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Shankar Prasad Nagaraju, Srinivas Vinayak Shenoy, Indu Ramachandra Rao, Mohan V Bhojaraja, Dharshan Rangaswamy, Ravindra Attur Prabhu Department of Nephrology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, 576104, IndiaCorrespondence: Mohan V Bhojaraja, Email mohan.vb@manipal.eduAbstract: Chronic kidney disease (CKD) is extremely common all over the world and is strongly linked to cardiovascular disease (CVD). The great majority of CKD patients have hypertension, which raises the risk of cardiovascular disease (CVD), end-stage kidney disease, and mortality. Controlling hypertension in patients with CKD is critical in our clinical practice since it slows the course of the disease and lowers the risk of CVD. As a result, accurate blood pressure (BP) monitoring is crucial for CKD diagnosis and therapy. Three important guidelines on BP thresholds and targets for antihypertensive medication therapy have been published in the recent decade emphasizing the way we measure BP. For both office BP and out-of-office BP measuring techniques, their clinical importance in the management of hypertension has been well defined. Although BP measurement is widely disseminated and routinely performed in most clinical settings, it remains unstandardized, and practitioners frequently fail to follow the basic recommendations to avoid measurement errors. This may lead to misdiagnosis and wrong management of hypertension, especially in CKD patients. Here, we review presently available all BP measuring techniques and their use in clinical practice and the recommendations from various guidelines and research gaps emphasizing CKD patients.Keywords: ambulatory BP, office BP, chronic kidney disease, out-of-office BP, standardized BP

Shankar Prasad Nagaraju,1 Mohan V Bhojaraja,1 Ganesh Paramasivam,2 Ravindra Attur Prabhu,1 Dharshan Rangaswamy,1 Indu Ramachandra Rao,1 Srinivas Vinayak Shenoy1 1Department of Nephrology, Kasturba Medical College, Manipal, Manipal Academy Higher Education, Manipal, Karnataka, 576104, India; 2Department of Cardiology, Kasturba Medical College, Manipal, Manipal Academy Higher Education, Manipal, Karnataka, 576104, IndiaCorrespondence: Mohan V Bhojaraja Email mohan.vb@manipal.eduIntroduction: Pulmonary hypertension (PH) is an underestimated cardiovascular consequence and a mortality predictor in patients on hemodialysis (HD). Thus, we studied its prevalence, risk factors, association with inflammation/oxidative stress, and cardiac changes in HD patients.Methods: This was a single-center cross-sectional observational study conducted at a tertiary care hospital. Patients aged > 18 years on hemodialysis for at least three months were included and divided into those with and without PH; patients with secondary causes for PH were excluded. Clinical characteristics, HD-related factors, lab parameters (C-reactive protein and malondialdehyde with thiol assay were used as markers of inflammation and oxidative stress, respectively), and echocardiography details were compared. PH was defined as a mean pulmonary artery pressure of > 25 mmHg at rest, and it was further divided as mild (25– 40 mmHg), moderate (40– 60 mmHg), and severe (> 60 mmHg).Results: Of 52 patients, 28 patients had PH (mild 24, moderate 4, and none had severe PH) with prevalence of 54%. No difference was found in clinical characteristics, dialysis-related factors, biochemical parameters including inflammation (C-reactive protein; p=0.76), or oxidative stress (thiol; p=0.36 and MDA; p=0.46) between the groups. When compared to individuals without PH, HD patients with PH exhibited significantly more mitral regurgitation (p=0.002).Conclusion: Hemodialysis patients have a high prevalence of PH. PH was significantly associated with the presence of mitral regurgitation on echocardiography. Our study did not find differences in traditional risk factors, HD-related factors, and inflammation/oxidative markers between the groups with and without PH.Keywords: chronic kidney disease, hemodialysis, inflammation, oxidative stress, pulmonary hypertension

Ravindra Attur Prabhu,1 Srinivas V Shenoy,1 Shankar Prasad Nagaraju,1 Dharshan Rangaswamy,1 Indu Ramachandra Rao,1 Mohan V Bhojaraja,1 Deepak Nayak M,2 Sindhura Lakshmi Koulmane Laxminarayana,2 Karan Saraf,1,3 Ashok Ramaswamy1,4 1Department of Nephrology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India; 2Department of Pathology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India; 3Department of Nephrology, Excelcare Hospitals, Guwahati, Assam, India; 4Department of Nephrology, Saveetha Medical College, Chennai, Tamil Nadu, IndiaCorrespondence: Srinivas V ShenoyDepartment of Nephrology, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, IndiaTel +91 9844374705Email shenoy.srinivas@manipal.eduPurpose: Diabetic kidney disease (DKD) represents a unique subset of patients with chronic kidney disease (CKD). Acute kidney injury (AKI) is implicated in DKD progression; however, their interplay is not studied well. We studied risk factors for AKI and the effect of AKI on disease progression in a homogeneous group of patients with DKD.Patients and Methods: We conducted a retrospective open cohort study of patients with DKD at a single tertiary care centre between August 2016 – August 2019. Patients with a minimum follow-up of 2 years were included in the study. The incidence, etiology and risk factors for AKI were studied. The primary outcome studied was the effect of AKI on reduction in estimated glomerular filtration rate (eGFR) in DKD. Loss in eGFR by 50% and need for renal replacement therapy or reaching CKD stage V were studied as secondary outcomes.Results: Two hundred and ninety-two DKD patients meeting the study criteria with a follow-up of 29.57 (± 4.3) months were included. The incidence of AKI was 31.1%. Sepsis was the most common etiology (61%). Proteinuria was an independent risk factor for AKI after adjusting for covariates (adjusted OR - 1.158; 95% CI (1.018– 1.316); p=0.025). In patients with AKI, median decline in eGFR was 10.29 mL/min/1.73m2/year (IQR-5.58– 13.84) which was significantly higher compared to patients with no AKI [eGFR 7.25 (IQR 5.06– 11.38); p-0.014]. On subgroup analysis, sepsis-induced AKI (versus non-sepsis AKI; p< 0.001) and higher AKI stage (stage 2/3 versus stage 1; p=0.019) were associated with a faster decline in eGFR.Conclusion: AKI is common in patients with DKD with sepsis being the most common etiology. AKI in diabetic kidney disease is associated with a faster decline in eGFR. Baseline proteinuria is an independent risk factor for AKI.Keywords: diabetic kidney disease, acute kidney injury, GFR decline, proteinuria, sepsis

