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Introduction Solid organ transplant (SOT) recipients are at increased risk of Human Papillomavirus (HPV) persistent infection and disease. This study aimed to evaluate HPV seroprevalence, cervical HPV prevalence, genotype distribution, and frequency of HPV-related cervical lesions in SOT recipients in comparison to immunocompetent women. Methods Cross-sectional study including SOT and immunocompetent women aged 18 to 45 years who denied previous HPV-related lesions. Cervical samples were screened for HPV-DNA by a polymerase chain reaction (PCR)-based DNA microarray system (PapilloCheck®) and squamous intraepithelial lesions (SIL) by liquid-based cytology. A multiplexed pseudovirion-based serology assay (PsV-Luminex) was used to measure HPV serum antibodies. Results 125 SOT and 132 immunocompetent women were enrolled. Cervical samples were collected from 113 SOT and 127 immunocompetent women who had initiated sexual activity. HPV-DNA prevalence was higher in SOT than in immunocompetent women (29.6% vs. 20.2%, p = 0.112), but this difference was not statistically significant. High-risk (HR)-HPV was significantly more frequent in SOT than in immunocompetent women (19.4% vs. 7.9%, p = 0.014). Simultaneous infection with ≥2 HR-HPV types was found in 3.1% of SOT and 0.9% of immunocompetent women. HPV seropositivity for at least one HPV type was high in both groups: 63.8% of 105 SOT and 69.7% of 119 immunocompetent women (p = 0.524). Low-grade (LSIL) and high-grade SIL (HSIL) were significantly more frequent in SOT (9.7% and 5.3%, respectively) than in immunocompetent women (1.6% and 0.8%, respectively) (p = 0.001). Conclusions These results may reflect the increased risk of HPV persistent infection and disease progression in SOT women due to chronic immunosuppression.

Background Sickle cell disease (SCD) incurs vaso-occlusive episodes and organ damage, including nephropathy. Despite displaying characteristics of vascular dysfunction, SCD patients tend to present relatively lower systemic blood pressure (BP), via an unknown mechanism. We investigated associations between BP and renin-angiotensin-system (RAS) components in SCD and determined whether an inhibitor of angiotensin converting enzyme (ACE; often used to slow SCD glomerulopathy) further modulates BP and RAS components in a murine model of SCD. Methods BP was compared in human subjects and mice with/without SCD. Plasma angiotensin II, ACE and renin were measured by immunoassay. BP was reevaluated after treating mice with enalapril (25 mg/kg, 5x/week) for 5 weeks; plasma and organs were stored for angiotensin II and ACE activity measurement, and quantitative real-time PCR. Results Diastolic BP and systolic BP were significantly lower in patients and mice with SCD, respectively, compared to controls. Reduced BP was associated with increased plasma renin and markers of kidney damage (mice) in SCD, as well as significantly decreased plasma ACE concentrations and ACE enzyme activity. As expected, enalapril administration lowered BP, plasma angiotensin II and organ ACE activity in control mice. In contrast, enalapril did not further reduce BP or organ ACE activity in SCD mice; however, plasma angiotensin II and renin levels were found to be significantly higher in enalapril-treated SCD mice than those of treated control mice. Conclusion Relative hypotension was confirmed in a murine model of SCD, in association with decreased ACE concentrations in both human and murine disease. Given that ACE inhibition has an accepted role in decreasing BP, further studies should investigate mechanisms by which ACE depletion, via both Ang II-dependent and alternative pathways, could contribute to reduce BP in SCD and understand how ACE inhibition confers Ang II-independent benefits on kidney function in SCD.

Made available in DSpace on 2022-04-28T19:50:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 The Latin American Society of Nephrology and Hypertension conducted a prospective cohort, multinational registry of Latin American patients with kidney impairment associated to COVID-19 infection with the objective to describe the characteristics of acute kidney disease under these circumstances. The study was carried out through open invitation in order to describe the characteristics of the disease in the region. Eight-hundred and seventy patients from 12 countries were included. Median age was 63 years (54-74), most of patients were male (68.4%) and with diverse comorbidities (87.2%). Acute kidney injury (AKI) was hospital-acquired in 64.7% and non-oliguric in 59.9%. Multiorgan dysfunction syndrome (MODS) due to COVID-19 and volume depletion were the main factors contributing to AKI (59.2% and 35.7% respectively). Kidney replacement therapy was started in 46.2%. Non-recovery of renal function was observed in 65.3%. 71.5% of patients were admitted to ICU and 72.2% underwent mechanical ventilation. Proteinuria at admission was present in 62.4% of patients and proteinuria during hospital-stay occurred in 37.5%. Those patients with proteinuria at admission had higher burden of comorbidities, higher baseline sCr, and MODS was severe. On the other hand, patients with de novo proteinuria had lower incidence of comorbidities and near normal sCr at admission, but showed adverse course of disease. COVID-19 MODS was the main cause of AKI in both groups. All-cause mortality of the general population was 57.4%, and it was associated to age, sepsis as cause of AKI, severity of condition at admission, oliguria, mechanical ventilation, non-recovery of renal function, in-hospital complications and hospital stay. In conclusion, our study contributes to a better knowledge of this condition and highlights the relevance of the detection of proteinuria throughout the clinical course. Department of Nephrology Universidad de la República Clinical Hospital of Botucatu School Medicine HCFMB University of Sao Paulo State UNESP Hospital Obrero #2-C. N.S. School of Medicine Universidad Mayor de San Simón Universidad Simón Bolívar Hospital Nacional Arzobispo Loayza Servicio de Nefrología School of Medicine University of São Paulo Division of Nephrology Hospital Civil de Guadalajara Departamento de Nefrología Hospital General de Agudos Dr Cosme Argerich Serviço de Nefrología, Jau Santa Casa de Jau Department of Nephrology Hospital Provincial Nefrologia Pontificia Universidade Catolica do Rio de Janeiro Internal Medicine University of Rio de Janeiro Nephrology Hospital Universitario Dr JoséEleuterio González Centros de Diagnóstico y Medicina Avanzada Servicio de Nefrología Hospital Italiano Departamento de Medicina Interna Salud Renal MSP Department of Nephrology Pontificia Universidad Católica de Chile Servicio de Nefrología Hospital Español Departamento de Nefrología Hospital de Especialidades de las Fuerzas Armadas Servicio de Nefrología y Diálisis Hospital Rojas Nephrology School of Medicine University of São Paulo Hospital Federal Cardozo Fontes Universidade de Sá Departamento de Nefrología Hospital Regional General Dr Carlos Mac Gregor Sanchez Navarro Departamento de Nefrología Hospital de Pediatría CMN Siglo XXI Department of Nephrology School of Medicine University of Sao Paulo Centro Infantil del Riñón, Tucumán Hospital Regional de Ica Hospital Nacional Hipólito Unanue Clinical Hospital of Botucatu School Medicine HCFMB University of Sao Paulo State UNESP

PLOS ONE 17(1), e0262667 (2022). doi:10.1371/journal.pone.0262667, Published by PLOS, San Francisco, California, US

Polycystic kidney disease (PKD) is the most common genetic cause of kidney failure in humans. Among the various PKD-related molecules, PKD2L1 forms cation channels, but its physiological importance is obscure. In the present study, we established a transgenic mouse line by overexpressing the dominant-negative form of the mouse PKD2L1 gene (i.e., lacking the pore-forming domain). The resulting PKD2L1del-Tg mice exhibited supraventricular premature contraction, as well as enhanced sensitivity to β-adrenergic stimulation and unstable R-R intervals in electrocardiography. During spontaneous atrial contraction, PKD2L1del-Tg atria showed enhanced sensitivity to isoproterenol, norepinephrine, and epinephrine. Action potential recording revealed a shortened action potential duration in PKD2L1del-Tg atria in response to isoproterenol. These findings indicated increased adrenergic sensitivity in PKD2L1del-Tg mice, suggesting that PKD2L1 is involved in sympathetic regulation.

d-allulose is a rare sugar that has been reported to possess anti-hyperglycemic effects. In the present study, we hypothesized that d-allulose is effective in attenuating the progression of diabetic nephropathy in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model of type 2 diabetes mellitus. Drinking water with or without 3% d-allulose was administered to OLETF rats for 13 weeks. Long-Evans Tokushima Otsuka rats that received drinking water without d-allulose were used as non-diabetic control rats. d-allulose significantly attenuated the increase in blood glucose levels and progressive mesangial expansion in the glomerulus, which is regarded as a characteristic of diabetic nephropathy, in OLETF rats. d-allulose also attenuated the significant increases in renal IL-6 and tumor necrosis factor-α mRNA levels in OLETF rats, which is a proinflammatory parameter. Additionally, we showed that d-allulose suppresses mesangial matrix expansion, but its correlation with suppressing renal inflammation in OLETF rats should be investigated further. Collectively, our results support the hypothesis that d-allulose can prevent diabetic nephropathy in rats.

Purpose Taiwan is among the countries with the highest global prevalence of chronic renal disease. However, when advised to undergo dialysis therapy, patients with end-stage renal disease often hesitate. Attitudes toward medication and Taiwanese cultures are the main reasons for this delay, and delay conditioning requires urgent dialysis. This study aimed to explore the experience of urgent dialysis patients with end-stage renal disease. Methods This study used a purposive sampling strategy with semi-structured interviews leading to in-depth interviews. Patients were recruited from the nephrology ward and hemodialysis center of a northern Taiwanese hospital. All participants were aged over 20 years with end-stage renal disease. Although advised by doctors to undergo dialysis, these patients delayed their treatment and later suffered severe complications. After emergency hospitalization, the patients’ condition improved. Data were analyzed by content analysis. Results Interviews with five participants suffering from end-stage renal disease identified six themes: “experiencing a sudden jolt,” “silent organ brings the most pain,” “feeling angry: why me?,” “facing a dilemma,” “taking risks,” and “facing consequences.” Conclusion These patients delayed their treatment and later suffered severe complications, even though doctors advised them to undergo dialysis. Health professionals play an important role in communication and coordination, assisting patients in coping with their situation. The analysis of the reasons for the delay in undergoing dialysis, therefore, should help health professionals provide proper guidance and care to patients who are faced with the decision to accept dialysis treatment.

