Clinico-epidemiological characteristics of early- versus late-onset cytomegalovirus disease among renal transplant recipients: A two-decade experience.

BACKGROUND: Reactivation of cytomegalovirus (CMV) infection in transplant patients is high because of immunosuppression. We have evaluated the clinical and epidemiological characteristics of early versus late onset of CMV infection among renal transplant recipients. METHODS: A single center retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between January 2002 and December 2021. CMV disease was classified as early or late depending on its detection prior to or after 90 days post-transplantation. Herein, we reported the differences between early and late onset of CMV disease with respect to clinical symptoms, the use of immunosuppression and the impact on graft outcomes. RESULTS: Out of total 2164 renal transplant recipients, 156 patients (7.2%) were diagnosed with CMV disease. Among these 156 patients, 25 patients (16%) had early CMV while 131 patients (84%) had late CMV. Overall, the two groups did not differ with respect to the induction or maintenance of immunosuppressive agents. However, the proportion of CMV syndrome was greater among early (56.0%) than late (26.7%) CMV groups (p = 0.01). In contrast, tissue invasive disease was more frequent among late (73.3%) in comparison to early (44.0%) CMV groups (p = 0.01). Among clinical symptoms, diarrhea was more frequent in late (63.4%) vs. early (36%) CMV-affected patients (p = 0.01). Graft loss occurred in 4.0% of early CMV group vs. 25.2% of late CMV group (p = 0.03). Neither of the clinical groups differed with respect to occurrence of biopsy-proven allograft rejection post-infection. CONCLUSIONS: Early CMV disease presents more frequently as CMV syndrome while late CMV disease usually manifests itself as tissue invasive disease. Graft loss is more common in patients with late onset of CMV disease.

Capacity for the management of kidney failure in the International Society of Nephrology South Asia region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The South Asia region is facing a high burden of chronic kidney disease (CKD) with limited health resources and low expenditure on health care. In addition to the burden of CKD and kidney failure from traditional risk factors, CKD of unknown etiologies from India and Sri Lanka compounds the challenges of optimal management of CKD in the region. From the third edition of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA), we present the status of CKD burden, infrastructure, funding, resources, and health care personnel using the World Health Organization's building blocks for health systems in the ISN South Asia region. The poor status of the public health care system and low health care expenditure resulted in high out-of-pocket expenditures for people with kidney disease, which further compounded the situation. There is insufficient country capacity across the region to provide kidney replacement therapies to cover the burden. The infrastructure was also not uniformly distributed among the countries in the region. There were no chronic hemodialysis centers in Afghanistan, and peritoneal dialysis services were only available in Bangladesh, India, Nepal, Pakistan, and Sri Lanka. Kidney transplantation was not available in Afghanistan, Bhutan, and Maldives. Conservative kidney management was reported as available in 63% (n = 5) of the countries, yet no country reported availability of the core CKM care components. There was a high hospitalization rate and early mortality because of inadequate kidney care. The lack of national registries and actual disease burden estimates reported in the region prevent policymakers' attention to CKD as an important cause of morbidity and mortality. Data from the 2023 ISN-GKHA, although with some limitations, may be used for advocacy and improving CKD care in the region.

Nocardiosis in kidney transplant recipients: A tertiary care center experience.

INTRODUCTION: Kidney transplant recipients are at increased risk of opportunistic infections, including Nocardia. The incidence of nocardiosis in kidney transplant recipients is 0.4-1.3%. The data regarding its epidemiology and outcomes is limited. METHODS: This was a 10-year retrospective observational study from January 2012 to December 2021 at a tertiary care center in northern India, in which all kidney transplant recipients with Nocardia infection were included and followed. RESULTS: 12 (1.1%) patients had a Nocardia infection among the 1108 kidney transplant recipients. All were living donor kidney transplant recipients, and the mean age at diagnosis was 48.67 ± 12.60 years. Nocardia infection occurred at a median of 26 months (range 4-235) post-transplantation, with 4 (33.1%) of the cases occurring within a year of transplant. Breakthrough infection occurred in 7 (58.3%) patients on cotrimoxazole prophylaxis. 41.7% (n = 5) cases had an episode of rejection in the preceding year of Nocardia diagnosis. Concurrent cytomegalovirus (CMV) infection was present in one (8.3%) case. The lung was the most frequently involved organ. Microscopy was positive in all the cases; while culture was positive in 10 cases, and antimicrobial susceptibility testing (AST) were performed for these isolates. The majority (60%) of isolates were resistant to cotrimoxazole. All tested isolates remained susceptible to Amikacin, Imipenem, and Linezolid. No patients experienced Nocardia recurrence after completion of antibiotic therapy. The mortality at 12 months was 66.7% (n = 4), and only one death was Nocardia-related. CONCLUSION: Nocardia may cause a late-manifesting infection beyond the traditional window. The cotrimoxazole prophylaxis may not be sufficient for Nocardia prevention.