Introduction: Patients with chronic kidney disease (CKD) are at increased risk of developing tuberculosis (TB). These patients may also be at higher risk of developing antitubercular treatment (ATT)-associated adverse drug reactions (ADRs). Although dose modification has been recommended, data regarding the impact of impaired kidney function on ATT-associated ADRs is sparse. We studied the incidence and profile of ATT-associated ADRs in patients with CKD and compared them with those with normal kidney function., Methodology: This retrospective study analyzed all patients initiated on ATT from January 2016 to August 2019. Patients were grouped into CKD and normal kidney function based on their eGFR. Data on ATT-associated ADRs were collected from medical records. Predictors of ADRs were assessed using univariable and multivariable logistic regression. Additionally, Propensity score matching and analysis were done for CKD and normal kidney function in 1:3 ratio., Results: Of 1815 patients on ATT, 75 (4.1%) had CKD. ADRs were more frequent [36/75 (48.0%) vs. 239/1740 (13.7%), p  ≤ 0.0001] and more severe [15/46 (32.6%) vs. 43/283 (15.1%), p  = 0.010] in CKD than those with normal kidney function. The most common ADRs were hepatobiliary [23/75 (30.6%) vs. 156/1740 (8.9%), p  ≤ 0.0001], neuropsychiatric [8/75(10.6%) vs. 21/1740(1.2%), p  ≤ 0.0001], renal [4/75(5.3%) vs. 8/1740(0.4%), p  = 0.001], and gastrointestinal [5/75(6.6%) vs. 34/1740 (1.9%), p  = 0.020]. CKD was an independent predictor for ADRs (OR -4.96, 95% CI: 2.79-8.82; p  ≤ 0.0001). The matched cohort showed similar results., Conclusion: ATT-associated ADRs were more common and severe in patients with CKD, despite drug dose modifications. Optimal dosing of ATT in CKD needs to be further evaluated.

Introduction: Chloride is the most abundant extracellular anion; however, abnormalities of serum chloride (dyschloremia) are often overlooked. This study aimed to study the association of dyschloremia with AKI and major adverse kidney events at Day 30 (MAKE30) in critically ill patients with sepsis. Materials and Methods: This prospective single-center cohort study included adult patients with sepsis admitted in a tertiary care hospital in India. Patients with advanced chronic kidney disease, requiring dialysis at admission, or with hospital stay of less than 72 h were excluded. Hyperchloremia and hypochloremia were defined as chloride levels of > 110 mEq/L and < 95 mEq/L, respectively. The primary outcome measure was MAKE30-a composite of death, need for dialysis, or sustained loss of kidney function at Day 30. Results: In a cohort of 400 patients with a mean age of 60 (±15) years, AKI was seen in 301 (75.2%) and MAKE30 in 171 (42.8%). Hyperchloremia and hypochloremia were seen in 19.3% ( n  = 77) and 32.3% ( n  = 129), respectively, in the first 72 h of ICU stay. Hypochloremia, but not hyperchloremia, was independently associated with both MAKE30 (OR: 2.56, 95% CI: 1.13-5.79; p =0.024) and new-onset or worsening AKI (OR: 2.52, 95% CI: 1.17-5.41; p =0.019). There was no association between hyperchloremia and either MAKE30 (OR: 1.07, 95% CI: 0.43-2.69; p =0.882) or new-onset/worsening AKI (OR: 0.89, 95% CI: 0.38-2.09; p =0.781). Conclusion: Hypochloremia, but not hyperchloremia, was associated with MAKE30 in this cohort of critically ill patients with sepsis. Trial Registration: Clinical Trial Registry identifier: CTRI//2022/02/040519., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Saurabh M. Thanekar et al.)

Percutaneous renal biopsy, although essential for renal disease diagnosis, is associated with a number of post-biopsy complications ranging from gross haematuria to AV fistula to death. In this study, we carried out an active haematoma surveillance and attempted to correlate renal sonological parameters-kidney length, renal parenchymal changes, renal cortical and parenchymal thickness for their potential use in prediction of post-renal biopsy complications., Methods: This was a prospective study done from April 2022 to April 2023 on all adult patients undergoing native or transplant kidney biopsy. Baseline clinical, laboratory and renal sonological parameters were noted prior to biopsy. USG-guided renal biopsy was done and any haematoma at 0 h, 12 h and 24 h post-biopsy noted. Biopsy complications including need for any interventions were noted., Results: Out of the 240 patients enrolled in the study, 58.3% experienced post-biopsy complications. Among these, 5% of patients encountered major complications, with 3.33% necessitating medical intervention following renal biopsy procedures. A high percentage, 98.89%, exhibited hematoma formation within 12 h post-biopsy. Furthermore, our analysis revealed that a hematoma size exceeding 1.2 cm at the 12-h mark exhibited a sensitivity of 100% and specificity of 71% in predicting the need for blood transfusion. Renal parenchymal changes were the most reliable sonological parameters for predicting post-biopsy complication on multivariate analysis., Conclusion: The incidence of major complications requiring interventions following renal biopsy is notably low. Our study highlights the significance of renal sonological characteristics, including parenchymal thickness, cortical thickness and parenchymal changes, in predicting these complications. Furthermore, we emphasize the utility of hematoma surveillance immediately post-biopsy and at the 12 h, as a valuable tool for predicting the necessity of post-biopsy interventions. This approach can aid in efficiently triaging patients and determining the need for further observation post-renal biopsy., (© 2024. The Author(s).)

