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.

Antibody response to ChAdOx1 nCoV-19 (Covishield®) vaccine in people on maintenance hemodialysis.

INTRODUCTION: People on renal replacement therapy (RRT) have a high risk of COVID-19 infection and subsequent death. COVID-19 vaccination is strongly recommended for those on RRT. Data are limited on the immune response of the ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine in patients on RRT. METHODS: A prospective cohort of adult (age > 18 years), on RRT in the form of hemodialysis were included and received two intramuscular doses of Covishield®. A blood specimen of 5.0 mL was collected at two time points, within a few days before administering the first dose of the vaccine and at 4-16 weeks after the second dose. According to their prior COVID-19 infection status, the participants were grouped as (i) prior symptomatic COVID-19 infection, (ii) prior asymptomatic COVID-19 infection, and (iii) no prior COVID-19 infection. RESULTS: A large proportion (81%) of participants had anti-spike antibodies (ASAb) before vaccination, and a reasonable proportion (30%) also had neutralizing antibodies (NAb). The titer of ASAb was relatively low (207 U/mL) before vaccination. The ASAb titer (9405 [1635-25,000] U/mL) and percentage of NAb (96.4% [59.6-98.1%]) were markedly increased following the administration of two doses of the vaccine. The participants' prior COVID-19 exposure status did not influence the rise in ASAb titer and NAb percentage. Further, administering two doses of the Covishield vaccine helps them achieve a high ASAb titer. CONCLUSION: Two doses of ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine, given 12 weeks apart, achieve a high titer of ASAb and a high percentage of NAb in people on hemodialysis.

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.

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.

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.

The adverse effects of high-dose corticosteroid on infectious and non-infectious sequelae in renal transplant recipients with coronavirus disease-19 in India.

INTRODUCTION: The corticosteroid dosing modulation in renal transplant recipients (RTRs) with coronavirus disease-19 (COVID-19) is not well defined. We aimed to analyze the outcomes and infectious and non-infectious sequelae in RTR with COVID-19 with reference to corticosteroid dosing and the first and second pandemic waves of COVID-19. MATERIALS AND METHODS: This study included RTRs admitted during two pandemic waves between March 25, 2020, and July 31, 2021. Patients were categorized into mild, moderate, and severe COVID-19. The outcomes and predictors of survival at 4 weeks were analyzed. The survivors were also followed for 6 months and were studied for mortality, readmission rates, and infectious and non-infectious sequelae with reference to high-dose and standard-dose corticosteroids. RESULTS: A total of 251 RTRs, 104 during the first wave and 147 during the second wave, were treated. Overall mortality was 15.1% (11.5% in the first wave vs. 17.5% in the second wave, p = .23). The use of high-dose steroids was also significantly high in non-survivors (85.8% vs. 11.3%, p = .001). On multivariate analysis, the severity of COVID-19, graft dysfunction, and high dose of corticosteroid therapy were associated with increased odds of mortality. Among survivors, 6-month mortality (17.3% vs. 0.5%, p = .001), readmission rate (91.3% vs. 23.7%, p = .001), fungal infection (30.4% vs. 2.2%, p < .001), and post-COVID lung sequelae (21.7% vs. 4.4%, p = .008) were significantly higher in the high-dose corticosteroid group than in the standard-dose group. CONCLUSION: High-dose corticosteroid dosing in RTRs with COVID-19 was associated with increased infections, particularly fungal infections, and non-infectious sequelae with higher mortality on subsequent follow-up.

Risk of tuberculosis among renal transplant recipients receiving rituximab therapy.

BACKGROUND: Rituximab is an anti-CD 20 agent used widely in renal transplant recipients. Its use is associated with various infections; however, its association with tuberculosis (TB) is not well established and has not been studied in post renal transplantation patients. METHODS: This is a single-center, retrospective analysis of 56 renal transplant recipients who received rituximab as a part of desensitization protocol or as rescue therapy for rejections and 287 post-renal transplant patients who did not receive rituximab during the study period from January 2013 to June 2017. The association between use of rituximab and occurance of TB was studied. Other factors associated with TB were also investigated. RESULTS: Baseline characteristics were similar in both the groups. Mean time for occurrence of TB was 18.4 ± 10.6 months after renal transplantation. Rituximab use was not significantly associated with TB or any other infection. Higher number of rejection episodes (60% vs. 32.72%, p = .029) was the only factor associated with greater incidence of TB. However, no specific type of rejection was associated with TB. Use of plasmapheresis in post-transplant period for treatment of humoral rejections was associated with significantly higher incidence of TB (33.33% vs. 13.41%, p = .031); however, when pre-transplant plasmapheresis was also considered, there was no significant difference. The choice of induction agent was not associated with higher incidence of TB. CONCLUSION: Use of rituximab is not associated with higher incidence of TB when compared to other immunosuppressive agents. Routine screening and prophylaxis may not be advisable, especially in a country like India with high prevalence of TB, as it will further delay transplantation and may adversely affect the outcome of the patients.

