Chronic Renal Replacement Therapy Research Articles

#1556 An unusually high prevalence of TMEM67 c.1843T>C (p.Cys615Arg) variant in Russia

Abstract Background and Aims A hypomorphic TMEM67 variant c.1843T>C (p.Cys615Arg) (rs201893408) is associated with an autosomal-recessive condition characterized by a combination of nephronophthisis and liver fibrosis, and, in some cases, neurologic manifestations. According to the gnomAD database, it reaches the highest prevalence in Swedish population (MAF=17/26128, 0.00065). In two large European studies of nephronophthisis and related conditions, the contribution of this pathogenic allele to TMEM67-associated disorders reached 15%-27%. The report presents the first evidence for the major contribution of this recurrent variant to nephronophthisis in Russia. Method Blood DNA samples of 29 pediatric patients, undergoing chronic renal replacement therapy in a dialysis department of a large pediatric medical center, were evaluated by targeted (“clinical exome”) sequencing. KAPA HyperCap Heredity Panel (Roche) was used for target enrichment. Sequencing was performed on Illumina Nextseq2000 device. The alignment on GRCh37 reference genome sequence was made using BWA 0.7.12; HaplotypeCaller (GATK 3.3.0) was used for variant calling. Causative variants were verified by Sanger sequencing. Results Among other findings, we have identified two unrelated Russian patients, homozygous for TMEM67 p.Cys615Arg mutation; none of them have previously been diagnosed with nephronophthisis. Patient D, a 11-year-old girl, presented with unexplained chronic kidney disease with unremarkable ultrasound findings. Patient B was an 8-year-old girl with chronic kidney disease linked to bilateral ureterohydronephrosis. In both patients, cholestatic hepatitis of unknown etiology was diagnosed. No neurological involvement was reported. The parents of both girls denied consanguinity. One more Russian patient homozygous for p.Cys615Arg variant had been previously described [Andreeva and Savenkova, 2022; in Russian]: the 2-year-old child born from non-consanguineous parents had prenatally identified multiple renal cysts, nephrogenic arterial hypertension, and laboratory signs of cholestasis. The analysis of Ruseq database (ruseq.ru) confirmed high prevalence of TMEM67 c.1843T>C (p.Cys615Arg) variant in Russian population (MAF=14/10860, 0.0013). Conclusion TMEM67 c.1843T>C (p.Cys615Arg) allele is particularly common in Russian pediatric patients with chronic kidney disease and liver involvement, and, therefore, deserves to be analyzed in other countries with predominantly Slavic population.

Anakinra for Refractory Pseudogout in Patients with End-stage Renal Disease on Haemodialysis.

Calcium pyrophosphate deposition (CPPD) arthritis is the second most common type of crystal-induced arthritis after gout. Acute flares are commonly treated with non-steroidal anti-inflammatory drugs, intra-articular or short-term systemic glucocorticoids or colchicine. However, since there is no pharmacological treatment to reduce CPPD crystal burden, relapsing or chronic CPPD arthritis may be challenging to treat, particularly in patients with end-stage renal disease who are at risk for toxicity of the above medications. Since IL-1β appears to be driving CPPD arthritis, we treated two patients with chronic CPPD arthritis and end-stage renal disease on haemodialysis with the IL-1β receptor antagonist anakinra. In both patients, arthritis resolved quickly, while continuation of anakinra maintained remission and allowed complete glucocorticoid withdrawal. Therefore, anakinra may be a safe and effective option both for short and long-term treatment of CPPD arthritis in patients on chronic renal replacement therapy.

Prevalence and impact of chronic dysglycaemia among patients with COVID-19 in Swedish intensive care units: a multicentre, retrospective cohort study

ObjectiveUsing glycated haemoglobin A1c (HbA1c) screening, we aimed to determine the prevalence of chronic dysglycaemia among patients with COVID-19 admitted to the intensive care unit (ICU). Additionally, we aimed to...

