La diabetes insípida nefrogénica es causada por la resistencia parcial o total al efecto de la AVP. La diabetes insípida nefrogénica congénita es una alteración. Nephrogenic diabetes insipidus (NDI) is characterized by inability to concentrate the urine, which results in polyuria (excessive urine.
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Nephrogenic diabetes insipidus
University of Washington, Seattle; February 12, ; Last Update: Nephrogenic diabetes insipidus NDI is characterized by inability to concentrate the urine, which results in polyuria excessive urine production and polydipsia excessive thirst. Affected untreated infants usually have poor feeding and failure to thrive, and rapid onset of severe dehydration with illness, hot environment, or the withholding of water.
Short stature and secondary dilatation of the ureters and bladder from the high urine volume is common in untreated individuals. The clinical diagnosis of NDI relies on demonstration of subnormal ability to concentrate the urine despite the presence of the antidiuretic hormone pituitary-derived arginine vasopressin AVP.
Monitoring of growth and development in infants and children; periodic measurement of serum sodium concentration to identify unrecognized hyperosmolality and early dehydration; annual renal ultrasound evaluation to monitor for hydronephrosis and megacystis. Evaluation of relatives at risk: Evaluation of at-risk infants as early as possible to allow for prompt diagnosis and treatment to reduce morbidity from hypernatremia, dehydration, and dilation of the urinary tract.
The risks to sibs and offspring depend on the mode of inheritance and the carrier status of the parents, which can be established in most families using molecular genetic testing. Prenatal testing is possible for at-risk pregnancies if the disease-causing pathogenic variant s in the family have been identified.
The results of these tests may be difficult to interpret in individuals with “partial diabetes insipidus,” which results from either subnormal amounts of vasopressin secretion partial neurogenic DI or partial response of the kidney to normal vasopressin concentrations partial nephrogenic DI. These two disorders can be distinguished by comparing the ratio of urine osmolarity to plasma vasopressin concentration against normal standards.
However, direct measurement of vasopressin is hampered by technical difficulties. As such, it holds promise as a diagnostic tool in polyuria-polydipsia syndromes [ Fenske et al ].
Females heterozygous for X-linked NDI. An overnight urinary concentration test in female relatives, proposed as a method of carrier detection, is unreliable. View in own window. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants. The ability of the test method used to detect a variant that is present in the indicated gene. Sequence analysis detects variants that are benign, likely benign, of uncertain significancelikely pathogenic, or pathogenic.
For issues to consider in interpretation of sequence analysis results, click here. Exon and partial- and whole- gene deletions have been reported see Table A. Linkage testing cannot be used to confirm the diagnosis of NDI [ Arthus et al ]. However, if the family pedigree structure is sufficient and family members are cooperative with the testing process, linkage analysis may be performed to confirm cosegregation of a potential pathogenic variant identified by sequence analysis with the disease phenotype in individual families.
Carrier testing for female relatives at risk for X-linked NDI requires prior identification of the pathogenic variant in the family. Carrier testing for relatives at risk for autosomal recessive NDI requires prior identification of the pathogenic variants in the family. Carriers are heterozygotes for this autosomal recessive disorder and are not at risk of developing the disorder. Prenatal diagnosis and preimplantation genetic diagnosis PGD for at-risk pregnancies require prior identification of the pathogenic variants in the family.
Nephrogenic diabetes insipidus NDI. Individuals with NDI typically have polyuria and polydipsia. However, in some infants, polydipsia and polyuria are often unappreciated or unremarkable.
These infants may present with vomiting, gagging or retching, poor feeding, constipation or diarrhea, failure to thrive, unexplained fevers, and lethargy or irritability.
The majority of affected individuals are diagnosed in the first year of life [ van Lieburg et al ]. Doabetes initial symptoms in nefrogeniica dominant NDI usually appear later, in some cases not before early adulthood. Occasionally, the presenting sign is hydronephrosis, hydroureter, or megacystis. Dehydrated individuals who have not been diagnosed to have NDI or who are unable to communicate their complaints run the risk of being improperly treated with IV administration of normal saline, especially in emergency situations.
This may exacerbate hypernatremia. Prolonged, unrecognized, or repeated episodes of hypernatremic dehydration may result in seizures, permanent brain damage, developmental delay, and cognitive impairment.
With early diagnosis and proper management, intelligence and life span are usually normal. Chronic excretion of large volumes of urine in untreated persons results in hydronephrosis, hydroureter, and megacystis huge bladder. Some degree of urinary tract distension may be seen on ultrasound examination even in infants [ Yoo et al ]. These complications may occur as early as the second decade of life [ Shalev et al ]. Lifestyle is substantially affected by the need to have constant access to potable water and by the increased frequency of urination.
The unavailability of restroom facilities, even for a short time, is a problem in societies in which public urination is taboo. School and other social or group activities may be disrupted. Affected individuals are almost always less than 50th centile for height; most are more than one standard deviation below the mean. Failure to thrive or short stature may result from unsuccessful management or inadequate nutrition related to polydipsia.
Idabetes the majority of cases catch-up growth does not occur later in childhood [ van Lieburg et al ]. Partial nephrogenic diabetes insipidus. Individuals with partial NDI tend to be diagnosed in later childhood. Heterozygotes for X-linked NDI. Female carriers of X-linked NDI may have no symptoms or a variable degree of polyuria and polydipsia, or they may be as severely affected as males.
