Hyponatremia and Renal Sodium Wasting in patients receiving cisplatinum

Three children with malignant solid tumors developed hyponatremia with renal sodium wasting associated with other signs of tubular dysfunction, such as hypokalemia or hypomagnesemia, a few days after cisdiammine dichloroplatinum (CDDP) administration. The normalization of serum electrolyte disturbances was obtained with increased parenteral intakes in fluids and electrolytes, and renal sodium wasting stopped by itself a few days later     

Hyponatremia and Renal Sodium Wasting in patients receiving cisplatinum

Three children with malignant solid tumors developed hyponatremia with renal sodium wasting associated with other signs of tubular dysfunction, such as hypokalemia or hypomagnesemia, a few days after cisdiammine dichloroplatinum (CDDP) administration. The normalization of serum electrolyte disturbances was obtained with increased parenteral intakes in fluids and electrolytes, and renal sodium wasting stopped by itself a few days later     

Fludrocortisone therapy in cerebral salt wasting

Cerebral salt wasting is an increasingly recognized condition in pediatrics and is characterized by inappropriate natriuresis and volume contraction in the presence of cerebral pathology. Diagnosis can be difficult and therapy challenging. A few single case reports of the successful use of fludrocortisone exist. We report 4 patients with cerebral salt wasting, all of whom presented with hyponatremia in the presence of known intracerebral pathology. All had clinically significant hyponatremia, and 3 had hyponatremic seizures. Two of the patients also satisfied clinical criteria for diabetes insipidus. They all were treated with regimens using increased sodium and fluid administration but experienced ongoing salt wasting. Fludrocortisone was instituted in all 4 patients and in 3 resulted in rapid improvement in net sodium balance, enabling the weaning of hypertonic fluids and stabilization of serum electrolytes. In 3 patients, fludrocortisone treatment was complicated by hypokalemia, and in 1 patient by hypertension, which necessitated a dose reduction or brief cessation of therapy. Duration of therapy was 4 to 125 days. Cerebral salt wasting presents considerable management challenges; however, fludrocortisone therapy can be an effective adjunct to treatment.     

Central Diabetes Insipidus and Cisplatin‐Induced Renal Salt Wasting Syndrome: A Challenging Combination

We describe a 2‐year‐old female with a suprasellar primitive neuroectodermal tumor and central diabetes insipidus (DI) who developed polyuria with natriuresis and subsequent hyponatremia 36 hr after cisplatin administration. The marked urinary losses of sodium in combination with a negative sodium balance led to the diagnosis of cisplatin‐induced renal salt wasting syndrome (RSWS). The subsequent clinical management is very challenging. Four weeks later she was discharged from ICU without neurological sequela. The combination of cisplatin‐induced RSWS with DI can be confusing and needs careful clinical assessment as inaccurate diagnosis and management can result in increased neurological injury.     

Renal response to vasopressin in premature infants: what is new?

Clinical and experimental data indicate that the neonatal pituitary is capable of responding with arginine vasopressin (AVP) release to physiological stimulation and pathological events commonly seen in the perinatal period. The limited concentrating performance of the newborn kidney is thought, therefore, to be accounted for by the diminished end-organ responsiveness to AVP and the inability of the immature kidney to generate and maintain deep corticopapillary osmotic gradient. Evidence has been provided to indicate that in low birth weight premature infants the impaired renal tubular sodium transport, the renal salt wasting and late hyponatremia, and the increased renal prostaglandin production may be important factors in attenuating renal response to AVP.     

Intracraneal epidural abscess as a complication of sinusitis

Familiar hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare syndrome belonging to the group of heterogeneous tubular diseases whose common characteristic is renal magnesium wasting. We present a 9 year old boy with polyuria, polydipsia and enuresis. Radiologic and ultrasonographic examinations showed nephrocalcinosis. Hypomagnesemia, normokaliemia, hypermagnesiuria, hypercalciuria, incomplete distal tubular acidosis, hypocitraturia and mild renal failure were found. Treatment with magnesium salts, hydrochlorothiazide, potassium citrate and sodium bicarbonate did not restore magnesium or calcium levels to normal. Renal function and nephrocalcinosis remain stable after 3 year's treatment. In conclusion, we report a new case of this rare syndrome caused by a congenital defect in magnesium reabsorption and discuss the evolution of the illness during 3 years' treatment.     

