Severe Kidney Disease Research Articles

Хронічна хвороба нирок у дітей (огляд літератури)

У статті наводяться сучасні уявлення про хронічну хворобу нирок у дітей як про стан, що розвивається внаслідок необоротного зниження ниркових гомеостатичних функцій при будь-якому тяжкому прогресуючому захворюванні нирок. Показані епідеміологічні дані про поширеність, етіологічні фактори, методи діагностики, стадії і клінічний перебіг хронічної хвороби нирок у дітей. Крім того, зазначено, що раннє виявлення і своєчасне лікування хронічної хвороби нирок у дітей є важливою передумовою для запобігання або віддалення від її несприятливого результату. Більш того, показані високий ступінь інвалідизації і значне зниження якості життя пацієнтів, складність і висока вартість терапії хворих із термінальною хронічною нирковою недостатністю, що робить дуже актуальним запобігання її розвитку в пацієнтів із нефропатіями. Викладено основні принципи патогенетичної терапії, засновані на аналізі вітчизняних і зарубіжних керівництв із лікування хронічної хвороби нирок у дітей. Наведено схеми лікування білково-енергетичної недостатності, артеріальної гіпертензії, анемії, корекції порушень мінерального обміну. Обговорюються питання про зниження рівня азотемії різними препаратами і розробка нових препаратів із метою раннього початку лікування і запобігання розвитку тяжких форм хронічної хвороби нирок у дітей. Пошук потрібних літературних джерел проводився в базах даних Scopus, MedLine, The Cochrane Library, CyberLeninka, РІНЦ.

Overtreatment and undertreatment in a sample of elderly people with diabetes.

In older adults with type 2 diabetes (T2D), overtreatment remains prevalent and undertreatment ignored. The main objective is to estimate the prevalence and examine factors associated with potential overtreatment and undertreatment. Observational study conducted within an administrative database of older adults with T2D who registered in 2018 at the Portuguese Diabetes Association. Participants were categorized either as potentially overtreated (HbA1c≤7.5%), appropriately on target (HbA1c ≥7.5 to ≤9%), or potentially undertreated (HbA1c>9%). The study included 444 participants: potential overtreatment and undertreatment were found in 60.5% and 12.6% of the study population. Taking the patients on target as a comparator, the group of potentially overtreated showed to be more men (61.3% vs 52.2%), less-obese (34.1% vs 39.2), higher cardiovascular diseases (13.7% vs 11%), peripheral vascular diseases (16.7% vs 12.8%), diabetic foot (10% vs 4.5%), and severe kidney disease (5.2% vs 4.5%). Conversely, the potentially undertreated participants were more women (64.2% vs 47.7%), obese (49% vs 39.2%), had more dyslipidemia (69% vs 63.1%), peripheral vascular disease (14.2% vs 12.8%), diabetic foot (8.9% vs 4.5%), and infections (14.2% vs 11.9%). The odds of potential overtreatment were mostly decreased by 59% of women, 73.5% in those with retinopathy, and 86.3% in insulin, 65.4% sulfonylureas, and 66.8% in SGLT2 inhibitors users. Contrariwise, an increase in the odds of potential undertreatment was more than 4.8 times higher in insulin, and more than 3.1 times higher in sulfonylureas users. Potential overtreatment and undertreatment in older adults with T2D in routine clinical practice should guide the clinicians to balance the use of newer oral antidiabetic agents considering its safety profile regarding hypoglycemia.

Assessment of Plasma Phospholipid Very-Long-Chain Saturated Fatty Acid Levels and Healthy Aging

