Hypomagnesemia in type 2 diabetic nephropathy: a novel predictor of end-stage renal disease

OBJECTIVE

There is now growing evidence that magnesium (Mg) deficiency is implicated in type 2 diabetes and its complications. However, it has not been fully elucidated whether hypomagnesemia is a predictor of end-stage renal disease (ESRD) in type 2 diabetic nephropathy.

RESEARCH DESIGN AND METHODS

This retrospective cohort study included 455 chronic kidney disease (CKD) patients (144 with type 2 diabetic nephropathy and 311 with nondiabetic CKD) who were hospitalized at Osaka General Medical Center for a CKD educational program between April 2001 and December 2007. The primary outcome was progression to renal replacement therapy. Participants were categorized based on serum Mg level into Low-Mg (serum Mg level ≤1.8 mg/dL) and High-Mg (serum Mg level >1.8 mg/dL) groups with the previously published normal lower limit chosen as the cutoff point.

RESULTS

Of the subjects with type 2 diabetic nephropathy, 102 progressed to ESRD during follow-up (median, 23 months). A multivariate Cox proportional hazards model showed that after adjustment for various demographic factors and laboratory data, the Low-Mg group had a 2.12-fold higher risk of ESRD than the High-Mg group (95% CI 1.28–3.51; P = 0.004). In contrast, 135 of the nondiabetic CKD subjects progressed to ESRD during follow-up (median, 44 months). No significant difference in outcome was found between the Low- and High-Mg groups of this population (adjusted hazard ratio, 1.15; 95% CI 0.70–1.90; P = 0.57).

CONCLUSIONS

Hypomagnesemia is a novel predictor of ESRD in patients with type 2 diabetic nephropathy.Magnesium (Mg) is the fourth most abundant cation in the human body and plays a key role in many fundamental biological processes, including energy metabolism and DNA synthesis. Mg deficiency has been shown to cause endothelial cell dysfunction, inflammation, and oxidative stress, which are major contributors to atherosclerosis (1–3). Some epidemiologic studies have reported associations between low Mg intake or serum Mg level and hypertension, coronary artery disease, and ischemic stroke (4–6).Mg and type 2 diabetes have a close relationship. Approximately one-third of patients with type 2 diabetes have hypomagnesemia, mainly caused by enhanced renal excretion (7). Mg deficiency is associated with poor glycemic control, and Mg supplementation improves insulin sensitivity (8). Moreover, there is substantial evidence of associations between hypomagnesemia and various complications of type 2 diabetes, including neuropathy, retinopathy, foot ulcers, and albuminuria (9–12). The relationship between Mg deficiency and advanced type 2 diabetic nephropathy, however, remains to be fully elucidated. Pham et al. (13) reported that serum Mg level was significantly associated with the slope of inverse serum creatinine (SCr) in type 2 diabetes with near-normal renal function. However, they failed to show a significant association between hypomagnesemia and hard renal outcome (doubling of SCr and initiation of renal replacement therapy [RRT]), probably due to low statistical power (14). Therefore, the aim of the current study was to determine whether hypomagnesemia is a predictor of end-stage renal disease (ESRD) in patients with advanced type 2 diabetic nephropathy. We also compared the impact of hypomagnesemia on renal outcome in type 2 diabetic nephropathy with that in nondiabetic chronic kidney disease (CKD).     

ACTN4 copy number increase as a predictive biomarker for chemoradiotherapy of locally advanced pancreatic cancer

Background:

Several clinical trials have compared chemotherapy alone and chemoradiotherapy (CRT) for locally advanced pancreatic cancer (LAPC) treatment. However, predictive biomarkers for optimal therapy of LAPC remain to be identified.We retrospectively estimated amplification of the ACTN4 gene to determine its usefulness as a predictive biomarker for LAPC.

Methods:

The copy number of ACTN4 in 91 biopsy specimens of LAPC before treatment was evaluated using fluorescence in situ hybridisation (FISH).

Results:

There were no statistically significant differences in overall survival (OS) or progression-free survival (PFS) of LAPC between patients treated with chemotherapy alone or with CRT. In a subgroup analysis of patients treated with CRT, patients with a copy number increase (CNI) of ACTN4 had a worse prognosis of OS than those with a normal copy number (NCN) of ACTN4 (P=0.0005, log-rank test). However, OS in the subgroup treated with chemotherapy alone was not significantly different between patients with a CNI and a NCN of ACTN4. In the patients with a NCN of ACTN4, the median survival time of PFS in CRT-treated patients was longer than that of patients treated with chemotherapy alone (P=0.049).