Contains fulltext : 244767.pdf (Publisher’s version ) (Open Access) Glomerulonephritis is an acquired serious glomerular disease, which involves the interplay of many factors such as cytokines, chemokines, inflammatory cells, and heparan sulfate (HS). We previously showed that blocking of inflammatory heparan sulfate domains on cultured glomerular endothelium by specific anti-HS single chain antibodies reduced polymorphonuclear cell (PMN) adhesion and chemokine binding. We hypothesized that injection of anti-HS antibodies in PMN-driven experimental glomerulonephritis should reduce glomerular influx of PMNs and thereby lead to a better renal outcome. In contrast to our hypothesis, co-injection of anti-HS antibodies did not alter the final outcome of anti-glomerular basement membrane (anti-GBM)-induced glomerulonephritis. Glomerular PMN influx, normally peaking 2 hours after induction of glomerulonephritis with anti-GBM IgG was not reduced by co-injection of anti-HS antibodies. Four days after induction of glomerulonephritis, albuminuria, renal function, glomerular hyalinosis and fibrin deposition were similar in mice treated and not treated with anti-HS antibodies. Interestingly, we observed transient effects in mice co-injected with anti-HS antibodies compared to mice that did not receive anti-HS antibodies: (i) a decreased renal function 2 hours and 1 day after induction of glomerulonephritis; (ii) an increased albuminuria after 2 hours and 1 day; (iii) an increased glomerular fibrin deposition after 1 day; (iv) a reduced glomerular macrophage influx after 1 day; (v) a sustained glomerular presence of PMNs at day 1 and 4, accompanied by an increased renal expression of IL-6, CXCL1, ICAM-1, L-selectin, CD11b and NF-κB. The mechanism underlying these observations induced by anti-HS antibodies remains unclear, but may be explained by a temporarily altered glycocalyx and/or altered function of PMNs due to the binding of anti-HS antibodies. Nevertheless, the evaluated anti-HS antibodies do not show therapeutic potential in anti-GBM-induced glomerulonephritis. Future research should evaluate other strategies to target HS domains involved in inflammatory processes during glomerulonephritis.

Diabetic nephropathy is one of the common microvascular complications of diabetes. Iron death is a recently reported way of cell death. To explore the effects of iron death on diabetic nephropathy, iron death score of diabetic nephropathy was analyzed based on the network and pathway levels. Furthermore, markers related to iron death were screened. Using RNA-seq data of diabetic nephropathy, samples were clustered uniformly and the disease was classified. Differentially expressed gene analysis was conducted on the typed disease samples, and the WGCNA algorithm was used to obtain key modules. String database was used to perform protein interaction analysis on key module genes for the selection of Hub genes. Moreover, principal component analysis method was applied to get transcription factors and non-coding genes, which interact with the Hub gene. All samples can be divided into two categories and principal component analysis shows that the two categories are significantly different. Hub genes (FPR3, C3AR1, CD14, ITGB2, RAC2 and ITGAM) related to iron death in diabetic nephropathy were obtained through gene expression differential analysis between different subtypes. Non-coding genes that interact with Hub genes, including hsa-miR-572, hsa-miR-29a-3p, hsa-miR-29b-3p, hsa-miR-208a-3p, hsa-miR-153-3p and hsa-miR-29c-3p, may be related to diabetic nephropathy. Transcription factors HIF1α, KLF4, KLF5, RUNX1, SP1, VDR and WT1 may be related to diabetic nephropathy. The above factors and Hub genes are collectively involved in the occurrence and development of diabetic nephropathy, which can be further studied in the future. Moreover, these factors and genes may be potential target for therapeutic drugs.

Made available in DSpace on 2022-04-28T19:47:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-01 Background Atypical Hemolytic Uremic Syndrome (aHUS) is an ultra-rare disease that potentially leads to kidney graft failure due to ongoing Thrombotic Microangiopathy (TMA). The aim was evaluating the frequency of TMA after kidney transplantation in patients with aHUS in a Brazilian cohort stratified by the use of the specific complement-inhibitor eculizumab. Methods This was a multicenter retrospective cohort study including kidney transplant patients diagnosed with aHUS. We collected data from 118 transplant centers in Brazil concerning aHUS transplanted patients between 01/01/2007 and 12/31/2019. Patients were stratified into three groups: no use of eculizumab (No Eculizumab Group), use of eculizumab for treatment of after transplantation TMA (Therapeutic Group), and use of eculizumab for prophylaxis of aHUS recurrence (Prophylactic Group). Results Thirty-eight patients with aHUS who received kidney transplantation were enrolled in the study. Patients' mean age was 30 years (24-40), and the majority of participants was women (63% of cases). In the No Eculizumab Group (n = 11), there was a 91% graft loss due to the TMA. The hazard ratio of TMA graft loss was 0.07 [0.01-0.55], p = 0.012 in the eculizumab Prophylactic Group and 0.04 [0.00-0.28], p = 0.002 in the eculizumab Therapeutic Group. Conclusion The TMA graft loss in the absence of a specific complement-inhibitor was higher among the Brazilian cohort of kidney transplant patients. This finding reinforces the need of eculizumab use for treatment of aHUS kidney transplant patients. Cost optimization analysis and the early access to C5 inhibitors are suggested, especially in low-medium income countries. Department of Internal Medicine-UNESP Univ Estadual Paulista Departamento de Pediatria Hospital de Clinicas Universidade Estadual de Campinas, SP Transplant Unit São Jose Rio Preto/FAMERP Transplant Unit Santa Casa de Misericórdia de Porto Alegre-ISCMPA Santa Casa de Belo Horizonte Department of Internal Medicine-UNESP Univ Estadual Paulista

Appropriate dietary adjustment in patients with chronic kidney disease (CKD) is important, and nutritional guidelines recommend different dietary management depending on the CKD stage. However, there is no study, to our knowledge, of the characteristics of dietary intake according to CKD stages. We tried to assess the comparison of nutritional intake according to CKD stages. A cross-sectional study was conducted to reveal the characteristics of dietary intake among patients with CKD based on the Korean National Health and Nutritional Examination Survey between 2011 and 2014. Of 16,878 participants, we classified non-CKD (n = 14,952) and CKD (n = 1,926), which was stratified into five groups (I, II, IIIa, IIIb, and IV–V). We investigated the characteristics of dietary intake, such as energy, water, protein, fat, carbohydrate, sodium, potassium, calcium, and phosphorus, according to stage of CKD. We also explored nutritional intake according to CKD stage among patients with early CKD (stage I and II) and advanced CKD (stage IIIa, IIIb, and IV–V). Intake of majority of nutrients and energy tended to be decreased as CKD progressed. In early CKD stage, intake of energy, water, protein, fat, carbohydrate, potassium, calcium and phosphorus seemed to be statistically significant decreased as CKD progressed. In advanced CKD stage, intake of potassium and calcium seemed to be decreased as CKD progressed, but the intake of energy was about to be lower limit. Appropriate dietary education and CKD recognition are needed to improve nutritional intake depending on the CKD stage.

Introduction After stage 3 CKD, the risk of adverse cardiovascular events increased significantly. Therefore, we performed a meta-analysis to investigate the cardiovascular protective effect of SGLT2 inhibitors in patients with stage 3/4 CKD with different baseline kidney function or underlying diseases. Method To identify eligible trials, we systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021. The primary cardiovascular outcome was defined as a combination of cardiovascular mortality and hospitalization due to heart failure. Baseline kidney functions (stage 3a CKD: eGFR45-59mL/min per 1.73m2, stage 3b CKD: eGFR30-44mL/min per 1.73m2, stage 4 CKD: eGFR Results In the present study, a total of eleven trials were included that involved a total of 27,823 patients with stage 3/4 CKD. The treatment and control groups contained 14,451 and 13,372 patients, respectively. In individuals with stage 3/4 CKD, SGLT2 inhibitors reduced the risk of primary cardiovascular outcomes by 26% (HR 0.74, [95% CI 0.69–0.80], I2 = 0.00%), by 30% in patients with stage 3a CKD (HR 0.70, [95% CI 0.59–0.84], I2 = 18.70%), by 23% in patients with stage 3b CKD (HR 0.77, [95% CI 0.66–0.90], I2 = 2.12%), and by 29% in patients with stage 4 CKD (HR 0.71, [95% CI 0.53–0.96], I2 = 0.00%). The risk of primary outcomes was reduced by 29% (HR 0.71, [95% CI 0.63–0.80], I2 = 0.00%) in patients with type 2 diabetes, by 28% (HR 0.72, [95% CI 0.56–0.93], I2 = 37.23%) in patients with heart failure with preserved ejection fraction, by 21% (HR 0.79, [95% CI 0.70–0.89], I2 = 0.00%) in patients with heart failure with reduced ejection fraction, and by 25% (HR 0.75, [95% CI 0.64–0.88], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease. Conclusions For stage 3/4 CKD, SGLT2 inhibitors significantly decreased the risk of primary cardiovascular outcomes, and these benefits were consistent throughout the spectrum of different kidney functions, even in stage 4 CKD. There was no evidence of increased adverse outcomes across different baseline clinical complications, such as type 2 diabetes, heart failure, or atherosclerotic cardiovascular disease.