Nephrogenic Diabetes Insipidus
In females nefrogenicq for AVPR2 pathogenic variants, a correlation between urine-concentrating ability and symptoms and skewed X-chromosome inactivation in leukocytes has been reported [ Kinoshita et diabeetesFaerch et al ]. X-linked and autosomal recessive NDI are similar with respect to initial symptoms and, with a few exceptions, age of onset.
Thus, three families had the missense variant p. Asp85Asn associated with decreased ligand-binding affinity and decreased coupling to G sand one had the missense variant p. An individual representing a simplex case a single affected individual in a family had the missense variant p.
Recently, two other pathogenic variants p. TyrSer were shown to result in dlabetes partial NDI phenotype. The partial loss of function of these variants results from defective membrane trafficking [ Takahashi et al ]. The name “nephrogenic diabetes insipidus” was coined by Williams and Henry in In the literature it has been used synonymously with the terms “vasopressin- or ADH-resistant diabetes insipidus” or “diabetes insipidus renalis.
The exact prevalence of NDI is not known but it is assumed to be rare. In the Dutch population of approximately 16 million, 50 affected families are known. Diabetes insipidus is the excretion of abnormally large volumes i. In addition to inherited forms of nefrovenica diabetes insipidus NDIcauses of diabetes insipidus include the following:. Polyuria associated with diabetes mellitus is characterized by glucose in the urine and increased urine specific gravity.
Because of the nonspecific nature of the presenting signs of NDI, infants with NDI may go undiagnosed or be misdiagnosed while under care for failure to thrive, unexplained fever, urinary reflux, or other symptoms.
To establish the extent nefrogfnica disease in an individual diagnosed with nephrogenic diabetes insipidus NDIthe following evaluations are recommended:. Management is usually best accomplished by a team consisting of a nutritionist, a pediatric or adult nephrologist or endocrinologist, and a clinical nefrobenica.
The essence of management is the provision of free access to drinking water and to toilet facilities. Infants, who are naturally unable to seek out water when thirsty, must be offered water between regular feedings. Children and adults who are heavy sleepers may need to be awakened at night by a family member or an alarm clock in order to drink water and to urinate.
As long as an individual’s thirst mechanism remains intact and the person is otherwise well, these measures prevent hypernatremic dehydration. Education of friends, teachers, caretakers, and neighbors and a willingness to find creative solutions are helpful. Therapy is considered effective when urine output declines below a documented baseline in individuals with ad libitum water intake.
Objective measurements of hour urine volume are more valuable than subjective reports of the volume or frequency of voiding, although reduction in the latter provides a benefit to lifestyle.
Emergency treatment for dehydration.
Nephrogenic diabetes insipidus | Boletín Médico del Hospital Infantil de México (English Edition)
When individuals with NDI present with dehydration or shock, it is essential to establish whether the deficit is primarily in free water through water deprivation or excessive urine, stool, or sweat or in extracellular fluid bleeding, insipoda extravasation. The natural tendency of healthcare providers to treat dehydration with normal saline 0.
Rapid increases or decreases in plasma osmolality can cause seizures, coma, brain damage, and death. Individuals being prepared for surgery are often denied oral intake for many nefrogenida and are described as having ‘NPO’ nothing per ora status.
In individuals with NDI, an IV must be provided from the beginning of NPO status and the person’s oral intake of water for that period, which is typically much larger than that of an individual who does not have NDI, should be given intravenously as 2.
Hydronephrosis, hydroureter, and megacystis. Treatment involves medical management to reduce urine output and continuous or intermittent bladder catheterization when significant post-void urinary bladder residuals are present.
Children with a history of an episode of severe dehydration, delayed developmental milestones, or a delay in establishing the correct diagnosis and management warrant a formal developmental evaluation and intervention before school age. Prevention of primary manifestations see Treatment of Manifestations is possible when the diagnosis is made promptly after birth via molecular genetic testing. A genetic diagnosis may be performed after a few days; treatment and monitoring may then start immediately.
Prevention or reduction of serious renal, ureteral, or bladder dilatation may be achieved by reduction of urine production by drug therapy and voiding at two-hour intervals. It is appropriate to test at-risk infants for the family-specific pathogenic variant s as early as possible to allow for prompt diagnosis and treatment to reduce morbidity from hypernatremia, dehydration, and dilation of the urinary tract. Since autosomal dominant NDI is usually less severe than X-linked or autosomal recessive NDI, genetic testing of sibs of affected children may be performed at a later stage.
Asymptomatic female family members of a male with X-linked NDI who are at risk of being a carrier of the pathogenic variant may undergo genetic counseling and genetic testing when they are of reproductive age.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. Carriers of X-linked nephrogenic diabetes insipidus may experience a mild increase in urinary output and associated thirst during pregnancy. Polyhydramnios is found in a minority of pregnancies in which the fetus is affected by NDI. In cases of severe polyhydramnios and maternal discomfort, frequent amniotic fluid drainage may be necessary [ Kollamparambil et al ].
Effectiveness and safety of this treatment in partial NDI needs to be explored further.