Mucosal melanomas account for less than 1% of all sinonasal malignancies and are aggressive tumours originating from melanocytes in various mucosal epithelia. Diagnosis is often delayed due to nonspecific symptoms, contributing to challenges in treatment and management. We present a case of a 75-year-old female with epistaxis and nasal blockage, ultimately diagnosed with amelanotic sinonasal melanoma. Despite diagnostic difficulties exacerbated by profuse bleeding during biopsy attempts, a comprehensive approach involving clinical evaluation, imaging, and histopathology led to a definitive diagnosis. Immunohistochemistry played a crucial role in confirming the diagnosis, ruling out differential diagnoses such as olfactory neuroblastoma and lymphoma. Surgical excision, despite intraoperative bleeding, was successful, followed by adjuvant chemotherapy and radiotherapy due to the tumor's advanced stage. The case underscores the importance of a multidisciplinary approach and personalized treatment strategies, considering the tumor's molecular characteristics for improved outcomes in managing this rare malignancy., Competing Interests: Competing InterestsNot applicable., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Haematological abnormalities following renal transplantation are frequently observed and have a significant effect on survival and graft outcomes. The pattern of haematological abnormalities varies globally. Few studies have been conducted in Asian countries. We aimed to evaluate the patterns of haematological abnormalities in post-transplant recipients in our center during the first year after post-renal transplant and the association of post-transplant anemia with graft function., Methods: This single-center retrospective study was conducted on renal transplantation recipients between 2014 and 2019. The study included all patients who received kidney transplants from live/cadaveric donors and had follow-up data collected up to 12 months after the transplant. The outcome studied was the prevalence of haematological abnormalities and the association between post-transplant anemia (PTA) and graft function in post-transplant recipients., Results: A total of 106 renal transplant recipients were included in the study. The prevalence of PTA was 98% in the first week, 75% at one month, 35% at three months, 32% at six months, and 27% at 12 months. The other cytopenia cases were leukopenia (43.4%), thrombocytopenia (33.2%), and pancytopenia (15.1%). Post-transplant erythrocytosis was observed in 17.9% of patients. 18 patients with severe PTA in the first week of transplant had significant allograft dysfunction (p=0.04). Patients with and without PTA had similar graft functions at six and 12 months (p=0.50)., Conclusions: Haematological abnormalities are common in renal transplant recipients. PTA is highly prevalent during the first week and improves over time. Other haematological abnormalities observed were leukopenia, thrombocytopenia, pancytopenia, and post-transplant erythrocytosis. Leucopenia was primarily drug-induced, and thrombocytopenia and pancytopenia were frequently caused by infections in our cohort. Additionally, severe PTA was significantly associated with graft dysfunction in the first week post-transplant, whereas similar graft function was observed at 6 and 12 months post-transplant, irrespective of the presence or absence of PTA., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Laxminarayana SLK et al.)

Tumor growth is intricately linked to the process of angiogenesis, with a key role played by vascular endothelial growth factor (VEGF) and its associated signaling pathways. Notably, these pathways also play a pivotal "housekeeping" role in renal physiology. Over the past decade, the utilization of VEGF signaling inhibitors has seen a substantial rise in the treatment of diverse solid organ tumors, diabetic retinopathy, age-related macular degeneration, and various ocular diseases. However, this increased use of such agents has led to a higher frequency of encountering renal adverse effects in clinical practice. This review comprehensively addresses the incidence, pathophysiological mechanisms, and current evidence concerning renal adverse events associated with systemic and intravitreal antiangiogenic therapies targeting VEGF-A and its receptors (VEGFR) and their associated signaling pathways. Additionally, we briefly explore strategies for mitigating potential risks linked to the use of these agents and effectively managing various renal adverse events, including but not limited to hypertension, proteinuria, renal dysfunction, and electrolyte imbalances., (© 2024. The Author(s).)

Objectives: The existing biomarkers used to promptly identify graft dysfunction after kidney transplantation lack consistency. Neutrophil gelatinase-associated lipocalin (NGAL) appears to be a promising biomarker but its levels measured from serum and urine have demonstrated varying predictive values. Our study aimed to explore the potential of NGAL as a biomarker in predicting graft dysfunction in kidney transplant patients, including live and deceased donor recipients., Methods: A single-centered observational cohort study with live and deceased kidney recipients as participants was conducted between 2018 and 2022 at a tertiary care hospital in Southern India. Serum creatinine levels were monitored daily; creatinine reduction on day two and day seven were calculated. The recipients were categorized based on graft recovery into three groups: delayed graft function (DGF), slow graft function (SGF), or immediate graft function (IGF). Analysis of serum and urine NGAL was conducted two hours after the transplant and their predictive values were evaluated by the area under the curves (AUC) method., Results: Of the 40 participants, 34 (85.0%) received their transplant from live-related donors, while six (15.0%) received kidneys from deceased donors. DGF occurred in four (10.0%) patients, SGF in 12 (30.0%), and 24 (60.0%) patients achieved IGF. Serum NGAL demonstrated higher sensitivity compared to urine NGAL. At a cut-off value of 678 ng/mL (AUC = 0.77), serum NGAL showed 90.0% sensitivity and 53.0% specificity. Urine NGAL had 70.0% sensitivity and 74.0% specificity at a cut-off value of 489 ng/mL (AUC = 0.72)., Conclusions: Kidney recipients in SGF and DGF categories had elevated levels of serum and urine NGAL compared to those without IGF. Although serum NGAL showed higher sensitivity than urine NGAL in predicting graft dysfunction, both markers lacked the specificity needed for accurate predictions., (Copyright © 2024, Oman Medical Journal.)

