Ranking patients on the kidney transplant waiting list based on fuzzy inference system

Background Kidney transplantation is the best treatment for people with End-Stage Renal Disease (ESRD). Kidney allocation is the most important challenge in kidney transplantation process. In this study, a Fuzzy Inference System (FIS) was developed to rank the patients based on kidney allocation factors. The main objective was to develop an expert system, which would mimic the expert intuitive thinking and decision-making process in the face of the complexity of kidney allocation. Methods In the first stage, kidney allocation factors were identified. Next, Intuitionistic Fuzzy Analytic Hierarchy Process (IF-AHP) has been used to weigh them. The purpose of this stage is to develop a point scoring system for kidney allocation. Fuzzy if-then rules were extracted from the United Network for Organ Sharing (UNOS) dataset by constructing the decision tree, in the second stage. Then, a Multi-Input Single-Output (MISO) Mamdani fuzzy inference system was developed for ranking the patients on the waiting list. Results To evaluate the performance of the developed Fuzzy Inference System for Kidney Allocation (FISKA), it was compared with a point scoring system and a filtering system as two common approaches for kidney allocation. The results indicated that FISKA is more acceptable to the experts than the mentioned common methods. Conclusion Given the scarcity of donated kidneys and the importance of optimal use of existing kidneys, FISKA can be very useful for improving kidney allocation systems. Countries that decide to change or improve the kidney allocation system can simply use the proposed model. Furthermore, this model is applicable to other organs, including lung, liver, and heart.

Genome-wide Analysis Reflects Novel 5-Hydroxymethylcytosines Implicated in Diabetic Nephropathy

Long-term complications of type 2 diabetes (T2D) are the major causes for T2D-related disability and mortality. Notably, diabetic nephropathy (DN) has become the most frequent cause of end-stage renal disease (ESRD) in most countries. Understanding epigenetic contributors to DN can provide novel insights into this complex disorder and lay the foundation for more effective monitoring tools and preventive interventions, critical for achieving the ultimate goal of improving patient care and reducing healthcare burden. We have used a selective chemical labeling technique (5hmC-Seal) to profile genome-wide distributions of 5-hydroxymethylcytosines (5hmC), a gene activation mark, in patient-derived circulating cell-free DNA (cfDNA). Differentially modified 5hmC genes were identified across T2D patients with DN (n = 12), T2D patients with non-DN vascular complications (non-DN) (n = 29), and T2D patients with no complications (controls) (n = 14). Specifically, differential 5hmC markers between DN and controls revealed relevant pathways such as NOD-like receptor signaling pathway and tyrosine metabolism. A ten-gene panel was shown to provide differential 5hmC patterns between controls and DN, as well as between controls and non-DN patients using a machine learning approach. The 5hmC profiles in cfDNA reflected novel DN-associated epigenetic modifications relevant to the disease pathogenesis of DN. Importantly, these findings in cfDNA, a convenient liquid biopsy, have the potential to be exploited as a clinically useful tool for predicting DN in high risk T2D patients. Keywords: diabetes, nephropathy, epigenetics, 5-hydroxymethylcytosine, cfDNA

A study on evaluating blood urea and serum creatinine in diabetes mellitus patients

Diabetes is one of the leading causes for end stage renal disease and nephropathy. Increases of blood urea and serum creatinine are due to abnormal renal function and also reduction in glomerular filtration rate. So, Urea and Creatinine are the ideal biomarkers to correlate the progression of diabetic nephropathy. Aim of the study is to evaluate the blood urea & serum creatinine with HbA1C in Diabetes mellitus patients.: A total of 50 cases and 30 controls were selected in our study. Blood samples were collected for blood urea, serum creatinine, HbA1C, Fasting plasma glucose and Post prandial blood sugar with age limit of 35-65 years. Mean ±SD was calculated for all these parameters. Blood urea and Serum creatinine are statistically significant in Diabetic patients when compared to the controls.Our study shows that blood urea and serum creatinine can be used as biomarkers in the early detection of diabetic nephropathy. These parameters help in reducing the severity of renal failure.

Patient Survival Between Hemodialysis and Peritoneal Dialysis Among End-Stage Renal Disease Patients Secondary to Myeloperoxidase-ANCA-Associated Vasculitis

