Treatment For End-stage Kidney Disease Research Articles

The Impact of Reduced Immunosuppression on Alloimmunity: A Retrospective Study of Pediatric Kidney Transplant Recipients.

Kidney transplantation is the best treatment for end-stage kidney disease but requires immunosuppressive medications, which have significant side effects. Many pediatric recipients experience these side effects, leading to dosage reductions, which potentially increase the risk of alloimmunity. We aimed to describe the alteration in immunosuppressive medication, explore the reasons for the reductions, and assess the potential impact on alloimmunity. Data from 49 pediatric kidney transplant recipients receiving an allograft from 2009 to 2020 were retrospectively studied. The recipients were screened for HLA antibodies after the transplantation. The median age of recipients was 11 years (IQR 8), with a median follow-up of 5 years (IQR 5). Eighty percent of the transplantations were corticosteroid-free. During follow-up, 11% developed de novo donor-specific antibodies (dnDSA), and 60% had detectable HLA antibodies. The 1-year rejection rate was 4%. Immunosuppressive medication was altered substantially in most recipients, resulting in 72% being on mono- or dual therapy with a reduced mycophenolate mofetil (MMF) dosage by the end of the first posttransplant year. The median MMF dose was nearly half of the intended. Tacrolimus levels were maintained close to the target of 5 ng/mL. No association was found between reduced immunosuppression and dnDSA or rejections. Reductions were primarily due to MMF-related side effects: leukopenia in 77%, gastrointestinal issues in 34%, and infections with Epstein-Barr virus, cytomegalovirus, and BK polyomavirus in 49%. Reduced MMF with a sufficient trough tacrolimus level in a population of mainly corticosteroid-free pediatric kidney transplant recipients did not lead to unacceptable alloimmunity.

Infectious disease events in people with HIV receiving kidney transplantation: Analysis of the Swiss HIV Cohort Study and the Swiss Transplant Cohort Study

BackgroundSince the implementation of universal antiretroviral therapy, kidney transplantation (K-Tx) has become a valuable option for treatment of end-stage kidney disease for people with HIV (PWH) with similar patient and graft survival as compared to HIV-uninfected patients. Little is known about the hazards and manifestations of infectious disease (ID) events occurring in kidney transplant recipients with HIV.MethodsUsing linked information collected in the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS), we described in-depth demographical and clinical characteristics of PWH who received a K-Tx since 2008. Further, we performed recurrent time to event analyses to understand whether HIV was an independent risk factor for ID events.ResultsOverall, 24 PWH with 57 ID events were included in this study (100% match of SHCS to STCS). Of these, 17 (70.8%) patients had at least one ID event: 22 (38.6%) viral (HIV not counted), 18 (31.6%) bacterial, one (1.8%) fungal and 16 (28.1%) probable infections. Most ID events affected the respiratory tract (25, 37.3%) or the urinary tract (13, 19.4%). Pathogen types and infection sites were similar in PWH and a matched control group of HIV-uninfected patients. HIV was not an independent risk factor for ID events (adjusted hazard ratio 0.94, p = 0.9).ConclusionBy linking data from two large national Swiss cohorts, we provided in-depth information on ID events in PWH receiving a K-Tx in Switzerland. HIV infection was not associated with an increased hazard for ID events after K-Tx.

Barriers and facilitators for the adoption of peritoneal dialysis: protocol for a systematic review of qualitative studies

IntroductionPeritoneal dialysis (PD) is an effective home-based treatment for end-stage kidney disease (ESKD) that offers several advantages over in-centre haemodialysis, including better quality of life, increased autonomy and lower costs....

Effectiveness of a Customized Peritoneal Dialysis Training Program in Reducing Infection and Dropout Rates: Insights From a Singapore Hospital.

