Kidney and Dialysis

Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage kidney disease (ESKD). To date, no trial has been adequately powered to evaluate the effects of different dialysis modalities on cardiovascular events or mortality. To properly assess the risks and benefits of each modality for individual patients, it is crucial to understand the unique cardiovascular risk factors in patients undergoing dialysis. This review explores the existing literature on cardiovascular risk assessment in this population. It examines the mechanisms contributing to increased risk, including volume overload, blood pressure abnormalities, mineral bone disorder, vascular calcification, uremia, anemia, and chronic inflammation. Additionally, we discuss data from trials assessing cardiovascular outcomes and compare various dialysis modalities, including in-center hemodialysis, frequent dialysis, nocturnal dialysis, and peritoneal dialysis. Full article

Animated video could improve the reach of health education to kidney transplant (KT) seekers and their social network. Usage outcomes are rarely considered. This exploratory study aims to investigate use patterns of an animated video-based intervention (KidneyTIME) and examined associations with patient characteristics. Descriptive, quantitative analyses were conducted on user data (April 2022–March 2024) of KT-seekers allocated to the intervention arm of an ongoing randomized controlled trial of KidneyTIME. Of 195 KT-seekers allocated to KidneyTIME, optional use (defined as ≥1 video view or share) was 74% at 6 months follow-up and significantly higher among patients in the pre-evaluation phase (Odds Ratio [OR] 2.63, p = 0.0051) and with an active Facebook account (OR 2.93, p = 0036). Higher total video viewings were associated with single adult household (p = 0.0496). Not employed participants viewed more different videos (p = 0.0168). More days of viewing was significantly (p < 0.05) associated with older age, worse health, not employed, and single adult household. Video sharing was significantly associated with social media use (OR 2.86, p = 0.0264), active Facebook account (OR 2.55, p = 0.0411), and lower health literacy score (OR 2.80, p = 0.0274) and inversely associated with lower social support score (OR 0.35, p = 0098) and male sex (OR 0.48, p = 0.0394). Web-based animated video education promoted through email or text links is a viable modality to reach diverse KT-seekers. Full article

Primary aldosteronism (PA) is a major cause of hypertension, especially in younger patients. Early diagnosis and treatment are crucial to prevent damage to vital organs, including the heart and kidneys. Independent of blood pressure, aldosterone excess has direct deleterious effects on the kidneys, leading to tubulointerstitial fibrosis, glomerular hypertrophy, and glomerulosclerosis. Emerging biomarkers such as albuminuria and liver fatty acid-binding protein may have the potential to detect renal injury in PA, particularly in the setting of glomerular hyperfiltration. Comprehensive risk assessment of long-term renal dysfunction, based on both modifiable and non-modifiable risk factors, would aid clinicians in prediction and would even, in some cases, allow them to mitigate the risk of patients developing CKD in the setting of PA. Full article

Background: Whether hemodialysis patients want caregivers to discuss spirituality is poorly studied, especially in Europe. The goal of this qualitative study was to explore the spirituality and spiritual expectations of hemodialysis patients in a Swiss dialysis center. Methods: Semi-structured, qualitative interviews were performed by an experienced sociologist with dialysis patients in the ambulatory dialysis unit of the University Hospital of Lausanne. The interviews included a set of open questions on the role that spirituality plays in patients’ lives, in coping with their illness and in the recent COVID-19 epidemic. All interviews were recorded, transcribed, coded and analyzed following the approach of content analysis. Findings: Twenty interviews were performed in 2022. In total, 14/20 patients practiced some form of religion (believers), four were agnostics, and two defined themselves as atheist. The majority (15/20) confirmed that spirituality plays a positive role to preserve hope and to manage the difficulties caused by the disease and its treatment; one out of four wishes to discuss spirituality in the hospital setting. The largest needs are related to social dimensions (isolation, loneliness, need to talk, financial problems). Their level of spirituality has not been impacted by the COVID-19 pandemic. Discussion: In this pilot study, spirituality in a broad sense was important for the majority of the patients, and a quarter of them would like it to be actively addressed by healthcare professionals. They also ask for more attention to social and socio-economic difficulties. Full article