Hyponatriämie bei Säuglingen und Kleinkindern

Background

Oral as well as intravenous application of sodium chloride (NaCl) in infants and small children with hyponatremia is not free of problems when given for a longer period.

Patients and methods

We report here on seven children (diagnoses: Bartter syndrome (n=2), cerebral salt wasting syndrome, congenital adrenal hyperplasia with salt wasting, chronic renal failure, syndrome of inappropriate ADH secretion, pseudohypoaldosteronism) who were treated with microencapsulated NaCl. Crystalline NaCl was coated by a fluid bed spray procedure with ammonium methacrylate copolymer (Eudragit^®).

Results

Median patient age at treatment start was 19 months (range: 3 weeks–4 years); median duration of therapy was 9 months (7 weeks–14 months). Treatment was well tolerated, because the granulate could be easily mixed with the preferred food of the children, such as pudding and pap. From the mothers’ viewpoints coated NaCl for oral substitution was preferred to oral sodium solutions.

Discussion

Microencapsulated NaCl can be used successfully for oral treatment of hyponatremia in infants and young children.     

Fludrocortisone treatment in a child with severe cerebral salt wasting.

Hyponatremia is a common complication of intracranial disease or surgery. An evaluation should be undertaken to determine whether cerebral salt wasting (CSW) or inappropriate secretion of antidiuretic hormone is present as a cause. Since the treatment principles are completely different in the two pathological states, differential diagnosis is very important. CSW is defined as the renal loss of sodium leading to hyponatremia and decreased extracellular fluid volume. In the literature, it has been noted that mineralocorticoid administration can be useful in CSW cases. We herein present an 11-year-old boy who developed hyponatremic seizures after intracranial tumor resection. He was diagnosed with CSW on the basis of high urinary sodium excretion and increased urine output, together with signs and symptoms of dehydration. Despite intensive fluid and salt therapy, we were unable to decrease the urinary output. Therefore, fludrocortisone therapy was administered and his urinary output and sodium excretion were decreased and his serum sodium level was normalized. In conclusion, in addition to fluid and salt replacement, mineralocorticoid supplementation also seems to be a safe and effective treatment for CSW.     

Cerebral salt wasting in a child with cervicothoracic hematoma

Although the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is commonly observed in patients with acute or chronic central nervous system (CNS) disorders, cerebral salt wasting (CSW) that results in hyponatremia has rarely been reported in children. Both SIADH and CSW result in increased urinary sodium excretion and hyponatremia. However, the management protocols for these two conditions are quite different; volume restriction is used in treating SIADH, while volume expansion is necessary for the treatment of CSW. We present a case of CSW in a child with cervicothoracic hematoma secondary to head and cervicothoracic trauma, without evidence of brain edema. The child was diagnosed on the basis of high urinary sodium excretion resulting in hyponatremia and low serum osmolarity. Improvements in serum sodium levels after saline hydration confirmed this diagnosis. We believe that potentially dangerous cases of hyponatremia should be carefully evaluated in children with cervicothoracic hematoma secondary to trauma, including situations in which brain edema is absent.     

Hyponatraemia and hypovolemic shock with tuberculous meningitis

A 12-year-old boy with tuberculous meningitis and hydrocephalous, after undergoing revision of ventriculo-peritoneal shunt had persistent impairment of sensorium and episodes of hyponatremia (serum sodium 104 to 125 mmol/l), accompanied by polyuria, signs of poor peripheral, perfusion hypotension and low CVP, and high urinary sodium excretion (114–60 mmol/ I). A diagnosis of cerebral salt wasting syndrome (CSWS) was made and was treated with saline replacement and fludrocortisone (10 μg/kg/day). Within next 3 days the sensorium, signs of shock, urine output and serum and urinary sodium returned to normal. The case illustrates that life-threatening hyponatremia in a child with neurological illness could be caused by CSWS, which must be differentiated from Syndrome of inappropriate antidiuretic hormone secretion (SIADH), as CSWS requires rigorous salt and volume replacement in contrast to fluid restriction in SIADH.     

Chronic hypomagnesemia and hypokalemia due to renal wasting in siblings

A 13 year old girl with carpopedal spasm is presented. Investigation values showed hypomagnesemia and hypokalemia. Her younger brother and sister demonstrated the same biochemical abnormalities without any symptoms. Their urinary excretion of magnesium and potassium were inappropriately high compared with their serum levels. Treatment with oral magnesium sulfate failed to correct the abnormalities, but serum levels of magnesium and potassium were just below the lower limits. This familial disease may represent congenital renal wasting of magnesium and potassium.     