Conclusions:

The copy number of ACTN4 is a predictive biomarker for CRT of LAPC.     

Morphological characteristics of basal-like subtype of breast carcinoma with special reference to cytopathological features

Expression profiling of invasive breast carcinomas by DNA microarray techniques has identified five distinct subtypes of tumors (luminal A, luminal B, normal breast-like, HER2 overexpression, and basal-like) that are associated with different clinical outcomes and with different chemotherapy. Basal-like carcinoma is associated with younger patient age, high histological grade, aggressive clinical course, development of distant metastasis, poor prognosis, and relatively high mortality rate. Basal-like carcinomas do not express estrogen receptor, progesterone receptor, or HER2 (triple-negative phenotype). Therefore, patients with basal-like carcinomas are not likely to benefit from endocrine therapies or trastuzumab, but are likely to benefit from systemic chemotherapy. Although genetic, morphological, and immunohistochemical features of basal-like carcinomas have been reported, there is no universal definition for those tumors. Furthermore, there are no specific morphological and immunohistochemical features that can identify those tumors in routine diagnostic materials. In the present paper, we present data of histological and cytological features of basal-like breast carcinoma, and discuss about its morphological spectrum.     

Rubidium-82 PET-CT for quantitative assessment of myocardial blood flow: validation in a canine model of coronary artery stenosis

Purpose

Absolute quantification of myocardial blood flow expands the diagnostic potential of PET for assessment of coronary artery disease. ⁸²Rb has significantly contributed to increasing utilization of PET; however, clinical studies are still mostly analysed qualitatively. The aim of this study was to reevaluate the feasibility of ⁸²Rb for flow quantification, using hybrid PET-CT in an animal model of coronary stenosis.

Methods

Nine dogs were prepared with experimental coronary artery stenosis. Dynamic PET was performed for 8 min after ⁸²Rb(1480–1850 MBq) injection during adenosine-induced vasodilation. Microspheres were injected simultaneously for reference flow measurements. CT angiography was used to determine the myocardial regions related to the stenotic vessel. Two methods for flow calculation were employed: a two-compartment model including a spill-over term, and a simplified retention index.

Results

The two-compartment model data were in good agreement with microsphere flow (y?=?0.84x + 0.20; r?=?0.92, p<0.0001), although there was variability in the physiological flow range <3 ml/g per minute (y?=?0.54x + 0.53; r =?0.53, p?=?0.042). Results from the retention index also correlated well with microsphere flow (y?=?0.47x + 0.52; r?=?0.75, p?=?0.0004). Error increased with higher flow, but the correlation was good in the physiological range (y?=?0.62x + 0.29; r?=?0.84, p?=?0.0001).

Conclusion

Using current state-of-the-art PET-CT systems, quantification of myocardial blood flow is feasible with ⁸²Rb. A simplified approach based on tracer retention is practicable in the physiological flow range. These results encourage further testing of the robustness and usefulness in the clinical context of cardiac hybrid imaging.     

Efficacy of peroral pancreatoscopy in the diagnosis of pancreatic diseases

BACKGROUND: The aim of this study was to evaluate the usefulness of peroral pancreatoscopy in the diagnosis of pancreatic diseases. METHODS: Both 3.7-mm (thin) and 0.8-mm (ultra-thin) diameter fiberoptic pancreatoscopes were used in 115 cases (pancreatic cancer, 35; benign ductal stenosis, 20; intraductal papillary-mucinous tumor, 60). RESULTS: Observation rates for pancreatic cancer, benign ductal stenosis, and intraductal papillary-mucinous tumor were, respectively, 63%, 80%, and 95%. Tumor vessels and papillary tumor were observed when pancreatic cancer was smaller than 2 cm but not when the tumor was larger than 2 cm. Stenosis without significant mucosal changes was observed in 62% of cases of benign ductal stenosis. Coarse mucosa and friability were observed more frequently in association with pancreatic cancer than benign ductal stenosis. Granular mucosa or papillary tumor could be observed in 74% of cases of intraductal papillary-mucinous tumor. Papillary tumor was observed with increasing frequency in cases of intraductal papillary-mucinous tumor as the degree of malignancy increased. CONCLUSIONS: Peroral pancreatoscopy with an ultra-thin fiberscope is useful in the diagnosis of minute pancreatic lesions. Peroral pancreatoscopy with a thin fiberscope can provide a definitive diagnosis of intraductal papillary-mucinous tumor including the degree of malignancy.