Hepatocellular Carcinoma in ADA-SCID Patient After Hematopoietic Stem Cell Transplantation.

Adenosine deaminase (ADA) deficiency is one of the most prevalent forms of severe combined immunodeficiency and results in the accumulation of toxic substrates which creates a systemic metabolic disease. It predisposes patients to the development of malignancies, most commonly lymphoma. We report an 8-month-old infant with ADA deficient severe combined immunodeficiency who developed progressive liver dysfunction and hepatocellular carcinoma after successful hematopoietic stem cell transplantation. This is the first case report of an ADA-deficient patient who presented with hepatocellular carcinoma and gives an insight into the complex etiology that can lie behind liver dysfunction in these patients.

Potential Use of SGLT-2 Inhibitors in Obstructive Sleep Apnea: A new treatment on the horizon.

BACKGROUND: Obstructive sleep apnea (OSA) is characterized by hypoxic episodes due to collapse of the airway during sleep and is frequently associated with obesity, type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). There is currently no pharmacological agent approved for the treatment of OSA. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have the potential to both increase life expectancy and quality of life of these patients making them promising agents for this role. There are relatively few studies investigating this possible beneficial relationship between these drugs and OSA. METHOD: We aimed to increase awareness on the potential benefits of SGLT2 inhibitors in OSA patients by describing the current evidence on the effectiveness of these inhibitors in both overall and cardiovascular morbidity and mortality. We performed a literature search for articles reporting on the use of SGLT2 inhibitors in patients with OSA and T2DM. RESULTS: We identified 4 manuscripts studying the use of SGLT2 inhibitors in 475 OSA patients with T2DM. Among them, 332 patients were administered SGLT2 inhibitors, and 143 patients were in a control group. SGLT2 inhibitors have many potential positive impacts on OSA patients by targeting various mechanisms involved in OSA pathogenesis. CONCLUSION: SGLT2 inhibitors are prime pharmacological candidates for the treatment of OSA, and additional studies are needed to better explore mechanisms and outcomes unique to this population. Additionally, patients with OSA often have multiple comorbidities that are clinical indications for SGLT2 inhibitor therapy. Physicians should recognize and encourage the use of these agents in such patients.

A meta-analysis for the role of aminoglycosides and tigecyclines in combined regimens against colistin- and carbapenem-resistant Klebsiella pneumoniae bloodstream infections.

We aimed to describe the effect of aminoglycosides and tigecycline to reduce the mortality in colistin- and carbapenem-resistant Klebsiella pneumoniae (ColR-CR-Kp) infections. We included the studies with defined outcomes after active or non-active antibiotic treatment of ColR-CR-Kp infections. The active treatment was defined as adequate antibiotic use for at least 3 days (72 h) after the diagnosis of ColR-CR-Kp infection by culture. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and the checklist of PRISMA 2020 was applied. Crude and adjusted odds ratios (OR) with 95% confidence interval (CI) were calculated and pooled in the random effects model. Adding aminoglycosides to the existing treatment regimen reduced overall mortality significantly (OR 0.34, 95% CI 0.20-0.58). Overall mortality was 34% in patients treated with aminoglycoside-combined regimens and was 60% in patients treated with non-aminoglycoside regimens. Treatment with tigecycline is not found to reduce mortality (OR: 0.76, 95% CI: 0.47-1.23). Our results suggest that aminoglycoside addition to the existing regimen of colistin- and carbapenem-resistant Klebsiella pneumoniae infections reduces mortality significantly.

Immunogenicity of SARS-CoV-2 mRNA vaccine in dialysis and kidney transplant patients: A systematic review.