High mortality and residual kidney damage with Coronavirus disease-19-associated acute kidney injury in northern India.

BACKGROUND: Acute kidney injury (AKI) is associated with morbidity and mortality in COVID-19 patients. The incidence of AKI and its outcomes vary in different parts of the world. We aimed to analyze the AKI incidence, predictors of AKI, mortality, and renal function outcomes on follow-up in hospitalized patients with COVID-19. MATERIALS AND METHODS: The study was designed as a retrospective, observational study of electronically captured data on the hospital information system of laboratory-confirmed COVID-19 patients, with and without AKI, between March 2020 to June 2021. The predictor of AKI and mortality and residual damage in recovered AKI patients were analyzed. RESULTS: Of the 3395 patients, 3010 COVID-19 patients were eligible. AKI occurred in 951 (31.5%); with stages 1, 2, and 3 in 605 (63.7%), 138 (14.5%), and 208 (21.8%) patients, respectively. AKI severity increased with COVID-19 severity. Of 951 AKI patients, 403 died, and 548 were discharged. AKI group had higher mortality (42.3%) than the non-AKI (6.6%). At discharge, complete recovery was noticed in 370(67.5%), while 178 (32.5%) had residual damage. At three months of follow-up, 108 (69.6%) of 155 patients showed complete recovery. Residual damage was observed in 47 (30.3%). In 14 (9%) patients, serum creatinine remained elevated above the baseline. Thirty-three (21.2%) patients showed proteinuria (n = 24) and microscopic hematuria (n = 9). CONCLUSIONS: AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Residual kidney damage post-COVID-19 in recovered AKI patients may increase the CKD burden.

Delayed onset bleed after percutaneous kidney biopsy: is it the same as early bleed?

BACKGROUND: While the majority of bleeding complications after a percutaneous kidney biopsy (PKB) occur early (≤24 h), delayed onset bleeding complications (>24 h) have been rarely reported and can be catastrophic for the patient. PURPOSE: To describe the incidence, risk factors, and outcomes of delayed bleeding complications after PKB. MATERIAL AND METHODS: We retrospectively studied native and graft kidney biopsies in patients who developed delayed bleeding complications (>24 h) after the biopsy performed in the Department of Nephrology and Renal Transplantation of a tertiary care medical institution in north India between January 2014 to December 2018. RESULTS: Of the 4912 renal biopsies reviewed, 20 patients (16 men, 4 women; 0.40%) had a delayed biopsy bleeding complication. Of these patients, 95% had major bleeding complications requiring blood transfusions and 85% needed intervention like gelfoam/coil embolization. Despite intervention, one patient (5%) had mortality due to complications of bleeding and sepsis. When compared to a control group of patients with early biopsy bleed, patients with the delayed biopsy bleed had similar demographic and clinical profiles except for higher pre-biopsy hemoglobin and lower systolic and diastolic blood pressure. CONCLUSION: A post-PKB delayed onset bleed is not uncommon, and the vast majority of these patients had major bleeding complications requiring blood transfusions and/or intervention like embolization. They had a similar demographic and clinical profile presentation as early bleed patients. Meticulous outpatient monitoring and patient education after discharge may be useful to detect this complication promptly and to intervene early to have good patient outcome.

Midterm eGFR Predicts Pregnancy Outcomes: An Observational Study.