Small interfering RNAs (siRNAs) are short, double-stranded RNA molecules that play a crucial role in the regulation of gene expression, particularly through a natural process called RNA interference (RNAi). Their discovery, about 25 years ago, paved the way for a whole series of research leading to synthetic molecules. The gene silencing potential of these siRNAs was initially oriented towards diseases resulting from genetic dysfunctions. This led to the development of the first synthetic siRNAs approved for human use in hereditary transthyretin amyloidosis. Subsequently, the field of application expanded beyond the confines of genetic diseases. The refinement of pharmacological techniques has led to the synthesis of a variety of siRNAs capable of blocking the production of individual proteins responsible for various disease conditions, thus expanding their field of therapeutic application. The kidney has also been affected by this new therapeutic tool, largely indirectly but also, with some difficulty, directly. The structural complexity of the kidney has made the search for siRNAs targeting its individual components very challenging. Nevertheless, the first results of the application of this new therapeutic technology to the kidney are beginning to be seen in experimental animals and in humans. siRNAs have been approved for the treatment of amyloidosis with patisiran and oxalosis with lumasiran and nedosiran. Studies are ongoing for the use of siRNAs as anti-complement drugs in IgA nephropathy, as angiotensinogen inhibitors in hypertension, or against some mediators of acute kidney injury. In this review, the biological mechanisms underlying the use of siRNAs are briefly exposed. The results of the therapeutic application of RNA interference to the kidney and its diseases are also analyzed and discussed. Full article

Follow-up studies evaluating the relationship between dyslipidemia and chronic kidney disease (CKD) in non-diabetic populations are limited. This longitudinal study (1998–2024) examined whether the prevalence of dyslipidemia is associated with the subsequent development of CKD in non-diabetic Japanese adult citizens of Zentsuji, Kagawa Prefecture, Japan. Dyslipidemia was defined as low-density lipoprotein cholesterol concentrations ≥ 140 mg/dL, high-density lipoprotein cholesterol concentrations < 40 mg/dL, and/or triglyceride concentrations ≥ 150 mg/dL. Participants were considered to have developed CKD if their estimated glomerular filtration rate was <60 mL/min/1.73 m². The proportional hazards assumption was violated. Therefore, the Weibull accelerated failure-time model was selected using the Akaike and Bayesian information criteria. The final cohort included 5970 participants, 41.6% of whom were men. The mean follow-up was 7.09 years. After the follow-up, 1890 (31.7%) participants developed CKD. Participants with dyslipidemia had a 5% shorter survival time (95% confidence interval: 3–7%) to incident CKD compared with those without dyslipidemia in the full model. High-density lipoprotein cholesterol concentrations < 40 mg/dL and triglyceride concentrations ≥ 150 mg/dL also reduced the survival time to CKD onset by 5–6%. Our results indicate that controlling the lipid profile to an appropriate range may contribute to reducing the risk of future onset of CKD. Full article

IgA nephropathy (IgAN), first described in 1968, is one of the most common forms of glomerulonephritis and can progress to end-stage kidney disease (ESKD) in 25 to 30 percent of patients within 20 to 25 years from the onset. It is histologically characterized by mesangial proliferation with prominent IgA deposition. The prognosis may be difficult to predict, but important risk factors for disease progression of kidney disease have been recognized: usually proteinuria above 0.75–1 g/day with or without hematuria, hypertension, high-risk histologic features (such as crescent formation, immune deposits in the capillary loops, mesangial deposits, glomerulosclerosis, tubular atrophy, interstitial fibrosis, and vascular disease), and a reduced Glomerular Filtration Rate (GFR). In the absence of reliable specific biomarkers, current standards of care are addressed to decrease proteinuria, as a surrogate endpoint, and control blood pressure. For a long time, corticosteroids have been considered the only cure for proteinuric patients or those at risk of progression to ESKF; however, unfortunately, like other immunosuppressive agents, they are burdened with high collateral risks. Therefore, optimal treatment remains a challenge, even if, to date, clinicians have many more options available. Here, we will review the main therapies proposed, such as the stronghold of RAAS inhibition and the use of SGLT2 inhibitors; it is expected that ongoing clinical trials may find other therapies, apart from corticosteroids, that may help improve treatment, including both immunosuppressive monoclonal antibodies and other strategies. At the current time, there are no disease-specific therapies available for IgAN, because no largescale RCTs have demonstrated a reduction in mortality or in major adverse kidney or cardiovascular events with any therapy. Full article

