Kidney and Dialysis

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

Leptospirosis is a re-emerging zoonotic disease that has had an unprecedented impact on most health systems in the world. The spectrum of symptoms is variable and usually ranges from asymptomatic cases to severe manifestations involving multiple organ dysfunction accompanied by jaundice, hemorrhage, meningitis, and acute kidney injury that requires the need for intensive care assistance. Although early antibiotic treatment is usually effective, in severe cases, it may require renal replacement therapy, invasive mechanical ventilation, vasoactive support, and invasive hemodynamic monitoring, increasing the risk of death. In Latin America, the real burden of acute kidney injury in this condition is unknown and may be underestimated due to the rapid progression of the disease, similar to other vector zoonoses, and the low coverage of diagnostic tests in primary care, especially in rural regions. Therefore, below, we review the clinical aspects and describe the scientific, clinical, and therapeutic evidence of acute kidney injury attributed to Leptospira spp. and its relevance in patients with severe leptospirosis in Latin America. Full article

Pregnancy in the dialysing population is an infrequent but increasing event. There is a lack of contemporary guidance regarding the nutritional management of this complex patient group. The aim of this scoping review was to identify, evaluate and summarise the evidence base describing nutritional recommendations for pregnant women receiving dialysis. A systematic search strategy of four databases and the grey literature was conducted. Eligible publications contained reference to recommendations regarding nutrition, supplements, breastfeeding, dietary patterns, and/or weight recommendations for pregnant dialysing women. A total of 136 eligible records were included for synthesis including 66 case reports/case series, 46 reviews, 15 book chapters, 5 editorials, and 4 consensus guidelines/position papers. Recommendations regarding energy, protein, dietary patterns, weight, and vitamin and mineral supplementation were common. However, significant discrepancy across these recommendations was evident. There were limited recommendations regarding other nutrients and breastfeeding. A summary of nutritional recommendations to guide clinical practice was constructed. Pregnancy planning, pre-conception dietetic counselling, interprofessional education, and the guidance synthesised in this review could be utilised by clinicians to improve clinical management and optimise outcomes in these patients. Future research should explore the experiences and perspectives of pregnant dialysing women, investigate nutrient losses during intensive dialysis, and evaluate postpartum follow-up. Full article

A perturbation in the water balance rather than any change in salt content is the main cause of hyponatremia, the most frequent electrolyte abnormality, defined as a serum sodium concentration <135 mEq/L. Hyponatremia may be divided between mild (Na > 120 mEq/L) or severe (Na < 120 mEq/L) hyponatremia, and is most frequently observed in elderly ICU hospitalized patients. Based on tonicity, hyponatremia may be hypotonic (a decreased concentration of the solute), isotonic, and hypertonic (falsely low sodium). According to the volume of extracellular fluid (ECF), hyponatremia is further divided among hypovolemic, euvolemic, or hypervolemic hyponatremia. Finally, hyponatremia may develop rapidly as acute (<48 h), usually with severe symptoms, or slowly as chronic hyponatremia, usually being asymptomatic or with mild symptoms. Acute severe hyponatremia presents with severe CNS problems, increased hospitalization rates, and mortality. The treatment with 3% sodium chloride and a 100 mL IV bolus based on severity and persistence of symptoms needs careful monitoring. A non-severe hyponatremia may be treated with oral urea. In asymptomatic mild hyponatremia, an adequate solute intake with an initial fluid restriction of 500 mL/d adjusted according to the serum sodium levels is preferred. Vaptans could be considered in patients with high ADH activity regardless of whether they are euvolemic or hypervolemic. In general, the treatment of hyponatremia should be based on the underlying cause, the duration and degree of hyponatremia, the observed symptoms, and volume status of patient. Full article

