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The polyuria and polydipsia state in diabetes insipidus (DI) can be challenging to manage for patients and clinicians with significant impact on the patients' well-being. A review of literature shows that nonsteroidal anti-inflammatory drugs (NSAIDs), thiazide and potassium-sparing diuretics, along with low dietary solute and protein, and high water intake remain the standard medical therapy. Although these therapeutic approaches improve symptoms, the urine-concentrating defect is still considerable, posing a serious risk to patient's life from hypovolemia if high fluid intake is not maintained. Our case describes the challenges faced with the medical management of a patient with nephrogenic DI that was only partially responsive to standard medical therapy, resulting in debilitating effects on the patient's quality of life.

A 3-month-old infant was examined for inconsolable crying with polydipsia, polyuria, and rapid weight gain. Unexpectedly, the symptoms resolved spontaneously during hospitalization but were aggravated 2 weeks after discharge, with the patient presenting a Cushingoid appearance. Investigations ruled out diabetes mellitus and nephrogenic diabetes insipidus but indicated adrenocortical suppression by exogenous glucocorticoids, which were discovered via toxicologic analysis of her previously compounded omeprazole suspension. After discontinuing the omeprazole suspension, the infant recovered fully and the laboratory results normalized. This case shows us that the assumption of appropriate medication intake may conceal unexpected medication errors. Following this case, the current literature on the benefits and risks of compounding and its impact on patient health is discussed., Competing Interests: Declaration of Competing Interest The authors declare no conflicts or financial interest., (Copyright © 2023 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background: Intensive care management of diabetic ketoacidosis (DKA) is targeted to reverse ketoacidosis, replace the fluid deficit, and correct electrolyte imbalances. Adequate restoration of circulation and treatment of shock is key. Pediatric treatment guidelines of DKA have become standard but complexities arise in children with co-morbidities. Congenital nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by impaired kidney concentrating ability and treatment is challenging. NDI and DKA together have only been previously reported in one patient., Case Diagnosis/treatment: We present the case of a 12-year-old male with NDI and new onset DKA with hyperosmolality. He presented in hypovolemic shock with altered mental status. Rehydration was challenging and isotonic fluid resuscitation resulted in increased urine output and worsening hyperosmolar state. Use of hypotonic fluid and insulin infusion led to lowering of serum osmolality faster than desired and increased the risk for cerebral edema. Despite the rapid decline in serum osmolality his mental status improved so we allowed him to drink free water mixed with potassium phosphorous every hour to match his urinary output (1:1 replacement) and continued 0.45% sodium chloride based on his fluid deficit and replacement rate with improvement in his clinical status., Conclusions: This case illustrates the challenges in managing hypovolemic shock, hyperosmolality, and extreme electrolyte derangements driven by NDI and DKA, as both disease processes drive excessive urine output, electrolyte and acid-base imbalances, and rapid fluctuation in osmolality., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Rationale: Almost 90% of congenital nephrogenic diabetes insipidus (NDI) cases are caused by mutations in the arginine vasopressin receptor 2 gene, which has X-linked recessive inheritance. Although NDI is commonly diagnosed in early infancy based on its characteristic findings, clinical diagnosis can be