Inequalities in the management of diabetic kidney disease in UK primary care: A cross-sectional analysis of a large primary care database.

AIMS: To determine differences in the management of diabetic kidney disease (DKD) relevant to patient sex, ethnicity and socio-economic group in UK primary care. METHODS: A cross-sectional analysis as of January 1, 2019 was undertaken using the IQVIA Medical Research Data dataset, to determine the proportion of people with DKD managed in accordance with national guidelines, stratified by demographics. Robust Poisson regression models were used to calculate adjusted risk ratios (aRR) adjusting for age, sex, ethnicity and social deprivation. RESULTS: Of the 2.3 million participants, 161,278 had type 1 or 2 diabetes, of which 32,905 had DKD. Of people with DKD, 60% had albumin creatinine ratio (ACR) measured, 64% achieved blood pressure (BP, <140/90 mmHg) target, 58% achieved glycosylated haemoglobin (HbA1c, <58 mmol/mol) target, 68% prescribed renin-angiotensin-aldosterone system (RAAS) inhibitor in the previous year. Compared to men, women were less likely to have creatinine: aRR 0.99 (95% CI 0.98-0.99), ACR: aRR 0.94 (0.92-0.96), BP: aRR 0.98 (0.97-0.99), HbA1c : aRR 0.99 (0.98-0.99) and serum cholesterol: aRR 0.97 (0.96-0.98) measured; achieve BP: aRR 0.95 (0.94-0.98) or total cholesterol (<5 mmol/L) targets: aRR 0.86 (0.84-0.87); or be prescribed RAAS inhibitors: aRR 0.92 (0.90-0.94) or statins: aRR 0.94 (0.92-0.95). Compared to the least deprived areas, people from the most deprived areas were less likely to have BP measurements: aRR 0.98 (0.96-0.99); achieve BP: aRR 0.91 (0.8-0.95) or HbA1c : aRR 0.88 (0.85-0.92) targets, or be prescribed RAAS inhibitors: aRR 0.91 (0.87-0.95). Compared to people of white ethnicity; those of black ethnicity were less likely to be prescribed statins aRR 0.91 (0.85-0.97). CONCLUSIONS: There are unmet needs and inequalities in the management of DKD in the UK. Addressing these could reduce the increasing human and societal cost of managing DKD.

Current management of chronic kidney disease in type-2 diabetes-A tiered approach: An overview of the joint Association of British Clinical Diabetologists and UK Kidney association (ABCD-UKKA) guidelines.

A growing and significant number of people with diabetes develop chronic kidney disease (CKD). Diabetes-related CKD is a leading cause of end-stage kidney disease (ESKD) and people with diabetes and CKD have high morbidity and mortality, predominantly related to cardiovascular disease (CVD). Despite advances in care over the recent decades, most people with CKD and type 2 diabetes are likely to die of CVD before developing ESKD. Hyperglycaemia and hypertension are modifiable risk factors to prevent onset and progression of CKD and related CVD. People with type 2 diabetes often have dyslipidaemia and CKD per se is an independent risk factor for CVD, therefore people with CKD and type 2 diabetes require intensive lipid lowering to reduce burden of CVD. Recent clinical trials of people with type 2 diabetes and CKD have demonstrated a reduction in composite kidney end point events (significant decline in kidney function, need for kidney replacement therapy and kidney death) with sodium-glucose co-transporter-2 (SGLT-2) inhibitors, non-steroidal mineralocorticoid receptor antagonist finerenone and glucagon-like peptide 1 receptor agonists. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have previously undertaken a narrative review and critical appraisal of the available evidence to inform clinical practice guidelines for the management of hyperglycaemia, hyperlipidaemia and hypertension in adults with type 2 diabetes and CKD. This 2024 abbreviated updated guidance summarises the recommendations and the implications for clinical practice for healthcare professionals who treat people with diabetes and CKD in primary, community and secondary care settings.

P4 protein of an Indian isolate of rice tungro bacilliform virus modulates gene silencing.