Introduction Peritoneal dialysis (PD) is an essential home-based treatment for end-stage kidney disease, known for enhancing patients' quality of life and being more cost-effective compared to hemodialysis. However, in Singapore, PD education lacks of standardization, with each unit adopting varied methods based on their own experiences and resources. To address this, our hospital developed a tailored four-day PD training program guided by the International Society for Peritoneal Dialysis guidelines, adapted to meet local needs and resource availability. Methodology This study employed a retrospective cohort design, including all incident adult patients aged 18 years and above who initiated PD at our hospital from September 2018 to July 2023. Data on PD dropout rates and PD-related infection rates, such as PD peritonitis and exit site infection rates, were obtained from electronic medical records. Results This study comprised 99 patients who began PD and completed their PD training program at our hospital between September 2018 and July 2023. Our tailored PD training program successfully reduced dropout rates and maintained infection rates within the International Society for Peritoneal Dialysis guidelines. Specifically, exit site infection rates fluctuated between 0.18 and 0.29 episodes per year, PD peritonitis rates ranged from 0.2 to 0.26 episodes per patient-year, and dropout rates significantly improved from 40% in 2019 to 7% in 2023 (OR = 0.45, 95% CI = 0.49 to 0.84, p = 0.010). Conclusions The tailored PD training program at our hospital effectively reduced PD-related infections and dropout rates among end-stage kidney disease patients. These findings suggest that structured, locally adapted training programs can substantially improve patient outcomes in PD.

Determining Predictors of Actual Living Kidney Donation Based on Potential Donor Characteristics.

Living donor kidney transplantation is the optimal treatment for end-stage kidney disease; however, few living donor candidates (LDCs) who begin evaluation actually donate. While some LDCs are deemed medically ineligible, others discontinue for potentially modifiable reasons. At five transplant centers, we conducted a prospective cohort study measuring LDCs' clinical and psychosocial characteristics, educational preparation, readiness to donate, and social determinants of health. We followed LDCs for 12 months after evaluation to determine whether they donated a kidney, opted to discontinue, had modifiable reasons for discontinuing, were medically ineligible, or had other recipient-related reasons for discontinuing. Among 2184 LDCs, 18.6% donated, 38.2% opted to or had modifiable reasons for discontinuing, and 43.2% were deemed ineligible due to medical or recipient-related reasons. Multivariable analyses comparing successful LDCs with those who did not complete donation for modifiable reasons (N=1241) found that LDCs who discussed donation with the recipient before evaluation (OR, 2.31; 95% CI, 1.54-3.46), had completed high school (OR, 2.01; 95% CI, 1.21-3.35), or were a "close relation" to their recipient (OR, 1.89; 95% CI, 1.33-2.69) were more likely to donate. Conversely, LDCs who reported religion as important (OR, 0.55; 95% CI, 0.38-0.80), were Non-White (OR, 0.70; 95% CI, 0.49-1.00), or had overall higher anxiety scores (OR, 0.92; 95% CI, 0.86-0.99) were less likely to donate. With fewer than a fifth of LDCs donating, developing programs to provide greater emotional support and facilitate open discussions between LDCs and recipients earlier may increase living donation rates.

Cysteine as an Innovative Biomarker for Kidney Injury.

Kidney transplantation is a widely used treatment for end-stage kidney disease. Nevertheless, the incidence of acute kidney injury (AKI) in deceased donors poses a potential hazard because it significantly increases the risk of delayed graft function and potentially exerts an influence on the kidney allograft outcome. It is crucial to develop a diagnostic model capable of assessing the existence and severity of AKI in renal grafts. However, no suitable kidney injury markers have been developed thus far. We evaluated the efficacy of the molecular probe NPO-B, which selectively responds to cysteine, as a new diagnostic tool for kidney injury. We used an in vitro model using ischemia/reperfusion injury human kidney-2 cells and an in vivo ischemia/reperfusion injury mouse model. Additionally, cysteine was investigated using urine samples from deceased donors and living donors to assess the applicability of detection techniques to humans. This study confirmed that the NPO-B probe effectively identified and visualized the severity of kidney injury by detecting cysteine in both in vitro and in vivo models. We observed that the fluorescence intensity of urine samples measured using NPO-B from the deceased donors who are at a high risk of renal injury was significantly stronger than that of the living donors. If implemented in clinical practice, this new diagnostic tool using NPO-B can potentially enhance the success rate of kidney transplantation by accurately determining the extent of AKI in renal grafts.

