Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and ...European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10
) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10
), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10
) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10
), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10
), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10
and OR = 3.39, P = 5.2 × 10
, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk.
The most common infections among renal transplant patients are urinary tract infections (UTI). Our main objective in this study is to determine the incidence of UTIs in patients who have undergone ...renal transplantation in our hospital, to identify the causative microbiological agents, risk factors and determine the effects of UTI on short-term graft survival.
Urinary tract infections, which developed within the first year of renal transplantation, were investigated. Patients were compared regarding demographic, clinical, laboratory characteristics and graft survival.
102 patients were included in our study. Fifty-three patients (53%) were male and 49 (48%) were female. Sixty-seven urinary tract infection attacks in 21 patients (20.5%) were recorded. Age (p = 0.004; 95% Confidence Interval CI: 1.032-1.184), longer indwelling urinary catheter stay time (p = 0.039; 95% Confidence Interval CI: 1.013-1.661) and urologic complications (p = 0.006; 95% Confidence Interval CI: 0.001-0.320) were found as risk factors for UTI development in the first year of transplantation. Escherichia coli and Klebsiella pneumoniae were the most frequently isolated microorganisms. Of these bacteria, 63.2% were found to be extended spectrum beta lactamase (ESBL) positive. Multidrug resistant microorganisms (MDROs) were more frequent in male patients (32 episodes in males vs. 14 episodes in females, p = <0.001). UTI had no negative impact on short-term graft survival.
Our study results represent the high incidence of UTI with MDROs in KT recipients. Infection control methods should be applied even more vigorously especially in male transplant patients since a higher incidence of UTI caused by resistant microorganisms was reported in male patients.
Purpose
Prognostic nutritional index (PNI), a composite indicator of inflammation and nutritional status, has recently been recognized as an independent prognostic marker for chronic kidney disease ...(CKD). We aimed to investigate PNI and its relationship with mortality in elderly patients with CKD.
Methods
Three hundred and fifty-nine patients over the age of 80 years with stage 3–4 CKD were enrolled in this retrospective study. PNI was used to assess the nutritional status of the patients. Patients were divided into two different groups as deceased and survived and as low PNI (< 39) and high PNI (≥ 39) according to median value of PNI.
Results
The mean age of the patients was 85.7 ± 3.7 years. One hundred and ninety-five (54.3%) patients died during follow-up. Multivariate analysis revealed that male gender, PNI, proteinuria, and diabetes mellitus (DM) were independent predictors of mortality in elderly patients with CKD. When patients with low PNI were compared to those with high PNI, initiation of dialysis and mortality rate were significantly higher whereas albumin, hemoglobin and lymphocyte count were lower. Pearson correlation analysis showed that PNI was significantly correlated with albumin (
r
= 1.000,
p
< 0.001), hemoglobin (
r
= 0.340,
p
< 0.001) and eGFR (
r
= 0.123,
p
= 0.020). Hemoglobin was an independent predictor of PNI in multivariate analysis.
Conclusion
In this study, we observed that PNI was significantly associated with mortality over the age of 80 years in patients with CKD and can be used to monitor nutritional status in this patient population.