delayed when no other family members have been diagnosed with NDI because several findings of NDI are nonspecific., Patient Concerns: A 3-month-old boy diagnosed with NDI presenting with osmotic demyelination syndrome (ODS) was admitted for poor weight gain after birth and poor feeding during the week prior to admission., Diagnosis: On admission, the initial blood examination showed hypernatremia (158 mmol/L), and treatment with intravenous fluids over the next 2 days further elevated the serum sodium level (171 mmol/L). After admission, polyuria was recognized, and polyuria in his grandmother and mother since childhood without a diagnosis of NDI was found. Magnetic resonance imaging showed multifocal, symmetrical lesions, including the lateral pons, on diffusion- and T2-weighted imaging, which led to a diagnosis of ODS., Intervention: The infusion was stopped, and the patient was fed milk diluted 2-fold with water., Outcomes: The serum sodium level gradually decreased to 148 mmol/L over the course of 1 week. Low-sodium milk was started at 4 months of age and maintained a serum sodium level of approximately 140 mmol/L, which was within the normal range. The developmental quotient was 94 at 4 years of age., Lessons: ODS is an encephalopathy resulting from extreme fluctuations in serum sodium concentration and plasma osmolality. ODS due to hypernatremia has been reported in several patients, although it usually occurs during rapid correction of hyponatremia. Consequences of the central nervous system are a critical complication of NDI that affects prognosis. These consequences can be avoided with treatment. Early blood examination or polyuria in the patient, mother, or another family member and hypernatremic dehydration with good urine output should lead to an early diagnosis and prevent central nervous system consequences., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: The genetic characteristics in neonates admitted to the NICU with recurrent hypernatremia remained unknown. We aimed to implement early genetic sequencing to identify possible genetic etiologies, optimize the treatment, and improve the outcome., Methods: We prospectively performed exome sequencing or targeted panel sequencing on neonates diagnosed with recurrent hypernatremia (plasma sodium ≥150 mEq/L, ≥2 episodes) from January 1, 2016, to June 30, 2020., Results: Among 22,375 neonates admitted to the NICU, approximately 0.33% (73/22,375) developed hypernatremia. The incidence of hypernatremia >14 days and ≤14 days was 0.03% and 0.3%, respectively. Among 38 neonates who had ≥2 hypernatremia episodes, parents of 28 patients consented for sequencing. Genetic diagnosis was achieved in 25% neonates (7/28). Precision medicine treatment was performed in 85.7% (6/7) of the patients, including hydrochlorothiazide and indomethacin for 57.1% (4/7) with arginine vasopressin receptor 2 (AVPR2) deficiency-associated congenital nephrogenic diabetes insipidus; a special diet of fructose formula for 1 patient with solute carrier family 5 member 1 deficiency-associated congenital glucose-galactose malabsorption (1/7, 14.3%); and kallikrein-inhibiting ointment for 1 patient with serine protease inhibitor of Kazal-type 5 deficiency-associated Netherton syndrome (1/7, 14.3%). Only hypernatremia onset age (adjusted odds ratio 1.32 [1.01-1.72], p = 0.040) independently predicted the underlying genetic etiology. The risk of a genetic etiology of hypernatremia was 9.0 times higher for neonates with a hypernatremia onset age ≥17.5 days (95% confidence interval, 1.1-73.2; p = 0.038)., Conclusions: Single-gene disorders are common in neonates with recurrent hypernatremia, and >50% of cases are caused by AVPR2 deficiency-associated congenital nephrogenic diabetes insipidus. Early genetic testing can aid the diagnosis of unexplained recurrent neonatal hypernatremia and improve therapy and outcome., (© 2021 S. Karger AG, Basel.)

