Association of elevated extracellular HSP72 in albuminuria with systemic inflammation and disease progression in type 2 diabetic kidney disease.

BACKGROUND: Sub-clinical inflammation in hyperglycemia is tied to the pathogenesis of diabetic kidney disease (DKD). Though well known for its immunostimulatory function, the significance of extracellular heat shock protein 72 (eHSP72) in DKD is not well studied. We aimed to determine the association of extracellular HSP72 with systemic inflammation and the progression of DKD, and explore its possible clinical significance in DKD. METHODS: 160 type 2 diabetic individuals were enrolled in the study. Their anthropometric data, routine biochemical parameters, urinary renal function parameters, and blood count parameters were estimated. Plasma from patients' blood samples were used to estimate HSP72 and interleukin 1ß (IL-1ß) using sandwich immunoassays. RESULTS: Plasma eHSP72 is elevated in DKD. Pairwise comparisons showed the drastic elevation of eHSP72 in the presence of albuminuria. A significant positive relationship was observed between plasma levels of eHSP72 and IL-1ß. eHSP72 levels did not statistically differ between micro and macro-albuminuric DKD. However, it was inversely associated with estimated glomerular filtration rate, the index of disease severity, independent of age, gender, diabetes duration and absolute monocyte count. At a cutoff of 0.52 ng/ml, with sensitivity of 64.1 % and specificity of 69.2 %, plasma eHSP72 differentiated the presence of DKD in type 2 diabetics with statistical significance. CONCLUSION: The positive relationship of eHSP72 and IL-1ß with worsening DKD likely indicates their participation in immunostimulatory pathways of renal fibrosis. eHSP72 may be closely linked to albuminuria-induced tubular injury and likely contributes to fibrotic changes in the progression of DKD. From our study, we infer the possible clinical significance of eHSP72 as a marker of sub-clinical renal damage in DKD, and the implication of IL-1ß-associated mechanisms in DKD progression.

Circulating 18-Glycosyl Hydrolase Protein Chitiotriosidase-1 is Associated with Renal Dysfunction and Systemic Inflammation in Diabetic Kidney Disease.

Introduction: Chitotriosidase-1 (CHIT-1) is a marker of macrophage activation and recently attributed to type 2 diabetes mellitus (T2DM). However, its role in the development and progression of diabetic kidney disease (DKD) has been sparsely discussed in the recent literature. Materials and Methods: In this cross-sectional exploratory study, 81 participants with T2DM were classified into two groups based on the presence of DKD. Their anthropometric, biochemical, and pathological profiles were estimated. Circulatory CHIT-1 concentration was determined using the enzyme-linked immuno-sorbent assay (ELISA) in plasma. Results: CHIT-1 was significantly elevated in diabetic nephropathy, independent of age and gender. It is associated with severity of kidney disease, as assessed using urinary protein-creatinine ratio (uPCR) in a multiple linear regression model, independent of age, gender, diabetes duration, and insulin resistance. CHIT-1 positively predicted the likelihood of DKD in the study population (area under the curve = 0.724, P < 0.05). The duration of diabetes correlated positively with uPCR and negatively with estimated glomerular-filtration rate. Neutrophil-Lymphocyte ratio was elevated in participants with DKD. This well-established marker of systemic inflammation exhibited significant positive association with CHIT-1. Conclusion: Plasma CHIT-1 protein is elevated in DKD and associated with disease progression. It is capable of reflecting disease severity and is closely related to systemic inflammation possibly caused by pro-inflammatory circulatory immune cells.

Association of serum omentin-1, apelin and chemerin concentrations with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients.

Omentin-1 is a novel adipokine with anti-inflammatory functions. Apelin is associated with hyperinsulinemia and pathological angiogenesis. Chemerin has both pro- and anti-inflammatory actions and implicated in insulin resistance and metabolic syndrome. The aim of this study was to assess serum omentin-1, apelin and chemerin concentrations and to investigate their association with the presence and severity of DR in T2DM patients. Serum omentin-1, apelin and chemerin were measured in 112 patients with DR and 56 patients without DR. Bivariate analysis showed omentin-1 correlated negatively with hsCRP and TyG index; while apelin correlated positively with chemerin. Linear regression data showed that apelin and chemerin were independent predictors of DR severity. ROC curve revealed that omentin-1 was the best discriminant for DR while apelin was the best discriminant for vision threatening retinopathy. Serum omentin-1 concentration correlates negatively, while serum apelin and chemerin concentrations correlate positively with DR presence and severity in T2DM patients.