#3479 RISK FACTORS OF DEATH OR CHRONIC RENAL REPLACEMENT THERAPY REQUIREMENTS IN PATIENTS WITH THROMBOTIC MICROANGIOPATHIES WITHOUT ADAMTS-13 DEFICIENCY

Abstract Background and Aims Thrombotic microangiopathy without severe ADAMTS-13 deficiency activity levels (TMA-13n) has a high mortality rate. Early recognition of patients at higher risk of dying or needing chronic renal replacement therapy (composite outcome: CO) has become of paramount importance since treatments such as eculizumab could ameliorate the prognosis of this group of patients. Plasmic score have been shown to predict severe ADAMTS-13 deficiency; however, its role as a prognostic factor of CO in TMA-13n is unknown. Method We retrospectively evaluate the potential factors associated with the risk of CO. Patients diagnosed with TMA-13n (defined by microangiopathic anaemia, thrombocytopenia, organ damage and ADAMTS-13 activity ≥ 10%) from January 2008 to May 2018 in our centre were included in the study. Results Forty-two consecutive patients were included. Mean (SD) age: 41(20) years. Twenty-five (60% were females. Mean (SD) ADAMTS-13 activity: 69 (24%). Twenty-six (62%) patients required dialysis at admission. Nineteen (45%) met CO (10 patients died). Higher age, lower lactate dehydrogenase, PLASMIC score values ≤ 4, neuroradiological damage and early eculizumab use [median (IQR): 4 (0-16) days from hospital admission: 5] were factors associated with the risk for developing CO. Only three factors were independently associated with CO mortality by logistic regression: early use of eculizumab (OR: 0.14; 95% CI: 0.02-0.94) and neuroradiological damage (OR: 6.67; 95% CI: 1.12-39.80) and PLASMIC score ≤ 4 (OR: 7.39; 95% CI: 1.18-46.11). Conclusion In TMA-13n patients, neuroradiological damage, low PLASMIC score and early use of eculizumab were independent prognostic factors of death and chronic renal replacement therapy requirements.

#2654 USE OF SUPERVISED DEEP LEARNING ALGORITHM TO PREDICT RISK OF RENAL REPLACEMENT THERAPY(RRT) IN PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD)

Abstract Background and Aims Chronic kidney disease (CKD) is one of the most common causes of mortality, affecting around 10% adults worldwide [1]. Although statistical models for predicting risk of renal replacement therapy (RRT) have been developed for a decade [2], referral of patients with CKD to nephrology service is often based on clinical experience of primary care physicians. The use of deep learning algorithms (DLAs) allow clinicians to capture complex, multidimensional, non-linear relationships instead of relying on linear relationships between independent variables and outcome. Our study aims to develop a DLA that has at least non-inferior performance compared to the Kidney Failure Risk Equation (KFRE), which is a well-established and validated risk prediction tool [3]. Method This is a retrospective cohort study carried out in 3 major acute hospitals in Hong Kong providing a total of 3000 beds from Jan 1, 2009 to Mar 31, 2022. All patients aged > 18 with an estimated glomerular filtration rate (eGFR)<30ml/min/1.73 m2 according to the CKD-EPI formula, who attended follow-up for at least 3 months in nephrology clinic of the 3 hospitals, were recruited. Those who were on chronic RRT, received renal transplantation or had an eGFR<15 ml/min/1.73 m2 before referral were excluded. Supervised DLAs of different structures and their combinations were created and trained. Data in the test set were fed into models to predict the risk of requiring RRT in 2 years and 5 years. Predictive performance of these models were compared with that of KFRE [3]. Results 4992 patients were recruited in the study. Data of 499 patients were isolated as test set and were not used for model training. 1576 patients progressed to stage 5 CKD during their follow-up, and 989 patients required initiation of RRT during the study timeframe. When compared with KFRE (4-variable: ROC-AUC = 0.84, 95%CI:0.835-0.852; 8-variable: ROC-AUC = 0.84, 95%CI:0.830-0.847), almost all DLAs showed statistically significant superior robustness in predicting the risk of requiring RRT (Figure 1). No significant difference was found between performance of DLAs combining different neural network layers and those with single structures (CNN+LSTM+ANN layers ROC-AUC = 0.90, 95%CI:0.896-0.902; CNN ROC-AUC = 0.91, 95%CI:0.907-0.914) (Table 1). Conclusion The use of DLAs provided better prediction in the risk of requiring RRT when compared with KFRE.

