Clinical characteristics of congenital nephrogenic diabetes insipidus / 中华内科杂志

The purpose of this study was to improve the ability to visualize and diagnose congenital nephrogenic diabetes insipidus (CNDI). The clinical manifestations, laboratory examination findings, imaging features and treatment outcomes of 22 patients with CNDI admitted to the First Affiliated Hospital of Zhengzhou University from May 2013 to May 2020 were retrospectively analyzed. Among the 22 patients with CNDI, 86.4% (19 cases) were male. The age of the 22 patients ranged from 2 months to 47 years old, in which 20 cases were younger than 30 years old and 2 cases were older than 30 years old. The clinical manifestations were polydipsia and polyuria, accompanied with various degrees of fever, defects in growth and development, and increased serum creatinine in some patients. Fifteen patients (68.2%) had different degrees of bilateral kidney and ureteral hydronephrosis, and increased residual urine volume in the bladder. Pituitary magnetic resonance imaging (MRI) enhanced scan showed that the high signal intensity in the posterior pituitary lobe was not detectable in 5 cases (22.7%), and blurred in 6 cases (27.3%). Seven tested patients were all found AVPR2 gene mutation. For patients with suspected CNDI, water-inhibiting vasopressin test and genetic testing should be performed in time so as to confirm diagnosis and treat as early as possible.

Lithium, an old friend and a forgotten enemy

SUMMARY INTRODUCTION: Nephrogenic diabetes insipidus (DI) is a polyuric and polydipsic syndrome and can have multiple causing factors. CASE DESCRIPTION: A 69-year-old woman with bipolar disorder medicated with lithium 400mg for 12 years on a daily basis. The patient was admitted, after psychiatric decompensation, with hypernatremia unresponsive to hypotonic iv fluids. The diagnosis of DI was made with high plasmatic osmolality measurement, low urine osmolality, and high levels of antidiuretic hormone. Full clinical recovery was possible with lithium suspension, hydration, and chlorthalidone. DISCUSSION: Although frequently used in the past, Lithium (Li) is nowadays rarely used in clinical practice for prolonged treatments because of its potentially devastating side effects. Clinicians must be aware of those side effects in order to prevent organ damage, mainly in patients with severe bipolar disease and precarious response to alternative treatments.

RESUMO INTRODUÇÃO: O diabetes insípido nefrogênico faz parte das síndromes poliúricas polidipsicas e pode ter múltiplos fatores causais. CASO CLÍNICO: Mulher de 69 anos, com doença bipolar medicada com lítio 400 mg por dia durante 12 anos. A doente foi internada, após descompensação da doença bipolar, por hipernatremia não responsiva a fluidoterapia hipotônica endovenosa. O diagnóstico de DI foi realizado com base na elevação da osmolaridade plasmática, baixa osmolaridade urinária e níveis elevados de hormona antidiurética. Verificou-se recuperação clínica completa com suspensão do lítio, hidratação e clorotalidona. DISCUSSÃO: Apesar do seu uso frequente no passado, o lítio (Li) é hoje em dia raramente utilizado na prática clínica por períodos prolongados pelos seus efeitos potencialmente devastadores. Os médicos devem ter em conta os potenciais efeitos secundários de forma a prevenir lesão de órgão em doentes com doença bipolar de difícil controle com outra terapêutica.

X-linked congenital renal diabetes insipidus caused by AVPR2 gene mutation: a case report / 天津医药

@#Objective A case of congenital renal diabetes insipidus caused by mutation of arginine vasopressin receptor 2 (AVPR2) gene was reported to explore the clinical significance of AVPR2 gene mutation in congenital nephrotic diabetes insipidus and improve the understanding of the disease. Methods The clinical data of proband and his parents were retrospectively analyzed, and the related literature was reviewed. All exons of AVPR2 were amplified by PCR, and the amplified products were purified and sequenced in two directions. Results The clinical manifestations of the children were recurrent fever and hypernatremia, and hyperchloremia was difficult to correct. There was no abnormality in pituitary nuclear magnetic resonance in the child at the beginning. Short T1 signal disappeared in the posterior pituitary lobe after reexamination. Central diabetes insipidus was not excluded from clinical practice. However, vasopressin test supported renal diabetes insipidus, which caused troubles in clinical diagnosis. The treatment of vasopressin acetate tablets was ineffective. The results of gene analysis confirmed that mutations were found in the subregion of AVPR2 gene in the proband: c.359T (thymine)>G (guanine) caused amino acid changes: p.Met120Arg, which was located on the X chromosome, and the mother of the patient was the carrier of the mutation of AVPR2 gene. Clinical application of hydrochlorothiazide and amiloride in the treatment of the child with urinary volume significantly reduced, confirmed as congenital renal diabetes insipidus. Conclusion Congenital renal diabetes insipidus in infants and young children is rare and its clinical manifestations are not specific. It can only be manifested by repeated fever and electrolyte disturbance, which causes troubles in clinical diagnosis. AVPR2 gene detection can be used for screening and gene diagnosis of congenital renal diabetes insipidus.

