Kidney and lipids: novel potential therapeutic targets for dyslipidemia in kidney disease?

INTRODUCTION: Altered lipid distribution and metabolism may lead to the development and/or progression of chronic kidney disease (CKD). Dyslipidemia is a major risk factor for CKD and increases the risk of cardiovascular events and mortality. Therefore, lipid-lowering treatments may decrease cardiovascular risk and prevent death. AREAS COVERED: Key players involved in regulating lipid accumulation in the kidney; contribution of lipids to CKD progression, lipotoxicity, and mitochondrial dysfunction in kidney disease; recent therapeutic approaches for dyslipidemia. EXPERT OPINION: The precise mechanisms for regulating lipid metabolism, particularly in kidney disease, are poorly understood. Guidelines for lipid-lowering therapy for CKD are controversial. Several hypolipemic therapies are available, but compared to others, statin therapy is the most common. No clinical trial has evaluated the efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in preventing cardiovascular events or improving kidney function among patients with CKD or kidney transplant recipients. Attractive alternatives, such as PCSK9-small interfering RNA (siRNA) molecules or evinacumab are available. Additionally, several promising agents, such as cyclodextrins and the FXR/TGR5 dual agonist, INT-767, can improve renal lipid metabolism disorders and delay CKD progression. Drugs targeting mitochondrial dysfunction could be an option for the treatment of dyslipidemia and lipotoxicity, particularly in renal diseases.

Vaccination and COVID-19 in Polish Dialysis Patients: Results from the European Clinical Dialysis Database.

Background: Patients with end-stage kidney disease undergoing hemodialysis are particularly vulnerable to severe COVID-19 as a result of older age and multimorbidities. Objectives: Data are still limited and there are no published data on mortality in hemodialyzed patients in Poland, in particular when vaccines became available. We assessed the epidemiologic and clinical data of patients with laboratory-confirmed COVID-19 and assessed the mortality in 2019, 2020, and 2021, as well as the vaccination rate in 2021. Patients and Methods: Retrospectively collected data from 73 Fresenius Nephrocare Poland hemodialysis centers and one public unit were analyzed. Results: In 2021, the vaccination rate was 96%. The unadjusted mortality (number of deaths divided by number of patients) in 2019 was 18.8%, while the unadjusted (after exclusion of COVID-related deaths) mortality in 2020 was 20.8%, and mortality in 2021 was 16.22%. The prevalence of cardiovascular deaths in 2019 and 2020 was almost identical (41.4% vs. 41.2%, respectively), and in 2021, the figures increased slightly to 44.1%. The prevalence of sudden cardiac deaths in 2019 was higher than in 2020 (19.6% vs. 17.3%, respectively) and consequently decreased in 2021 (10.0%), as well as strokes (6.2% vs. 5.4%, and 3.31% in 2021), whereas deaths due to gastrointestinal tract diseases were lower (2.5% vs. 3.2%, and 2.25% in 2021), diabetes complications (0.5% vs. 1.3%, and 0.5% in 2021), sepsis (5.1% vs. 6.3%, and 8.79% in 2021), respiratory failure (1.2 vs. 1.6%, and 2.83% in 2021), and pneumonia (1.4% vs. 2.0%, and 0.82%). There were 1493 hemodialyzed COVID-19 positive patients, and among them, 191 died in 2020 (12.79%). In 2021, there were 1224 COVID-19 positive patients and 260 died (21.24%). The mortality of COVID-19 positive dialyzed patients contributed 13.39% in 2020 and 16.21% in 2021 of all recorded deaths. Conclusions: The mortality among HD patients was higher in 2021 than in 2020 and 2019, despite the very high vaccination rate of up to 96%. The higher non-COVID-19 mortality may be due to the limited possibility of hospitalization and dedicated care during the pandemic. This information is extremely important in order to develop methods to protect this highly vulnerable patient group. Prevention plays a key role; other measures are essential in the mitigation and spread of COVID-19 in HD centers.

Lack or insufficient predialysis nephrology care worsens the outcomes in dialyzed patients - call for action.

