Donor-Derived Cell-Free DNA as a Non-Invasive Biomarker for Graft Rejection in Kidney Transplant Recipients: A Prospective Study among the Indian Population.

Monitoring graft health and detecting graft rejection is crucial for the success of post-transplantation outcomes. In Western countries, the use of donor-derived cell-free DNA (dd-cfDNA) has gained widespread recognition as a diagnostic tool for kidney transplant recipients. However, the role of dd-cfDNA among the Indian population remains unexplored. The recipients were categorized into two groups: the post-transplant recipient (PTR) group (n = 16) and the random recipient (RR) group (n = 87). Blood samples were collected daily from the PTR group over a 7-day period, whereas the RR group's samples were obtained at varying intervals. In this study, we used a targeted approach to identify dd-cfDNA, which eliminated the need for genotyping, and is based on the minor allele frequency of SNP assays. In the PTR group, elevated dd-cfDNA% levels were observed immediately after transplantation, but returned to normal levels within five days. Within the RR group, heightened serum creatinine levels were directly proportional to increased dd-cfDNA%. Sixteen recipients were advised to undergo biopsy due to elevated serum creatinine and other pathological markers. Among these sixteen recipients, six experienced antibody-mediated rejection (ABMR), two exhibited graft dysfunctions, two had active graft injury, and six (37.5%) recipients showed no rejection (NR). In cases of biopsy-proven ABMR and NR, recipients displayed a mean ± SD dd-cfDNA% of 2.80 ± 1.77 and 0.30 ± 0.35, respectively. This study found that the selected SNP assays exhibit a high proficiency in identifying donor DNA. This study also supports the use of dd-cfDNA as a routine diagnostic test for kidney transplant recipients, along with biopsies and serum creatinine, to attain better graft monitoring.

Comprehensive overview of 2022 human monkeypox outbreak and its pathology, prevention, and treatment: A strategy for disease control.

The 2022 Monkeypox virus, an evolved DNA strain originating in Africa, exhibits heightened human-to-human transmissibility and potential animal transmission. Its host remains unidentified. While its initial slow transmission rate restrained global impact, 2022 saw a surge in cases, causing widespread concern in over 103 countries by September. This virus's distinctive human-to-human transmission marks a crucial shift, demanding a prompt revaluation of containment strategies. However, the host source for this shift requires urgent research attention. Regrettably, no universal preventive or curative methods have emerged for this evolved virus. Repurposed from smallpox vaccines, only some vaccinations offer a partial defense. Solely one therapeutic drug is available. The article's essence is to provide a comprehensive grasp of the virus's epidemiology, morphology, immune invasion mechanisms, and existing preventive and treatment measures. This knowledge equips researchers to devise strategies against its spread and potential public health implications.

An update on SARS-CoV-2 immunization and future directions.

Millions of people have died as a result of SARS-CoV-2, which was first discovered in China and has since spread globally. Patients with SARS-CoV-2 infection may show a range of symptoms, including fever, coughing, and shortness of breath, or they may show no symptoms at all. To treat COVID-19 symptoms and avoid serious infections, many medications and vaccinations have been employed. However, to entirely eradicate COVID-19 from the world, next-generation vaccine research is required because of the devastating consequences it is having for humanity and every nation's economy. Scientists are working hard to eradicate this dangerous virus across the world. SARS-CoV-2 has also undergone significant mutation, leading to distinct viral types such as the alpha, beta, gamma, delta, and omicron variants. This has sparked discussion about the effectiveness of current vaccines for the newly formed variants. A proper comparison of these vaccinations is required to compare their efficacy as the number of people immunized against SARS-CoV-2 globally increases. Population-level statistics evaluating the capacity of these vaccines to reduce infection are therefore being developed. In this paper, we analyze the many vaccines on the market in terms of their production process, price, dosage needed, and efficacy. This article also discusses the challenges of achieving herd immunity, the likelihood of reinfection, and the importance of convalescent plasma therapy in reducing infection.

