Diagnosis Of Nephrogenic Diabetes Insipidus Research Articles

Desmopressin responding female nephrogenic diabetes insipidus: a case report

Nephrogenic diabetes insipidus, decreased ability to concentrate urine, with production of large amounts of urine, is caused by the refractory response of renal tubules to the action of antidiuretic hormone. This rare disorder, known as X-linked nephrogenic diabetes insipidus, is caused by a mutation in the arginine vasopressin receptor 2 gene. Because it is hereditary, most patients are male. This report highlights a case of nephrogenic diabetes insipidus in a 3-year 5-month-old female; upon presentation to the hospital, her symptoms included frequent urination and consumption of a significant amount of water, which had begun 2 years ago. The results of blood tests showed increased levels of serum antidiuretic hormone, and sellar magnetic resonance imaging showed no abnormality. The results of the water restriction test and the desmopressin administration test confirmed the diagnosis of nephrogenic diabetes insipidus showing a partial response to desmopressin. The results of genetic testing indicated the presence of an arginine vasopressin receptor 2 mutation, a heterozygous missense mutation (p.Val88Met), suggesting inheritance of X-linked nephrogenic diabetes insipidus. This report describes a significant case of symptomatic X-linked nephrogenic diabetes insipidus in a female patient who showed a partial response to desmopressin.

Nephrogenic diabetes insipidus: a comprehensive overview.

Nephrogenic diabetes insipidus (NDI) is characterized by the inability to concentrate urine that results in polyuria and polydipsia, despite having normal or elevated plasma concentrations of arginine vasopressin (AVP). In this study, we review the clinical aspects and diagnosis of NDI, the various etiologies, current treatment options and potential future developments. NDI has different clinical manifestations and approaches according to the etiology. Hereditary forms of NDI are mainly caused by mutations in the genes that encode key proteins in the AVP signaling pathway, while acquired causes are normally associated with specific drug exposure, especially lithium, and hydroelectrolytic disorders. Clinical manifestations of the disease vary according to the degree of dehydration and hyperosmolality, being worse when renal water losses cannot be properly compensated by fluid intake. Regarding the diagnosis of NDI, it is important to consider the symptoms of the patient and the diagnostic tests, including the water deprivation test and the baseline plasma copeptin measurement, a stable surrogate biomarker of AVP release. Without proper treatment, patients may developcomplications leading to high morbidity and mortality, such as severe dehydration and hypernatremia. In that sense, the treatment of NDI consists in decreasing the urine output, while allowing appropriate fluid balance, normonatremia, and ensuring an acceptable quality of life. Therefore, therapeutic options include nonpharmacological interventions, including sufficient water intake and a low-sodium diet, and pharmacological treatment. The main medications used for NDI are thiazide diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), and amiloride, used isolated or in combination.

Sevoflurane sedation and nephrogenic diabetes insipidus in patients affected with severe acute respiratory syndrome coronavirus 2.

Sevoflurane sedation and nephrogenic diabetes insipidus in patients affected with severe acute respiratory syndrome coronavirus 2.

A Novel Intragenic Deletion Related to the Arginine Vasopressin V2 Receptor Causes Nephrogenic Diabetes Insipidus

Nephrogenic diabetes insipidus (NDI) is a disease characterized by a defective response to the antidiuretic hormone (ADH) of the renal collecting duct leading to a decline in the ability of the pro-urine concentration. A 23-year-old man presented with an over 20-year history of polyuria concomitant with hydronephrosis. The diagnosis of NDI was established by gene analysis as well as a water-deprivation and vasopressin test. All exons of arginine vasopressin V2 receptor (AVPR2) gene were amplified and sequenced. A novel hemizygous intragenic inframe deletion, cDNA 255th bp to 263th bp in exon 2 of AVPR2, was identified. These relevant translations from the 85th amino acid Asp to 88th amino acid Val were missed and replaced by amino acid Glu. After treating the patient with hydrochlorothiazide, his symptoms improved significantly. The genetic analysis revealed a novel X-linked intragenic inframe deletion, AVPR2 gene cDNA 255th bp to 263th bp, causing NDI.

Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus.

Healthy kidneys maintain fluid and electrolyte homoeostasis by adjusting urine volume and composition according to physiological needs. The final urine composition is determined in the last tubular segment: the collecting duct. Water permeability in the collecting duct is regulated by arginine vasopressin (AVP). Secretion of AVP from the neurohypophysis is regulated by a complex signalling network that involves osmosensors, barosensors and volume sensors. AVP facilitates aquaporin (AQP)-mediated water reabsorption via activation of the vasopressin V2 receptor (AVPR2) in the collecting duct, thus enabling concentration of urine. In nephrogenic diabetes insipidus (NDI), inability of the kidneys to respond to AVP results in functional AQP deficiency. Consequently, affected patients have constant diuresis, resulting in large volumes of dilute urine. Primary forms of NDI result from mutations in the genes that encode the key proteins AVPR2 and AQP2, whereas secondary forms are associated with biochemical abnormalities, obstructive uropathy or the use of certain medications, particularly lithium. Treatment of the disease is informed by identification of the underlying cause. Here we review the clinical aspects and diagnosis of NDI, the various aetiologies, current treatment options and potential future developments.