Background: Diabetes insipidus (DI) can be a common cause of polydipsia and polyuria. Here, we present a case of congenital nephrogenic diabetes insipidus (CNDI) accompanied with central diabetes insipidus (CDI) secondary to pituitary surgery., Case Presentation: A 24-year-old Chinese woman came to our hospital with the complaints of polydipsia and polyuria for 6 months. Six months ago, she was detected with pituitary apoplexy, and thereby getting pituitary surgery. However, the water deprivation test demonstrated no significant changes in urine volume and urine gravity in response to fluid depression or AVP administration. In addition, the genetic results confirmed a heterozygous mutation in arginine vasopressin receptor type 2 (AVPR2) genes., Conclusions: She was considered with CNDI as well as acquired CDI secondary to pituitary surgery. She was given with hydrochlorothiazide (HCTZ) 25 mg twice a day as well as desmopressin (DDAVP, Minirin) 0.1 mg three times a day. There is no recurrence of polyuria or polydipsia observed for more than 6 months. It can be hard to consider AVPR2 mutation in female carriers, especially in those with subtle clinical presentation. Hence, direct detection of DNA sequencing with AVPR2 is a convenient and accurate method in CNDI diagnosis.

Background: Disorders of water and sodium balance can occur after brain injury. Prolonged polyuria resulting from central diabetes insipidus and cerebral salt wasting complicated by gradient washout and a type of secondary nephrogenic diabetes insipidus, however, has not been described previously, to the best of our knowledge. We report an unusual case of an infant with glioblastoma who, after tumor resection, was treated for concurrent central diabetes insipidus and cerebral salt wasting complicated by secondary nephrogenic diabetes insipidus., Case Presentation: A 5-month-old Hispanic girl was found to have a large, hemorrhagic, suprasellar glioblastoma causing obstructive hydrocephalus. Prior to mass resection, she developed central diabetes insipidus. Postoperatively, she continued to have central diabetes insipidus and concurrent cerebral salt wasting soon after. She was managed with a vasopressin infusion, sodium supplementation, fludrocortisone, and urine output replacements. Despite resolution of her other major medical issues, she remained in the pediatric intensive care unit for continual and aggressive management of water and sodium derangements. Starting on postoperative day 18, her polyuria began increasing dramatically and did not abate with increasing vasopressin. Nephrology was consulted. Her blood urea nitrogen was undetectable during this time, and it was thought that she may have developed a depletion of inner medullary urea and osmotic gradient: a "gradient washout." Supplemental dietary protein was added to her enteral nutrition, and her fluid intake was decreased. Within 4 days, her blood urea nitrogen increased, and her vasopressin and fluid replacement requirements significantly decreased. She was transitioned soon thereafter to subcutaneous desmopressin and transferred out of the pediatric intensive care unit., Conclusions: Gradient washout has not been widely reported in humans, although it has been observed in the mammalian kidneys after prolonged polyuria. Although not a problem with aquaporin protein expression or production, gradient washout causes a different type of secondary nephrogenic diabetes insipidus because the absence of a medullary gradient impairs water reabsorption. We report a case of an infant who developed complex water and sodium imbalances after brain injury. Prolonged polyuria resulting from both water and solute diuresis with low enteral protein intake was thought to cause a urea gradient washout and secondary nephrogenic diabetes insipidus. The restriction of fluid replacements and supplementation of enteral protein appeared adequate to restore the renal osmotic gradient and efficacy of vasopressin.

Background: Xylitol is an approved food additive that is widely used as a sweetener in many manufactured products. It is also used in pharmaceuticals. Secondary oxalosis resulting from high dietary oxalate has been reported. However, reported cases of oxalosis following xylitol infusion are rare., Case Presentation: A 39-year-old man with a 16-year history of organic psychiatric disorder was hospitalized for a laparoscopic cholecystectomy because of cholecystolithiasis. He had been treated with several antipsychotics and mood stabilizers, including lithium. The patient had polyuria (> 4000 mL/day) and his serum sodium levels ranged from 150 to 160 mmol/L. Urine osmolality was 141 mOsm/L, while serum arginine vasopressin level was 6.4 pg/mL. The patient was diagnosed with nephrogenic diabetes insipidus (NDI), and lithium was gradually discontinued. Postoperative urine volumes increased further to a maximum of 10,000 mL/day, and up to 10,000 mL/day of 5% xylitol was administered. The patient's consciousness level declined and serum creatinine increased to 4.74 mg/dL. This was followed by coma and metabolic acidosis. After continuous venous hemodiafiltration, serum sodium improved to the upper 140 mmol/L range and serum creatinine decreased to 1.25 mg/dL at discharge. However, polyuria and polydipsia of approximately 4000 mL/day persisted. Renal biopsy showed oxalate crystals and decreased expression of aquaporin-2 (AQP2) in the renal tubules. Urinary AQP2 was undetected. The patient was discharged on day 82 after admission., Conclusions: Our patient was diagnosed with lithium-induced NDI and secondary oxalosis induced by excess xylitol infusion. NDI became apparent perioperatively because of fasting, and an overdose of xylitol infusion led to cerebrorenal oxalosis. Our patient received a maximum xylitol dose of 500 g/day and a total dose of 2925 g. Patients receiving lithium therapy must be closely monitored during the perioperative period, and rehydration therapy using xylitol infusion should be avoided in such cases.

Background: Nephrogenic diabetes insipidus (DI) secondary to a urinary tract obstruction is a rare condition. Herein, we report a case of partial nephrogenic DI due to obstructive uropathy in a patient with Castleman's disease., Case Presentation: A 78-year-old man underwent computed tomography (CT) at his local hospital because of persistent edema of the leg and polyuria (both lasting approximately 2 months); retroperitoneal fibrosis was detected on the CT scan. An abdominal CT scan showed bilateral hydronephrosis, and a surgical biopsy of the para-aortic lymph node revealed Castleman's disease. To resolve the hydronephrosis, a double J stent was inserted; however, his polyuria continued. As his serum osmolality (311 mOsm/kg) was greater than 300 mOsm/kg, and his serum sodium level was 149 mEq/L, a water deprivation test was not performed. On a vasopressin challenge test, his urine was not sufficiently concentrated to the expected range, indicating partial nephrogenic DI. He was treated with hydrochlorothiazide (25 mg/day), and his urine output gradually decreased to within the normal range. The patient recovered uneventfully and underwent treatment for Castleman's disease., Conclusion: To the best of our knowledge, this is the first case of partial nephrogenic DI due to obstructive uropathy associated with Castleman's disease.