Community-acquired acute kidney injury in India: data from ISN-acute kidney injury registry.

Background: Acute kidney injury (AKI), particularly community-acquired AKI (CA-AKI), is a major health concern globally. The International Society of Nephrology's "0 by 25" initiative to reduce preventable deaths from AKI to zero by 2025 is not achievable in low and middle income countries, such as India, possibly due to a lack of data and measures to tackle this urgent public health issue. In India, CA-AKI predisposes younger patients to hospitalization, morbidity, and mortality. This is the first multicenter, prospective, cohort study investigating CA-AKI and its consequences in India. Methods: This study included data from patients with CA-AKI (>12 years of age) housed in the Indian Society of Nephrology-AKI registry, involving 9 participating tertiary care centers in India, for the period between November 2016 and October 2019. The etiological spectrum and renal and patient outcomes of CA-AKI at the index visit and at 1-month and 3-month follow-ups were analyzed. The impact of socioeconomic status (SES) on outcomes was also analyzed. Findings: Data from 3711 patients (mean [±SD] age 44.7 ± 16.5 years; 66.6% male) were analyzed. The most common comorbidities included hypertension (21.1%) and diabetes (19.1%). AKI occurred in medical, surgical, and obstetrical settings in 86.7%, 7.3%, and 6%, respectively. The most common causes of AKI were associated with sepsis (34.7%) and tropical fever (9.8%). Mortality at the index admission was 10.8%. Complete recovery (CR), partial recovery (PR), and dialysis dependency among survivors at the time of discharge were 22.1%, 57.7%, and 9.4%, respectively. Overall, at 3 months of follow-up, mortality rate, CR, PR, and dialysis dependency rates were 11.4%, 72.2%, 7.2%, and 1%, respectively. Multivariate analysis revealed that age >65 years, alcoholism, anuria, hypotension at presentation, thrombocytopenia, vasopressor use, transaminitis, and low SES were associated with mortality at the index admission. Interpretation: Sepsis and tropical fever were the most common causes of CA-AKI. Presentation of CA-AKI to tertiary care units was associated with high mortality, and a significant number of patients progressed to CKD. Individuals with a low SES had increased risk of mortality and require immediate attention and intervention. Funding: This study was funded by the Indian Society of Nephrology.

Micro-vascular complications of post-transplant diabetes mellitus in renal transplant recipients- an observational study.

INTRODUCTION: The incidence of post-transplant diabetes mellitus (PTDM) ranges from 2.5% to 20% in kidney transplant recipients. Diabetic retinopathy (DR), diabetic kidney disease (DKD), and distal symmetric polyneuropathy (DSPN) are the microvascular complications frequently seen in both type 1 and 2 diabetes mellitus (DM). However, the data regarding these complications in patients with PTDM is lacking. METHOD: A retrospective and prospective observational study of PTDM conducted at a tertiary care hospital from November 2018 to December 2020. 115 kidney transplant recipients who had PTDM of ≥5 years duration were included and analysed. RESULTS: The mean duration of PTDM was 8.8 ± 3.0 years, and the mean of all available HbA1c values was 7.0 ± 0.9%. while none of the patients had evidence of diabetic retinopathy on direct ophthalmoscopy, 37.4% of patients (n = 43) had DSPN and this was associated with the duration of PTDM and age. The mean estimated glomerular filtration rate (eGFR) was 59.24 ± 21.82 ml/min/1.73m2, and patients had a median proteinuria of 620 mg/day (IQR 1290). Out of 115 patients, 20% of them (n = 23) underwent graft kidney biopsy, and 10 biopsies were diagnosed as de-novo DKD. Patients with biopsy proven DKD had a mean PTDM duration of 143.3 ± 52.4 months; a mean HbA1c level of 7.9 ± 1.3%; a mean eGFR of 44.8 ± 21.8 ml/min; and a median proteinuria of 2653 mg (IQR 2758). An additional analysis of all 23 biopsied patients showed that HbA1c level and degree of proteinuria were significantly associated with de-novo DKD. CONCLUSION: PTDM in transplant patients had milder microvascular complications than usually expected in Type 1/2 diabetes in non-transplant patients. DR was not strongly associated with DKD in PTDM patients. Furthermore, de-novo DKD development was associated with poor glycaemic control and increased proteinuria.