Background: Whether patients commence haemodialysis with a central venous catheter (CVC), or an arteriovenous fistula (AVF) is used to audit the quality of a vascular access service. However, this crude metric of measurement can miss the increasing nuance and complexity of vascular access planning. We aimed to understand whether commencing haemodialysis with a CVC represented an ‘optimal’ or ‘suboptimal’ outcome and how this could influence the assessment of a vascular access service. Methods: From a prospective clinical database, patients known to nephrology >90 days prior to initiating haemodialysis as first-ever renal replacement therapy (2011–2020) from a single centre were included. Results: A total of 158/254 patients started haemodialysis with a CVC, and 96 with arteriovenous fistula. For 91 patients, the CVC was deemed ‘optimal’ care due to factors such as unpredictable deterioration in renal function (n = 41) and inadequate veins for AVF creation (n = 24). For 67 patients, the CVC was ‘suboptimal’ due to factors such as no/late referral to access assessment (n = 25) and delays in the AVF creation pathway (n = 13). There was no difference in mean survival between the AVF and ‘suboptimal’ groups (2.53 vs. 2.21 years, p = 0.31). There was a survival difference between AVF versus CVC (2.53 vs. 1.97 years, p = 0.002) and ‘suboptimal’ versus ‘optimal’ CVC cohorts (2.21 vs. 1.40 years, p = 0.16). Conclusions: Understanding whether a CVC is ‘optimal’ or ‘suboptimal’ allows a more nuanced analysis of service provision. High mortality in the ‘optimal’ group suggests a frailer cohort where CVC is potentially the best care. Studying ‘suboptimal’ CVC starts helps identify practice and system issues preventing ‘optimal’ care. Full article

Background: For our society, chronic kidney disease is a major public health problem associated with high mortality, morbidity, reduced quality of life and a progressive increase in health costs. The aim of this study was to analyze and compare the current cost of kidney transplantation (KT) and kidney–pancreas transplantation (KPT) among the different Regional Health Services (RHS) in Spain. Methods: A descriptive comparative study analyzing the public prices of RHS in Spain. The Official Gazette of the different communities was consulted, where the latest available order on this type of cost was sought. A descriptive analysis was made of the stipulated cost of the KT and KPT, for each degree of severity, RHS, year of publication and cost calculation method. Mean cost and standard deviation were calculated. Results: KT prices were found for 15 of the 18 RHS (83.33%). The average cost of KT in Spain was EUR 33,926.53 ± 6950.053 (range from EUR 23,140.37 in the Canary Islands to EUR 48,205.75 in Catalonia). For KPT, costs were found for 5 of the 18 RHS (27.8%). The mean cost of KPT was EUR 65,792.38 ± 11,273.12 (ranging from EUR 49,418.81 in Navarra to EUR 78,363.20 in Andalusia). Conclusions: There is a large variability in KT and KPT costs in Spain between RHS. Our study underlines the importance of adopting standardized and updated costing methods for KT and KPT. Full article

The history of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is so long and started in 1835 when Petersen extracted a compound called phlorizin from apple tree bark. About fifty years later, von Mering discovered its glucosuric properties. In the 1980s, it was discovered that the glucosuria resulted from inhibition by phlorizin of glucose reabsorption by the renal tubules, which lowered blood glucose levels in diabetic rats. Nowadays, beyond their glucose-lowering effects, growing evidence suggests significant cardiorenal benefits associated with SGLT2i therapy. Indeed, several clinical trials, including landmark studies such as EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, have demonstrated robust reductions in cardiovascular events, particularly heart failure hospitalizations and cardiovascular mortality, among patients treated with SGLT2i. However, subsequent trials showed that SGLT2i benefits extend beyond the diabetic population, encompassing individuals with and without diabetes. Additionally, SGLT2i exhibit nephroprotective effects, manifesting as a slowing of the progression of chronic kidney disease and a reduction in the risk of end-stage kidney disease. The mechanisms underlying the cardiorenal benefits of SGLT2i are multifactorial and include improvements in glycemic control, reduction in arterial stiffness, modulation of inflammation and oxidative stress, reduction of intraglomerular pression and promotion of natriuresis and diuresis through inhibition of SGLT2 in the luminal brush border of the first segments of the proximal kidney tubule. This narrative review aims to explore the cardiorenal outcomes of SGLT2i, encompassing their mechanisms of action, clinical evidence, safety profile, and implications for clinical practice. Full article

Despite the lack of evidence that suggests hemodiafiltration (HDF) offers a better survival outcome than standard hemodialysis (HD), the number of patients initiating HDF in Japan continues to rise. This study examined the temporal change in the number of HDF incidents, evaluated factors associated with all-cause mortality, and compared the mortality risk and survival time of patients on HDF with patients receiving standard HD in three sets of 2-year cohorts. The primary analyses included the insurance claims data of 460 HDF patients and propensity score-matched 903 standard HD patients who initiated dialysis therapy between 1 April 2012 and 31 March 2018. Patient follow-up was censored at the time of death or the end of the 2-year study period. The number of patients who initiated HDF and the proportion of all-cause mortality cases were evaluated. Additionally, the survival outcomes between propensity score-matched HDF and standard HD patient groups were compared throughout cohorts. The number of HDF patients increased throughout cohorts, but the proportions of mortality cases across cohorts slowly decreased. Adjusting for all study covariates, we observed that HDF patients had a lower mortality risk and longer survival time than patients on standard HD. This study supports the notion that HDF lowers all-cause mortality compared with standard HD in an incident dialysis population in Fukuoka Prefecture, Japan. Full article