Circulating adropin and vascular endothelial growth factor receptor-2 levels in age-related macular degeneration and T2DM patients-A cross-sectional study.

BACKGROUND: Macular drusen formation and angiogenesis are the two chief processes associated with age-related macular degeneration. Adropin and vascular endothelial growth factor receptor-2 (VEGFR-2) may be involved in these pathologies. By altering lipid metabolism, adropin may contribute in the early stages of age-related macular degeneration (AMD). VEGFR-2 may participate in the later form of AMD, by promoting angiogenesis. This study compared the circulatory levels of adropin and VEGFR-2 in AMD and patients without AMD and assessed their association with disease severity, to understand their possible role in AMD. OBJECTIVES: This study aimed to assess and compare the serum levels of adropin and VEGFR-2 in patients with AMD and type 2 diabetes patients without AMD, and, to investigate the correlation between these two parameters with disease severity. METHODS: Our study involves two groups of 39 each. Group A (age-related macular degeneration) and Group B (diabetes patients without age-related macular degeneration). Routine parameters fasting blood sugar (FBS), lipid profile, and liver function tests (LFT) were estimated by using autoanalyzer. Serum adropin and VEGFR-2 were assessed by ELISA. RESULTS: Among the basic parameters, systolic blood pressure and fasting blood glucose alone were significantly different across the groups. We did not find significant alterations in adropin and VEGFR-2 levels between the study groups. Our lipid profile parameters (triglycerides and total cholesterol) have significant positive association. VEGFR-2 showed a positive correlation with the severity of AMD. Adropin did not exhibit any correlation with disease severity and with VEGFR-2. CONCLUSION: We could not find any observable alterations of statistical significance, in adropin and VEGFR-2 levels. VEGFR-2's correlation with disease severity could be important. Adropin might have subtler roles in AMD, though not evident from our study, and requires a deeper observation at the molecular level to elucidate its function.

Community Acquired AKI: A Prospective Observational Study from a Tertiary Level Hospital in Southern India.

INTRODUCTION: Pattern of acute kidney injury (AKI) differs vastly from region to region in India. Moreover, prospective data on community-acquired AKI (CAAKI) using the KDIGO criteria for AKI are limited. Our objective was to study the etiology, clinical characteristics, and short-term outcome of CAAKI in adults. METHODS: This was a prospective observational study in the medical wards of a tertiary care hospital. Patients fulfilling the 2012 KDIGO AKI criteria of community acquired acute kidney injury (CAAKI) were included. Patients who developed AKI 48 hours after admission, those hospitalized >48 hours elsewhere, and patients with chronic kidney disease were excluded. The study did not include obstetric or surgical cases of AKI. Serum creatinine and urine output was monitored. Daily progress, in particular development of hypotension, oliguria, acute respiratory distress syndrome, sepsis, and renal replacement therapy, was noted. RESULTS: Of 186 CAAKI patients (mean age, 46.13 ± 15.2 years), 86/186 was infective etiology, 93/186 was non-infective etiology, 7/186 was due to intrinsic renal pathology. Pyelonephritis 33/186 (17.7%) was the most common infective etiology, and snakebite in 49 (26.3%) was the most common non-infective etiology; 28/186 (15.1%) died. On logistic regression, hypotension, mechanical ventilation, thrombocytopenia, and anuria were associated with mortality. CONCLUSIONS: Acute pyelonephritis and snakebite-related AKI emerged as the two most common medical causes of CAAKI in our region. Such environmental and infectious causes that largely are preventable causes of AKI are also associated with significant morbidity and mortality.

A fatal case of bone marrow embolism of unknown cause masquerading clinically as dengue shock syndrome.

Bone marrow fat embolism usually occurs following multiple bone fractures, intraosseous surgical procedures, following vigorous cardiac resuscitation, ecclampsia, sickle cell anemia, malignancies, etc. We present a case of 70-year-old male who presented with fever, cough with expectoration, respiratory distress, altered sensorium, hypotension and thrombocytopenia, and diagnosed to have dengue shock syndrome and expired within 1 day of admission. Postmortem lung biopsy revealed bone marrow fat embolism.