#5532 COVID-19 INFECTION MODIFIES GLOMERULAR DISEASE EVOLUTION

Abstract Background and Aims A fibrotic effect of the SARS-Cov2 virus (Covid-19) has been described and the risk for acute renal failure in glomerular disease (GD) patients; however, the long-term renal effect in these patients is unknown. We evaluate the impact of the Covid-19 infection on eGFR, the influence of proteinuria, the effect of the drugs used to control glomerulonephritis and the use of Paxlovid (nirmatrelvir/ritonavir) for covid infection control. Method We retrospectively evaluate the eGFR (mL/min/1.73m2) at month 12 and 6 before infection (pre-infection period), during infection, 6 months after infection and at the last visit post-infection in renal biopsy-proven glomerulonephritis patients. Patients were included from January/2020 to July/2022. All patients were followed up for six months or more from infection. Results Forty-seven patients were included. The mean follow-up was 13 months (min: 6-max = 33). Sex Female 24 (52%), Age (mean[SD]) = 47 (14) years. 39(85%) were vaccinated before infection. At infection time, 31(66%) of the patients presented proteinuria (protein/creatinine ratio > 0,2 mg/mg). 27(54%) received oral steroids, 27(54%) mycophenolate, 24(51%) prednisone, and 27(54%) renin-angiotensin system inhibitors (RASi). Four (8%) started chronic renal replacement therapy during the follow-up, and 12(25%) required hospital admission. During the pre-infection period, eGFR remained stable (mean change (95%CI): -2.2 (-8.2 to 3.7) mL/min/1.73m2, P = 1. Compared with month six before infection, eGFR decreased at the end of the follow-up by 9.1 (95% CI: 0.96 to 17.2) mL/min/1.73m2, P = 0.019. After stratifying by the presence of proteinuria, eGFR decreased only in those with proteinuria 14.5 (95%CI: 3.7 to 25.4) mL/min/1,73m2, while no changes were observed in those without proteinuria. No changes in proteinuria level after infection were observed. No interaction between drugs used, hospitalisation requirements and eGFR evolution was observed. In the sub-group of patients treated with Paxlovid (all previously vaccinated) after six months of follow-up, no patients required hospitalisation; however, eGFR evolution was similar to the whole group, which decreased only in those with proteinuria at baseline. Conclusion The Covid-19 infection in proteinuric GD patients changed the renal function evolution dramatically. The medication used (mycophenolate, steroid and RASi), including Paxlovid, did not influence this evolution. At the end of the follow-up, the accelerated renal function deterioration continues. Urgent therapeutic measures for controlling eGFR decline in these patients are needed.

#2969 IS DIABETES MELLITUS ASSOCIATED WITH WORSE KIDNEY OUTCOME IN PATIENTS WITH GLOMERULOPATHIES?

