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.

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.