Determinants of non-diabetic kidney diseases in type 2 diabetic patients: Twenty years of single center experience.

BACKGROUND: Diabetic nephropathy is one of the most common complications associated with diabetes. However, non-diabetic kidney disease has been reported in patients with type 2 diabetes at varying incidence rates. The objective of our study is to investigate the occurrence, clinicopathological characteristics, and inflammatory markers linked to diabetic and non-diabetic nephropathy (NDN) in patients with type 2 diabetes mellitus (DM). Additionally, we aimed to explore the possibility of identifying non-diabetic pathology using different biopsy indications. MATERIALS AND METHODS: A total of 159 patients with type 2 DM who underwent renal biopsy at a tertiary care nephrology clinic between January 2000 and January 2022 were enrolled in the study. We collected comprehensive data, including patient demographics, co-morbidities, diabetes duration, renal biopsy indications and results, serological markers, renal function, diabetic retinopathy (DRP), full blood count, blood biochemistry, urinalysis, and inflammatory markers. Patients were categorized based on their biopsy indications, and their biopsy results were classified into three groups: isolated NDN, isolated diabetic nephropathy (DN), and mixed nephropathy with concurrent NDN. We evaluated the relationship between biopsy indications and accompanying pathologies and statistically assessed the likelihood of each biopsy indication detecting non-diabetic renal pathology. Additionally, differences in other data, including demographic and laboratory results and medical histories, among the three groups were investigated. RESULTS: The most frequent indication of renal biopsy was atypical presentations of nephrotic syndrome or nephrotic range proteinuria (ANS/ANP) in 25.1% of patients. Other indications included unexplained renal failure (URF) in 22.6%, atypical presentations of non-nephrotic range proteinuria (ANNP) in 18.2%, acute kidney injury or rapidly progressive kidney dysfunction (AKI/RPKD) in 16.9%, microscopic hematuria in 15.7%, URF with ANNP in 11.3%, and severe nephrotic range proteinuria (SNP) in 9.4%. Renal biopsy revealed isolated NDN in 64.8%, DN in 25.1%, and mixed nephropathy in 10.1% of patients. Primary glomerular diseases were the main non-diabetic renal pathology, predominantly focal segmental glomerulosclerosis (FSGS) (36.4%) followed by MN (10.6%) and IgA nephropathy (7.5%). In comparison with the isolated DN and mixed nephropathy groups, patients in the isolated NDN group had significantly shorter diabetes duration, fewer DRP, as well as lower serum creatinine and neutrophil-to-lymphocyte ratio (NLR). Multivariate logistic regression analysis revealed that presence of hematuria (OR 4.40; 95% CI 1.34 - 14.46, p = 0.014), acute nephrotic range proteinuria (OR 11.93; 95% CI 1.56 - 90.77, p = 0.017), and AKI/APKD (OR 41.08; 95% CI 3.40 - 495.39, p = 0.003) were strong predictors of NDN. Lower NLR (OR 0.77; 95% CI 0.60 - 0.98, p = 0.035), shorter duration of diabetes (OR 0.90; 95% CI 0.84 - 0.97, p = 0.010), and absence of DRP (OR 0.35; 95% CI 0.12 - 0.98, p = 0.046) were also found to be independent indicators of NDN. Receiver operating characteristic curve (ROC) analysis revealed a cut-off value of ≤ 3.01 for NLR (sensitivity of 63.1%, specificity of 63.5%) with regards to predicting non-diabetic renal pathology (p = 0.006). CONCLUSION: Renal biopsy findings in patients with type 2 DM highlight that the prevalence of NDN may be higher than assumed, as presented mainly in the form of primary glomerular disease. The presence of AKI/RPKD, hematuria, and ANS/ANP serves as a reliable indicator of non-diabetic renal pathology. In more ambiguous situations, factors such as a shorter duration of diabetes, absence of DRP, and a lower NLR value may assist clinicians in biopsy decision.

The role of calcitonin gene-related peptide and substance P in the pathogenesis of dialysis headache.