Plant hosts and their viral pathogens are engaged in a constant cycle of defense and counter-defense as part of a molecular arms race, principal among them being the plant RNAi defense and the viral RNAi suppressor counter-defense. Rice tungro bacilliform virus (RTBV), member of the family Caulimoviridae, genus Tungrovirus, species Tungrovirus oryzae, infects rice in South- and Southeast Asia and causes severe symptoms of stunting, yellow-orange discoloration and twisting of leaf tips. To better understand the possible counter-defensive roles of RTBV against the host RNAi defense system, we explored the ability of the P4 protein of an Indian isolate of RTBV to act as a possible modulator of RNAi. Using a transient silencing and silencing suppression assay in Nicotiana benthamiana, we show that P4 not only displays an RNAi suppressor function, but also potentially enhances RNAi. The results also suggests that the N-terminal 168 amino acid residues of P4 are sufficient to maintain RNAi suppressor activity. Taken together with the earlier reports this work strengthens the view that the P4 protein carries out RNAi suppressor and a potential RNAi enhancer function.

Transient expression analysis of promoters of okra enation leaf curl virus in Nicotiana benthamiana, cotton and okra plants.

Viral promoters can be used to drive heterologous gene expression in transgenic plants. As part of our quest to look for new promoters, we have explored, for the first time, the promoters of okra enation leaf curl virus (OELCuV), a begomovirus infecting okra (Abelmoschus esculentus). The Rep and CP promoters of OELCuV fused with the gfp reporter gene, were expressed transiently in the natural host okra and the laboratory host cotton and Nicotiana benthamiana. The expression levels of the promoters were quantified through confocal laser scanning microscopy and GFP assay in N. benthamiana and okra. The results indicated that the Rep promoter was more active than the CP promoter, whose activity was similar to that of CaMV 35S promoter. Additionally, the Rep and CP promoters showed increase of expression, probably due to transactivation, when assayed following inoculation of OELCuV and betasatellite DNAs in cotton plants. A moderate increase in promoter activity in N. benthamiana was also seen, when assayed following the inoculation of the heterologous begomovirus Sri Lankan cassava mosaic virus.

Clinical practice guideline for the management of lipids in adults with diabetic kidney disease: abbreviated summary of the Joint Association of British Clinical Diabetologists and UK Kidney Association (ABCD-UKKA) Guideline 2024.

The contribution of chronic kidney disease (CKD) towards the risk of developing cardiovascular disease (CVD) is magnified with co-existing type 1 or type 2 diabetes. Lipids are a modifiable risk factor and good lipid management offers improved outcomes for people with diabetic kidney disease (DKD).The primary purpose of this guideline, written by the Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) working group, is to provide practical recommendations on lipid management for members of the multidisciplinary team involved in the care of adults with DKD.

Bio-impedance spectroscopy added to a fluid management protocol does not improve preservation of residual kidney function in incident hemodialysis patients in a randomized controlled trial.

Avoiding excessive dialysis-associated volume depletion may help preserve residual kidney function (RKF). To establish whether knowledge of the estimated normally hydrated weight from bioimpedance measurements (BI-NHW) when setting the post-hemodialysis target weight (TW) might mitigate rate of loss of RKF, we undertook an open label, randomized controlled trial in incident patients receiving HD, with clinicians and patients blinded to bioimpedance readings in controls. A total of 439 patients with over 500 ml urine/day or residual GFR exceeding 3 ml/min/1.73m2 were recruited from 34 United Kingdom centers and randomized 1:1, stratified by center. Fluid assessments were made for up to 24 months using a standardized proforma in both groups, supplemented by availability of BI-NHW in the intervention group. Primary outcome was time to anuria, analyzed using competing-risk survival models adjusted for baseline characteristics, by intention to treat. Secondary outcomes included rate of RKF decline (mean urea and creatinine clearance), blood pressure and patient-reported outcomes. There were no group differences in cause-specific hazard rates of anuria (0.751; 95% confidence interval (0.459, 1.229)) or sub-distribution hazard rates (0.742 (0.453, 1.215)). RKF decline was markedly slower than anticipated, pooled linear rates in year 1: -0.178 (-0.196, -0.159)), year 2: -0.061 (-0.086, -0.036)) ml/min/1.73m2/month. Blood pressure and patient-reported outcomes did not differ by group. The mean difference agreement between TW and BI-NHW was similar for both groups, Bioimpedance: -0.04 kg; Control: -0.25 kg. Thus, use of a standardized clinical protocol for fluid assessment when setting TW is associated with excellent preservation of RKF. Hence, bioimpedance measurements are not necessary to achieve this.