Prevalence, risk, and outcomes of venous thromboembolic events in kidney transplant recipients: a nested case-control study.

INTRODUCTION: Thromboembolism is more common in kidney transplant recipients (KTRs) than in the general population. Studies evaluating arterial and venous thromboembolism (VTE) in KTRs are scarce and the magnitude and risk factors are mostly undefined. METHODS: A nested control study was conducted from January 1, 2007, to December 31, 2019. Adult KTRs who were detected to have VTE events during this period were included. The primary outcome was to assess the prevalence of VTE in this population. Secondary outcomes were the assessment of the time to occurrence of the thromboembolic events after transplantation and assessing the risk factors and patient survival. For each subject studied, 4 controls were matched from the data set. RESULTS: Amongst 2158 patients, 97 (4.5%) were found to have VTE. The median follow-up time was 3.9 years (6-156 months). A total of 101 VTE events were recorded. The most common site of VTE was the lower limb deep vein thrombosis in 79 patients (0.03%)).In multivariate Cox regression analysis, serum creatinine of more than 3 mg/dl [HR 1.30, 95% CI (1.03-1.38)] was independently associated with increased VTE risk. Patients who developed a VTE had higher mortality as compared to patients who did not develop VTE. No increased risk of graft failure was found in VTE patients. CONCLUSION: This study suggests that kidney transplantation surgery is a moderate risk factor for VTE, and VTE is associated with higher morbidity and mortality. However, prospective studies are needed to establish a definite role of VTE in outcomes in KTRs.

Association of underlying comorbidities and progression of COVID-19 infection amongst 2586 patients hospitalised in the National Capital Region of India: a retrospective cohort study.

This study is conducted to observe the association of diabetes (DM), hypertension (HTN) and chronic kidney disease (CKD) on the prognosis and mortality of COVID-19 infection in hospital admitted patients with above mentioned comorbidities. This is a single centre, observational, retrospective study carried out at Sir Ganga Ram Hospital, Delhi, India. The burden of comorbidities on the prognosis and clinical outcome of COVID-19 patients admitted patients from April 8, 2020, to October 4, 2020. Chi-square and relative risk test were used to observe the association of comorbidities and disease prognosis. A total of 2586 patients were included in the study consisting of 69.6% of male patients. All the comorbidities were significantly associated with ICU admission and mortality. The relative risk showed that CKD is most prone to severity as well as mortality of the COVID-19 infection followed by HTN and DM. Further with the increase in number of underlying comorbidities, the risk of ICU admission and mortality also increases. Relative risk of the severity of COVID-19 infection in younger patients with underlying comorbidities are relatively at higher risk of severity of disease as well as to mortality compared to the elderly patients with similar underlying condition. Similarly, it is found that females are relatively at higher risk of mortality as compared to the males having same comorbid conditions except for the hypertensive patients. Diabetes, hypertension and CKD, all are associated with progression of COVID-19 disease to severity and higher mortality risk. The number of underlying comorbid condition is directly proportional to the progression of disease severity and mortality.

Short- and long-term outcomes of early initiation of peritoneal dialysis following catheter insertion.

INTRODUCTION: Early-start peritoneal dialysis (PD) (use of PD catheter within 48 hours of insertion) is an innovative approach for prompt initiation of PD. AIM: This study was conducted to analyze the outcomes of early-start PD. MATERIALS AND METHODS: A total of 100 patients on PD were retrospectively analyzed. Patients were grouped according to the "break-in period": < 48 hours (PD1) and ≥ 14 days (PD2). PD was initiated with low dwell volumes (500 mL) in a recumbent position within 48 hours of surgery. PD prescription was gradually incremented over 10 days to minimize any complications. RESULTS: In our study, there were 48 patients in the PD1 group and 52 in the PD2 group. The most common cause of end-stage kidney disease (ESKD) was diabetes mellitus in both groups. Incidence of early mechanical complications (within 30 days of catheter insertion), such as catheter obstruction, early catheter leakage, catheter malposition, tip migration, and infectious complications, were not found to be higher in the PD1 group. 1- and 4-year catheter patency rates were 97.0% and 96.2% in the PD1 group, respectively. These rates were comparable with those in the PD2 group. Early-start PD was not associated with an increased incidence of catheter failure (HR = 1.0, 95% CI 0.28 - 3.47). CONCLUSION: An early break-in period of < 48 hours is a feasible option for ESKD patients without any significantly increased risk of mechanical or infectious complications. It offers a safe and efficacious option for renal replacement therapy.