Abstract Background and Aims Diabetes mellitus (DM) is the leading cause of end stage kidney disease and a major risk factor for cardio-vascular disease and death. While it is known that subjects with diabetic nephropathy (DN) have a worse kidney outcome compared to other non-diabetic glomerulopathies, it is not certain whether DM independently influences the kidney outcome in subjects diagnosed with glomerulopathies (GP) other than diabetic nephropathy. Method This retrospective study included 1200 adults [50 (95%CI 48 to 51) years, 56% males, eGFR 48.5 (95%CI 45.9 to 51.3) mL/min], with kidney biopsy (KB) proven GP between 1st Jan. 2008 and 31st Dec. 2017. Subjects were followed for a mean of 89 (95%CI 85.5 to 92.4) months until 31st May 2018. The primary endpoints were the initiation of chronic renal replacement therapy (RRT) or death. Subjects with inappropriate biopsy sample, insufficient data and RRT prior to KB were excluded. Demographic, clinical and laboratory data at the time of biopsy were retrieved from medical records. Kidney survival was evaluated by Kaplan-Meier method and a competitive risk to event analysis was used to estimate the risk of RRT, considering death as a competing event. Variables related to kidney outcome were evaluated by the subdistribution hazard function using Fine-Gray model. According to the presence or absence of DM and the types of GP, subjects were divided in three groups: GP without DM (n = 987 pts.), GP with DM (n = 65 pts.), and DN (n = 148 pts.). Results GP with DM subjects were older (60 (95%CI 56 to 64) years vs. 55.5 (95%CI 54 to 59) years in DN group vs. 47 (95%CI 45 to 48) years in GP without DM; p<0.001). Males were predominant in all groups, with higher frequency in DN group (66.9% vs. 54.9% - GP without DM vs. 61.5% - GP with DM; p = 0.01). DN group had higher Charlson comorbidity index [5 (95%CI 4 to 5) vs. 2 (95%CI 2 to 2) in GP without DM vs. 3 (95%CI 3 to 4) in GP with DM; p<0.001], lower eGFR (31.3 (95%CI 25.4 to 36.7)mL/min vs. 51.9 (95%CI 48.9 to 55.8)mL/min in GP without DM vs. 43.2 (95%CI 35.4 to 51.3) mL/min in GP with DM; p<0.001) and higher proteinuria (4.9 (95%CI 3.8 to 6) g/g vs. 2.6 (95%CI 2.35 to 2.9) g/g in GP without DM vs. 4.3 (95%CI 2.7 to 6.7) g/g in GP with DM); p<0.001]. During the follow-up period, 24.3% needed RRT, while 11.4% died. The highest RRT initiation and death frequency was in DN group (40.5% vs. 21.7% in GP without DM vs. 27.7% in GP with DM; p<0.001, and 18.2% vs. 10% in GP without DM vs. 19.9% in GP with DM; p = 0.004). In the univariate time-dependent analysis, subjects with DN had the worse kidney outcome (log rank p<0.001) (Fig. 1), however the kidney survival was similar between GP with DM and GP without DM subjects (log rank p = 0.1). In the competitive risk time to event analysis where death is considered the competing event, diabetic nephropathy subjects had worse kidney survival than GP with DM subjects [CIF 2.3 vs. 1.3, p<0.001], while GP with DM had similar survival with GP without DM (CIF 1,3; p = 0.2) (Fig. 2). After adjusting for the risk factors for CKD progression, DM was not associated with an increased risk of RRT (HR = 0.98, p = 0.9). Predictors for RRT were diabetic nephropathy on KB, along with younger age, lower serum albumin, and lower baseline eGFR. Conclusion In this large cohort of subjects with glomerulopathies, diabetes mellitus complicated with diabetic nephropathy seem to have a worse kidney outcome, while DM in subjects with glomerulopathies other than DN doesn't seem to influence the progression to RRT.

CARD26: Renal replacement therapy after Left Ventricular Assist Device (LVAD) placement: a single center post hospitalization outcome analysis

Background: Historically, advanced chronic kidney disease (CKD) stage 4 or greater and dialysis are often considered to be a relative contraindication for left ventricular assist device (LVAD) implantation. We aim to describe our experience with advanced CKD patients receiving LVADs. Methods: Data was collected by retrospective chart review at our institution. We reviewed all CKD patients who underwent durable LVAD placement requiring perioperative renal replacement therapy (RRT) at our institution between November 2014 and July 2021. Fifty-nine patients were identified, inclusive of patients acutely requiring perioperative RRT and those going on to require chronic RRT. Clinical events of interest included need for dialysis, mortality, infection, thrombotic events, bleeding, and readmission rates at 1, 3, 6 and 12 months. Data was analyzed using multivariate logistic regression. Results: Of the 59 patients, 88.7% were male with an average age of 56 years. Twenty eight had HeartMate III (HM3) LVAD, 24 had HVAD and 7 had HMII. Patients with CKD at baseline were stratified by their pre-VAD CKD stages and majority fell in CKD stage 3a/b. Table 1 depicts further analysis for patients with CKD and non-CKD pre-VAD. CKD stage prior to LVAD did not show a correlation with the need for dialysis post implant (p=0.34, table 2). Conclusion: In this small, single center, retrospective analysis, pre-VAD CKD stage is not necessarily predictive of dialysis. Furthermore, no significant difference was identified between CKD and non-CKD patients. Further studies to determine risk factors for dialysis and subsequent morbidity and mortality in this population to appropriately characterize risk for CKD patients will be of utmost importance.

Encefalopatía inducida por contraste en pacientes con enfermedad renal crónica avanzada: aquello que el nefrólogo necesita saber

Contrast-induced encephalopathy is a neurological complication related to contrast used in endovascular procedures or computed tomography (CT). The main risk factors are arterial hypertension, diabetes mellitus, chronic kidney disease (CKD), hyperosmolar contrasts, the amount of infused contrast and its direct infusion in the posterior cerebral territory, or pathologies with blood–brain barrier damage. Symptomatology is non-specific and may present as altered level of consciousness, neurological focality or seizures. Diagnosis is done by exclusion after ischemic or hemorrhagic stroke has been ruled out; CT or MRI are useful for differentiation. Generally, it appears shortly after exposure and the symptoms lasts 48–72 h with complete recovery, although cases with persistence of symptoms or longer duration have been described. Treatment consists of monitoring, supportive measures and renal replacement therapy (RRT) with hemodialysis (HD) in patients in chronic RRT program. It is important for the nephrologist to be aware of this entity given the susceptibility of the patient on HD as well as its potential therapeutic role in these patients.

