Gender and kidney transplantation.

Kidney transplantation provides the best form of kidney replacement therapy with improvement in quality of life and longevity. However, disparity exists in its availability, utilisation and outcomes, not only due to donor availability or financial constraints but also arising from the influence of biological sex and its sociocultural attribute i.e., Gender. Women make up the majority of kidney donors but are less likely to be counselled regarding transpantation, be waitlisted or receive living/deceased donor kidney. Biological differences also contribute to differences in kidney transplantation among the sexes. Women are more likely to be sensitised owing to pregnancy, especially in multiparous individuals, complicating donor compatibility. A heightened immune system in women, evidenced by more autoimmune illnesses, increases the risk of allograft rejection and loss. Differences in the pharmacokinetics of transplant drugs owing to biological variances could also contribute to variability in outcomes. Transgender medicine is also increasingly becoming a relevant topic of study, providing greater challenges in the form of hormonal manipulations and anatomic changes. It is thus important to determine and study transplantation and its nuances in this backdrop to be able to provide relevant sex and gender-specific interventions and design better practices for optimum kidney transplant utilisation and outcomes.

Prevention of dialysis disequilibrium syndrome in children with advanced uremia with a structured hemodialysis protocol: A quality improvement initiative study.

BACKGROUND: Dialysis disequilibrium syndrome (DDS) is a rare but significant concern in adult and pediatric patients undergoing dialysis initiation with advanced uremia or if done after an interval. It is imperative to gain insights into the epidemiological patterns, pathophysiological mechanisms, and preventive strategies aimed at averting the onset of this ailment. DESIGN: Prospective observational quality improvement initiative cohort study. SETTING AND PARTICIPANTS: A prospective single-center study involving 50 pediatric patients under 18 years recently diagnosed with chronic kidney disease stage V with blood urea ≥200 mg/dL, admitted to our tertiary care center for dialysis initiation from January 2017 to October 2023. QUALITY IMPROVEMENT PLAN: A standardized protocol was developed and followed for hemodialysis in pediatric patients with advanced uremia. This protocol included measures such as lower urea reduction ratios (targeted at 20%-30%) with shorter dialysis sessions and linear dialysate sodium profiling. Prophylactic administration of mannitol and 25% dextrose was also done to prevent the incidence of dialysis disequilibrium syndrome. MEASURES: Incidence of dialysis disequilibrium syndrome and severe dialysis disequilibrium syndrome, mortality, urea reduction ratios (URRs), neurological outcome at discharge, and development of complications such as infection and hypotension. Long-term outcomes were assessed at the 1-year follow-up including adherence to dialysis, renal transplantation, death, and loss to follow-up. RESULTS: The median serum creatinine and urea levels at presentation were 7.93 and 224 mg/dL, respectively. A total of 20% of patients had neurological symptoms attributable to advanced uremia at the time of presentation. The incidence of dialysis disequilibrium syndrome was 4% (n = 2) with severe dialysis disequilibrium syndrome only 2% (n = 1). Overall mortality was 8% (n = 4) but none of the deaths were attributed to dialysis disequilibrium syndrome. The mean urea reduction ratios for the first, second, and third dialysis sessions were 23.45%, 34.56%, and 33.50%, respectively. The patients with dialysis disequilibrium syndrome were discharged with normal neurological status. Long-term outcomes showed 88% adherence to dialysis and 38% renal transplantation. LIMITATIONS: This study is characterized by a single-center design, nonrandomized approach, and limited sample size. CONCLUSIONS: Our structured protocol served as a framework for standardizing procedures contributing to low incidence rates of dialysis disequilibrium syndrome.

Guidelines on antibody use in physiology research.

Antibodies are one of the most used reagents in scientific laboratories and are critical components for a multitude of experiments in physiology research. Over the past decade, concerns about many biological methods, including those that use antibodies, have arisen as several laboratories were unable to reproduce the scientific data obtained in other laboratories. The lack of reproducibility could be largely attributed to inadequate reporting of detailed methods, no or limited verification by authors, and the production and use of unvalidated antibodies. The goal of this guideline article is to review best practices concerning commonly used techniques involving antibodies, including immunoblotting, immunohistochemistry, and flow cytometry. Awareness and integration of best practices will increase the rigor and reproducibility of these techniques and elevate the quality of physiology research.

Management and Outcomes of Acute Kidney Injury due to Burns: A Literature Review.