AIM: The present study aims to establish the role of serum CGRP and SP levels in the disease pathophysiology in patients with dialysis headache not accompanied by primary or secondary headaches, and also whether there is a correlation between these vasoactive peptides and the severity of headache. METHOD: This study was designed as prospective and multicenter. A total of 30 dialysis headache patients and 30 patients without headache as the control group in the Nephrology outpatient clinics which implement similar dialysis procedures were included in the study. Blood samples were taken from all the patients before hemodialysis, and post-hemodialysis samples were collected. CGRP and SP contents in serum samples were measured using the ELISA method with detection kits. RESULTS: A total of 60 patients were included in the study with 17 female and 13 male patients in the dialysis headache group and 18 female and 12 male patients in the control group, and there were no significant differences in sex and age between the groups. CGRP levels in the headache group were found to be significantly higher compared with the control group both before and after hemodialysis. Furthermore, pre-hemodialysis CGRP levels were significantly higher than post-hemodialysis CGRP levels in both the headache and control groups. Serum SP levels in the headache group were found to be higher compared with the control group both before and after hemodialysis, there was no significant difference between the groups. Even though SP levels in both groups decreased after hemodialysis, there was again no significant difference between the groups. No correlation was found between the patients' severity of headache and serum CGRP and SP levels. CONCLUSION: This study concludes that CGRP and SP, even though the latter is not statistically significant, play a role in the pathophysiology of the dialysis headache, and further studies with a larger and more specific patient population may reveal the relationship between the neuropeptides and dialysis headache more clearly.

Peritoneal dialysis related non-infectious complications: A single-center experience over 20 years.

OBJECTIVES: Non-infectious complications of peritoneal dialysis (NICPD) are common and could be an important cause of technical failure, especially in the early period of peritoneal dialysis (PD) initiation. NICPD are also center- and provider-dependent. This study aimed to investigate the frequency, etiology, and associated outcomes of NICPD in a single center over a period of 20 years. MATERIALS AND METHODS: Data were retrospectively collected in 262 patients who were initiated on PD between April 2001 and April 2021. Inclusion criteria were age 18 years or older and a minimum follow-up period of 3 months. Patients were grouped according to the reason of NICPD: catheter-related, increased intra-abdominal pressure-related, metabolic, and other complications. RESULTS: There were 142 females and 120 males in the study, with a mean age of 44 ± 16.9 years. The mean time on PD was 52.6 ± 40 months. During the follow-up period, 185 (71%) patients experienced 382 NICPD episodes. 26 patients (9.9%) were switched to maintenance hemodialysis (HD) due to NICPD. Outflow failure was the most common NICPD (n = 97). It was also the most common reason for catheter revision (n = 23) and PD discontinuation (n = 12). Catheter intervention was required in 32 patients (12.2%). Prior HD treatment and male gender were independent risk factors for NICPD and catheter-related complications (OR 2.076; p = 0.037; OR: 1.797, p = 0.042, respectively). Early-start PD was associated with a lower risk for NICPD development (OR: 0.393, p = 0.013). CONCLUSION: In this select cohort of PD patients, we found that NICPD are common and outflow failure is the most common cause of NICPD. NICPD are associated with major complications requiring catheter removal or transfer to in-center HD. Early recognition and appropriate management of NICPD are essential to prolonging time on PD in end-stage renal disease patients.

Humoral Response to BNT162b2 and CoronaVac in Patients Undergoing Maintenance Hemodialysis: A Multicenter Prospective Cohort Study.