Prognostic significance of circulating microparticles in IgA nephropathy.

PURPOSE: Endothelial injury, involved in the pathogenesis of renal fibrosis, can generate microparticles (MPs). These are 0.1-1 µm membrane-bound vesicles shed from the damaged or activated cell surfaces. We analyzed the presence of circulating MPs and EnMPs in IgAN and correlated with markers of endothelial injury and disease activity. METHODS: The study included 30 IgAN (mean age 31.5 ± 9 years), 25 healthy controls and Lupus nephritis (n = 10) as disease controls. Circulating MPs were quantitated by Flow cytometry and EnMPs were analyzed using anti-CD31-FITC and anti-CD146-PE antibodies. Their levels were correlated with serum von Willebrand Factor, histological Oxford MEST-C score and renal outcome. A prospective validation group of 20 patients of biopsy-proven IgA nephropathy was also included. RESULTS: IgAN had significantly higher levels of MPs, EnMPs and vWF compared to controls. On multivariate analysis, plasma levels of total MPs, EnMPs and serum vWF correlated significantly with the presence of hypertension and E1 on histology. E1 and high MPs (> 130 counts/µl) were associated with shorter time to doubling of serum creatinine. MPs cutoff level of 130 counts/µl had a sensitivity of 75%, specificity of 93.3% and diagnostic accuracy of 89.5% for E1 in the validation cohort. CONCLUSION: Circulating MPs and EnMPs in IgAN correlate with E1 on histology and have a potential as non-invasive biomarkers to predict disease activity and renal outcome.

Fulminant ruptured septic aneurysm complicating the catheter related blood stream infection in a patient on maintenance hemodialysis: A case report.

Metastatic infections can complicate catheter-related blood stream infections (CRBSI) in dialysis dependent patients. However, an infected/septic aneurysm involving the aorta or its branches as a direct complication of CRBSI without an underlying infective endocarditis is not reported so far in the literature. We report a 43-year female, who presented with CRBSI 2 weeks following a tunneled dialysis catheter (TDC) insertion. Due to the lack of defervescence after 72 h of antibiotics given as per the culture sensitivity reports, the TDC was removed. Blood cultures grew Pseudomonas aeruginosa. After a catheter free interval of 4 days, a TDC was reinserted, an antibiotic course was completed, and she was discharged in stable condition. Five days later, she presented with acute abdominal pain and fever. A tender, firm, and pulsatile mass was noted in the hypogastrium with a bruit. Contrast-enhanced CT revealed a pseudoaneurysm of the aorta, and left common iliac artery at the site of origin. She was started on IV antibiotics and planned for an endovascular prosthesis but had a sudden collapse during her hospital stay due to a ruptured aneurysm. CRBSI due to certain pathogens such as Pseudomonas might require prolonged and dual antibiotic therapy to prevent fulminant complications.

Indian TrANslational GlomerulonephrItis BioLogy nEtwork (I-TANGIBLE): Design and Methods.

Background and Aim: Primary glomerular disease accounts for one-sixth of all chronic kidney diseases (CKDs) in India. We remain limited in our ability to effectively treat these conditions because of lack of understanding of the disease mechanisms and lack of predictors to identify the clinical course and therapeutic responsiveness. We propose to develop a network of investigators in glomerular diseases, collect information in a systematic fashion to understand the clinical outcomes, answer translational research questions better, and identify and recruit patients for clinical trials. Materials and Methods: This is a prospective, observational study. The Indian TrANslational GlomerulonephrItis BioLogy nEtwork (I-TANGIBLE) cohort will enroll patients (>18 years) with biopsy-proven minimal change disease (MCD), focal segmental glomerulonephritis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), or membranoproliferative glomerulonephritis (MPGN) (immune complex- and complement-mediated), with first biopsy taken within 2 years of enrollment. Patients with estimated glomerular filtration (eGFR) rate <15 ml/min/1.73 m2 for >3 months at the time of screening, kidney transplant or bone marrow transplant recipients, patients with active malignancy, and patients with active hepatitis B/C replication or human immunodeficiency virus (HIV)-I/II will be excluded. Clinical details including history, medication history and details, and family history will be obtained. Consenting patient's blood and urine samples will be collected and stored, aligned to their clinical follow-up. Expected Outcomes: The network will allow accurate ascertainment of disease burden of glomerular diseases across study sites, establishment of the treatment pattern of common glomerular diseases, investigation of medium- and long-term outcomes (remission, relapse, rate of eGFR decline), and building a suitable infrastructure to carry out clinical trials in primary glomerular disease.