Background: A significant proportion of diabetic kidney disease (DKD) experience a rapid decline in eGFR, leading to end-stage kidney disease (ESKD) within months. This single-centered retrospective cohort study aimed to assess the prevalence, clinical profile, and predictors for rapid progression in type 2 diabetes mellitus (T2DM) patients with DKD., Method: Three hundred fifty-nine T2DM patients with DKD between January 2018 and 2022 were included and those with superimposed non-diabetic kidney disease, chronic kidney disease 5, and < 6 months follow-up were excluded. They were classified as rapid and non-rapid progressors based on the annual eGFR decline of > 5 ml/min/1.73 m 2 /year. The primary outcome analyzed was the progression to ESKD. The secondary outcomes were the onset of microvascular and macrovascular complications and predictors for rapid progression as well as ESKD., Results: In a median follow-up of 3.5 years, 61.3% were rapid progressors (mean eGFR decline of 15.4 ml/1.73m 2 /year) and 38.7% were non-rapid progressors (mean eGFR decline 1.8 ml/1.73m 2 /year. Among rapid progressors, 61.4% reached ESKD. Severe proteinuria, the presence of retinopathy, and acute kidney injury (AKI) episodes were strong predictors of rapid progression. Cardiovascular disease and diabetic retinopathy (microvascular complications) were significantly higher among rapid progressors and had a mortality rate of 7.2%., Conclusion: The majority of type 2 DKD patients were rapid progressors and two-thirds of them developed ESKD. The prevalence of hypertension, cardiovascular disease, diabetic retinopathy, AKI episodes, and mortality was higher in rapid progressors. Severe proteinuria and diabetic retinopathy were found to be strong predictors for rapid eGFR decline and its progression to ESKD., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Diabetic kidney disease (DKD) is the most devastating complication of diabetes mellitus. Identification of patients at the early stages of progression may reduce the disease burden. The limitation of conventional markers such as serum creatinine and proteinuria intensify the need for novel biomarkers. The traditional paradigm of DKD pathogenesis has expanded to the activation of the immune system and inflammatory pathways. Monocyte chemo-attractant protein-1 (MCP-1) is extensively studied, as a key inflammatory mediator that modulates the development of DKD. Recent evidence supports the diagnostic role of MCP-1 in patients with or without proteinuria in DKD, as well as a significant role in the early prediction and risk stratification of DKD. In this review, we will summarize and update present evidence for MCP-1 for diagnostic ability and predicting the progression of DKD., (Copyright © 2023 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Objectives: To compare pre- and post-operative pure tone audiometric and impedance audiometric analysis following conventional and endoscopic microdebrider assisted adenoidectomy and compare the outcomes., Methods: Patients diagnosed with chronic adenoiditis were divided in groups of 25 each. Patients in the first group underwent conventional curettage adenoidectomy, while those in second group underwent endoscopic microdebrider assisted adenoidectomy. Pre- and post-operative pure tone and impedance audiometry were performed for all patients and outcomes were compared., Results: The endoscopic microdebrider assisted method resulted in significantly better outcomes compared to conventional curettage. Criteria such as hearing threshold (p value 0.004 at second follow-up), peak pressure (p value 0.045 at first follow-up) and tympanogram (p value 0.016) showed that the endoscopic method was better, while peak compliance (p value 0.340 at first follow-up) did not show any significant difference between groups., Conclusions: The endoscopic microdebrider assisted method for adenoidectomy has a definite advantage of better visualisation resulting in better clearance of tissue, leading to enhanced middle ear function compared to conventional curettage., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background: Uremic pruritus has an impact on the quality of life and sleep of hemodialysis patients, but the majority of cases go unreported and untreated unless severe, due to a lack of awareness. The purpose of this study is to determine the prevalence, associated factors, and impact on health-related quality of life (HR-QOL) and sleep in hemodialysis patients., Methodology: A single-center observational study of 3 months wherein 120 adults on maintenance hemodialysis were included. Baseline characteristics, dialysis-related factors, and lab parameters influencing uremic pruritus were recorded. Those with uremic pruritus completed "12-item pruritus severity scale (12-PSS)", "SKINDEX10", and "Itch-MOS" questionnaires to evaluate severity, impact on HR-QOL, and sleep respectively., Results: Sixty seven over one hundred twenty (55.83%) patients had pruritus and majority were mild (40.83%) as per 12-PSS. Those with pruritus (n=67) had a mean age of 56.5±11.3 years, most were males (82%), chronic glomerulonephritis (29.1%) was the commonest cause of end-stage kidney disease, 3 active smokers, and 4 seropositive. 65(97%) patients were on twice-weekly dialysis, 36/67 had <5 years' dialysis vintage and acceptable adequacy. There was no significant association between uremic pruritus and dialysis-related/laboratory parameters. Patients with uremic pruritus demonstrated significantly worse "HR-QOL" (p<0.001) on the "SKINDEX-10", and patients' "Itch-MOS" scores demonstrated a significant decline in sleep quality with increasing pruritus severity (p<0.001)., Conclusion: The majority of patients on maintenance hemodialysis experience uremic pruritus. None of the clinical characteristics, dialysis-related factors, and laboratory parameters affected uremic pruritus. Uremic pruritus patients had the worst HR-QOL & their sleep quality significantly declined as pruritus severity escalated., Trial Registration Number and Date of Registration: Study approval was obtained from Institutional Research Committee and Institutional Ethical Committee (IEC 642/2021). Clinical Trial Registry of India (CTRI) registration (CTRI/2022/01/039143) was also obtained., (© 2023. The Author(s).)

