Factors Affecting Bone Health in Kidney Transplant Recipients: Klotho Gene Single-Nucleotide Polymorphisms and Other Clinical Features.

OBJECTIVES: Posttransplant bone diseases are a major cause of morbidity in kidney transplant recipients. We investigated the relationship between klotho gene single-nucleotide polymorphisms and bone diseases after kidney transplant. We also aimed to identify possible risk factors for development of bone disease. MATERIALS AND METHODS: The study consisted of 251 kidney transplant recipients (164 men and 87 women) with minimum follow-up of 3 years after kidney transplant. Patients with prolonged immobilization, malignancy, parathyroidectomy, glomerular filtration rates less than 30 mL/min/1.73 m², hypo- or hyperthyroidism, and treatment with drugs that affect bone metabolism were excluded. We investigated the relationship between 6 single-nucleotide polymorphisms of the klotho gene (rs480780, rs211234, rs576404, rs211235, rs9536314, and rs1207568) and development of osteoporosis, avascular bone necrosis, and persistent hyperparathyroidism. RESULTS: Longer dialysis treatment (odds ratio, 1.13; P = .002) and rs211235 single-nucleotide polymorphism in the klotho gene (odds ratio, 9.87; P = .001 for GG genotype) were significantly associated with persistent hyperparathyroidism. A higher magnesium level was detected as a protective factor from development of persistent hyperparathyroidism (odds ratio, 0.19; P = .009). Persistent hyperparathyroidism was defined as a risk factor for development of osteopenia/osteoporosis (odds ratio, 2.76; P = .003) and avascular bone necrosis (odds ratio, 2.52; P = .03). Although the rs480780 (odds ratio, 8.73; P = .04) single-nucleotide polymorphism in the klotho gene was defined as a risk factor for development of osteopenia/osteoporosis, none of the klotho single-nucleotide polymorphisms was found to be associated with development of avascular bone necrosis. CONCLUSIONS: Persistent hyperparathyroidism could be an important indicator for development of bone disease in kidney transplant recipients. Also, some of the klotho gene single-nucleotide polymorphisms are associated with higher risk for bone disease after kidney transplant.

Discontinuation of Eculizumab treatment after hematological remission in patients with atypical and drug-induced hemolytic uremic syndrome.

Introduction. The aim was to evaluate the effect of therapeutic plasma exchange (TPE) and eculizumab on hematological and renal survival in atypical hemolytic uremic syndrome (aHUS), and additionally, to examine the reliability of discontinuation of eculizumab treatment.Methods. This was an observational and retrospective study of 18 patients diagnosed with aHUS.Results. The median age of the study population was 30 (22-66) years. Four of 18 patients achieved hematological remission with the TPE alone. However, one patient died after three sessions of TPE. Eculizumab was used in 13 patients and no death was observed. One year after treatment, improved kidney function was observed in 2 of 3 (66%) patients for TPE and 5 of 9 (56%) patients for Eculizumab. We discontinued eculizumab treatment in 9 patients. One of the patients who had a C3 gene mutation experienced disease relapse after Eculizumab discontinuation. None of the patients who had drug associated aHUS developed disease relapse after Eculizumab discontinuation.Conclusion. Eculizumab treatment is a life-saving therapy in aHUS. Treatment discontinuation may be considered at least six months after hematologic remission in patients who had stable renal function or no expectancy for renal survival. Moreover, drug-associated cases seem to tend not to develop disease relapse in the long term.

Effects of phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A expression in glomerular basement membranes on treatment response and renal outcome in membranous nephropathy.

BACKGROUND: The aim of this study was to define the clinicopathologic features of phospholipase A2 receptor (PLA2R) and/or thrombospondin type-1 domain-containing 7A (THSD7A) associated membranous nephropathy(MN) focusing on their impact to disease relapse and response to treatment. METHODS: A total of 201 patients were enrolled for baseline clinical and histopathological features and 102 patients with a clinical follow-up for more than 1 year were evaluated for outcomes. Immunohistochemical staining was performed with PLA2R and THSD7A antibodies on kidney biopsies and glomerular staining was evaluated. RESULTS: PLA2R expression was observed in 75% of the patients' biopsies; however, THSD7A expression was present only in 7 patients' biopsies (3.5%). No significant difference was found between histopathological and clinical features of PLA2R positive and negative patients, collectively. Glomerular PLA2R expression was significantly associated with complete and complete/partial remission with first-line treatment; however, overall complete, and complete/partial remission rates did not differ from PLA2R negative patients (p = 0.2 and p = 0.8). Male gender, the presence of IgG4 staining and a necessity of immunosuppressive treatment were significantly associated with glomerular PLA2R expression. One patient, who developed end-stage renal disease, had glomerular expression for both PLA2R and THSD7A. Three patients with THSD7A-positive MN achieved complete remission. CONCLUSIONS: The probability of achieving complete remission is high in patients with PLA2R-positive MN for whom the relapse rate was also higher. The overall renal outcome did not differ from PLA2R negative cases. Low incidence of THSD7A-positive MN reduces the possibility of future randomized controlled trials.

The reliability and success of peritoneal dialysis during the COVID-19 pandemic.

