Prevalence, predictors, and prognosis of serious infections in Takayasu arteritis - a cohort study.

OBJECTIVE: To describe the incidence, risk factors, and outcomes associated with serious infections in patients with Takayasu arteritis (TAK). METHODS: Serious infections (defined as infections resulting in hospitalization or death or unusual infections like tuberculosis) were identified from a cohort of patients with TAK. Corticosteroids and disease-modifying anti-rheumatic drug (DMARD) use at the time of serious infection was noted. Demographic characteristics, clinical presentation, angiography, and disease activity at presentation and the use of DMARDs during follow-up were compared between patients with TAK with or without serious infections. Mortality in patients with TAK who developed serious infections was compared with those without was compared using hazard ratios (HR, with 95%CI). RESULTS: Of 238 patients with TAK, 38 (15.97%) had developed serious infections (50 episodes, multiple episodes in 8, three episodes resulted in death). Among the 38 initial episodes, 11/38 occurred in those not on corticosteroids and 14/38 in those not on DMARDs. Pneumonia (n=19) was the most common infection, followed by tuberculosis (n=12). Patients with TAK who developed serious infections vs those without had higher disease activity at presentation (active disease 97.37% vs 69.50%, ITAS2010 12.66±7.29 vs 10.16±7.02, DEI.TAK 11.21± 6.14 vs 8.76±6.07) and more frequently were initiated on corticosteroids or DMARDs. Hazard ratios calculated using exponential parametric regression survival-time model revealed increased mortality rate in patients with TAK who developed serious infections (HR 5.52, 95%CI 1.75-17.39). CONCLUSION: Serious infections, which occurred in the absence of immunosuppressive treatment in about one-fifth, were associated with increased mortality in patients with TAK.

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.

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.

Renal artery involvement is associated with increased morbidity but not mortality in Takayasu arteritis: a matched cohort study of 215 patients.

BACKGROUND: We analyzed differences in presentation and survival of Takayasu arteritis (TAK) with or without renal artery involvement (RAI) from a large monocentric cohort of patients with TAK. METHODS: Clinical and angiographic features were compared between TAK with versus without RAI, with bilateral versus unilateral RAI, and with bilateral RAI versus without RAI using multivariable-adjusted logistic regression. Inter-group differences in survival were analyzed [hazard ratios (HR) with 95% confidence intervals (95%CI)] adjusted for gender, age at disease onset, diagnostic delay, baseline disease activity, and significant clinical/angiographic inter-group differences after multivariable-adjustment/propensity score matching (PSM). RESULTS: Of 215 TAK, 117(54.42%) had RAI [66(56.41%) bilateral]. TAK with RAI or with bilateral RAI had earlier disease onset than without RAI (p < 0.001). Chronic renal failure (CRF) was exclusively seen in TAK with RAI. TAK with RAI (vs without RAI) had more frequent hypertension (p = 0.001), heart failure (p = 0.047), abdominal aorta (p = 0.001) or superior mesenteric artery involvement (p = 0.018). TAK with bilateral RAI (vs unilateral RAI) more often had hypertension (p = 0.011) and blurring of vision (p = 0.049). TAK with bilateral RAI (vs without RAI) more frequently had hypertension (p = 0.002), heart failure (p = 0.036), abdominal aorta (p < 0.001), superior mesenteric artery (p = 0.002), or left subclavian artery involvement (p = 0.041). Despite higher morbidity (hypertension, CRF), mortality risk was not increased with RAI vs without RAI (HR 2.32, 95%CI 0.61-8.78), with bilateral RAI vs unilateral RAI (HR 2.65, 95%CI 0.52-13.42) or without RAI (HR 3.16, 95%CI 0.79-12.70) even after multivariable adjustment or PSM. CONCLUSION: RAI is associated with increased morbidity (CRF, hypertension, heart failure) but does not adversely affect survival in TAK. Key Points •Renal artery involvement in TAK is associated with chronic renal failure. •TAK with renal artery involvement more often have heart failure and hypertension. •Bilateral renal artery involvement (compared with unilateral) is more often associated with hypertension and visual symptoms. •Renal artery involvement is not associated with an increased risk of mortality in TAK.

Increased mortality rate in Takayasu arteritis is largely driven by cardiovascular disease-a cohort study.