Acute kidney injury (AKI), a common and severe complication following burn injuries, presents a significant challenge due to its broad clinical manifestations and diverse etiologies. AKI, previously known as acute renal failure, can present abruptly following burns or thermal injuries, causing detrimental health outcomes such as progressive kidney dysfunction, increased hospital length of stay, and requirement of renal replacement therapy (RRT). AKI affects the maintenance of homeostasis of fluid and electrolytes, elimination of metabolic wastes and byproducts, and acid-base balance. Aggressive nutritional support is particularly necessitated in burn patients to prevent protein-energy wasting and a negative nitrogen balance. Understanding the pathogenesis of AKI in burns and improving its prevention and early diagnosis are active areas of research in this field. Despite the potential benefits, the optimal timing and threshold for RRT initiation in burn patients with AKI remain unclear, warranting further studies. Ongoing investigations focus on refining RRT techniques, evaluating biomarkers for early detection of AKI, and exploring adjunctive therapies to enhance renal recovery. The aim of this study is to review the etiology, diagnostic tools, and interventions that improve outcomes associated with AKI in burn-related settings.

Acute kidney injury occurs in nearly one-quarter of people with severe burns and leads to increased mortality rates. Burn injuries can be associated with numerous complications, such as hypermetabolic response, hypovolemia, hypotension, and sepsis, and involves early burn- and late burn-related complications. Validated metrics for classifying the extent of burn injuries, such as the Abbreviated Burn Severity Index on admission, Sequential Organ Failure Assessment Score on admission, Modified Marshall Score, baseline blood urea nitrogen, and serum creatinine all serve to discriminate the risk of acute kidney injury. With no current consensus on predictive energy equations or ideal nutritional goals, optimal nutritional support in burn patients with acute kidney injury largely relies on the burn severity, individual presentation of malnourishment, and timely resuscitation. Although novel biomarkers such as plasma and urinary NGAL levels, KIM-1, and IL-18 are still being investigated as diagnostic tools for acute kidney injury in both the early and late burn periods, and artificial intelligence/machine learning may soon be incorporated as an efficacious assessment tool in the future. Renal replacement therapy is often indicated in the setting of acute kidney injury due to severe burns, especially if the metabolic and fluid disturbances due to acute kidney injury are not adequately managed with fluid resuscitation, diuretics, electrolyte repletion, and other supportive measures. However, with over a third of all burn-related acute kidney injury patients requiring some form of renal replacement therapy, elevated mortality rates remain a cause for concern.

Renal Transplantation in Patients With Tuberculosis: A Single-center Experience From an Endemic Region.

Background: Despite being a common infection in end-stage kidney disease patients, there are no evidence-based guidelines to suggest the ideal time of transplantation in patients on antitubercular therapy (ATT). This study aimed to examine the outcome of transplantation in patients while on ATT compared with those without tuberculosis (TB). Methods: This was a retrospective study. Renal transplant recipients transplanted while on ATT were compared with a 1:1 matched group (for age, sex, diabetic status, and type of induction agent) of patients without TB at the time of transplant. Patient outcomes included relapse of TB and graft and patient survival. Results: There were 71 patients in each group. The mean duration for which ATT was given pretransplant was 3.8 ± 2.47 mo. The average total duration of ATT received was 12.27 ± 1.25 mo. Mortality in both the groups was similar (8.4% in the TB group versus 4.5% in the non-TB group; P = 0.49). None of the surviving patients had recurrence of TB during the follow-up. Death-censored graft survival (98.5% in the TB group versus 97% in the non-TB group; P = 1) and biopsy-proven acute rejection rates (9.86% in the TB group versus 8.45% in the non-TB group; P = 1) were also similar in both the groups. Conclusions: Successful transplantation in patients with end-stage kidney disease on ATT is possible without any deleterious effect on patient and graft survival and no risk of disease recurrence. Multicentric prospective studies are needed.

Low-MFI (median fluorescence intensity) pre-transplant DSA (donor specific antibodies) leading to anamnestic antibody mediated rejection in live-related donor kidney transplantation.

"In solid organ transplantation, the compatibility between recipient and donor relies on testing prior to transplantation as a major determinant for the successful transplant outcomes. This compatibility testing depends on the detection of donor-specific antibodies (DSAs) present in the recipient. Indeed, sensitized transplant candidates are at higher risk of allograft rejection and graft loss compared to non-sensitized individuals. Most of the laboratories in India have adopted test algorithms for the appropriate risk stratification of transplants, namely: 1) donor cell-based flow-cytometric cross-match (FCXM) assay with patient's serum to detect DSAs; 2) HLA-coated beads to detect anti-HLA antibodies; and 3) complement-dependent cytotoxicity crossmatch (CDCXM) with donor cells to detect cytotoxic antibodies. In the risk stratification strategy, laboratories generally accept a DSA median fluorescence index (MFI) of 1000 MFI or lower MFI (low-MFI) as a negative value and clear the patient for the transplant. We present two cases of live-related donor kidney transplants (LDKTs) with low-MFI pre-transplant DSA values who experienced an early acute antibody-mediated rejection (ABMR) as a result of an anamnestic antibody response by DSA against HLA class II antibodies. These results were confirmed by retesting of both pre-transplant and post-transplant archived sera from patients and freshly obtained donor cells. Our examples indicate a possible ABMR in patients with low MFI pre-transplant DSA. Reclassification of low vs. high-risk may be appropriate for sensitized patients with low-MFI DSA."