Aims Impaired renal function is a major contributor to the low proportion of mineralocorticoid receptor antagonist (MRA) treatment in patients with heart failure with reduced ejection fraction (HFrEF). Our aims were to investigate the impact of MRA treatment on all-cause mortality and worsening renal function (WRF) in patients with HFrEF and moderately impaired renal function. Methods Retrospective data between 2010–2018 on HFrEF patients from a single-centre hospital with estimated glomerular renal function (eGFR) < 60 ml/min/1.73 m2 were analysed. WRF was defined as a decline of by eGFR ≥ 20%. Results 416 patients were included, 131 patients on MRA and 285 without MRA, mean age was 77 years (SD ± 9) and 82 years (SD ± 9), respectively. Median follow-up was 2 years. 128 patients (32%) experienced WRF, 25% in the MRA group and 30% in patients without MRA (p = 0.293). In multivariable analysis, hospitalization for heart failure and systolic blood pressure were associated with WRF (p = 0.015 and p = Conclusion In this cohort of elderly HFrEF patients with moderately impaired renal function, MRA did not increase risk for WRF or all-cause mortality.

Background Upper urinary tract urothelial carcinomas are relatively rare and have a cancer-specific survival rate of 20%–30%. The current gold standard treatment for nonmetastatic high-grade urinary tract urothelial carcinoma is radical nephroureterectomy with bladder cuff resection. Objective This study aimed to compare conditional cancer-specific survival between open radical nephroureterectomy and laparoscopic radical nephroureterectomy in patients with nonmetastatic stage pT3-4 or TxN(+) locally advanced urinary tract urothelial carcinoma from five tertiary centers. Methods The medical records of 723 patients were retrospectively reviewed. The patients had locally advanced and nodal staged tumors and had undergone open radical nephroureterectomy (n = 388) or laparoscopic radical nephroureterectomy (n = 260) at five tertiary Korean institutions from January 2000 and December 2012. To control for heterogenic baseline differences between the two modalities, propensity score matching and subgroup analysis were conducted. Conditional survival analysis was also conducted to determine survival outcome and to overcome differences in follow-up duration between the groups. Results During the median 50.8-month follow up, 255 deaths occurred. In univariate analysis, significant factors affecting cancer-specific survival (e.g., age, history of bladder cancer, American Society of Anesthesiologists score, pathological N stage, and presence of lymphovascular invasion and carcinoma in situ) differed in each subsequent year. The cancer-specific survival between patients treated with open radical nephroureterectomy and laparoscopic radical nephroureterectomy was not different between patients with and without a history of bladder cancer. After adjusting baseline differences between the two groups by using propensity score matching, both groups still had no significant differences in cancer-specific survival. Conclusion The two surgical modalities showed no significant differences in the 5-year cancer-specific survival in patients with locally advanced urinary tract urothelial carcinoma.

ObjectiveTo determine whether bladder size is associated with an unfavorable neonatal outcome, in the case of first-trimester megacystis.Materials and methodsThis was a retrospective observational study between 2009 and 2019 in two prenatal diagnosis centers. The inclusion criterion was an enlarged bladder (> 7 mm) diagnosed at the first ultrasound exam between 11 and 13+6weeks of gestation. The main study endpoint was neonatal outcome based on bladder size. An adverse outcome was defined by the completion of a medical termination of pregnancy, the occurrence of in utero fetal death, or a neonatal death. Neonatal survival was considered as a favorable outcome and was defined by a live birth, with or without normal renal function, and with a normal karyotype.ResultsAmong 75 cases of first-trimester megacystis referred to prenatal diagnosis centers and included, there were 63 (84%) adverse outcomes and 12 (16%) live births. Fetuses with a bladder diameter of less than 12.5 mm may have a favorable outcome, with or without urological problems, with a high sensitivity (83.3%) and specificity (87.3%), area under the ROC curve = 0.93, 95% CI (0.86–0.99), p< 0.001. Fetal autopsy was performed in 52 (82.5%) cases of adverse outcome. In the 12 cases of favorable outcome, pediatric follow-up was normal and non-pathological in 8 (66.7%).ConclusionBladder diameter appears to be a predictive marker for neonatal outcome. Fetuses with smaller megacystis (7–10 mm) have a significantly higher chance of progressing to a favorable outcome. Urethral stenosis and atresia are the main diagnoses made when first-trimester megacystis is observed. Karyotyping is important regardless of bladder diameter.

Background The conventional one-size-fits-all approach has been criticized for almost all drugs used especially for chronic diseases, including gout. The present study was aimed to explore the need of individualization and optimization of the dose of anti-gout medications among gout patients. Methods Cross-sectional study was carried out among 384 randomly selected new gout patients visiting two gout treatment centers at Lalitpur Metropolitan City, Nepal and who were taking antigout medications. Patients not taking anti-gout medications and not showing willingness to participate were excluded. The eGFR was calculated with the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation (2009). Doses to be individualized were decided based on the Renal Drug Handbook and verified with the BNF 80. Data were analyzed via R 4.0.3 by applying the multinomial logistic regression to analyze statistical significance of risk with various predictors, and considering a p-value Results The high risk of progression to CKD increased in the age range 54–63 and ≥84 years by 17.77 and 43.02 times, respectively. Also, high risk increased by 29.83 and 20.2 times for the overweight and the obese respectively. Aceclofenac 100mg was prescribed for maximum patients (30.5%). Need of dose individualization was realized in 30 patients, with maximum (7) in case of etoricoxib 90mg. Various glucocorticoids were prescribed for 36.9% patients, out of whom 3.8%required dose individualization and 15.9% patients with xanthine oxidase inhibitors, out of whom 1.3% required dose individualization. Conclusion Thirty cases required dose individualization, which was although minimal but could have meaningful impact on the clinical success of the individual patient. Based on the recommendation on dose individualization, those patients could be optimized on their therapy on future follow ups.

Purpose The purpose of this study was to compare the clinical characteristics and the survival of CHEK2 mutation positive and CHEK2 mutation negative patients diagnosed with bladder or kidney cancer. Materials and methods 1016 patients with bladder and 402 cases with kidney cancer and 8302 controls were genotyped for four CHEK2 variants: 1100delC, del5395, IVS2+1G>A and I157T. Predictors of survival were determined among CHEK2 pathogenic variant carriers using the Cox proportional hazards model. The median follow-up was 17.5 years. Covariates included age (≤60; >61 years), sex (female; male), clinical characteristics (stage: TNM, grade, histopathological type), smoking status (non-smoking; smoking) and cancer family history (negative; positive). Results We found no impact of CHEK2 mutations on bladder or kidney cancer survival. However, we observed a possible increased survival in the subgroup of patients with stage T1 bladder cancer with CHEK2 mutations but this did not meet statistical significance (HR = 0.14; 95% CI 0.02–1.04; p = 0.055). Moreover, we observed that the missense mutations were more frequent in the low grade invasive bladder cancer patient group (OR = 7.9; 95% CI 1.50–42.1; p = 0.04) and in patients with bladder cancer with stage Ta (OR = 2.4; 95% CI 1.30–4.55; p = 0.006). The different results where missense mutations occurs less often we observed among patients with high grade invasive bladder cancer (OR = 0.12; 95% CI 0.02–0.66; p = 0.04) and those with stage T1 disease (OR = 0.2; 95% CI 0.07–0.76; p = 0.01). Our investigations revealed that any mutation in CHEK2 occurs more often among patients with stage Ta bladder cancer (OR = 2.0; 95% CI 1.19–3.47; p = 0.01) and less often in patients with stage T1 disease (OR = 0.31; 95% CI 0.12–0.78; p = 0.01). In the kidney cancer patients, truncating mutations were present more often in the group with clear cell carcinoma GII (OR = 8.0; 95% CI 0.95–67.7; p = 0.05). The 10-year survival for all CHEK2 mutation carriers with bladder cancer was 33% and for non-carriers 11% (p = 0.15). The 10-year survival for CHEK2 mutation carriers with kidney cancer 34% and for non-carriers 20% (p = 0.5). Conclusion CHEK2 mutations were not associated with any change in bladder or kidney cancer survival regardless of their age, sex, smoking status and family history. We observed a potentially protective effect of CHEK2 mutations on survival for patients with stage T1 bladder cancer. CHEK2 missense mutations were more common among patients with low grade invasive bladder cancer and in patients with stage Ta diease. The frequencies of the I157T CHEK2 pathogenic variant were less in patients with high grade invasive bladder cancer and those with stage T1 disease. Among patients with bladder cancer with stage Ta disease, the OR for any mutation in CHEK2 was 2.0 but for those with stage T1 disease, the OR was 0.3. We observed truncating CHEK2 mutations were associated with kidney cancer patients with GII clear cell carcinoma.

Objectives To investigate whether partner bereavement is associated with adverse cardiovascular and kidney-related events in people with reduced kidney function. Design Two parallel matched cohort studies using linked routinely collected health data. Setting England (general practices and hospitals using linked Clinical Practice Research Datalink, Hospital Episode Statistics, and Office of National Statistics) and Denmark (hospitals and community pharmacies using the Danish National Patient, Prescription and Education Registries and the Civil Registration System). Participants Bereaved people with reduced kidney function (estimated glomerular filtration rate (eGFR) 2 (England) or hospital-coded chronic kidney disease (Denmark)) and non-bereaved people with reduced kidney function similarly defined, matched on age, sex, general practice (England), and county of residence (Denmark) and followed-up from the bereavement date of the exposed person. Main outcome measures Cardiovascular disease (CVD) or acute kidney injury (AKI) hospitalization, or death. Results In people with reduced kidney function, we identified 19,820 (England) and 5,408 (Denmark) bereaved individuals and matched them with 134,828 (England) and 35,741 (Denmark) non-bereaved individuals. Among the bereaved, the rates of hospitalizations (per 1000 person-years) with CVD were 31.7 (95%-CI: 30.5–32.9) in England and 78.8 (95%-CI: 74.9–82.9) in Denmark; the rates of hospitalizations with AKI were 13.2 (95%-CI: 12.5–14.0) in England and 11.2 (95%-CI: 9.9–12.7) in Denmark; and the rates of death were 70.2 (95%-CI: 68.5–72.0) in England and 126.4 (95%-CI: 121.8–131.1) in Denmark. After adjusting for confounders, we found increased rates of CVD (England, HR 1.06 [95%-CI: 1.01–1.12]; Denmark, HR 1.10 [95%-CI: 1.04–1.17]), of AKI (England, HR 1.20 [95%-CI: 1.10–1.31]; Denmark HR 1.36 [95%-CI: 1.17–1.58]), and of death (England, HR 1.10 [95%-CI: 1.05–1.14]; Denmark HR 1.20 [95%-CI: 1.15–1.25]) in bereaved compared with non-bereaved people. Conclusions Partner bereavement is associated with an increased rate of CVD and AKI hospitalization, and death in people with reduced kidney function. Additional supportive care for this at-risk population may help prevent serious adverse events.