Severe renal osteodystrophy without elevated serum immunoreactive parathyroid hormone concentrations in hypomagnesemia due to renal magnesium wasting

An 8 1/2-year-old girl presented with a long history of seizures, growth retardation, muscle weakness, gait disturbance, and hearing loss. Her evaluation revealed chronic moderate renal failure (serum creatinine 2.2 mg/dL), severe hypocalcemia (5 mg/dL), hyperphosphatemia (8.1 mg/dL), hypomagnesemia (1.5 mg/dL), increased urinary magnesium excretion (2 mg/kg/d), high fractional excretion of magnesium (21.7%), hypokalemia (3.2 mEq/L), and hyperkaliuria (26 mEq/L). Low circulating immunoreactive parathyroid hormone levels for the degree of the hypocalcemia (serum N-parathyroid hormone 212 pg/mL) and severe rickets without evidence of osteitis fibrosa cystica were found. The patient probably has primary renal leak hypomagnesemia (magnesuric hypomagnesemia) which caused impaired secretion of immunoreactive parathyroid hormone leading to severe hypocalcemia and calcium deficiency rickets. Treatment with magnesium and calcium supplements, calcitriol, and aluminum hydroxide resulted in marked clinical, biochemical, and radiologic improvement. Calcium deficiency rickets due to primary or secondary renal magnesium wasting in conjunction with moderate renal failure represents a largely unrecognized metabolic bone disease.     

Familial hypomagnesemia, hypercalciuria with nephrocalcinosis syndrome: report of a case

Familial hypomagnesemia and hypercalciuria with nephrocalcinosis is a rare autosomal recessive disease characterized by renal calcium and magnesium wasting, evolving in the progressive decrease of renal function, eventually requiring kidney transplant. Clinical findings include urinary infection, polyuria, polydipsia, cramps, tremors, convulsions, among others; these, associated to ocular and/or auditive abnormalities. We present a 4 year-old female with the syndrome, which was manifested by typical signs and symptoms in daily practice: fever, abdominal pain, polyuria and polydipsia. These symptoms may defer the diagnosis of the syndrome.     

Bilateral slipped capital femoral epiphysis in a male adolescent with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), chronic renal failure, and severe hyperparathyroidism

Slipped capital femoral epiphysis (SCFE) is the most common orthopedic hip disorder affecting otherwise healthy adolescents. The majority of SCFE cases are classified as idiopathic; rarely, it may be secondary to different endocrinopathies including hyperparathyroidism due to chronic renal failure (CRF). However, over the last decades, the association between SCFE and CRF has almost disappeared, probably due to better management of renal osteodystrophy. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC, OMIM no. 248250) is a rare autosomal recessive tubulopathy characterized by renal wasting of calcium and magnesium leading to hypomagnesemia, hypercalciuria, nephrocalcinosis, and CRF. Patients usually show hyperparathyroidism before the onset of advanced CRF caused by FHHNC-related metabolic disturbances. We report on a 15-year-old patient with FHHNC and CRF who developed extreme hyperparathyroidism and high-grade bilateral SCFE after self-discontinuation of supportive treatment of underlying conditions. Conclusion: We believe that SCFE was caused not only by untreated CRF but also by metabolic disturbances related to FHHNC. To prevent this complication, careful management of disturbances of calcium, phosphate, and magnesium homeostasis seems to be crucial.     

Fetal pseudohypoaldosteronism: another cause of hydramnios

Pseudohypoaldosteronism (PHA) is a rare hereditary salt–wasting syndrome which is caused by decreased renal tubular responsiveness to aldosterone. The syndrome consists of hyponatremia, hyperkalemia, dehydration, failure to thrive and increased urinary salt loss. A case of PHA was previously described where fetal polyuria was the probable cause of hydramnios. We present four new cases of PHA, from two families, who were born after pregnancies complicated by severe hydramnios and premature labor. We suggest that PHA should be included in the differential diagnosis of hydramnios, since appropriate investigations might lead to the early diagnosis and treatment of a life–threatening disease.     