Principles and practice of virus induced gene silencing for functional genomics in plants.

Virus induced gene silencing (VIGS) has, of late, emerged as an important tool for transient silencing of genes in plants. This is now being increasingly used to determine functions of novel genes in a wide variety of plants, many of which are important crops yielding food and fiber or are sources of products having pharmaceutical uses. The technology for VIGS comprises the development of vectors derived from viruses, choosing the optimal orientation and size of the gene to be targeted and adopting the most suitable method of inoculation. This review gives a brief overview of the main aspects of VIGS technology as is being practiced. It also discusses the challenges the technology faces and the possible way ahead to improve its robustness, so that the technology finds wider applications.

Do we practice what we preach? Dialysis modality choice among healthcare workers in the United Kingdom.

BACKGROUND: In the United Kingdom, over 80% of end-stage kidney disease patients receive in-center hemodialysis. We conducted a survey of UK renal healthcare workers on their preferred dialysis modality if they needed dialysis themselves. METHODS: An anonymized online survey was disseminated to all renal healthcare workers in the United Kingdom. We asked "Assume you are an otherwise well 40-year-old (and, separately, 75-year-old) person approaching end stage kidney disease, you have no living kidney donor options at present. There are no contraindications to any dialysis options. Which dialysis therapy would you choose?" We also asked about factors influencing their choice. RESULTS: 858 individuals with a median age of 44.3 years responded. 70.2% were female, 37.4% doctors, and 31.1% were senior nurses. There was a preference for peritoneal dialysis over in-center hemodialysis (50.47% v. 6.18%; p < 0.001 for 40-year-old and 49.18% v. 17.83%; p < 0.001 for 75-year-old assumption) and home hemodialysis (50.47% v. 39.28%; p < 0.001 for 40-year-old and 49.18% v. 18.41% for 75-year-old assumption). There was a preference for home hemodialysis over in-center hemodialysis for 40-year-old (39.28% v. 6.18%; p < 0.001) but not for 75-year-old. On logistic regression, senior doctors were more likely to opt for PD when compared to nurses. Nurses, allied healthcare professionals, and those of Asian/British Asian ethnicity were more likely to choose in-center hemodialysis. CONCLUSIONS: Most healthcare workers in renal medicine would choose home-based treatment for themselves although the majority of end-stage kidney disease patients receive in-center hemodialysis in the United Kingdom; the reasons for the discrepancy need to be explored.

Obesity Without Metabolic Abnormality and Incident CKD: A Population-Based British Cohort Study.

RATIONALE & OBJECTIVE: Metabolically healthy obesity (obesity without any metabolic abnormality) is not considered to be associated with increased risk of morbidity and mortality. We examined and quantified the association between metabolically healthy overweight/obesity and the risk of incident chronic kidney disease (CKD) in a British primary care population. STUDY DESIGN: Retrospective population-based cohort study. SETTING & PARTICIPANTS: 4,447,955 of the 5,182,908 adults in The Health Improvement Network (THIN) database (United Kingdom, 1995-2015) with a recorded body mass index (BMI) at the time of registration date who were free of CKD and cardiovascular disease. EXPOSURE: 11 body size phenotypes were created, defined by BMI categories (underweight, normal weight, overweight, and obesity) and 3 metabolic abnormalities (diabetes, hypertension, and dyslipidemia). OUTCOME: Incident CKD defined as a recorded code for kidney replacement therapy, a recorded diagnosis of CKD, or by an estimated glomerular filtration rate of<60mL/min/1.73m2 for≥90 days, or a urinary albumin-creatinine ratio>3mg/mmol for≥90 days. RESULTS: Of the 4.5 million individuals, 1,040,921 (23.4%) and 588,909 (13.2%) had metabolically healthy overweight and metabolically healthy obesity, respectively. During a mean follow-up interval of 5.4±4.3 (SD) years, compared with individuals with a metabolically healthy normal weight (n=1,656,231), there was a higher risk of incident CKD among those who had metabolically healthy overweight (adjusted HR, 1.30 [95% CI, 1.28-1.33]) and metabolically healthy obesity (adjusted HR, 1.66 [95% CI, 1.62-1.70]). The association was stronger in those younger than 65 years of age. In all BMI categories, there was greater risk of incident CKD with a greater number of metabolic abnormalities in a graded manner. LIMITATIONS: Potential misclassification of metabolic status due to delayed diagnosis and residual confounding due to unmeasured factors. CONCLUSIONS: Overweight and obesity without metabolic abnormality are associated with a higher risk of incident CKD compared with those with normal body weight and no metabolic abnormality.