Background: Reduced free thiols in plasma are indicative of oxidative stress, which is an important contributor to ischaemia-reperfusion injury (IRI) in kidney transplantation leading to kidney damage and possibly delayed graft function (DGF). In a post-hoc, exploratory analysis of the randomised controlled CONTEXT trial, we investigated whether higher (i.e. less oxidised) plasma levels of free thiols as a biomarker of reduced oxidative stress are associated with a better initial graft function or a higher GFR.Methods: Free thiol levels were measured in plasma at baseline, 30 and 90 minutes after reperfusion of the kidney as well as at Day 1, Day 5 and twelve months after kidney transplantation in 217 patients from the CONTEXT study. Free thiol levels were compared to the kidney graft function measured as the estimated time to a 50% reduction in plasma creatinine (tCr50), the risk of DGF and measured GFR (mGFR) at Day 5 and twelve months after transplantation.Results: Higher levels of free thiols at Day 1 and Day 5 are associated with higher mGFR at Day 5 (pConclusion: Higher levels of plasma free thiols at Day 1 and Day 5, which are reflective of lower levels of oxidative stress, are associated with better early and late graft function in recipients of a kidney graft from deceased donors.Trial registration: ClinicalTrials.gov Identifier: NCT01395719. Background Reduced free thiols in plasma are indicative of oxidative stress, which is an important contributor to ischaemia-reperfusion injury (IRI) in kidney transplantation leading to kidney damage and possibly delayed graft function (DGF). In a post-hoc, exploratory analysis of the randomised controlled CONTEXT trial, we investigated whether higher (i.e. less oxidised) plasma levels of free thiols as a biomarker of reduced oxidative stress are associated with a better initial graft function or a higher GFR. Methods Free thiol levels were measured in plasma at baseline, 30 and 90 minutes after reperfusion of the kidney as well as at Day 1, Day 5 and twelve months after kidney transplantation in 217 patients from the CONTEXT study. Free thiol levels were compared to the kidney graft function measured as the estimated time to a 50% reduction in plasma creatinine (tCr50), the risk of DGF and measured GFR (mGFR) at Day 5 and twelve months after transplantation. Results Higher levels of free thiols at Day 1 and Day 5 are associated with higher mGFR at Day 5 (p

Introduction Cauda Equina Syndrome (CES) can cause persisting life-changing dysfunction. There is scarce literature regarding the long-term assessment of CES symptoms, and rarer still is the impact of these symptoms on mental wellbeing investigated. This study assessed the long-term patient reported mental wellbeing outcomes of post-operative CES patients. Methods Patients who underwent surgery for CES between August 2013 and November 2014 were identified using an ethically approved database. They then completed validated questionnaires over the telephone assessing their mental and physical functioning (Short-Form 12 Questionnaire), generating the Physical Component Summary (PCS) and Mental Component Summary (MCS). Bladder, bowel and sexual function were also assessed using validated questionnaires. MCS scores were compared to both the Scottish mean and previously published cut-offs indicating patients at risk of depression. Correlations of MCS with bladder, bowel, sexual and physical dysfunction were examined and multifactorial regression to predict MCS from these variables analysed. Independent t-tests assessed the mean difference in MCS between patients presenting with incomplete CES (CES-I) and CES with retention (CES-R) and between those with radiologically confirmed and impending CES. Results Forty-six participants with a mean follow-up time of 43 months completed the study. The mean (±SD) MCS was 49 (±11.8) with 22% demonstrating poor mental health related quality of life in comparison to the Scottish mean. Overall, 37% had scores consistent with being at risk for depression with in the last 30 days, and 45% within the last 12 months. MCS was significantly correlated with Urinary Symptoms Profile (USP) score (-0.608), NBDS score (-0.556), ASEX score (-0.349) and PCS score (0.413) with worse bladder, bowel, sexual and physical dysfunction associated with worse MCS score. Multifactorial regression analysis demonstrated both urinary (USP score p = 0.031) and bowel function (NBDS score p = 0.009) to be significant predictive variables of mental health related quality of life. There were no significant mean differences in MCS between those presenting with CES-I and CES-R or those with radiologically complete and impending CES. Discussion This study demonstrates a high frequency of being at risk for depression in patients with CES and identifies outcome measures (physical, sexual and more so bladder and bowel dysfunction) associated with poorer mental wellbeing. Our large cohort and long follow-up highlight that CES patients should be considered at risk of depression, and the need to consider mental health outcomes following CES surgery.

Uricase-deficient rats could be one of the optimal model animals to study hyperuricemia. The present study aimed to find the biological differences between uricase-deficient (Kunming-DY rats) and wild-type male rats. Uricase-deficient rats and wild-type rats were commonly bred. Their body weight, water and food consumption, 24-h urine and feces, uric acid in serum and organs, and serum indexes were recorded or assayed. Organs, including the heart, liver, spleen, lung, kidney, thymus, stomach, duodenum, and ileum, were examined using a routine hematoxylin-eosin staining assay. We found that the growth of male uricase-deficient rats was retarded. These rats excreted more urine than the wild-type rats. Their organ indexes (organ weight body weight ratio), of the heart, liver, kidney, and thymus significantly increased, while those of the stomach and small intestine significantly decreased. The uricase-deficient rats had a significantly higher level of serum uric acid and excreted more uric acid via urine at a higher concentration. Except for the liver, uric acid increased in organs and intestinal juice of uricase-deficient rats. Histological examination of the uricase-deficient rats showed mild injuries to the heart, liver, spleen, lung, kidney, thymus, stomach, duodenum, and ileum. Our results suggest that uricase-deficient rats have a different biological pattern from the wild-type rats. Uricase deficiency causes growth retardation of young male rats and the subsequent increase in serum uric acid results in mild organs injuries, especially in the kidney and liver.

It can be difficult for anesthesiologists to determine the optimal dose of propofol for end-stage kidney disease (ESKD) patients due to changes in drug disposition. The purpose of this study was to evaluate the potency of propofol for inducing loss of consciousness in ESKD patients. Patients with normal kidney function (Control group, n = 15), those with ESKD (ESKD group, n = 15), and those with ESKD undergoing cervical epidural anesthesia (ESKD-CEB group, n = 15) were administered propofol by target-controlled infusion (TCI) using the Schneider model. The effect-site concentration (Ce) of propofol started at 0.5 μg/ml and increased in increments of 0.5 μg/ml until the patient did not respond to verbal commands. The relationship between the probability (P) of loss of consciousness and the Ce of propofol was analyzed in each group using logistic regression. The Ce values of propofol at the time of loss of consciousness were 4.3 ± 0.9, 3.7 ± 0.9, and 3.3 ± 1.0 μg/ml for the Control, ESKD, and ESKD-CEB* groups, respectively (*significant difference vs. control, P < 0.05). The estimated Ce50 values for lost ability to respond to verbal command were 4.56, 3.75, and 3.21 μg/ml for the Control, ESKD, and ESKD-CEB groups, respectively. In conclusion, when inducing anesthesia in ESKD patients, we recommend using an initial dose similar to that of patients with normal kidney function, or rather starting with a lower dose.

AimA recent meta-analysis of genome-wide linkage studies (GWLS) has identified multiple genetic regions suggestive of linkage with DN harboring hundreds of genes. Moving this number of genetic loci forward into biological insight is truly the next step. Here, we approach this challenge with a gene ontology (GO) analysis in order to yield biological and functional role to the genes, an over-representation test to find which GO terms are enriched in the gene list, pathway analysis, as well as protein network analysis.MethodGO analysis was performed using protein analysis through evolutionary relationships (PANTHER) version 14.0 software and P-values less than 0.05 were considered statistically significant. GO analysis was followed by over-representation test for the identification of enriched terms. Statistical significance was calculated by Fisher’s exact test and adjusted using the false discovery rate (FDR) for correction of multiple tests. Cytoscape with the relevant plugins was used for the construction of the protein network and clustering analysis.ResultsThe GO analysis assign multiple GO terms to the genes regarding the molecular function, the biological process and the cellular component, protein class and pathway analysis. The findings of the over-representation test highlight the contribution of cell adhesion regarding the biological process, integral components of plasma membrane regarding the cellular component, chemokines and cytokines with regard to protein class, while the pathway analysis emphasizes the contribution of Wnt and cadherin signaling pathways.ConclusionsOur results suggest that a core feature of the pathogenesis of DN may be a disturbance in Wnt and cadherin signaling pathways, whereas the contribution of chemokines and cytokines need to be studied in additional studies.

