TH1 Cell Frequency and Neutrophil-to-Lymphocyte Ratio in Hemodialysis: Potential Contributions to Patient Monitoring.

Introduction: Patients undergoing hemodialysis (HD) often exhibit an impaired cellular immune response, which may contribute to an increased susceptibility to infections and other complications. Th1 cells, a subset of T-helper cells, play a crucial role in cellular immunity. However, the modulation of Th1 cells by HD treatment remains unclear. Objective: This study aims to investigate the levels of circulating T cells, especially Th1 cells, and the neutrophil-to-lymphocyte ratio (NLR) in HD patients. Methods: We recruited 26 HD patients and 10 healthy volunteers. Demographical data were collected, and peripheral blood samples were analyzed. Absolute blood cell counts were determined, and T-cell populations were identified using flow cytometry. Th1 cells were defined as IFN-γ-producing CD4+ T cells after in vitro activation, and NLR was calculated through the ratio between the neutrophil and lymphocyte counts measured in peripheral blood. Results: We have observed a significant decrease in Th1 subpopulation frequency in HD patients, as well as significant correlations between immunological and demographic parameters, among which are the NLR values and the absolute values of T-cell subsets. Conclusions: These results seem to clarify the role of Th1 cells in modulating the immune responses of hemodialysis-treated patients, potentially considering its frequency as an indicator for CKD development.

Tumoral calcinosis in chronic renal failure: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Tumor calcinosis is a rare and benign disorder characterized by calcified periarticular soft tissue masses. It may be idiopathic or caused by a condition known as hyperphosphatemia. There is still no definitive guideline for treating this disease, with excision being one of the primary treatment modalities. CASE PRESENTATION: 2 patients with a history of longstanding diabetes and dialysis presented with a painless lump on their right buttock, measuring 18 × 30 cm in the right gluteal region. Laboratory examinations showed a high ureum, creatinine, and serum phosphate. A radiograph revealed opacity on the right hip joint, without involvement of the proximal femur bone. A biopsy confirmed the diagnosis of tumor calcinosis. Both patients were treated with calcium carbonate to control their high serum phosphate levels. Both patients showed excellent tumor control without progression. CLINICAL DISCUSSION: Tumoral calcinosis (TC) is an extra-articular benign but aggressive tumor. The precise mechanism of TC remains unknown, which partly explains the lack of established treatment modality. We treat our patients with calcium carbonate to reduce the serum phosphate and treat the tumor without surgery. The treatment yielded a satisfactory clinical result. CONCLUSION: This study showed that a secondary TC may be conservatively treated without any surgical excision if we address the underlying problem. But it may not result in a reduction of the tumor's size.

Recent Progress and Perspectives in Sodium-Glucose Co-transporter 1/2 Inhibitors.

Sodium-Glucose Co-transporter-1/2 (SGLT1/2) inhibitors (also called glifozins) are a class of glucose-decreasing drugs in adults with Type 2 Diabetes (T2D). SGLT2 inhibitors diminish sodium and glucose reabsorption in the renal proximal convoluted tubule. Recent clinical trials have revealed that SGLT2 inhibitors might be beneficial for treating diseases other than diabetes, including chronic renal disease and Heart Failure (HF). Currently, SGLT2 inhibitors are recommended not only for the glycemic management of T2D but also for cardiovascular protection. SGLT2 inhibitors have become one of the foundational drugs for HF with reduced Ejection Fraction (HFrEF) treatment and the first medications with proven prognostic benefit in HF with preserved Ejection Fraction (HFpEF). At present, 11 SGLT1/2 inhibitors have been approved for clinical use in different countries. Beyond their anti-hyperglycemic effect, these inhibitors have shown clear cardio- and nephroprotective properties. A growing body of research studies suggests that SGLT1/2 inhibitors may provide potential clinical benefits in metabolic as well as oncological, hematological, and neurological disorders.

Higher post procedural bleeding in patients with advanced chronic kidney disease undergoing percutaneous coronary intervention.

