Identification of as a First Susceptibility Gene for Lithium-Induced Nephrogenic Diabetes Insipidus in Mice.

Background: Lithium, mainstay treatment for bipolar disorder, causes nephrogenic diabetes insipidus and hypercalcemia in about 20% and 10% of patients, respectively, and may lead to acidosis. These adverse effects develop in only a subset of patients treated with lithium, suggesting genetic factors play a role.

Methods: To identify susceptibility genes for lithium-induced adverse effects, we performed a genome-wide association study in mice, which develop such effects faster than humans.

Lithium reduces blood glucose levels, but aggravates albuminuria in BTBR-ob/ob mice.

Glycogen synthase kinase 3 (GSK3) plays an important role in the development of diabetes mellitus and renal injury. GSK3 inhibition increases glucose uptake in insulin-insensitive muscle and adipose tissue, while it reduces albuminuria and glomerulosclerosis in acute kidney injury. The effect of chronic GSK3 inhibition in diabetic nephropathy is not known.

Lithium induces aerobic glycolysis and glutaminolysis in collecting duct principal cells.

Lithium, given to bipolar disorder patients, causes nephrogenic diabetes insipidus (Li-NDI), a urinary-concentrating defect. Li-NDI occurs due to downregulation of principal cell AQP2 expression, which coincides with principal cell proliferation. The metabolic effect of lithium on principal cells, however, is unknown and investigated here.

Lithium-induced NDI: acetazolamide reduces polyuria but does not improve urine concentrating ability.

Lithium is the mainstay treatment for patients with bipolar disorder, but it generally causes nephrogenic diabetes insipidus (NDI), a disorder in which the renal urine concentrating ability has become vasopressin insensitive. Li-NDI is caused by lithium uptake by collecting duct principal cells and downregulation of aquaporin-2 (AQP2) water channels, which are essential for water uptake from tubular urine. Recently, we found that the prophylactic administration of acetazolamide to mice effectively attenuated Li-NDI.

Lithium in the Kidney: Friend and Foe?

Trace amounts of lithium are essential for our physical and mental health, and administration of lithium has improved the quality of life of millions of patients with bipolar disorder for >60 years. However, in a substantial number of patients with bipolar disorder, long-term lithium therapy comes at the cost of severe renal side effects, including nephrogenic diabetes insipidus and rarely, ESRD. Although the mechanisms underlying the lithium-induced renal pathologies are becoming clearer, several recent animal studies revealed that short-term administration of lower amounts of lithium prevents different forms of experimental AKI.

Acetazolamide Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus.

To reduce lithium-induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA-specific blocker acetazolamide in lithium-NDI.

Lithium causes G2 arrest of renal principal cells.

Vasopressin-regulated expression and insertion of aquaporin-2 channels in the luminal membrane of renal principal cells is essential for urine concentration. Lithium affects urine concentrating ability, and approximately 20% of patients treated with lithium develop nephrogenic diabetes insipidus (NDI), a disorder characterized by polyuria and polydipsia. Lithium-induced NDI is caused by aquaporin-2 downregulation and a reduced ratio of principal/intercalated cells, yet lithium induces principal cell proliferation.

Hydrochlorothiazide attenuates lithium-induced nephrogenic diabetes insipidus independently of the sodium-chloride cotransporter.

Lithium is the most common cause of nephrogenic diabetes insipidus (Li-NDI). Hydrochlorothiazide (HCTZ) combined with amiloride is the mainstay treatment in Li-NDI. The paradoxical antidiuretic action of HCTZ in Li-NDI is generally attributed to increased sodium and water uptake in proximal tubules as a compensation for increased volume loss due to HCTZ inhibition of the Na-Cl cotransporter (NCC), but alternative actions for HCTZ have been suggested.

Diagnostic performance of rapid tests for detection of fecal calprotectin and lactoferrin and their ability to discriminate inflammatory from irritable bowel syndrome.

Background: Ruling out somatic bowel disease, such as inflammatory bowel disease (IBD), is an important goal in the management of abdominal complaints. Endoscopy is commonly used but is invasive and expensive. Mucosal inflammation in IBD can be detected through fecal biomarkers, though the present enzyme-linked immunoabsorbent assay (ELISA) tests require laboratory facilities.

Analytical and clinical performance of three natriuretic peptide tests in the emergency room.

Background: The aim of the present study was to investigate the analytical and diagnostic utility of B-type natriuretic peptide (BNP) and the N-terminus of this prohormone, N-terminal pro-BNP (NT-pro-BNP) testing in the emergency department to identify acute congestive heart failure (CHF).

Methods: A blood sample taken from patients presenting to the emergency department with acute dyspnoea (n=80) was analyzed for natriuretic peptides using three different assays [Triage BNP (Biosite), Centaur BNP (Bayer) and Elecsys NT-pro-BNP (Roche)]. A cardiologist and a pulmonologist, blinded to the actual natriuretic peptide levels, reviewed all test results (including echocardiography, etc.

Urine osmolality, cyclic AMP and aquaporin-2 in urine of patients under lithium treatment in response to water loading followed by vasopressin administration.

Lithium is the drug that is most frequently associated with acquired nephrogenic diabetes insipidus (NDI). The exact mechanism of lithium-induced NDI in man is unknown. The aim of the present study was to investigate the kidney response to minimal and maximal stimulation of the kidney urine concentrating mechanism by measuring urine osmolality, and urine levels of cAMP and AQP-2 in urine of patients under long-term lithium treatment.

An evaluation of blood volume changes during ultrafiltration pulses and natriuretic peptides in the assessment of dry weight in hemodialysis patients.

Changes in blood volume (BV) during dialysis as well as plasma levels of brain natriuretic peptide (BNP) and N-terminal (NT) pro-BNP levels are possible tools to assess dry weight in hemodialysis (HD) patients. The aim of the study was to compare these parameters with other non-invasive techniques used to assess dry weight in HD patients, and to study their relation with intradialytic hypotension (IDH) and the presence of cardiovascular disease BV changes during HD, both during regular dialysis and during an ultrafiltration pulse, plasma levels of NT pro-BNP and BNP, and vena cava diameter index (VCDI) were assessed in a cohort of 66 HD patients, which was subdivided according to tertiles of total body water (TBW) corrected for body weight, assessed by bioimpedance analysis. Parameters were also related to the presence of IDH and history of cardiovascular disease.

Effects of a long-distance run on cardiac markers in healthy athletes.

Background: Running a marathon is a stressful event for athletes. Limited research exists on the role of cardiac markers during such a strenuous event. The aim of this study was to investigate detailed changes in cardiac markers before and after a long-distance run.

Recurrent acute hemolytic transfusion reactions by antibodies against Doa antigens, not detected by cross-matching.

An 81-year-old male patient suffered from recurrent acute hemolytic transfusion reactions after transfusion with phenotyped cross-match-negative red blood cells (RBCs). Extensive posttransfusion workup eventually revealed Dombrock (a) (Do(a)) antibodies. Because commercially available cell panels do not allow for identification of anti-Do(a) and owing to the lack of Do(a) typing serum samples, selection of matched units of RBCs is dependent on negative cross-match results.