Ureterovesical Leak Following Renal Transplant and Effects of Acute Rejection and Antirejection Therapy: A Nested Case-Control Analysis and Outcome of 1102 Consecutive Renal Transplant Recipients.

OBJECTIVES: Studies on nontechnical risk factors for ureterovesical leak after renal transplant are scarce. This study aimed to report the possible pre- and postoperative risk factors and the role of acute rejection and antirejection therapies for urine leak after transplant and its effect on graft and patient survival. MATERIALS AND METHODS: We conducted a retrospective analysis of 13 patients (1.17%) with urine leak (case group) and 52 patients without leak (control group) (case-to-control ratio of 1:4) from 1102 living related (first degree) renal transplant recipients seen between January 2012 and December 2021. We analyzed demographic and clinical details and biochemical and outcome parameters using a nested case-control design. RESULTS: Cases were olderthan controls (P = .018), were more ABO incompatible (P = .009), and had more 6/6 HLA mismatch transplants (P = .047). Donors of cases were older than donors of controls (P = .049). The rate of postoperative hypoalbuminemia was greaterin the case group (P = .050). Rates of acute rejection (P = .012) and plasmapheresis (P = .003) were greaterin the case group than in the control group. On multivariate logistic regression analysis, recipient age, 6/6 HLA mismatch, and plasmapheresis were found to independently associated with urine leak. None ofthe patient required surgical repair, as all responded to conservative therapy. Urine leak did not affect graft outcomes (P = .324), but overall survival was less in cases than in controls. CONCLUSIONS: Nontechnical risk factors that cause posttransplant ureteric leak include older donor and recipient age and ABO incompatible and 6/6 HLA mismatch transplants. Acute rejection and plasmapheresis predispose leak, and an indwelling double J stent can allow adequate healing of the anastomosis. High index of suspicion and prompt management are imperative to preserve graft and patient outcome.

Higher pro-inflammatory cytokines IL-6 and IFN-γ are associated with anti-SARS-CoV-2 spike protein-specific seroconversion in renal allograft recipients.

BACKGROUND: Maintenance immunosuppressive regimens are speculated to hamper immunogenic response against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in renal transplant recipients (RTRs) compared to the healthy population. Healthy people with SARS-CoV-2 infection often develop neutralizing antibodies and secret copious quantities of cytokines, leading to virus clearance and sometimes more severe immune-related complications. METHODS: RTRs, either acquired SARS-CoV-2 infection (infection group, n = 132) or were vaccinated with two vaccine doses (vaccination group, n = 78) against SARS-CoV-2, were recruited in the study. Thirty-five unvaccinated RTRs, without anti-SARS-CoV-2 spike protein-specific antibodies, were also included as control. Cytokines interleukine-6 (IL-6), interferon-γ (IFN-γ), TGF-ß, and IL-10 were measured using ELISA. The SARS-CoV-2 spike protein-specific IgG-titer was measured by chemiluminescent microparticle immunoassay methods. RESULTS: The seroconversion rate in the infection group was 115/132 (87.12%), with a median antibody titer 706.40 au/mL (IQR, 215.45-1844.42), and in the vaccination group was 63/78 (80.76%) with antibody titer 1454.20 au/mL (IQR, 80.52-3838.75). The IL-6, IFN-γ, TGF-ß, and IL-10 levels were significantly higher in both the infection and vaccination group compared to healthy control. In the infection group, pro-inflammatory cytokines IL-6 (55.41 ± 24.30 vs. 31.64 ± 16.98 pg/mL, p < .001) and IFN-γ (91.21 ± 33.09 vs. 61.69 ± 33.28 pg/mL, p = .001) were significantly higher in the seroconverter group as compared to non-seroconverter. Similarly, in the vaccination group, pro-inflammatory cytokines IL-6 (50.31 ± 25.67 vs. 30.00 ± 11.19 pg/mL; p = .002) and IFN-γ (65.70 ± 39.78 vs. 32.14 ± 17.48 pg/mL; p = .001) were significantly higher in the seroconverter group compared to non-seroconverter. In contrast, TGF-ß (820.96 ± 415.78 vs. 1045.57 ± 204.66; p = .046) was higher in non-seroconverter. CONCLUSIONS: Pro-inflammatory cytokines IL-6 and IFN-γ were significantly associated with seroconversion after SARS-CoV-2 infection and vaccination in RTRs.