BACKGROUND: Advanced chronic kidney disease (ACKD) is common in patients undergoing percutaneous coronary intervention (PCI). Post-PCI bleeding has been shown to increase mortality and remains an important challenge in these patients. Previous studies have shown increased post-PCI bleeding in CKD patients but often ACKD patients are excluded from these trials. The goal of this study was to evaluate if patients undergoing PCI with advanced renal disease have higher bleeding complications. METHODS: We analyzed the National Inpatient Sample (NIS) database to compare the post-PCI bleeding rates for ACKD (CKD stage 3 and above) undergoing PCI between 2006 and 2011 to those without ACKD in patients over the age of 40. Specific ICD-9 CM codes were used to identify these patients. RESULTS: A total of 49,192 patients had post-PCI bleeding during the study period of which 3,675 (7.5%) had ACKD. Patients with ACKD were older (68.7±11.7 years). During the study period, there was a decline in post-PCI bleeding rates in both ACKD and control groups. Patients with ACKD have significantly higher post-PCI bleeding rates compared to the control group. For example, in 2006, 133.9 in patients with ACKD had bleeding vs. 104.4 per 100,000 in patients without ACKD (P<0.05). After multivariate adjustment for bassline comorbidities, ACKD remained independently associated with post-PCI bleeding risk (OR: 1.07, CI: 1.03-1.11, P<0.001). CONCLUSION: Despite the overall decline in post-PCI bleeding in patients undergoing PCI, ACKD remains independently associated with post-procedural bleeding.

Comorbidity and Medication Trends in Chronic Kidney Disease and Incident Atrial Fibrillation: A Nationwide Cohort Study.

INTRODUCTION: Chronic kidney disease (CKD) is associated with an increased incidence of atrial fibrillation (AF). Also, patients with AF are prone to adverse kidney outcomes. We examined comorbidities and medication use in patients with CKD and incident AF. METHODS: The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide retrospective register-linkage study including data from 168,233 patients with incident AF from 2007 to 2018, with laboratory data from 2010 onwards. Estimated glomerular filtration rate (eGFR) was available for 124,936 patients. The cohort was divided into 5 CKD stages with separate groups for dialysis and kidney transplantation. RESULTS: At AF diagnosis eGFR <60 mL/min/1.73 m2 was found in 27%, while 318 (0.3%) patients were on dialysis, and 188 (0.2%) had a functioning kidney transplant. Lowering eGFR yielded more comorbidities and medications. During 2010-2018 in patients with eGFR <60 mL/min/1.73 m2 prevalence of hypertension, dyslipidaemia, and diabetes increased from 82 to 88%, from 50 to 66% and from 25 to 33%, respectively (<0.001). Throughout the observation period, lipid-lowering medication was underused. CONCLUSION: More than one-fourth of patients with incident AF also had CKD stage 3-5 (eGFR <60 mL/min/1.73 m2). Both comorbidities and medication use increased with worsening kidney function. Prevalence of major cardiovascular (CV) risk factors increased during 2010-2018, but the use of survival-affecting medications, such as lipid-lowering medication, was suboptimal at all stages of CKD. More attention should be given to the optimal treatment of risk factors in this high CV risk population.

Renoprotective strategies.

Kidney disease remains a condition with an increasing incidence, high morbidity and mortality associated with cardiovascular events. The incidence of end-stage renal disease is expected to increase. Despite of the technical improvement, dialysis never achieved a full clearance of the blood dialysis. Therefore, the demand for new renoprotective measures has never been greater. Here, we report new strategies for preventing renal damage.

A lentivirus-vectored feline erythropoietin gene therapy strategy in tissue culture and rodent models for the potential treatment of chronic renal disease-associated anemia.