OBJECTIVES: To analyze the risk, causes, and predictors of mortality in Takayasu arteritis (TAK). METHODS: Survival was assessed in a cohort of patients with TAK using Kaplan-Meier curves. Age- and sex-standardized mortality ratio (SMR = observed: expected deaths) for TAK were calculated by applying age- and sex-specific mortality rates for the local population to calculate expected deaths. Hazard ratios (HR with 95%CI) for predictors of mortality based on demographic characteristics, presenting features, baseline angiographic involvement, disease activity, number of immunosuppressive medications used, procedures related to TAK, and any serious infection were calculated using Cox regression or exponential parametric regression models. RESULTS: Among 224 patients with TAK (159 females, mean follow-up duration 44.36 months), survival at 1, 2, 5, and 10 years was 97.34%, 96.05%, 93.93%, and 89.23%, respectively. Twelve deaths were observed, most of which were due to cardiovascular disease (heart failure, myocardial infarction, stroke). Mortality risk was significantly higher with TAK (SMR 17.29, 95%CI 8.95-30.11) than the general population. Earlier age at disease onset (HR 0.90, 95%CI 0.83-0.98; or pediatric-onset vs adult-onset disease, HR 5.51, 95%CI 1.57-19.32), higher disease activity scores (ITAS2010: HR 1.15, 95%CI 1.05-1.25, DEI.TAK: HR 1.18, 95%CI 1.08-1.29), any serious infections (HR 5.43, 95%CI 1.72-17.12), heart failure (HR 7.83, 95%CI 2.17-28.16), or coeliac trunk involvement at baseline (HR 4.01, 95%CI 1.26-12.75) were associated with elevated mortality risk. CONCLUSION: Patients with TAK had an elevated risk of mortality as compared with the general population. Cardiovascular disease was the leading cause of death in TAK.

Association of Wilms tumor-1 protein in urinary exosomes with kidney injury: a population-based cross-sectional study.

Objective: Loss of Wilms tumor-1 (WT1) protein, a podocytopathy marker, through urine exosome (uE), could be an early indication of kidney injury. We examined WT1 in uE (uE-WT1), along with other urine markers of glomerular and kidney tubule injury, in individuals without chronic kidney disease (CKD). Methodology: The cross-sectional study included individuals who reported having no evidence of chronic kidney disease (CKD). Albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used to assess kidney function. eGFR was calculated using the 2009 CKD-EPI (CKD-Epidemiological) equation. WT1 was analyzed in uE from humans and Wistar rats (before and after the 9th week of diabetes, n = 20). uE-WT1, urinary neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were estimated using ELISA. The Kruskal-Wallis H test, Mann-Whitney U test, and stepwise multivariable linear regression were performed. Results: Urine NGAL and ACR increase with uE-WT1 quartiles (n = 146/quarter). Similarly, uE-WT1, KIM-1, and NGAL were positively associated with ACR. Furthermore, KIM-1, NGAL, and uE-WT1 correlated with ACR. uE-WT1 outperformed KMI-1 and NGAL to explain ACR variability (25% vs. 6% or 9%, respectively). Kidney injury in streptozotocin-induced diabetic rats was associated with a significant rise in uE-WT1. Moreover, the findings were confirmed by the histopathology of kidney tissues from rats. Conclusion: uE-WT1 was strongly associated with kidney function in rats. In individuals without CKD, uE-WT1 outperformed NGAL as a determinant of differences in ACR.

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.

Paediatric-onset Takayasu's arteritis associates with worse survival than adult-onset Takayasu's arteritis. A matched retrospective cohort study.