Investigating dialysis membrane surface charge and hydrophobicity effects on fibrinogen adsorption using synchrotron radiation micro-computed tomography (SR-CT)

Hemodialysis, a critical treatment for end-stage kidney disease (ESKD), efficiently eliminates toxic metabolic waste from the bloodstream. This study probes the complex interactions among surface charge, wettability, and roughness of Polyethersulfone (PES) membranes and their influence on fibrinogen (FB) adsorption, a key culprit in membrane fouling that compromises the dialysis efficacy. Utilizing non-invasive X-ray synchrotron-based micro-tomography (SR-CT), we analyzed an array of PES membranes—ranging from unmodified to superhydrophobic surfaces achieved via surface hydrophobization or hydrophobic mixed matrix methods, heparin-immobilized versions, zwitterionically coated with sulfobetaine and carboxibetaine, and uremic metabolite-modified membranes, each with intensified coatings. Our findings highlight that superhydrophobic membranes, particularly hydrophobic mixed matrix membrane, significantly repel FB, reducing fouling due to their high contact angle. Additionally, membranes with lower surface charges corresponded with lower protein adsorption, emphasizing the pivotal role of electrostatic interactions. Intriguingly, hydrophobic membranes outperformed their hydrophilic counterparts despite having higher surface roughness, suggesting that peak hemodialysis membrane performance is achieved through a synergistic balance of reduced surface charge and enhanced hydrophobicity. These insights drive home the importance of integrating charge, wettability, and texture considerations in membrane design to foster the next generation of low-fouling, high-performance hemodialysis membranes.

Creatine homeostasis and the kidney: comparison between kidney transplant recipients and healthy controls

Creatine is a natural nitrogenous organic acid that is integral to energy metabolism and crucial for proper cell functioning. The kidneys are involved in the first step of creatine production. With kidney transplantation being the gold-standard treatment for end-stage kidney disease, kidney transplant recipients (KTR) may be at risk of impaired creatine synthesis. We aimed to compare creatine homeostasis between KTR and controls. Plasma and urine concentrations of arginine, glycine, guanidinoacetate, creatine and creatinine were measured in 553 KTR and 168 healthy controls. Creatine intake was assessed using food frequency questionnaires. Iothalamate-measured GFR data were available in subsets of 157 KTR and 167 controls. KTR and controls had comparable body weight, height and creatine intake (all P > 0.05). However, the total creatine pool was 14% lower in KTR as compared to controls (651 ± 178 vs. 753 ± 239 mmol, P < 0.001). The endogenous creatine synthesis rate was 22% lower in KTR as compared to controls (7.8 ± 3.0 vs. 10.0 ± 4.1 mmol per day, P < 0.001). Despite lower GFR, the plasma guanidinoacetate and creatine concentrations were 21% and 41% lower in KTR as compared to controls (both P < 0.001). Urinary excretion of guanidinoacetate and creatine were 66% and 59% lower in KTR as compared to controls (both P < 0.001). In KTR, but not in controls, a higher measured GFR was associated with a higher endogenous creatine synthesis rate (std. beta: 0.21, 95% CI: 0.08; 0.33; P = 0.002), as well as a higher total creatine pool (std. beta: 0.22, 95% CI: 0.11; 0.33; P < 0.001). These associations were fully mediated (93% and 95%; P < 0.001) by urinary guanidinoacetate excretion which is consistent with production of the creatine precursor guanidinoacetate as rate-limiting factor. Our findings highlight that KTR have a disturbed creatine homeostasis as compared to controls. Given the direct relationship of measured GFR with endogenous creatine synthesis rate and the total creatine pool, creatine supplementation might be beneficial in KTR with low kidney function.Trial registration ID: NCT02811835.Trial registration URL: https://clinicaltrials.gov/ct2/show/NCT02811835.

Treatment Patterns for End-Stage Kidney Failure in Patients With Systemic Lupus Erythematous.

This study aims to examine the treatment patterns of end-stage kidney disease (ESKD) among SLE patients and to compare the outcome of hemodialysis (HD) and peritoneal dialysis (PD). SLE patients identified from the national administration dataset in 2005-2021 were linked to the Australia and New Zealand Dialysis and Transplant Registry to identify ESKD cases. The adjusted odds ratio of having PD instead of HD as the first treatment for ESKD for Asian, Māori, and Pacific compared with European/others was estimated with the logistic regression model. The adjusted hazards ratio of all-cause mortality for patients having PD first compared with HD first was calculated. Two hundred ten ESKD patients with SLE were identified. Two thirds (137/210) of the ESKD patients had HD as the first treatment, and one third (68, 32.4%) had PD first. Around 60% of Asian patients had PD as the first treatment, compared with 30% in other ethnic groups. The adjusted odds ratio of having PD as the first treatment for Asian patients compared with European/others was 3.00 (95% confidence interval, 1.16-7.73). The adjusted hazards ratio of all-cause mortality for patients in the PD group compared with the HD group was 0.60 (95% confidence interval, 0.37-0.97). Asian patients with ESKD were more likely to have PD as the first treatment. The optimal dialysis type for ESKD patients with SLE might be different from ESKD patients caused by other diseases. ESKD patients with SLE receiving PD first had superior outcomes than patients receiving HD first.