BackgroundA significant proportion of anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis eventually progresses to end-stage renal disease (ESRD) thus requiring long-term dialysis. There is no consensus about which dialysis modality is more recommended for those patients with associated vasculitis (AAV-ESRD). The primary objective of this study was to compare patient survival in patients with AAV-ESRD treated with hemodialysis (HD) or peritoneal dialysis (PD).MethodsThis double-center retrospective cohort study included dialysis-dependent patients who were treated with HD or PD. Clinical data were collected under standard format. The Birmingham vasculitis activity score (BVAS) was used to evaluate disease activity at diagnosis and organ damage was assessed using the vasculitis damage index (VDI) at dialysis initiation.ResultsIn total, 85 patients were included: 64 with hemodialysis and 21 with peritoneal dialysis. The patients with AAV-PD were much younger than the AAV-HD patients (48 vs. 62, P < 0.01) and more were female (76.2 vs. 51.6%, P = 0.05). The laboratory data were almost similar. The comorbidities, VDI score, and immuno-suppressive therapy at dialysis initiation were almost no statistical difference. Patient survival rates between HD and PD at 1 year were 65.3 vs. 90% (P = 0.062), 3 year were 59.6 vs. 90% (P < 0.001), and 5 years were 59.6 vs. 67.5% (P = 0.569). The overall survival was no significant difference between the two groups (P = 0.086) and the dialysis modality (HD or PD) was not shown to be an independent predictor for all-cause death (hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.31–1.7; P = 0.473). Cardio-cerebrovascular events were the main cause of death among AAV-HD patients while infection in patients with AAV-PD.ConclusionThese results provide real-world data that the use of either hemodialysis or peritoneal dialysis modality does not affect patient survival for patients with AAV-ESRD who need long-term dialysis.

Activation of Notch3 in Renal Tubular Cells Leads to Progressive Cystic Kidney Disease

Background: Polycystic kidney disease (PKD) is a genetic disorder affecting millions of people worldwide that is characterized by fluid-filled cysts and leads to end-stage renal disease (ESRD). The hallmarks of PKD are proliferation and dedifferentiation of tubular epithelial cells, cellular processes known to be regulated by Notch signaling. Methods: We found increased Notch3 expression in human PKD and renal cell carcinoma biopsies. To obtain insight into the underlying mechanisms and the functional consequences of this abnormal expression, we developed a transgenic mouse model with conditional overexpression of the intracellular Notch3 (ICN3) domain specifically in renal tubules. We evaluated the alterations in renal function (creatininemia, BUN) and structure (cysts, fibrosis, inflammation) and measured the expression of several genes involved in Notch signaling and the mechanisms of inflammation, proliferation, dedifferentiation, fibrosis, injury, apoptosis and regeneration. Results: After one month of ICN3 overexpression, kidneys were larger with tubules grossly enlarged in diameter, with cell hypertrophy and hyperplasia, exclusively in the outer stripe of the outer medulla. After three months, mice developed numerous cysts in proximal and distal tubules. The cysts had variable sizes and were lined with a single- or multilayered, flattened, cuboid or columnar epithelium. This resulted in epithelial hyperplasia, which was observed as protrusions into the cystic lumen in some of the renal cysts. The pre-cystic and cystic epithelium showed increased expression of cytoskeletal filaments and markers of epithelial injury and dedifferentiation. Additionally, the epithelium showed increased proliferation with an aberrant orientation of the mitotic spindle. These phenotypic tubular alterations led to progressive interstitial inflammation and fibrosis. Conclusions: In summary, Notch3 signaling promoted tubular cell proliferation, the alignment of cell division, dedifferentiation and hyperplasia, leading to cystic kidney diseases and pre-neoplastic lesions.

Central Venous Reflux, a Rare Cause of Neurological Manifestations in Hemodialysis Patients: A Case Report and Literature Review

Central venous disease (CVD) is a serious complication in hemodialysis patients. Neurological manifestations are rare. We describe a female with end-stage renal disease with throbbing headache accompanied by paresthesia, weakness, and abnormal posture of her right hand during dialysis sessions. Motor symptoms completely resolved after each dialysis session, although the headaches persisted for several hours. No neurological deficit was evidenced on physical examination. Digital subtraction angiography identified an incomplete thrombosis of the left brachiocephalic vein with retrograde flow in the internal jugular vein, sigmoid sinus, and transverse sinus on the left side. This case illustrates that cerebral venous congestion due to CVD can produce neurological symptoms. Furthermore, we systematically review the literature to identify the characteristics of the cases described so far. This allows clinicians to know the entity and have a high index of suspicion in a hemodialysis patient who develops neurological symptoms.

Fluconazole in Hypercalciuric Patients with Increased 1,25(OH)2D Levels: The Prospective, Randomized, Placebo-Controlled, Double Blind FLUCOLITH Trial.