Renal injury, biomarkers, and myositis, an understudied aspect of disease: prospective study in the MyoCite cohort.

Introduction: The mechanisms leading to chronic kidney disease (CKD) in patients with idiopathic inflammatory myopathies (IIMs) are poorly understood. We assessed the prevalence of subclinical renal injury in patients with IIMs, through elevation in biomarker levels of tubular injury and fibrosis (NGAL, KIM1, Activin A, CD163, and Cys-c), and assessed differences between subtypes of IIMs, and the effect of disease activity and duration. Materials and methods: Clinical data, core set measures, sera and urine were prospectively collected from all patients enrolled in the MyoCite cohort from 2017 to 2021. Twenty healthy subjects (HC) and 16 patients with acute kidney injury (AKI) were included as controls. Baseline and follow up data for IIMs were included. Enzyme-linked immunosorbent assay (ELISA) was used to measure urine NGAL (Human Lipocalin-2/NGAL Duoset ELISA, Cat no: DY1757), KIM1 (Human TIM-1/KIM 1/HAVCR Duoset ELISA, Cat.no: DY1750B), Activin A (Human Activin A Duoset ELISA, Cat no: DY338), CD163 (Human CD163 Duoset ELISA,Cat no: DY1607-05), and Cys-c (Human Cystatin C Duoset ELISA, Cat. no.: DY1196) levels, while eGFR (unit mL/min/1.73 m2) was calculated by the Cockcroft-Gault formula and CKD-EPI formula. Results: Analysis of 201 visits of 110 adult patients with IIMs indicated higher normalized biomarker levels compared to HCs, and comparable to patients with AKI, with the exception of NGAL, which was higher in the AKI group. Notably 72 (49%) patients with IIMs had eGFR<90; the levels of the 5 biomarkers were comparable between active and inactive IIMs, and different subtypes of IIMs. Similarly, a poor correlation between urine biomarker levels and core set measures of activity and damage was found. Changes in biomarker levels on follow-up did not correlate with eGFR changes. Discussion: This exploratory analysis of urinary biomarkers identified low eGFR and elevated biomarkers of CKD in nearly half of the patients with IIMs, comparable to patients with AKI and higher than HCs, indicative of potential renal damage in IIMs that may have a lead to complications in other systems.

Lower Circulating Cytotoxic T-Cell Frequency and Higher Intragraft Granzyme-B Expression Are Associated with Inflammatory Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Recipients.

Background and Objectives: Inflammatory interstitial fibrosis and tubular atrophy (i-IFTA) is an inflammation in the area of tubular atrophy and fibrosis. i-IFTA is poorly associated with graft outcome and associated with infiltration of inflammatory mononuclear cells. A cytotoxic T cell is a granzyme B+CD8+CD3+ T cell, mainly secret granzyme B. Granzyme B is a serine protease that may mediate allograft injury and inflammatory interstitial fibrosis and tubular atrophy (i-IFTA). However, there is no report identifying the association of granzyme B with i-IFTA after a long post-transplant interval. Material and Methods: In this study, we have measured the cytotoxic T-cell frequency with flow cytometry, serum and PBMCs culture supernatants granzyme-B levels with ELISA and intragraft granzyme-B mRNA transcript expression with the RT-PCR in RTRs in 30 patients with biopsy-proven i-IFTA and 10 patients with stable graft function. Result: The frequency of cytotoxic T cells (CD3+CD8+ granzyme B+) in SGF vs. i-IFTA was (27.96 ± 4.86 vs. 23.19 ± 3.85%, p = 0.011), the serum granzyme-B level was (100.82 ± 22.41 vs. 130.32 ± 46.60, p = 0.038 pg/mL) and the intragraft granzyme-B mRNA transcript expression was (1.01 ± 0.048 vs. 2.10 ± 1.02, p < 0.001 fold). The frequency of CD3+ T cells in SGF vs. i-IFTA was (66.08 ± 6.8 vs. 65.18 ± 9.35%; p = 0.68) and that of CD3+CD8+ T cells was (37.29 ± 4.11 vs. 34.68 ± 5.43%; p = 0.28), which were similar between the 2 groups. CTLc frequency was negatively correlated with urine proteinuria (r = -0.51, p < 0.001), serum creatinine (r = -0.28, p = 0.007) and eGFR (r = -0.28, p = 0.037). Similarly, the PBMC culture supernatants granzyme-B level was negatively correlated with urine proteinuria (r = -0.37, p < 0.001) and serum creatinine (r = -0.31, p = 0.002), while the serum granzyme-B level (r = 0.343, p = 0.001) and intragraft granzyme-B mRNA transcript expression (r = 0.38, p < 0.001) were positively correlated with proteinuria. Conclusions: A decrease in the CTLc frequency in circulation and an increased serum granzyme-B level and intragraft granzyme-B mRNA expression shows that cytotoxic T cells may mediate the allograft injury in RTRs with i-IFTA by releasing granzyme B in serum and intragraft tissue.