INTRODUCTION: Data regarding inactivated vaccines for SARS-CoV-2 in patients undergoing maintenance hemodialysis (MHD) are limited. We aimed to investigate humoral responses induced by CoronaVac compared to BNT162b2 in this population. METHODS: In this multicenter prospective cohort study, adult patients undergoing MHD who lacked a history of COVID-19 and decided to get vaccinated with BNT162b2 or CoronaVac were enrolled. Participants provided serum samples before, 1 and 3 months after 2 doses. Anti-SARS-CoV-2 IgG antibodies against receptor-binding domain of the virus were measured, and levels ≥50 AU/mL were considered as positive. Breakthrough infections and adverse events were recorded. RESULTS: Ninety-two patients were included, 68 (73.9%) of whom were seronegative at baseline. BNT162b2 and CoronaVac were administered in 38 (55.9%) and 30 (44.1%) patients. At 1 month, seropositivity was 93.1% in BNT162b2 and 88% in CoronaVac groups (p = 0.519). Quantitative antibody levels were significantly higher in BNT162b2 (p < 0.001). At 3 months, both seropositivity (96.4% and 78.3%, p = 0.045) and antibody levels (p = 0.001) remained higher in BNT162b2 compared to CoronaVac. Five patients (7.4%) experienced breakthrough COVID-19. Adverse events were more frequent with BNT162b2, although all of them were mild. Multiple linear regression model showed that only vaccine choice (BNT162b2) was related to the humoral response (ß = 0.272, p = 0.038). Seropositive patients at baseline (n = 24) had higher antibody levels at any time point. CONCLUSIONS: BNT162b2 and CoronaVac induced humoral responses in naïve patients undergoing MHD, which were more robust and durable for 3 months after BNT162b2. Both vaccines created high antibody levels in patients who were seropositive at baseline.

Factors Associated with Long-Term Survival in Maintenance Hemodialysis Patients: A 5-Year Prospective Follow-Up Study.

Objectives: In addition to an increase in the prevalence of dialysis treatments for end-stage renal disease worldwide, the mortality rates among patients on maintenance hemodialysis remain higher than that of the general population. This study aims to evaluate factors associated with long-term survival in stable maintenance hemodialysis patients. Methods: A total of 100 patients initiating hemodialysis by February 2013 were included in this prospective cross-sectional 5-year follow-up study. Data on patient demographics, anthropometric-nutritional parameters, systolic and diastolic blood pressure levels, and hemodialysis parameters, including etiology of kidney failure, hemodialysis duration, peritoneal dialysis history, relative interdialytic weight gain (RIDWG), and Kt/V, were recorded. Results: Overall 5-year survival rate was 56.6%. The 5-year survival rate was higher in patients with younger age (71.4% below median vs. 42.0% above median, p=0.023), lower systolic (63.3 vs. 50%, respectively, p=0.005) and diastolic (62.5 vs. 51.0%, respectively, p=0.02) blood pressure levels, higher Kt/V (46.9 vs. 66.0%, respectively, p=0.044), lower RIDWG (54.0 vs. 32.7%, respectively, p=0.026), and lower serum leptin levels (63.3 vs. 50.0%, respectively, p=0.047). Cox-regression analysis revealed that only systolic blood pressure (B = 1.081, 95% CI, 0.152 to 0.756, p=0.08) was a significant risk factor for poor survival. Conclusion: Our findings revealed pre-dialysis systolic blood pressure as the sole risk factor for poor long-term survival in stable maintenance hemodialysis patients. Malnutrition-inflammation, measures of nutrition, inflammation, and anemia had no significant impact on long-term survival.

The Longitudinal Evolution of Post-COVID-19 Outcomes Among Hemodialysis Patients in Turkey.