BackgroundHypercalciuria is one of the most frequent metabolic disorders associated with nephrolithiasis and/or nephrocalcinosis possibly leading to chronic kidney disease (CKD) and bone complications in adults. Orphan diseases with different underlying primary pathophysiology share inappropriately increased 1,25(OH)2D levels and hypercalciuria, e.g., hypersensitivity to vitamin D and renal phosphate wasting. Their management is challenging, typically based on hyperhydration and dietary advice. The antifungal azoles are known to inhibit the 1α-hydroxylase and therefore decrease 1,25(OH)2D levels; they are commonly used, with well described pharmacokinetic and tolerability data. Fluconazole has been successfully reported to reduce calciuria in patients with CYP24A1 or SLC34A3 mutations, with no safety warnings. Thus, based on these case reports, we hypothesize that fluconazole is effective to decrease and normalize calciuria in patients with hypercalciuria and increased 1,25(OH)2D levels.MethodsThe FLUCOLITH trial is a prospective, interventional, randomized in parallel groups (1:1), placebo-controlled, double blind trial. A total of 60 patients (10-60years) with nephrolithiasis and/or nephrocalcinosis history, hypercalciuria (> 0.1 mmol/kg/d), increased 1,25(OH)2D levels (> 150 pmol/L) and 25-OH-D levels >20 nmol/L, will be included. Inclusions will be performed only from mid-September to the beginning of February to avoid bias due to sunlight-induced vitamin D synthesis. The primary endpoint will be the proportion of patients with normalization of 24-hour calciuria between baseline and 16 weeks, or with a relative decrease of at least 30% of 24-hour calciuria in patients who still display at W16 a 24-hour hypercalciuria. DiscussionThe current challenge is to propose an efficient treatment to patients with hypercalciuria and increased 1,25(OH)2D levels in order to prevent later complications and notably CKD that can ultimately lead to end-stage renal disease. Based on improvement of knowledge in phosphate/calcium metabolism, pathophysiology and genetics, the “off-label” use of fluconazole was recently reported to be useful in hypercalciuric patients with increased 1,25(OH)2D levels. Thus, the FLUCOLITH study is a unique opportunity to develop a new indication of a well-known and not expensive drug in orphan renal diseases, the ultimate objective being the secondary prevention of CKD worsening in these patients. Trial RegistrationClinicalTrial.gov, ID: identifier: NCT04495608. Registered on July 23rd, 2020

A Prognostic Merit of Statins in Patients with Chronic Hemodialysis after Percutaneous Coronary Intervention—A 10-Year Follow-Up Study

Background: Patients with end-stage renal disease (ESRD) on chronic hemodialysis who are complicated by coronary artery disease (CAD) are at very high risk of cardiovascular (CV) events and mortality. However, the prognostic benefit of statins, which is firmly established in the general population, is still under debate in this particular population. Methods: As a part of a prospective single-center percutaneous coronary intervention (PCI) registry database, this study included consecutive patients on chronic hemodialysis who underwent PCI for the first time between 2000 and 2016 (n = 201). Participants were divided into 2 groups by following 2 factors, such as (1) with or without statin, and (2) with or without high LDL-C (> and ≤LDL-C = 93 mg/dL, median) at the time of PCI. The primary endpoint was defined as CV death, and the secondary endpoints included all-cause and non-CV death, and 3 point major cardiovascular adverse events (3P-MACE) which is the composite of CV death, non-fatal myocardial infarction and stroke. The median and range of the follow-up period were 2.8, 0–15.2 years, respectively. Results: Kaplan–Meier analyses showed significantly lower cumulative incidences of primary and secondary endpoints other than non-CV deaths in patients receiving statins. Conversely, no difference was observed when patients were divided by the median LDL-C at the time of PCI (p = 0.11). Multivariate Cox proportional hazard analysis identified statins as an independent predictor of reduced risk of CV death (Hazard ratio of statin use: 0.43, 95% confidence interval 0.18–0.88, p = 0.02), all-cause death (HR: 0.50, 95%CI 0.29–0.84, p = 0.007) and 3P-MACE (HR: 0.50, 95%CI 0.25–0.93, p = 0.03). Conclusions: Statins were associated with reduced risk of adverse outcomes in patients with ESRD following PCI.

The Rate and Risk Factors of Acute Kidney Injury among Cancer Patients’ Admissions in Palestine: A Single-Center Study

Introduction. Acute kidney injury (AKI) remains a critical issue for cancer patients despite recent treatment improvements. This study aimed to assess the incidence of AKI in cancer patients and its related risk factors. Methods. A Retrospective cohort study was conducted at tertiary hospitals in the period 2016–2018. A data abstraction sheet was used to collect related variables from patients’ records. During admission, the incidence of AKI was assessed using creatinine measurements. RIFLE criteria were used to classify it into five categories of severity: risk, injury, failure, loss, and end-stage renal disease. Results. Using RIFLE (Risk, Injury, Failure, Loss, and End-stage renal disease) criteria, 6.9% of admissions were complicated with AKI. The severity of these fell into the categories of risk, injury, and failure, 3.3%, 1.7%, and 1.9%, respectively. In the multivariate model, the odds for developing AKI was significantly higher for patients with congestive heart failure (AOR = 17.1, 95% CI 1.7–80.1), chronic kidney disease (adjusted OR = 6.8, 95% CI 1.4–32.2 ( P value 0.017)), sepsis (AOR = 4.4, 95% CI 1.9–10.1), hypercalcemia (AOR = 8.4, 95% CI 1.3–46.1), and admission to the ICU (AOR = 5.8, 95% CI 2.1–16.2). In addition, the mortality rate was nearly seven times higher for patients complicated by AKI (relative risk = 7.6, 95% CI 3.2–18.2). Conclusion. AKI was significantly associated with congestive heart failure, chronic kidney disease, sepsis, ICU admission, and hypercalcemia in cancer patients, resulting in poorer outcomes and higher mortality rates. AKI assessment for hospitalized cancer patients should be performed regularly, especially for patients at increased risk.