OBJECTIVES: A subset of Takayasu's arteritis (TAK) begins in the paediatric age group (≤18 years). Differences in prognosis between paediatric-onset and adult-onset TAK are unclear. We compared the differences in the presentation and survival between paediatric-onset and adult-onset TAK in our cohort of TAK. METHODS: From a retrospective cohort of TAK, clinical presentation, angiographic features, treatments received, disease activity, and survival were compared between paediatric-onset and adult-onset TAK. Multivariable-adjusted logistic regression models were used to compute adjusted odds ratio (aOR) with 95% confidence intervals (95%CI) for paediatric-onset vs. adult-onset TAK. Hazard ratios (HR, with 95%CI) for mortality with paediatric-onset vs adult-onset TAK (crude, adjusted for prognostic covariates or differences in presentation) and propensity score-matched survival analyses were estimated. RESULTS: Among 56 paediatric-onset and 135 adult-onset TAK, chest pain (aOR 3.21, 95%CI 1.06-9.74), heart failure (aOR 3.16, 95%CI 1.05-9.53), headache (aOR 2.60, 95%CI 1.01-6.74), ascending aorta (aOR 3.02, 95%CI 1.04-8.80) and left renal artery involvement (aOR 2.45, 95%CI 1.04-5.80) were more frequent in paediatric-onset TAK. Despite similar longitudinal patterns of disease activity and glucocorticoid or disease-modifying antirheumatic drug (DMARD) use, mortality was higher for paediatric-onset TAK (HR, unadjusted 6.13, 95%CI 1.51-24.91; adjusted for prognostic covariates gender, diagnostic delay, baseline disease activity, number of conventional and biologic/targeted synthetic DMARDs used, 4.97, 95%CI 1.20-20.58; adjusted for differences between groups 5.54, 95%CI 1.22-25.09; after propensity-score matching for prognostic covariates, 54 pairs, log-rank p-value 0.026). CONCLUSIONS: Considering the greater mortality risk, greater vigilance is required while managing paediatric-onset TAK.

Comparing Estimated and Measured Glomerular Filtration Rate in Children with Posterior Urethral Valve.

Background: Posterior urethral valve (PUV) is obstructive uropathy that may lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD) in children. Glomerular filtration rate (GFR) measurement remains the gold standard for renal function measurement. However, due to its less availability and cumbersome, it is not commonly used, and GFR is estimated utilizing various endogenous filtration markers. Objective: This study includes pediatric patients with PUV. We aimed to compare the measured GFR (mGFR) with various creatinine-based estimated GFR methods (eGFR). Materials and Methods: A single-center retrospective study included 62 treated cases of PUV, postvalve fulguration. The mGFR measured by 99mTc-diethylenetriaminepentaacetate in vitro method and compared with eight eGFR (Schwartz, Cockcroft-Gault [CG], Counahan-Barratt [CB], CKD Epidemiology Collaboration [CKD-EPI], full-age spectrum [FAS] age, FAS height (FAS Ht), Schwartz-Lyon [SL], and Ht independent). Patients were subdivided into different CKD grades and compared with various eGFR. Discussion: PUV is a common cause of CKD in children and needs special consideration as there is growth retardation associated with it. It decreases creatinine production and thus fallacies in eGFR measurement. There is a requisite to identify and closely monitor the subset of patients with baseline decreased renal function and therefore at risk of developing ESRD. Results: A total of 62 patients were included. Mean age and serum creatinine levels were 8.02 ± 5.53 years and 1.15 ± 0.95 mg/dl (range: 0.4-4.5), respectively. The mean mGFR was 61.6 ± 31.80 mL/min/1.73 m2 and a positive variable correlation was 0.46-0.77 between mGFR and eGFR. Based on mGFR, there were 14 (22.6%), 21 (33.8%), 13 (20.9%), 9 (14.5%), and 5 (8.1%) patients in Grades I-V, respectively. The correct classification of the CKD grades was noted in 25 (40.3%), 16 (25.8%), 32 (51.6%), 16 (25.8%), 25 (40.3%), 27 (43.5%), 26 (41.9%), and 28 (45.2%) patients by Schwartz, CG, CB, CKD-EPI, FAS age, FAS Ht, SL, and Ht-independent equation. The eGFR overestimates GFR at the lower level and underestimates at higher levels. Conclusion: Our results confirm the considerable limitations of various creatinine-based clearance methods for estimating actual GFR. The creatinine clearance-based eGFR should not replace the measurement of the GFR. An initial measure of the mGFR followed by serial follow-up with the eGFR equation may be done. The most accurate eGFR equations are CB for Grade II, SL or Ht independent for Grade III, FAS age for Grade IV, and SL for Grade V CKD.

QTc Interval of Healthcare Workers from India: Baseline and Effect of Hydroxychloroquine Prophylaxis during the COVID-19 Pandemic.