Background Hepatic and biliary diseases are prevalent worldwide, but the majority of people lack access to diagnostic medical imaging for their assessment. The liver and gallbladder are readily amenable to sonographic examination, and ultrasound is a portable, cost-effective imaging modality suitable for use in rural and underserved areas. However, the deployment of ultrasound in these settings is limited by the lack of experienced sonographers to perform the exam. In this study, we tested an asynchronous telediagnostic system for right upper quadrant abdominal ultrasound examination operated by individuals without prior ultrasound experience to facilitate deployment of ultrasound to rural and underserved areas. Methods The teleultrasound system utilized in this study employs volume sweep imaging and a telemedicine app installed on a tablet which connects to an ultrasound machine. Volume sweep imaging is an ultrasound technique in which an individual scans the target region utilizing preset ultrasound sweeps demarcated by easily recognized external body landmarks. The sweeps are saved as video clips for later interpretation by an experienced radiologist. Teleultrasound scans from a Peruvian clinic obtained by individuals without prior ultrasound experience were sent to the United States for remote interpretation and quality assessment. Standard of care comparison was made to a same-day ultrasound examination performed by a radiologist. Results Individuals without prior ultrasound experience scanned 144 subjects. Image quality was rated “poor” on 36.8% of exams, “acceptable” on 38.9% of exams, and “excellent” on 24.3% of exams. Among telemedicine exams of “acceptable” or “excellent” image quality (n = 91), greater than 80% of the liver and gallbladder were visualized in the majority of cases. In this group, there was 95% agreement between standard of care and teleultrasound on whether an exam was normal or abnormal, with a Cohen’s kappa of 0.84 (95% CI 0.7–0.98, p Conclusion This asynchronous telediagnostic system allows individuals without prior ultrasound experience to effectively scan the liver, gallbladder, and right kidney with a high degree of agreement with standard of care ultrasound. This system can be deployed to improve access to diagnostic imaging in low-resource areas.

Background Recommendations regarding dialysis education and treatment are provided in various (inter)national guidelines, which should ensure that these are applied uniformly in nephrology and dialysis centers. However, there is much practice variation which could be explained by good practices: practices developed by local health care professionals, which are not evidence-based. Because an overview of good practices is lacking, we performed a scoping review to identify and summarize the available good practices for dialysis education, treatment, and eHealth. Methods Embase, Pubmed, the Cochrane Library, CINAHL databases and Web of Science were searched for relevant articles using all synonyms for the words ‘kidney failure’, ‘dialysis’, and ‘good practice’. Relevant articles were structured according to the categories dialysis education, dialysis treatment or eHealth, and assessed for content and results. Results Nineteen articles (12 for dialysis education, 3 for dialysis treatment, 4 for eHealth) are identified. The good practices for education endorse the importance of providing complete and objective predialysis education, assisting peritoneal dialysis (PD) patients in adequately performing PD, educating hemodialysis (HD) patients on self-management, and talking with dialysis patients about their prognosis. The good practices for dialysis treatment focus mainly on dialysis access devices and general quality improvement of dialysis care. Finally, eHealth is useful for HD and PD and affects both quality of care and health-related quality of life. Conclusion Our scoping review identifies 19 articles describing good practices and their results for dialysis education, dialysis treatment, and eHealth. These good practices could be valuable in addition to guidelines for increasing shared-decision making in predialysis education, using patients’ contribution in the implementation of their dialysis treatment, and advanced care planning.

Introduction Many studies have explored patients’ experiences of dialysis and other treatments for kidney failure. This is the first qualitative multi-site international study of how staff perceive the process of a patient’s transition from peritoneal dialysis to in-centre haemodialysis. Current literature suggests that transitions are poorly coordinated and may result in increased patient morbidity and mortality. This study aimed to understand staff perspectives of transition and to identify areas where clinical practice could be improved. Methods Sixty-one participants (24 UK and 37 Australia), representing a cross-section of kidney care staff, took part in seven focus groups and sixteen interviews. Data were analysed inductively and findings were synthesised across the two countries. Results For staff, good clinical practice included: effective communication with patients, well planned care pathways and continuity of care. However, staff felt that how they communicated with patients about the treatment journey could be improved. Staff worried they inadvertently made patients fear haemodialysis when trying to explain to them why going onto peritoneal dialysis first is a good option. Despite staff efforts to make transitions smooth, good continuity of care between modalities was only reported in some of the Australian hospitals where, unlike the UK, patients kept the same consultant. Timely access to an appropriate service, such as a psychologist or social worker, was not always available when staff felt it would be beneficial for the patient. Staff were aware of a disparity in access to kidney care and other healthcare professional services between some patient groups, especially those living in remote areas. This was often put down to the lack of funding and capacity within each hospital. Conclusions This research found that continuity of care between modalities was valued by staff but did not always happen. It also highlighted a number of areas for consideration when developing ways to improve care and provide appropriate support to patients as they transition from peritoneal dialysis to in-centre haemodialysis.

Background To investigate the efficacy and safety of a second-generation bipolar transurethral electro vaporization of the prostate (B-TUVP) with the new oval-shaped electrode for large benign prostatic enlargement (BPE) with prostate volume (PV) ≥100ml. Materials and methods 100 patients who underwent second-generation B-TUVP with the oval-shaped electrode for male lower urinary tract symptom (LUTS) or urinary retention between July 2018 and July 2020 were enrolled in this study. The patients’ characteristics and treatment outcome were retrospectively compared between patients with PV Results 17/41 (41.5%) cases of PV ≥100ml and 24/59 cases (40.7%) of PV max) significantly increased after surgery only in PV Conclusions This is the first study investigating short-term efficacy and safety of second-generation B-TUVP with the oval-shaped electrode on large BPE. B-TUVP appears to be effective and safe for treating moderate-to-severe lower urinary tract symptoms and urinary retention in patients with large BPE.

Background Acquiring a reliable estimate of glomerular filtration rate (eGFR) at the emergency department (ED) is important for clinical management and for dosing renally excreted drugs. However, renal function formulas such as CKD-EPI can give biased results when serum creatinine (SCr) is not in steady-state because the assumption that urinary creatinine excretion is constant is then invalid. We assessed the extent of this by analysing variability in SCr in patients who visited the ED of a tertiary care centre. Methods Data from ED visits at the University Medical Centre Utrecht, the Netherlands between 2012 and 2019 were extracted from the Utrecht Patient Oriented Database. Three measurement time points were defined for each visit: last SCr measurement before visit as baseline (SCr-BL), first measurement during visit (SCr-ED) and a subsequent measurement between 6 and 24 hours during admission (SCr-H1). Non-steady-state SCr was defined as exceeding the Reference Change Value (RCV), with 15% decrease or 18% increase between successive SCr measurements. Exceeding the RCV was deemed as a significant change. Results Of visits where SCr-BL and SCr-ED were measured (N = 47,540), 28.0% showed significant change in SCr. Of 17,928 visits admitted to the hospital with a SCr-H1 after SCr-ED, 27,7% showed significant change. More than half (55%) of the patients with SCr values available at all three timepoints (11,054) showed at least one significant change in SCr over time. Conclusion One third of ED visits preceded and/or followed by creatinine measurement show non-stable serum creatinine concentration. At the ED automatically calculated eGFR should therefore be interpreted with great caution when assessing kidney function.

Some patients have a decline in renal function after contrast medium injection, and this phenomenon is called contrast-induced acute kidney injury (CI-AKI); a small number of people even suffer severe renal failure. To date, the mechanism of CI-AKI remains unclear. We aimed to identify novel potential biomarkers in the urine of patients with CI-AKI through LC-MS/MS and bioinformatics analysis. We enrolled patients who underwent coronary angiography (contrast agent: iohexol). The CI-AKI group included 4 cases, and the non-CI-AKI group included 20 cases. We mixed the 4 CI-AKI samples and 20 non-CI-AKI samples. Then, a 0.6 ml urine sample was used for proteome analysis with LC-MS/MS approach. Metascape, ExPASy, and the Human Protein Atlas were utilized for bioinformatics analysis. We obtained 724 and 830 urine proteins from the CI-AKI and non-CI-AKI groups, respectively. The distribution of the pI values and molecular weights (MWs) of postoperative urine proteins showed no significant difference between the CI-AKI group and the non-CI-AKI group. A total of 99differentially expressed proteins (DEPs) were detected, among which 18 proteins were detected only in tubule cells, and 19 proteins were detected in both tubule cells and glomeruli. With GO analysis, the GEPs were mainly associated with immune response and inflammation. Although biomarkers cannot be asserted from this single pilot study, our results may help advance the understanding of the mechanisms of CI-AKI and identify potential novel biomarkers for further investigation.

BackgroundAlthough COVID-19 is an acute disease that usually resolves rapidly in most cases, the disease can be fatal and has a mortality rate of about 1% to 56%. Alveolar injury and respiratory failure are the main causes of death in patients with COVID 19. In addition, the effect of the disease on other organs is not fully understood. Renal system affection has been reported in patients with COVID 19 and is associated with a higher rate of diverse outcomes, including mortality. Therefore, in the present work, we reported the clinical characteristics and laboratory data of hospitalized patients with COVID-19 and analyzed the manifestations that indicated renal system involvement and their impact on clinical outcomes.Materials and methodsThis was an observational retrospective study conducted at King Fahd Specialist Hospital, Buraydah, Saudi Arabia. All patients with COVID-19 who were admitted to this Hospital from April to December 2020 were included in the study. The patients’ findings at presentation were recorded. Demographic data and laboratory results (hematuria, proteinuria, urinary sediment cast and pus cell presence, and kidney function tests) were retrieved from electronic patient records.ResultsOne hundred and ninety-three patients with confirmed COVID 19 were included in the study. Dipstick examinations of all urine samples showed proteinuria and hematuria in 53.9% and 22.3% of patients, respectively, whereas microscopic examination revealed the presence of pus and brown muddy granular casts in 33.7% and 12.4% of samples, respectively. Acute kidney injury was reported in 23.3% of patients. A multivariable analysis demonstrated that hematuria was associated with acute kidney injury (AKI) (OR, 2.4; 95% CI, 1.2–4.9;P= 0.001), ICU admission (OR, 3.789; 95% CI, 1.913–7.505;P =0.003), and mortality (OR, 8.084; 95% CI, 3.756–17.397;P =0.002). Conversely, proteinuria was less significantly associated with the risk of AKI (OR, 1.56; 95% CI, 1.91–7.50;P =0.003), ICU admission (OR, 2.493; 95% CI, 1.25–4.72;P =0.001), and mortality (OR, 2.764; 95% CI, 1.368–5.121;P =0.003). Patients with AKI had a higher probability for mortality than did those without AKI (OR, 14.208; 95% CI, 6.434–31.375;P =0.003).ConclusionThe manifestations of the involvement of the renal system are not uncommon in COVID-19. These manifestations included proteinuria, hematuria, and AKI and were usually associated with a poor prognosis, including high incidences of both ICU admission and mortality.