Clinicopathologic characteristics and outcomes of late onset lupus nephritis: a single centre experience.

Systemic Lupus Erythematosus (SLE) occurs in the reproductive age group. Renal involvement occurs less frequently in late-onset SLE than in reproductive-age SLE patients. Here, we aimed to study the clinical, serological and histopathological characteristics of late-onset lupus nephritis (LN). Late-onset LN was defined as disease onset after 47 years of age, corresponding to the average menopausal age. Records of biopsy proven late-onset lupus nephritis patients diagnosed between June 2000 and June 2020 were reviewed. Late-onset LN constituted 53 of 4420 patients (1.2%) biopsied during the study period. Females represented 90.65% of the cohort. Mean age of the cohort was 49.5 ± 7.05 years at the time of SLE diagnosis while its renal presentation was delayed by median duration of 10 months (IQR 3-48 months). Renal failure was present in 28 patients (52.8%) with acute kidney injury (AKI) (28.3%, n = 15) as the most common presentation. On histopathological analysis, class IV was observed in 23 patients (43.5%), crescents were observed in one-third cases and lupus vasculopathy in 4 patients (7.5%). All patients received steroids. Majority of patients (43.3%; n = 23) received Euro lupus protocol for induction. On median follow up duration of 82 months, renal flares were noted in 9 patients (17%) and 8 patients (15.1%) became dialysis dependent. Among 11 patients (21%) with infectious complications, 7 patients (13.2%) suffered from tuberculosis. Infections caused three-fourth of the deaths. Late-onset lupus nephritis is rare and presents as renal failure in majority. Renal biopsy affects the clinical decision of judicious use of immunosuppression which is imperative due to high rate of infections in this cohort.

Comparative Analysis of Determinants and Outcome of Early and Late Acute Antibody Mediated Rejection (ABMR).

Introduction: Antibody-mediated rejection (ABMR) is one of the major determinants of graft survival. Although diagnostic precision and treatment options have improved, response to therapy and graft survival has not improved very significantly. The phenotypes of early and late acute ABMR differ in many ways. In this study, we assessed the clinical characteristics, response to therapy, DSA positivity, and outcomes of early and late ABMR. Methods: During the study period, 69 patients with acute ABMR diagnosed on renal graft histopathology were included with a median follow-up of 10 months after rejection. Recipients were stratified into early acute ABMR (<3 months of transplant; n = 29) and late acute ABMR (>3 months of transplant; n = 40). Graft survival, patient survival, response to therapy, and doubling of serum creatinine were assessed and compared between the two groups. Results: Baseline characteristics and immunosuppression protocols were comparable between the early and late ABMR groups. Late acute ABMR had an increased risk of doubling of serum creatinine than the early ABMR group (P = 0.002). Graft and patient survival were not statistically different between the two groups. Response to therapy was inferior in the late acute ABMR group (P = 0.00). Pretransplant DSA was present in 27.6% in the early ABMR group. Late acute ABMR was frequently associated with nonadherence or suboptimal immunosuppression and low DSA positivity (15%). Infections such as CMV, bacterial, and fungal infections were similar in the earlier and late ABMR groups. Conclusion: Late acute ABMR group had a poor response to anti-rejection therapy and also an increased risk of doubling of serum creatinine compared to the early acute ABMR group. There was also a tendency toward increased graft loss in late acute ABMR patients. Late acute ABMR patients are more frequently associated with nonadherence/suboptimal immunosuppression. There was also a low incidence of anti-HLA DSA positivity in late ABMR.