Novel mutations associated with nephrogenic diabetes insipidus. A clinical-genetic study.

Molecular diagnosis is a useful diagnostic tool in primary nephrogenic diabetes insipidus (NDI), an inherited disease characterized by renal inability to concentrate urine. The AVPR2 and AQP2 genes were screened for mutations in a cohort of 25 patients with clinical diagnosis of NDI. Patients presented with dehydration, polyuria-polydipsia, failure to thrive (mean ± SD; Z-height -1.9 ± 2.1 and Z-weight -2.4 ± 1.7), severe hypernatremia (mean ± SD; Na 150 ± 10 mEq/L), increased plasma osmolality (mean ± SD; 311 ± 18 mOsm/Kg), but normal glomerular filtration rate. Genetic diagnosis revealed that 24 male patients were hemizygous for 17 different putative disease-causing mutations in the AVPR2 gene (each one in a different family). Of those, nine had not been previously reported, and eight were recurrent. Moreover, we found those same AVPR2 changes in 12 relatives who were heterozygous carriers. Further, in one female patient, AVPR2 gene study turned out to be negative and she was found to be homozygous for the novel AQP2 p.Ala86Val alteration. Genetic analysis presumably confirmed the diagnosis of nephrogenic diabetes insipidus in every patient of the studied cohort. We emphasize that we detected a high presence (50 %) of heterozygous females with clinical NDI symptoms. • In most cases (90 %), inherited nephrogenic diabetes insipidus (NDI) is an X-linked disease, caused by mutations in the AVPR2 gene. • In rare occasions (10 %), it is caused by mutations in the AQP2 gene. What is new: • In this study, we report 10 novel mutations associated with NDI. • We have detected a high presence (50 %) of heterozygous carriers with clinical NDI symptoms.

Novel AQP2 mutation causing congenital nephrogenic diabetes insipidus: challenges in management during infancy

Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder, mostly caused by AVPR2 mutations. Less than 10% of cases are due to mutations in the aquaporin-2 (AQP2) gene. Diagnosis and management of this condition remain challenging especially during infancy. Here, we report two unrelated patients, a 6-month-old Thai boy and a 5-year-old Emirati girl, with a history of failure to thrive, chronic fever, polydipsia, and polyuria presented in early infancy. The results of water deprivation test were compatible with a diagnosis of NDI. The entire coding regions of the AVPR2 and AQP2 gene were amplified by polymerase chain reaction and sequenced. Patient 1 was homozygous for a novel missense AQP2 mutation p.G96E, inherited from both parents. Patient 2 harbored a previously described homozygous p.T126M mutation in the AQP2 gene. Both patients were treated with a combination of thiazide diuretics and amiloride. Patient 1 developed paradoxical hyponatremia and severe dehydration 2 weeks after medical treatment began. In conclusion, we report a novel mutation of the AQP2 gene and highlight an important role of genetic testing for definite diagnosis. Vigilant monitoring of the fluid status and electrolytes after beginning the therapy is mandatory in infants with NDI.

Multiple autoimmune syndrome revealed by nephrogenic diabetes insipidus and hypokalaemic paralysis

A presentation of postpartum polydipsia and polyuria followed by periodic weakness led to the diagnosis of nephrogenic diabetes insipidus and hypokalaemic paralysis, both of which are complications of primary Sjögren's syndrome (pSS). The clinically dominant pSS was taken to coexist with long-latent systemic lupus erythematosus and asymptomatic autoimmune thyroid disease. This case of multiple autoimmune syndrome is a distinctive subgroup of autoimmune disorders that is increasingly recognized. Female hormone levels appeared to play a role in disease pathogenesis in this case. The patient was predicted to have a favourable prognosis due to the absence of major organ involvement. This case revealed an uncommon form of complex polyautoimmune phenomena and should prompt physicians to extend immunological screening, particularly for females with multiple illnesses.

Physiopathology and diagnosis of nephrogenic diabetes insipidus

Nephrogenic diabetes insipidus (NDI) is caused by an improper response of the kidney to the antidiuretic hormone arginine vasopressin (AVP), leading to a decreased ability to concentrate urine which results in polyuria and polydipsia. The clinical diagnosis of NDI relies on demonstration of subnormal ability to concentrate urine despite the presence of AVP. NDI is most commonly acquired, secondary to kidney disorders, electrolyte imbalance and various drugs. Congenital forms of NDI are rare, and most commonly inherited in a X-linked manner with mutations of the AVP receptor type 2 (AVPR2). Mutations of the water channel aquaporin-2 (AQP2) can be detected in autosomal recessive or dominant forms of NDI. Management of NDI should focus on free access to drinking water and reduction of polyuria.

