Hyponatremia is the most common electrolyte abnormality in hospitalized patients. When symptomatic (hyponatremic encephalopathy), the overall morbidity is 34%. Individuals most susceptible to death or permanent brain damage are prepubescent children and menstruant women. Failure of the brain to adapt to the hyponatremia leads to brain damage. Major factors that can impair brain adaptation include hypoxia and peptide hormones. In children, physical factors—discrepancy between skull size and brain size—are important in the genesis of brain damage. In adults, certain hormones—estrogen and vasopressin (usually elevated in cases of hyponatremia)—have been shown to impair brain adaptation, decreasing both cerebral blood flow and oxygen utilization. Initially, hyponatremia leads to an influx of water into the brain, primarily through glial cells and largely via the water channel aquaporin (AQP)4. Water is thus shunted into astrocytes, which swell, largely preserving neuronal cell volume. The initial brain response to swelling is adaptation, utilizing the Na⁺-K⁺-ATPase system to extrude cellular Na⁺. In menstruant women, estrogen + vasopressin inhibits the Na⁺-K⁺-ATPase system and decreases cerebral oxygen utilization, impairing brain adaptation. Cerebral edema compresses the respiratory centers and also forces blood out of the brain, both lowering arterial Po₂ and decreasing oxygen utilization. The hypoxemia further impairs brain adaptation. Hyponatremic encephalopathy leads to brain damage when brain adaptation is impaired and is a consequence of both cerebral hypoxia and peptide hormones.

There is a growing number of patients returning to dialysis after a failed kidney transplant, and there is increasing evidence of higher mortality among this population. Whether removal of the failed renal allograft affects survival while receiving long-term dialysis is not well understood. We identified all adults who received a kidney transplant and returned to long-term dialysis after renal allograft failure between January 1994 and December 2004 from the US Renal Data System. Among 10,951 transplant recipients who returned to long-term dialysis, 3451 (31.5%) received an allograft nephrectomy during follow-up. Overall, 34.6% of these patients died during follow-up. Receiving an allograft nephrectomy associated with a 32% lower adjusted relative risk for all-cause death (adjusted hazard ratio 0.68; 95% confidence interval 0.63 to 0.74) after adjustment for sociodemographic characteristics, comorbidity burden, donor characteristics, interim clinical conditions associated with receiving allograft nephrectomy, and propensity to receive an allograft nephrectomy. In conclusion, within a large, nationally representative sample of high-risk patients returning to long-term dialysis after failed kidney transplant, receipt of allograft nephrectomy independently associated with improved survival.

Hip fractures represent a serious health risk in the elderly, with significant associated morbidity and mortality. There is now an emerging literature that suggests that chronic hyponatremia increases the adjusted odds ratio (OR) for both falls and fractures in the elderly. Hyponatremia appears to contribute to falls and fractures by two mechanisms: (i) it produces mild cognitive impairment resulting in unsteady gait and falls and (ii) it directly contributes to osteoporosis and increased bone fragility by inducing increased bone resorption to mobilize sodium. There is debate over the effect of hyponatremia on the production of osteoporosis, as one study found decreased bone mineral density (BMD) and another did not. Should we be screening for low serum sodium in patients with osteoporosis or assessing BMD in patients with hyponatremia? The final answer is yet to come from prospective studies that allocate elderly individuals with mild hyponatremia to receive active treatment or not for hyponatremia and see if this intervention prevents gait disturbances and changes in BMD reducing fracture risk. In the meantime, physicians caring for elderly patients must be aware of the association between hyponatremia and bone problems. As serum sodium is a readily available, simple and affordable biochemical measurement, clinicians should look for hyponatremia in elderly patients who take medications that can cause hyponatremia. Also, elderly patients with unsteady gait and/or confusion should be checked for the presence of mild hyponatremia and if present it should not be ignored. Finally, elderly patients presenting with an orthopedic injury should have serum sodium checked and corrected if hyponatremia is present.