INTRODUCTION: The hemodynamic adjustments during pregnancy play a pivotal role in sustaining the gestation, however, its clinical connotation on midterm renal hyperfiltration and its consequence on maternal and fetal outcomes need a greater appraisal. The present retrospective study looked into the midterm estimated glomerular filtration rate (eGFR) among pregnant females without overt pieces of evidence of chronic kidney disease (CKD) as a surrogate marker for midterm hyperfiltration and its implication on maternal and fetal outcomes. MATERIALS AND METHODS: All pregnancies among females aged 18-50 years with available pregestational baseline serum creatinine were included in the study. Maternal renal hyperfiltration was expressed as the highest eGFR, using the creatinine clearance method. Its association with adverse maternal and fetal outcomes was assessed. RESULTS: A total of 1,045 pregnancies were assessed during the study. According to midterm eGFR, among them, 65% of pregnancies showed midterm eGFR between 120 and 150, however, 4.3% of pregnancies had values more than 150 mL/min per 1.73 m2 . The risk of poor pregnancy outcome was observed for eGFR levels below and above the reference level of 120-150 mL/min per 1.73 m2 (1.97 for values ≥150 mL/min per 1.73 m2 , and 1.72 for 90-120 mL/min per 1.73 m2 ). Pregnancies with eGFR between 60 and 90 mL/min per 1.73 m2 had odds ratios (ORs) of 5.64. CONCLUSION: A distinctive relationship was observed between the midterm eGFR and adverse pregnancy outcomes with the best outcomes for midterm eGFR levels between 120 and 150 mL/min per 1.73 m2 . Despite no apparent functional renal deterioration, a poor maternal hyperfiltration response may play a crucial impact on poor pregnancy outcomes.

Overexpression of P-glycoprotein and MRP-1 are pharmacogenomic biomarkers to determine steroid resistant phenotype in childhood idiopathic nephrotic syndrome.

Steroid remains the keystone therapy for Idiopathic Nephrotic Syndrome (NS). Besides genetic factors and histological changes, pharmacogenomic factors also affect the steroid response. The upregulation of P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP-1) modulate the pharmacokinetics of steroids and may contribute to steroid resistance. Flow-cytometric analysis of P-gp, MRP-1 expression and functional activity on peripheral blood mononuclear cells (PBMCs) was carried out in steroid-sensitive nephrotic syndrome (SSNS) (n = 171, male 103, mean age = 8.54 ± 4.3); and steroid-resistant nephrotic syndrome (SRNS) (n = 83, male 43, mean age = 7.43 ± 4.6) patients. The genotypings of MDR-1 gene were carried out using PCR-RFLP. We observed that the percentage expression of P-gp (10.01 ± 2.09 and 3.79 ± 1.13, p < 0.001); and MRP-1 (15.91 ± 3.99 and 7.40 ± 2.33, p < 0.001) on lymphocyte gated population were significantly higher in SRNS than that of SSNS. The functional activity of P-gp and MRP-1 was also significantly escalated in SRNS as compared to SSNS (68.10 ± 13.35 and 28.93 ± 7.57, p < 0.001); (72.13 ± 8.34 and 31.56 ± 8.65, p < 0.001) respectively. AUC-ROC curve analysis revealed that P-gp and MRP-1 expression with a cut-off value of 7.13% and 9.62% predicted SRNS with the sensitivity of 90% and 80.7%; and specificity 90% and 80%, respectively. Moreover, MDR-1 homozygous mutant TT+AA for G2677T/A (rs2032582) was significantly associated with SRNS (p = 0.025, OR = 2.86 CI = 1.14-7.14). The expression of P-gp (9.68 ± 4.99 v/s 5.88 ± 3.38, p = 0.002) was significantly higher in the patients of homozygous mutant alleles compared to wildtype GG. The increased expression and functionality of P-gp and MRP-1 contribute to steroid resistance, and MDR-1 homozygous mutant G2677T/A promotes steroid resistance by inducing P-gp expression in NS.

Aftermath of fortnightly universal testing for severe acute respiratory corona virus-2 infection in maintenance hemodialysis patients.

INTRODUCTION: Asymptomatic maintenance hemodialysis patients with acute respiratory corona virus-2 (SARS-COV-2) are missed with pre-dialysis screening without testing. The possible ideal strategy of testing each patient before each shift with reverse transcription polymerase chain reaction (RT-PCR) is not feasible. We aimed to study the effectiveness of fortnightly screening with RT-PCR for SARS-CoV-2 in curbing transmission. METHODS: Between July 1, 2020 and September 30, 2020, all 273 patients receiving hemodialysis were subjected to fortnightly testing for SARS-Cov-2 in the unit to detect asymptomatic patients. The cost and effectiveness of universal testing in preventing transmission were analyzed using susceptible-infectious-removed (SIR) modeling assuming R0 of 2.2. RESULTS: Of 273 MHD patients, 55 (20.1%) found infected with SARS-CoV-2 over 3 months. Six (10.9%) were symptomatic, and 49 (89.1%) asymptomatic at the time of testing. Six (10.9%) asymptomatic patients develop symptoms later, and 43 (78.2%) remained asymptomatic. A total of seven (6.1%) HCWs also tested positive for the virus. Fortnightly universal testing is cost-effective, and SIR modeling proved effective in preventing person-to-person transmission. CONCLUSIONS: Repeated universal testing in maintenance hemodialysis patients detected 89% of asymptomatic SARS-CoV-2 patients over 3 months and appeared to be an effective strategy to prevent person-to-person transmission in the dialysis unit.