Nephrogenic diabetes insipidus (NDI), a rare cause of polyuria and polydipsia in children, is usually managed with medications and careful monitoring of water intake. We present a child who was incidentally found to have right hydronephrosis secondary to ureteropelvic junction obstruction, and was subsequently also diagnosed with NDI. After being medically managed, he underwent open right pyeloplasty. His polydipsia abated within 1 month of surgery, and he has done well off of medications since that time. NDI resolution after correction of obstructive uropathy in adults has been reported, but this represents a novel case in pediatrics., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A 3-day-old term, male infant presented to the emergency department for evaluation of bloody stools. The infant was born after an uncomplicated pregnancy followed by a normal spontaneous vaginal delivery. The mother was group B Streptococcus colonized, and received antenatal penicillin prophylaxis. The infant received routine delivery room care, and was given ophthalmic erythromycin and intramuscular vitamin K. Circumcision was performed without bleeding and he was discharged from the newborn nursery and the hospital after 48 hours. On the day of presentation, he had streaky bright red blood in 4 consecutive stools. After discussion with the infant's pediatrician, the parents took him to the emergency department. The infant was afebrile, nursing well without emesis, and had made ∼10 wet diapers that day. The physical examination revealed a fussy infant with mild tachycardia, tachypnea, and scleral icterus. The complete blood count was unremarkable. Serum total bilirubin was 11.9 mg/dL, sodium 156 mmol/L, chloride 120 mmol/L, potassium 4.7 mmol/L, and bicarbonate 16 mmol/L. International normalized ratio was prolonged at 2.7, prothrombin time 26.6 seconds, partial thromboplastin time 38.9 seconds. The stool was hemeoccult positive. An obstructive radiograph series of the abdomen showed a nonobstructed gas pattern. Official radiology interpretation the following day reported possible pneumatosis intestinalis in the left and right colon. Our multidisciplinary panel will discuss the assessment of bloody stools in the term newborn, evaluation of electrolyte abnormalities, the diagnosis, and patient management., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

We present a case of undiagnosed nephrogenic diabetes insipidus as a cause of acute urinary retention in a 21-year-old male soldier. Soldiers live in close quarters, and have a regimented lifestyle that may not allow for frequent voiding; therefore, undiagnosed nephrogenic diabetes insipidus may result in acute urinary retention., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Nephrogenic diabetes insipidus (NDI) is a condition resulting from the kidney's impaired response to circulating antidiuretic hormone (ADH), leading to polydipsia and polyuria. Urinary tract dilatation caused by NDI is a rare situation. Here, we report a case of congenital NDI presented with bilateral hydronephrosis.A 15-year-old boy complaining a history of intermittent fever was admitted to Peking Union Medical College Hospital. He voided 10 to 15 L of urine daily. Radiographic examination revealed severe dilatation of bilateral renal pelvis, ureter, and bladder. Urinalysis shows hyposthenuria.He was diagnosed NDI since born. Transient insertion of a urethral catheter helped to relieve fever. Medical therapy of hydrochlorothiazide and amiloride was prescribed and effective.Dilatation of urinary tract caused by diabetes insipidus is rare, but may be present in severe condition. Therefore, it is crucial for clinicians to perform early treatment to avoid impairment of renal function.