Pathophysiological and Diagnostic Aspects of Sarcopenia in Hemodialysis Patients

Chronic kidney disease and renal replacement therapy, particularly hemodialysis, contribute to the development of negative protein balance and muscle dysfunction in dialysis patients, from the development of protein-energy malnutrition to sarcopenia. Due to multifactorial etiology and complex pathophysiological patterns, sarcopenia has proven to be a significant predictor of cardiovascular events and is associated with a higher risk of overall mortality. Screening methods of chronic kidney patients and patients on hemodialysis who are at higher risk of developing sarcopenia, as well as diagnostic methods for this group of patients are not clearly defined, hence methods used for the general population of elderly patients, especially based on the revised European consensus on definition and diagnosis of sarcopenia of the European Working Group on Sarcopenia in Older People (EWGSOP2), are utilized in this subpopulation as well. Therefore, there is a need to define new biomarkers of sarcopenia such as the existing 24h urine excretion of creatinine, a product of estimated glomerular filtration of cystatin C and creatinine or myostatin and their use in routine work with dialysis patients to identify this condition among them and reduce morbidity and mortality.

Inequalities in end-stage renal disease: underprivileged and ethnic minority members are at higher risk.

Incidence of end-stage renal disease (ESRD) is higher in Israel than the European average. Socio-economic differences in ESRD have been reported globally, but many countries lack a national register. Using national data, we assessed which socio-demographic factors are associated with 5-year incidence of ESRD in Israel, where there is universal access to renal replacement therapy (RRT). Data on all incident ESRD cases aged ≥20 years receiving chronic RRT between 1 January 2014 and 31 December 2018 (N = 7883) were collected from Israel's National Dialysis & Renal Transplant Register. Individual-level data on ESRD cases requiring RRT included residential area, age, gender, ethnicity (Jewish or Arab) and ESRD cause (diabetes, other, unknown/missing). Area-level data included age and sex distribution, socio-economic status (SES) and proportion of Arab population. The associations between individual-level socio-demographic characteristics and ESRD cause were tested in bivariate comparisons. The risk of developing ESRD during the study period (from all and specific causes) was estimated using multiple Poisson regression models with negative binomial distribution, using four parameters, namely sex, ethnicity, SES category and age strata, based on area-level distribution of these parameters, and with the whole population (aged ≥20 years) as the denominator. A socio-economic gradient was seen for ESRD from all causes, more marked for diabetic aetiology [rate ratio (RR)=0.45, 95% CI: 0.39-0.52 highest vs lowest SES categories] than from other (RR = 0.64, 95% CI: 0.55-0.75) or unknown cause (RR = 0.79, 95% CI: 0. 62-0.99). Based on population area-level data, predominantly Arab neighbourhoods showed higher risk for ESRD requiring RRT for all causes, with the strongest association for diabetes (RR = 1.69, 95% CI: 1.53-1.86) adjusted for SES, age and sex. A strong socio-economic gradient was demonstrated for ESRD requiring RRT. Arab ethnicity was associated with higher risk for ESRD, especially due to diabetes. Our findings suggest the need for allocation of health resources according to needs and culturally appropriate interventions for improving control of modifiable risk factors for chronic renal failure.

(770) Chronic Renal Replacement Therapy in Patients with Durable Left Ventricular Assist Devices

(770) Chronic Renal Replacement Therapy in Patients with Durable Left Ventricular Assist Devices

Effects of age and comorbidities on prognosis and mortality in geriatric patient groups in ıntensive Care.