Outcomes of symptomatic coronavirus disease 19 in maintenance hemodialysis patient in India.

BACKGROUND: Maintenance hemodialysis (MHD) patients face disadvantages with higher risk of acquiring SARS-CoV-2 infection, atypical manifestations, and associated multiple comorbidities. We describe patients' outcomes with symptomatic COVID-19 on MHD in a large cohort of patients from India. METHODS: Data were collected prospectively from hemodialysis units in 11 public and private hospitals between March 15, 2020, and July 31, 2020. The survival determinants were analyzed using stepwise backward elimination cox-regression analysis. RESULTS: Of the 263 total patients (mean age 51.76 ± 13.63 years and males 173) on MHD with symptomatic COVID-19, 35 (13.3%) died. Those who died were older (p = 0.01), had higher frequency of diabetic kidney disease (p = 0.001), comorbidities (p = 0.04), and severe COVID-19 (p = 0.001). Mortality was higher among patients on twice-weekly MHD than thrice-weekly (p = 0.001) and dialysis through central venous catheter (CVC) as compared to arteriovenous fistula (p = 0.001). On multivariate analysis, CVC use (HR 2.53, 95% CI 1.26-5.07, p = 0.009), disease severity (HR = 3.54, 95% CI 1.52-8.26, p = 0.003), and noninvasive ventilatory support (HR 0.59, 95% CI 0.25-0.99, p = 0.049) had significant effect on mortality. CONCLUSION: The adjusted mortality risk of COVID-19 in MHD patients is high in patients associated with severe COVID-19 and patients having CVC as vascular access.

Clinicopathological characteristics and predictors of poor outcome in anti-glomerular basement membrane disease - a fifteen year single center experience.

INTRODUCTION: Anti-glomerular basement membrane (anti-GBM) disease is a small vessel vasculitis affecting the renal and lung capillary beds. We aim to study the clinicopathological characteristics and predictors of poor outcome of this disease in our population. MATERIALS AND METHODS: This is a 15 year retrospective, single center observational study of Indian cohort. Patients with biopsy proven anti-GBM disease were studied. RESULTS: Anti-GBM disease was found in 0.5% of the total cases. The mean age at presentation was 46.7 years. Compared to renal limited disease those with pulmonary-renal syndrome had a higher frequency of hypertension, oliguria, percentage of crescents, interstitial inflammation and glomerulosclerosis. Double positive (anti-GBM and ANCA antibodies) patients showed more of glomerulosclerosis, tubular atrophy/interstitial fibrosis (IFTA) as well as periglomerular granulomas on biopsy. Patient survival at one year was 40.4% and death censored renal survival was 9.7%. Factors affecting the dialysis dependency at presentation were oligoanuria (p = .04), creatinine levels >5.7 mg/dl (p = .003), and high mean anti-GBM titers (p = .008). Atypical cases accounted for 8.3% of these patients. Oligoanuria (HR = 5.0, p = .05), high serum creatinine (HR = 1.55, p = .05), severe glomerulosclerosis (HR = 1.09, p = .03), and IFTA (HR = 2, p = .04) were associated with poor renal outcome. Advanced age (HR = 1.92, p = .03), high serum creatinine (HR = 1.9, p = .04) and high anti-GBM titers (HR = 1.01, p = .03) were associated with poor patient survival. CONCLUSIONS: Anti-GBM is a rare disease with poor prognosis and varied presentations. Patients with pulmonary-renal syndrome showed severe disease whereas double positive had more of chronic changes. The predictors of poor prognosis include advanced age, oliguria, serum anti-GBM levels, serum creatinine levels, degree of glomerulosclerosis and IFTA. Atypical anti-GBM cases should be kept in mind while evaluating renal biopsies.