The Renal Histological Correlates of Refractory Renal Dysfunction After Liver Transplantation.

Background: Kidney dysfunction is common after liver transplantation (LT) and is often attributed to calcineurin inhibitors (CNIs). Very few studies have looked at histological causes. Material and methods: The study is a retrospective analysis of histological findings and diagnosis in all patients who underwent a kidney biopsy after LT from 2010 to 2020. Data are shown as mean ± standard deviation or medians (25-75 interquartile range). Results: The study cohort consisted of 26 patients (25 males, 1 female), aged 55 ± 7 years at the time of the kidney biopsy. Kidney biopsies were done at 27.5 (6.7-60.7) months after LT. At the time of the kidney biopsy, the median serum creatinine was 2.10 (1.50-2.86) mg/dl and proteinuria was 3.8 (1.8-5.9) gm/day. Twenty-four (92%) patients were on CNIs. The diagnoses on kidney biopsies were diabetic nephropathy (n = 7), focal segmental glomerulosclerosis (n = 4), CNI nephrotoxicity (n = 3), IgA nephropathy (n = 4), chronic glomerulonephritis (n = 3), hypertensive nephropathy (n = 1), membranous glomerulonephritis (n = 1), acute on chronic interstitial nephritis (n = 1), and C1q nephropathy (n = 1), and the sample was inadequate in one patient. A total of sixteen patients had progression of kidney disease. The kidney function remained stable/improved in 6 (23%) patients, follow-up data were not available for 4 patients. Fourteen (53.8%) patients (including one with CNI nephrotoxicity) required hemodialysis at 13.5 (5.7-29) months after the kidney biopsy. Conclusion: Although the kidney biopsy diagnosed the cause of unexplained renal insufficiency in LT recipients, the majority of patients progressed to end-stage renal disease despite treatment modifications. The use of CNIs was an uncommon cause of renal impairment.

Patient outcome in antibody-positive systemic vasculitis treated with therapeutic plasma exchange.

BACKGROUND: Therapeutic plasma exchange (TPE) has been advocated as an adjunct to steroids and cytotoxic drugs in treating patients suffering from vasculitis and presenting with active disease, but we still have insufficient evidence on its effectiveness in improving the clinical response, especially in India. This study was planned to study the clinical outcome in severe vasculitic presentations treated with TPE as an adjunctive therapy. MATERIALS AND METHODS: A retrospective analysis of TPE procedures performed from July 2013 to July 2017 in the department of transfusion medicine at a large tertiary care hospital was done. All consecutive patients admitted with new diagnosis of systemic vasculitis presenting with active disease and severe presentations such as advanced renal failure or severe respiratory abnormalities or life-threatening vasculitis affecting the gastrointestinal tract, neurological and musculoskeletal system; who needed TPE for removal of preformed antibodies, were included in the study. RESULTS: There were a total of 31 patients in whom TPE was performed for severe systemic vasculitis; 26 adults and five pediatric. Six patients tested positive for perinuclear fluorescence, 13 for cytoplasmic fluorescence (cANCA), two for atypical antineutrophil cytoplasmic autoantibody, seven for anti-glomerular basement membrane antibodies, two for antinuclear antibodies (ANA), and one patient tested positive for ANA as well as cANCA before the augmentation of TPE. Out of 31, seven patients showed no clinical improvement and succumbed to the disease. At the end of desired number of procedures, 19 tested negative and five tested weak positive for their respective antibodies. CONCLUSION: Favorable clinical outcomes were observed with TPE in patients with antibody-positive systemic vasculitis.

Switching from continuous veno-venous hemodiafiltration to intermittent sustained low-efficiency daily hemodiafiltration (SLED-f) in pediatric acute kidney injury: A prospective cohort study.