OBJECTIVE: The aim of this study was to assess the efficacy and safety of a third-generation lentivirus-based vector encoding the feline erythropoietin (EPO) (feEPO) gene in vitro and in rodent models in vivo. This vector incorporates a genetic mechanism to facilitate the termination of the therapeutic effect in the event of supraphysiologic polycythemia, the herpes simplex virus thymidine kinase (HSV-TK) "suicide gene." ANIMALS: CFRK cells and replication-defective lentiviral vectors encoding feEPO were used for in vitro experiments. Eight Fischer rats were enrolled in the pilot in vivo study, 24 EPO-deficient mice were used in the initial mouse study, and 15 EPO-deficient mice were enrolled in the final mouse study. METHODS: Efficacy of a third-generation lentivirus encoding feEPO was determined in vitro using western blot assays. Subsequently, in a series of rodent experiments, animals were administered the viral vector in progressively increasing inoculation doses with serial measurements of blood packed cell volume (PCV) over time. RESULTS: We documented production of feEPO protein in transduced CRFK cells with subsequent cessation of production when treated with the HSV-TK substrate ganciclovir. In vivo, we demonstrated variably persistent elevated PCV values in treated rats and mice with eventual return to baseline values over time. CLINICAL RELEVANCE: These results provide justification for a lentiviral gene therapy approach to the treatment of nonregenerative anemia associated with chronic renal disease in cats.

Guía de práctica clínica para la atención a niños y adolescentes con enfermedad renal crónica / Clinical practice guide for the care to children and adolescents with chronic renal disease

La enfermedad renal crónica constituye un problema de salud por su impacto sobre los individuos, la sociedad y la economía. Teniendo en cuenta lo anterior, y luego de una amplia búsqueda bibliográfica, se diseñó una guía de práctica clínica en el Policlínico Luis Augusto Turcios Lima de la provincia de Pinar del Río, dirigida a los profesionales de la atención primaria de salud, con el objetivo de mejorar la calidad de vida de niños y adolescentes con dicha enfermedad. Esta fue elaborada por los métodos de la medicina basada en la evidencia, según el consenso y la opinión de los expertos. Se logró generalizar esta herramienta, emitir recomendaciones y actualizarla acorde con las nuevas evidencias médicas. Finalmente, resultó evaluada por los expertos como muy recomendada.

Chronic renal disease constitutes a health problem due to its impact on individuals, society and economy. Taking into account the above-mentioned, and after a wide literature search, a clinical practice guide was designed in Luis Augusto Turcios Lima Polyclinic from Pinar del Río province, directed to primary health care professionals, aimed at improving the life quality of children and adolescents with this disease. It was elaborated by medicine methods based on the evidence, according to the consent and opinion of experts. It was possible to generalize this tool, give recommendations and up to date according to the new medical evidences. Finally, it was evaluated by experts as very recommended.

Pros of Inpatient Sodium Glucose Cotransporter-2 Inhibitor Use.

OBJECTIVE: Sodium-glucose-cotransporter 2 (SGLT-2) inhibitors are widely used for diabetes management especially because their effects go beyond glucose control. More recently, their indications and usage have expanded to heart failure (HF) and renal dysfunction therapy in patients both with and without diabetes. Beneficial effects, especially for HF readmission, accrue very early in their treatment trajectory, and this has promoted their use in the hospital setting. Data on their safety and efficacy for inpatient use are accumulating but have lagged behind the outpatient data for their use. The objective of this counterpoint piece is to highlight areas of benefit for starting or continuing SGLT-2 inhibitors in the inpatient setting. METHODS: Discussion after literature review of available studies with a focus on HF outcomes and SGLT-2 inhibitor use. RESULTS: The benefits of starting or continuing an SGLT-2 inhibitor in the inpatient setting are well documented, mainly in HF. Similar data are not available for glucose or renal outcomes alone. Starting in the hospital allows the ability to titrate medications with similar effects, such as diabetes and HF agents, as well as reducing treatment inertia to obtain and start new medications after patients are discharged home. It is important to choose patients appropriately and hold these drugs when patients are without nutrition or on low-carbohydrate diets which can lead to diabetic ketoacidosis. CONCLUSION: In the right setting, using an SGLT-2 inhibitor in the hospital can affect multiple aspects of a patient's treatment trajectory and should be a consideration.

Associations between short-term exposure to ambient temperature and renal disease mortality in Japan during 1979-2019: A time-stratified case-crossover analysis.