Breathability and Safety Testing of Personal Protective Equipment: "Human-comfort" Factor Remains Undefined.

Healthcare systems all over the world have been enormously affected by the COVID-19 pandemic. Healthcare workers (HCWs) taking care of these patients need personal protective equipments (PPEs) standardized for full protection from droplets and aerosols carrying viral load to variable distances. There has been a surge of manufacturers supplying these protective gears in India and regulatory agencies have issued technical specifications pertaining to PPEs focusing solely on synthetic blood penetration tests (SBPTs) and keeping the upper limit of non-woven fabric to 95 g/m2 (GSM). These PPE specifications are silent on air permeability (AP) and water/moisture vapor transmission rate (WVTR/MVTR) of the fabric. As a result, most of the PPE kits, despite having appropriate SBPT certifications from regulatory agencies, have extremely poor permeability and breathability. The acceptability of PPEs by HCWs can be vastly improved when the end-users are proactively invited to participate in "comfort testing" of PPEs before getting issuance of certification for marketing. "Field testing" or "end-user trials" in which HCWs don the PPE and assess it for comfort while performing different types of clinical work, e.g., in intensive care units (ICUs), operation theaters, cath labs, etc., also takes into account a hitherto often ignored "human-comfort-factor" that not only enhances the understanding of HCWs about the need for the PPEs but can also motivate them to use it without worrying about discomfort. We hereby propose that comfort fit testing (COmfort and Material Fit is an Obviously Required Test) should be a part of the mandatory testing and certification process for PPE, so that the industry invests wisely in manufacturing PPE kits that are not only certified for fabric but are also tested for comfort factors. How to cite this article: Kapoor A, Baronia AK, Azim A, Agarwal G, Prasad N, Mishra R, et al. Breathability and Safety Testing of Personal Protective Equipment: "Human-comfort" Factor Remains Undefined. Indian J Crit Care Med 2021;25(1):12-15.

Long-term outcomes of lupus nephritis treated with regimens based on cyclophosphamide and mycophenolate mofetil.

INTRODUCTION: Lupus nephritis (LN) has a considerable impact on the morbidity and mortality of systemic lupus erythematosus (SLE) patients. Long-term comparative outcome data from the Indian subcontinent on treatment regimens with cyclophosphamide (CYP) and mycophenolate mofetil (MMF) are sparse. We assessed renal and patient survival for these patients in terms of the types of induction - CYP or MMF - and the two maintenance therapies - MMF or azathioprine (AZA). METHODS: We retrospectively analysed outcomes of 100 LN patients, 67 treated with CYP (26 class III, 25 class IV, 6 class III + V and 10 class IV + V; 40 Euro lupus regimen and 27 National Institutes of Health regimen) and 33 treated with a MMF-based regimen with steroids between July 2008 and June 2018. Data regarding demographic, clinical and histopathological features and the treatment given to all patients were extracted. Outcomes between the two regimens CYP and MMF were compared in terms of remission, dialysis and patient survival. RESULTS: The clinical characteristics were similar in both groups, except that the activity index was higher in CYP patients (6.13 ± 4.48 vs. 4.61 ± 2.80). However, the chronicity index was similar. The overall remission rate was 70% at the end of induction. The rates of complete remission, partial remission and non-responders in the CYP group were 46.2%, 23.9% and 29.9%, respectively. However, in the MMF group, the corresponding rates were 57.6%, 12.1% and 30.3%, respectively. The 1-, 2-, 3-, 4-, 5- and 10-year patient survival rates in the CYP group were 89.5%, 86.2%, 86.2%, 83.8%, 83.8% and 83.8%, respectively. In the MMF induction group, the corresponding rates were 93.9%, 93.9%, 89%, 89%, 89% and 89%, respectively. At the end of the study, rates of end-stage renal disease in the MMF group and CYP group were 7.5% and 12.1%, respectively. The death-censored and non-censored renal survival rates were also similar in the long term. With regard to maintenance therapy, 3/56 (5.3%) in the MMF group and 7/34 (20.5%) in the AZA group experienced doubling of serum creatinine (p = 0.03). CONCLUSIONS: Long-term outcomes in terms of patient and renal survival of LN patients treated with CYP and MMF induction are similar. Doubling of serum creatinine occurred more with AZA-based maintenance therapy than with MMF-based maintenance therapy. Most deaths occurred during induction, and sepsis was the most common cause of death.