Introduction: Hemodialysis (HD) patients have increased risk for short-term adverse outcomes of COVID-19. However, complications and survival at the post-COVID-19 period have not been published extensively. Methods: We conducted a national, multicenter observational study that included adult maintenance HD patients recovered from confirmed COVID-19. A control HD group without COVID-19 was selected from patients in the same center. We investigated the characteristics and outcomes in the follow-up of HD patients and compare them with the non-COVID-19 group. Results: A total of 1223 patients (635 patients in COVID-19 group, 588 patients in non-COVID-19 group) from 47 centers were included in the study. The patients' baseline and HD characteristics were almost similar. The 28th-day mortality and mortality between 28th day and 90th day were higher in the COVID-19 group than non-COVID-19 group (19 [3.0%] patients vs. none [0%]; 15 [2.4%] patients vs. 4 [0.7%] patients, respectively). The presence of respiratory symptoms, rehospitalization, need for home oxygen therapy, lower respiratory tract infection, and arteriovenous (AV) fistula thrombosis was significantly higher in the COVID-19 group in both the first 28 days and between 28 and 90 days. In the multivariable analysis, age (odds ratio [OR] [95% CI]: 1.029 [1.004-1.056]), group (COVID-19 group vs. non-COVID-19 group) (OR [95% CI]: 7.258 [2.538-20.751]), and vascular access type (tunneled catheter/AV fistula) (OR [95% CI]: 2.512 [1.249-5.051]) were found as independent parameters related to 90-day mortality. Conclusion: In the post-COVID-19 period, maintenance HD patients who have had COVID-19 have increased rehospitalization, respiratory problems, vascular access problems, and high mortality compared with the non-COVID-19 HD patients.

Comparison of lung ultrasound and other volumetric methods in peritoneal dialysis patients.

ABSTRACT: Although many alternative methods are present, maintaining ideal volume status in peritoneal dialysis (PD) patients still rely on clinical evaluation due to lack of an evidence-based method. Lung ultrasound (LUS) is a new method for evaluation of hidden congestion in this group.LUS findings and its relationship with other volumetric methods are investigated in this observational cross-sectional study.In this observational cross sectional study, LUS was performed to all PD patients and compared with symptoms of hypervolemia, physical examination, vascular endothelial growth factor-C (VEGF-C), and N-terminal pro-brain natriuretic peptide levels, chest radiography, echocardiography, bioelectrical impedance analysis.Data of 21 PD patients were evaluated. There was correlation between number of B lines and VEGF-C levels (r = 0.447, P = .042), daily urine output (r = 0.582, P = .007) and left ventricle mass index (r = -0.456, P = .038). Correlations with all other parameters were not significant. Daily urine output and VEGF-C levels were significantly different when B lines were grouped into 2 according to the median level (P < .05 for all).This is the widest spectrum study looking for LUS findings and other volumetric parameters in a small PD cohort. LUS might be useful to evaluate hidden hypervolemia. Its correlation with VEGF-C level is a novel finding.

Determinants of mortality in a large group of hemodialysis patients hospitalized for COVID-19.

BACKGROUND: Maintenance hemodialysis (MHD) patients are at increased risk for coronavirus disease 2019 (COVID-19). The aim of this study was to describe clinical, laboratory, and radiologic characteristics and determinants of mortality in a large group of MHD patients hospitalized for COVID-19. METHODS: This multicenter, retrospective, observational study collected data from 47 nephrology clinics in Turkey. Baseline clinical, laboratory and radiological characteristics, and COVID-19 treatments during hospitalization, need for intensive care and mechanical ventilation were recorded. The main study outcome was in-hospital mortality and the determinants were analyzed by Cox regression survival analysis. RESULTS: Of 567 MHD patients, 93 (16.3%) patients died, 134 (23.6%) patients admitted to intensive care unit (ICU) and 91 of the ones in ICU (67.9%) needed mechanical ventilation. Patients who died were older (median age, 66 [57-74] vs. 63 [52-71] years, p = 0.019), had more congestive heart failure (34.9% versus 20.7%, p = 0.004) and chronic obstructive pulmonary disease (23.6% versus 12.7%, p = 0.008) compared to the discharged patients. Most patients (89.6%) had radiological manifestations compatible with COVID-19 pulmonary involvement. Median platelet (166 × 103 per mm3 versus 192 × 103 per mm3, p = 0.011) and lymphocyte (800 per mm3 versus 1000 per mm3, p < 0.001) counts and albumin levels (median, 3.2 g/dl versus 3.5 g/dl, p = 0.001) on admission were lower in patients who died. Age (HR: 1.022 [95% CI, 1.003-1.041], p = 0.025), severe-critical disease clinical presentation at the time of diagnosis (HR: 6.223 [95% CI, 2.168-17.863], p < 0.001), presence of congestive heart failure (HR: 2.247 [95% CI, 1.228-4.111], p = 0.009), ferritin levels on admission (HR; 1.057 [95% CI, 1.006-1.111], p = 0.028), elevation of aspartate aminotransferase (AST) (HR; 3.909 [95% CI, 2.143-7.132], p < 0.001) and low platelet count (< 150 × 103 per mm3) during hospitalization (HR; 1.864 [95% CI, 1.025-3.390], p = 0.041) were risk factors for mortality. CONCLUSION: Hospitalized MHD patients with COVID-19 had a high mortality rate. Older age, presence of heart failure, clinical severity of the disease at presentation, ferritin level on admission, decrease in platelet count and increase in AST level during hospitalization may be used to predict the mortality risk of these patients.