Background: Previous studies have indicated that renal disease mortality is sensitive to ambient temperatures. However, most have been limited to the summer season with inconclusive evidence for changes in population vulnerability over time. Objective: This study aims to examine the association between short-term exposure to ambient temperatures and mortality due to renal diseases in Japan, and how this association varied over time. Methods: We conducted a two-stage, time-stratified case-crossover study from 1979 to 2019 across 47 prefectures of Japan. We obtained the data of daily mortality counts for all renal diseases, acute renal failure, and chronic renal disease. We fitted a conditional quasi-Poisson regression model with a distributed lag nonlinear model. A random-effects meta-analysis was applied to calculate national averages. We performed additional analyses by four subperiods, sex, and age groups. Results: We analyzed 997,590 renal mortality cases and observed a reversed J-shaped association. Lower temperatures were associated with increased mortality in all renal disease categories. The cumulative relative risks at 2.5th percentile compared to the minimum mortality temperature percentile were 1.34 (95% confidence interval [CI] = 1.29, 1.40), 1.51 (95% CI = 1.33, 1.71), and 1.33 (95% CI = 1.24, 1.43) for all renal, acute renal failure, and chronic renal disease mortality, respectively. The associations were observed in individuals of both sexes and aged 65 years and above. The associations of kidney mortality with low temperature remained consistent, while the associations with high temperature were pronounced in the past, but not in recent periods. Conclusions: Protection for individuals with impaired renal function from exposure to low temperatures during cold seasons is warranted.

Causal associations between prostate diseases, renal diseases, renal function, and erectile dysfunction risk: a 2-sample Mendelian randomization study.

Background: Previous observational studies have found a potential link between prostate disease, particularly prostate cancer (PCa), and kidney disease, specifically chronic renal disease (CKD), in relation to erectile dysfunction (ED), yet the causal relationship between these factors remains uncertain. Aim: The study sought to explore the potential causal association between prostate diseases, renal diseases, renal function, and risk of ED. Methods: In this study, 5 analytical approaches were employed to explore the causal relationships between various prostate diseases (PCa and benign prostatic hyperplasia), renal diseases (CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, and kidney ureter calculi), as well as 8 renal function parameters, with regard to ED. All data pertaining to exposure and outcome factors were acquired from publicly accessible genome-wide association studies. The methods used encompassed inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode residual sum and outlier techniques. The MR-Egger intercept test was utilized to assess pleiotropy, while Cochran's Q statistic was employed to measure heterogeneity. Outcomes: We employed inverse variance weighting MR as the primary statistical method to assess the causal relationship between exposure factors and ED. Results: Genetically predicted PCa demonstrated a causal association with an elevated risk of ED (odds ratio, 1.125; 95% confidence interval, 1.066-1.186; P < .0001). However, no compelling evidence was found to support associations between genetically determined benign prostatic hyperplasia, CKD, immunoglobulin A nephropathy, membranous nephropathy, nephrotic syndrome, kidney ureter calculi, and the renal function parameters investigated, and the risk of ED. Clinical Implications: The risk of ED is considerably amplified in patients diagnosed with PCa, thereby highlighting the importance of addressing ED as a significant concern for clinicians treating individuals with PCa. Strengths and Limitations: This study's strength lies in validating the PCa-ED association using genetic analysis, while its limitation is the heterogeneity in study results. Conclusion: The results of this study suggest a potential link between PCa and a higher risk of ED.

Chronic kidney disease and left ventricular diastolic dysfunction (CKD-LVDD) alter cardiac expression of mitochondria-related genes in swine.