Update on Coronavirus 2019 Vaccine Guidelines for Transplant Recipients.

The coronavirus disease 2019 (COVID-19) vaccine and its utility in solid organ transplantation need to be timely revised and updated. These guidelines have been formalized by the experts-the apex technical committee members of the National Organ and Tissue Transplant Organization and the heads of transplant societies-for the guidance of transplant communities. We recommend that all personnel involved in organ transplantation should be vaccinated as early as possible and continue COVID-19-appropriate behavior despite a full course of vaccination. For specific guidelines of recipients, we suggest completing the full schedule before transplantation whenever the clinical condition permits. We also suggest a single dose, rather than proceeding unvaccinated for transplant, in case a complete course is not feasible. If vaccination is planned before surgery, we recommend a gap of at least 2 weeks between the last dose of vaccine and surgery. For those not vaccinated before transplant, we suggest waiting 4 to 12 weeks after transplant. For the potential living donors, we recommend the complete vaccination schedule before transplant. However, if this is not feasible, we suggest receiving at least a single dose of the vaccine 2 weeks before donation. We suggest that suitable transplant patients and those on the waiting list should accept a third dose of the vaccine when one is offered to them. We recommend that organs from a deceased donor with suspected/proven vaccine-induced thrombotic thrombocytopenia should be avoided and are justified only in cases of emergency situations with informed consent and counseling.

Stretching the boundaries: suitability of an arteriovenous fistula in elderly patients on hemodialysis-a northern India experience.

PURPOSE: Considering various factors, such as multiple co-morbidities, unsuitable vessels for access creation, non-maturation, vascular calcifications, the outcome of arteriovenous fistula (AVF) in the elderly population, may not be similar to the younger people. Our study aims to analyze the outcomes of AVF in elderly patients (> 65 year). METHODS: It was a prospective observational study. Patients of more than 65 years of age in whom AVF was created from January 2012 to December 2015 were included in the study. These patients were followed up for 4 years. The primary endpoint of our study was to assess primary and secondary patency rates. RESULTS: A total of 450 AVFs were included in the study. The mean age was 68.5 years. The most common site of AVF was radiocephalic (RCAVF) in 70% (n = 315), brachiocephalic (BCAVF) in 24% (n = 108) and basilic vein transposition (BVT) in 6% (n = 27). At 48 months, the primary patency rate of RCAVF, BCAVF, and BVT was 55%, 61.6%, and 60.4%, respectively. The commonest cause of access failure was thrombosis followed by non-maturation. CONCLUSION: AVF remains the preferred vascular access for hemodialysis even in the elderly population. Failure to mature and thrombosis continue to be a concern with AVF. Location of the AV access does not seem to impact the long-term patency.

Implications of oxidative stress in chronic kidney disease: a review on current concepts and therapies.

Moderate levels of endogenous reactive oxygen species (ROS) are important for various cellular activities, but high levels lead to toxicity and are associated with various diseases. Levels of ROS are maintained as a balance between oxidants and antioxidants. Accumulating data suggest that oxidative stress is a major factor in deterioration of renal function. In this review, we highlight the possible mechanism by which oxidative stress can lead to chronic kidney disease (CKD). This review also describes therapies that counter the effect of oxidative stress in CKD patients. Numerous factors such as upregulation of genes involved in oxidative phosphorylation and ROS generation, chronic inflammation, vitamin D deficiency, and a compromised antioxidant defense mechanism system cause progressive detrimental effects on renal function that eventually lead to loss of kidney function. Patients with renal dysfunction are highly susceptible to oxidative stress, as risk factors such as diabetes, renal hypertension, dietary restrictions, hemodialysis, and old age predispose them to increased levels of ROS. Biomolecular adducts (DNA, proteins, and lipids) formed due to reaction with ROS can be used to determine oxidative stress levels. Based on the strong correlation between oxidative stress and CKD, reversal of oxidative stress is being explored as a major therapeutic option. Xanthine oxidase inhibitors, dietary antioxidants, and other agents that scavenge free radicals are gaining interest as treatment modalities in CKD patients.

