先天性腎性尿崩症

Lithium is the most common and effective mood stabiliser in the management of bipolar disorder. Lithium-induced nephrogenic diabetes insipidus (NDI) is a well-recognised complication of long-term mood stabiliser therapy. However, management becomes exponentially more complex when therapeutic options, such as thiazides or amiloride, are contraindicated due to advanced chronic kidney disease (CKD) or electrolyte instability. We are reporting the case of a man in his 60s with a 40-year history of lithium use who presented with acute-on-chronic kidney injury (AKI) and severe hypernatraemia (164 mmol/L) refractory to standard desmopressin therapy. This case highlights the limitations of conventional NDI treatments in the setting of a low estimated glomerular filtration rate (eGFR) and the necessity of intensive, multidisciplinary care.

BACKGROUND: Congenital nephrogenic diabetes insipidus (CNDI) is most frequently caused by mutations in the AVPR2 gene. Patients exhibit persistent polyuria due to renal insensitivity to antidiuretic hormone. Chronic high urine output predisposes to bladder dysfunction and upper urinary-tract dilatation, notably hydronephrosis. Although pharmacotherapy can partially reduce urine volume, its capacity to reverse established hydronephrosis is limited. Clean intermittent catheterization (CIC), a mainstay in managing neurogenic bladder, warrants investigation regarding its utility in CNDI-associated hydronephrosis. CASE DESCRIPTION: A 9-year-old Chinese boy presented with lifelong polydipsia and polyuria, with a peak 24-h urine output of approximately 7100 mL. Renal ultrasonography demonstrated bilateral moderate hydronephrosis. Whole-exome sequencing identified a hemizygous nonsense mutation, AVPR2 c.968G>A (p.Trp323*); his mother was a heterozygous carrier of the same variant. After one month of standard therapy with hydrochlorothiazide and indomethacin, his daily urine volume decreased to approximately 3400 mL/d, but the hydronephrosis showed no improvement. A subsequent video urodynamic study revealed decreased bladder sensation, reduced compliance, and diminished detrusor contractility. In addition to the continued pharmacological regimen, clean intermittent catheterization (performed three times daily at home) was introduced. Follow-up ultrasonography one month later showed significant improvement in the bilateral hydronephrosis. CONCLUSIONS: For pediatric CNDI patients with persistent incomplete bladder emptying and hydronephrosis despite pharmacotherapy, short-term clean intermittent catheterization can break the vicious cycle of "chronic urinary retention-elevated bladder pressure-upper urinary tract dilatation," representing a safe, effective, and readily implementable adjuvant intervention.

Sedation is often required to facilitate comfort and provide necessary care for patients who are critically ill and require mechanical ventilation. Intravenous sedatives are the current standard of care in this patient population. Inhaled volatile agents that are routinely used for general anesthesia, like isoflurane and sevoflurane, are also being explored for their potential role in the ICU setting. Already, inhaled volatile agents are prescribed for routine ICU sedation in several countries, though their use for ICU sedation is not approved by United States regulatory authorities as of the time of this writing. The efficacy and safety profiles of inhaled sedatives for short-term use are well understood through decades of experience in the operating room. Their rapid onset and elimination via the lungs, potential opioid-sparing effects, and preservation of spontaneous breathing make them intriguing potential alternatives or adjuncts to standard-of-care sedation during critical illness. Technological advancements, consisting of compact vaporizers, volatile agent reflectors, and scavenger systems, allow the delivery of inhaled sedatives via modern ICU ventilators. However, these systems require specialized clinical training and considerations. Rigorous clinical trials evaluating the use of inhaled volatile agents for prolonged sedation of patients receiving mechanical ventilation remain limited, and whether these theoretical advantages translate to patient-centered benefit, relative to intravenous agents, remains unknown. Recent findings suggest prolonged deep sedation with inhaled sevoflurane predisposes to nephrogenic diabetes insipidus and acute kidney injury during critical illness, and that it is potentially harmful in patients with ARDS. Isoflurane may have a more favorable safety profile, but rigorous data are sparse on isoflurane use for more than a few days. This narrative review evaluates the evidence regarding the use of inhaled sedatives in patients in ICU who require mechanical ventilation. It also provides an overview of the clinical and technical aspects of this therapy to inform health care providers of a novel option, in many countries, for the sedation of patients undergoing mechanical ventilation.

Lithium (Li) salts have been widely used to treat bipolar disorder and unipolar depression for more than 50 years. However, up to 40% of people taking Li develop Nephrogenic Diabetes Insipidus (NDI). NDI is associated with cellular remodeling in the rodent kidney collecting duct and reduced aquaporin-2. Patients taking Li for more than 10-20 years are at risk of chronic kidney disease, which ultimately can lead to end-stage renal disease, hemodialysis, transplantation, or death. The purpose of this study was to investigate whether the rat urinary proteome can be used as an indicator of Li-induced changes in kidney. Extracellular vesicles were isolated from the urine of rats treated with Li for 2 or 4 weeks followed by LC-MS/MS analysis. The results showed a limited correlation between protein changes in urine and kidney. However, the urine contained markers of mitochondrial dysfunction. The cytoskeletal protein, Keratin 8, showed a tendency to be higher in the urine and was greatly increased in collecting duct principal cells in response to Li, suggesting a potential role in cellular remodeling. Canonical Histone H4 was increased in the urine, and was observed in the nuclei of collecting duct principal and intercalated cells following Li. Moreover, Histone H4 positive cells co-localized with the proliferation marker, PCNA. This correlates with the known increased proliferation in the collecting duct in response to Li. Thus, replication-dependent Histone H4 is a possible urinary marker for the Li induced cellular remodeling of the collecting duct.