Neonatal renal venous thrombosis followed by secondary pseudohypoaldosteronism

A male infant was diagnosed as having renal venous thrombosis (RVT) in association with bilateral flank masses, macroscopic hematuria, and thrombocytopenia. In the course of supportive treatment, hyponatremia, hyperkalemia, and metabolic acidosis became prominent. Plasma renin activity (PRA) and aldosterone increased markedly. Treatment with sufficient sodium chloride and sodium bicarbonate intake was effective. It is important to note that tubular damage by RVT causes secondary pseudohypoaldosteronism.     

Calcitonin therapy of children with osteogenesis imperfecta

Two children, ages 13 2/12 and 6 6/12 years, with osteogenesis imperfecta were treated with salmon calcitonin. During the course of therapy the older child developed calcitonin dose-related hypomagnesemia on two occasions. The younger child, coincident with otitis media and vomiting, developed hypomagnesemia, hypophosphatemia, hyponatremia, and hypokalemia. Since rib biopsies obtained before and after one year of treatment with salmon calcitonin failed to demonstrate any histologic changes, therapy was discontinued because of the induced metabolic consequences of calcitonin therapy.     

Acute and chronic effects of cisplatin therapy on renal magnesium homeostasis

Although the acute renal toxicity of cisplatin has been well documented, long-term follow-up studies in cisplatin-treated children are scanty. We have evaluated the incidence and characteristics of both acute and chronic nephrotoxicity in 22 children (median age 8 years) treated with cisplatin as part of different chemotherapeutic protocols. All patients exhibited a significant and progressive decrease in plasma magnesium (Mg) values soon after cisplatin administration. Magnesiuria also increased immediately after therapy. Hypomagnesemia (plasma Mg <1.4 mg/dl) occurred in 10 patients and it was dose-dependent. Minimal and mean cumulated doses inducing hypomagnesemia were 300 and 500 mg/m², respectively. In 18 children we followed renal function prospectively for a mean time of 2.3 years after arrest of cisplatin therapy. Chronic hypomagnesemia and moderate elevation of plasma creatinine were observed in 6 children, hypocalciuria in 5 children, and hypokalemia in 1 child. Presence of hypomagnesemia was unrelated to the total dose received or the time elapsed since cisplatin therapy. Renal function studies, performed in the 6 children with chronic hypomagnesemia, revealed different degrees of impairment in Mg reabsorption. The functional characteristics of chronic cisplatin nephrotoxicity found in the present series—contrary to prior reports—are not comparable to those present in the inherited Gitelman's syndrome. © 1997 Wiley-Liss, Inc.     

Cerebral salt wasting syndrome following brain injury in three pediatric patients: suggestions for rapid diagnosis and therapy

The association between hyponatremia and intracranial pathology has been well described. When accompanied by natriuresis, hyponatremia has most commonly been attributed to inappropriate secretion of antidiuretic hormone. However, there is growing evidence to suggest that many of these patients may actually have cerebral mediated salt losses, a disorder referred to as the cerebral salt wasting syndrome (CSWS). While this syndrome has been reasonably well described in adults, data regarding CSWS in pediatric-aged patients remains sparse. Since fluid management of these disorders is different, it is important that the clinician be able to rapidly differentiate between them. We report three cases of CSWS in acutely brain-injured children and comment on the role that early quantitation of urine volume and urine sodium concentration had in rapidly establishing the correct diagnosis.     

Hyponatremia in hospitalized critically Ill children : Current concepts

Hyponatremia (serum sodium to <136 mEqJl) is the most common electrolyte abnormality in critically ill children. It could result from a deficit of sodium, or surplus of water. Impaired water excretion, ‘inappropriate’ release of vasopressin, use of hypotonic fluids, redistribution of sodium and water, sick cell syndrome, several drugs and primary illness all may contribute to hyponatremia. Acute hyponatremia, defined as a fall in serum sodium to -120 mEqJl within 48 hours may result in acute cerebral edema and brain stem herniation particularly in children. However, there is paucity of data on hyponatremia in hospitalized critically ill patients. Studies addressing incidence, cause and outcome of hyponatremia in critically ill patients are needed to plan rational fluid therapy protocols, and resolve the current debate, which calls for abandonment of NJ5 saline in 5% dextrose solution as maintenance intravenous fluid in favour of normal saline to prevent hyponatremia. At present it is not fully correct to assume that isotonic maintenance fluids would be superior to current maintenance fluids. Reducing the volume of maintenance fluid to about 75% of normal maintenance volume may be more appropriate way to prevent hyponatremia in view of water retaining effect of high ADH and reduced renal free water clearance in critically ill children.