Context: The polyuria-polydipsia syndrome comprises primary polydipsia (PP) and central and nephrogenic diabetes insipidus (DI). Correctly discriminating these entities is mandatory, given that inadequate treatment causes serious complications. The diagnostic "gold standard" is the water deprivation test with assessment of arginine vasopressin (AVP) activity. However, test interpretation and AVP measurement are challenging., Objective: The objective was to evaluate the accuracy of copeptin, a stable peptide stoichiometrically cosecreted with AVP, in the differential diagnosis of polyuria-polydipsia syndrome., Design, Setting, and Patients: This was a prospective multicenter observational cohort study from four Swiss or German tertiary referral centers of adults >18 years old with the history of polyuria and polydipsia., Measurements: A standardized combined water deprivation/3% saline infusion test was performed and terminated when serum sodium exceeded 147 mmol/L. Circulating copeptin and AVP levels were measured regularly throughout the test. Final diagnosis was based on the water deprivation/saline infusion test results, clinical information, and the treatment response., Results: Fifty-five patients were enrolled (11 with complete central DI, 16 with partial central DI, 18 with PP, and 10 with nephrogenic DI). Without prior thirsting, a single baseline copeptin level >21.4 pmol/L differentiated nephrogenic DI from other etiologies with a 100% sensitivity and specificity, rendering a water deprivation testing unnecessary in such cases. A stimulated copeptin >4.9 pmol/L (at sodium levels >147 mmol/L) differentiated between patients with PP and patients with partial central DI with a 94.0% specificity and a 94.4% sensitivity. A stimulated AVP >1.8 pg/mL differentiated between the same categories with a 93.0% specificity and a 83.0% sensitivity., Limitation: This study was limited by incorporation bias from including AVP levels as a diagnostic criterion., Conclusion: Copeptin is a promising new tool in the differential diagnosis of the polyuria-polydipsia syndrome, and a valid surrogate marker for AVP. Primary Funding Sources: Swiss National Science Foundation, University of Basel.

X-linked nephrogenic diabetes insipidus (X-NDI) is a disease caused by inactivating mutations of the vasopressin (AVP) type 2 receptor (V2R) gene. Loss of V2R function prevents plasma membrane expression of the AQP2 water channel in the kidney collecting duct cells and impairs the kidney concentration ability. In an attempt to develop strategies to bypass V2R signaling in X-NDI, we evaluated the effects of secretin and fluvastatin, either alone or in combination, on kidney function in a mouse model of X-NDI. The secretin receptor was found to be functionally expressed in the kidney collecting duct cells. Based on this, X-NDI mice were infused with secretin for 14 days but urinary parameters were not altered by the infusion. Interestingly, secretin significantly increased AQP2 levels in the collecting duct but the protein primarily accumulated in the cytosol. Since we previously reported that fluvastatin treatment increased AQP2 plasma membrane expression in wild-type mice, secretin-infused X-NDI mice received a single injection of fluvastatin. Interestingly, urine production by X-NDI mice treated with secretin plus fluvastatin was reduced by nearly 90% and the urine osmolality was doubled. Immunostaining showed that secretin increased intracellular stores of AQP2 and the addition of fluvastatin promoted AQP2 trafficking to the plasma membrane. Taken together, these findings open new perspectives for the pharmacological treatment of X-NDI.

Fanconi syndrome is a complex of multiple tubular dysfunctions of proximal tubular cells, occurring alone or in association with a variety of inherited (primary) or acquired (secondary) disorders. It is characterized by aminoaciduria, normoglycemic glycosuria, tubular proteinuria without hematuria, metabolic acidosis without anion gap and excessive urinary excretion of phosphorous, calcium, uric acid, bicarbonate, sodium, potassium and magnesium. Diabetes insipidus is a disease of collecting tubules and children mainly present with dehydration and hypernatremia. We are reporting the first case of idiopathic Fanconi's syndrome along with nephrogenic diabetes insipidus in a child who presented to us with vitamin D resistant rickets. Medline search did not reveal any case of nephrogenic diabetes insipidus (NDI) associated with idiopathic Fanconi syndrome. We hypothesized that the NDI may be due to to severe hypokalemia induced tubular dysfunction.

Introduction: There are numerous causes for intracranial calcification in children. We describe an unusual cause of intracranial calcification in a child, namely, nephrogenic diabetes insipidus (NDI)., Case Report: A 12-year-old boy presented with seizures and developmental delay. MRI of the brain revealed intracranial calcification. Evaluation showed findings suggestive of NDI. The lack of evidence of any other metabolic defect suggests that these calcifications were secondary to NDI. He also had anemia for which he was investigated and diagnosed as thalassemia minor. Detailed literature review failed to reveal any reported association between NDI and thalassemia minor., Conclusion: We report this case to emphasize the importance of early diagnosis and treatment of NDI to prevent organic brain damage.