Clinical practice guidelines for management of hyperglycaemia in adults with diabetic kidney disease.

A significant percentage of people with diabetes develop chronic kidney disease and diabetes is also a leading cause of end-stage kidney disease (ESKD). The term diabetic kidney disease (DKD) includes both diabetic nephropathy (DN) and diabetes mellitus and chronic kidney disease (DM CKD). DKD is associated with high morbidity and mortality, which are predominantly related to cardiovascular disease. Hyperglycaemia is a modifiable risk factor for cardiovascular complications and progression of DKD. Recent clinical trials of people with DKD have demonstrated improvement in clinical outcomes with sodium glucose co-transporter-2 (SGLT-2) inhibitors. SGLT-2 inhibitors have significantly reduced progression of DKD and onset of ESKD and these reno-protective effects are independent of glucose lowering. At the time of this update Canagliflozin and Dapagliflozin have been approved for delaying the progression of DKD. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have undertaken a literature review and critical appraisal of the available evidence to inform clinical practice guidelines for management of hyperglycaemia in adults with DKD. This 2021 guidance is for the variety of clinicians who treat people with DKD, including GPs and specialists in diabetes, cardiology and nephrology.

Chronic kidney disease, physical activity and cognitive function in older adults-results from the National Health and Nutrition Examination Survey (2011-2014).

BACKGROUND: Cognitive impairment is common among persons with chronic kidney disease (CKD), due in part to reduced kidney function. Given that physical activity (PA) is known to mitigate cognitive decline, we examined whether associations between CKD stage and global/domain-specific cognitive function differ by PA. METHODS: We leveraged 3223 participants (≥60 years of age) enrolled in National Health and Nutrition Examination Survey (NHANES, 2011-2014), with at least one measure of objective cognitive function [immediate recall (CERAD-WL), delayed recall (CERAD-DR), verbal fluency (AF), executive function/processing speed (DSST), global (average of four tests) or self-perceived memory decline (SCD)]. We quantified the association between CKD stage {no CKD: estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2 and albuminuria [albumin:creatinine ratio (ACR)] <30 mg/g; stages G1-G3: eGFR ≥60 mL/min/1.73 m2 and ACR ≥30 mg/g or eGFR 30-59 mL/min/1.73 m2; stages G4 and G5: eGFR <30 mL/min/1.73 m2} and cognitive function using linear regression (objective measures) and logistic regression (SCD), accounting for sampling weights for nationally representative estimates. We tested whether associations differed by PA [Global Physical Activity Questionnaire, high PA ≥600 metabolic equivalent of task (MET) · min/week versus low PA <600 MET · min/week] using a Wald test. RESULTS: Among NHANES participants, 34.9% had CKD stages G1-G3, 2.6% had stages G4 and G5 and 50.7% had low PA. CKD stages G4 and G5 were associated with lower global cognitive function {difference = -0.38 standard deviation [SD] [95% confidence interval (CI) -0.62 to -0.15]}. This association differed by PA (Pinteraction = 0.01). Specifically, among participants with low PA, those with CKD stages G4 and G5 had lower global cognitive function [difference = -0.57 SD (95% CI -0.82 to -0.31)] compared with those without CKD. Among those with high PA, no difference was found [difference = 0.10 SD (95% CI -0.29-0.49)]. Similarly, the CKD stage was only associated with immediate recall, verbal fluency, executive function and processing speed among those with low PA; no associations were observed for delayed recall or self-perceived memory decline. CONCLUSIONS: CKD is associated with lower objective cognitive function among those with low but not high PA. Clinicians should consider screening older patients with CKD who have low PA for cognitive impairment and encourage them to meet PA guidelines.