Background Acute kidney injury (AKI) is common in coronavirus disease-2019 (COVID-19) and the severity of AKI is linked to adverse outcomes. In this study, we investigated the factors associated with ...in-hospital outcomes among hospitalized patients with COVID-19 and AKI. Methods In this multicenter retrospective observational study, we evaluated the characteristics and in-hospital renal and patient outcomes of 578 patients with confirmed COVID-19 and AKI. Data were collected from 34 hospitals in Turkey from March 11 to June 30, 2020. AKI definition and staging were based on the Kidney Disease Improving Global Outcomes criteria. Patients with end-stage kidney disease or with a kidney transplant were excluded. Renal outcomes were identified only in discharged patients. Results The median age of the patients was 69 years, and 60.9% were males. The most frequent comorbid conditions were hypertension (70.5%), diabetes mellitus (43.8%), and chronic kidney disease (CKD) (37.6%). The proportions of AKI stages 1, 2, and 3 were 54.0%, 24.7%, and 21.3%, respectively. 291 patients (50.3%) were admitted to the intensive care unit. Renal improvement was complete in 81.7% and partial in 17.2% of the patients who were discharged. Renal outcomes were worse in patients with AKI stage 3 or baseline CKD. The overall in-hospital mortality in patients with AKI was 38.9%. In-hospital mortality rate was not different in patients with preexisting non-dialysis CKD compared to patients without CKD (34.4 versus 34.0%, p = 0.924). By multivariate Cox regression analysis, age (hazard ratio HR 95% confidence interval (95%CI): 1.01 1.0-1.03, p = 0.035, male gender (HR 95%CI: 1.47 1.04-2.09, p = 0.029), diabetes mellitus (HR 95%CI: 1.51 1.06-2.17, p = 0.022) and cerebrovascular disease (HR 95%CI: 1.82 1.08-3.07, p = 0.023), serum lactate dehydrogenase (greater than two-fold increase) (HR 95%CI: 1.55 1.05-2.30, p = 0.027) and AKI stage 2 (HR 95%CI: 1.98 1.25-3.14, p = 0.003) and stage 3 (HR 95%CI: 2.25 1.44-3.51, p = 0.0001) were independent predictors of in-hospital mortality. Conclusions Advanced-stage AKI is associated with extremely high mortality among hospitalized COVID-19 patients. Age, male gender, comorbidities, which are risk factors for mortality in patients with COVID-19 in the general population, are also related to in-hospital mortality in patients with AKI. However, preexisting non-dialysis CKD did not increase in-hospital mortality rate among AKI patients. Renal problems continue in a significant portion of the patients who were discharged.
Objective
Although liver dysfunction is not considered the main organ involvement in Systemic Lupus Erythematosus (SLE), the frequency of liver dysfunction or abnormal liver enzyme values may be ...observed in 50–60% of patients. The aim of this study was to assess fatty liver and liver fibrosis in SLE patients using Fibroscan as well as determine associated factors such as immunosuppressive medications.
Methods
Sixty SLE patients and 30 healthy controls were included. Patients with HBV, HCV or cirrhosis, malignancy, cardiac disease, or patients on dialysis were excluded. All participants underwent Fibroscan measurements.
Results
The prevalence of fatty liver disease was similar between SLE patients and healthy controls (21.7 vs 26.7%, p = .597). Liver fibrosis was also similar between the two groups (26.7 vs 10.0%, p = .069). Since the majority of SLE patients were female, we performed a subgroup analysis in female patients (n = 51) and controls (n = 25). Fatty liver disease was similar between female SLE patients and controls (23.5 vs 24.0%, p = .964). However, liver fibrosis in female patients with SLE was increased compared to female controls (29.4 vs 4.0%, p = .011) and was associated with age (Exp (B) 95% CI: 1.083 (1.006–1.166), p = .034) and low-dose cumulative glucocorticoid use (Exp (B) 95% CI: 14.116 (1.213–164.210), p = .034).
Conclusion
The prevalence of fatty liver was similar between SLE patients and controls, while liver fibrosis was increased in the female patient group as compared to controls. Furthermore, liver fibrosis was associated with age and low dose cumulative glucocorticoid use. Interestingly, fatty liver did not precede liver fibrosis in the majority of cases, contrary to what is observed in the general population. Larger studies are needed to confirm our findings and determine whether immunosuppressive use has any impact on the development of liver fibrosis in SLE patients.
Carotid intima‐media thickness (CIMT) is an early marker of atherosclerosis and is increased in peritoneal dialysis (PD) patients. Association of CIMT with cardiovascular disease (CVD) or mortality ...is less clear. Fibroblast growth factor‐23 (FGF‐23) is a hormone associated with vascular calcification, atherosclerosis, and mortality in the hemodialysis population. We investigated whether baseline CIMT and FGF‐23 are associated with CVD and mortality in PD patients. Fifty‐five PD patients were included. CVD was defined as ischemic heart disease, stroke, or peripheral artery disease. Intact FGF‐23 was measured in plasma. CIMT was measured by ultrasonography. Twenty‐one patients developed CVD and 12 died over 47.1 ± 33.8 months. Patients with CVD were older (55.9 ± 10.5 vs. 42.5 ± 12.9 years, P < .01), had lower albumin (3.8 ± 0.5 vs. 4.2 ± 0.3 g/dL, P < .01) and higher CIMT (0.87 ± 0.22 vs. 0.61 ± 0.11 mm, P < .01). Patients with mortality were also older (53.5 ± 11.5 vs. 45.8 ± 13.8 years, P = .05), had lower albumin (3.7 ± 0.6 vs. 4.1 ± 0.3 g/dL, P < .01), higher CRP (15.0 ± 8.5 vs. 7.6 ± 8.4 mg/L, P < .01) and CIMT (0.9 ± 0.3 vs. 0.6 ± 0.1 mm, P < .01). Albumin and CIMT were associated with CVD and CIMT > 0.75 mm was associated with cardiovascular mortality. FGF‐23 did not show any correlations. CIMT at baseline is associated with CVD and mortality in PD patients.