Identifying novel factors that protect against age-related diseases and promote healthy aging is critical to public health. Higher levels of circulating very-long-chain saturated fatty acids (VLSFAs) are integrated biomarkers of diet and metabolism shown to have beneficial associations in cardiovascular disease and total mortality, but whether they are associated with overall healthy aging is unknown. To examine the association of circulating levels of 3 VLSFAs with unhealthy aging events, including incident chronic disease (cardiovascular disease, cancer, lung disease or severe kidney disease), physical dysfunction, and cognitive decline. This cohort study used 1992 to 2014 data from the Cardiovascular Health Study (CHS). The CHS is a multicenter, population-based study of cardiovascular disease among older adults. Among the 4559 CHS participants with available fatty acid data, 1879 participants who had an age-related event before their first measurement were excluded. Data analysis was performed in 2020. Plasma phospholipid VLSFA levels were measured by thin-layer chromatography followed by gas chromatography. The main outcome was the hazard ratio (HR) of an incident unhealthy aging event associated with serial measures of plasma arachidic acid, behenic acid, and lignoceric acid. Among the 2680 study participants (976 men [36.4%]), the mean (SD) age was 74.7 (4.8) years old at entry. During a median (interquartile range) of 6.4 (2.9-12.9) years of follow-up, 2484 participants experienced an unhealthy event. Compared with the lowest quintile, levels of behenic acid in the highest quintile of the fatty acid distribution were associated with 15% lower risk of an unhealthy event (HR, 0.85; 95% CI, 0.74-0.97; P for trend = .01) after adjustment for demographic characteristics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of lignoceric acid were similarly associated with 16% lower risk of an unhealthy event (HR, 0.84; 95% CI, 0.73-0.95; P for trend = .001). These findings suggest that higher levels of circulating behenic acid and lignoceric acid are associated with lower risk of unhealthy aging events. These results highlight the need to explore determinants of circulating VLSFAs for potential novel efforts to promote healthy aging.

Oxygen-sensitive Magnetic Resonance Imaging: A Noninvasive Step Forward for Diagnosing Vasculopathy in the Cardiac Allograft.

Oxygen-sensitive Magnetic Resonance Imaging: A Noninvasive Step Forward for Diagnosing Vasculopathy in the Cardiac Allograft.

Failure to rescue: variation in mortality after cardiac surgery.

Measures to prevent surgical complications are critical components of optimal patient care, and adequate management when complications occur is equally crucial in efforts to reduce mortality. This study aims to elucidate clinical realities underlying in-hospital variations in failure to rescue (FTR) after cardiac surgery. Using a statewide database for a quality improvement program, we identified 62 450 patients who had undergone adult cardiac surgery between 2011 and 2018 in 1 of the 33 Michigan hospitals performing adult cardiac surgery. The hospitals were first divided into tertiles according to their observed to expected (O/E) ratios of 30-day mortality: low-mortality tertile (O/E 0.46-0.78), intermediate-mortality tertile (O/E 0.79-0.90) and high-mortality tertile (O/E 0.98-2.00). We then examined the incidence of 15 significant complications and the rates of death following complications among the 3 groups. A total of 1418 operative deaths occurred in the entire cohort, a crude mortality rate of 2.3% and varied from 1.3% to 5.9% at the hospital level. The death rates also diverged significantly according to mortality score tertiles, from 1.6% in the low-mortality group to 3.2% in the high-mortality group (P < 0.001). Hospitals ranked in a high- or intermediate-mortality tertile had similar rates of overall complications (21.3% and 20.7%, P = 0.17), while low-mortality hospitals had significantly fewer complications (16.3%) than the other 2 tertiles (P < 0.001). FTR increased in a stepwise manner from low- to high-mortality hospitals (8.3% vs 10.0% vs 12.7%, P < 0.001, respectively). Differences in FTR were related to survival after cardiac arrest, multi-system organ failure, prolonged ventilation, reoperation for bleeding and severe acute kidney disease that requires dialysis. This study demonstrates that timely recognition and appropriate treatment of complications are as important as preventing complications to further reduce operative mortality in cardiac surgery. FTR tools may provide vital information for quality improvement initiatives.

1017-P: Association between Death at Day 28 and Components of Microvascular Disease of with Diabetes Hospitalized for Coronavirus Disease-2019 (COVID-19): The CORONADO Study

