Search Results (9)

A knowledge gap may exist when attempting to identify the pathogenetic mechanisms resulting in the syndrome of inappropriate antidiuretic hormone (SIADH) or hypotonic hyponatremia. Ectopic secretion of antidiuretic hormone [ADH] is the classic cause of SIADH. But another form of inappropriate secretion of ADH occurs when interleukin 6 is activated. Hypotonic hyponatremia can also occur in patients with cerebral salt wasting, but the secretion of ADH is appropriate, responding to volume depletion induced by excessive natriuresis. Reset osmostat (RO) is another cause of hypotonic hyponatremia caused by an unknown anomaly in the hypothalamus. This review discusses the pathophysiology of and the identical laboratory findings found in classic ectopic ADH secretion, interleukin 6-mediated ADH secretion, cerebral salt wasting-induced ADH secretion, and RO. This review also discusses potential methods to discern which hypotonic hyponatremic syndrome is present and current recommendations for treatment. Full article

A 12-year-old spayed female domestic short cat was presented with tetraplegia. The cat also showed signs of hyponatremia and dehydration, which were rapidly corrected by intravenous fluid infusion. Based on thorough physical and neurological examinations, the patient was suspected of having an intracranial disease. MRI revealed a high-signal T2 image of the bilateral parietal cerebral cortical gray matter junction, which is associated with fast electrolyte calibration, and a high-signal T2 image of the C2 spinal cord ventral area, which is associated with ischemic myelopathy. The cat reappeared three days later due to anorexia. Laboratory examinations revealed that the cat was clinically dehydrated and exhibited hyponatremia. Other causes of hyponatremia were excluded through history-taking, laboratory examination, imaging, and therapeutic response to fluid therapy, except for cerebral salt-wasting syndrome (CSWS). The cat was discharged 3 days after the start of fludrocortisone therapy with electrolytes within the normal range. Magnetic resonance imaging (MRI) was performed again 1 month after hospitalization, and the cerebral lesion disappeared, but the spinal cord lesion worsened compared to the previous image. The patient was euthanized due to the progression of the spinal lesion, with a poor prognosis and poor quality of life. This is the first case of suspected CSWS with a cervical spinal lesion in a cat. Full article

The application of pathophysiologic tenets has created significant changes in our approach to hyponatremia and hyponatremia-related conditions. This new approach incorporated the determination of fractional excretion (FE) of urate before and after the correction of hyponatremia and the response to isotonic saline infusion to differentiate the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from renal salt wasting (RSW). FEurate simplified the identification of the different causes of hyponatremia, especially the diagnosis of a reset osmostat and Addison’s disease. Differentiating SIADH from RSW has been extremely difficult because both syndromes present with identical clinical parameters, which could be overcome by successfully carrying out the difficult protocol of this new approach. A study of 62 hyponatremic patients from the general medical wards of the hospital identified 17 (27%) to have SIADH, 19 (31%) with reset osmostat, and 24 (38%) with RSW with 21 of these RSW patients presenting without clinical evidence of cerebral disease to warrant changing the nomenclature from cerebral to renal salt wasting. The natriuretic activity found in the plasma of 21 and 18 patients with neurosurgical and Alzheimer’s disease, respectively, was later identified as haptoglobin-related protein without signal peptide (HPRWSP). The high prevalence of RSW creates a therapeutic dilemma of deciding whether to water-restrict water-logged patients with SIADH as compared to administering saline to volume-depleted patients with RSW. Future studies will hopefully achieve the following: 1. Abandon the ineffective volume approach; 2. Develop HPRWSP as a biomarker to identify hyponatremic and a projected large number of normonatremic patients at risk of developing RSW, including Alzheimer’s disease; 3. Facilitate differentiating SIADH from RSW on the first encounter and improve clinical outcomes. Full article

