Nephrogenic diabetes insipidus in children

Introduction to children with renal diabetes insipidus Renal diabetes insipidus (nephrogenicdiabetesinsipidus) is a disease of renal tubular hydration dysfunction. It belongs to the category of urinary concentrating dysfunction disease. It is due to AVP low resistance, hereditary and acquired NDI. basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: hyperosmolar dehydration chronic renal failure

Causes of pediatric renal diabetes insipidus

(1) Causes of the disease

1. Hereditary genital recessive inheritance, the vast majority of men.

2. Secondary can occur in a variety of chronic kidney diseases (such as hypokalemia, interstitial nephritis, chronic pyelonephritis) drug-induced renal damage.

(two) pathogenesis

1. Hereditary renal diabetes insipidus distal renal tubules and collecting ducts are not sensitive to ADH, or may be due to insufficient cAMP production in renal tubular epithelial cells or cAMP acting on the luminal side membrane to cause water permeability dysfunction, The onset of the disease is related to two genetic mutations:

(1) Vasopressin type-2 receptor (V2R) gene mutation: one is the V2R gene mutation (sexual linkage recessive inheritance), which is located on the X chromosome q27-28, has been found more than 60 In a variant, the mutated V2R could not bind to ADH, and adenylate cyclase could not be activated (post-receptor signaling disorder), and 90% of congenital NDI patients were associated with this mutation.

(2) Aquaporin-2 (AQP2) gene mutation: The other is AQP2 gene mutation, which is autosomal dominant or recessive, the coding gene is located on autosome 12q13, and AQP2 is regulated by ADH. First, ADH stimulated the cytoplasmic vesicles containing AQP2 to translocate to the apical membrane of the main cell, and then the long-term phase of ADH increased the expression of AQP2 in the collecting duct, and 10% of congenital NDI was associated with AQP2 gene mutation.

2. Secondary renal diabetes insipidus is caused by the primary disease destroying the hyperosmolar state of the renal medulla and making the tubular dysfunction.

Pediatric renal diabetes insipidus prevention

Focus on the prevention of secondary NDI, because a considerable part of it is iatrogenic, clinical should be vigilant, and CDI prevention must refer to other birth defects, in order to reduce the incidence of this disease, prevention should be from pre-pregnancy to prenatal To strengthen the consultation of genetic diseases, pre-marital physical examination plays an active role in preventing birth defects. The size of the effect depends on the examination items and contents, including serological examination (such as hepatitis B virus, Treponema pallidum, HIV) and reproductive system examination ( Such as screening for cervical inflammation), general physical examination (such as blood pressure, electrocardiogram) and asking about the family history of the disease.

Personal medical history, family history, etc., pregnant women should avoid harmful factors as much as possible, including away from smoke, alcohol, drugs, radiation, pesticides, noise, volatile harmful gases, toxic and harmful heavy metals, etc., in the process of antenatal care during pregnancy Screening of birth defects in the system, including regular ultrasound examination, serological screening, etc., if necessary, chromosomal examination, if abnormal results occur, it is necessary to determine whether to terminate the pregnancy; the safety of the fetus in the uterus; whether it exists after birth The sequelae, whether it can be treated, how the prognosis, etc., take practical measures for diagnosis and treatment.

Pediatric renal diabetes insipid complications Complications hyperosmolar dehydration chronic renal failure

Hyperosmolar dehydration, convulsions, growth and development disorders, mental retardation, urinary tract hydrops and chronic renal failure.

Pediatric renal diabetes insipidus symptoms common symptoms polydipsia polyuria growth slow hypernatremia water loss diabetes collapse mental retardation convulsions urine osmotic pressure drop high fever

1. More urine and more drinks

For the prominent clinical manifestations of this disease, about 90% of hereditary people occur in males. They can be expressed as polyhydramnios before birth. They can have polyuria and polydipsia symptoms at birth, usually only after the birth to 10 years old. The main symptoms are polyuria (low specific gravity urine), polydipsia, polydipsia, growth and development disorders, etc., severe cases of patients with high fever, convulsions, dehydration, hypernatremia and other clinical symptoms and corresponding performance, this type with age Symptoms can be gradually relieved, secondary symptoms first manifest the symptoms of the primary disease, and later appear polyuria, polydipsia, dehydration, blood concentration and other symptoms and signs, laboratory tests may have hypernatremia, hyperchloremia Wait.