Kidney transplant recipients and dialysis patients constitute a risk group for severe COVID-19. They are highly advised to get vaccinated according to the current guidelines. However, data on antibody response, cell responses and protection from events, and factors that might alter this response after a routine full series of vaccination remain incomplete for these populations. The aim of this article was to analyze the antibody responses after a full series of mRNA-based SARS-CoV-2 vaccination in kidney transplantation and dialysis patients and to define the factors that alter seroconversion status in these populations. In this systematic review, 18 studies investigating the antibody response to full vaccination with two doses of COVID-19 mRNA vaccines in hemodialysis, peritoneal dialysis, and kidney transplant patients were included. Kidney transplant and dialysis patients have a lower seroconversion rate after mRNA-based SARS-CoV-2 vaccination than the healthy population: 27.2% for kidney transplantation, 88.5% for dialysis patients while all healthy control in these studies seroconverted. Moreover, anti-S antibody titers were lower in seroconverted kidney transplantation or dialysis patients than in healthy control in all studies that assessed this variable. Older age and dialysis vintage, immunosuppressive or chemotherapy treatment, and lower serum albumin, white blood cell, lymphocyte and hemoglobin counts were associated with lower/no antibody response to vaccination. Dialysis patients and kidney transplant recipients have lower seroconversion rates after a full series of mRNA-based SARS-CoV-2 vaccination than the general population. Several factors are associated with an altered antibody response. A third dose could be considered in this patient group.

Donor obesity and weight gain after transplantation: two still overlooked threats to long-term graft survival.

The effect of donor obesity on kidney transplantation success has long been an overlooked clinical research area. Even though there is no strict guideline in most countries prohibiting donation from obese individuals, most candidates with a body mass index >35-40 kg/m2 are rejected due to concerns regarding long-term renal functional deterioration in the donor. The effects of excessive fat mass on renal function and allograft survival have been analysed by several longitudinal and follow-up studies. These studies have documented the deleterious effect on long-term graft outcomes of excessive body mass in living kidney donors and de novo obesity or pre-existing obesity worsening after transplantation on kidney outcomes. However, there is a paucity of clinical trials aimed at countering overweight and obesity in living and deceased kidney donors and in transplant patients. In this review we will briefly discuss the mechanism whereby fat excess induces adverse kidney outcomes and describe the effects on graft function and survival in living obese donors.

Dialysis after kidney transplant failure: how to deal with this daunting task?

The best treatment for patients with end-stage kidney disease is kidney transplantation, which, if successful provides both a reduction in mortality and a better quality of life compared to dialysis. Although there has been significant improvement in short-term outcomes after kidney transplantation, long-term graft survival still remains insufficient. As a result, there has been an increase in the number of individuals who need dialysis again after kidney transplant failure, and increasingly contribute to kidney transplant waiting lists. Starting dialysis after graft failure is a difficult task not only for the patients, but also for the nephrologists and the care team. Furthermore, recommendations for management of dialysis after kidney graft loss are lacking. Aim of this narrative review is to provide a perspective on the role of dialysis in the management of patients with failed kidney allograft. Although numerous studies have reported higher mortality in patients undergoing dialysis following kidney allograft failure, reports are contrasting. A patient-centered, individualized approach should drive the choices of initiating dialysis, dialysis modality, maintenance of immunosuppressive drugs and vascular access.

Future treatments in hypertension: Can we meet the unmet needs of patients?

The prevalence of arterial hypertension is approximately 47% in the United States and 55% in Europe. Multiple different medical therapies are used to treat hypertension including diuretics, beta blockers, calcium channel blockers, angiotensin receptor blockers, angiotensin converting enzyme inhibitors, alpha blockers, central acting alpha receptor agonists, neprilysin inhibitors and vasodilators. However, despite the numerous number of medications, the prevalence of hypertension is on the rise, a considerable proportion of the hypertensive population is resistant to these therapeutic modalities and a definitive cure is not possible with the current treatment approaches. Therefore, there is a need for novel therapeutic strategies to provide better treatment and control of hypertension. In this review, our aim is to describe the latest developments in the treatment of hypertension including novel medication classes, gene therapies and RNA-based modalities.

The Mitochondrion: A Promising Target for Kidney Disease.