Conventional hemodialysis (HD) (a 4 h session three times a week) is not appropriate for everyone and is excessive in the presence of substantial residual kidney function (RKF). However, it can be safely replaced by a softer incremental approach guided by the urea kinetic model (UKM), starting with one or two sessions a week. Observational data suggest that RKF may be lost less quickly if dialysis is initiated less frequently than 3 times a week. Incremental HD means that, in the presence of substantial RKF, kidney replacement therapy can begin with low doses and/or frequencies, which, however, must be adequately increased to compensate for any subsequent losses of RKF, keeping the total clearance level (kidney + dialysis) always above the minimum levels of adequacy. In HD, there are complexities in combining the dialysis dose with RKF, but tools have been developed to facilitate this issue. The literature findings lend support to the safety of incremental HD and highlight the potential for this method to be implemented as a new standard of care in dialysis patients with substantial RKF. Ongoing and future trials will likely generate further evidence of the clinical and healthcare benefits of incremental HD in routine practice. Full article

Urgent-start peritoneal dialysis (USPD) is defined as peritoneal dialysis initiated within 14 days of catheter insertion. In this review, the authors describe the most recent data on USPD, including outcomes, complications, barriers to implementation, and areas for future research. Outcomes appear similar between catheter insertion techniques, so patient factors and institutional workflow should guide practice. Mechanical complications may occur at a higher rate in USPD, but it does not impact technique survival or mortality. Infectious complications appear unchanged in USPD, and there may be fewer complications compared to urgent-start hemodialysis. Barriers to implementation are multifactorial, including physician and staff unfamiliarity and lack of institutional support. A significant limitation within the field includes lack of uniform terminology and definitions. Full article

Magnesium is an essential element with a pleiotropic role in human biology. Despite tight intestinal and renal regulation of its balance, insufficient intake can finally result in hypomagnesemia, which is a proxy of intracellular deficiency. Conditions such as diabetes, cancer, and infections are often associated with hypomagnesemia, which mostly predicts an unfavorable outcome. The effects of hypomagnesemia can either be direct and include neurological and cardiovascular symptoms or indirect, taking a mechanistic role in inflammation, endothelial dysfunction, and oxidative stress. The indication for intravenous magnesium as a treatment of torsades de pointes and pre-eclampsia is unrefuted, but new indications of peroral or intravenous supplementation, albeit with less supporting evidence, have emerged suggesting, respectively, an attenuation of vascular calcification in chronic kidney disease and improved rate control in atrial fibrillation. Other potential beneficial properties of magnesium, which were claimed by observational data, such as lipid lowering and renal protection, were not, or only partially, investigated in randomized controlled trials. Thus, the role of peroral supplementation of mild chronic asymptomatic hypomagnesemia should be separated from the more targeted prescription of magnesium in specific study populations. (Severe) hypermagnesemia is potentially life-threatening and occurs almost uniformly in subjects with severe renal failure exposed to either supplements or to magnesium-containing cathartics or antacids. Moderate hypermagnesemia is very common in pre-eclamptic women treated with intravenous magnesium. For most (but not all) studied endpoints, mild hypermagnesemia yields a survival benefit. Long-lasting concerns about the potential negative effects of mild hypermagnesemia on bone physiology and structure have so far not been unequivocally demonstrated to be troublesome. Full article

Nephrotic syndrome (NS) is a complex clinical entity characterized by proteinuria, hypoalbuminemia, and edema. In this review, we propose the view of NS as a podocytopathy, highlighting the importance of understanding the role of podocytes in the development of this condition. We discuss the various etiologies of NS, ranging from congenital to primary renal diseases, as well as secondary forms due to systemic diseases. We also delve into the mechanisms underlying podocyte injury, which plays a crucial role in the development of NS. By viewing NS as a podocytopathy, we suggest potential implications for the diagnosis and treatment of this condition, including the use of podocyte-specific biomarkers and targeted therapies. Our review provides a comprehensive overview of NS and its underlying mechanisms, emphasizing the importance of a multidisciplinary approach to the diagnosis and management of this condition. Further research is essential to better understand the complex interplay between podocyte injury and the development of NS, with the ultimate goal of improving patient outcomes. Full article