Treatment of geriatric intensive care patients is tiring and difficult for intensive care physicians due to comorbidities, accompanying acute illnesses and vulnerabilities. The aim of our study was to determine other factors affecting mortality and morbidity with age in geriatric intensive care patients. A total of 937 geriatric intensive care patients were divided into three groups as young-old (65-74 years), middle-old (75-84 years), and oldest-old (85 years and more). Demographic characteristics such as age, gender, and comorbid diseases (oncological malignancy, chronic renal failure, sepsis, chronic anemia, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, pulmonary embolism) were recorded. The number of patients who needed a mechanical ventilator, developed decubit ulcers, underwent percutaneous tracheostomy, and renal replacement therapy were recorded. In addition, the number of central venous catheter insertions for patients, Acute Physiology and Chronic Health Evaluation II scores (APACHE II), hospitalization days, and mortality rates were recorded and compared. In the comparison between the groups in terms of gender, in the 65-74 years' age group, male gender was higher, while in the age group of 85 years and more, the female gender was found to be statistically higher. Among comorbid diseases, the rate of oncological malignancy was found to be statistically significantly lower in patients aged 85 years and more. Comparing the APACHE II scores of the patients as per the groups, scores were found to be statistically significantly higher in the oldest-old group. APACHE II Score, central venous catheter application, chronic obstructive pulmonary disease, chronic renal failure, sepsis, oncological malignancy, and renal replacement therapy were shown to be statistically significant as factors affecting death. The factors affecting the survival or hospitalization time of the patients of decubit ulcer, mechanical ventilator, percutaneous tracheostomy, chronic obstructive pulmonary disease, Sepsis, APACHE II Score, and age were shown to be statistically significant. Our study showed that not only age has an effect on mortality and morbidity in geriatric intensive care patients but also comorbidities and intensive care treatments of the patients are also effective in this process.

High-Volume Hemodiafiltration with Step-Down Approach versus Standard-of-Care Continuous Renal Replacement Therapy Approach in Critically Ill Burn Patients

Introduction: Acute kidney injury (AKI) is a common complication of severe burn injuries and contributes to morbidity and mortality. It is exacerbated in burn patients by elevated serum creatinine and pro-inflammatory cytokines, leading to immune dysregulation. Chronic renal replacement therapy is standard of care and removes cytokines to return the body to homeostasis. Continuous veno-venous hemodiafiltration (CVVHDF) is a high-filtration method to enhance cytokine clearance; we analyze a step-down approach for improved outcomes in burn patients. Methods: This study reviewed 15 burn patients at Akron Children’s Hospital stratified into 2 groups: high-flow CVVHDF with step-down approach versus standard CVVHDF. A normocarbia bicarbonate-based dialysate solution and citrate anticoagulation was applied, and blood flow rate was maintained greater than 200 mL/min. Results: Fifteen burn patients at Akron Children’s Hospital were separated into groups managed with high-flow CVVHDF (n = 9) and standard-flow CVVHDF (n = 6). All 15 developed AKI symptoms and diuretic-resistant fluid overload, with 4/15 displaying fluid overload greater than 40%. The most common indication for hemofiltration was acute tubular necrosis (11/15). Average time on CVVHDF was 20.2 days and length of admission was 58.6 days. Vasodepressor dependency index was significantly reduced in the high-flow group at 48 h, but no significant difference in mortality was identified. No significant difference was identified in adverse reactions, notably electrolyte imbalances. Conclusion: The literature on the efficacy of high-flow CVVHDF is limited. This study suggests improved mortality rates and length of stay with high flow compared to the literature. Further studies with multicenter involvement are necessary.

How useful is kidney biopsy for the management of glomerulopathies in the elderly?

The use of kidney biopsy in elderly individuals is still matter of discussion. The purpose of this study isto assess the utility of kidney biopsy for the management of glomerulopathies in an Eastern European cohort, targetingpatients older than 65years. This retrospective study included 875 adults (147 older than 65years), with biopsy-proven glomerulopathies, followed up for 71.1 (95% CI 68.2-73.9) months. The primary endpoint was chronic renal replacement therapy initiation.Statistical evaluation wasperformed with IBM SPSS software version 20, Analyse-it, and SAS Studio. The Kaplan-Meier method was used to estimate the time to death and the log-rank test was used for comparisons. The multivariate Cox proportional hazard analysis was used to evaluate the risk of death. Secondary glomerulopathies were more frequent in patients aged > 65years (52.4% vs. 41.9%, p = 0.004). Membranous nephropathy and amyloidosis were the most frequent primary and secondary glomerulopathies in this age group. Kidney biopsy complications were low (< 4%) in both age groups. In 42% of the elderly, the result of biopsy guided the immunosuppressive therapy. While the all-cause mortality rate was higher (OR 4.2; 95% CI 2.7-6.7; p < 0.0001) in elderly individuals, the rate of renal replacement therapy initiation was similar (31.3 vs 26%; p = 0.1) in both age groups. In the competitive risk analysis, kidney survival was similar irrespective of age [CIF 0.4 (95% CI 0.26-0.53) vs. 0.34 (95% CI 0.28-0.39), p = 0.08]. However, after adjusting for the confounding factors, younger age was associated with an increased risk of renal replacement therapy (HR = 1.57, p = 0.01), along with secondary glomerulopathies. The diagnosis of an underlying glomerulopathy guided the therapy in almost one-half of the elderlypatients who underwent a kidney biopsy, provided important prognostic information and had a low complications rate; kidney biopsy may therefore be considered a safe, reliable procedure in the management of glomerulopathies, even in patients over 65years of age.