INTRODUCTION: Continuous kidney replacement therapy (CKRT) is the preferred modality in critically ill children with acute kidney injury. Upon improvement, intermittent hemodialysis is usually initiated as a step-down therapy, which can be associated with several adverse events. Hybrid therapies such as Sustained low-efficiency daily dialysis with pre-filter replacement (SLED-f) combines the slow sustained features of a continuous treatment, ensuring hemodynamic stability, with similar solute clearance along with the cost effectiveness of conventional intermittent hemodialysis. We examined the feasibility of using SLED-f as a transition step-down therapy after CKRT in critically ill pediatric patients with acute kidney injury. METHODS: A prospective cohort study was conducted in children admitted to our tertiary care pediatric intensive care units with multi-organ dysfunction syndrome including acute kidney injury who received CKRT for management. Those patients receiving fewer than two inotropes to maintain perfusion and failed a diuretic challenge were switched to SLED-f. RESULTS: Eleven patients underwent 105 SLED-f sessions (mean of 9.55 +/- 4.90 sessions per patient), as a part of step-down therapy from continuous hemodiafiltration. All (100%) our patients had sepsis associated acute kidney injury with multiorgan dysfunction and required ventilation. During SLED-f, urea reduction ratio was 64.1 +/- 5.3%, Kt/V was 1.13 +/- 0.1, and beta-2 microglobulin reduction was 42.5 +/-4%. Incidence of hypotension and requirement of escalation of inotropes during SLED-f was 18.18%. Filter clotting occurred twice in one patient. CONCLUSION: SLED-f is a safe and effective modality for use as a transition therapy between CKRT and intermittent hemodialysis in children in the PICU.

Vasoactive-ventilation-renal score and outcomes in infants and children after cardiac surgery.

Introduction: There is a need to index important clinical characteristics in pediatric cardiac surgery that can be obtained early in the postoperative period and accurately predict postoperative outcomes. Methodology: A prospective cohort study was conducted in the pediatric cardiac ICU and ward on all children aged <18 years undergoing cardiac surgery for congenital heart disease from September 2018 to October 2020. The vasoactive-ventilation-renal (VVR) score was analyzed to predict outcomes of cardiac surgeries with a comparison of postoperative variables. Results: A total of 199 children underwent cardiac surgery during the study period. The median (interquartile range) age was 2 (0.8-5) years, and the median weight was 9.3 (6-16) kg. The most common diagnoses were ventricular septal defect (46.2%) and tetralogy of Fallot (37.2%). At the 48th h, area under the curve (AUC) (95% CI) values were higher for the VVR score than those for other clinical scores measured. Similarly, at the 48th h, AUC (95% CI) values were higher for the VVR score than those for the other clinical scores measured for the length of stay and mechanical ventilation. Discussion: The VVR score at 48 h postoperation was found to best correlate with prolonged pediatric intensive care unit (PICU) stay, length of hospitalization, and ventilation duration, with the greatest AUC-receiver operating characteristic (0.715, 0.723, and 0.843, respectively). The 48-h VVR score correlates well with prolonged ICU, hospital stay, and ventilation.

South Asian Transplant Infectious Disease Guidelines for Solid Organ Transplant Candidates, Recipients, and Donors.

These guidelines discuss the epidemiology, screening, diagnosis, posttransplant prophylaxis, monitoring, and management of endemic infections in solid organ transplant (SOT) candidates, recipients, and donors in South Asia. The guidelines also provide recommendations for SOT recipients traveling to this region. These guidelines are based on literature review and expert opinion by transplant physicians, surgeons, and infectious diseases specialists, mostly from South Asian countries (India, Pakistan, Bangladesh, Nepal, and Sri Lanka) as well as transplant experts from other countries. These guidelines cover relevant endemic bacterial infections (tuberculosis, leptospirosis, melioidosis, typhoid, scrub typhus), viral infections (hepatitis A, B, C, D, and E; rabies; and the arboviruses including dengue, chikungunya, Zika, Japanese encephalitis), endemic fungal infections (mucormycosis, histoplasmosis, talaromycosis, sporotrichosis), and endemic parasitic infections (malaria, leishmaniasis, toxoplasmosis, cryptosporidiosis, strongyloidiasis, and filariasis) as well as travelers' diarrhea and vaccination for SOT candidates and recipients including travelers visiting this region. These guidelines are intended to be an overview of each topic; more detailed reviews are being published as a special supplement in the Indian Journal of Transplantation .

AKI in Adults with COVID-19 Infection: Mechanisms of Development and Role of Blood Filtration Devices in Treatment.

During the coronavirus disease 2019 (COVID-19) pandemic, acute kidney injury (AKI) was a common sequela of COVID-19 infection and predicted disease severity and mortality. Extracorporeal blood purification techniques involving blood filtration devices are an emerging treatment for AKI in the setting of severe COVID-19 infections. In this review, we discuss potential mechanisms for the development of AKI in COVID-19 patients as well as the various available blood filtration devices and the role they may play in managing the AKI in COVID-19 patients. A total of seven blood filters currently available were compared based on their potential in treating AKI in COVID-19 patients. Blood filtration devices show potential as an emerging treatment modality for COVID-19-induced AKI, but further clinical trials are necessary before their widespread adoption and usage.