The phenomenon of patients with advanced renal failure accepted for dialysis at a late stage in the disease process (late referral [LR]) is known almost from the beginning of dialysis therapy. It may also be associated with worse outcomes. The aim of the study was to assess the effect of referral time on the outcomes, such as number of hospitalizations, length of stay, kidney transplantation, and mortality. A study of 1303 patients with end-stage renal failure admitted for dialysis in the same period in Fresenius Nephrocare Poland dialysis centers was initiated. The type of vascular access during the first dialysis was accepted as the criterion differentiating LR (n = 457 with acute catheter) from early referral (ER; n = 846). The primary endpoint was the occurrence of death during the 13-month observation. By the end of observation, 341 (26.2%) of patients died. The frequency of death was 18.1 for ER and 37.9 for LR per 1000 patient-months. It can be estimated that 52.1% (95% CI: 40.5-61.5%) of the 341 deaths were caused by belonging to the LR group. Patients from LR group had longer hospitalizations, more malignancies, lower rate of vascular access in the form of a-v fistula, higher comorbidity index. It seems that establishing a nephrological registry would help to improve the organization of care for patients with kidney disease, particularly in the pandemic era.

PET/MRI-guided GTV delineation during radiotherapy planning in patients with squamous cell carcinoma of the tongue.

PURPOSE: The aim of the study was to evaluate the usefulness and accuracy of 18-fluorine-labeled fluorodeoxyglucose (PET) and magnetic resonance imaging (MRI) hybrid in gross tumor volume (GTV) delineation during radiotherapy planning in patients with carcinoma of the tongue. METHODS: Ten patients with squamous cell carcinoma (SCC) of the tongue underwent computed tomography (CT) and PET/MRI examination. The GTV for primary tumor and lymph nodes (nGTV) were defined on CT (GTV-CT) and compared to GTVs obtained from PET (GTV-PET) and MRI (GTV-MRI) images. Two methods of GTV determination were used: visual interpretation of CT, PET (GTV-PETvis) and MRI images and quantitative automatic method (Syngovia, Siemens) based on a chosen threshold value (20%, 30%, 40%, 50%) of standardized uptake values (SUVmax) from PET examination (GTV-PET20%, GTV-PET30%, etc.). Statistical analysis of differences in GTV values obtained from CT, PET and MRI studies was performed. GTV-CT was used as a reference. RESULTS: In all, 80% of GTV-MRI and 40% of GTV-PETvis were larger than GTV-CT. Respectively, 20% of GTV-MRI and 60% of GTV-PETvis were smaller than GTV-CT. Taking into account all threshold measurements, 70% of volumes were smaller than GTV-CT. GTV-PET30% were the most closely related volumes to GTV-CT from all threshold methods in 50% of patients. GTV-PETvis generated the most similar volumes in relation to GTV-CT from all PET measurements. Statistical analysis confirmed those results. Compared to nGTV-CT, 70% of nGTV-MRI and 20% of nGTV-PETvis were larger. The remaining nGTV-MRI and nGTV-PETvis measurements were smaller than nGTV-CT. Measurements of all thresholds nGTVs were smaller than nGTV-CTV in 52.5% of cases. nGTV-PET20% were the most closely related volumes to nGTV-CT in 40% of the cases. Statistical analysis showed that nGTV-PET20% (p = 0.0468), nGTV-PETvis (p = 0.0166), and nGTV-PET50% (p = 0.0166) diverge significantly from nGTV-CT results. nGTV-MRI (p = 0.1141), nGTV-PET30% (p = 0.2845), and nGTV-PET40% (p = 0.5076) were significantly related with nGTV-CT. CONCLUSION: Combination of PET/MRI provides more information during target tumor mass delineation in radiotherapy planning of patients with SCC of the tongue than other standard imaging methods. The most frequently matching threshold value was 30% of SUVmax for primary tumor delineation and 30-40% of SUVmax for nGTV determination.

Personalized Radiation Therapy in Cancer Pain Management.

The majority of advanced cancer patients suffer from pain, which severely deteriorates their quality of life. Apart from analgesics, bisphosphonates, and invasive methods of analgesic treatment (e.g., intraspinal and epidural analgesics or neurolytic blockades), radiation therapy plays an important role in pain alleviation. It is delivered to a growing primary tumour, lymph nodes, or distant metastatic sites, producing pain of various intensity. Currently, different regiments of radiation therapy methods and techniques and various radiation dose fractionations are incorporated into the clinical practice. These include palliative radiation therapy, conventional external beam radiation therapy, as well as modern techniques of intensity modulated radiation therapy, volumetrically modulated arch therapy, stereotactic radiosurgery or stereotactic body radiation therapy, and brachytherapy or radionuclide treatment (e.g., radium-223, strontium-89 for multiple painful osseous metastases). The review describes the possibilities and effectiveness of individual patient-tailored conventional and innovative radiation therapy approaches aiming at pain relief in cancer patients.