This study was carried out to look for diagnostic and prognostic role of neutrophil gelatinase-associated lipocalin (NGAL) in early diabetic nephropathy (DN) in type 2 diabetes individuals. NGAL was measured in both urinary and serum sample of 144 type 2 diabetes individuals stratified into three categories based on urinary albumin-creatinine ratio and 54 control populations with estimated glomerular filtration rate >60 mL/min/1.73 m2 and serum creatinine <1.2 mg/dl. The serum NGAL (sNGAL), urine NGAL (uNGAL), and uNGAL/urine creatinine were significantly higher in diabetic individuals than in the control populations with significant difference in between the groups (P < 0.05). Difference of above values between control value and normoalbuminuria was also statistically significant (P < 0.05). Again, sNGAL and uNGAL correlate positively with albuminuria (P < 0.05). Tubular injury may precede glomerular injury in diabetic individuals, and NGAL can be used as a biomarker to diagnose DN even earlier to incipient nephropathy. Both sNGAL and uNGAL can predict albuminuria and be used as a noninvasive tool for diagnosis, staging, and progression of DN.

Purpose We evaluated T helper lymphocyte profile, including novel Th17 subsets Th17.1 (secrete IFN-γ, associate with corticosteroid resistance) and PD1+Th17 (secrete TGF-β1, implicated in fibrosis), and related cytokines in peripheral blood of Takayasu arteritis (TAK). Materials and Methods We evaluated circulating Th1, Th2, Th17, Th17.1, PD1+CD4+ T lymphocytes, PD1+Th17, and Treg lymphocytes, inflammatory (IFN-γ, IL-4, IL-6, IL-17A, IL-23, IL-1β, TNF-α) and regulatory (IL-10, TGF-β1) cytokines in peripheral blood of TAK (n = 57; median age 35 (interquartile range 26–45) years; 40 females) in a cross-sectional design. We studied inflammatory and regulatory cytokines in culture supernatant of peripheral blood mononuclear cells (PBMCs) from TAK following stimulation with anti-CD3/anti-CD28 and their modulation by tacrolimus (immunosuppressive) with/without tadalafil (anti-fibrotic). Furthermore, we followed up immunosuppressive-naïve active TAK (n = 16) and compared T helper lymphocyte populations and cytokines before and after immunosuppressive therapy. Healthy controls (HC, n = 21) and sarcoidosis (disease control, n = 11) were compared against TAK. Results TAK had higher Th17, Th17.1 and PD1+Th17 lymphocytes than HC (p < 0.001), and higher PD1+CD4+ T lymphocytes than sarcoidosis (p < 0.001). Th17 lymphocytes associated with active TAK after multivariable-adjusted logistic regression (p = 0.008). TAK had greater cytokine secretion from PBMCs (IFN-γ, IL-17A, IL-10 versus HC; IL-6, TNF-α, IL-1β versus HC or sarcoidosis) (p < 0.05). In-vitro, PBMCs from TAK showed reduced secretion of all inflammatory cytokines with tacrolimus, with synergistic reduction in IL-17A, IL-6, IL-1β and IL-10 following addition of tadalafil to tacrolimus. Serial follow-up of immunosuppressive-naïve TAK (n = 16) showed reduction in serum IL-6 and TGF-β1 (p < 0.05) and IL-6 in culture supernatant (p < 0.05) following immunosuppressive therapy. Conclusion Novel Th17 sub-populations (Th17.1 and PD1+Th17) are elevated in TAK. Th17 lymphocytes associate with active TAK. In-vitro experiments on cultured PBMCs suggest promise for further evaluation of a combination of immunosuppressive tacrolimus with anti-fibrotic tadalafil (or other anti-fibrotic therapies) in clinical trials of TAK.

Introduction: Tacrolimus (TAC) is the mainstay immunosuppressant for renal transplantation. A narrow therapeutic index, multiple drug interactions, and interindividual variability in pharmacokinetics make it obligatory to monitor therapeutic drug levels. The Multidrug resistance gene 1 (MDR1) and CYP3A5 gene polymorphism may blend to achieve the optimal level. The optimal dose as per body weight is difficult to single out in the early posttransplantation period. In this study, we aimed to analyze the melding effect of both gene polymorphisms and to elicit the dose depending on the combination of genetic single nucleotide polymorphisms (SNPs) in northern Indian transplant recipients, for whom data are limited. Methods: The daily TAC dose, weight-adjusted doses (mg/kg per day), TAC trough blood concentration (average of at least 3 levels), dose normalized with a corresponding dose using TAC concentration/weightadjusted dose ratio (ng/ml per mg/kg per day) of 248 patients were recorded. All recipients were genotyped for the SNPs of CYP3A5 at intron 3 A6986G (the *3 or *1 allele), MDR1 at exons 12 (C1236T), 21 (G2677A/T), and 26 (C3435T). We analyzed the blending effect of mutant SNPs of the MDR gene and CYP3A5 for optimized TAC levels. Results: Among CYP3A5 genotypic variants, the dose-adjusted TAC level was significantly lower, and the TAC dose required to achieve the target level was significantly higher, in CYP3A5*1*1 (expressor) than that of CYP3A5*1*3 and CYP3A5*3*3. Of the MDR1 gene SNPs, only the G2677T/A homozygous mutant was significantly associated with TAC level, and it was strongly correlated with P-gp expression.The daily TAC dose requirement was highest with a combination of CYP3A5*1*1 and homozygous mutant TTþAA genotype of G2677T/A, and was lowest with CYP3A5*3*3 and wild-type GG of the G2677T/A genotype. Conclusion: Both CYP gene and MDR1 gene polymorphism affect TAC dose requirements, and there is a need to look for both in an individual to achieve the target trough concentration.

