Correction to: Serum magnesium, mortality and disease progression in chronic kidney disease.

Following publication of the original article [1], we have been notified that the name of one author was spelled incorrectly as Georges N. Na khoul, when the correct spelling is Georges N. Nakhoul.

Serum magnesium, mortality and disease progression in chronic kidney disease.

INTRODUCTION: Magnesium disorders are commonly encountered in chronic kidney disease (CKD) and are typically a consequence of decreased kidney function or frequently prescribed medications such as diuretics and proton pump inhibitors. While hypomagnesemia has been linked with increased mortality, the association between elevated magnesium levels and mortality is not clearly defined. Additionally, associations between magnesium disorders, type of death, and CKD progression have not been reported. Therefore, we studied the associations between magnesium levels, CKD progression, mortality, and cause specific deaths in patients with CKD. METHODS: Using the Cleveland Clinic CKD registry, we identified 10,568 patients with estimated Glomerular Filtration Rate (eGFR) between 15 and 59 ml/min/1.73 m2 in this range for a minimum of 3 months with a measured magnesium level. We categorized subjects into 3 groups based on these magnesium levels (≤ 1.7, 1.7-2.6 and > 2.6 mg/dl) and applied cox regression modeling and competing risk models to identify associations with overall and cause-specific mortality. We also evaluated the association between magnesium level and slope of eGFR using mixed models. RESULTS: During a median follow-up of 3.7 years, 4656 (44%) patients died. After adjusting for relevant covariates, a magnesium level < 1.7 mg/dl (vs. 1.7-2.6 mg/dl) was associated with higher overall mortality (HR = 1.14, 95% CI: 1.04, 1.24), and with higher sub-distribution hazards for non-cardiovascular non-malignancy mortality (HR = 1.29, 95% CI: 1.12, 1.49). Magnesium levels > 2.6 mg/dl (vs. 1.7-2.6 mg/dl) was associated with a higher risk of all-cause death only (HR = 1.23, 95% CI: 1.03, 1.48). We found similar results when evaluating magnesium as a continuous measure. There were no significant differences in the slope of eGFR across all three magnesium groups (p = 0.10). CONCLUSIONS: In patients with CKD stage 3 and 4, hypomagnesemia was associated with higher all-cause and non-cardiovascular non-malignancy mortality. Hypermagnesemia was associated with higher all-cause mortality. Neither hypo nor hypermagnesemia were associated with an increased risk of CKD progression.

Degeneration of retinal ganglion cells in diabetic dogs and mice: relationship to glycemic control and retinal capillary degeneration.

PURPOSE: The purpose of this study was to investigate (i) the effect of diabetes on retinal ganglion cell death in diabetic dogs and mice, (ii) the effect of prolonged glycemic control on diabetes-induced death of retinal ganglion cells, (iii) whether retinal ganglion cell death in diabetes is associated with degeneration of retinal capillaries, and (iv) the effect of diet on diabetes-induced degeneration of retinal ganglion cells in mice. METHODS: Diabetes was induced in dogs using streptozotocin, and levels of glycemic control (good, moderate, and poor) were maintained for 5 years. Diabetes was studied in two mouse models (diabetes induced in C57Bl/6J mice using streptozotocin and spontaneously diabetic Ins2Akita mice). Retinal ganglion cell death was investigated by counting the number of axons from the ganglion cells in the optic nerve and with terminal transferase deoxyuridine triphosphate nick-end labeling and annexin V staining in mice. RESULTS: As reported previously, the development and severity of vascular lesions of diabetic retinopathy in diabetic dogs were strongly associated with glycemic control. Loss of retinal ganglion cells was extensive in dogs kept in poor glycemic control, and was essentially prevented in diabetic dogs kept in good glycemic control for the 5 years of study. In contrast, "moderate" glycemic control (intermediate between poor and good glycemic control) caused a significant increase in vascular pathology, but did not cause loss of retinal axons in the optic nerve. Using this validated optic nerve axon counting method, the two mouse models of diabetic retinopathy were studied to assess ganglion cell death. Despite 10 months of diabetes (a duration that has been shown to cause retinal capillary degeneration in both models), neither mouse model showed loss of optic nerve axons (thus suggesting no loss of retinal ganglion cells). Likewise, other parameters of cell death (terminal transferase deoxyuridine triphosphate nick-end labeling and annexin V labeling) did not suggest ganglion cell death in diabetic C57Bl/6J mice, and ganglion cell death was not increased by a different commercial diet. CONCLUSIONS: Retinal ganglion cell death in diabetic dogs is significantly inhibited by good or even moderate glycemic control. The finding that diabetic dogs in moderate glycemic control had appreciable vascular disease without apparent retinal ganglion cell degeneration does not support the postulate that neural degeneration causes the vascular pathology. Studies of diabetic mice in our colony again fail to find evidence of ganglion cell death due to prolonged diabetes in this species.

Sh3pxd2b mice are a model for craniofacial dysmorphology and otitis media.

Craniofacial defects that occur through gene mutation during development increase vulnerability to eustachian tube dysfunction. These defects can lead to an increased incidence of otitis media. We examined the effects of a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) on the progression of otitis media and hearing impairment at various developmental stages. We found that all mice that had the Sh3pxd2b(nee) mutation went on to develop craniofacial dysmorphologies and subsequently otitis media, by as early as 11 days of age. We found noteworthy changes in cilia and goblet cells of the middle ear mucosa in Sh3pxd2b(nee) mutant mice using scanning electronic microscopy. By measuring craniofacial dimensions, we determined for the first time in an animal model that this mouse has altered eustachian tube morphology consistent with a more horizontal position of the eustachian tube. All mutants were found to have hearing impairment. Expression of TNF-α and TLR2, which correlates with inflammation in otitis media, was up-regulated in the ears of mutant mice when examined by immunohistochemistry and semi-quantitative RT-PCR. The mouse model with a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) mirrors craniofacial dysmorphology and otitis media in humans.