Background: The aim of this study was to access the incidence of prolonged QTc interval and changes, if any, among Indian healthcare workers (HCWs) taking hydroxychloroquine (HCQ) prophylaxis while managing coronavirus disease 2019 (COVID-19) cases. Methods: At the beginning of the COVID-19 pandemic, as per the Indian Council of Medical Research (ICMR) policy, HCWs were advised to take HCQ as prophylaxis after getting an electrocardiogram (ECG) while being posted to look after COVID-19 patients. A follow-up ECG was repeated for those who took HCQ. The normal upper limit for QTc interval of 460 milliseconds (ms) for females and 450 ms for males was considered. Results: A baseline ECG was analyzed for 250 HCWs with a median age of 35 (30-43) years. The median QTc was 410 (395-421) ms with the prevalence of prolonged QTc of 1.8% in females and 0% in males. A follow-up ECG after HCQ intake for 43 HCWs was further analyzed. They had a median age of 35 (31-39) years and took an average dose of HCQ of 2372 ± 839 mg. Pre- and post-HCQ chemoprophylaxis QTc interval (ms) was as follows: 408 (386-419) and 405 (387-417), with P = 0.434, respectively. Conclusion: Among Indian HCWs, the prevalence of prolonged QTc is 1.8% and 0% in females and males, respectively. HCQ intake as chemoprophylaxis for COVID-19 did not affect their QTc interval.

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.

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.

Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus: A Changing Spectrum with Therapeutic Ascendancy.

BACKGROUND AND OBJECTIVES: Owing to changing epidemiology and therapeutic practices, a change in the spectrum of renal involvement in Type-2 diabetes mellitus (T2DM) has also been noted. The treatment of non-diabetic kidney disease (NDKD) differs from diabetic kidney disease (DKD) and the reversibility of NDKD in many cases to normal, prompts biopsy for rapid and accurate diagnosis. Data are scarce on kidney biopsy findings in T2DM. STUDY DESIGN & SETTING: In this observational study, we prospectively collected the data of kidney biopsies of patients aged ≥ 18 years with T2DM admitted between 1 August 2005 and 31 July 2022. The clinical, demographic and histopathological data were evaluated. The spectrum of kidney involvement in the form of DKD and/or NDKD was studied. The impact of these findings with the use of drugs retarding disease progression was also analyzed. RESULTS: A total of 5485 biopsies were performed during the study period and of these 538 patients had T2DM. The mean age of the study population was 56.9 ± 11.5 years and 81% were males. The mean duration of DM was 6.4 ± 6.1 years. Diabetic retinopathy (DR) was noted in 29.7%. The most common indication for biopsy was an acute rise in creatinine (147, 27.3%). Amongst the 538 diabetic patients who underwent biopsy, histological features only of DKD were noted in 166 patients (33%), NDKD alone in 262 (49%) and NDKD with DKD lesions in 110 (20%). On multivariate analysis, duration of DM less than 5 years, absence of CAD, absence of DR, oliguria at presentation, an acute rise in creatinine and low C3 were associated with NDKD. CONCLUSIONS: The prevalence of NDKD among diabetics and ATIN in particular might be on an increasing trend in the current era of changing T2DM epidemiological patterns. The use of anti-pro-teinuric agents was associated with lesser degrees of histopathological chronicity in T2DM.

Pre-Pulseless Takayasu Arteritis is Associated with Distinct Clinical and Angiographic Features but Similar Outcomes - A Cohort Study.

Objectives: To compare the presentation, angiographic features, evolution, and prognosis of prepulseless Takayasu arteritis (TAK) with TAK with pulse loss. Methods: Pre-pulseless TAK (defined as without pulse loss in the upper limbs, lower limb, carotid, or subclavian arteries) were identified from a cohort of TAK. Demographic characteristics, clinical features, angiographic involvement, baseline and longitudinal patterns of disease activity, medication use, and mortality rates were compared between pre-pulseless TAK and TAK with pulse loss. Adjusted odds ratios (aOR, with 95%CI) for categorical variables between pre-pulseless TAK and TAK with pulse loss were computed using multivariable-adjusted logistic regression models. Time-to-event data was compared using hazard ratios (HR) with 95%CI. Results: Compared with TAK with pulse loss, pre-pulseless TAK (91/238, 38.24%) more frequently had deranged renal function (aOR 4.43, 95%CI 1.58-12.37) and Hata's type IV disease (aOR 8.02, 95%CI 2.61-24.65), and less often had pulse or blood pressure asymmetry (aOR 0.34, 95%CI 0.18-0.63), limb claudication (aOR for upper limb 0.38, 95%CI 0.18-0.82, for lower limb 0.28, 95%CI 0.12-0.68), right subclavian (aOR 0.45, 95%CI 0.23-0.90) or left carotid artery involvement (aOR 0.42, 95%CI 0.21-0.84). Only two patients with pre-pulseless TAK developed pulse loss on follow-up. Despite fewer pre-pulseless TAK having active disease at presentation, similar proportions of patients in both groups had active disease on follow-up. Survival was similar in both groups (HR for mortality 0.41, 95%CI 0.09-1.90). Conclusion: Pulse loss on follow-up is uncommon in those with prepulseless TAK. Pre-pulseless TAK is associated with similar long-term outcomes to TAK with pulse loss.