Congenital nephrogenic diabetes insipidus is a rare, hereditary in nature, characterized by an inability of the kidney to concentrate urine, secondary to the manifold resistance to the action of vasopressin. X-linked forms of transmission (90%) are expressed in boys, from the neonatal period in general, by polyuria and polydipsia. Symptomatology in transmissive girls is variable but can sometimes be quite marked. These forms are secondary to mutations in the gene encoding the vasopressin V2 receptor, located at position Xq28, responsible for a loss of function of this receptor. Some of these mutations may cause a partial phenotype, less severe. Forms of autosomal, recessive or dominant are more rare (10%). Treatment is symptomatic, sometimes difficult in infants. It aims to avoid episodes of dehydration. It is based on a conventional diet hypo-osmotic and administration of hydrochlorothiazide and indomethacin. We report here the case of a child with congenital nephrogenic diabetes insipidus hospitalized at Children's Hospital of Rabat and throughout this case we review the pathophysiology and clinical and biological characteristics of the disease and including importance of contribution of clinical biochemistry laboratory in the diagnosis and monitoring of this disease.

Polyuria has been defined as an urine output exceeding 3 I/day in adults and 2 I/m2/day in children. The most common causes are: psychogenic polydipsia, diabetes insipidus (central and nephrogenic), chronic kidney disease and uncontrolled diabetes mellitus. The article focuses on diagnostic approach to a patient with polyuria.

We present a female neonate with arthrogryposis, renal tubular abnormalities and cholestasis syndrome and complex renal structural and functional abnormalities that include medullary nephrocalcinosis, hydronephrosis, nephrogenic diabetes insipidus, Fanconi syndrome, proximal and distal hyperkalemic renal tubular acidosis, near-nephrotic range proteinuria, hypercalciuria and severe hypovitaminosis D.

We report 4 boys with diabetes insipidus associated with renal impairment and hydroureteronephrosis. The high flow states caused the bladder to become trabeculated in the absence of infravesical obstruction. Urodynamics have shown the bladder itself to be compliant, but drainage is poor leading to further renal impairment and overflow incontinence. All 4 boys have been managed with cystostomy button drainage and have done well on close follow-up., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Fanconi's syndrome is a serious condition characterized by type II proximal renal tubular dysfunction, with urinary loss of glucose, amino acids, phosphate, bicarbonate, and potassium. Ifosfamide-induced Fanconi's syndrome is reported in about 1.4-5% of children being treated for solid tumors, yet only a few cases have been reported in adults. We describe a 54-year-old man who came to the hospital with symptoms of neutropenic fever 4 days after his fourth cycle of ifosfamide and doxorubicin treatment for recurrent sarcoma with metastases to the lung. During admission, he was noted to have severe renal tubular dysfunction; ifosfamide-induced nephrogenic diabetes insipidus and Fanconi's syndrome were suspected. He received supportive therapy that resulted in incomplete resolution of signs and symptoms. The patient was discharged after a 5-day hospital stay when his white blood cell count increased from 0.1-2.5 × 10(3) /mm(3) and his fever had resolved. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of diabetes insipidus and Fanconi's syndrome and his use of ifosfamide. This dual diagnosis of diabetes insipidus and Fanconi's syndrome in an adult makes this case unusual, as well as therapeutically challenging. We conducted a review of the existing literature regarding ifosfamide-induced Fanconi's syndrome and describe the proposed mechanisms and therapeutic options. This case suggests that patients treated with ifosfamide should be monitored closely for renal function to identify, and perhaps prevent, these rare adverse events. Preliminary animal models show promise for adding N-acetylcysteine to ifosfamide treatment, but more research is necessary before using this drug as a therapeutic option., (© 2012 Pharmacotherapy Publications, Inc.)

Fanconi's syndrome is a complex of multiple tubular dysfunctions of proximal tubular cells occurring alone or in association with a variety of inherited (primary) or acquired (secondary) disorders. It is characterized by aminoaciduria, normoglycemic glycosuria, tubular proteinuria without hematuria, metabolic acidosis without anion gap and excessive urinary excretion of phosphorous, calcium, uric acid, bicarbonate, sodium, potassium and magnesium. Diabetes insipidus is a disease of collecting tubules and a child mainly presents with dehydration and hypernatremia. We report the first case of idiopathic Fanconi's syndrome along with nephrogenic diabetes insipidus (NDI) in a child who presented to us as resistant rickets. Medline search did not reveal any case of nephrogenic diabetes insipidus associated with idiopathic Fanconi's syndrome. We hypothesized that the NDI may be due to severe hypokalemia induced tubular dysfunction. The child was treated for hypophosphatemic rickets with severe metabolic acidosis and the treatment for NDI was also given. Now he has healed rickets and normal blood pH, sodium and osmolarity.