We evaluated the symptoms, changes in laboratory findings during the novel coronavirus disease (COVID-19) pandemic, and the effect of depression in patients with peritoneal dialysis (PD). This is an observational and cross-sectional study. All patients were asked to fill the clinical assessment form and Beck depression and anxiety inventory. Also, the last two laboratory evaluations during this period were examined. A total of 123 patients performing PD were included. None of the patients were diagnosed with COVID-19. In the total study population, parathyroid hormone (PTH), serum albumin, phosphorus and ferritin levels significantly elevated at the end of 97 ± 31 days. PTH and phosphorus levels remained stable in remote monitoring automated PD (RM-APD) group (p = 0.4 and p = 0.5), they tended to increase in continuous ambulatory PD group and significantly increased in automated PD group (p = 0.09 and p = 0.01 for PTH and p = 0.06 and p = 0.001 for phosphorus, respectively). Moderate to severe depression was associated with dyspnoea, weight gain more than 5 kg, fatigue, palpitation and increased anxiety. PD is a reliable and successful form of dialysis and can be safely administered even if hospital access is restricted. Also, RM-APD may be a better choice because of providing more stable bone-mineral metabolism. Moreover, evaluating depression and anxiety is essential for the accurate clinical assessment.

Effect of remote patient management in peritoneal dialysis on haemodynamic and volume control.

AIM: Reduced treatment compliance in patients with peritoneal dialysis facilitates the development of fluid overload and as a result increased blood pressure and vascular stiffness in the long term. We aimed to evaluate blood pressure change and anti-hypertensive needs of patients within 1 year after the changeover to remote monitoring automated peritoneal dialysis (RM-APD) and compare the effect of RM-APD and continuous ambulatory peritoneal dialysis (CAPD) on peripheral and central haemodynamic parameters, volume status of patients and anti-hypertensive drug needs. METHODS: This was an observational and cross-sectional study. We enrolled 15 patients performing CAPD, 20 patients performing RM-APD, and 38 age, and gender-matched healthy control. We measured pulse wave velocity to assess arterial stiffness, peripheral and central haemodynamic parameters. We measured the volume status of participants via bioimpedance spectroscopy. RESULTS: The mean excess hydration of patients who underwent CAPD were higher than those who performed RM-APD and healthy control (P = .02). We found that mean diastolic blood pressure, heart rate, central systolic and diastolic blood pressure, and central pulse pressure were significantly different between the RM-APD, CAPD and healthy control (P = .02, P = .05, P = .007, P = .05 and P = .005, respectively). Post hoc analysis of these results showed that the differences between the groups were caused by the healthy control group and the patients with underwent CAPD. Daily anti-hypertensive drug count in patients with performing RM-APD was reduced over time (P < .001). CONCLUSION: The RM-APD provides better control of peripheral blood pressure and decrease of central haemodynamic parameters via controlling the excess body water.

Could drug burden be associated with severe periodontitis in patients receiving haemodialysis?

BACKGROUND: Periodontitis increases the risk of cardiovascular disease in the general population by triggering systemic inflammation. AIM: To investigate the relationship between systemic inflammation and periodontitis, and clarify any association between severe periodontitis and the medications used by patients receiving haemodialysis. DESIGN: A cross-sectional study. PARTICIPANTS: The study was undertaken with 56 patients receiving haemodialysis. MEASUREMENTS: Demographic and laboratory data and prescribed drugs regularly used by patients were recorded from hospital records. During the dialysis session, a validated Xerostomia Inventory score was completed. A complete dental/periodontal examination was also undertaken on all patients by the same periodontist. RESULTS: In the study population, stage I periodontitis was determined in 41%, stage II periodontitis in 17%, stage III periodontitis in 21%, and stage IV periodontitis in 21%. Male gender, hypertension, coronary artery disease, ß antagonists, calcium channel blockers, sodium polystyrene sulphonate, teeth brushing less than twice a day and high sensitive C-reactive protein > 8 mg/l were significantly associated with severe periodontitis. CONCLUSION: Drugs, including ß antagonists, calcium channel blockers, polystyrene sulphonate, co-morbid conditions and poor or insufficient oral care could facilitate an increase in the severity of periodontitis in patients receiving haemodialysis. Severe periodontitis also seems to be associated with cardiovascular disease and inflammation in patients with chronic renal disease.

Oral Candida Colonization as a Risk Factor for Chronic Inflammation and Atherosclerosis in Hemodialysis Patients.

The purpose of this study was to determine the prevalence of oral Candida spp. in HD patients and to investigate its relation with systemic inflammation and atherosclerosis. Microbiological samples were taken from buccal mucosa, palate, and dental prosthesis with a cotton swab. High-sensitivity CRP (hsCRP) and IL-6 were measured as inflammation markers. A total of 69 patients (58% male and median age 62 years) were enrolled in this study; 53.6% of total patients had oral Candida colonization. HsCRP and IL-6 levels were found to be significantly higher in the oral Candida colonization positive group than in the Candida colonization negative group (P = 0.002 and P = 0.01, respectively). HDL levels were significantly lower in the Candida colonization positive group (P = 0.03). Peripheral artery disease (P = 0.05) and oral Candida colonization (P = 0.002) were significantly associated with inflammation. In addition to conventional risk factors such as age (P = 0.03), diabetes (P = 0.001), and peripheral artery disease (P = 0.002), oral Candida colonization is associated with coronary artery disease (P = 0.04). Oral Candida colonization might be associated with chronic inflammation and development of atherosclerosis in HD patients.