Frequency of depressive symptoms in Syrian refugees and Turkish maintenance hemodialysis patients during COVID-19 pandemic.

INTRODUCTION: Pneumonia of unknown cause was detected on 30 December 2019 in China. It was categorized as an outbreak and named as COVID-19 by the World Health Organization. The pandemic affects all people, but patient groups such as hemodialysis (HD) patients have been particularly affected. We do not know if refugees suffered more during the outbreak. In this study, we compared depressive symptom frequency between Syrian refugee HD patients and Turkish ones. METHODS: The study had a single-center, cross-sectional design. Demographic and clinical data were collected retrospectively from patients' files containing details about past medical history, demographic variables and laboratory values. Validated Turkish and Arabic forms of Beck Depression Inventory (BDI) were used to assess depressive symptoms. BDI scores were compared according to nationality, demographic features and clinical data. A BDI score more than 14 was accepted as suspicion of depression. RESULTS: 119 patients were enrolled in the study. After the exclusion of 22 patients, 75 Turkish and 22 Syrian patients were included for further analysis. The median BDI (interquartile range) score for Turkish and Syrian patients were 12 (7-23) and 19.5 (12.7-25.2), respectively (p = 0.03). Suspicion of depression was present at 42.7% of Turkish, and 72.7% of Syrian HD patients (p = 0.013). Regarding all patients, phosphorus level, Kt/V, and nationality were significantly different between patients with and without suspicion of depression (p = 0.023, 0.039, 0.013, respectively). CONCLUSION: Syrian patients had higher BDI scores and more depressive symptoms than Turkish patients. Additional national measures for better integration and more mental support to Syrian HD patients are needed.

Pentraxin-2 is Associated with Renal Fibrosis in Patients Undergoing Renal Biopsy.

OBJECTIVES: Progressive renal disease is characterized by histological changes in the kidney and fibrosis is a common outcome. Renal biopsy is the only diagnostic tool to evaluate these histopathological changes. Pentraxin-2 (PTX-2) is an anti-inflammatory constitutive plasma protein associated with the innate immune system. Recently, as a biomarker, the circulating level of PTX-2 is shown to be decreased in chronic fibrotic diseases. In this study, we aimed to investigate the relationship between renal fibrosis severity and serum PTX-2 levels in patients undergoing renal biopsy. METHODS: This cross-sectional study included 45 patients and 16 healthy individuals (HIs). The severity of renal fibrosis was evaluated according to the Banff and Sethi scoring systems by the same pathologist. PTX-2 was measured by an enzyme-linked immunosorbent assay and compared with the demographical, clinical, biochemical, and histopathological data of the patients and HIs. RESULTS: PTX-2 levels were lower in the biopsy group than in the HI group (p=0.12). Patients with moderate renal fibrosis had significantly lower serum PTX-2 levels than those in patients with minimal and mild fibrosis (p=0.017 and p=0.010, respectively). PTX-2 concentrations were correlated with serum albumin (r=0.30, p=0.016), and were negatively correlated with serum creatinine levels (rho=-0.42, p=0.01) and body mass index (r=-0.32, p=0.011). CONCLUSIONS: The results indicated that PTX-2 levels are significantly lower in patients with renal fibrosis than HIs, and declining further in patients with severe fibrosis.