Hydroxychloroquine is one of the oldest disease-modifying anti-rheumatic drugs in clinical use. The drug interferes with lysosomal activity and antigen presentation, inhibits autophagy, and decreases transcription of pro-inflammatory cytokines. Owing to its immunomodulatory, anti-inflammatory, anti-thrombotic effect, hydroxychloroquine has been an integral part of therapy for systemic lupus erythematosus and lupus nephritis for several decades. The therapeutic versatility of hydroxychloroquine has led to repurposing it for other clinical conditions, with recent studies showing reduction in proteinuria in IgA nephropathy. Research is also underway to investigate the efficacy of hydroxychloroquine in primary membranous nephropathy, Alport's syndrome, systemic vasculitis, anti-GBM disease, acute kidney injury and for cardiovascular risk reduction in chronic kidney disease. Hydroxychloroquine is well-tolerated, inexpensive, and widely available and therefore, should its indications expand in the future, it would certainly be welcomed. However, clinicians should be aware of the risk of irreversible and progressive retinal toxicity and rarely, cardiomyopathy. Monitoring hydroxychloroquine levels in blood appears to be a promising tool to evaluate compliance, individualize the dose and reduce the risk of retinal toxicity, although this is not yet standard clinical practice. In this review, we discuss the existing knowledge regarding the mechanism of action of hydroxychloroquine, its utility in lupus nephritis and other kidney diseases, the main adverse effects and the evidence gaps that need to be addressed in future research. Created with Biorender.com. HCQ, hydroxychloroquine; GBM, glomerular basement membrane; mDC, myeloid dendritic cell; MHC, major histocompatibility complex; TLR, toll-like receptor., (© 2023. The Author(s).)

The term chronic kidney disease of unknown aetiology (CKDu) refers to chronic kidney disease (CKD) in the absence of diabetes, long-standing hypertension, glomerulonephritis, obstructive uropathy or other apparent causes. An increasing number of CKDu cases have been reported from Latin America, Sri Lanka, India and others over the last two decades. These regional nephropathies share the following common attributes: (a) they affect low-to-middle income countries with tropical climates, (b) involve predominantly rural agricultural communities, (c) male predilection, (d) absence of significant proteinuria and hypertension, and (e) chronic tubulointerstitial nephritis on kidney biopsy. The current body of literature suggests that CKDu may be caused by heat stress, agrochemicals, contaminated drinking water or heavy metals; however, considerable regional disparities in CKDu research make it difficult to establish a common causal link. In the absence of a definite aetiology, specific preventive and therapeutic interventions are lacking. Improvement of working conditions of farmers and labourers, provision of safe drinking water and changes in agricultural practices are some of the measures that have been implemented; however, there is lack of data to assess their impact on the incidence and progression of CKDu. There is a need for a concerted global effort to address the current knowledge gaps, and to develop effective and sustainable strategies to tackle this devastating disease., (© 2023 John Wiley & Sons Ltd.)

Hyperuricemia is a risk factor for the progression of chronic kidney disease (CKD). We compared febuxostat versus allopurinol in the progression of CKD and hyperuricemia in 101 patients with Stage 3-4 CKD treated with febuxostat or allopurinol for at least 6 months for hyperuricemia (>7 mg/dL) between January 2012 and December 2016. Baseline characteristics, serum uric acid (SUA), serum creatinine, and estimated glomerular filtration rate (eGFR) at entry and 6 months were compared. The primary outcome was the decline in eGFR and the secondary outcomes were reductions in SUA and adverse events. Fifty-four were in the febuxostat group and 47 were in the allopurinol group. The baseline characteristics were comparable except for age. The mean dose of febuxostat and allopurinol was 43.70 ± 14.5 mg and 108.51 ± 40 mg, respectively. After 6 months, the median rate of decline in eGFR was 1.2 mL/min/1.73 m2 (IQR: 1.2, 5.5) in the febuxostat group and 3.1 mL/min/1.73 m2 (0.6, 6.2) in the allopurinol group, but this was not statistically significant (P = 0.136). The mean reduction in SUA was significantly better (P = 0.004) in the febuxostat group (3.9 ± 1.7 mg/dL) compared with the allopurinol group (2.1 ± 1.0 mg/dL). Both drugs had no serious adverse events. Febuxostat was better at reducing hyperuricemia than allopurinol, but there was no significant difference in the progression of CKD. Large randomized trials and long-term follow-up are necessary to see whether febuxostat has a favorable effect on the progression of CKD., (Copyright © 2023 Copyright: © 2023 Saudi Journal of Kidney Diseases and Transplantation.)

Post-translational modifications (PTMs) are one of the compulsive and predominant biological processes that regulate the diverse molecular mechanism, modulate the onset of disease, and are the reason behind the functional diversity of proteins. Despite the widespread research findings in neuroproteomics, one of the key drawbacks has been the lack of proteome-level knowledge of hemispheric lateralization. We have investigated the proteome level expression in different neuroanatomical regions under the Human Brain Proteome Project (HBPP) and developed the global interhemispheric brain proteome map (Brainprot) earlier. Furthermore, this study has extended to decipher the phosphoproteome map of human brain interhemispheric regions through high-resolution mass spectrometry. The phosphoproteomics examination of 12 unique interhemispheric neurological brain regions using Orbitrap fusion liquid chromatography with tandem mass spectrometry provided comprehensive coverage of 996 phosphoproteins, 2010 phosphopeptides, and 3567 phosphosites. Moreover, interhemispheric phosphoproteome profiling has been categorized according to synaptic ontologies and interhemispheric expression to understand the functionality. Finally, we have integrated the phosphosites data under the PhosphoMap section in the Inter-Hemispheric Brain Proteome Map Portal (https://www.brainprot.org/) for the advancement and support of the ongoing neuroproteomics research worldwide. Data is available via ProteomeXchange with the identifier PXD031188.