Remdesivir Administration in COVID-19 Patients With Renal Impairment: A Systematic Review.

Remdesivir (RDV) is the main antiviral for the treatment of moderate to severe forms of Coronavirus disease 2019 (COVID-19). Several studies revealed a shortening time to clinical improvement of COVID-19 and mortality benefits in patients receiving RDV. The patients with renal disease were excluded from large clinical trials of RDV, and the probable nephrotoxicity of the drug, its metabolites, and the vehicle (sulfobutylether-β-cyclodextrin) have led to the recommendation against using RDV in patients with an estimated glomerular filtration rate of <30 mL/min. This systematic review aimed to collect data about the necessity and safety administration of RDV in the setting of renal impairment. Search through databases including MEDLINE, ScienceDirect, Cochrane Library, and PubMed was performed. The studies were carried out in adults and enrolled patients with different types of renal impairment (ie, acute kidney injury, chronic kidney disease, kidney transplant, and renal replacement therapy) were included. Eligible studies were assessed, and required data were extracted. Twenty-two cross-sectional studies, cohorts, case reports, and case series were included in this review. The mortality rate was between 7.3% and 50%, and various severity of COVID-19 was included in the studies. None of them reported an increase in adverse effects attributed to RDV administration. A decrease in inflammatory mediators and other benefits were obvious. Although the manufacturer's labeling does not recommend RDV administration in patients with severe renal impairment, it seems that nephrotoxicity is less concerning in the population of these patients. Moreover, RDV may be helpful in acute kidney injury induced by the viral invasion of COVID-19. To the best of our knowledge, this is the first systematic review of the use of RDV in kidney failure. Larger, well-designed, and pharmacokinetic studies are required to have a safe and logical recommendation about the use of RDV in patients with renal disorders.

COVID-19 impact on kidneys

Introduction and purposeThe COVID-19 pandemic, which has been ongoing since early 2020, has significantly affected the health care system worldwide. SARS-CoV-2 virus being the etiological factor of the disease has a high affinity for the renal organ. The purpose of this study was to provide an overview of the current knowledge of the problem of frequent AKI in the course of coronavirus infection, the impact of COVID-19 disease in patients with chronic kidney disease and on renal replacement therapy or dialysis.Review methodIn the process of writing, we used available articles and scientific papers in Pubmed and Google Scholar databases based on keywords: COVID-19, SARS-CoV-2, AcuteKidneyInjury, ChronicKidneyDisease.State of knowledgeSARS-CoV-2 virus enters target cells through the ACE2 receptor. In the pathophysiology of AKI in the course of COVID-19, a key role is attributed to secondary damage mechanisms such as cytokine storm, hypoperfusion with hypoxia, endothelial dysfunction. The incidence of acute kidney injury ranges from 5.1% to 36.6%. The development of AKI, renal transplant status, the presence of chronic kidney disease or renal replacement therapy is associated with an increased risk of severe course and higher mortality on COVID-19. SummaryThe COVID-19 pandemic has posed new logistical and therapeutic challenges to the health care system. Due to the high tropism of SARS-CoV-2 to the kidneys and the frequent occurrence of AKI during the course of the infection, nephrology patients, those on renal replacement therapy and those awaiting transplantation should be placed under special surveillance. Patients in these groups are at particular risk for a severe course of COVID-19.

Circulating Omentin-1, Sustained Inflammation and Hyperphosphatemia at the Interface of Subclinical Atherosclerosis in Chronic Kidney Disease Patients on Chronic Renal Replacement Therapy.