ANCA-associated vasculitides (AAV) are rare, autoimmune conditions associated with end-stage kidney disease (ESKD) and mortality. Data have predominately been from White populations of European ancestry although geographical differences are well documented. Few studies have looked at the incidence, phenotype and clinical outcomes of ethnic minority patients, in particular Indo-Asian populations. A two-center, retrospective cohort study was conducted of patients with ANCA-associated glomerulonephritis (AAGN), self-identifying as Indo-Asian in the North West, UK between 2009 and 2023. A control group of White patients was identified from the same databases and recruited consecutively in relation to the original cohort of Indo-Asian patients. A total of 66 patients were included, 24 patients of Indo-Asian ethnicity and a control cohort of 42 patients of White ethnicity. Indo-Asian patients had a lower median age at diagnosis (53.0 vs. 57.5 years, p = 0.15) and there was an increased prevalence of diabetes mellitus (33.3% vs. 4.8%, p = 0.002) and a higher incidence of previous TB exposure (12.5% vs. 0%, p = 0.019). Outcomes including relapse, ESKD and mortality were similar. We demonstrated an increased crude incidence of AAGN in Indo-Asian patients in the UK compared to similar epidemiological studies. Consideration needs to be given to epidemiological and genetic research, achieved by collaboration and broader recruitment in clinical trials. Full article

Chronic kidney disease—mineral and bone disorder (CKD-MBD) plays a significant role in causing cardiovascular morbidity and mortality related to CKD. CKD-MBD has been studied during advanced stages when changes in inorganic phosphate (Pi) and its hormonal regulation are obvious. The initial phases of myocardial remodeling (MR) in early CKD-MBD remain poorly understood. We induced mild CKD-MBD in spontaneously hypertensive rats using 3/4 nephrectomy. Animals were fed standard chow, containing 0.6% phosphate. In each animal, we analyzed indices of chronic kidney injury, bone turnover and Pi exchange, and assessed the myocardial histology and gene expression profile. Applied CKD-MBD models corresponded to human CKD S1-2 with low bone turnover and without an increase in systemic Pi-regulating factors (parathyroid hormone and fibroblast growth factor 23). In mild CKD-MBD models, we found MR features characterized by cardiomyocyte hypertrophy, interstitial and perivascular fibrosis, intramyocardial artery media thickening, along with alterations in Ppp3ca, Mapk1, Jag1, Hes1, Ptch1, Numb, Lgr4 and Bmp4 genes. Among other genes, the down-regulation of Jag1 was most tightly associated with either myocardial hypertrophy or fibrosis. Myocardial alterations concurrently occurred with mild CKD-MBD and comprised fibrosis preceding cardiomyocyte hypertrophy. The histological features of MR were associated with myocardial P accumulation in settings of low bone turnover, prior to a response of systemic Pi-regulating factors and with alterations in calcineurin, ERK1/2, Notch, BMP and Hedgehog genes. Full article

Cardiovascular medicine, especially for ischemic heart disease, has evolved and advanced over the past two decades, leading to substantially improved outcomes for patients, even those with chronic kidney disease. However, the prognosis for patients with end-stage kidney disease (ESKD) has not improved so greatly. Recent studies have reported that myocardial fibrosis in chronic kidney disease patients is characterized by patchy and interstitial patterns. Areas of fibrosis have been located in the perivascular space, and severe fibrotic lesions appear to spread into myocardial fiber bundles in the form of pericellular fibrosis. These findings are fully consistent with known characteristics of reactive fibrosis. In hemodialysis patients, a greater extent of myocardial fibrosis is closely associated with a poorer prognosis. In this review, we focus on non-ischemic cardiomyopathy, especially reactive myocardial fibrosis, in ESKD patients. Full article