The global burden of diabetic kidney disease (DKD) is escalating, and it remains as a predominant cause of the end-stage renal disease (ESRD). DKD is associated with increased cardiovascular disease and morbidity in all types of diabetes. Prediction of progression with albuminuria and eGFR is challenging in DKD, especially in non-proteinuric DKD patients. The pathogenesis of DKD is multifactorial characterized by injury to all components of the nephron, whereas albuminuria is an indicator of only glomerular injury. The limits in the diagnostic and prognostic value of urine albumin demonstrate the need for alternative and clinically significant early biomarkers, allowing more targeted and effective diabetic treatment, to reduce the burden of DKD and ESRD. Identification of biomarkers, based on multifactorial pathogenesis of DKD can be the crucial paradigm in the treatment algorithm of DKD patients. This review focuses on the potential biomarkers linked to DKD pathogenesis, particularly with the hope of broadening the diagnostic window to identify patients with different stages of DKD progression., (© 2022. The Author(s).)

Otoacariasis is the presence of ticks and mites within the ear canal. Though the coexistence of ticks and humans is known for thousands of years, tick infestation is relatively rare in urban population. The most common presenting symptoms are usually itching, otalgia and a foreign body sensation and less frequent ones are tinnitus and otorrhoea. We report cases of otoacariasis with unusual presentation. A total of 43 cases presented to the ENT clinic in our hospital over a period of three years from 2018 to 2021. We present patients who presented with unusual symptoms of conductive hearing loss, ear bleed, and facial palsy. Total of 6 cases of otoacariasis had unusual presentation. 2 cases presented with lower motor neuron palsy, 1 case with ear bleed, and 3 cases with hearing loss. Otocariasis can present with unusual symptoms of hearing loss, ear bleed or facial palsy and this should be included in the differential diagnosis of a patient with history of close proximity to domestic or wild animals. Detailed examination often reveals the presence of the tick and identification and complete removal along with appropriate medication for associated symptoms often results in complete recovery., Competing Interests: Conflict of interestAll the authors declare they have no conflicts of interest and have not received any funding., (© Association of Otolaryngologists of India 2021.)

Osteomyelitis is an infection of the bone which is accompanied by bony destruction and sequestrum formation. Osteomyelitis of frontal bone requires us to deal with great caution as it can lead to a great deal of morbidity and mortality. Often when surgical treatment provided, it is radical and leaves behind surgical defect over the frontal bone. We report a case of a 14 year old boy diagnosed with frontal bone osteomyelitis of the left side who was treated using antibiotic loaded bone cement., Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-021-02667-w., Competing Interests: Conflicts of interestAll the authors declare they have no conflicts of interest and have not received any funding., (© Association of Otolaryngologists of India 2021.)

Frailty is common in end stage renal disease (ESRD) and is a marker of poor outcomes. Its prevalence increases as chronic kidney disease (CKD) progresses. There are different measurement tools available to assess frailty in ESRD. The pathogenesis of frailty in ESRD is multifactorial including uraemia and dialysis related factors. In this current review, we discuss the importance of frailty, its pathogenesis, screening methods, prognostic implications and management strategies in context of ESRD., (Copyright © 2021 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Hyponatremia is a frequent finding in hospitalized patients and is associated with poor clinical outcomes. While hyponatremia is known to commonly occur in certain infections, its association with melioidosis has not been studied previously. We studied incidence and impact of hyponatremia on clinical outcomes in melioidosis., Methods: This was a retrospective analysis of a single-center hospital registry of culture-positive patients with melioidosis hospitalized during a 10-year period (January 01, 2010, through January 31, 2021). Hyponatremia was defined as serum sodium of <135 mmol/L, and severe hyponatremia as serum sodium <120 mmol/L. The association of hyponatremia with in-hospital mortality, need for intensive care unit (ICU) stay and mechanical ventilation was studied., Results: Of 201 patients with melioidosis, 169 (84.1%) had hyponatremia, with severe hyponatremia in 35 (17.4%) patients. Older age (adjusted odds ratios [OR] 1.03, 95% confidence intervals [CI]: 1.00-1.06; P = 0.049) and acute kidney injury (AKI) (adjusted OR 3.30, 95% CI: 1.19-9.19; P = 0.02) were independently associated with hyponatremia. Twenty-two patients had been evaluated for cause of hyponatremia and of these, 11 (50%) had syndrome of inappropriate antidiuresis. Severe hyponatremia was associated with in-hospital mortality (adjusted OR 3.75, 95% CI: 1.37-10.27; P = 0.01), need for ICU stay (adjusted OR 7.04, 95% CI: 2.88-17.19; P < 0.001) and mechanical ventilation (adjusted OR 3.99, 95% CI: 1.54-10.32; P = 0.004)., Conclusion: Hyponatremia occurs in 84.1% of hospitalized patients with melioidosis. Older age and AKI are associated with a higher incidence of hyponatremia. The presence of severe hyponatremia is an independent predictor of in-hospital mortality, need for mechanical ventilation and ICU stay., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Global Infectious Diseases.)

Proteomics has enormous applications in human and animal research. However, proteomic studies in fisheries science are quite scanty particularly for economically important species. Few proteomic studies have been carried out in model fish species, but comprehensive proteomics of aquaculture species are still scarce. This study aimed to perform a comprehensive organ-based protein profiling of important tissue samples for one of the most important aquaculture species, Labeo rohita .Deep proteomic profiling of 17 histologically normal tissues, blood plasma, and embryo provided mass-spectrometric evidence for 8498 proteins at 1% false discovery rate that make up about 26% of the total annotated protein-coding sequences in Rohu. Tissue-wise expression analysis was performed, and the presence of several biologically important proteins was also verified using a targeted proteomic approach. We identified the global post-translational modifications (PTMs) in terms of acetylation (N-terminus and lysine), methylation (N-terminus, lysine, and arginine), and phosphorylation (serine, threonine, and tyrosine) to present a comprehensive proteome resource. An interactive web-based portal has been developed for an overall landscape of protein expression across the studied tissues of Labeo rohita (www.fishprot.org). This draft proteome map of Labeo rohita would advance basic and applied research in aquaculture to meet the most critical challenge of providing food and nutritional security to an increasing world population.

