Background:

Although the precipitating events of hepatorenal syndrome (HRS) development have been well characterized, the actual baseline risk of these events resulting in HRS is much less studied.

Aim:

To assess the predictive value of hyponatremia in the development of HRS.Patients and methods: We performed a retrospective observational cohort study including consecutive patients with decompensated liver cirrhosis and normal creatininemia admitted to tertiary center in Slovakia. Patients were censored at two months, development of renal failure, classified either as HRS or renal failure not fulfilling criteria of HRS, was the main outcome.

Results:

Out of 202 patients 18 developed HRS and 14 renal failure not fulfilling the HRS criteria. A significant difference was found between patients with and without HRS in serum sodium (135.76 ± 5.01 vs. 130.78 ± 3.574 mmol/l; p < 0.0001), creatinine, (81 ± 20.11 vs. 98.18 ± 25.032 µmol/l; p = 0.006), bilirubin (90.4 ± 104.82 vs.175.42 ± 174.12 µmol/l; p < 0.0001), MELD (15.17 ± 5.52 vs. 21.61 ± 6.0; p < 0.0001) and MELD-Na score (19.96 ± 6.0 vs. 25.89 ± 4.96; p < 0.0001). Sodium, creatinine, bilirubin, MELD, MELD-Na score were found to be significant predictors of HRS in univariate analysis. Multivariate analysis two prediction models (Model 1: Bilirubin, creatinin, sodium and Model 2: Sodium, MELD) showed that sodium together with creatinine are the strongest HRS predictors, followed by bilirubin or MELD score.

Conclusion:

Serum levels of sodium, creatinine and parameters of liver function are important predictors of hepatorenal syndrome.

There is evidence that chronic hyponatremia, even when mild, may cause neurological signs and symptoms. These have been traditionally associated with water movement into nervous cells, as a result of the hypotonic state. The aim of the present study was to determine whether low extracellular sodium directly exerts negative effects on human neuronal cells, independently of reduced osmolality. We exposed neuroblastoma SK-N-AS and SH-SY5Y cells to sustained low extracellular sodium, thus mimicking a condition of chronic hyponatremia, both in the presence of reduced and in the presence of unaltered osmolality. We found that very low sodium (i.e., 115 mmol/L in SK-N-AS and 90 mmol/L in SH-SY5Y) significantly reduced cell viability. However, intermediate low sodium was able to cause cell distress, as assessed by the altered expression of anti-apoptotic genes and the reduced ability to differentiate into a mature neuronal phenotype. Noteworthy, these effects were observed also in the presence of unaltered osmolality. Moreover, we performed a comprehensive microarray analysis in cells maintained in normal sodium or in low sodium and unaltered osmolality, and we found that the most altered pathway included genes involved in "cell death and survival." Among the more than 40 differentially expressed genes, the Heme oxygenase gene, which represents a transcriptional response to oxidative stress, showed the highest increase in the expression level. This study demonstrates that low extracellular sodium causes detrimental effects in neuronal cells that are at least in part independent of reduced osmolality. These findings further support the recommendation to effectively correct hyponatremia, even when mild and chronic.

To determine the clinical manifestations and outcome of shigellosis among children infected with different species of Shigella.We identified all patients <15 years infected with Shigella admitted to the icddr, b Dhaka hospital during one year. Study staff reviewed admission records and repeated the physical examinations and history of patients daily.Of 792 children with shigellosis 63% were infected with S. flexneri, 20% with S. dysenteriae type 1, 10% with S. boydii, 4% with S. sonnei, and 3% with S. dysenteriae types 2-10. Children infected with S. dysenteriae type 1, when compared to children infected with other species, were significantly (P<0.05) more likely to have severe gastrointestinal manifestations: grossly bloody stools (78% vs. 33%), more stools in the 24 h before admission (median 25 vs. 11), and rectal prolapse (52% vs. 15%) - and extra-intestinal manifestations - leukemoid reaction (22% vs. 2%), hemolytic-uremic syndrome (8% vs. 1%), severe hyponatremia (58% vs. 26%) and neurologic abnormalities (24% vs. 16%). The overall fatality rate was 10% and did not differ significantly by species. In a multiple regression analysis young age, malnutrition, hyponatremia, lesser stool frequency, documented seizure, and unconsciousness were predictive of death.Both severe intestinal disease and extra-intestinal manifestations of shigellosis occur with infection by any of the four species of Shigella, but are most common with S. dysenteriae type 1. Among these inpatient children, the risk of death was high with infection of any of the four Shigella species.

Hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) during amiodarone therapy is a rare but potentially lethal adverse effect. We report a case of severe hyponatremia associated with amiodarone, and discuss its clinical implications.An 84-year-old Caucasian man with a past medical history of hypertension and diabetes was admitted to the hospital with a non-ST elevation myocardial infarction. He underwent coronary artery bypass graft and developed atrial fibrillation on postoperative day 2. A loading dose of amiodarone followed by a maintenance dose was started. The serum sodium level was 136 mmol/l at discharge and subsequently decreased to 105 mmol/l 11 days later, at which time the patient represented with altered mental status. The diagnosis of SIADH was made based on euvolemic hypoosmotic hyponatremia, lack of any other medication known to cause SIADH and urine that was less than maximally dilute. The serum sodium increased gradually to 123 mmol/l after 36 h of treatment with hypertonic saline, demeclocycline and fluid restriction.SIADH-induced hyponatremia associated with amiodarone occurs rarely. Since severe hyponatremia is associated with significant neurological damage and mortality, clinicians should carefully monitor serum sodium during amiodarone therapy.