Congenital nephrogenic diabetes insipidus with end-stage renal disease

No abstract available.

Diabetes insípida: generalidades y diagnóstico en pacientes pediátricos / Diabetes insipidus: overview and diagnosis in pediatric patients

La diabetes insípida es una enfermedad caracterizada por la incapacidad parcial o total para concentrar la orina, debido a una deficiencia en la secreción de vasopresina (diabetes insípida central), resistencia en la acción de la misma (diabetes insípida nefrogénica) o a ingesta excesiva de agua (polidipsiaprimaria). Las principales manifestaciones son polidipsia, poliuria y nicturia; la diabetes insípida central tiene un inicio repentino, mientras que la nefrogénica tiene un inicio más gradual. Gracias a los avances en laboratorio clínico, imaginología y biología molecular, ha mejorado el diagnóstico etiológico de la diabetes insípida, pasando de 50% de casos idiopáticos a solo entre 10% y 20%, de forma que se ha logrado un tratamiento más oportuno, con la consecuente reducción del riesgo de secuelas. En este sentido, es de especial importancia descartar causas secundarias, tales como medicamentos o desórdenes metabólicos en la diabetes insípida nefrogénica y tumores cerebrales, traumatismos craneoencefálicos, enfermedades infiltrativas, enfermedades autoinmunes o infecciones de sistema nervioso central en el caso de la diabetes insípida central. En cuanto al tratamiento, para la diabetes insípida central se recomienda el uso de desmopresina, análogo sintético de la vasopresina, y para la nefrogénica aporte de agua, limitación a la ingesta de sal y el consumo de diuréticos y antinflamatorios no esteroideos. En este artículo de revisión se describirá la fisiopatología, manifestaciones clínicas, diagnóstico y tratamiento de la diabetes insípida en la edad pediátrica.

Diabetes insipidus is a disease characterized by partial or total inability to concentrate urine; the disease can be caused by vasopressin secretion deficiency (central diabetes insipidus), resistance to its action (nephrogenic diabetes insipidus) or an excessive consumption of water (primary polydipsia). The main signs and symptoms of the disease are polydipsia, polyuria, and nocturia; in addition, central diabetes insipidus has an insidious onset, whereas nephrogenic diabetes insipidus has a gradual onset. Because of the advances in clinical laboratory, imaging techniques and molecular biology, the etiologic diagnosis of diabetes insipidus has improved, and the rate of idiopathic diabetes insipidus, which initiallycorresponded to 50% of patients, has dramatically decreased to 10%-20% of patients; therefore, it has been achieved more timely treatments, resulting in reduction of the risk of sequelae. Accordingly, it is pivotal to rule out secondary causes of diabetes insipidus, such as drug consumption or metabolic disorders in patients with nephrogenic diabetes insipidus, and brain tumors, encephalic trauma, infiltrative diseases, autoimmune disorders or central nervous system infections in case of patients suffering of central diabetes insipidus. Regarding treatment, it is recommended to use desmopressin, an analogue of vasopressin, for the treatment of central diabetes insipidus, whereas water consumption, decrease of salt consumption and treatment with diuretic and non-steroidal anti-inflammatory drugs are recommended for treatment of patients with nephrogenic diabetes insipidus. This review article describes physiopathology, signs and symptoms, diagnosis, and treatment of children with diabetes insipidus.