Mitochondrial dysfunction is important in the pathogenesis of various kidney diseases and the mitochondria potentially serve as therapeutic targets necessitating further investigation. Alterations in mitochondrial biogenesis, imbalance between fusion and fission processes leading to mitochondrial fragmentation, oxidative stress, release of cytochrome c and mitochondrial DNA resulting in apoptosis, mitophagy, and defects in energy metabolism are the key pathophysiological mechanisms underlying the role of mitochondrial dysfunction in kidney diseases. Currently, various strategies target the mitochondria to improve kidney function and kidney treatment. The agents used in these strategies can be classified as biogenesis activators, fission inhibitors, antioxidants, mPTP inhibitors, and agents which enhance mitophagy and cardiolipin-protective drugs. Several glucose-lowering drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1-RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors are also known to have influences on these mechanisms. In this review, we delineate the role of mitochondrial dysfunction in kidney disease, the current mitochondria-targeting treatment options affecting the kidneys and the future role of mitochondria in kidney pathology.

Hypoxia-inducible factor signaling in vascular calcification in chronic kidney disease patients.

Chronic kidney disease (CKD) affects approximately 15% of the adult population in high-income countries and is associated with significant comorbidities, including increased vascular calcifications which is associated with a higher risk for cardiovascular events. Even though the underlying pathophysiology is unclear, hypoxia-inducible factor (HIF) signaling appears to play a central role in inflammation, angiogenesis, fibrosis, cellular proliferation, apoptosis and vascular calcifications which is influenced by multiple variables such as iron deficiency anemia, serum phosphorus and calcium levels, fibroblast growth factor-23 (FGF-23) and Klotho. Along with the growing understanding of the pathology, potential therapeutic alternatives have emerged including HIF stabilizers and SGLT-2 inhibitors. The aim of this review is to discuss the role of HIF signaling in the pathophysiology of vascular calcification in CKD patients and to identify potential therapeutic approaches.

Increase in the global burden of chronic kidney disease: might it be attributable to air pollution?

Air pollution is an emerging etiology of chronic kidney disease (CKD). Evidence regarding this causative relationship has been shown by several studies. Recently, Lin et al. conducted the first community-based study investigating the association between CKD prevalence and air pollutant levels utilizing a Fuzzy Logic Interference model. Despite the study's limitations, the results correlate with the previous meta-analysis and observational studies. Higher fine particular matter (PM2.5) levels are associated with the increased global burden of CKD and may also influence the unequal distribution of burden in low-to-middle income countries. Despite growing evidence of the association of air pollution with CKD risk, the underlying pathophysiology has yet to be fully understood. Future studies investigating the pathophysiology and efficiency of the potential therapeutic and preventive measures against air pollution-related kidney injury are required to reduce the CKD burden.

On the importance of the interplay of residual renal function with clinical outcomes in end-stage kidney disease.

Chronic kidney disease (CKD) is one of the most important public health concerns of the century, and is associated with high rates of morbidity, mortality and social costs. CKD evolving towards end-stage kidney disease (ESKD) is on the rise resulting in a greater number of patients requiring peritoneal dialysis (PD) and hemodialysis (HD). The aim of this manuscript is to review the current literature on the interplay of residual renal function (RRF) with clinical outcomes in ESKD. The persistence of RRF is one of the most important predictors of decreased morbidity, mortality, and better quality of life in both PD and HD patients. RRF contributes to the well-being of ESKD patients through various mechanisms including higher clearance of solutes, maintenance of fluid balance, removal of uremic toxins and control of electrolytes. Furthermore, RRF has beneficial effects on inflammation, anemia, malnutrition, diabetes mellitus, obesity, changes in the microbiota, and cardiac diseases. Several strategies have been proposed to preserve RRF, such as blockade of the renin-angiotensin-aldosterone system, better blood pressure control, incremental PD and HD. Several clinical trials investigating the issue of preservation of RRF are ongoing. They are needed to broaden our understanding of the interplay of RRF with clinical outcomes in ESKD.