Characterization of the functional domains of nuclear shuttle protein (NSP) of Indian cassava mosaic virus using green fluorescent protein as reporter.

Indian cassava mosaic virus (ICMV), responsible for the cassava mosaic disease in India, harbours two circular genomic components, DNA-A and DNA-B; the former being responsible for the encapsidation and replication and the latter for intra- and inter-cellular movement of the viral DNA. Two proteins, encoded by DNA-B, the movement protein (MP) and the nuclear shuttle protein (NSP), act in concert on the newly replicated viral DNA to move it from the nucleus to the cell periphery. To map the functional domains of NSP, the intra-cellular localization of its full-length protein and deletion derivatives was studied in the epidermal cells of detached leaves of the laboratory host plant, Nicotiana benthamiana, where the target proteins were transiently expressed as GFP fusions. This analysis revealed domains for nuclear localization at the N-terminus, as well as for localization towards the cell periphery both at the C-terminus and center of the NSP.

The interplay of plant hormonal pathways and geminiviral proteins: partners in disease development.

Viruses belonging to the family Geminiviridae infect plants and are responsible for a number of diseases of crops in the tropical and sub-tropical regions of the World. The innate immune response of the plant assists in its defense against such viral pathogens by the recognition of pathogen/microbe-associated molecular patterns through pattern-recognition receptors. Phytohormone signalling pathways play a vital role in plant defense responses against these devastating viruses. Geminiviruses, however, have developed counter-defense strategies that prevail over the above defense pathways. The proteins encoded by geminiviruses act as suppressors of plant immunity by interacting with the signalling components of several hormones. In this review we focus on the molecular interplay of phytohormone pathways and geminiviral infection and try to find interesting parallels with similar mechanisms known in other plant-infecting viruses and strengthen the argument that this interplay is necessary for disease development.

Acute kidney injury in critically ill COVID-19 infected patients requiring dialysis: experience from India and Pakistan.

BACKGROUND: Acute kidney injury (AKI) was common in the first two waves of the SARS-COV-2 pandemic in critically ill patients. A high percentage of these patients required renal replacement therapy and died in the hospital. METHODS: The present study examines the clinical presentation, laboratory parameters and therapeutic interventions in critically ill patients with AKI admitted to the ICU in two centres, one each in India and Pakistan. Patient and outcome details of all critically ill COVID 19 patients admitted to the ICU requiring renal replacement therapy were collected. Data was analysed to detect patient variables associated with mortality. RESULTS: A total of 1,714 critically ill patients were admitted to the ICUs of the two centres. Of these 393 (22.9%) had severe acute kidney injury (AKIN stage 3) requiring dialysis. Of them, 60.5% were men and the mean (± SD) age was 58.78 (± 14.4) years. At the time of initiation of dialysis, 346 patients (88%) were oligo-anuric. The most frequent dialysis modality in these patients was intermittent hemodialysis (48.1%) followed by slow low efficiency dialysis (44.5%). Two hundred and six (52.4%) patients died. The mortality was higher among the Indian cohort (68.1%) than the Pakistani cohort (43.4%). Older age (age > 50 years), low serum albumin altered sensorium, need for slower forms of renal replacement therapy and ventilatory support were independently associated with mortality. CONCLUSION: There was a very high mortality in patients with COVID-19 associated AKI undergoing RRT in the ICUs in this cohort from the Indian sub-continent.

Clinical characteristics do not reliably identify non-adherence in patients with uncontrolled hypertension.