Two Novel Mutations in the Aquaporin 2 Gene in a Girl with Congenital Nephrogenic Diabetes Insipidus

Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by insensitivity of the kidney to the antidiuretic effect of vasopressin. There are three inheritance patterns of CNDI: the X-linked recessive form associated with vasopressin V2 receptor gene mutations, and the autosomal recessive and dominant forms associated with aquaporin-2 gene (AQP2) mutations. The evaluation for polyuria and polydipsia in a one-month-old Korean girl revealed no response to vasopressin and confirmed the diagnosis of CNDI. Because the child was female without family history of CNDI, her disease was thought to be an autosomal recessive form. We analyzed the AQP2 gene and detected a compound heterozygous missense point mutation: (70)Ala (GCC) to Asp (GAC) in exon 1 inherited from her father and (187)Arg (CGC) to His (CAC) in exon 3 inherited from her mother. The first mutation is located within the first NPA motif of the AQP2 molecule and the second one right after the second NPA motif. This is the first report to characterize AQP2 mutations in Korean patients with autosomal recessive CNDI, and expands the spectrum of AQP2 mutations by reporting two novel mutation, (70)Ala (GCC) to Asp (GAC) and (187)Arg (CGC) to His (CAC).

Sj gren's syndrome associated with voltage defect distal renal tubular acidosis and nephrogenic diabetes insipidus / 대한내과학회지

Distal renal tubular acidosis is a condition characterized by an inability of the distal nephron to acidify urine, causing hyperchloremic metabolic acidosis. Distal renal tubular acidosis is classified as proton secretory defect, permeability defect and voltage defect based on its pathophysiology. In the former two, serum level of potassium decreases due to increased excretion of potassium. But in the latter (voltage defect), hyperkalemia is characteristic by impaired the generation of an optimal electrical gradient for hydrogen ion and potassium secretion. We experienced a case of Sj gren's syndrome associated with both voltage defect distal renal tubular acidosis and nephrogenic diabetes insipidus. The patient was a 58- year-old woman who complained of general weakness, nausea and xerostomia. Laboratory analysis showed metabolic acidosis with alkaline urine and hyperkalemia. Anti-nuclear antibody and anti-ds DNA antibody were positive. She presented with polyuria, low urine osmolarity and inadequate response to DDAVP. The response to Shirmer test was decreased. Salivary scintigraphy showed decrease of uptake in the parotid and submandibular salivary glands. We believe this is the first case report in which Sj gren's syndrome is associated with both voltage defect distal renal tubular acidosis and nephrogenic diabetes insipidus.

Sj gren's syndrome associated with voltage defect distal renal tubular acidosis and nephrogenic diabetes insipidus / 대한내과학회지

Distal renal tubular acidosis is a condition characterized by an inability of the distal nephron to acidify urine, causing hyperchloremic metabolic acidosis. Distal renal tubular acidosis is classified as proton secretory defect, permeability defect and voltage defect based on its pathophysiology. In the former two, serum level of potassium decreases due to increased excretion of potassium. But in the latter (voltage defect), hyperkalemia is characteristic by impaired the generation of an optimal electrical gradient for hydrogen ion and potassium secretion. We experienced a case of Sj gren's syndrome associated with both voltage defect distal renal tubular acidosis and nephrogenic diabetes insipidus. The patient was a 58- year-old woman who complained of general weakness, nausea and xerostomia. Laboratory analysis showed metabolic acidosis with alkaline urine and hyperkalemia. Anti-nuclear antibody and anti-ds DNA antibody were positive. She presented with polyuria, low urine osmolarity and inadequate response to DDAVP. The response to Shirmer test was decreased. Salivary scintigraphy showed decrease of uptake in the parotid and submandibular salivary glands. We believe this is the first case report in which Sj gren's syndrome is associated with both voltage defect distal renal tubular acidosis and nephrogenic diabetes insipidus.

Identification of a mutation in the arginine vasopressin receptor 2 gene in a Chinese pedigree with congenital nephrogenic diabetes insipidus / 中华内分泌代谢杂志

Genomic DNA was extracted from the blood samples of 3 patients from 1 pedigree with congenital nephrogenie diabetes insipidus (NDI) and their 12 family members.The whole coding region of the arginine vasopressin receptor 2 (AVPR2) gene was amplified by PCR and then directly sequenced,A mutation of AVPR2 gene [g1236T→C (L292P)]was found in 3 patients.The patients' mothers were found to have both mutant and normal alleles.