Desmopressin Acetate Before Percutaneous Ultrasound-Guided Kidney Biopsy in Patients with Renal Failure - Is it Really Beneficial?

Introduction: The most common complication of percutaneous renal biopsy is bleeding, which can be seen in up to one-third of cases. The aim of this study was to evaluate the effect of prebiopsy administration of intranasal desmopressin acetate in reducing the incidence of biopsy-related bleeding complications in patients with significant renal dysfunction who underwent renal biopsy. Methods: This was a retrospective, observational study of percutaneous native renal biopsies performed at our center from July 2014 to June 2018. Bleeding complication rates of patients with renal failure (estimated glomerular filtration rate [eGFR] <30 mL/minute/1.73 m2) who received desmopressin and those who did not receive desmopressin were compared. Results: Desmopressin administration before renal biopsy in patients with eGFR <30 mL/minute/1.73 m2 was associated with a significant reduction of bleeding complications (major and minor together; P = 0.025) and no significant reduction in major complications (P = 0.616) or intervention rates (P = 0.251) when compared with a group that did not receive desmopressin. Conclusions: While prebiopsy intranasal desmopressin use was associated with a significant reduction of overall bleeding complications including major and minor complications, there was no reduction in the rate of other major complications and interventions.

Impact of Geographic Location on Diagnosis and Initial Management of Takayasu Arteritis: A Tale of Two Cohorts from Italy and India.

The present study compares disease characteristics, imaging modalities used, and patterns of treatment in two large cohorts of Takayasu arteritis (TAK) from Italy and India. Clinic files were retrospectively reviewed to retrieve information about initial choices of vascular imaging and immunosuppressive therapies. Unpaired t-tests compared means, and proportions were compared using Fisher's exact test or Chi square test [Odds ratios (OR) with 95% confidence intervals (95%CI) calculated where appropriate]. The cohorts comprised 318 patients [Italy (n = 127), India (n = 191)] with similar delays to diagnosis. Ultrasound (OR Italy vs. India 9.25, 95%CI 5.02−17.07) was more frequently used in Italy and CT angiography in India (OR 0.32, 95%CI 0.20−0.51). Corticosteroid use was more prevalent and for longer duration in Italy. TAK from Italy had been more often treated with methotrexate, leflunomide or azathioprine, as opposed to tacrolimus in TAK from India (p < 0.05). Biologic or targeted synthetic disease-modifying agents were almost exclusively used in Italy. Survival on first immunosuppressive agent was longer from Italy than from India (log rank test p value 0.041). Considerable differences in the choice of initial vascular imaging modality and therapies for TAK from Italy and India could relate to prevalent socio-economic disparities. These should be considered while developing treatment recommendations for TAK.

Comparison of Presentation and Prognosis of Takayasu Arteritis with or without Stroke or Transient Ischemic Attack-A Retrospective Cohort Study.

Takayasu arteritis (TAK) could cause a stroke or transient ischemic attack (TIA) in young individuals due to inflammatory vascular occlusion or intracerebral hemorrhage. We compared the clinical presentation, angiographic features, longitudinal patterns of disease activity, medical treatments, and survival in 34 TAK patients with stroke/TIA and 157 without stroke/TIA from a single-center retrospective cohort. TAK patients with stroke/TIA were older (p = 0.044) with a greater proportion of males (p = 0.022), more frequent vision loss (odds ratio (OR) for stroke/TIA vs. without stroke TIA 5.21, 95% CI 1.42-19.14), and less frequent pulse or blood pressure inequality (OR 0.43, 95% CI 0.19-0.96) than TAK patients without stroke/TIA. Hata's angiographic type IIa was more common in TAK patients with stroke/TIA (OR 11.00, 95%CI 2.60-46.58) and type V in TAK patients without stroke/TIA (OR 0.27, 95% CI 0.12-0.58). Cyclophosphamide was used more often in TAK patients with stroke/TIA (p = 0.018). Disease activity at baseline, 6, 12, and 24 months of follow-up was mostly similar for both groups. Risk of mortality was similar in TAK patients with or without stroke/TIA (hazard ratio unadjusted 0.76, 95% CI 0.15-3.99; adjusted for gender, age of disease onset, delay to diagnosis, baseline disease activity, and the number of conventional or biologic/targeted synthetic immunosuppressants used 1.38, 95% CI 0.19-10.20) even after propensity score-matched analyses. Stroke or TIA does not appear to affect survival in TAK patients adversely.