Purpose: Arteriovenous fistula(AVF) is preferred vascular access for hemodialysis but has primary failure in 20-60%. Studying predictors of AVF failure would help plan appropriate management.We studied AVF outcomes, clinical and vascular factors predicting their failure in patients requiring hemodialysis., Methods: Retrospective study of patients with AVF creation from January 2017 to December 2018. Outcomes studied were immediate (< 72 h), primary (3 months) AVF failure, six-month/one-year patency, analyzed for predictive clinical, vascular factors as assessed using Pre-operative Doppler Ultrasound(DUS)., Results: Of 530 AVFs in 460 patients, DUS was done in 426/530 (80.4%), 349/460 (75.8%) were males, mean age was 53.10 ± 14.54 (18-91), 215/460(46.7%) had Diabetes mellitus(DM), 423/460(92%) hypertension. AVFs were radiocephalic in 79/530 (14.9%), brachiocephalic 418/530 (78.9%), brachiobasilic 33/530 (6.2%). AVF Immediate/Primary failure was seen in 64/530 (12.1%), 90/352 (25.6%); Patency at six months/one year in 253/352(71.8%),191/305 (62.6%), respectively. Older age had less immediate failures (AOR 0.97, CI 0.95-0.99, p 0.03). Feeding arterial diameter predicted immediate and primary failure on univariate analysis [OR 0.64 (95% CI 0.49-0.83), 0.62 (95% CI 0.47-0.89), respectively], but not multivariate. Artery diameter of > 4.0 mm had less failures [immediate (p 0.01), primary (p 0.02)], < 2.0 mm had specificity 95.9% and 95.4% for immediate, primary failure respectively., Conclusion: AVF failure is 12.1%, immediately; 25.6% three months after construction, Patency at 6 months is 71.8%, one year 62.6%. Immediate failures decrease with age. Artery diameters > 4.0 mm had less, < 2.0 mm had more failures., (© 2021. The Author(s).)

This study, which performs an extensive mass spectrometry-based analysis of 19 brain regions from both left and right hemispheres, presents the first draft of the human brain interhemispheric proteome. This high-resolution proteomics data provides comprehensive coverage of 3300 experimentally measured (nonhypothetical) proteins across multiple regions, allowing the characterization of protein-centric interhemispheric differences and synapse biology, and portrays the regional mapping of specific regions for brain disorder biomarkers. In the context of the Human Proteome Project (HPP), the interhemispheric proteome data reveal specific markers like chimerin 2 (CHN2) in the cerebellar vermis, olfactory marker protein (OMP) in the olfactory bulb, and ankyrin repeat domain 63 (ANKRD63) in basal ganglia, in line with regional brain transcriptomes mapped in the Human Protein Atlas (HPA). In addition, an in silico analysis pipeline was used to predict the structure and function of the uncharacterized uPE1 protein ANKRD63, and parallel reaction monitoring (PRM) was applied to validate its region-specific expression. Finally, we have built the Interhemispheric Brain Proteome Map (IBPM) Portal (www.brainprot.org) to stimulate the scientific community's interest in the brain molecular landscape and accelerate and support research in neuroproteomics. Data are available via ProteomeXchange with identifier PXD019936.

Background: Melioidosis is a potentially fatal tropical infection caused by Burkholderia pseudomallei. Kidney involvement is possible, but has not been well described., Aim: This study aimed to assess the risk of acute kidney injury (AKI) and its outcomes in melioidosis., Methods: A retrospective observational cohort study was performed. Case records of consecutive patients with culture-confirmed melioidosis, observed from January 1st, 2012 through December 31st, 2019 were analysed for demographics, presence of comorbidities, including chronic kidney disease (CKD), diabetes mellitus (DM), and presence of bacteraemia, sepsis, shock, AKI, and urinary abnormalities. The outcomes we studied were: mortality, need for hospitalisation in an intensive care unit (ICU), duration of hospitalization. We then compared the outcomes between patients with and without AKI., Results: Of 164 patients, AKI was observed in 59 (35.98%), and haemodialysis was required in eight (13.56%). In the univariate analysis, AKI was associated with CKD (OR 5.83; CI 1.140-29.90, P = 0.03), bacteraemia (OR 8.82; CI 3.67-21.22, P < 0.001) and shock (OR 3.75; CI 1.63-8.65, P = 0.04). In the multivariate analysis, CKD (adjusted OR 10.68; 95% CI 1.66-68.77; P = 0.013) and bacteraemia (adjusted OR 8.22; 95% CI 3.15-21.47, P < 0.001) predicted AKI. AKI was associated with a greater need for ICU care (37.3% vs. 13.3%, P = 0.001), and mortality (32.2% vs. 5.7%, P < 0.001). Mortality increased with increasing AKI stage, i.e. stage 1 (OR 3.52, CI 0.9-13.7, P = 0.07), stage 2 (OR 6.79, CI 1.92-24, P = 0.002) and stage 3 (OR 17.8, CI 5.05-62.8, P < 0.001), however kidney function recovered in survivors. Hyponatremia was observed in 138 patients (84.15%) and isolated urinary abnormalities were seen in 31(18.9%)., Conclusions: AKI is frequent in melioidosis and occurred in 35.9% of our cases. Hyponatremia is likewise common. AKI was predicted by bacteraemia and CKD, and was associated with higher mortality and need for ICU care; however kidney function recovery was observed in survivors., (© 2021. The Author(s).)