The prognostic role of microvascular complications (MVC) for all-cause death in patients with diabetes hospitalized for COVID-19 has been suggested. However, no detailed analysis of the microvascular burden is available so far. The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalized for COVID-19. The patients were enrolled after hospital admission from 03/10/2020 to 04/10/2020. MVC were defined as severe diabetic retinopathy (DR) and/or diabetic kidney disease (DKD, eGFR 300mg/g) and/or diabetic foot ulcer (DFU). We analysed the association of MVC with death within 28 days after admission. The status for all 3 MVC was ascertained for 1755 participants including 1048 (60%) free of MVC. Patients with MVC were older, had lower BMI, HbA1c, AST/ALT concentration, lymphocyte and platelet counts, while sex, type of diabetes and CRP were not significantly different. Patients with any MVC had a sex- and age-adjusted OR for death of 2.54 (95%CI: 1.94-3.31, P Disclosure P. Saulnier: None. S. Hadjadj: Advisory Panel; Self; Valbiotis, Consultant; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi. L. Kessler: None. M. Marre: Board Member; Self; Merck Sharp & Dohme Corp., Consultant; Self; Novo Nordisk. J. Halimi: None. M. Wargny: None. P. Gourdy: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Research Support; Self; Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Sanofi. B. Cariou: Board Member; Self; Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Sanofi, Research Support; Self; Amgen Inc., AstraZeneca, Regeneron Pharmaceuticals Inc., Speaker’s Bureau; Self; Abbott Diabetes, Akcea Therapeutics. For the coronado study group: n/a.

MO637THE HIDDEN PREVALENCE OF DIABETIC KIDNEY DISEASE IN A HOSPITAL-BASED REAL-WORLD DATA ANALYSIS

Abstract Background and Aims Correct identification of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients is crucial to implement therapeutic interventions to prevent disease progression and premature death. Method We have analyzed the prevalence of DKD according to lab criteria and the rate of identification of DKD and/or chronic kidney disease (CKD) on 516,578 hospital care electronic medical records (EMR) in a tertiary hospital-based population using Savana Manager®. Results Out of 24,129 T2DM patients, 15,304 met inclusion criteria. DKD was defined as eGFR&amp;lt;60 ml/min/1.73m2 or urinary albumin to creatinine ratio (UACR) &amp;gt;30 mg/g or urinary protein to creatinine ratio (UPCR) &amp;gt;0.3 g/g after excluding acute kidney injury (AKI). A total of 4,526 (29.6%) T2DM patients had DKD according to lab criteria. However, the terms “CKD” or “DKD” were only present in 33.1% and 7.5% of the 4,526 EMR, with a hidden prevalence of CKD and DKD of 66.9% and 92.5%, respectively. Less severe kidney disease (lower UACR or UPCR, higher eGFR values), female sex, and lack of insulin prescription were associated with the absence of “DKD” or “CKD” terms in EMR (p&amp;lt;0.001) in the patients fulfilling laboratory criteria for DKD. However, while younger age (&amp;lt;70 years) was associated with a missing CKD diagnosis, older age (≥70 years) was associated with a missing DKD diagnosis in EMR. Conclusion In conclusion, the prevalence of DKD among T2DM patients according to laboratory data is higher than prevalence based on specific diagnosis written in EMR. This could imply underdiagnosis of DKD, especially in patients with less severe disease who may benefit the most from optimized therapy

Current jakinibs for the treatment of rheumatoid arthritis: a systematic review.

One-third of patients with severe rheumatoid arthritis (RA) do not achieve remission or low disease activity, or they have side effects from cDMARD and bDMARD. They will need a new treatment option such as the small molecule JAK inhibitors. In this systematic review, we evaluate the efficacy and safety data of the current jakinibs: tofacitinib, peficitinib, decernotinib, upadacitinib, baricitinib and filgotinib in patients in whom treatment with conventional or biological disease-modifying antirheumatic drugs (cDMARD and/or bDMARD) failed. We searched for randomized controlled trials comparing efficacy and safety of jakinibs for RA treatment using the Web of Science, Scopus, PubMed, and clinicaltrials.gov databases with the terms: "rheumatoid arthritis" OR "arthritis rheumatoid" OR "RA" AND "inhibitor" OR "jak inhibitor" AND "clinical trial" OR "treatment" OR "therapy". All jakinibs achieved good results in ACR 20, 50, 70 and with CRP-DAS28 for LDA and remission, upadacitinib showed better results compared to the others. In ESR-DAS28 for remission, tofacitinib achieved the best result. Regarding the safety of all jakinibs, peficitinib, baricitinib and filgotinib did not register deaths in their studies unlike tofacitinib that presented 11 deaths. Despite all benefits of jakinibs, the use in patients with severe liver and kidney disease should be avoided. Jakinibs in monotherapy or in combination with methotrexate can be considered a viable alternative in the treatment of moderate-to-severe RA. Even after failures with combination of cDMARDS and bDMARDS, jakinibs demonstrated efficacy.