A 19-year-old girl presented at our emergency room with hypokalemic periodic paralysis. She had a thyrotoxic goiter and had experienced three paralytic attacks during the previous 2 years on occasions when she stopped taking antithyroid drugs. In addition to thyrotoxic periodic paralysis (TPP), she had metabolic acidosis, urinary potassium loss, polyuria and polydipsia. Her reduced ability to acidify urine during spontaneous metabolic acidosis was confirmed by detection of coexisting distal renal tubular acidosis (RTA). The polyuria and polydipsia were caused by nephrogenic diabetes insipidus, which was diagnosed using the water deprivation test and vasopressin administration. Her recurrent and frequent paralytic attacks may have been the combined effects of thyrotoxicosis and RTA. Although the paralytic attack did not recur after improving the thyroid function, mild acidosis and nephrogenic DI have been remained subsequently. Patients with TPP, especially females with atypical metabolic features, should be investigated for possible precipitating factors.

Central pontine myelinolysis (CPM) has been described in alcoholic patients and in the aftermath of rapid correction of chronic hyponatraemia. We describe a case of CPM occurring secondary to nephrogenic diabetes insipidus (DI), which developed as a consequence of severe hypokalaemia. A 63-year-old man with alcohol dependence was admitted to hospital with severe pulmonary sepsis and type 1 respiratory failure. On admission, he had euvolaemic hyponatraemia of 127 mmol/L, consistent with a syndrome of inappropriate antidiuretic hormone secondary to his pneumonia. Following admission, his plasma potassium dropped from 3.2 to a nadir of 2.3 mmol/L. Mineralocorticoid excess, ectopic adrenocorticotrophic hormone production and other causes of hypokalaemia were excluded. The hypokalaemia provoked significant hypotonic polyuria and a slow rise in plasma sodium to 161 mmol/L over several days. Plasma glucose, calcium and creatinine were normal. The polyuria did not respond to desmopressin, and subsequent correction of his polyuria and hypernatraemia after normalization of plasma potassium confirmed the diagnosis of nephrogenic DI due to hypokalaemia. The patient remained obtunded, and the clinical suspicion of osmotic demyelination was confirmed on magnetic resonance imaging. The patient remained comatose and passed away 10 days later. This is the first reported case of nephrogenic DI resulting in the development of CPM, despite a relatively slow rise in plasma sodium of less than 12 mmol/L/24 h. Coexisting alcohol abuse, hypoxaemia and hypokalaemia may have contributed significantly to the development of CPM in this patient.

We report on a child with X-linked nephrogenic diabetes insipidus (NDI) who developed Wilms tumor (WT). Nephrogenic diabetes insipidus is caused by mutations of the arginine vasopressin receptor (AVPR2) or aquaporin-II (AQP2) genes. Wilms tumor is also genetically heterogeneous and is associated with mutations of WT1 (15-20%), WTX (20-30%) and other loci. The boy presented at 5 months with failure to thrive, polyuria, hypernatremia and abdominal mass. Analysis of leukocyte DNA showed a novel missense mutation (Q174H) of the AVPR2 gene, which was not present in his mother. In cells (WitS) isolated from the tumor, WTX mRNA expression and coding sequence were intact. However, we identified a 44-kb homozygous deletion of the WT1 gene spanning exons 4 to 10. The WT1 deletion was not present in leukocyte DNA from the patient or his mother. We also noted strong beta-catenin (CTNNB1) expression in the tumor cells and identified a heterozygote missense Ser45Cys mutation of exon 3 of CTNNB1. However, the mutation was absent both in the constitutional DNA of the patient and his mother. The concurrence of WT and NDI has not been previously reported and may be unrelated. Nevertheless, this case nicely illustrates the sequence of events leading to sporadic Wilms tumor.