Vaccination-induced SARS-CoV-2 neutralizing antibodies are required for herd immunity. Vaccine availability and poor vaccine response in renal transplant recipients (RTRs) remain a concern. There is no report on the efficacy of Covaxin and Covishield vaccines in RTRs. We recruited 222 live donors RTRs and analyzed the serum titer of anti-SARS-CoV-2 spike protein antibody by chemiluminescent magnetic microparticle immunoassay. Patients were categorized into three groups: group1 with SARS-CoV-2 infection and no vaccination (n = 161); group 2 with only vaccination and no SARS-CoV-2 infection (n = 41); and group 3 with both vaccination and SARS-CoV-2 infection (n = 20). Overall seroconversion rate was 193/222 (86.9%) with a median titer 1095.20 AU/mL. The median IgG titer value in group 1 was 647.0 AU/mL; group 2 was 1409.0 AU/mL; and group 3 was 1831.30 AU/mL. Covaxin associated seroconversion was observed in 16/19 (84.21%), with a median titer of 1373.90 AU/mL compared to that of Covishield 32/42 (76.19%), whose median titer was 1831.10 AU/mL. The seroconversion rate due to SARS-CoV-2 infection was 145 (90.06%), it was lowest with the vaccination-only group (70.7%), and with both vaccination and SARS-CoV-2 infection group it was highest (95%). In RTRs, SARS-CoV-2 infection and both Covaxin and Covishield vaccination effectively induce a humoral immune response against the SARS-CoV-2 spike protein; however, seroconversion rate was lower and the antibody titer was higher with vaccine than infection.

Kidney transplant recipients (KTRs) are at a much higher risk of complications and death following COVID-19 and are poor vaccine responders. The data are limited on the immune response to Covishield® in KTRs. We prospectively recruited a cohort of 67 KTRs aged >18 between April 2021 and December 2021. Each participant was given two intramuscular doses of Covishield®, each of 0.5 mL, at an interval of 12 weeks. A blood specimen of 5.0 mL was collected from each participant at two points within a few days before administering the first dose of the vaccine and at any time between 4–12 weeks after administering the second dose. The sera were tested for anti-RBD antibody (ARAb) titre and neutralising antibody (NAb). An ACE2 competition assay was used as a proxy for virus neutralization. According to the prior COVID-19 infection, participants were grouped as (i) group A: prior symptomatic COVID-19 infection, (ii) group B: prior asymptomatic COVID-19 infection as evidenced by detectable ARAb in the prevaccination specimen, (iii) Group C: no prior infection with COVID-19, (iv) group D: Unclassified, i.e., participants had no symptoms suggestive of COVID-19, but their prevaccination specimen was not available for ARAb testing before vaccination. Fifty of sixty-seven participants (74.6%) provided paired specimens (group A 14, group B 27, and group C 9) and 17 participants (25.4%) provided only postvaccination specimens (group D). In the overall cohort (n = 67), 91% and 77.6% of participants developed ARAb and NAb, respectively. Their ARAb titre and NAb proportion were 2927 (520–7124) U/mL and 87.9 (24.4–93.2) %, respectively. Their median ARAb titre increased 65.6 folds, from 38.2 U/mL to 3137 U/mL. Similarly, the proportion of participants with NAb increased from 56% to 86%, and the NAb proportion raised 2.7 folds, from 23% to 91%. A comparison of vaccine response between the study groups showed that all those with or without prior COVID-19 infection showed a significant rise in ARAb titre (p < 0.05) and NAb proportion (p < 0.05) after the two doses of vaccine administration. The median value of folds rise in anti-RBD and NAb between groups A and B were comparable. Hence, ARAb is present in more than 3/4th of KTRs before the ChAdOx1 vaccine in India. The titer of ARAb and the proportion of NAb significantly increased after the two doses of the ChAdOx1 vaccine in KTRs.