Intensive management of obesity in people with severe chronic kidney disease: A review

Obesity is highly prevalent worldwide, including among people with chronic kidney disease (CKD). The presence of severe and/or end-stage kidney disease complicates the treatment of obesity for several reasons, including restrictions on protein and fluid intake and renal excretion of several medications indicated for the treatment of obesity. The aim of this review is to assess the safety of intensive obesity treatments, such as very-low-energy diets (VLEDs), obesity pharmacotherapy and/or bariatric surgery, in people with end-stage kidney disease. A literature search was conducted to identify studies reporting safety outcomes for VLEDs, liraglutide, phentermine, phentermine-topiramate, naltrexone-bupropion and bariatric surgery in people with an estimated glomerular filtration rate of less than 30 mL/min/1.73m2 or on dialysis. Limited data were insufficient to recommend VLEDs but highlighted their potential efficacy and the need for close clinical and biochemical monitoring. There were no data regarding centrally acting obesity pharmacotherapy in this population, although some glucagon-like peptide-1 analogues appear to safely induce weight loss at doses used for the treatment of type 2 diabetes. Some studies suggest an increased rate of complications of bariatric surgery in individuals with severe or end-stage CKD. Further prospective evaluation of intensive obesity management in the growing population with obesity and severe, end-stage and dialysis-dependent CKD is required.

Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? CON.

Vasculitis associated with the formation of ANCA manifests in several forms defined by the extent of organ involvement (renal limited or systemic), with or without granulomatous tissue involvement, and by the presence and nature of the ANCA (antimyeloperoxidase or antiproteinase 3 and associated autoantibodies, in particular antiglomerular basement membrane [anti-GBM] autoantibodies) (1). Severe kidney disease with extensive crescentic involvement and a clinical syndrome of rapidly progressive GN is common in all forms of ANCA-associated vasculitis (AAV) (1). Diffuse alveolar hemorrhage (DAH), of varying severity, can be seen in many kinds of GN (Goodpasture syndrome) but is particularly common in AAV, with or without anti-GBM antibody (2). The therapy of AAV has greatly improved in recent years, and the use of rituximab (RTX), cyclophosphamide (CYC), or combinations of RTX and CYC plus moderate doses of steroids can effectively and safely induce a complete or partial remission in the great majority of patients (3 ⇓–5). The role of adjunctive therapy with plasmapheresis (PLEX) has been controversial, except in cases where anti-GBM autoantibody disease is found alone or concomitantly with AAV. The publication of the large Plasma Exchange and glucocorticoid dosing in treatment of anti-neutrophil cytoplasmic antibody associated vasculitis (PEXIVAS) trial in 2020 has generated much attention to this controversy (6). This debate focuses on this controversy by laying out a precise question: should PLEX be used for severe AKI and/or pulmonary hemorrhage in patients with AAV? For this debate, I will interpret “severe” as meaning the need for artificial organ support (dialysis for AKI or mechanical ventilation for DAH). I will also interpret ANCA vasculitis as meaning a positive (antimyeloperoxidase or antiproteinase 3 autoantibody in the absence of anti-GBM antibody and clinical or morphologic evidence of a vasculitis involving the kidney without or with extrarenal involvement, including DAH. …

Direct Oral Anticoagulants versus Vitamin K Antagonists in Patients Aged 80 Years and Older.

The effectiveness of direct oral anticoagulants (DOAC) is non-inferior to vitamin K antagonists (VKA) to treat atrial fibrillation and venous thromboembolism (VTE). In this cross-sectional study, we compared older persons taking DOACs to those taking VKAs. We included ambulatory individuals ≥80 years, affiliated to Mutualité Sociale Agricole of Burgundy, who were refunded for a medical prescription in September 2017. The demographic conditions, registered chronic diseases (RCD), and number and types of prescribed drugs were compared in the DOAC group and VKA group. Of the 3190 included individuals, 1279 (40%) were prescribed DOACs and 1911 (60%) VKAs. Individuals taking VKAs were older than those taking DOACs (87.11 vs. 86.35 years). In the DOAC group, there were more women (51.92% vs. 48.25%) (p = 0.043), less RCD (89.60% vs. 92.73%) (p = 0.002), less VTE (1.80% vs. 6.59%), less severe heart failure (58.09% vs. 67.87%), less severe hypertension (18.22% vs. 23.60%), less severe kidney diseases (1.49% vs. 3.82%), and fewer drugs per prescription (6.15 vs. 6.66) (p < 0.01 for all). The DOAC group were also less likely to be taking angiotensin receptor blockers (10.79% vs. 13.97%), furosemide (40.81% vs. 49.66%) or digoxin (10.32% vs. 13.66%) than the VKA group (p = 0.009, p < 0.001, and p = 0.005). DOACs were less prescribed than VKAs. Individuals taking VKAs were older and had more severe comorbidities and more drugs per prescription than those taking DOACs.