Renal Biopsy and Clinical Outcomes in Patients With ABO-Incompatible Renal Transplant: Experience From a Tertiary Care Hospital.

OBJECTIVES: Renal transplant with ABO-incompatible donors expands the donor pool. Earlier studies have focused the use of protocol biopsies in ABO-incompatible transplant patients. Our study described outcomes of indication (for cause) renal biopsies and clinical outcomes in patients with ABO-incompatible renal transplant. MATERIALS AND METHODS: This retrospective study included 164 patients from January 2012 to June 2019. Biochemical parameters, serial immunoglobulin G anti-ABO titers, and class I and II donor-specific antibody findings were obtained from hospital records, and renal graft biopsies were reviewed according to the Banff 2017 update. RESULTS: We analyzed the results of 65 biopsies from 54 patients. Biopsy-proven acute antibody-mediated rejection (12.8%) was found to be more prevalent than acute cellular rejection (1.8%). Patients with antibodymediated rejection all had microvascular inflammation (g+ptc score of 2 or more, where g+ptc is the sum of the glomerulitis and peritubular capillaritis scores) and were positive for C4d. Acute tubular injury per se was seen in 10.3% of patients; 65% of these patients had C4d positivity in peritubular capillaries, and only 1 patient developed chronic active antibody-mediated rejection on follow-up. Patient and death-censored graft survival rates were 92% and 98% at 1 year after transplant and 88% and 91% at 3 years, respectively. Patients with an episode of antibody-mediated rejection had lower rates of patient (76.5%) and deathcensored graft survival (84.6%) at 1 year. CONCLUSIONS: The microvascular inflammation score (g+ptc score of 2 or higher) is more reliable than diffuse C4d positivity to determine antibody-mediated rejection in ABO-incompatible transplants because diffuse C4d positivity may also be seen in etiologies unrelated to antibody-mediated rejection. Acute tubular injury with C4d positivity without microvascular injury does not confirm antibody-mediated rejection. We suggest that Banff classification be updated in ABO-incompatible transplants to include diagnostic criteria for the diagnosis of antibody-mediated rejection.

Urinary tract infection in renal transplant recipient: A clinical comprehensive review.

Since the initial times of renal transplantation in the 1950s, understanding various aspects influencing graft survival and outcome have been progressively improving. However, infections especially urinary tract infections (UTIs), are an important factor leading to an increase in morbidity and graft failure. UTI degrades the health-related quality of life and can potentially impair graft function. UTI occurs in 25% of kidney transplant recipients within one year of transplant and accounts for 45% of infectious complications. Asymptomatic bacteriuria (ASB), uncomplicated UTI, and complicated UTI comprise 44%, 32%, and 24% of cases, respectively. This article reviews important aspects regarding posttransplant UTI, including definition, incidence, predisposing factors, recommendations, ASB, and controversies in management. UTI after renal transplantation is still an under-estimated aspect, despite its degrading effects on allograft and recipient health.

Comparison of short-term outcomes with and without induction therapy in low-risk renal transplant recipients.