Kidney transplantation (KT) recipients are at increased risk of low bone density (LBD) and fractures. In this retrospective study, we investigated bone mineral density (BMD), vertebral fractures, ...calculated risk for major osteoporotic fractures (MOF), and hip fractures in the KT recipients.
Patients who completed at least one year after KT were included in the analysis. Demographic, clinical, and laboratory data were recorded. Measurements of BMD were performed by dual-energy X-ray absorptiometry. Vertebral fractures were assessed using semi-quantitative criteria with conventional radiography. The ten-year risk for MOF and hip fracture were calculated using the FRAX@ tool with BMD.
One hundred fifty-three KT recipients were included in the study. The population included 77 women. The mean age at evaluation was 46,5±11,9 years. Seventy-eight (50.9%) patients had normal femoral neck BMD while osteoporosis and osteopenia at the femoral neck were present in 12 (7.8%) and 63 (41.1%) of the patients, respectively. Age at evaluation was the risk factor for LBD (OR 1.057; 95% CI 1.024-1.091; p = 0.001). In female KT recipients, LBD was principally affected by menopausal status whereas in males, mammalian target of rapamycin (mTOR) inhibitor use and lower BMI levels were the risk factors. The prevalent vertebral fracture was found in 43.4% of patients. In multivariate analysis, only steroid use (OR 0.121; 95% CI 0.015-0.988; p = 0.049) was found to be associated with prevalent fracture. Among all KT recipients, 1.9% had a high MOF probability (≥20% risk of fracture), and 23.5% had high hip fracture probability (≥3% risk of hip fracture) according to FRAX.
Exploring the prevalence of LBD and vertebral fracture and the risk factors would help clinicians to modify long-term follow-up strategies. Furthermore, the high hip fracture risk probability in our cohort suggested that there is a need for longitudinal studies to confirm the validity of the FRAX tool in the transplant population.
Objective Patients with preeclampsia (PE) have endothelial dysfunction and an increased future risk of cardiovascular (CV) mortality. The number of circulating endothelial cells (CECs) is markedly ...increased in conditions associated with a high degree of endothelial cell activation/injury including PE. We hypothesized that the number of CECs continues to be increased in women with a history of PE, reflecting ongoing endothelial cell activation/injury. Study Design CECs, flow-mediated vasodilation, levels of adhesion molecules and soluble vascular endothelial growth factor receptor-1 (sVEGFR1), and urine albumin/creatinine ratio were determined in 21 healthy women with ongoing normal pregnancy, 24 healthy currently nonpregnant women with a history of normal pregnancy, a total of 17 women with currently active mild (n = 11) or severe (n = 6) PE without hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, and 16 currently nonpregnant women with a history of mild (n = 10) or severe (n = 6) PE. Results Blood samples from women with active preeclampsia had higher CECs (9.9 ± 7.9 cells/mL) than healthy pregnant women (3.0 ± 4.1 cells/mL; P < .001), healthy nonpregnant women with a history of normal pregnancy (3.4 ± 4.0 cells/mL; P < .001), or women with a history of preeclampsia (2.4 ± 2.0 cells/mL; P < .001). The number of CECs were similar between women with a history of preeclampsia and healthy nonpregnant women with a history of normal pregnancy. Patients with active preeclampsia had significantly higher soluble vascular cell adhesion molecule-1, soluble E-selectin, sVEGFR1, and urinary albumin/creatinine ratio than healthy pregnant women. However, soluble vascular cell adhesion molecule-1, soluble E-selectin, urinary albumin/creatinine ratio were similar in women with a history of preeclampsia and healthy nonpregnant women with a history of normal pregnancy. However, women with a history of preeclampsia had higher sVEGFR1 levels than women with a history of normal pregnancy ( P < .05). Conclusion Markers of endothelial activation, dysfunction, and damage were increased in patients with PE. After the delivery, this activation status is similar to the age-matched nonpregnant women with a history of normal pregnancy. However, sVEGFR-1 levels remain higher in women with a history of preeclampsia compared with women without a history of preeclampsia.