Safety and utility of kidney biopsy in patients with estimated glomerular filtration rate < 30ml/min/1.73 m2.

Kidney biopsy (KBx) is the gold standard for evaluation of kidney disease, but is associated with a higher risk of complications in patients with reduced glomerular filtration rate (GFR). We studied the safety and utility of KBx in patients with eGFR <30 ml/min/1.73 m2 . Consecutive adult patients with eGFR <30 ml/min/1.73 m2 , who were planned for a KBx and consented to participate were prospectively enrolled. Patients with solitary/transplant kidney or acute kidney injury were excluded. Haemoglobin was checked on the day of KBx and repeated 18-24 h later along with a screening ultrasound. Post-KBx complications were noted and their risk-factors analysed. The utility of the KBx was graded as effecting significant, some, or no change to subsequent management. Of the 126 patients included, 75% were male, 27.7% were diabetic, and the median eGFR was 13.5ml/min/1.73m2 . Major complications occurred in 5.6%. Peri-renal haematomas were detected in 37.3%, and haematomas ≥2cm were significantly more frequent in those with eGFR <15 ml/min/1.73 m2 (29.2% vs. 13%, p= .032). Dialysis was a risk factor, while pre KBx blood transfusion, diabetes and higher serum albumin were protective against any complication. KBx was more likely to make a significant difference in management in those with eGFR 15-29 ml/min/1.73m2 (44.1% vs. 11.1%, p< .001). Increasing age, lower serum creatinine and albumin were independently associated with KBx utility. KBx is relatively safe in severe kidney disease but its risk to benefit balance needs to be carefully considered when eGFR is <15 ml/min/1.73m2 .

POS-428 PROTEIN-TRUNCATING PKD1 MUTATIONS YET MILD AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE IS UNDER-RECOGNIZED

Progression of autosomal dominant polycystic kidney disease (ADPKD) is highly variable between patients. On average, protein-truncating PKD1 mutations are associated with the most severe kidney disease among all mutation classes, yet within family disease variability is a recognized feature of ADPKD. The penetrance of protein-truncating PKD1 mutations cannot be adequately evaluated if only index probands with severe disease are tested. Here, we evaluated the patients with protein-truncating PKD1 mutations yet mild kidney disease from the extended Toronto Genetic Epidemiologic Study of Polycystic Kidney Disease. The extended Toronto Genetic Epidemiologic Study of Polycystic Kidney Disease cohort included probands with ADPKD (n=612) and their affected relatives (n=778) from a total of 612 unrelated families. 487 patients from 442 unrelated families had both PKD1 and PKD2 sequencing and typical ADPKD imaging patterns by magnetic resonance imaging or computed tomography. Mayo Clinic Imaging Classification based on age- and height-adjusted total kidney volume was used to assess their cystic disease severity. Among 174 study patients with protein-truncating PKD1 mutations, 32 (18%) from 27 families were found to have mild disease based on imaging results (i.e. Mayo Clinic Imaging Class 1A-1B), with their mutations spanning across the entire gene. 23 of 32 were over the age of 30 making incorrect risk stratification unlikely. In patients with Mayo Clinic Imaging Class 1A-1B, the slopes of log-transformed height-adjusted total kidney volume (βPKD1= 1.0% larger kidney per year vs. βPKD2= 1.3% larger per year, P=0.3) and eGFR (βPKD1= -1.29 ml/min/1.73m2 per year vs. βPKD2= -1.46 ml/min/1.73m2 per year, P=0.6) overlap regardless of whether they had protein-truncating PKD1 or PKD2 mutation. Comparing patients with Mayo Clinic Imaging Class 1A-1B by multivariable analyses, patients with PKD2 mutations had only marginally smaller kidney volumes (β = -7.7%; 95% CI: -13.9% to -0.01%; P=0.02) and their eGFR was not significantly different (β = 9.0 ml/min/1.73m2; 95% CI: -0.4 to 18.3 ml/min/1.73m2, P=0.06) compared to those with protein-truncating PKD1 mutations. Most of these mildly affected patients with protein-truncating PKD1 mutations reported a positive family history of ADPKD in preceding generations and displayed significant intra-familial disease variability. One patient had confirmed somatic mosaicism. Despite having the most severe mutation class, 18% of patients with protein-truncating PKD1 mutations had mild disease based on clinical and imaging assessment that was similar to patients with PKD2 mutations. The presence of a positive family history of ADPKD in most of these patients makes somatic mosaicism an unlikely explanation for their mild disease. By contrast, significant within-family variability suggests a protective modifier effect from yet unknown genetic and environmental factors.