PURPOSE: Chemical adherence testing is a reliable method to assess adherence to antihypertensive drugs. However, it is expensive and has limited availability in clinical practice. To reduce the number and costs of chemical adherence tests, we aimed to develop and validate a clinical screening tool to identify patients with a low probability of non-adherence in patients with uncontrolled hypertension. MATERIALS AND METHODS: In 495 patients with uncontrolled hypertension referred to the University Medical Centre Utrecht (UMCU), the Netherlands, a penalised logistic regression model including seven pre-specified easy-to-measure clinical variables was derived to estimate the probability of non-adherence. Non-adherence was defined as not detecting at least one of the prescribed antihypertensive drugs in plasma or urine. Model performance and test characteristics were evaluated in 240 patients with uncontrolled hypertension referred to the Heartlands Hospital, United Kingdom. RESULTS: Prevalence of non-adherence to antihypertensive drugs was 19% in the UMCU and 44% in the Heartlands Hospital population. After recalibration of the model's intercept, predicted probabilities agreed well with observed frequencies. The c-statistic of the model was 0.63 (95%CI 0.53-0.72). Predicted probability cut-off values of 15%-22.5% prevented testing in 5%-15% of the patients, carrying sensitivities between 97% (64-100) and 90% (80-95), and negative predictive values between 74% (10-99) and 70% (50-85). CONCLUSION: The combination of seven clinical variables is not sufficient to reliably discriminate adherent from non-adherent individuals to safely reduce the number of chemical adherence tests. This emphasises the complex nature of non-adherence behaviour and thus the need for objective chemical adherence tests in patients with uncontrolled hypertension.

CRISPR/Cas-Mediated Resistance against Viruses in Plants.

CRISPR/Cas9 provides a robust and widely adaptable system with enormous potential for genome editing directed towards generating useful products. It has been used extensively to generate resistance against viruses infecting plants with more effective and prolonged efficiency as compared with previous antiviral approaches, thus holding promise to alleviate crop losses. In this review, we have discussed the reports of CRISPR/Cas-based virus resistance strategies against plant viruses. These strategies include approaches targeting single or multiple genes (or non-coding region) in the viral genome and targeting host factors essential for virus propagation. In addition, the utilization of base editing has been discussed to generate transgene-free plants resistant to viruses. This review also compares the efficiencies of these approaches. Finally, we discuss combinatorial approaches, including multiplexing, to increase editing efficiency and bypass the generation of escape mutants.

Association of British Clinical Diabetologists and Renal Association guidelines on the detection and management of diabetes post solid organ transplantation.

Post-transplant diabetes mellitus (PTDM) is common after solid organ transplantation (SOT) and associated with increased morbidity and mortality for allograft recipients. Despite the significant burden of disease, there is a paucity of literature with regards to detection, prevention and management. Evidence from the general population with diabetes may not be translatable to the unique context of SOT. In light of emerging clinical evidence and novel anti-diabetic agents, there is an urgent need for updated guidance and recommendations in this high-risk cohort. The Association of British Clinical Diabetologists (ABCD) and Renal Association (RA) Diabetic Kidney Disease Clinical Speciality Group has undertaken a systematic review and critical appraisal of the available evidence. Areas of focus are; (1) epidemiology, (2) pathogenesis, (3) detection, (4) management, (5) modification of immunosuppression, (6) prevention, and (7) PTDM in the non-renal setting. Evidence-graded recommendations are provided for the detection, management and prevention of PTDM, with suggested areas for future research and potential audit standards. The guidelines are endorsed by Diabetes UK, the British Transplantation Society and the Royal College of Physicians of London. The full guidelines are available freely online for the diabetes, renal and transplantation community using the link below. The aim of this review article is to introduce an abridged version of this new clinical guideline ( https://abcd.care/sites/abcd.care/files/site_uploads/Resources/Position-Papers/ABCD-RA%20PTDM%20v14.pdf).

The effect of admission and pre-admission serum creatinine as baseline to assess incidence and outcomes of acute kidney injury in acute medical admissions.