The therapeutic options for preventing or slowing the progression of chronic kidney disease (CKD) have been thus far limited. While angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are, without a doubt, safe and effective drugs, a significant proportion of patients with CKD still progress to end-stage kidney disease. After decades of negative trials, nephrologists have finally found cause for optimism with the introduction of sodium-glucose cotransporter-2 (SGLT2) inhibitors and non-steroidal mineralocorticoid receptor antagonists (MRAs). Recent trials such as EMPA-REG OUTCOME and CREDENCE have provided evidence of the renal benefits of SGLT2 inhibitors, which have now found widespread acceptance as first-line agents for diabetic CKD, in addition to ACEi/ARBs. Considering results from the DAPA-CKD study, it is expected that their use will soon be expanded to other causes of albuminuric CKD as well, although confirmation from further trials, such as the EMPA-KIDNEY study is awaited. Likewise, although the role of mineralocorticoid receptor overactivation in CKD progression has been known for decades, it is only now with the FIDELIO-DKD study that we have evidence of benefits of MRAs on hard renal endpoints, specifically in patients with diabetic CKD. While further research is ongoing, given the evidence of synergism between the three drug classes, it is foreseeable that a combination of two or more of these drugs may soon become the standard of care for CKD, regardless of underlying aetiology. This review describes pathophysiologic mechanisms, current evidence and future perspectives on the use of SGLT2 inhibitors and novel MRAs in CKD., (© 2021 Asian Pacific Society of Nephrology.)

Intracranial abscesses are uncommon, serious and life-threatening infections. A brain abscess is caused by inflammation and collection of infected material, coming from local or remote infectious sources. Patients with chronic kidney disease on dialysis are prone to invasive bacterial infections like methicillin-resistant Staphylococcus aureus (MRSA) especially in the presence of central venous catheters or arteriovenous grafts. However, intracranial abscess formation due to MRSA is rare. Here, we present a case of MRSA brain abscess with an atypical clinical presentation in the absence of traditional risk factors.Intracranial abscesses are uncommon, serious, and life-threatening infections. A Brain abscess is caused by inflammation and collection of infected material, coming from local or remote infectious sources. Patients with chronic kidney disease on dialysis are prone to invasive bacterial infections like methicillin-resistant staphylococcus aureus (MRSA) especially in the presence of central venous catheters or arterio-venous grafts. However intracranial abscess formation due to MRSA is rare. Here we present a case of MRSA brain abscess with an atypical clinical presentation in the absence of traditional risk factors. A 46-year-old male with chronic kidney disease (CKD) secondary to chronic glomerulonephritis, on haemodialysis for 4 years through a left brachio-cephalic AVF developed an episode of generalised tonic-clonic seizures lasting 2 min during his scheduled dialysis session. He reported no complaints before entry to the dialysis. On clinical examination, he was drowsy with the absence of any focal motor deficits. His blood pressure was recorded to be 200/120 mm Hg. He was managed in the intensive care unit with mechanical ventilation, intravenous nitroglycerine for blood pressure control, levetiracetam for seizures and empirical vancomycin. Radiological evaluation showed a brain abscess in the midline involving bosth basi-frontal lobes. After medical optimization, the abscess was drained surgically, and the pus cultured. As culture grew Methicillin Resistant Staphylococcus aureus, he was treated with intravenous vancomycin for 6 weeks. On follow up, the abscess had resolved and the patient recovered without any neurological deficits., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Thyroiditis can be due to infection/autoimmunity with different clinical presentations. Correctly diagnosing and initiating treatment is a challenge to the treating physician. We present two cases of thyroiditis, who approached the physician for different complaints. The first was a female with a change in voice, foreign body sensation in throat, laryngoscopy showing left vocal cord paralysis, reduced thyroid stimulating hormone. An ultrasound neck was suggestive of thyroiditis, and a contrast enhanced computed tomography scan showed a bulky thyroid with enlarged cervical lymphadenopathy. The second patient was a female with high-grade fever, chills and the inability to take fluids-food. Assessment revealed bilateral enlarged, inflamed tonsils-membranous exudate, tender jugulo-digastric lymphadenopathy and a Technetium-99 thyroid scan suggestive of thyroiditis. Patients were admitted, treated with steroids, antipyretics, antibiotics, cured and discharged. At the three-month follow-up, they were asymptomatic, video laryngoscopy showed normal vocal cords with equal mobility in the first patient and the thyroid profile within normal range for both patients. These cases highlight that thyroiditis can co-exist with benign vocal cord palsy or occasionally also with inflammations of local tissues, such as the tonsils., Competing Interests: No conflict of interests declared

In patients with end-stage kidney disease (ESKD), when there maybe situations where dialysis does not offer benefits in terms of survival or health-related quality of life, dialysis should not be viewed as the default therapy. Such patients can be offered comprehensive conservative care as an alternative to dialysis. Conservative (nondialytic) management of ESKD includes careful attention to fluid balance, treatment of anemia, correction of acidosis and hyperkalemia, blood pressure, and calcium/phosphorus metabolism management and dietary modification. Individualized symptom management and supportive care are crucial to maximize the quality of life. We propose that model of comprehensive conservative care in ESKD should manage both diseases as well as provide supportive care. Facilitating implementation of comprehensive conservative care requires coordination between nephrology and palliative care at patient, professional, administrative, and social levels to maximize benefit with the motto to improve the overall quality of life., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Palliative Care.)

Purpose: To investigate cases of trauma in head and neck region; to elucidate the characteristic problems in a developing country., Design and Setting: Prospective study; 324 patients with trauma related to head and neck analysed in a tertiary care center from August 1999 to August 2005, Results: 33.6% of patients fell in 21-30 year age group. Road traffic accidents (41.4%) were the most common cause of trauma. Nasal bone fractures were the most common fractures. 72.84% presented with bleeding and 72.22% with pain. 92.9% had tenderness. Only 15% of the patients could afford a CT scan. Plain radiograph diagnosed fractures in 83.33% of cases. ORIF was the treatment of choice in cases of fractures of the zygoma, maxilla and mandible. Open reduction and internal fixation (ORIF) gave good long-term results with satisfactory cosmosis. Most of our patients did not have any significant sequelae. Cerebral concussion was the most common associated injury (35.48%)., Conclusion: In developing countries, one cannot follow the approaches used for RTAs in developed countries. Treating surgeons will have to select investigation tools and treatment options according to the socioeconomical and cultural variations, which differ from country to country, and also within different parts of the country.