POS-460 FOCAL SEGMENTAL GLOMERULOSCLEROSIS: ABOUT A SERIES OF 18 CHILDREN.

Focal segmental glomerulosclerosis (FSGS) is a glomerular histopathological finding characterized by segmental (affecting part of the flocculus) and focal (affecting only certain glomeruli) sclerosis. It is severe kidney disease with a complex pathophysiology. To determine the epidemiology and outcome of FSGS in our patients, we conducted a retrospective study on 18 cases diagnosed between January 2010 and December 2019. Out of 345 renal biopsies performed in that period of time, the prevalence of FSGS was of 5.2%. The mean age of these FSGS patients was 9 years old. Boys were predominant with a sex ratio of 2. Consanguinity was found in one-third of our cases. Nephrotic syndrome was the main revealing pattern and was always steroid resistant (100%). Meanwhile, hypertension was found in 30% of our children, and hematuria in 47% of them. Two cases had kidney failure at diagnosis. Primitive FSGS was found in 39% of the cases, four of them reached complete remission after stating calcineurin inhibitors (CIN), while the remaining cases were resistant to CIN, and one case developed chronic kidney disease after only seven months of acute onset. As for adaptative FSGS, it was more common in our children, with 61% of cases. The outcome was marked by increased evolution towards chronic kidney disease and poor response to immunosuppressive therapies. Finally, two cases of FSGS were seen after the prolonged use of CNI inhibitors for the treatment of nephrosis. One of these patients ultimately evolved into chronic kidney disease. Management of FSGS is still challenging, especially in children. More studies, especially in the field of genetics, are needed to improve the outcome of this dreadful glomerulopathy.

Long Non-coding RNA H19 Augments Hypoxia/Reoxygenation-Induced Renal Tubular Epithelial Cell Apoptosis and Injury by the miR-130a/BCL2L11 Pathway.

Acute kidney injury (AKI) is a severe kidney disease defined by partial or abrupt loss of renal function. Emerging evidence indicates that non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs), function as essential regulators in AKI development. Here we aimed to explore the underlying molecular mechanism of the lncRNA H19/miR-130a axis for the regulation of inflammation, proliferation, and apoptosis in kidney epithelial cells. Human renal proximal tubular cells (HK-2) were induced by hypoxia/reoxygenation to replicate the AKI model in vitro. After treatment, the effects of LncRNA H19 and miR-130a on proliferation and apoptosis of HK-2 cells were investigated by CCK-8 and flow cytometry. Meanwhile, the expressions of LncRNA H19, miR-130a, and inflammatory cytokines were detected by qRT-PCR, western blot, and ELISA assays. The results showed that downregulation of LncRNA H19 could promote cell proliferation, inhibit cell apoptosis, and suppress multiple inflammatory cytokine expressions in HK-2 cells by modulating the miR-130a/BCL2L11 pathway. Taken together, our findings indicated that LncRNA H19 and miR-130a might represent novel therapeutic targets and early diagnostic biomarkers for the treatment of AKI.

Patients with Protein-Truncating PKD1 Mutations and Mild ADPKD.