Background: Historically, a large gender-related disparity in vascular access (VA) has been demonstrated, with there being a lower prevalence of women with arteriovenous fistula (AVF) compared to men, and women have worse maturity rates. The cause of this difference is not entirely clear, although several reasons that could contribute to it have been hypothesized. The emergence of new percutaneous FAV (pFAV) systems could be an alternative for reducing these differences. Objective: This study aims to determine whether there is a gender difference in the creation of AVFs using new percutaneous systems. Material and Methods: A systematic review of the literature was conducted by searching PubMed and Google Scholar using the following terms: “percutaneous arteriovenous fistula”, “endovascular arteriovenous fistula”, and “hemodialysis”. All clinical trials, comparative studies, and descriptive studies involving patients who underwent a pAVF were included. Results: Finally, the review includes 19 studies, comprising 14 retrospective studies and 5 prospective studies. Of these, six studies are comparative, five of which compare pAVFs with surgically created AVFs (sAVFs), and one compares pAVFs performed using different systems with each other. A total of 1269 patients were included in the review. Of the total number of patients, only 414 were women, representing 32.62% of patients. Conclusions: The number of women included in the various studies analyzing pAVF remains very low, representing less than one-third of all patients. Although the causes of this difference are not entirely clear, several reasons have been hypothesized, such as socioeconomic factors, anatomical factors, or even patients’ preferences. Given these results, further studies are needed to try to clarify the reasons for this gender disparity and to establish different strategies to mitigate the barriers faced by women in accessing AVFs. Full article

Continuous venovenous hemofiltation (CVVH) with citrate anticoagulation has been shown to be associated with substantial losses of calcium and negative calcium balance in ICU patients, which may lead to excessive bone loss and osteoporosis. The aim of this study is to investigate whether plasma parathormone monitoring can identify patients with negative calcium balance during CVVH. This is a retrospective single-center study of all adult ICU patients treated with citrate CVVH from 2021 to 2023. PTH was measured routinely once per week. Calcium excretion in ultrafiltrate fluid and CVVH calcium balance were measured daily. In total, 274 PTH measurements were performed in 111 patients. In 61 measurements (22%), PTH was higher than the upper limit of normal (>8 pmol/L). If PTH was higher than normal, plasma ionized calcium was less than 1.16 mmol/L in 77% of cases and hypercalcemia was never present. In a subgroup of patients treated with CVVH for at least 36 h in the preceding 72 h, PTH values were similar for quartiles by cumulative calcium balance. Increased plasma concentrations of PTH are frequently found in ICU patients treated with citrate CVVH, but no association was found between PTH and the CVVH calcium balance over the last 72 h. Full article

Prof. Dr. George Bakris was an Editorial Board Member of Kidney and Dialysis. His invaluable contributions were instrumental in guiding the journal’s direction and enhancing its success. We are deeply grateful for his unwavering dedication, commitment, and active involvement in the journal’s development. Full article

The Ralstonia species (RB) and Burkholderia species (BB) are bacteria responsible for nosocomial infections in frail patients such as hemodialyzed (HD) patients. Here, we report how we managed an outbreak caused by RB and BB that occurred in a dialysis unit. From the 7th to the 16th of April 2021, an infection due to RB and BB occurred in 7 out of 39 (17.9%) HD patients with central venous catheter (CVC). Disinfectants, CVC-lock therapy solutions, water by reverse osmosis unit (ROW) and dialysis concentrates were cultured, including the biofilm from the loading plastic tubes (LPTs) that connect the hemodialysis consoles (HCs) to the ROW delivery line. The antibiotic treatment was successful for all patients. RB and BB were isolated in the biofilm of 11/37 LPTs. Three out of 11 positive LPTs were associated with the infected patients. The ROW delivery line was modified to provide a whole disinfection with the HCs connected, avoiding the risk of new contamination of the LPTs. A filtration module of 0.01 mm was added prior to the ROW delivery line. Our experience suggests that outbreaks sustained by unusual bacteria such as RB and BB should be promptly investigated to treat the infected patients with the appropriate therapy and to identify the possible source of infection, making the needful changes to achieve a safer dialysis unit. Full article