Identification of two novel aquaporin-2 mutations in a Thai girl with congenital nephrogenic diabetes insipidus

To describe a Thai girl with congenital nephrogenic diabetes insipidus (NDI) and perform mutation analysis of the AQP2 gene. Case report. A 6-year old girl with a history of failure to thrive, polydipsia and polyuria was studied. Polyuria and polydipsia were observed within the first few months of life. Despite normal serum osmolality and electrolyte, the result of water deprivation test was compatible with a diagnosis of NDI. The entire coding regions of the AQP2 gene were assessed by polymerase chain reaction and sequencing analysis. The presence of mutations was also confirmed by restriction enzyme digestion analysis. Two heterozygous novel missense mutations were identified. Both were located in exon 1; a guanine-to-thymine substitution at nucleotide position 3 (c.3G-->T) inherited from her mother and a guanine-to-adenine at position 85 (c.85G-->A) inherited from her father, resulting in a methionine to isoleucine at codon 1 (p.M1I) and glycine to serine at codon 29 (p.G29S), respectively. These mutations have never been previously described and were not detected in 100 ethnic-matched unaffected control chromosomes. We report two novel mutations of the AQP2 gene, p.M1I and p.G29S, associated with autosomal recessive congenital NDI. This study expands the genotypic spectrum of AQP2 mutations and emphasizes an important role of genetic testing for definite diagnosis and genetic counseling.

An unusual case of polyuria in a lithium-treated patient

A 60-year-old woman, who had been taking lithium for 36 years for bipolar affective disorder, was referred to an endocrinologist by her psychiatrist for investigation of polydipsia and polyuria. Water deprivation did not concentrate her urine, nor did desmopressin, indicating the diagnosis of nephrogenic diabetes insipidus (NDI). She was started on chlorthalidone, a treatment for NDI, and her symptoms improved dramatically. Her polyuria was well controlled on chlorthalidone for 4 years, until she started feel tired and weak and her polyuria worsened. Initially these symptoms were attributed to her depression and lithium therapy. However, routine blood testing revealed a random blood glucose of 18.5 mmol/litre, thereby confirming the diagnosis of type 2 diabetes, and a corrected calcium of 3.02 mmol/litre (normal range 2.1–2.6 mmol/litre). She was started on a diabetic diet, resulting in good diabetes control (confirmed by haemoglobin A1c) and her symptoms improved. The patient's chlorthalidone was stopped as thiazide diuretics can cause hypercalcaemia and her calcium was repeated. The repeat value was higher at 3.07 mmol/litre and her parathormone was alsoelevated at 11.24 pmol/litre, confirming hyperparathyroidism. A parathyroid adenoma was sought but a nuclear medicine scan (Tc99m ssesta-MIBI; technetium 99m-sesta 2-methoxy isobutyl isonitrille) and ultrasound examination of the neck failed to localize an adenoma. It was felt that she had developed parathyroid hyperplasia secondary to chronic lithium therapy (Mallette and Eichhorn, 1986), so her lithium was withdrawn and replaced with sodium valproate. Her NDI and hyperparathyroidism resolved on withdrawal of lithium.

Diabetes insipidus as an early clinical manifestation of pineal tumor

OBJECTIVE: To present a pineal tumor diagnosed after long clinical course of diabetes insipidus.CASE REPORT: A ten years old male patient, with symptoms of polyuria, polydipsia and nocturia for 18 months was admitted at the Nephrology Unit with the diagnosis of nephrogenic diabetes insipidus. Six months prior to his admission, he had been submitted to a computed tomography scan, which was considered inconclusive. The diagnosis of central diabetes insipidus was confirmed by a water deprivation test. A head magnetic resonance imaging demonstrated two masses suggesting germinoma.CONCLUSIONS: Our observations show that patients with central diabetes insipidus need close clinical, laboratory and neuroradiological follow-up in order to detect the intracranially tumors in an early stage.

Effect of DDAVP on nocturnal enuresis in a patient with nephrogenic diabetes insipidus

The case of an 8 year old boy with both nocturnal enuresis and nephrogenic diabetes insipidus is presented. Diagnosis of nephrogenic diabetes insipidus was based on a typical medical history,...

Nephrogenic diabetes insipidus: identification of the genetic defect.

Congenital nephrogenic diabetes insipidus (NDI) is an X-linked inherited disorder characterized by renal resistance to the antidiuretic hormonal action of arginine vasopressin. The disease gene has been assigned to the subtelomeric region of the X chromosome long arm by demonstrating close linkage between NDI and several X-chromosomal DNA markers. The finding of closely linked genetic markers is useful in the diagnosis of NDI. Receptor studies in patients have indicated that NDI might be due to the absence or an abnormality of the adenylate cyclase-bound vasopressin type 2 receptor. This assumption was supported by the discovery of functional vasopressin V2 receptor activity in somatic cell hybrid cell lines that carried at least the distal part of the human X chromosome long arm. Definite evidence for a V2 receptor defect being the cause of NDI was found in a recent study demonstrating point mutations in the V2 receptor gene from affected individuals. Direct mutation analysis is now applicable for accurate carrier detection and early (prenatal) diagnosis.