Progression of autosomal dominant polycystic kidney disease (ADPKD) is highly variable. On average, protein-truncating PKD1 mutations are associated with the most severe kidney disease among all mutation classes. Here, we report that patients with protein-truncating PKD1 mutations may also have mild kidney disease, a finding not previously well recognized. From the extended Toronto Genetic Epidemiologic Study of Polycystic Kidney Disease, 487 patients had PKD1 and PKD2 sequencing and typical ADPKD imaging patterns by magnetic resonance imaging or computed tomography. Mayo Clinic Imaging Classification on the basis of age- and height-adjusted total kidney volume was used to assess their cystic disease severity; classes 1A or 1B were used as a proxy to define mild disease. Multivariable linear regression was performed to test the effects of age, sex, and mutation classes on log-transformed height-adjusted total kidney volume and eGFR. Among 174 study patients with typical imaging patterns and protein-truncating PKD1 mutations, 32 (18%) were found to have mild disease on the basis of imaging results (i.e., Mayo Clinic Imaging class 1A-1B), with their mutations spanning the entire gene. By multivariable analyses of age, sex, and mutation class, they displayed mild disease similar to patients with PKD2 mutations and Mayo Clinic Imaging class 1A-1B. Most of these mildly affected patients with protein-truncating PKD1 mutations reported a positive family history of ADPKD in preceding generations and displayed significant intrafamilial disease variability. Despite having the most severe mutation class, 18% of patients with protein-truncating PKD1 mutations had mild disease on the basis of clinical and imaging assessment. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_02_18_CJN11100720_final.mp3.

Antikoagulantna terapija u bolesnika s fibrilacijom atrija i kroničnom renalnom insuficijencijom

Atrial fibrillation is the most common cardiac arrhythmia and it is associated with a significantly increased risk of stroke and systemic embolism. To reduce this risk it is important to start these patients on life-term oral anticoagulation. Many patients with atrial fibrillation also have some degree of renal insufficiency, which further increases the risk of stroke and thromboembolism, as well as the risk of bleeding. Therefore it is crucial to carefully choose a type of anticoagulant medication that is effective and safe for patients suffering from atrial fibrillation and renal insufficiency. There are two types of oral anticoagulants, vitamin K antagonists and new oral anticoagulants (NOAC). Warfarin is the most commonly used vitamin K antagonist, while NOACs include dabigatran, rivaroxaban, apixaban and edoxaban. Considering NOACs are mostly renally excreted, only patients with mild to moderate renal insufficiency were included in the original clinical trials, but these trials showed that NOACs are as effective or superior to warfarin and are now the treatment of choice for patients with atrial fibrillation and mild or moderate renal insufficiency. Few NOAC pharmacokinetic studies were performed and found doses of these drugs that produce stable plasma levels in patients with severe renal insufficiency and could be effective in preventing thromboembolism. The results of studies that included warfarin treatment in these patients are heterogeneous, showing it could produce a satisfactory anticoagulant effect or it could even increase the stroke risk. Major bleeding also seems to be less frequent in patients with severe renal insufficiency treated with NOACs then in those treated with warfarin. Besides bleeding, an important factor of safety to keep in mind while treating patients with renal insufficiency is the progression of their kidney disease and the development of acute kidney injury. A specific type of kidney injury known as anticoagulant related nephropathy is a severe adverse effect of oral anticoagulant therapy, related mostly to warfarin use. It can occur even in patients with mild renal insufficiency or normal kidney function, often leading to life-long hemodialysis. Considering their superior safety profile as well as the possibility of achieving stable plasma levels even in severe kidney disease, NOACs seem to be a better option for anticoagulant treatment of patients with atrial fibrillation and renal insufficiency.

Estimating Nosocomial Infection and its Outcomes in Hospital Patients in England with a Diagnosis of COVID-19 Using Machine Learning