Purpose
Prognosis in ANCA-associated vasculitis (AAV) has greatly improved with immunosuppressive use whereas incidence of treatment-related comorbidities such as osteoporosis has increased. However, ...studies investigating bone disease in AAV are limited. Fracture Risk Assesment Tool (FRAX) was developed to estimate 10-year hip and major osteoporotic fracture risks. Aim of this study was to estimate FRAX scores in AAV patients and compare them to healthy controls.
Methods
30 AAV patients and 20 healthy controls were included. Demographic, disease, and medication history were recorded from patient files. Femoral neck, lumbar spine and forearm bone mineral densitometry, and thoracolumbar radiographs were performed. FRAX fracture risk scoring was assessed for all participants.
Results
There were 18 male and 12 female patients. Mean age was 58.5 ± 11.7 years. Osteoporosis and osteopenia were present in 23.3% and 50% of patients, respectively. There were fractures in eight patients (26.7%). FRAX major fracture (9.4 ± 7.3% vs 5.9 ± 3.2%,
p
= 0.02) and hip fracture (2.2 ± 3.2% vs 0.9 ± 0.8%,
p
= 0.03) scores were higher in patients than controls. In seven (23.3%) patients, the 10-year probability of hip fracture was ≥ 3% and in five (16%) patients the 10-year risk of a major osteoporosis-related fracture was ≥ 20%. None of the controls exceeded these thresholds.
Conclusion
AAV patients are at high risk for future fractures as calculated with FRAX. Life-long monitoring for bone disease and fractures are essential. Large studies with longer follow-up are needed to determine the accuracy of FRAX risk scoring in predicting fractures.
Studies assessing peritoneal thickness by CT in peritoneal dialysis (PD) patients are lacking. In this study, we aimed to investigate the association between peritoneal thickness as measured by CT ...and dialysis adequacy with peritoneal membrane characteristics in PD patients. Ninety‐four PD patients were enrolled. Peritoneal thickness was measured by CT. Patients with and without a decrease in Kt/V of at least 0.3 over time were classified as Group 1 and Group 2, respectively. An increase of 0.1 unit of dialysate/plasma (D/P) creatinine over time were considered significant. The relationship between peritoneal membrane thickness, change in Kt/V, and peritoneal membrane characteristics were investigated. There were 31 (33.0%) patients in Group 1. The duration of PD (86.0 ± 64.1 vs. 59.6 ± 45.2 months, p: 0.023), peritoneal thickness (1.02 ± 0.37 vs. 0.87 ± 0.21 mm, p: 0.015), peritoneal calcification (7 22.6% vs. 3 4.8% patients, p: 0.013, increased D/P creatinine ratio (14 45.2% vs. 14 22.2% patients, p: 0.031) and CRP (13.9 ± 11.2 vs. 7.1 ± 4.8 mg/L, p: 0.045) were significantly higher in Group 1, whereas albumin (3.6 ± 0.5 vs. 3.8 ± 0.6 g/dL, p: 0.047) and parathyroid hormone (355.2 ± 260.2 vs. 532.1 ± 332.9 ng/L, p: 0.015) levels were significantly lower. Peritoneal thickness was significantly correlated with duration of PD (r: 0.775, p < 0.001) and CRP (r: 0.282, p: 0.006). Regression analysis showed that peritoneal thickness (Exp (B) 95% CI: 0.029 0.003–0.253, p: 0.001) was independent predictor of decreased Kt/V in PD patients. In conclusion, prolonged PD duration and increased peritoneal thickness are associated with a decrease in Kt/V over time. CT may be an alternative and noninvasive method instead of peritoneal biopsy for determining the structural changes of the peritoneal membrane .
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