Exploring the unmet needs and experiences of informal caregivers of patients with end-stage kidney disease (ESKD) receiving haemodialysis - a qualitative study.

Patients with end stage kidney disease (ESKD) receiving haemodialysis experience multiple symptoms, which can present physical and emotional challenges for both patients and their informal caregivers. Caregivers can experience anxiety, depression, and social isolation negatively impacting their overall wellbeing and resulting in caregiver burden. The needs of this group of caregivers have been largely neglected, with little emphasis placed on supportive interventions that might assist and support them in their caring role. The aim of this study Is to explore the unmet needs and experiences of caregivers of patients with ESKD receiving haemodialysis, and to determine the components of a supportive intervention. A qualitative study using semi-structured interviews (n = 24) with informal caregivers. An interpretive qualitative framework was employed to generate a rich understanding of the unmet needs and experiences of caregivers. Data was analysed using thematic analysis. Interviews were transcribed verbatim and data management was assisted through NVIVO version 11. Twenty-four informal caregivers were purposively recruited from two haemodialysis settings within Northern Ireland. Three themes were identified: (1) The negative impact of distress, anxiety, and isolation on caregivers due to their caregiving responsibilities (2) Inadequate information and knowledge about the complexities of renal care (3) The benefits of spiritual beliefs, stress management and peer support in relieving the caregiving burden. Caregivers of patients with ESKD receiving haemodialysis are at increased risk of physical and psychological distress and burden arising from their caregiving role. The unpredictable nature of ESKD and haemodialysis treatment negatively impacts the caregiver experience and adds to the challenges of the role. The information needs of caregivers are not always adequately met and they subsequently lack appropriate knowledge, skills, and guidance to assist them in their caregiving role. Supportive interventions are essential for caregivers to enhance their capability to deliver effective care and improve their quality of life.

Glycosylation and Characterization of Human Transferrin in an End-Stage Kidney Disease.

Chronic kidney disease (CKD) is a global health concern affecting approximately one billion individuals worldwide. End-stage kidney disease (ESKD), the most severe form of CKD, is often accompanied by anemia. Peritoneal dialysis (PD), a common treatment for ESKD, utilizes the peritoneum for solute transfer but is associated with complications including protein loss, including transferrin (Tf) a key protein involved in iron transport. This study investigated Tf characteristics in ESKD patients compared to healthy individuals using lectin microarray, spectroscopic techniques and immunocytochemical analysis to assess Tf interaction with transferrin receptors (TfRs). ESKD patients exhibited altered Tf glycosylation patterns, evidenced by significant changes in lectin reactivity compared to healthy controls. However, structural analyses revealed no significant differences in the Tf secondary or tertiary structures between the two groups. A functional analysis demonstrated comparable Tf-TfR interaction in both PD and healthy samples. Despite significant alterations in Tf glycosylation, structural integrity and Tf-TfR interaction remained preserved in PD patients. These findings suggest that while glycosylation changes may influence iron metabolism, they do not impair Tf function. The study highlights the importance of a glucose-free dialysis solutions in managing anemia exacerbation in PD patients with poorly controlled anemia, potentially offering a targeted therapeutic approach to improve patient outcomes.

Rehabilitation exercises for kidney transplant recipients in an organ transplant ward: a best practice implementation project.

Kidney transplantation is an effective treatment for end-stage kidney disease. Kidney transplant recipients (KTRs) are prone to experiencing reduced physical function, depression, fatigue, and lack of exercise motivation due to their sedentary lifestyle before surgery. Exercise is an effective intervention for KTRs, but it has not been properly implemented in many practice settings. This project aimed to promote evidence-based exercises as part of KTRs' rehabilitation to improve their health outcomes. This project was informed by the JBI Evidence Implementation Framework. The project was conducted in the organ transplant ward of a tertiary comprehensive hospital in Changsha, China. Based on a summary of best evidence, 12 audit criteria were developed for the baseline and follow-up audits involving 30 patients and 20 nursing staff. The JBI Practical Application of Clinical Evidence System (PACES) and Getting Research into Practice (GRiP) tool were used to identify barriers and facilitators and develop targeted strategies to improve issues. Compared with the baseline audit, significant improvements were achieved in most of the criteria in the follow-up audit, with 9 of the 12 criteria reaching 100% compliance. Notably, the 6-minute walk distance test results were significantly higher, while the Self-Rating Depression Scale and Self-Rating Anxiety Scale scores were significantly lower ( p < 0.05). This project demonstrates that evidence-based practice can improve the clinical practice of rehabilitation exercises for KTRs. The GRiP strategies proved to be extremely useful, notably, the formulation of a standardized rehabilitation exercise protocol, training, and enhancement of the exercising environment. Head nurses' leadership and decision-making also played an important role in the success of this project. http://links.lww.com/IJEBH/A180.