Long-term outcomes in children on chronic continuous ambulatory peritoneal dialysis: a retrospective cohort study from a developing country.

BACKGROUND: Peritoneal dialysis (PD) is the preferred modality of dialysis among children with end-stage renal disease. METHODS: To study the incidence of technique failure and survival among children with end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD), we included children younger than 18 years of age who commenced and continued PD for more than 3 months as their primary form of dialysis between 1st January 2005 and 31st December 2016. Kaplan-Meier survival analysis was applied to analyze the CAPD outcomes. RESULTS: A total of 68 Tenckhoff (58 double cuffs, and ten single cuffs) catheters were inserted in 66 patients (mean age 12.3 ± 3.91 years) during the study period. Of the 66 children, 31 (47%) experienced 45 episodes of peritonitis. The total duration on CAPD was 107.58 years with a peritonitis rate of 0.42 episodes per year. Overall, the mean patient survival was 41 (95% confidence interval (CI) 29-54) months, with mean patient survival of 72% at 12 months, declining to 30% at 36 months and then remaining stable until the end of follow-up (106 months). The overall mean technique survival was 55 (95% CI 40-69) months, with mean technique survival of 69% at 12 months, declining to 44% at 36 months and then remaining stable until the end of follow-up (106 months). CONCLUSION: CAPD is a viable option for end-stage renal disease in children from developing countries with a lack of access to automated PD and pediatric hemodialysis centers.

Isolation of bacterial DNA followed by sequencing and differing cytokine response in peritoneal dialysis effluent help in identifying bacteria in culture negative peritonitis.

AIM: The treatment of peritoneal dialysis related culture negative peritonitis is empirical which increases the cost of therapy and moreover antibiotic resistance. We aimed the study to isolate bacterial DNA from PD effluent and indentify bacteria causing peritonitis in culture negative situations. We have also studied the cytokine response with different bacteria causing peritonitis. METHODS: We have isolated bacterial DNA from PD effluent of culture negative and culture positive peritonitis patients. Bacterial DNA was subjected to polymerase chain reaction using universal bacteria specific primers and subsequently to Gram type specific primers for the differentiation of the etiologic agents into Gram-positive and Gram-negative. The amplified products were sequenced and subjected to blast search to identify agent at genus/ species level. RESULTS: Of the 30 molecular method positive samples, 16 (53.33%) samples were positive for Gram-negative bacteria and 4 (13.33%) for Gram-positive, while the remaining10 (33.33%) were positive for both Gram-positive and Gram-negative bacteria. We have found organisms that usually do not grow on normal culture methods. TNF-α was significantly associated with Gram-positive peritonitis and regulatory cytokine IL-10 with Gram-negative peritonitis. CONCLUSIONS: The molecular techniques are helpful in detecting and identifying organisms from culture negative PD effluent.

Recurrent Acute Kidney Injury in Tropics-Epidemiology and Outcomes.

BACKGROUND: Acute kidney injury (AKI) is now an established and preventable cause for chronic Kidney disease. Poor outcome of Acute Kidney Injury is influenced by severity and duration of AKI. We hypothesize that recurrent episodes of acute kidney injury are associated with adverse renal and patient related outcome. METHODS: Study was undertaken to look into etiological risk factors for recurrent AKI and its effect on renal and patient related outcome. This retrospective analytical study was conducted at tertiary care health care centre from northern part of India from January 2003 to December 2013. All patients with the diagnosis of "acute renal failure" or "acute kidney injury" as their hospital admission diagnosis was identified and individuals with recurrent Acute Injury were included in the study. RESULTS: Recurrent acute kidney injury was found in 21 (0.56%) of 3698 patients who presented with acute kidney injury during the 10 years period. Topical infections were the most common etiology of recurrent AKI followed by rhabdomyolysis and intravascular hemolysis leading to pigment nephropathy. Acute tubular necrosis was the most common histopathological diagnosis among patients biopsied. As the episodes of AKI increased from 2 to >2 episodes, there was poor immediate as well as late renal outcome. 50% were protienuric and 87.5% were hypertensive at 1 year among patients who had >2 episodes of AKI while it was 15.3% and 7.69% among patients having < 2 episodes respectively. CONCLUSION: Recurrent episodes of AKI are associated with poor patient and renal outcome suggesting that each episode of acute kidney injury needs close evaluation and follow up following hospital discharge with particular attention to renal outcomes.