Aims/hypothesis We carried out a urinary metabolomic study to gain insight into low estimated GFR (eGFR) in patients with non-proteinuric type 2 diabetes. Methods Patients were identified as being non-proteinuric using multiple urinalyses. Cases (n=44) with low eGFR and controls (n=46) had eGFR values <60 and ≥60 ml min , respectively, as calculated using the Modification of Diet in Renal Disease formula. Urine samples were analysed by liquid chromatography/mass spectrometry (LC/ MS) and GC/MS. False discovery rates were used to adjust for multiple hypotheses testing, and selection of metabolites that best predicted low eGFR status was achieved using least absolute shrinkage and selection operator logistic regression. Results Eleven GC/MS metabolites were strongly associated with low eGFR after correction for multiple hypotheses testing (smallest adjusted p value=2.62×10
Activation of the TNF-alpha system may potentially exert independent effects on ln ACR and eGFR in type 2 diabetes. Because of the study design, one may also consider the possibility that changes in these renal traits may conversely be responsible for such an inflammatory response.
Considerable evidence attests to the role of the hypothalamic-pituitary endocrine axis (HPA) in the maintenance of normal immunocompetence. The immune and neuroendocrine systems are integrally linked and coordinated with bidirectional communication maintaining immune balance. Any disturbance of the normal function of the HPA may significantly alter native immunocompetence and therefore be associated with the development of disorders which have a clearly established autoimmune basis. Molecular and functional evidence shows prolactin, produced by the anterior pituitary, to be a cytokine, exerting its effect via both paracrine and endocrine mechanisms [1]. Its involvement in the activation of multiple immune responses may adversely upregulate certain autoimmune diseases. Myasthenia gravis (MG) has long been recognized as an autoimmune disorder. In this mini review, we present the coterminous presentation of MG and prolactin-secreting macroadenoma. We review published cases in the world literature, discuss pathological mechanism, and consider future targeted therapies.
Aims
Recommendations for metformin use are dependent on eGFR category: eGFR >45 ml/min/1.73 m2 – “first-line agent”; eGFR 30–44 – “use with caution”; eGFR<30 – “do not use”. Misclassification of metformin eligibility by creatinine-based MDRD GFR estimates (eGFRcr) may contribute to its misuse. We investigated the impact of cystatin c estimates of GFR (eGFRcys) on metformin eligibility.
Methods
In a consecutive cohort of 550 Veterans with diabetes, metformin use and eligibility were assessed by eGFR category, using eGFRcr and eGFRcys. Discrepancy in eligibility was defined as cases where eGFRcr and eGFRcys categories (<30, 30–44, 45–60, and >60 ml/min/1.73 m2) differed with an absolute difference in eGFR of >5 ml/min/1.73 m2. We modeled predictors of metformin use and eGFR category discrepancy with multivariable relative risk regression and multinomial logistic regression.
Results
Subjects were 95% male, median age 68, and racially diverse (45% White, 22% Black, 11% Asian, 22% unknown). Metformin use decreased with severity of eGFRcr category, from 63% in eGFRcr >60 to 3% in eGFRcr <30. eGFRcys reclassified 20% of Veterans into different eGFR categories. Factors associated with a more severe eGFRcys category compared to eGFRcr were older age (aOR = 2.21 per decade, 1.44–1.82), higher BMI (aOR = 1.04 per kg/m2, 1.01–1.08) and albuminuria >30 mg/g (aOR = 1.81, 1.20–2.73).
Conclusions
Metformin use is low among Veterans with CKD. eGFRcys may serve as a confirmatory estimate of kidney function to allow safe use of metformin among patients with CKD, particularly among older individuals and those with albuminuria.
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