Nonadherence to exercise-related trials in hemodialysis (HD) patients is a significant burden worldwide. To address this issue, we assessed the feasibility and preliminary efficacy of a combined pre-habilitative virtual-reality-based mindfulness (VRM) program and a personalized activity prescription (PARx) in HD patients with elevated depressive symptoms. Ten HD patients (age = 59.60 ± 13.66) with elevated depressive symptoms completed a 10-week intervention. Participants were randomized into either a VRM+PARx (n = 6) or PARx alone (n = 4) group. During the 2-week prehabilitation, the VRM+PARx group completed our VRM program, while the PARx alone group received usual HD care. Post-prehabilitation, both groups began our 8-week PARx program. Feasibility was assessed by rates of recruitment, retention, adherence, and acceptability and adoption. Preliminary efficacy was measured using metrics of depressive symptoms, mindfulness, fatigue, and physical activity (PA) energy expenditure. A 25% recruitment rate was documented, with 90% retention. A 75% exercise adherence rate was observed and PARx demonstrated high perceived autonomy support (M = 27.6 ± 2.1). Post-prehabilitation, the VRM+PARx group showed significant between-group improvement in mindfulness (p = 0.02) and a significant within-group reduction in depressive symptoms (p = 0.05); however, no difference between groups was observed (p = 0.07). Post-PARx, no between-group difference was evident in PA energy expenditure; however, within the VRM+PARx group, a significant increase in PA energy expenditure was observed (p < 0.01). Fatigue remained unchanged. Our VRM and PARx programs demonstrated feasibility and potential efficacy for HD patients. However, to validate these findings, future trials should consider a larger sample size and a longer duration. Full article

Recently, as the number of elderly dialysis patients has been increasing, complications associated with low nutritional status such as infectious disease have had a strong influence on the prognosis of dialysis patients. Nutritional disorders are caused by the inadequate intake of the three major nutrients—proteins, fats, and carbohydrates—as well as vitamin and mineral deficiencies. Minerals are composed of various elements, including small-amount elements and trace elements, which are present in the human body in very small quantities lower than that of iron. In dialysis and predialysis patients, zinc, manganese, and selenium are the three major elements that are significantly depleted as compared to normal subjects; these deficiencies are sometimes symptomatic. Zinc deficiency is manifest as anemia, taste abnormality, and delayed wound healing, while selenium deficiency is associated with impaired cardiac function and immunocompromised condition. Zinc has multiple functions, since various enzymes, including DNA polymerase and RNA polymerase, need zinc as a cofactor, while selenium is a component of selenoproteins, including glutathione peroxidase and thioredoxin reductases, which are major antioxidative stress enzymes. These elements can only be supplemented exogenously and contribute to the sustainable QOL of dialysis patients. On the other hand, as regards other trace elements, including copper, chromium, manganese, lead, arsenic, etc., the association of their deficiency or intoxication with various involvements of dialysis patients were investigated, although all investigations were performed in cross-sectional studies or observational studies. Therefore, the supplementation of these elements is inconclusive, given the scarcity of other intervention studies. More conclusive studies are endorsed for the establishment of proper supplementation strategies. Full article

Body composition (BC), a measure of body fat mass (FM), lean body mass (LBM), and bone mineral content (BMC), can be used as a predictor of cardiorespiratory fitness (CRF). Prior studies have established a relationship between BC and VO_2max in healthy individuals over 35 years of age. However, this relationship is poorly understood in chronic disease populations. The focus of the study was to assess the relationship between BC, cardiorespiratory fitness, and chronic kidney disease (CKD). A cross-sectional analysis was conducted among 24 (9 males and 15 females) individuals diagnosed with mid-spectrum CKD (stages G2–G3b) who completed a health screening, dual-energy X-ray absorptiometry (DEXA) scan, and underwent a VO_2max exercise test. Normality tests, descriptive statistics, Pearson’s correlations, t-tests, and ANOVAs were conducted in SAS v.9.4. The average percent body fat (%BF) was 36.28 ± 8.47%, LBM was 109.4 ± 29.1 lb, BMC was 2308.7 ± 735.1 g, and VO_2max was 20.13 ± 5.04 mL/kg/min⁻¹. BC was able to predict CRF via VO_2max (R2 = 0.721, p < 0.001) and CKD stage (R2 = 0.390, p < 0.017). Positive correlations were observed in LBM (r = 0.750, p < 0.0018) and BMC (r = 0.647, p < 0.001), and negative correlations were observed with FM (r = −0.384, p < 0.032) and %BF (r = −0.802, p < 0.0001). BC was able to predict both CRF and CKD stages, with significant associations observed between BC, VO_2max, and CKD stage. The progression of the CKD stage was associated with lower LBM, BMC, and VO_2max values, indicating a graded effect of BC on CRF and CKD stage. Full article