Clinicopathologic Manifestations of Immunoglobulin A Nephropathy in a Northern Indian Cohort: A Mute Assassin with Delayed Diagnosis.

Introduction: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, but there is a marked geographic difference in its prevalence and prognosis. IgAN is known to have an aggressive course in Asians. However, its exact prevalence and clinicopathologic spectrum in North India are not well documented. Materials and Methods: The study included all patients aged above 12 years with primary IgAN on kidney biopsy from January 2007 to December 2018. Clinical and pathological parameters were noted. Two histopathologists independently reviewed all kidney biopsies, and MEST-C score was assigned as per the Oxford classification. Results: IgAN was diagnosed in 681 (11.85%) out of 5751 native kidney biopsies. The mean age was 32 ± 12.3 years, and the male to female ratio was 2.5:1. At presentation, 69.8% had hypertension, 68% had an estimated glomerular filtration rate (eGFR) of less than 60 ml/min, 63.2% had microscopic hematuria, and 4.6% had gross hematuria. The mean proteinuria was 3.61 ± 2.26 g/day, with 46.8% showing nephrotic range proteinuria and 15.2% showing nephrotic syndrome manifestation. Histopathologically, 34.4% of patients had diffuse global glomerulosclerosis. Oxford MEST-C scoring revealed M1 in 67%, E1 in 23.9%, S1 in 46.9%, T1/T2 in 33%, and crescents in 19.6% of biopsies. The mean serum creatinine was significantly higher in cases with E1, T1/2, and C1/2 scores (P < 0.05). Hematuria and proteinuria were significantly higher (P < 0.05) with E1 and C1/2 scores. Coexisting C3 was associated with higher serum creatinine at presentation (P < 0.05). Conclusion: IgAN patients with late presentation and advanced disease became less amenable to immunomodulation in our cohort. The implementation of point-of-care screening strategies, early diagnosis, and retarding disease progression should be prioritized in the Indian strategy.

Headache Associated with PPE During COVID-19 Pandemic in Health Care Workers.

PURPOSE: In the pandemic coronavirus disease 2019 (COVID-19), health care workers (HCWs) are at very high risk. Personal protective equipment (PPE) and masks are not only difficult to wear while working but also causes various complications. The present self-administered questionnaire- based study aimed to explore the headache and complications in HCWs on wearing PPE during the COVID-19 pandemic. METHODS: The present study was performed by obtaining a self-administered questionnaire from HCWs, which provides evidence of various complications due to the use of a PPE and mask. RESULTS: Out of a total of 329 respondents, 189(57.45%), 67(20.36%), 238(72.34%), 213(64.74%), 177(53.80%), and 34(10.33%) reported headache, breathlessness, suffocation, nose pain, ear pain, and leg pain respectively. Out of 329 respondents, 47(14.29%) had pre-existing headaches. Headache was significantly high for those who wore PPE for 4-6h (121/133; 87.05%) than that of those who wore up to 4h (18/26; 69.23%). Of the 34(24.46%) required medication who reported headaches wearing PPE. Acetaminophen is quite helpful in most health care workers to decrease headaches. Nose-related complications occur frequently in health care workers after regular shifts for more than 6 days. Gelatinous adhesives patch was a wonderful prophylactic remedy as it was helpful to prevent nose- related complications in 24 HCWs out of 25(96%). CONCLUSIONS: More than half of the HCWs reported headache, suffocation, nose pain, and ear pain. Duration of PPE use of more than 4h is significantly associated with headache. Short duration PPE use prevent HCWs from headache and various ill effects.

Therapeutic potential of urine exosomes derived from rats with diabetic kidney disease.