BACKGROUND: Acute kidney injury (AKI) in hospital-admitted patients is a common complication associated with increased mortality. The diagnosis of AKI relies on the ascertainment of peak increase in serum creatinine (SCr). This study evaluated the incidence of AKI using the increase from mean 7-365 days pre-admission (AKIpre) and admission (AKIadm) SCr levels, and examined the associations of AKI and changes in SCr levels with all-cause mortality. METHODS: A total of 2436 patients admitted to a tertiary hospital were recruited and followed-up for a median of 47.70 (interquartile range 18.20) months. AKI incidence and severity were defined according to the Kidney Disease: Improving Global Outcomes-AKI Guidelines. Follow-up data were collected from the Hospital Episode Statistics and Office of National Statistics. Mortality was evaluated during a short- (30 days), mid- (1 year) and long-term (4 years) period. RESULTS: No difference in the AKI rates using AKIpre and AKIadm (12.5% versus 12.2%; P = 0.695) or in the AKI severity (P = 0.261) was evident. Agreement between the two definitions was modest (Kappa-statistic = 0.596, P < 0.001). Patients with AKIpre or AKIadm had increased all-cause mortality compared with those without AKI during all follow-up periods. In fully adjusted regression analysis, AKIpre [hazard ratio (HR) = 2.226, 95% confidence interval (CI) 1.140-4.347; P = 0.027] and AKIadm (HR = 2.105, 95% CI 1.090-4.064; P = 0.027) remained associated with 30-day mortality. Results for the 1- and 4-year periods were similar. Increases of >4.00 µmol/L and >6.06% from pre-admission or >6.00 µmol/L and >17.24% from admission SCr levels presented increased mortality risk during follow-up. CONCLUSIONS: Use of admission or pre-admission SCr provides similar incidence rates, but they diagnose different sets of patients. Even minor increases in SCr, below those required for the classification of AKI, were associated with increased mortality. These findings can help the clinicians to identify patients at higher risk for adverse outcomes.

The titers of rice tungro bacilliform virus dictate the expression levels of genes related to cell wall dynamics in rice plants affected by tungro disease.

Rice tungro disease (RTD) is a devastating disease of rice caused by combined infection with rice tungro bacilliform virus (RTBV) and rice tungro spherical virus (RTSV), with one of the main symptoms being stunting. To dissect the molecular events responsible for RTD-induced stunting, the expression patterns of 23 cell-wall-related genes were examined in different rice lines with the same titers of RTSV but different titers of RTBV and in lines where only RTBV was present. Genes encoding cellulose synthases, expansins, glycosyl hydrolases, exostosins, and xyloglucan galactosyl transferase showed downregulation, whereas those encoding defensin or defensin-like proteins showed upregulation with increasing titers of RTBV. RTSV titers did not affect the expression levels of these genes. A similar relationship was seen for the reduction in the cellulose and pectin content and the accumulation of lignin. In silico analysis of promoters of the genes indicated a possible link to transcription factors reported earlier to respond to viral titers in rice. These results suggest a common network in which the genes related to the cell wall components are affected during infection with diverse viruses in rice.

Kidney transplant dysfunction in a patient with COVID - 19 infection: role of concurrent Sars-Cov 2 nephropathy, chronic rejection and vitamin C-mediated hyperoxalosis: case report.

BACKGROUND: COVID-19 infection in kidney transplant recipients often lead to allograft dysfunction. The allograft injury has various histopathological manifestations. Our case illustrates the unusual combination of allograft rejection, acute kidney injury secondary to oxalate nephropathy and SARS CoV-2 nephropathy as the cause of irreversible allograft failure. CASE PRESENTATION: A 56 year old renal allograft recipient presented with a history of fever and diarrhoea for the preceding 4 weeks, tested positive for Sars-CoV2 on nasal swab and was found to have severe allograft dysfunction, necessitating haemodialysis. He subsequently underwent an allograft biopsy, which demonstrated antibody mediated rejection along with the presence of extensive oxalate deposition in the tubules. Ultrastructural examination demonstrated spherical spiked particles in the glomerular capillary endothelium and the presence of tubulo-reticular inclusions suggestive of an active COVID-19 infection within the kidney. The intra-tubular oxalate deposition was considered to be the result of high dose, supplemental Vitamin C used as an immune booster in many patients with COVID - 19 infection in India. CONCLUSIONS: This case highlights the complex pathology that may be seen in following COVID-19 disease and the need for kidney biopsies in these patients to better understand the aetiology of disease.