secondary Nephrogenic Diabetes Insipidus Associated with Cystinosis

A Novel Renal Collecting Duct Model to Study Secondary Nephrogenic Diabetes Insipidus Associated with Cystinosis