2. Low permeability urine

The urine specific gravity often lasts below 1.005, or the urinary exudation is less than 200mOsm/(kg·H2O), and the solute diuresis can only reach an extent of isotonicity of 280-300 mOsm/(kg·H2O) with plasma.

3. Hypertonic dehydration

Insufficient blood volume due to infants and young children can not express thirst, prone to hyperosmolar dehydration and insufficient blood volume, can lead to central nervous system symptoms and infant mental development disorders, such as severe water loss can lead to death, dehydration caused by factors other than CDI and NDI When the urine should be concentrated urine, so the infant dehydration with dilute urine, should be alert to the possibility of this disease, adult patients in the inappropriate water limit or with impaired central nervous system, can also occur severe hypertonic dehydration .

4. Growth retardation

Seen in congenital NDI.

5. Mental retardation and psychological abnormalities

It is generally believed that mental retardation is one of the major complications of congenital NDI. Hoekstra et al. studied 17 patients and found that the IQ of more than half of the patients can reach normal levels, and less than half of the patients have varying degrees of IQ. , distraction and psychological barriers.

6. urinary tract water

Patients with this disease have long-term urinary flow, urinary tract obstruction can also occur urinary tract water, long-term urinary tract water can induce or aggravate chronic renal failure, Zender et al reported a case of NDI adult patients, bilateral hydronephrosis, Ureteral effusion, bladder dilatation, chronic renal failure, rupture of the left ureter after minor trauma.

7. Brain tissue calcification

The disease is often accompanied by intracranial calcification, and its incidence increases with the prolongation of the disease course. It is related to the quality control of polyuria and polydipsia, which can cause seizures.

8. High prostaglandin E syndrome (hyperprostaglandin E syndrome)

Urinary prostaglandin E excretion increased significantly, congenital and acquired have occurred, control of this phenomenon can make the clinical manifestations of NDI ease.

9. The performance of the primary disease

Acquired NDI has the clinical manifestations of the underlying disease and the corresponding renal pathological changes. Some patients have mild symptoms and are incomplete NDI. In addition to the long-term use of lithium salt, drug-induced NDI causes NDI to be mainly found in ICU. Critically ill patients who receive multiple medications, especially antibiotics and antineoplastics.

10. Pathological changes

There is no significant pathological change in this disease. Adult patients can find some ultra-microscopic changes. Ishii reported a case of 58-year-old congenital NDI. Kidney biopsy found that the mitochondria of the collecting duct epithelial cells became smaller and rounded, and the brush margin decreased.

Pediatric renal diabetes insipidus examination

1. The disease is related to two gene mutations

One is the vasopressin type 2 receptor gene mutation (sexually linked recessive inheritance), located on the X chromosome q27-28, has found more than 60 variants, and the second is the water channel-2 gene mutation, which is autosomal dominant or Recessive inheritance, the coding gene is located on the autosome 12q13.

2. Urine check

The urine specific gravity is less than 1.005, the urinary permeation is less than 200mOsm/(kg·H ₂ O), and the solute diuretic can only be 280-300mOsm/(kg·H ₂ O).

3. Blood test

May have hypernatremia, hyperchloremia and so on. Blood sodium>150mmol/L, advanced NPN and creatinine can be increased, B-ultrasound, imaging and other tests can find too much amniotic fluid, hydronephrosis after birth, ureteral hydrops, bladder dilatation, etc., brain X-ray examination, CT examination can be found in brain tissue calcification, EEG has abnormal waves or epileptiform discharge.

Diagnosis and diagnosis of renal diabetes insipidus in children

diagnosis

1. Qualitative diagnosis of adult patients with daily urine output greater than 2.5L, or daily urine output greater than 30ml / kg, exclusion of osmotic diuretic factors (using mannitol or diabetes) and the use of diuretics and other factors caused by polyuria, can be diagnosed For diabetes insipidus, according to the age of onset, typical symptoms (polyuria, dehydration, polydipsia, fever, etc.), combined with family history and laboratory tests and exclusion of other causes of polyuria can make the diagnosis of this disease.

2. Etiology diagnosis After the above qualitative diagnosis is diagnosed as NDI, it is necessary to further clarify whether NDI is primary or acquired. The primary person can be clearly identified through family survey, and the conditional hospital can also perform genetic analysis and acquisition. The clinical manifestations of the corresponding systemic diseases are not difficult to diagnose.

Differential diagnosis

After diagnosis of diabetes insipidus, it is necessary to identify pituitary diabetes insipidus, mental polydipsia, polyuria, CDI and NDI.