Extracellular vesicles as potential diagnostic markers for kidney allograft rejection.

Kidney transplantation is a highly effective treatment for end-stage kidney disease. However, allograft rejection remains a significant clinical challenge in kidney transplant patients. Although kidney allograft biopsy is the gold-standard diagnostic method, it is an invasive procedure. Since the current monitoring methods, including screening of serum creatinine and urinary protein, are not of sufficient sensitivity, there is a need for effective post-transplant monitoring to detect allograft rejection at an early stage. Extracellular vesicles are vesicles with a lipid bilayer that originate from different cell types in pathological and physiological conditions. The content of extracellular vesicles reflects the status of cells at the time of their production. This review comprehensively summarizes clinical, in vivo, and in vitro reports that highlight the potential of extracellular vesicles as diagnostic biomarkers for kidney allograft rejection. Clarification would facilitate differentiation between rejection and non-rejection and identification of the mechanisms involved in the allograft rejection. Despite increasing evidence, further research is necessary to establish the clinical utility of extracellular vesicles in the diagnosis and monitoring of allograft rejection in kidney transplant recipients. Using extracellular vesicles as non-invasive biomarkers for diagnosis of kidney allograft rejection could have tremendous benefits in improving patient outcomes and reduce the need for invasive procedures.

De-novo use of generic tacrolimus (Adoport) in renal transplant recipients: A single center experience from Türkiye

Objective: Renal transplantation is the best treatment for end-stage kidney disease, and tacrolimus has become an important immunosuppressive treatment for kidney transplant patients since it was introduced. After the first generic tacrolimus has been approved by the FDA, studies have begun to compare the effectiveness and safety of generic tacrolimus with the original tacrolimus. When using generic immunosuppressive therapies, it is also necessary to ensure that it provides adequate immunosuppression and does not cause severe toxicity. This study aims to compare clinical outcomes, including acute rejection, graft loss and adverse reactions, in patients receiving brand tacrolimus (Prograf, Astellas Pharma, U.S.) or generic tacrolimus (Adoport, Sandoz, UK) from the start of kidney transplant therapy. Study Design: Renal transplant recipients between 1 January 2015-1 March 2020 were screened retrospectively. All patients receiving de novo generic tacrolimus (n:51) and randomly selected 102 control renal transplant recipients receiving original tacrolimus were included in this study. Materials and Methods: We evaluated and recorded demographic, clinical and laboratory data including age, gender, primary kidney disease, donor type (live or dead), induction and death regimen, tacrolimus dose, tacrolimus through levels, serum creatinine, biopsy-confirmed acute rejection episodes, delayed transplant function, positive BK polyomavirus in the urine, BK polyomavirus-related nephropathy, cytomegalovirus infection in 1-year follow-up. Results: Most of the patients were male (64.1%) with a mean age of 38.3 years. There was no significant difference in demographic characteristics between the original and generic tacrolimus groups. No differences were found in terms of creatinine levels, total daily dose of tacrolimus and tacrolimus trough levels at discharge and the first year. Additionally, biopsy-confirmed acute rejection in the following year after transplantation, BKPyV positivity in urine, BKPyVAN, CMV viremia and adverse reactions related to tacrolimus were similar between the two groups. Conclusion: With this study, we aimed to contribute to the literature with our experience on the use of generic tacrolimus from our country. As a result of our study, we noted that generic tacrolimus can be safely preferred for de-novo use with close drug-level monitoring because it is an immunosuppressant agent with a narrow therapeutic index. There is a continuing need for randomized prospective-designed and multi-centric studies with a wide range of patients.

Normal Proteasome Function Is Needed to Prevent Kidney Graft Injury during Cold Storage Followed by Transplantation.

Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD). However, there is a shortage of transplantable kidneys, and donor organs can be damaged by necessary cold storage (CS). Although CS improves the viability of kidneys from deceased donors, prolonged CS negatively affects transplantation outcomes. Previously, we reported that renal proteasome function decreased after rat kidneys underwent CS followed by transplantation (CS + Tx). Here, we investigated the mechanism underlying proteasome dysfunction and the role of the proteasome in kidney graft outcome using a rat model of CS + Tx. We found that the key proteasome subunits β5, α3, and Rpt6 are modified, and proteasome assembly is impaired. Specifically, we detected the modification and aggregation of Rpt6 after CS + Tx, and Rpt6 modification was reversed when renal extracts were treated with protein phosphatases. CS + Tx kidneys also displayed increased levels of nitrotyrosine, an indicator of peroxynitrite (a reactive oxygen species, ROS), compared to sham. Because the Rpt6 subunit appeared to aggregate, we investigated the effect of CS + Tx-mediated ROS (peroxynitrite) generation on renal proteasome assembly and function. We treated NRK cells with exogenous peroxynitrite and evaluated PAC1 (proteasome assembly chaperone), Rpt6, and β5. Peroxynitrite induced a dose-dependent decrease in PAC1 and β5, but Rpt6 was not affected (protein level or modification). Finally, serum creatinine increased when we inhibited the proteasome in transplanted donor rat kidneys (without CS), recapitulating the effects of CS + Tx. These findings underscore the effects of CS + Tx on renal proteasome subunit dysregulation and also highlight the significance of proteasome activity in maintaining graft function following CS + Tx.

Two-day Static Cold Preservation of α1,3-Galactosyltransferase Knockout Kidney Grafts Before Simulated Xenotransplantation.

Transplantation remains the preferred treatment for end-stage kidney disease but is critically limited by the number of available organs. Xenografts from genetically modified pigs have become a promising solution to the loss of life while waiting for transplantation. However, the current clinical model for xenotransplantation will require off-site procurement, leading to a period of ischemia during transportation. As of today, there is limited understanding regarding the preservation of these organs, including the duration of viability, and the associated molecular changes. Thus, our aim was to evaluate the effects of static cold storage (SCS) on α1,3-galactosyltransferase knockout (GGTA1 KO) kidney. After SCS, viability was further assessed using acellular sub-normothermic ex vivo perfusion and simulated transplantation with human blood. Compared to baseline, tubular and glomerular interstitium was preserved after 2 days of SCS in both WT and GGTA1 KO kidneys. Bulk RNA-sequencing demonstrated that only eight genes were differentially expressed after SCS in GGTA1 KO kidneys. During sub-normothermic perfusion, kidney function, reflected by oxygen consumption, urine output, and lactate production was adequate in GGTA1 KO grafts. During a simulated transplant with human blood, macroscopic and histological assessment revealed minimal kidney injury. However, GGTA1 KO kidneys exhibited higher arterial resistance, increased lactate production, and reduced oxygen consumption during the simulated transplant. In summary, our study suggests that SCS is feasible for the preservation of porcine GGTA1 KO kidneys. However, alternative preservation methods should be evaluated for extended preservation of porcine grafts.

The Future for End-Stage Kidney Disease Treatment: Implantable Bioartificial Kidney Challenge

Despite limited organ availability and post-transplant complications, kidney transplantation remains the optimal treatment for End-Stage Kidney Disease (ESKD). However, innovative dialysis technologies such as portable, wearable, and implantable bioartificial kidney systems are being developed with the aim of addressing these issues and improving patient care. An ideal implantable device could combine bioreactors and blood ultrafiltration to replicate key native cell functions for solute reabsorption, secretion, and endocrinologic activities. Today, the feasibility of an implantable bioreactor for renal cell therapy opens the challenge of developing a fully implantable bioartificial kidney based on silicon nanopore membranes to ensure immunological isolation, cell viability, and the possibility of maintaining a blood substrate for metabolic activities. Current technology is not sufficient to obtain an efficient artificial bioreactor to reach physiological blood purification, which requires a more complex system to produce an ultrafiltrate from the blood that can be processed by cells and eliminated as urine. The number of cells in the bioreactor, endocrine activity, immunological cell isolation, solute and fluid secretion/reabsorption, cell viability, blood and ultrafiltration flow control, and thrombogenicity are fundamental issues that require a new technology that today appears to be a challenge for the design of an implantable artificial kidney. This review aims to analyze the state of the art in this particular field of kidney replacement therapy to highlight the current limitations and possible future technology developments to create implanted and wearable organs capable of treating ESKD with artificial organs that can replicate all native kidneys functions.