Primary nephrogenic diabetes insipidus (NDI) is a genetic, chronic disease characterised by lack of distal renal tubule to antidiuretic hormone. The condition produces polyuria, polydipsia, and consequently, reduced caloric intake and growth failure. There is very scarce information on physical growth of affected children. The objective of the paper is to describe long-term growth of 14 patients from 11 families, studied retrospectively and followed for 3-16 years (median 11.6 years). Diagnosis was made on the basis of clinical and laboratory data and concentration test under pitressin. Patients were treated with indomethacin, thiazides, and amiloride. Weight and standing height was measured periodically at the Laboratory of Anthropometry, following standardised techniques. Information was obtained from clinical notes. The majority of children grew below the third centile of local standards, and many showed improvement of weight, height, and body mass index (BMI) over time. Mean height, weight, and BMI gain during follow-up was 1.72, 1.06, and 1.46 standard deviations (SDs), respectively. Three children who did not adhere to treatment showed growth delay. Height gain during the first 2 years of follow-up was inversely associated with height deficit at diagnosis. Further studies on growth at adolescence and in different mutations are recommended.

Objectives: To determine the effect of long-term lithium therapy on glomerular filtration rate (GFR) and maximum renal concentrating capacity (Umax) in the elderly, to identify possible risk factors, to determine the clinical impact of a reduced Umax in this population and in case of polyuria to establish a diagnosis., Methods: This is a cross-sectional study with 48 outpatients of 65 years or over (mean 74.8 years), who were treated with lithium for more than 6 months (mean 9.2 years). The GFR was determined with the Cockcroft-Gault formula (GFR-CG) and the Umax was measured in a urine sample collected between 3 and 5 h after the patients received 40 microg desmopressin (DDAVP) intranasally., Results: No relation was found between duration of lithium treatment and GFR-CG, but there was a significant negative relation between duration of lithium treatment and Umax (B -0.73; CI: -1.249/-0.212); 73% of the patients had a moderate to severe concentrating defect. No other risk factors than duration of lithium therapy were identified. A reduced Umax caused polyuria (>2500 mL/24 h) in 33% but did not cause significant more thirst, incontinence or disturbed sleep., Conclusions: In this geriatric population a negative relation was found between duration of lithium treatment and Umax. But a reduced Umax did not result in significant more clinical symptoms. In case of polyuria other mechanisms beside nephrogenic diabetes insipidus were found to play a role in this age group.

Background: A 65-year-old woman presented with decreased oral intake, a reduced level of consciousness, hypercalcemia and hypernatremia. She had previously received lithium for 20 years for a schizoaffective disorder, but this treatment had been discontinued 3 years before presentation., Investigations: Physical examination, laboratory studies including measurement of serum calcium and parathyroid hormone levels, measurement of urine and serum osmolalities before and after desmopressin administration, blood and urine cultures, and a CT scan of the abdomen., Diagnosis: Urosepsis, dehydration, kidney stone disease, hyperparathyroidism, and nephrogenic diabetes insipidus., Management: Hydration, antibiotics, intravenous pamidronate for rapid control of hypercalcemia, parathyroidectomy, surgical removal of the large kidney stones, a low-protein and low-sodium diet, and initiation of treatment with a thiazide diuretic.

Background and Objective: Diabetes is associated with an increased risk for vascular disease and periodontitis. The aim of this study was to assess the effects of periodontal treatment in diabetes with respect to alterations in the pro-inflammatory potential of peripheral blood mononuclear cells., Material and Methods: Ten patients with diabetes and moderate to severe periodontitis received full-mouth subgingival debridement. Blood samples for serum/plasma and mononuclear cell isolation were collected prior to and 4 wk after therapy. Mononuclear cells were analyzed by flow cytometry and stimulated with lipopolysaccharide or ionomycin/phorbol ester to determine the pro-inflammatory capacity of macrophages and lymphocytes, respectively., Results: Following periodontal treatment, all patients demonstrated a significant improvement in clinical periodontal status (p < 0.05), despite only modest reduction in subgingival bacterial load or homologous serum immunoglobulin G titers. CD14(+) blood monocytes decreased by 47% (p < 0.05), and the percentage of macrophages spontaneously releasing tumor necrosis factor-alpha decreased by 78% (p < 0.05). There were no significant changes in the capacity of lymphocytes to secrete interferon-gamma. Among a number of serum inflammatory markers tested, high-sensitivity-C-reactive protein significantly decreased by 37% (p < 0.01) and soluble E-selectin decreased by 16.6% (p < 0.05)., Conclusion: These data suggest a reduced tendency for monocyte/macrophage-driven inflammation with periodontal therapy and a potential impact on atherosclerosis-related complications in diabetic individuals.