Background: COVID-19 nosocomial infections (NIs) may have played a significant role in the dynamics of the pandemic in England, but analysis of their impact at the national scale has been lacking. Our aim was to provide a comprehensive account of NIs, identify their characteristics and outcomes in patients with a diagnosis of COVID-19 and use machine learning modelling to refine these estimates.Methods: From the Hospital Episodes Statistics database all adult hospital patients in England with a diagnosis of COVID-19 and discharged between March 1st 2020 and March 31st 2021 were identified. A cohort of suspected COVID-19 NIs was identified using four empirical methods linked to hospital coding. A random forest classifier was designed to model the relationship between acquiring NIs and the covariates: patient characteristics, comorbidities, frailty, trust capacity strain and severity of COVID-19 infections.Findings: In total, 374,244 adult patients with COVID-19 were discharged during the study period. The four empirical methods identified 29,896 (8.0%) patients with NIs. The random forest classifier estimated a mean NI rate of 10.5%, with a peak close to 18% during the first wave, but much lower rates thereafter and around 7% in early spring 2021. NIs were highly correlated with longer lengths of stay, high trust capacity strain, greater age and a higher degree of patient frailty. NIs were also found to be associated with higher mortality rates and more severe COVID-19 sequelae, including pneumonia, kidney disease and sepsis.Interpretation: Identification of the characteristics of patients who acquire NIs should help trusts to identify those most at risk. The evolution of the NI rate over time may reflect the impact of changes in hospital management practices and vaccination efforts. Variations in NI rates across trusts may partly reflect different data recording and coding practice.Funding: None to declare. Declaration of Interest: None to declare.

Plasma exchange for the management of ANCA-associated vasculitis: the con position.

Advances in the diagnosis and treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis have led to continued improvement in survival and prognosis over the course of the last 4 decades. Nevertheless, the most acute and severe disease manifestations, including severe kidney disease and alveolar hemorrhage, continue to be associated with increased early mortality from disease activity or treatment complications as well as risk for the development of end-stage kidney disease (ESKD), which in turn directly affects the overall prognosis of ANCA-associated vasculitis. Plasma exchange (PLEX) has long been proposed and used for these most severe disease manifestations under the assumption that its effects are swift and supported by our understanding of the pathogenic role of ANCA. Yet convincing evidence of a beneficial effect of PLEX in ANCA-associated vasculitis has been lacking, as early studies and small trials have generated conflicting results. The controversy regarding PLEX has been accentuated recently as the largest randomized controlled trial ever conducted in ANCA-associated vasculitis, the Plasma Exchange and Glucocorticoids in Severe ANCA-associated Vasculitis trial, which was specifically designed to evaluate the efficacy of PLEX in patients with severe renal disease or alveolar hemorrhage, failed to show a difference in the combined primary outcome measure of death or ESKD in patients who received PLEX versus those who did not. In light of these disappointing results, we herein review the currently available data on PLEX for ANCA-associated vasculitis and explain why we believe that these data no longer support the use of PLEX in ANCA-associated vasculitis.

A preoperative modified Allen test result may be associated with long term mortality after hemodialysis access construction.

The modified Allen test (MAT) is a simple bedside method determining collateral hand circulation prior to hemodialysis (HD) access surgery. Hand ischemia as reflected by low systolic finger pressures (Pdig) is associated with high mortality rates in severe kidney disease (CKD) patients. Aim of the present study was to assess a possible relation between absolute finger pressure drop (∂Pdig) during a preoperative MAT and mortality after a first HD access construction. Pdig (systolic pressure, mmHg) was measured using digital plethysmography following compression of radial and ulnar arteries in CKD patients just before access surgery between January 2009 and December 2018 in one center. The greatest ∂Pdig of both index fingers was used for analysis. Cardiovascular and overall mortality were assessed during the following 4 years using the ERA-EDTA classification system (codes 11, 14-16, 18, 22-26, 29). Cox regression analysis determined possible associations between ∂Pdig and mortality. Complete data sets were available in 108 patients (male n = 71; age 70 years ±12; mean follow up (FU) 1.6 years ±0.1; FU index 99% ±1). Median ∂Pdig was 31 mmHg (range 0-167 mmHg). Patients having cardiovascular disease (CV+) demonstrated higher ∂Pdig values (CV+ 44 ± 5 mmHg vs CV- 29 ± 3 mmHg, p = 0.012). A total of 26 patients (24%) died during FU (CV+ death, n = 16; 62%). For each 10 mmHg ∂Pdig increase, overall mortality increased by 10%, and CV+ mortality by 15% (overall mortality: HR 1.10 [1.01-1.22], p = 0.048; CV+ mortality: 1.15 [1.03-1.29], p = 0.017). Following correction for age, ∂Pdig remained associated with CV+ mortality (HR 1.13 [1.00-1.26], p = 0.043). A large drop in systolic finger pressure during a preoperative MAT is related to mortality after primary HD access surgery. The role of this potential novel risk parameter requires confirmation in a larger population.