Liver Stiffness is Reduced to Normal After Successful Renal Transplantation: A Prospective Cohort Study.

Background: Liver stiffness (LS) may be falsely elevated in patients on maintenance hemodialysis (MHD) due to fluid overload. We measured LS change by transient elastography (TE) in MHD patients before and after successful renal transplantation. Method: Adults on ≥2 years of MHD, without additional risk factors for liver fibrosis or fluid overload, and planned for renal transplantation were prospectively recruited. LS was measured on two occasions, i.e., within two weeks before transplantation (pre-Tx LS) and after ≥ 3 months after successful transplantation (post-Tx LS). The participants with pre-Tx LS ≤ 7.0 KPa and >7.0 KPa were classified as "Group I" and "Group II," respectively. Categorical and numerical data are expressed as ratio/proportions and mean (SD), respectively. Results: Paired data from 43 participants (males 42 [97.7%]; age 32 [11] years) were analyzed. The pre-Tx and post-Tx LS of the entire cohort, measured at 307 (198) days of interval, were 8.5 (7.3) KPa and 6.7 (3.1) KPa, respectively. Before transplantation, 21 (49%) participants belonged to Group II and 22 (51%) to Group I. Among the Group II participants, 12 (57%) showed LS normalization after 312 (182) days of transplantation. Of the 22 participants in Group I, three (13.6%) showed LS elevation to >7.0 KPa after 303 (217) days of transplantation. The mean LS changes among the overall cohort, Group II, and Group I were -1.8 KPa, -4.1 KPa, and +0.2 KPa, respectively. Conclusion: LS in people on MHD may be falsely elevated, which is likely to normalize after successful renal transplantation.

Association of Human Leucocyte Antigen Polymorphism with Coronavirus Disease 19 in Renal Transplant Recipients.

Human leucocyte antigens (HLAs) are highly polymorphic glycoproteins expressed at the surface of all nucleated cells. It is required for the SARS-CoV-2 peptide antigen presentation to immune cells for their effector response. However, polymorphism in HLA significantly impacts the binding of SARS-CoV-2 antigenic peptide to the HLA pocket and regulates immune activation. In this study, 514 renal transplant recipients (RTRs) were recruited from the outpatient department and categorized either into symptomatic (n = 173) or asymptomatic groups (n = 341) based on Coronavirus disease-19 (COVID-19) symptoms. The anti-SARS-CoV-2 spike protein-specific IgG antibody titer was measured by chemiluminescent microparticle immune-assay methods in 310 RTRs. The HLA details of 514 patients were retrieved from the electronic medical records and analyzed retrospectively. We found that HLA antigen allele A*24 was significantly associated with asymptomatic infection in 22.78%, HLA C*02 in 4.51%, DRB1*12 in 10.85%, and HLA DQA1*02 in 27.74% of RTRs. Whereas HLA A*29 in 3.46%, A*33 in 26.01%, B*13 in 10.40%, DRB1*10 in 4.62%, DRB1*15 in 39.30%, DRB1*30 in 1.15%, and DQA1*60 in 3.57% of RTRs were associated with symptomatic infection. HLA DRB1*13 and DRB1*15 were associated with moderate to severe degrees of COVID-19 disease. The seroconversion rate in asymptomatic patients was 118/137 (86.13%), had a median titer of 647.80 au/ml, compared to symptomatic patients 148/173 (85.54%) with a median titer of 400.00 au/ml, which was not significant between the two groups (P = 0.88 and 0.13). In conclusion, HLA alleles A*24, C*02, DRB1*12, and DQA1*02 were significantly associated with asymptomatic infection, and A*29, A*33, B*13, DRB1*10, DRB*15, and DRB1*30 were significantly associated with symptomatic infection. HLA DRB1*13 and DRB1*15 were associated with moderate to severe degrees of COVID-19 disease.