Cardiovascular disease and heart failure doubles in patients with chronic kidney disease (CKD), but the underlying mechanisms remain obscure. Mitochondria are central to maintaining cellular respiration and modulating cardiomyocyte function. We took advantage of our novel swine model of CKD and left ventricular diastolic dysfunction (CKD-LVDD) to investigate the expression of mitochondria-related genes and potential mechanisms regulating their expression. CKD-LVDD and normal control pigs (n=6/group, 3 males/3 females) were studied for 14 weeks. Renal and cardiac hemodynamics were quantified by multidetector-CT, echocardiography, and pressure-volume loop studies, respectively. Mitochondrial morphology (electron microscopy) and function (Oroboros) were assessed ex vivo. In randomly selected pigs (n=3/group), cardiac mRNA-, MeDIP-, and miRNA-sequencing (seq) were performed to identify mitochondria-related genes and study their pre- and post -transcriptional regulation. CKD-LVDD exhibited cardiac mitochondrial structural abnormalities and elevated mitochondrial H2O2 emission but preserved mitochondrial function. Cardiac mRNA-seq identified 862 mitochondria-related genes, of which 69 were upregulated and 33 downregulated (fold-change ≥2, false discovery rate≤0.05). Functional analysis showed that upregulated genes were primarily implicated in processes associated with oxidative stress, whereas those downregulated mainly participated in respiration and ATP synthesis. Integrated mRNA/miRNA/MeDIP-seq analysis showed that upregulated genes were modulated predominantly by miRNAs, whereas those downregulated were by miRNA and epigenetic mechanisms. CKD-LVDD alters cardiac expression of mitochondria-related genes, associated with mitochondrial structural damage but preserved respiratory function, possibly reflecting intrinsic compensatory mechanisms. Our findings may guide the development of early interventions at stages of cardiac dysfunction in which mitochondrial injury could be prevented, and the development of LVDD ameliorated.

High Ferritin and Low Total Iron-Binding Capacity in Plasma Predict All-Cause Mortality During the First 3 Years of Hemodialysis in Patients with End-Stage Chronic Kidney Disease.

Aim: To determine all-cause mortality rate and the predictive value of plasma ferritin and total iron-binding capacity (TIBC) concentrations for mortality during the first 3 years of hemodialysis in patients with end-stage chronic renal disease (ESRD). Methods: We conducted a study on 174 ESRD patients (estimated Glomerular Filtration Rate < 15 mL/min/1.73m2). The plasma TIBC level was quantified by the ELISA method in all patients at the time before hemodialysis. Based on TIBC concentration, patients were divided equally into 2 groups. Each group had 87 patients. Patients were initiated on hemodialysis, and patients who died from any cause during the first 3 years of hemodialysis were recorded. Results: The all-cause mortality rate of ESRD patients in the first 3 years of maintenance hemodialysis was 22.9%. Plasma high hs-CRP, high ferritin, and low TIBC concentrations were independent factors associated with all-cause mortality in the patients. Plasma ferritin (cut-off value = 454.2 ng/L) and TIBC (cut-off value = 39.84 µmol/L) were predictors of all-cause mortality, AUC is: 0.772; 0.723, p < 0.001. Conclusion: Plasma ferritin and TIBC were good predictors of all-cause mortality in ESRD patients during the first 3 years of hemodialysis.

Lithium induced chronic renal disease: A case report.

We present a case of lithium-induced chronic renal disease in a 69-year-old female with past medical history of hypertension, and bipolar disorder, treated with long-term lithium-causing chronic renal disease.

The 50th Anniversary of the Implementation of PL 92-603: A Major Change in the Care of Patients with End Stage Kidney Disease.

Fifty years ago, in July 1973, providing care to patients with end stage kidney disease changed dramatically with the implementation of legislation (PL 92-603) that deemed chronic renal disease to be a disability and provided coverage under Medicare for the treatment of the disease. In this article, we discuss the impact of the implementation of PL 92-603.

Penile calciphylaxis with penoscrotal necrosis: A case report with literature review.

Penile calciphylaxis, also known as calcific uremic arteriolopathy is an uncommon condition of the penile vessels due to its extensive vascular network. The aim of this report is to report a very rare case of penile calciphylaxis with penoscrotal necrosis. A 54-year-old male patient presented with progressive penoscrotal necrosis within a duration of one month. He had a history of diabetes mellitus and stage 5 chronic kidney disease. Under spinal anesthesia, partial penectomy and excision of the necrotic scrotum were performed. Histopathological examination was consistent with calciphylaxis. Despite it is a rare occurrence, penile calciphylaxis should be included in the different diagnosis of any diabetic and end stage kidney disease patients who presented with penile pain.

Measurement of Ghrelin as a Marker of Appetite Dysregulation in Cats with and without Chronic Kidney Disease.