Background Nephrotic syndrome (NS) is associated with increased risk of venous thromboembolism (VTE). Guidelines suggest prophylactic anticoagulants to patients with high risk of thrombosis and low risk of bleeding, but the evidence behind this is poor. This study aims to investigate the effectiveness and risks of prophylactic anticoagulants (PAC) and investigate risk factors for VTE and bleeding in NS. Methods A retrospective medical records study including adults with NS, biopsy proven glomerular disease in the county of Västernorrland, Sweden. Outcomes were VTE, bleeding and death. Patients divided into PAC- and no PAC group were compared using Fisher’s exact test. Patient time was divided into serum/plasma(S/P)-albumin intervals ( Results In 95 included NS patients (PAC = 40, no PAC = 55), 7 VTE (7.4%) and 17 bleedings (18%) were found. Outcomes didn’t differ significantly between the PAC and no PAC group. Time with S/P-albumin 20g/L. Conclusion Duration of severe hypoalbuminemia (S/P-albumin

Background The assessment of self-reported outcomes in neuromyelitis optica spectrum disorder (NMOSD) is limited by the lack of validated disease-specific measures. The SymptoMScreen (SyMS) is a patient-reported questionnaire for measuring symptom severity in different domains affected by multiple sclerosis (MS), but has not been thoroughly evaluated in NMOSD. The aim of this study was to assess the psychometric properties of the SyMS in a sample of patients with NMOSD. Methods A non-interventional, cross-sectional study in adult subjects with NMOSD (Wingerchuk 2015 criteria) was conducted at 13 neuroimmunology clinics applying the SyMS. A non-parametric item response theory procedure, Mokken analysis, was performed to assess the underlying dimensional structure and scalability of items and overall questionnaire. All analyses were performed with R (v4.0.3) using the mokken library. Results A total of 70 patients were studied (mean age: 47.5 ± 15 years, 80% female, mean Expanded Disability Status Scale score: 3.0 [interquartile range 1.5, 4.5]). Symptom severity was low (median SyMS score: 19.0 [interquartile range 10.0, 32.0]). The SyMS showed a robust internal reliability (Cronbach’s alpha: 0.90 [95% confidence interval 0.86, 0.93]) and behaved as a unidimensional scale with all items showing scalability coefficients > 0.30. The overall SyMS scalability was 0.45 conforming to a medium scale according to Mokken’s criteria. Fatigue and body pain were the domains with the highest scalability coefficients. The SyMS was associated with disability (rho: 0.586), and physical and psychological quality of life (rho: 0.856 and 0.696, respectively). Conclusions The SyMS shows appropriate psychometric characteristics and may constitute a valuable and easy-to-implement option to measure symptom severity in patients with NMOSD.

IntroductionThere is limited data on the effects of low carbohydrate diets on renal outcomes particularly in patients with underlying diabetic kidney disease. Therefore, this study determined the safety and effects of very low carbohydrate (VLCBD) in addition to low protein diet (LPD) on renal outcomes, anthropometric, metabolic and inflammatory parameters in patients with T2DM and underlying mild to moderate kidney disease (DKD).Materials and methodsThis was an investigator-initiated, single-center, randomized, controlled, clinical trial in patients with T2DM and DKD, comparing 12-weeks of low carbohydrate diet (ResultsThe study population (n = 30) had a median age of 57 years old and a BMI of 30.68kg/m2. Both groups showed similar total calorie intake, i.e. 739.33 (IQR288.48) vs 789.92 (IQR522.4) kcal, by the end of the study. The VLCBD group showed significantly lower daily carbohydrate intake 27 (IQR25) g vs 89.33 (IQR77.4) g, pConclusionThis study demonstrated that dietary intervention of very low carbohydrate diet in patients with underlying diabetic kidney disease was safe and associated with significant improvements in glycemic control, anthropometric measurements including weight, abdominal adiposity and IL-6. Renal outcomes remained unchanged. These findings would strengthen the importance of this dietary intervention as part of the management of patients with diabetic kidney disease.

Renal functional deterioration is associated with physical and mental burdens for kidney transplant (KT) and chronic kidney disease (CKD) patients. However, the change in health-related quality of life (HRQOL) over time in KT patients compared to that of native CKD patients has not been evaluated. We addressed this issue using KT patients registered in the KNOW-KT cohort study and patients at CKD stage 1–3 registered in the KNOW-CKD cohort study. HRQOL scores were assessed using the Kidney Disease Quality of Life Short Form at baseline, 2-, and 4-years follow-up in 842 KT patients and at baseline and 5-year follow-up in 1,355 CKD patients. SF-36 scores declined at the 4-year follow-up, whereas CKD-targeted scores showed no change in the KT group. In contrast, CKD-targeted scores as well as SF-36 scores were decreased at the 5-year follow-up in CKD patients. When prognostic factors were analyzed for longitudinal HRQOL data over time, renal functions, diabetes, cardiovascular and cerebrovascular diseases, hemoglobin level, marital status, income, employment, and health care were significant prognostic factors. Furthermore, KT was an independent prognostic factor for better HRQOL. These results highlight that KT can offer a better HRQOL than that of CKD patients, even when renal function is similar.

Minipigs have remarkably similar physiology to humans, therefore, they it can be a good animal model for inflammation study. Thus, the conventional (serum chemistry, histopathology) and novel analytic tools [immune cell identification in tissue, cytokine level in peripheral blood mononuclear cells (PBMC) and serum, NF-kB target gene analysis in tissue] were applied to determine inflammation in Chicago Miniature Swine (CMS) minipig. Lipopolysaccharide (LPS)-induced acute systemic inflammation caused liver and kidney damage in serum chemistry and histopathology. Immunohistochemistry (IHC) also showed an increase of immune cell distribution in spleen and lung during inflammation. Moreover, NF-kB-target gene expression was upregulated in lung and kidney in acute inflammation and in heart, liver, and intestine in chronic inflammation. Cytokine mRNA was elevated in PBMC under acute inflammation along with elevated absolute cytokine levels in serum. Overall, LPS-mediated systemic inflammation affects the various organs, and can be detected by IHC of immune cells, gene analysis in PBMC, and measuring the absolute cytokine in serum along with conventional inflammation analytic tools.

A large number of studies have shown that the variation and disorder of miRNAs are important causes of diseases. The recognition of disease-related miRNAs has become an important topic in the field of biological research. However, the identification of disease-related miRNAs by biological experiments is expensive and time consuming. Thus, computational prediction models that predict disease-related miRNAs must be developed. A novel network projection-based dual random walk with restart (NPRWR) was used to predict potential disease-related miRNAs. The NPRWR model aims to estimate and accurately predict miRNA–disease associations by using dual random walk with restart and network projection technology, respectively. The leave-one-out cross validation (LOOCV) was adopted to evaluate the prediction performance of NPRWR. The results show that the area under the receiver operating characteristic curve(AUC) of NPRWR was 0.9029, which is superior to that of other advanced miRNA–disease associated prediction methods. In addition, lung and kidney neoplasms were selected to present a case study. Among the first 50 miRNAs predicted, 50 and 49 miRNAs have been proven by in databases or relevant literature. Moreover, NPRWR can be used to predict isolated diseases and new miRNAs. LOOCV and the case study achieved good prediction results. Thus, NPRWR will become an effective and accurate disease–miRNA association prediction model.

A living-donor kidney transplant (LDKT) is one of the best treatments for kidney failure. The UK’s LDKT activity falls behind that of many other countries, and there is evidence of socioeconomic inequity in access. We aimed to develop a UK-specific multicomponent intervention to support eligible individuals to access a LDKT. The intervention was designed to support those who are socioeconomically-deprived and currently disadvantaged, by targeting mediators of inequity identified in earlier work. We identified three existing interventions in the literature which target these mediators: a) the Norway model (healthcare practitioners contact patients’ family with information about kidney donation), b) a home education model, and c) a Transplant candidate advocate model. We undertook intervention development using the Person-Based Approach (PBA). We performed in-depth qualitative interviews with people with advanced kidney disease (n = 13), their family members (n = 4), and renal and transplant healthcare practitioners (n = 15), analysed using thematic analysis. We investigated participant views on each proposed intervention component. We drafted intervention resources and revised these in light of comments from qualitative ‘think-aloud’ interviews. Four general themes were identified: i) Perceived cultural and societal norms; ii) Influence of family on decision-making; iii) Resource limitation, and iv) Evidence of effectiveness. For each intervention discussed, we identified three themes: for the Norway model: i) Overcoming communication barriers and assumptions; ii) Request from an official third party, and iii) Risk of coercion; for the home education model: i) Intragroup dynamics; ii) Avoidance of hospital, and iii) Burdens on participants; and for the transplant candidate advocates model: i) Vested interest of advocates; ii) Time commitment, and iii) Risk of misinformation. We used these results to develop a multicomponent intervention which comprises components from existing interventions that have been adapted to increase acceptability and engagement in a UK population. This will be evaluated in a future randomised controlled trial.

Aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 (COVID-19). Here, we investigate associations between plasma ACE2 and outcome of COVID-19. Methods and results This analysis used data from a large longitudinal study of 306 COVID-19 positive patients and 78 COVID-19 negative patients (MGH Emergency Department COVID-19 Cohort). Comprehensive clinical data were collected on this cohort, including 28-day outcomes. The samples were run on the Olink® Explore 1536 platform which includes measurement of the ACE2 protein. High admission plasma ACE2 in COVID-19 patients was associated with increased maximal illness severity within 28 days with OR = 1.8, 95%-CI: 1.4–2.3 (P < 0.0001). Plasma ACE2 was significantly higher in COVID-19 patients with hypertension compared with patients without hypertension (P = 0.0045). Circulating ACE2 was also significantly higher in COVID-19 patients with pre-existing heart conditions and kidney disease compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively). Conclusion This study suggests that measuring plasma ACE2 is potentially valuable in predicting COVID-19 outcomes. Further, ACE2 could be a link between COVID-19 illness severity and its established risk factors hypertension, pre-existing heart disease and pre-existing kidney disease.

Renamezin® is a modified capsule-type oral spherical adsorptive carbon which lowers indoxyl sulfate levels in patients with advanced chronic kidney disease (CKD). This 24-week prospective observational cohort study was performed to evaluate the effect of Renamezin® upon attenuation of renal function decline. A total of 1,149 adult patients with baseline serum creatinine 2.0–5.0 mg/dL were enrolled from 22 tertiary hospital in Korea from April 2016 to September 2018. Among them, a total of 686 patients completed the study and were included in the intention-to-treat analysis. A total of 1,061 patients were included in the safety analysis. The mean age was 63.5 years and male patients were predominant (63.6%). Most of the patients (76.8%) demonstrated high compliance with study drug (6g per day). After 24 week of treatment, serum creatinine was increased from 2.86±0.72 mg/dL to 3.06±1.15 mg/dL (p2 to 22.1±9.1 mL/min/1.73m2, p = 0.243). Patients with age over 65 years old and those under good systolic blood pressure control ® treatment to preserve renal function. A total of 98 (9.2%) patients out of 1,061 safety population experienced 134 adverse events, of which gastrointestinal disorders were the most common. There were no serious treatment-related adverse events. Renamezin® can be used safely to attenuate renal function decline in moderately advanced CKD patients.

Background Immune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of side effects, including acute kidney injury (AKI). The aim of this study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI in patients receiving checkpoint inhibitors. Methods Patients receiving checkpoint inhibitors between January 2013 and May 2020 at the University Medical Center Utrecht, the Netherlands, were identified using the Utrecht Patient Oriented Database. AKI was defined as an increase in serum creatinine of ≥1.5 times the baseline value, based on the Kidney Disease: Improving Global Outcomes criteria. Cox proportional hazard regression analysis was used to assess risk factors for AKI and to evaluate the relationship between AKI and mortality. Persistent renal dysfunction was diagnosed in AKI patients with a final serum creatinine measurement of >1.3 times the baseline value. Results Among 676 patients receiving checkpoint inhibitors, the overall incidence of AKI was 14.2%. Baseline variables independently associated with AKI were a gynecologic malignancy, monotherapy with ipilimumab, and the use of a diuretic, angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, or proton pump inhibitor at baseline. AKI was checkpoint inhibitor-associated in one third of all patients with AKI. Checkpoint inhibitor-associated AKI was mostly low-grade, occurred a median of 15 weeks after checkpoint inhibitor initiation, and resulted in persistent renal dysfunction in approximately 40% of the patients. Patients with all-cause AKI had a twofold increased mortality risk, but checkpoint inhibitor-associated AKI was not associated with increased mortality. Conclusions In this study, patients receiving checkpoint inhibitors frequently developed AKI due to various etiologies. AKI directly related to the effect of checkpoint inhibitor toxicity did not increase mortality. However, AKI not related to the effect of checkpoint inhibitor toxicity was associated with increased mortality.

Introduction Hypertension is a major threat to public health globally. Especially in sub-Saharan African countries, this coexists with high burden of other infectious diseases, creating a complex public health situation which is difficult to address. Tackling this will require targeted public health intervention based on evidence that well defines the at risk population. In this study, using retrospective data from two referral hospitals in Burundi, we model the risk factors of hypertension in Burundi. Materials and methods Retrospective data of a sample of 353 randomly selected from a population of 4,380 patients admitted in 2019 in two referral hospitals in Burundi: Military and University teaching hospital of Kamenge. The predictive risk factors were carried out by fixed effect logistic regression. Model performance was assessed with Area under Curve (AUC) method. Model was internally validated using bootstrapping method with 2000 replications. Both data processing and data analysis were done using R software. Results Overall, 16.7% of the patients were found to be hypertensive. This study didn’t showed any significant difference of hypertension’s prevalences among women (16%) and men (17.7%). After adjustment of the model for cofounding covariates, associated risk factors found were advanced age (40–59 years) and above 60 years, high education level, chronic kidney failure, high body mass index, familial history of hypertension. In absence of these highlighted risk factors, the risk of hypertension occurrence was about 2 per 1000 persons. This probability is more than 90% in patients with more than three risk factors. Conclusion The relatively high prevalence and associated risk factors of hypertension in Burundi raises a call for concern especially in this context where there exist an equally high burden of infectious diseases, other chronic diseases including chronic malnutrition. Targeting interventions based on these identified risk factors will allow judicious channel of resources and effective public health planning.

Normothermic machine perfusion (NMP) of donor kidneys provides the opportunity for improved graft preservation and objective pre-transplant ex-vivo organ assessment. Currently, a multitude of perfusion solutions exist for renal NMP. This study aimed to evaluate four different perfusion solutions side-by-side and determine the influence of different perfusate compositions on measured renal perfusion parameters. Porcine kidneys and blood were obtained from a slaughterhouse. Kidneys underwent NMP at 37°C for 7 hours, with 4 different perfusion solutions (n = 5 per group). Group 1 consisted of red blood cells (RBCs) and a perfusion solution based on Williams’ Medium E. Group 2 consisted of RBCs, albumin and a balanced electrolyte composition. Group 3 contained RBCs and a medium based on a British clinical NMP solution. Group 4 contained RBCs and a medium used in 24-hour perfusion experiments. NMP flow patterns for solutions 1 and 2 were similar, solutions 3 and 4 showed lower but more stable flow rates. Thiobarbituric acid reactive substances were significantly higher in solution 1 and 4 compared to the other groups. Levels of injury marker N-acetyl-β-D glucosaminidase were significantly lower in solution 2 in comparison with solution 3 and 4. This study illustrates that the perfusate composition during NMP significantly impacts the measured perfusion and injury parameters and thus affects the interpretation of potential viability markers. Further research is required to investigate the individual influences of principal perfusate components to determine the most optimal conditions during NMP and eventually develop universal organ assessment criteria.

ObjectivesStudies have shown that acute kidney injury (AKI) occurrence post SARS-CoV-2 infection is complex and has a poor prognosis. Therefore, more studies are needed to understand the rate and the predications of AKI involvement among hospitalized COVID-19 patients and AKI’s impact on prognosis while under different types of medications.Patients and methodsThis study is a retrospective observational cohort study conducted at Bahrain Defence Force (BDF) Royal Medical Services. Medical records of COVID-19 patients admitted to BDF hospital, treated, and followed up from April 2020 to October 2020 were retrieved. Data were analyzed using univariate and multivariate logistic regression with covariate adjustment, and the odds ratio (OR) and 95% confidence (95% CI) interval were reported.ResultsAmong 353 patients admitted with COVID-19, 47.6% developed AKI. Overall, 51.8% of patients with AKI died compared to 2.2% of patients who did not develop AKI (p< 0.001 with OR 48.6 and 95% CI 17.2–136.9). Besides, deaths in patients classified with AKI staging were positively correlated and multivariate regression analysis revealed that moderate to severe hypoalbuminemia (ConclusionsThe incidence of AKI in hospitalized COVID-19 patients and the mortality rate among AKI patients were high and correlated with AKI staging. Furthermore, laboratory testing for serum albumin, hypercoagulability and cardiac injury markers maybe indicative for AKI development. Therefore, clinicians should be mandated to perform such tests on admission and follow-up in hospitalized patients.

Background Diabetes mellitus (DM) and chronic kidney disease (CKD) are common causes of morbidity and mortality. Flaxseed contains several bioactive compounds that have been shown to possess anti-inflammatory and antioxidative properties. The aim of the present study was to investigate the possible effect of flaxseed in diabetic rats with adenine–induced CKD. Methods Male Wister rats (n = 48) were randomly divided into seven equal groups and treated for 33 consecutive days as follows: G1: control. G2 adenine, G3: streptozotocin (STZ), G4: flaxseed, G5: adenine+flaxseed, G6: STZ+flaxseed, G7: adenine+STZ+flaxseed). DM or CKD were experimentally induced by a single intraperitoneal injection of streptozotocin (STZ) or by adenine via oral gavage, respectively. Results Rats fed adenine alone exhibited several changes including decreased body weight, increased food and water intake and urine output, increased urinary albumin/creatinine ratio. They also showed an increase in plasma urea and, creatinine, indoxyl sulfate, neutrophil gelatinase-associated lipocalin and cystatin C, and a decrease in renalase activity. These were associated with significant changes in inflammatory and oxidative biomarkers, e.g., increase in 8-isoprostane, 8 -hydroxy -2-deoxy guanosine and decrease in antioxidant enzymes, as well as increase in interleukins 1β and 6, and NF-κB, and a decrease in interlukin-10. Histopathologically, there was increased tubular necrosis and fibrosis. Concomitant administration of adenine and STZ further worsened the renal damage induced by adenine alone. Flaxseed significantly ameliorated the changes caused by adenine and STZ, given either singly or in combination. Conclusion These findings suggest that flaxseed is a potential therapeutic agent in attenuating the progression of CKD in diabetes.