The Role of Protocol Allograft Biopsies in Postrenal Transplantation: A Systematic Review and Meta-analysis

Introduction: Kidney transplantation is the preferred treatment for end-stage kidney disease, offering improved outcomes compared to dialysis. However, factors such as immunological rejection, drug toxicity, and infections limit its success. Incorporating protocol biopsies (PBs) into standard care for kidney transplant recipients varies widely. This study aims to review the literature on the practice, histopathological findings, and benefits of performing PB on allograft function. Materials and Methods: A systematic review was conducted using PubMed, ScienceDirect, and other databases from 2000 to 2023. Studies describing findings of PBs within 2 years posttransplant were included. Data extraction covered study design, immunosuppression, biopsy timing, incidence of subclinical rejection (SCR), clinical rejection, and allograft function measures. Statistical analysis was performed using R and RevMan software. Results: Among 25 studies (3384 patients) included, 8 were randomized controlled studies. Protocol biopsy timing varied, with the highest number performed at 1 year (44.84%). The pooled incidence of SCR was 13%, with heterogeneity across estimates. Subgroup analysis did not reveal significant differences in SCR rates between high- and low-immunologic risk patients. Patients who underwent PBs had lower clinical rejection rates (12.64% vs. 20.17%) and better allograft function. Incidence of calcineurin inhibitor toxicity ranged from 1.2% to 63.4%, and BK virus nephropathy ranged from 0% to 5.9% in included studies. Conclusion: Performing PB at 6 months, 1 year, and 2 years posttransplant can reveal SCR and potentially improve long-term graft outcomes. Treatment of SCR may reduce clinical rejection episodes. However, further research, particularly comparing PB with noninvasive methods, is needed to better understand their efficacy and complications in the modern transplant landscape.

Molecular landscape of kidney allograft tissues data integration portal (NephroDIP): a curated database to improve integration of high-throughput kidney transplant datasets.

Kidney transplantation is the optimal treatment for end-stage kidney disease; however, premature allograft loss remains a serious issue. While many high-throughput omics studies have analyzed patient allograft biospecimens, integration of these datasets is challenging, which represents a considerable barrier to advancing our understanding of the mechanisms of allograft loss. To facilitate integration, we have created a curated database containing all open-access high-throughput datasets from human kidney transplant studies, termed NephroDIP (Nephrology Data Integration Portal). PubMed was searched for high-throughput transcriptomic, proteomic, single nucleotide variant, metabolomic, and epigenomic studies in kidney transplantation, which yielded 9,964 studies. From these, 134 studies with available data detailing 260 comparisons and 83,262 molecules were included in NephroDIP v1.0. To illustrate the capabilities of NephroDIP, we have used the database to identify common gene, protein, and microRNA networks that are disrupted in patients with chronic antibody-mediated rejection, the most important cause of late allograft loss. We have also explored the role of an immunomodulatory protein galectin-1 (LGALS1), along with its interactors and transcriptional regulators, in kidney allograft injury. We highlight the pathways enriched among LGALS1 interactors and transcriptional regulators in kidney fibrosis and during immunosuppression. NephroDIP is an open access data portal that facilitates data visualization and will help provide new insights into existing kidney transplant data through integration of distinct studies and modules (https://ophid.utoronto.ca/NephroDIP).

Conservative Management in End-Stage Kidney Disease between the Dialysis Myth and Neglected Evidence-Based Medicine.

In the last few decades, the aging of the general population has significantly increased the number of elderly patients with end-stage kidney disease (ESKD) who require renal replacement therapy. ESKD elders are often frail and highly comorbid with social issues and seem to not benefit from dialysis in terms of survival and quality of life. Conservative management (CM) could represent a valid treatment option, allowing them to live for months to years with a modest impact on their habits. Despite these possible advantages, CM remains underused due to the myth of dialysis as the only effective treatment option for all ESKD patients regardless of its impact on quality of life and survival. Both CM and dialysis remain valid alternatives in the management of ESKD. However, assessing comorbidities, disabilities, and social context should drive the choice of the best possible treatment for ESKD, while in elderly patients with short life expectancies, referring them to palliative care seems the most reasonable choice.