Kidney disease is prevalent in diabetes. Urinary exosomes (uE) from animal models and patients with Diabetic nephropathy (DN) showed increased levels of miRs with reno-protective potential. We examined whether urinary loss of such miRs is associated with their reduced renal levels in DN patients. We also tested whether injecting uE can leverage kidney disease in rats. In this study (study-1) we performed microarray profiling of miRNA in uE and renal tissues in DN patients and subjects with diabetes without DN (controls). In study-2, diabetes was induced in Wistar rats by Streptozotocin (i.p. 50 mg/kg of body weight). Urinary exosomes were collected at 6th, 7th and 8th weeks, and injected back into the rats (100ug/biweekly, uE-treated n=7) via tail vein on weeks 9 and 10. Equal volume of vehicle was injected in controls (vehicle, n=7). uE from the human and rat showed the presence of exosome-specific proteins by immunoblotting. Microarray profiling revealed a set of 15 miRs having high levels in the uE, while lower in renal biopsies, from DN, compared to controls (n=5-9/group). Bioinformatic analysis also confirmed the Renoprotective potential of these miRs. Taqman qPCR confirmed the opposite regulation of miR-200c-3p and miR-24-3p in paired uE and renal biopsy samples from DN patients (n=15), relative to non-DN controls. A rise in 28 miRs levels, including miR-200c-3p, miR-24-3p, miR-30a-3p and miR-23a-3p were observed in the uE of DN rats, collected between 6th-8th weeks, relative to baseline (before diabetes induction). uE- treated DN rats had significantly reduced urine albumin-to-creatinine ratio, attenuated renal pathology, and lower miR-24-3p target fibrotic/inflammatory genes (TGF-beta, and Collagen IV), relative to vehicle treated DN rats. In uE treated rats, the renal expression of miR-24-3p, miR-30a-3p, let-7a-5p and miR-23a-3p was increased, relative to vehicle control. Patients with diabetic nephropathy had reduced renal levels, while higher uE abundance of miRs with reno-protective potential. Reverting the urinary loss of miRs by injecting uE attenuated renal pathology in diabetic rats.

Nuclear Magnetic Resonance-Based Metabolomics Approach Revealed the Intervention Effect of Using Complementary and Alternative Medicine (CAM) by CKD Patients.

Chronic kidney disease (CKD) is the end point of a number of systemic chronic diseases. The prevalence of CKD is increasing worldwide and recent epidemiological studies are showing the high prevalence of renal failure in CKD patients using complementary and alternative medicines (CAMs). Clinicians believe that biochemical profiles of CKD patients using CAM (referred here to as CAM-CKD) may be different compared to those on standard clinical treatment and should be managed differently. The present study aims to explore the potential of the NMR-based metabolomics approach to reveal the serum metabolic disparity between CKD and CAM-CKD patients with respect to normal control (NC) subjects and if the differential metabolic patterns can provide rationale for the efficacy and safety of standard and/or alternative therapies. Serum samples were obtained from 30 CKD patients, 43 CAM-CKD patients, and 47 NC subjects. The quantitative serum metabolic profiles were measured using 1D 1H CPMG NMR experiments performed at 800 MHz NMR spectrometer. The serum metabolic profiles were compared using various multivariate statistical analysis tools available on MetaboAnalyst (freely available web-based software) such as partial least-squares discriminant analysis (PLS-DA) and random forest (a machine learning) classification method. The discriminatory metabolites were identified based on variable importance in projection (VIP) statistics and further evaluated for statistical significance (i.e., p < 0.05) using either Student t-test or ANOVA statistics. PLS-DA models were capable of clustering CKD and CAM-CKD with considerably high values of Q 2 and R 2. Compared to CAM-CKD patients, the sera of CKD patients were characterized by (a) elevated levels of urea, creatinine, citrate, glucose, glycerol, and phenylalanine and phenylalanine-to-tyrosine ratio (PTR) and (b) decreased levels of various amino acids (such leucine, isoleucine, valine, and alanine), high-density lipoproteins, lactate, and acetate. These changes suggested that CKD patients manifest severe oxidative stress, hyperglycemia (with dampened glycolysis), increased protein energy wasting, and reduced lipid/membrane metabolism. Statistically significant and strong positive correlation of PTR with serum creatinine levels suggested the role of oxidative stress in the progression of kidney disease. Significant differences in metabolic patterns between CKD and CAM-CKD patients were observed. With respect to NC subjects, the serum metabolic changes were more aberrant in CKD patients compared to CAM-CKD patients. The aberrant metabolic changes in CKD patients with manifestations of higher oxidative stress compared to CAM-CKD patients could explain clinical discrepancies between CKD and CAM-CKD patients and further advocate the use of different treatment strategies for CKD and CAM-CKD patients.