Background Acute Kidney Injury (AKI) represents a clinical condition with poor prognosis. The incidence of AKI in hospitalized patients was about 22–57%. Patients undergoing cardiac surgery (CS) are particularly exposed to AKI because of the related oxidative stress, inflammation and ischemia-reperfusion damage. Hence, the risk profile of patients undergoing CS who develop AKI and who are consequently at increased mortality risk deserves further investigation. Methods We designed a retrospective study examining consecutive patients undergoing any type of open-heart surgery from January to December 2018. Patients with a history of AKI were excluded. AKI was diagnosed according to KDIGO criteria. Univariate associations between clinical variables and AKI were tested using logistic regression analysis. Variable thresholds maximizing the association with AKI were measured with the Youden index. Multivariable logistic regression analysis was performed to assess predictors of AKI through backward selection. Mortality risk factors were assessed through the Cox proportional hazard model. Results We studied 158 patients (mean age 51.2±9.7 years) of which 74.7% were males. Types of procedures performed were: isolated coronary artery bypass (CABG, 50.6%), valve (28.5%), aortic (3.2%) and combined (17.7%) surgery. Overall, incidence of AKI was 34.2%. At multivariable analysis, young age (p = 0.016), low blood glucose levels (p = 0.028), estimated Glomerular Filtration Rate (p = 0.007), pH (p = 0.008), type of intervention (p = 0.031), prolonged extracorporeal circulation (ECC, p = 0.028) and cross-clamp (p = 0.021) times were associated with AKI. The threshold for detecting AKI were 91 and 51 minutes for ECC and cross-clamp times, respectively. At survival analysis, the presence of AKI, prolonged ECC and cross-clamp times, and low blood glucose levels forecasted mortality. Conclusions AKI is common among CS patients and associates with shortened life-expectancy. Several pre-operative and intra-operative predictors are associated with AKI and future mortality. Future studies, aiming at improving prognosis in high-risk patients, by a stricter control of these factors, are awaited.

Publisher Copyright: © 2021 Kaartinen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Chronic kidney disease (CKD) is one of the most well-known extrahepatic manifestations caused by hepatitis C infection (HCV). CKD is typically discovered at a late stage. HCVnephropathy may show different histopathologic patterns, as both glomerular and tubulointerstitial damage have been described. Identification of patients with early renal manifestations would be beneficial to provide treatment and avoid progression to CKD. The observational prospective single-center HCVKID study assessed the prevalence of early renal manifestations in patients with chronic HCV and compared these patients with HCVnegative healthy controls cross-sectionally. HCV-positive patients with and without renal manifestations were also compared to define biomarkers suitable for identifying early manifestations in standard clinical practice. Tubular proteinuria as judged by urine α 1-microglobulin was the most common early renal manifestation found in 11% in HCV-positive patients, followed by hematuria in 8%. Kidney filtration was statistically significantly lower among HCV-positive patients with renal manifestation according to any calculation method. There were no significant differences in duration of infection or stage of liver fibrosis between patients with or without renal manifestations. Tubular cell damage may be the earliest sign of renal dysfunction caused by HCV. Complement activation also correlates with the dysfunction, indicating of contribution to HCV-induced renal manifestations even in their early phase.

Background Bariatric surgery (BS) might be a nephroprotective treatment in obese patients with chronic kidney disease (CKD), and the non-linear relation between body surface area (BSA) and extracellular fluid volume (ECFV) in obese people raises the question of the most relevant way to scale glomerular filtration rate (GFR) for assessing renal function changes after BS. Methods We screened 1774 BS candidates and analysed 10 consecutive participants with CKD stage 3. True GFR (mGFR), measured by the renal clearance of 51Cr-ethylenediaminetetraacetic acid (EDTA), was scaled either to BSA (mGFRBSA) or to ECFV measured by 51Cr-EDTA distribution volume (mGFRECFV) before and one year after BS. Results The 10 candidates for BS had a mean body mass index of 43.3 ± 3.6 kg/m2 and a mean GFR of 48 ± 8 mL/min/1.73 m2. Six participants had a sleeve gastrectomy and four had a Roux-en-Y gastric bypass. One year after BS, ECFV decreased (23.2 ± 6.2 to 17.9 ± 4.3 L, p = 0.001), absolute mGFR was not significantly modified (74 ± 23 versus 68 ±19 mL/min), mGFRBSA did not change significantly (53 ± 18 versus 56 ± 17 mL/min/1.73 m2) whereas mGFRECFV significantly increased (42 ± 13 versus 50 ± 14 mL/min/12.9 L, p = 0.037). The relation between mGFRECFV and mGFRBSA was different from the identity line before (p = 0.014) but not after BS (p = 0.09). Conclusion There is a difference between mGFRBSA and mGFRECFV following BS and the latter might better reflect the adequacy between renal function and corpulence.

Background The Coronavirus disease 2019 (COVID-19) pandemic has affected millions of people across the globe. It is associated with a high mortality rate and has created a global crisis by straining medical resources worldwide. Objectives To develop and validate machine-learning models for prediction of mechanical ventilation (MV) for patients presenting to emergency room and for prediction of in-hospital mortality once a patient is admitted. Methods Two cohorts were used for the two different aims. 1980 COVID-19 patients were enrolled for the aim of prediction ofMV. 1036 patients’ data, including demographics, past smoking and drinking history, past medical history and vital signs at emergency room (ER), laboratory values, and treatments were collected for training and 674 patients were enrolled for validation using XGBoost algorithm. For the second aim to predict in-hospital mortality, 3491 hospitalized patients via ER were enrolled. CatBoost, a new gradient-boosting algorithm was applied for training and validation of the cohort. Results Older age, higher temperature, increased respiratory rate (RR) and a lower oxygen saturation (SpO2) from the first set of vital signs were associated with an increased risk of MV amongst the 1980 patients in the ER. The model had a high accuracy of 86.2% and a negative predictive value (NPV) of 87.8%. While, patients who required MV, had a higher RR, Body mass index (BMI) and longer length of stay in the hospital were the major features associated with in-hospital mortality. The second model had a high accuracy of 80% with NPV of 81.6%. Conclusion Machine learning models using XGBoost and catBoost algorithms can predict need for mechanical ventilation and mortality with a very high accuracy in COVID-19 patients.

In this retrospective multicentric cohort study, we evaluate the potential benefits of a clinical decision support system (CDSS) for the automated detection of Acute kidney injury (AKI). A total of 80,389 cases, hospitalized from 2017 to 2019 at a tertiary care hospital (University of Leipzig Medical Center (ULMC)) and two primary care hospitals (Muldentalkliniken (MTL)) in Germany, were enrolled. AKI was defined and staged according to the Kidney disease: improving global outcomes (KDIGO) guidelines. Clinical and laboratory data was automatically collected from electronic patient records using the frameworks of the CDSS. In our cohort, we found an overall AKI incidence proportion of 12.1%. We identified 6,393/1,703/1,604 cases as AKI stage 1/2/3 (8.0%/2.1%/2.0%, respectively). Administrative coding with N17 (ICD-10-GM) was missing in 55.8% of all AKI cases with the potential for additional diagnosis related groups (DRG) reimbursement of 1,204,200 € in our study. AKI was associated with higher hospital mortality, increased length of hospitalisation and more frequent need of renal replacement therapy. A total of 19.1% of AKI cases (n = 1,848) showed progression to higher AKI stages (progressive AKI) during hospitalization. These cases presented with considerably longer hospitalization, higher rates of renal replacement therapy and increased mortality (p

Funder: GlaxoSmithKline; funder-id: http://dx.doi.org/10.13039/100004330, Introduction: Delayed graft function (DGF) following renal transplantation is a manifestation of acute kidney injury (AKI) leading to poor long-term outcome. Current treatments have limited effectiveness in preventing DGF. Interleukin-18 (IL18), a biomarker of AKI, induces interferon-γ expression and immune activation. GSK1070806, an anti-IL18 monoclonal antibody, neutralizes activated (mature) IL18 released from damaged cells following inflammasome activation. This phase IIa, single-arm trial assessed the effect of a single dose of GSK1070806 on DGF occurrence post donation after circulatory death (DCD) kidney transplantation. Methods: The 3 mg/kg intravenous dose was selected based on prior studies and physiologically based pharmacokinetic (PBPK) modeling, indicating the high likelihood of a rapid and high level of IL18 target engagement when administered prior to kidney allograft reperfusion. Utilization of a Bayesian sequential design with a background standard-of-care DGF rate of 50% based on literature, and confirmed via extensive registry data analyses, enabled a statistical efficacy assessment with a minimal sample size. The primary endpoint was DGF frequency, defined as dialysis requirement ≤7 days post transplantation (except for hyperkalemia). Secondary endpoints included safety, pharmacokinetics and pharmacodynamic biomarkers. Results: GSK1070806 administration was associated with IL18-GSK1070806 complex detection and increased total serum IL18 levels due to IL18 half-life prolongation induced by GSK1070806 binding. Interferon-γ−induced chemokine levels declined or remained unchanged in most patients. Although the study was concluded prior to the Bayesian-defined stopping point, 4/7 enrolled patients (57%) had DGF, exceeding the 50% standard-of-care rate, and an additional two patients, although not reaching the protocol-defined DGF definition, demonstrated poor graft function. Six of seven patients experienced serious adverse events (SAEs), including two treatment-related SAEs. Conclusion: Overall, using a Bayesian design and extensive PBPK dose modeling with only a small sample size, it was deemed unlikely that GSK1070806 would be efficacious in preventing DGF in the enrolled DCD transplant population. Trial registration: NCT02723786.