Background and Objectives: Subclinical atherosclerosis, reflected by abnormal carotid intima–media thickness (cIMT), is pervasive among chronic kidney disease patients on chronic renal replacement therapy (RRT), being mostly influenced by uremia-related rather than traditional risk factors. Materials and Methods: In this pilot study, we measured circulating levels of Omentin-1, a recently discovered adipokine with strong anti-atherogenic properties, in a heterogeneous cohort of 77 asymptomatic RRT individuals (40 chronic kidney transplant recipients, Ktx; and 37 chronic hemodialysis patients, HD) and in 30 age-matched controls. Results: Omentin-1 was increased in RRT individuals as compared with controls (p = 0.03). When stratifying for renal replacement modality, we found Ktx patients to have significantly lower Omentin-1 than HD patients (p = 0.01). Lower Omentin-1 levels were also found among RRT individuals with pathological cIMT (168.7 [51.1–457.8] vs. 474.9 [197.2–1432.1]; p = 0.004). Our multivariate correlations analysis revealed Omentin-1 as the most robust independent predictor of carotid atherosclerosis (β-0.687; p = 0.03), even more than total cholesterol, diastolic BP and age, and this adipokine was at the crossroad of a complex interplay with sustained inflammation (high CRP and ferritin) and hyperphosphatemia in predicting higher cIMT values. Conclusion: The findings reported extend to renal patients with advanced disease, with the possible involvement of Omentin-1 in the pathogenesis of atherosclerosis. This may set the stage for future interventional studies of Omentin-1 replacement to retard atherosclerosis progression, as it is currently being investigated in other disease settings.

A predictive risk score to diagnose hypocalcemia after parathyroidectomy in patients with secondary hyperparathyroidism: a 22-year retrospective cohort study

Hypocalcemia is a common complication found in patients with secondary hyperparathyroidism (SHPT) who undergo parathyroidectomy. This study aimed to construct a predictive risk score for the occurrence of hypocalcemia after parathyroidectomy in patients with SHPT who underwent chronic renal replacement therapy (RRT). This 22-year retrospective cohort study enrolled 179 patients with SHPT who had their first parathyroidectomy. Eighty-two percent of patients developed hypocalcemia within 16.9 (95% CI 14.5–19.5) h after parathyroidectomy. This study demonstrated four factors as independent risk factors for post-parathyroidectomy hypocalcemia, including duration of RRT, preoperative serum phosphate, preoperative serum alkaline phosphatase (ALP) and mean difference of serum intact parathyroid hormone (iPTH). By using logistic regression analysis, this study demonstrated cut-off points for these four risk factors for the diagnosis of hypocalcemia after parathyroidectomy: 5 years for the duration of RRT, 5 mg/dL for serum phosphate, 387 U/L for serum ALP, and 97% for the mean difference of serum iPTH. Finally, the predictive risk score was constructed by assigning a score of one to each factor. With a total score of at least 2, the proposed predictive risk score has an AuROC of 0.755 with a sensitivity of 78.2%, a specificity of 71.4%, and an accuracy of 76.9%.

A Murine Model of Hemodialysis Access-related Hand Dysfunction.

Chronic kidney disease is a major public health problem, and the prevalence of end-stage renal disease (ESRD) requiring chronic renal replacement therapies such as hemodialysis continues to increase. Autogenous arteriovenous fistula (AVF) placement remains a primary vascular access option for ESRD patients. Unfortunately, approximately half of the hemodialysis patients experience dialysis access-related hand dysfunction (ARHD), ranging from subtle paresthesia to digital gangrene. Notably, the underlying biologic drivers responsible for ARHD are poorly understood, and no adequate animal model exists to elucidate the mechanisms and/or develop novel therapeutics for the prevention/treatment of ARHD. Herein, we describe a new mouse model in which an AVF is created between the left common iliac artery and vein, thereby facilitating the assessment of limb pathophysiology. The microsurgery includes vessel isolation, longitudinal venotomy, creation of arteriovenous anastomosis, and venous reconstruction. Sham surgeries include all the critical steps except for AVF creation. Iliac AVF placement results in clinically relevant alterations in central hemodynamics, peripheral ischemia, and impairments in hindlimb neuromotor performance. This novel preclinical AVF model provides a useful platform that recapitulates common neuromotor perturbations reported by hemodialysis patients, allowing researchers to investigate the mechanisms of ARHD pathophysiology and test potential therapeutics.