Body sodium (Na) levels must be maintained within a narrow range for the correct functioning of the organism (Na homeostasis). Na disorders include not only elevated levels of this solute (hypernatremia), as in diabetes insipidus, but also reduced levels (hyponatremia), as in cerebral salt wasting syndrome. The balance in body Na levels therefore requires a delicate equilibrium to be maintained between the ingestion and excretion of Na. Salt (NaCl) intake is processed by receptors in the tongue and digestive system, which transmit the information to the nucleus of the solitary tract via a neural pathway (chorda tympani/vagus nerves) and to circumventricular organs, including the subfornical organ and area postrema, via a humoral pathway (blood/cerebrospinal fluid). Circuits are formed that stimulate or inhibit homeostatic Na intake involving participation of the parabrachial nucleus, pre-locus coeruleus, medial tuberomammillary nuclei, median eminence, paraventricular and supraoptic nuclei, and other structures with reward properties such as the bed nucleus of the stria terminalis, central amygdala, and ventral tegmental area. Finally, the kidney uses neural signals (e.g., renal sympathetic nerves) and vascular (e.g., renal perfusion pressure) and humoral (e.g., renin–angiotensin–aldosterone system, cardiac natriuretic peptides, antidiuretic hormone, and oxytocin) factors to promote Na excretion or retention and thereby maintain extracellular fluid volume. All these intake and excretion processes are modulated by chemical messengers, many of which (e.g., aldosterone, angiotensin II, and oxytocin) have effects that are coordinated at peripheral and central level to ensure Na homeostasis. Full article

Our understanding of hyponatremic conditions has undergone major alterations. There is a tendency to treat all patients with hyponatremia because of common subtle symptoms that include unsteady gait that lead to increased falls and bone fractures and can progress to mental confusion, irritability, seizures, coma and even death. We describe a new approach that is superior to the ineffectual volume approach. Determination of fractional excretion (FE) of urate has simplified the diagnosis of a reset osmostat, Addison’s disease, edematous causes such as congestive heart failure, cirrhosis and nephrosis, volume depletion from extrarenal salt losses with normal renal tubular function and the difficult task of differentiating the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from cerebral/renal salt wasting (C/RSW). SIADH and C/RSW have identical clinical and laboratory parameters but have diametrically opposite therapeutic goals of water-restricting water-loaded patients with SIADH or administering salt water to dehydrated patients with C/RSW. In a study of nonedematous patients with hyponatremia, we utilized FEurate and response to isotonic saline infusions to differentiate SIADH from C/RSW. Twenty-four (38%) of 62 hyponatremic patients had C/RSW with 21 having no clinical evidence of cerebral disease to support our important proposal to change cerebral to renal salt wasting (RSW). Seventeen (27%) had SIADH and 19 (31%) had a reset osmostat. One each from hydrochlorothiazide and Addison’s disease. We demonstrated natriuretic activity in the plasma of patients with neurosurgical and Alzheimer diseases (AD) in rat clearance studies and have now identified the natriuretic protein to be haptoglobin related protein without signal peptide (HPRWSP). We introduce a new syndrome of RSW in AD that needs further confirmation. Future studies intend to develop HPRWSP as a biomarker to simplify the diagnosis of RSW in hyponatremic and normonatremic patients and explore other clinical applications that can improve clinical outcomes. Full article

Serum uric acid levels are altered by kidney disorders because the kidneys play a dominant role in uric acid excretion. Here, major kidney disorders which accompany hyperuricemia or hypouricemia, including their pathophysiology, are discussed. Chronic kidney disease (CKD) and hyperuricemia are frequently associated, but recent clinical trials have not supported the pathogenic roles of hyperuricemia in CKD incidence and progression. Diabetes mellitus (DM) is often associated with hyperuricemia, and hyperuricemia may be associated with an increased risk of diabetic kidney disease in patients with type 2 DM. Sodium-glucose cotransporter 2 inhibitors have a uricosuric effect and can relieve hyperuricemia in DM. Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an important hereditary kidney disease, mainly caused by mutations of uromodulin (UMOD) or mucin-1 (MUC-1). Hyperuricemia and gout are the major clinical manifestations of ADTKD-UMOD and ADTKD-MUC1. Renal hypouricemia is caused by URAT1 or GLUT9 loss-of-function mutations and renders patients susceptible to exercise-induced acute kidney injury, probably because of excessive urinary uric acid excretion. Hypouricemia derived from renal uric acid wasting is a component of Fanconi syndrome, which can be hereditary or acquired. During treatment for human immunodeficiency virus, hepatitis B or cytomegalovirus, tenofovir, adefovir, and cidofovir may cause drug-induced renal Fanconi syndrome. In coronavirus disease 2019, hypouricemia due to proximal tubular injury is related to disease severity, including respiratory failure. Finally, serum uric acid and the fractional excretion of uric acid are indicative of plasma volume status; hyperuricemia caused by the enhanced uric acid reabsorption can be induced by volume depletion, and hypouricemia caused by an increased fractional excretion of uric acid is the characteristic finding in syndromes of inappropriate anti-diuresis, cerebral/renal salt wasting, and thiazide-induced hyponatremia. Molecular mechanisms by which uric acid transport is dysregulated in volume or water balance disorders need to be investigated. Full article