Apolipoprotein L1 (APOL1) nephropathy results from several podocyte dysfunctions involving morphological and motility changes, mitochondrial perturbations, inflammatory stress, and alterations in cation channel activity. I propose that this phenotype results from increased hydrophobicity of the APOL1 risk variants, which induces two distinct types of podocyte dysfunctions. On one hand, increased hydrophobic interactions with APOL3 cause intracellular variant isoforms to impair both APOL3 control of Golgi PI(4)P kinase-B (PI4KB) activity and APOL3 control of mitochondrial membrane fusion, triggering actomyosin reorganisation together with mitophagy and apoptosis inhibition (hit 1). On the other hand, increased hydrophobic interactions with the podocyte plasma membrane may cause the extracellular variant isoforms to activate toxic Ca²⁺ influx and K⁺ efflux by the TRPC6 and BK channels, respectively (hit 2), presumably due to APOL1-mediated cholesterol clustering in microdomains. I propose that hit 2 depends on low HDL-C/high extracellular APOL1 ratio, such as occurs in cell culture in vitro, or during type I-interferon (IFN-I)-mediated inflammation. Full article

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a complication of cardiopulmonary bypass surgery that frequently occurs in children. The increased availability of pediatric cardiac surgery leads to yearly increases in congenital heart disease (CHD) procedures performed worldwide. The number of complications, including pediatric CSA-AKI, has also increased. Children with CSA-AKI have worse postoperative periods and require more complex post-op intensive care. Thus, the timely commencement of interventions to prevent and to treat kidney injury in CHD children are one of a leading goals of pediatric cardiac intensive care. Full article

It is necessary to ensure adequate energy and protein intake in dialysis patients. However, in addition to the decline in dietary intake in older dialysis patients due to aging, the rate of anorexia is high in dialysis patients, which increases the risk of protein–energy wasting (PEW), sarcopenia, and frailty. There are many causes of anorexia in dialysis patients, including older dialysis patients, and approaches to improve the appetite of such patients have been reported; however, there has been no established approach to improve appetite adequately. Therefore, a key practical goal is to identify anorexia early and implement timely interventions before weight loss occurs. Appetite assessment tools and weight loss assessments are helpful for the screening and early identification of anorectic signs. Nutritional interventions include reducing dietary restrictions, using oral nutritional supplements, and intradialytic parenteral nutrition, as well as replenishing energy, protein, and zinc to prevent the development of nutritional disorders among older dialysis patients. Appetite assessments, early intervention, and dietary and nutritional counseling are key to improving appetite in these patients. The aging rate of dialysis patients in Japan is unprecedented globally, and I believe that this is a situation that will eventually occur in other countries as well. I discuss the factors that contribute to anorexia, especially in older dialysis patients, and Japan’s efforts to address this problem, such as the relaxation of dietary restrictions and the use of oral nutritional supplements. Full article

Background: Limited data exist on postoperative acute kidney injury (AKI) in patients who have undergone esophageal cancer surgery. The purpose of this study was to evaluate the incidence, risk factors, and consequences of postoperative acute kidney after esophagectomy. Methods: This was a retrospective cohort study. The study was conducted in a tertiary specialized cancer center in Italy. All patients undergoing elective esophageal cancer surgery between 2016 and 2021 were included in the study. AKI was defined according to Kidney Disease Improving Global Outcomes criteria (both serum creatinine and urine output), within 48 h after surgery. Preoperative and intraoperative data were registered. We also collected data concerning progression of AKI, need for renal replacement therapy, mortality, and medical (pulmonary, cardiovascular, septic) and surgical complications within 30 days from surgery, as well as length of hospital stay. Results: Incidence of postoperative AKI was 32%. The independent risk factors were body mass index and the use of an invasive surgical approach. Persistent AKI accounted for 15% of the cases and it was associated with increased risk of major cardiovascular events (odds ratio 4.14, 95% CI 1.05–15.8, p-value 0.036), pulmonary complications (OR 3.67, 95% CI 1.04–14.9, p-value 0.050), and increased length of hospital stay (AME 7.2, 0.5–13.9, p-value 0.035). Conclusions: Postoperative AKI is common after esophageal cancer surgery. BMI and a totally invasive surgical approach are independent risk factors. Persistent AKI lasting more than 48 h increased the risk for any cardiovascular or pulmonary complications, with prolonged length of hospital stay. Full article