With low rates of rejection with current immunosuppression consisting of steroids, mycophenolic acid and tacrolimus, the question arises whether induction offers any additional benefit in low-risk renal transplant recipients. This study evaluated outcomes with and without induction in low-risk renal transplant recipients. A prospective observational study in which 100 low-risk renal transplant recipients were included and divided into two groups - one that received induction (IND) and another that did not (NO IND). They were followed for 1.5 years. Three endpoints were compared - efficacy of induction, patient and graft survival, and adverse effects. Incidence of rejection in early posttransplant period did not differ (4% NO IND vs. 6% IND; P = 0.171). Rejection as cause of late graft dysfunction was seen in 16% in IND vs. 20% NO IND; (P = 0.603). No difference in serum creatinine at end of 1.5 years was seen. Graft survival was also similar. Relapsing and recurrent urinary tract infections (46% IND vs. 16% NO IND; P = 0.09), hospitalization requiring infections (76%IND vs. 64% NO IND; P = 0.119 NS) were more common in IND. Cytomegalovirus infection affected only IND (6% vs. none; P = 0.07). Patient survival at 1.5 years was comparable (94% IND vs. 96% NO IND; P = 0.646). The study showed comparable results between IND and NO IND with however an increased incidence of infections and hospitalizations in the IND group. The use of induction may be avoided in low-risk renal transplant recipients.

Clinical characteristics, outcomes, and management of COVID-19 in kidney transplant recipients across Asia: an ASTREGO report.

Background: Asia is the global epicenter of the coronavirus disease 2019 (COVID-19) pandemic; however, COVID-19-related mortality in Asia remains lower than in other parts of the world. It is uncertain whether the mortality of COVID-19-infected kidney transplant recipients (KTXs) from Asia follows the lower mortality trends of the younger Asian population. Methods: Specific transplant centers from countries in the Asian Society of Transplantation were invited to participate in a study to examine the epidemiology, clinical features, natural history, and outcomes of COVID-19 infections in KTXs. Data were analyzed and compared with those of large cohort studies from other countries. Results: The study population was 87 KTXs from nine hospitals in seven Asian countries. Within the study population, 9% were aged 60 years and older, and 79% had at least one comorbidity. The majority of patients (69%) presented with mild-to-moderate COVID-19 severity. Disease progression was more frequently encountered among those with moderate or severe infection (23%) and non-survivors (55%). The mortality rate was 23% (n=20) and differed according to the level of care 12% (n=1/8), 15% (n=10/67), and 100% (n=9/9) of patients managed as outpatients, in the general ward, and in the intensive care unit, respectively. Disease severity at the time of presentation was an independent predictor of mortality. Compared with the mortality rates in other studies worldwide, mortality rates in the current study were comparable. Conclusions: Mortality in Asian KTXs who were infected with COVID-19 remains high and could be related to comorbidity burden and the constraints of the general healthcare system when the COVID-19 caseload is high.

COVID-19 and the kidney: A matter of concern.

Starting from December 2019 in China, SARS-CoV-2, a novel coronavirus strain has rapidly spread to involve more than 150 countries. SARS-CoV-2 is not only responsible for causing pneumonia, but there are also concerns regarding the involvement of other organs such as the heart, liver, and kidneys. Here, we review kidney involvement in COVID 19, the mechanism of kidney injury, and its impact on mortality. Lastly, we focus on the challenges of COVID19 in dialysis and renal transplant patients.

Transplantation in Asia during the coronavirus disease-19 (COVID-19) pandemic: briefs from member countries of the Asian Society of Transplantation.

The coronavirus disease-19 (COVID-19) pandemic has affected 1,029,968 people in Asia as of May 16, 2020. Although Asia was the first continent to be affected, many countries in the region continue to battle COVID-19, which challenges the way transplant programs provide their services. Given the diversity of healthcare systems in Asia, the countermeasures in response to COVID-19 are as potentially diverse. This review reports the experiences of transplant services in member countries of the Asian Society of Transplantation (AST) as well as provides a platform for sharing of best practices during the COVID-19 pandemic. AST invited member countries to provide a short description of their transplant experiences during the COVID-19 pandemic. Whenever information is available, countries were asked to provide information on COVID-19 related statistics, status of transplant programs, mitigation measures taken to prevent COVID-19, and other areas of transplant programs impacted by COVID-19. Ten countries responded to the invitation of which seven still have active transplant programs at varying levels of activity. All countries have protocols for donor/recipient screening and countermeasures to prevent COVID-19 infections in recipients and healthcare providers. Interestingly, these countries report only 16 transplant recipients with COVID-19 infection but no cases of donor-transmitted COVID-19 infection. Despite the diversity of healthcare systems in Asia, transplant centers in Asia have taken appropriate precautions to avoid COVID-19 infections, though the long-term impact of COVID-19 remains unclear.