Little is known about delayed postoperative hyponatremia (DPH) accompanied with transsphenoidal surgery for non-adenomatous skull base tumors (NASBTs). Consecutive data on 30 patients with parasellar NASBT was retrospectively reviewed with detailed analyses on perioperative serial sodium levels. Serological DPH (sodium ≤ 135 mmol/L) was observed in eight (27%), with four (13%) of them being symptomatic. DPH developed on postoperative day 7–12 where the mean sodium levels were 134 mmol/L (a mean of 7 mmol/L drop from the baseline) in asymptomatic and 125 mmol/L (a mean of 17.5 mmol/L drop from the baseline) in symptomatic DPH. Serological DPH was accompanied with “weight loss and hemoconcentration (cerebral salt wasting type)” in four (50%), “weight gain and hemodilution (syndrome of inappropriate antidiuretic hormone secretion type)” in three (38%), and no significant weight change in one. Intraoperative extradural retraction of the pituitary gland was the only significant factor for serological DPH (p = 0.035; odds ratio, 12.25 (95% confidence interval, 1.27–118.36)). DPH should be recognized as one of the significant postsurgical complications associated with TSS for NASBTs. Although the underlying mechanism is still controversial, intraoperative extradural compression of the pituitary gland and subsequent dysregulation of the hypothalamo-hypophyseal axis may be responsible. Full article

Hyponatremia is the most common electrolyte abnormality. Its diagnostic and therapeutic approaches are in a state of flux. It is evident that hyponatremic patients are symptomatic with a potential for serious consequences at sodium levels that were once considered trivial. The recommendation to treat virtually all hyponatremics exposes the need to resolve the diagnostic and therapeutic dilemma of deciding whether to water restrict a patient with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or administer salt and water to a renal salt waster. In this review, we briefly discuss the pathophysiology of SIADH and renal salt wasting (RSW), and the difficulty in differentiating SIADH from RSW, and review the origin of the perceived rarity of RSW, as well as the value of determining fractional excretion of urate (FEurate) in differentiating both syndromes, the high prevalence of RSW which highlights the inadequacy of the volume approach to hyponatremia, the importance of changing cerebral salt wasting to RSW, and the proposal to eliminate reset osmostat as a subtype of SIADH, and finally propose a new algorithm to replace the outmoded volume approach by highlighting FEurate. This algorithm eliminates the need to assess the volume status with less reliance on determining urine sodium concentration, plasma renin, aldosterone and atrial/brain natriuretic peptide or the BUN to creatinine ratio. Full article

Hyponatremia is the most frequently encountered electrolyte abnormality in critically ill patients. Hyponatremia on admission has been identified as an independent predictor of in-hospital mortality in patients with spontaneous intracerebral hemorrhage (sICH). However, the incidence and etiology of hyponatremia (HN) during hospitalization in a neurointensive care unit following spontaneous intracerebral hemorrhage (sICH) remains unknown. This was a retrospective analysis of consecutive patients admitted to Detroit Receiving Hospital for sICH between January 2006 and July 2009. All serum Na levels were recorded for patients during the ICU stay. HN was defined as Na <135 mmol/L. A total of 99 patients were analyzed with HN developing in 24% of sICH patients. Patients with HN had an average sodium nadir of 130 ± 3 mmol/L and an average time from admission to sodium <135 mmol/L of 3.9 ± 5.7 days. The most common cause of hyponatremia was syndrome of inappropriate antidiuretic hormone (90% of HN patients). Patients with HN were more likely to have fever (50% vs. 23%; p = 0.01), infection (58% vs. 28%; p = 0.007) as well as a longer hospital length of stay (14 (8–25) vs. 6 (3–9) days; p < 0.001). Of the patients who developed HN, fifteen (62.5%) patients developed HN in the first week following sICH. This shows HN has a fairly high incidence following sICH. The presence of HN is associated with longer hospital length of stays and higher rates of patient complications, which may result in worse patient outcomes. Further study is necessary to characterize the clinical relevance and treatment of HN in this population. Full article