Zinc Alpha 2 Glycoprotein as an Early Biomarker of Diabetic Nephropathy in Type 2 Diabetes Mellitus Patients.

Background and objectives Microalbuminuria is an early sign of diabetic nephropathy (DN). However, pathological abnormalities occur before the onset of microalbuminuria. Renal impairment progresses in about 50% of cases in type 2 diabetes mellitus (T2DM) without significant albuminuria. Diabetes mellitus (DM) is linked with obesity, metabolic syndrome, and lifestyle changes, where adipokines play an important role. Zinc alpha 2 glycoprotein (ZAGP) is an adipokine, and in this study, it was assessed as a potential biomarker for early DN as well as its progression. Materials and methods This study was a cross-sectional case-control study conducted at a tertiary hospital in northern India. T2DM patients aged 18-65 years old were included in the study and were divided into four groups based on their albuminuria level. This study included 160 participants, with 40 participants in each group. Group I included healthy volunteers, while Groups II, III, and IV were normoalbuminuric, microalbuminuric, and macroalbuminuric diabetic patients, respectively. The groups were evaluated for demographic variables, biochemical parameters, urine albumin-creatinine ratio (UACR), and serum ZAGP. Data between the groups were compared statistically. Results This study included 160 participants, with 40 participants in each group. There was a significant difference between the groups based on the serum ZAGP (p<0.001). Serum ZAGP was significantly negatively correlated with serum creatinine, glycosylated hemoglobin (HbA1c), serum cholesterol, serum triglyceride, low-density lipoprotein (LDL) cholesterol, and UACR. ZAGP was positively correlated with the estimated glomerular filtration rate (eGFR). Conclusion The present study showed that ZAGP was an early biomarker of diabetic nephropathy, and its value decreased as DN progressed. It also suggested that ZAGP, an adipokine, has an anti-inflammatory mechanism of action and its depletion worsens the disease.

Association of Pulmonary Hypertension With Inflammatory Markers and Volume Status in Hemodialysis Patients of End-Stage Renal Disease.

Background and objectives Pulmonary hypertension (PH) is an independent risk factor for increased mortality, especially in patients undergoing hemodialysis (HD), but the mechanism of its development is unknown. This study aimed at evaluating volume overload and inflammation as potential variables to cause its development in patients undergoing maintenance hemodialysis. Materials and methods This was an observational cross-sectional study conducted on patients undergoing hemodialysis at a tertiary hospital in northern India. Patients of end-stage renal disease, aged 18 years or more, on maintenance hemodialysis for over two months were included in the study. The patients were divided into two groups based on the presence or absence of PH, determined by measuring systolic pulmonary arterial pressure (SPAP). The severity of PH was defined as: mild (SPAP 35-45 mmHg), moderate (SPAP 46-55 mmHg), and severe (SPAP> 55mmHg). The two groups were evaluated for demographic variables, type of vascular access, biochemical parameters, and markers of inflammation and fluid overload. Data between the two groups were compared statistically. Results This study included a total of 82 patients showing the prevalence of PH to be 25.6% with a men-to-women ratio of 2:1. Out of 21 cases of PH, mild PH was found in seven (33.3%) cases, moderate in 14 (66.7%), and cases with severe PH were none. The two groups differed significantly in ejection fraction and markers of inflammation and volume status. Laboratory data associated with PH were alpha-1-acid glycoprotein (p<0.05) and pro-b-type natriuretic peptide (p <0.05). Conclusion The present study showed higher levels of inflammatory markers alpha-1-acid glycoprotein and pro-b-type natriuretic peptide and lower levels of ejection fraction in patients undergoing HD, indicating a significant association with PH.

Is rheumatoid factor still a superior test for the diagnosis of rheumatoid arthritis?

The diagnosis of rheumatoid arthritis (RA) is based primarily on the 1987 revised American College of Rheumatology criteria for RA, which considers mainly the clinical symptoms. But typical clinical symptoms of RA are not manifested completely in early disease course. On the other hand, appreciable advantages have been made in the therapeutic strategy of RA in the last decade and highly effective disease-modifying anti-rheumatic drugs are available now for the control of RA. The treatment strategy for the control of early RA is aggressive. Thus, a highly specific and early diagnostic marker is needed for the detection of RA. Our study is an attempt to see the role of anti-CCP2 antibody (claimed to be highly specific and early diagnostic tool) in the diagnosis of RA. We studied 119 cases of RA in terms of clinical symptoms, disease duration and various autoantibody [including rheumatoid factor (RF), anti-CCP2 antibody, antinuclear antibody, anti-dsDNA] and C-reactive protein status. All the tests were also performed in 26 age and sex-matched healthy controls. Estimation of antibodies was done by quantitative ELISA. IgM RF was positive in 47.89% cases (p value = 0.000), followed by IgG RF (42.01%, p = 0.000) and IgA RF (36.97%, p = 0.000). RF was positive in 64.7% RA cases (p value = 0.000) when all three isotypes were tested together. RF was also detected in one healthy control. In 92 cases, anti-CCP2 Ab was done, hence other data were analyzed further in 92 cases only. Anti-CCP2 Ab was positive (cut-off = 15.0 U/ml) in only 50% RA patients but none of the healthy controls was positive for it. Swelling of joints was seen in 82.6% anti-CCP2 Ab positive cases (p value = 0.092) when compared with anti-CCP2 Ab negative cases (67.4%) while among RF positive cases, only 65.4% ((p value = 0.010) cases had swelling of joints. Out of 39 RA cases presenting with disease duration less than 1 year, only 48.71% patients were anti-CCP2 Ab positive while RF was positive in 61.53% patients. Utility of various combined autoantibody tests revealed that if one does all isotypes of RF (IgG, IgA and IgM) only, then 64.7% RA cases can be diagnosed and if anti-CCP2 Ab is added to it, the sensitivity increases to 75.56%. Thus, our study concludes that anti-CCP2 Ab is not a sensitive test for the diagnosis of RA neither it is useful in early diagnosis of RA, but it increases the sensitivity if added with all RF isotypes.

Association of various inflammatory diseases with human leukocyte antigens B27, B7, Bw4 and Bw6 in patients with SSA.

Seronegative spondyloarthropathies (SSA) are a group of inflammatory disorders, which clinically involve the axial skeleton and the sacroiliiac and shoulder joints. The aim of the present study was to study the association of HLA B27, B7, Bw4 and Bw6 with some inflammatory diseases, in SSA patients in our area. A total of 220 SSA patients were studied and HLA typing for these antigens were done by the complement-mediated microcytotoxicity method. The total positivity of B27 was found to be 68.64% in SSA patients. Tubercular infection (chi(2) = 8.06) and acute anterior uveitis (chi(2) = 6.19) were found to be statistically significant (P < 0.05) in B27-positive SSA patients. Tuberculosis was also found to be significantly (chi(2) = 6.40) associated with Bw4. In SSA urinary tract infection, gastrointestinal infection and streptococcal infection were not significantly associated with B27, B7, Bw4 or Bw6 antigens. Our study concludes that microbial infections do have some pathogenic role in causing SSA.