Importance of renal biopsy in patients aged 60 years and older: Experience from a tertiary care hospital.

As the life expectancy is increasing, there is a rise in elderly population and consequent increase in the patients with renal disease. There is an inconsistency between clinical and histopathological diagnosis in elderly, and so renal biopsy is important in these patients to decide appropriate clinical management and prognosis. This study outlines the importance of renal biopsy in elderly and describes the clinical and pathologic spectrum of renal diseases in patient ≥60 years. All patients (age ≥60 years) undergoing renal biopsies from January 2011 to December 2014 were included in this retrospective study. The clinical presentation and biochemical findings were recorded, and the patients were grouped based on their clinical presentation. Renal biopsies were also evaluated. The mean age of patients was 67.7 ± 6.4 years with a male:female ratio of 3:1. The most common clinical manifestation was nephrotic syndrome (37.4%) followed by rapidly progressive renal failure (RPRF) (20.6%). Amyloidosis and membranous nephropathy were two most common diagnoses in patients with nephrotic presentation whereas pauci-immune crescentic glomerulonephritis and cast nephropathy were common in patients presenting with RPRF. Clinical diagnosis differed from the histopathological diagnosis in 32% cases of nephrotic syndrome. There was good agreement between clinical diagnosis and histology in cases with RPRF. In 73% cases of elderly with (Type II) diabetes suspected of having nondiabetic renal disease clinically, renal biopsy showed evidence of diabetic nephropathy. Renal biopsy is essential in the diagnosis of renal diseases even in elderly. Amyloidosis and membranous nephropathy are common causes of nephrotic syndrome in elderly. Renal biopsy is very useful in diagnosing cast nephropathy and amyloidosis as they are not suspected clinically. It is also helpful in elderly diabetics without retinopathy to differentiate between diabetic and nondiabetic kidney diseases.

Epidemiology and risk factors of chronic kidney disease in India - results from the SEEK (Screening and Early Evaluation of Kidney Disease) study.

BACKGROUND: There is a rising incidence of chronic kidney disease that is likely to pose major problems for both healthcare and the economy in future years. In India, it has been recently estimated that the age-adjusted incidence rate of ESRD to be 229 per million population (pmp), and >100,000 new patients enter renal replacement programs annually. METHODS: We cross-sectionally screened 6120 Indian subjects from 13 academic and private medical centers all over India. We obtained personal and medical history data through a specifically designed questionnaire. Blood and urine samples were collected. RESULTS: The total cohort included in this analysis is 5588 subjects. The mean ± SD age of all participants was 45.22 ± 15.2 years (range 18-98 years) and 55.1% of them were males and 44.9% were females. The overall prevalence of CKD in the SEEK-India cohort was 17.2% with a mean eGFR of 84.27 ± 76.46 versus 116.94 ± 44.65 mL/min/1.73 m2 in non-CKD group while 79.5% in the CKD group had proteinuria. Prevalence of CKD stages 1, 2, 3, 4 and 5 was 7%, 4.3%, 4.3%, 0.8% and 0.8%, respectively. CONCLUSION: The prevalence of CKD was observed to be 17.2% with ~6% have CKD stage 3 or worse. CKD risk factors were similar to those reported in earlier studies.It should be stressed to all primary care physicians taking care of hypertensive and diabetic patients to screen for early kidney damage. Early intervention may retard the progression of kidney disease. Planning for the preventive health policies and allocation of more resources for the treatment of CKD/ESRD patients are imperative in India.