1. Clinical characteristics of mental polydipsia and CDI

(1) Mental polydipsia: more common in women, often have mental factors, variable urine output, nocturia is worse than white diarrhea, may be associated with other neurosis, long-term forced hydration can make kidney-medullary The osmotic gradient was eluted. Although ADH was applied to the renal tubules, although the water channel was open, there was no hyperosmotic state in the renal interstitium, water could not be absorbed, and urine remained confined, which made the differential diagnosis difficult.

(2) CDI: refers to the hypothalamic or (and) pituitary lesions caused by insufficient secretion of ADH secretion, the clinical feature is that in the presence of polyuria and polydipsia, physiological ADH secretion stimulating factors can not cause appropriate secretion and release of ADH.

2. Differential diagnosis steps

(1) Determination of plasma permeation and/or blood sodium concentration: Determination of basal plasma permeation and/or serum sodium ion concentration in the case of free water intake, if greater than 295 mOsm / (kg · H2O) or 143 mmol / L, respectively, Psychotic polydipsia can be ruled out, and the diagnosis process goes directly to step (3) to distinguish between CDI and NDI. When blood glucose and urea nitrogen are elevated, the determination of serum sodium concentration is more accurate.

(2) Water-retaining test: If the basal plasma osmotic amount and sodium concentration are not increased, the water-capture test is first performed. If the body weight drops by 5%, the plasma osmotic amount and serum sodium concentration increase to 295 mOsm/(kg·H2O) or 143 mmoL. /L, urine concentration, the diagnosis of mental polydipsia is established; if blood, osmolality and serum sodium concentration can not meet the above criteria, urine can not be concentrated, the diagnostic procedure goes to step (3).

(3) Injection of ADH water: 0.01U/kg, 1 time every 30 minutes in 2 hours, if the maximum urinary exudation is more than 50% more than before the test, the CDI diagnosis is established; if the above criteria are not met, then 0.05 U/kg ADH water was administered to distinguish between partial and complete NDI.

(4) Determination of ADH, plasma and urinary osmolality: if the water absorption test causes urine concentration, then mental polydipsia, partial NDI and incomplete CDI are possible, at this time, at the end of the water withdrawal test, Plasma ADH levels, plasma osmolality and urinary osmolality were measured and compared with serum ADH-serum osmolality or serum ADH-urinary osmolality. The former helped distinguish between mental polydipsia and CDI; the latter helped To distinguish between partial and complete NDI, if serum permeation is not sufficient to distinguish between normal and abnormal ADH [>295mOsm/(kg·H2O)], inject 3% sodium chloride at a rate of 0.1mg/(kg·min). 2h, repeated determination of plasma osmolality and ADH level, water-free test diagnosis of diabetes insipidus, about 25% of patients still can not be clearly diagnosed, the difficulty of differential diagnosis in the difference between mental polydipsia and partial CDI, single The serum ADH assay does not completely distinguish between the two conditions above.

(5) 1-Deamin-8-dextro-arginine vasopressin test: If it is difficult to determine serum ADH, the patient is hospitalized with 1-deamin-8-dextro-arginine vasopressin ( 1-desamino-8-d-arginine vasopressin) 25g, once every 12 hours, the course of treatment is 2 days, close observation of changes in the condition, such as polyuria and polydipsia correction, and no hyponatremia, CDI diagnosis is established, if more Urinary improvement, no change in drinking, or the occurrence of water poisoning, it is very likely to be mental polydipsia, immediately stop the above treatment, determine ADH, confirm the diagnosis, if ADH treatment does not improve polyuria and polydipsia, then For NDI, greater doses of ADH treatment in some patients can distinguish between complete and incomplete NDI.

(6) Determination of urinary AQP2: Kanno et al. studied the significance of measuring AQP2 in urine for the diagnosis of NDI. The results showed that the soluble components and binding components of AQP2 can be measured in the urine. After the normal person changes from the water-free state to the water load, Urinary AQP2 decreased significantly. After administration of desmopressin, urinary AQP2 increased significantly. The response of CDI patients after ADH was the same as that of normal people, but NDI patients did not have this reaction, so they believed that urine AQP2 measurement can be used for diagnosis. The renal response to ADH, it is worth noting that sometimes mental distress, CDI and NDI can coexist, which increases the complexity of differential diagnosis, Posner et al reported that a case of lithium salt caused by NDI patients with transient CDI, Sone et al reported a case of a 50-year-old patient with psychiatric polydipsia causing a gradient of renal cortical-medullary osmolality with concurrent NDI.

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