Human blood-pressure is dependent on balancing dietary salt intake with its excretion by the kidney. Mendelian-syndromes of altered blood pressure demonstrate the importance of the distal nephron in this process and of the thiazide-sensitive pathway in particular. Gordon-Syndrome(GS), the phenotypic inverse of the salt-wasting Gitelman syndrome, is a condition of hyperkalaemic hypertension that is reversed by low dose thiazide diuretics or a low salt diet. Variants within at least four genes (the With-No-lysine-(K)-kinases, WNKs1&4, Cullin3 and KeLch-like3) can cause the phenotype of GS. Details are still emerging for some of these genes, but it is likely that they all cause a gain-of-function in the thiazide sensitive Na-Cl Cotransporter (NCC) and hence salt retention. We discuss the key role of a kinase, STE20(sterile 20)/SPS1-related proline/Alanine-rich Kinase(SPAK), that functions as an intermediary between the WNK kinases and NCC and whose loss-of-function mutation produces a Gitelman-type phenotype in a mouse model. In addition to Mendelian blood pressure syndromes, the study of patients who develop Thiazide-Induced-Hyponatraemia(TIH) may give-further molecular insights into the role of the thiazide-sensitive pathway for salt reabsorption. We discuss the key features of TIH including its high degree of reproducibility on rechallenge, possible genetic predisposition and mechanisms involving excessive saliuresis and water-retention. Taken together, the study of Gordon syndrome and TIH may increase understanding of the molecular regulation of sodium trafficking via the thiazide-sensitive pathway and have important implications for hypertensive patients, both in the identification of new anti-hypertensive drug targets and avoidance of hyponatraemic side-effects. This article is protected by copyright. All rights reserved.

A 61-year-old woman presented with a right mandibular tumor and was diagnosed with DLBCL clinical stage IIIA from the biopsy results of the tumor and CT examination. An initial rituximab was administrated a week after the first CHOP treatment. During the infusion of rituximab, she exhibited disorientation, seizure, and consciousness disturbance. Hyponatremia due to SIADH and hypertension were coincidentally observed. MRI revealed T2 and FLAIR hyperintense signals involving the bilateral occipital, parietal, frontal lobes and the cerebellum that were consistent with reversible posterior leukoencephalopathy syndrome (RPLS). Her consciousness level recovered in parallel with corrections in serum sodium levels and blood pressure. Although she presented with transient cortical blindness, all neurological abnormalities disappeared 40 hours after the occurrence of seizure. She received a further 7 cycles of CHOP followed by 7 cycles of rituximab treatment with no relapse of RPLS. After irradiation for a residual abdominal tumor, she has maintained complete remission for 2 years. Although RPLS is a rare complication of rituximab-CHOP chemotherapy, it should be considered in patients with DLBCL who present with acute neurological deterioration.

Disturbances in sodium concentration are common in the critically ill patient and associated with increased mortality. The key principle in treatment and prevention is that plasma [Na+] (P-[Na+]) is determined by external water and cation balances. P-[Na+] determines plasma tonicity. An important exception is hyperglycaemia, where P-[Na+] may be reduced despite plasma hypertonicity. The patient is first treated to secure airway, breathing and circulation to diminish secondary organ damage. Symptoms are critical when handling a patient with hyponatraemia. Severe symptoms are treated with 2 ml/kg 3% NaCl bolus infusions irrespective of the supposed duration of hyponatraemia. The goal is to reduce cerebral symptoms. The bolus therapy ensures an immediate and controllable rise in P-[Na+]. A maximum of three boluses are given (increases P-[Na+] about 6 mmol/l). In all patients with hyponatraemia, correction above 10 mmol/l/day must be avoided to reduce the risk of osmotic demyelination. Practical measures for handling a rapid rise in P-[Na+] are discussed. The risk of overcorrection is associated with the mechanisms that cause hyponatraemia. Traditional classifications according to volume status are notoriously difficult to handle in clinical practice. Moreover, multiple combined mechanisms are common. More than one mechanism must therefore be considered for safe and lasting correction. Hypernatraemia is less common than hyponatraemia, but implies that the patient is more ill and has a worse prognosis. A practical approach includes treatment of the underlying diseases and restoration of the distorted water and salt balances. Multiple combined mechanisms are common and must be searched for. Importantly, hypernatraemia is not only a matter of water deficit, and treatment of the critically ill patient with an accumulated fluid balance of 20 litres and corresponding weight gain should not comprise more water, but measures to invoke a negative cation balance. Reduction of hypernatraemia/hypertonicity is critical, but should not exceed 12 mmol/l/day in order to reduce the risk of rebounding brain oedema.