Appetite abnormalities and weight loss are important comorbidities in the treatment of chronic kidney disease (CKD) in cats. Ghrelin, a key hormone involved in the regulation of appetite and metabolism, is a potential marker of appetite dysregulation in cats with CKD. The aim of this study was to compare the plasma concentrations of acylated, desacyl, and total ghrelin in normal cats and cats with CKD. Storage methodology was investigated prior to evaluating ghrelin concentrations in normal and CKD cats to facilitate clinical sample collection. Twelve normal cats and twelve cats with CKD were enrolled. Plasma acylated and total ghrelin concentrations were measured using radioimmunoassay. Desacyl ghrelin was calculated (total ghrelin minus acylated ghrelin). Cats with CKD had significantly increased total ghrelin and calculated desacyl ghrelin concentrations in comparison to normal cats (p < 0.0001 and p = 0.0001). There was no significant difference in active ghrelin concentrations between groups. Both total ghrelin and calculated desacyl ghrelin were significantly correlated with serum creatinine concentrations (p < 0.0001, r = 0.70 and p < 0.0001, r = 0.73). Elevated plasma desacyl ghrelin concentrations in cats with CKD provides evidence for dysregulation of appetite in feline CKD.

From Primary Cilia and Planar Cell Polarity to Kidney Injury and Repair.

Almost every cell in the kidney, including renal tubular epithelial cells, has a primary cilium, which is a membrane-bound, hair-like structure protruding from the cellular surface. Dysfunction of primary cilia has been linked to a wide spectrum of human genetic diseases, termed ciliopathies. Planar cell polarity (PCP) refers to the coordinated alignment of cells along the cell sheet or tissue plane, a fundamental process in embryo development and organogenesis. Interestingly, there is evidence that primary cilium and PCP are interconnected. However, very limited is known about the involvement of cilia and PCP in kidney injury and repair. By using cell and mouse models, we have demonstrated a protective role of primary cilia in acute kidney injury. Mechanistically, we unveiled a reciprocal promoting relationship between cilia and autophagy in kidney tubular cells, and, accordingly, cilia may protect tubular cells by enhancing autophagy. Our recent studies further demonstrated that PCP dysfunction exaggerates acute kidney injury and may also contribute to maladaptive kidney repair after acute kidney injury. These findings provide a novel dimension to further understanding kidney injury and repair from the standpoint of cell biology.

Computerized nailfold video-capillaroscopy in type 2 diabetes: A cross-sectional study on 102 outpatients.

BACKGROUND: Type 2 diabetes (T2D) is a chronic disease that negatively affects vascular health. A careful assessment of chronic complications, including microcirculation, is mandatory. The computerized nailfold video-capillaroscopy (CNVC) accurately examines the nailfold microvasculature, but its suitability in T2D is currently under investigation. AIMS: To describe nailfold microvasculature in T2D patients regarding the level of glucose control and chronic microvascular and macrovascular complications. METHODS: This is a cross-sectional study on 102 consecutive and unselected outpatients with T2D who had undergone CNVC examination. The examination was carried out by using an electronic video-capillaroscope with 300x magnification. Capillaroscopic appearance and capillary changes were described according to well-established parameters. Capillaroscopic parameters were compared between patients with poor glucose control (HbA1c ≥7%) and those with better glucose control (HbA1c <7%) and between patients with chronic complications and those without. Chronic complications were deduced from the anamnestic, laboratory, and instrumental data and the five-item International Index of Erectile Function (IIEF-5) questionnaire. RESULTS: Nailfold capillaries in patients with HbA1c ≥7% were thicker (p = .019) and longer (p = .021) than in those with better glucose control. Ectasias (p = .017) and microaneurysms (p = .045) were more frequently observed in patients with HbA1c ≥7.0% than those with HbA1c <7.0%. Patients with ED, compared to those without, had a lower frequency of bizarre-shaped capillaries (p = .02). Microaneurysms (p = .02) were more frequently described in patients with carotid stenosis (>20%) than those without. CONCLUSION: Relevant nailfold microvascular alterations were observed in T2D, most of which were associated with poor glycemic control, ED, and carotid stenosis. Further investigation is needed to recognize the role of CNVC in predicting the onset and evolution of chronic complications and monitoring the effectiveness of antihyperglycemic treatments on microcirculation.