Renal function after withdrawal of lithium.

OBJECTIVES: Patients on chronic lithium therapy sometimes develop chronic kidney disease. For clinical decision-making, it is important to know whether discontinuation of lithium can lead to improvement of renal function. We studied the trajectory of renal function in a population previously on chronic lithium therapy. METHODS: From a large database of patients on chronic lithium therapy, we selected a group of patients who stopped using lithium and whose creatinine values at least half a year after lithium withdrawal were available. We measured the slope of renal function (eGFR) before and after discontinuation of lithium. We compared the subgroup of patients with improvement of the renal function with those who showed further deterioration of the eGFR. RESULTS: eGFR slope significantly improved after discontinuation of lithium. Of patients with chronic kidney disease stage 3 or more (eGFR<60 ml/min), the vast majority showed an increase of eGFR or a decrease in the rate of decline after lithium withdrawal. The group of patients with further deterioration of the renal function had a mean eGFR of 32 ml/min, which was significantly lower than the patients with an improvement of the kidney function. CONCLUSIONS: Discontinuation of lithium leads in the majority of patients to improvement in renal function or at least less rapid deterioration.

Chronic kidney disease in lithium-treated patients, incidence and rate of decline.

BACKGROUND: Lithium-induced nephropathy is a known long-term complication, sometimes limiting the use of lithium as mood stabilizer. The aim of this study is to establish the incidence of chronic kidney disease and the rate of decline of renal function in patients using lithium and to identify risk factors. METHODS: We selected 1012 patients treated with lithium from the laboratory database of the Antes Centre for Mental Health Care spanning a period from 2000 to 2015. Serum lithium and creatinine concentrations were retrieved and eGFR was calculated using the 4-variable CKD-EPI formula. We calculated the incidence of renal insufficiency and the rate of decline. We compared patients with and without chronic kidney disease (CKD) stage 3 regarding duration of lithium exposure. RESULTS: Incidence of chronic kidney disease was 0.012 cases per exposed patient-year. Average decline of eGFR was 1.8 ml/min/year in patients who developed chronic kidney disease stage 3. Incidence of chronic kidney disease stage 4 was only 0.0004 per patient year. No cases of end stage renal disease were found in this cohort. Odds of reaching chronic kidney disease stage 3 were increased with longer duration of lithium exposure. CONCLUSIONS: The use of lithium seems to be related to a higher incidence of chronic kidney disease. Longer duration of lithium exposure significantly increased the risk of renal failure.

[Lithium: only acceptable with careful monitoring]. / Lithium, alleen verantwoord met zorgvuldige controle.

In the Netherlands, lithium is the mood stabilizer of choice for patients with bipolar disorder. Long-term treatment with lithium can only be implemented safely with frequent and appropriate monitoring of serum lithium concentrations. Here we use 3 cases to illustrate that severe complications can arise when careful monitoring is not performed: a 47-year-old woman with symptoms of a lithium intoxication with therapeutic plasma levels; a 73-year-old woman with chronic lithium intoxication; and a 56-year-old woman with end-stage renal failure after many years of probable toxic lithium levels.

Laparoscopic versus open peritoneal dialysis catheter insertion, the LOCI-trial: a study protocol.

BACKGROUND: Peritoneal dialysis (PD) is an effective treatment for end-stage renal disease. It allows patients more freedom to perform daily activities compared to haemodialysis. Key to successful PD is the presence of a well-functioning dialysis catheter. Several complications, such as in- and outflow obstruction, peritonitis, exit-site infections, leakage and migration, can lead to catheter removal and loss of peritoneal access. Currently, different surgical techniques are in practice for PD-catheter placement. The type of insertion technique used may greatly influence the occurrence of complications. In the literature, up to 35% catheter failure has been described when using the open technique and only 13% for the laparoscopic technique. However, a well-designed randomized controlled trial is lacking. METHODS/DESIGN: The LOCI-trial is a multi-center randomized controlled, single-blind trial (pilot). The study compares the laparoscopic with the open technique for PD catheter insertion. The primary objective is to determine the optimum placement technique in order to minimize the incidence of catheter malfunction at 6 weeks postoperatively. Secondary objectives are to determine the best approach to optimize catheter function and to study the quality of life at 6 months postoperatively comparing the two operative techniques. DISCUSSION: This study will generate evidence on any benefits of laparoscopic versus open PD catheter insertion. TRIAL REGISTRATION: Dutch Trial Register NTR2878.

Circling behavior in the Ecl mouse is caused by lateral semicircular canal defects.

The epistatic circler mouse (Ecl mouse) is a preexisting mutant, which displays a circling phenotype and hyperactivity. It has been shown that the circling phenotype in this mutant results from a complex inheritance pattern, but the vestibular pathology has not been analyzed. The present study deals with the morphological and functional basis responsible for the circling behavior in the Ecl mouse. Morphological examination of the inner ears revealed a bilateral malformation of the horizontal (lateral) semicircular canal and duct. No cochlear abnormalities were detected, and auditory brainstem response (ABR) measurements indicated that the auditory system is not affected. Investigation of the vestibuloocular reflex (VOR) in Ecl mice showed that their horizontal VOR on stimulation is virtually absent, which correlates with the morphological findings.

Vestibular dysfunction in the epistatic circler mouse is caused by phenotypic interaction of one recessive gene and three modifier genes.

Vestibular dysfunction is a frequent clinical problem, leading to dizziness and imbalance. Genes play an important role in its etiology, but the genetics are complex and poorly understood. In this study we have analyzed the complex inheritance pattern in the Epistatic circler mouse, which shows circling behavior indicative of vestibular dysfunction in the mouse. This phenotype exists in a proportion of the F2-generation from an intercross between C57L/J and SWR/J mouse strains. Genetic investigation indicates that the circling behavior is caused by a major recessively inherited gene derived from the SWR/J strain (the Ecs-gene) in combination with at least three different modifier genes derived from C57L/J (the Ecl-genes). Genetic mapping made it possible to localize the Ecs-gene to chromosome 14 and the Ecl-genes to chromosome 3, 4, and 13. This study illustrates the feasibility of identifying genes for multifactorial traits in mice.