Unexpectedly High Prevalence of Low Alpha-Galactosidase A Enzyme Activity in Patients with Focal Segmental Glomerulosclerosis.

OBJECTIVES: Fabry disease (FD) is a rare disease associated with sphingolipid accumulation. Sphingolipids are components of plasma membranes that are important in podocyte function and accumulate in various glomerular diseases such as focal segmental glomerulosclerosis (FSGS). Both FD and FSGS can cause podocyte damage and are classified as podocytopathies. In this respect, FD and FSGS share the same pathophysiologic pathways. Previous screening studies have shown that a significant proportion of end-stage renal disease (ESRD) patients receiving hemodialysis (HD) have unsuspected FD, and the prevalence of low alpha-galactosidase A (αGLA) enzyme activity in these patients is higher than that in the normal population. We aimed to compare αGLA enzyme activity in patients with biopsy-proven FSGS and ESRD receiving HD. METHODS: The records of 232 patients [62 FSGS (F/M: 33/29); 170 HD (M/F: 93/79)] were evaluated retrospectively. The screening was performed based on the αGLA enzyme activity on a dried blood spot, with the confirmation of plasma LysoGb3 levels, and the known GLA mutations were tested in patients with low enzyme activities. The two groups were compared using these parameters. RESULTS: The mean level of αGLA enzyme activity was found to be lower in FSGS patients than in the HD group (2.88±1.2 µmol/L/h versus 3.79±1.9 µmol/L/h, p<0.001). There was no significant relationship between the two groups with regard to the plasma LysoGb3 levels (2.2±1.22 ng/ml versus 1.7±0.66 ng/ml, p: 0.4). In the analysis of GLA mutations, a D313Y mutation [C(937G>T) in exon p] was found in one patient from the FSGS group. CONCLUSIONS: We found that αGAL activity in patients with FSGS is lower than that in patients undergoing HD. The low enzyme activity in patients with FSGS may be explained by considering the similar pathogenesis of FSGS and FD, which may also lead to sphingolipid deposition and podocyte injury.

Comparison of Circulating Levels of Uremic Toxins in Hemodialysis Patients Treated with Medium Cut-Off Membranes and High-Flux Membranes: Theranova in Sisli Hamidiye Etfal (THE SHE) Randomized Control Study.

INTRODUCTION: Removal of uremic toxins is a main objective of hemodialysis; however, whether high-flux and medium cut-off (MCO) membranes differ as regards removal of middle and large uremic toxins is not clear. OBJECTIVE: To compare medium cut-off and high-flux dialyzers as regards their intra- and interdialysis effect on circulating levels of middle and large uremic toxins and serum albumin. METHODS: Fifty-two patients were randomized to have hemodialysis with either 3 months of high-flux dialyzer followed by 3 months of MCO or vice versa. Blood samples were taken before and after dialysis at the first and last sessions of each dialyzer for analyses of middle and large uremic toxins including inflammatory mediators and vascular endothelial growth factor (VEGF), and serum albumin. RESULTS: Reduction rates were higher, and postdialysis levels of ß-2 microglobulin, free kappa and lambda light chains, and myoglobulin were lower at the first and last sessions with MCO dialyzers compared to high-flux dialyzers (p < 0.05 for all). Last session predialysis levels of ß-2 microglobulin, free kappa light chain, and free lambda light chain were lower than first session predialysis levels in MCO dialyzers as compared to high-flux dialyzers (p < 0.05 for all). Last session levels of interleukin-6, interleukin-10, interleukin-17, and interferon-gamma did not differ between dialyzers (p > 0.05 for all). VEGF level was lower in the MCO group compared to the high-flux group (p = 0.043). Last session level of serum albumin with MCO dialyzers was lower than that with high-flux dialyzers (3.62 [3.45-3.88] vs. 3.78 [3.58-4.02] g/L) (p = 0.04) and 6.7% lower (p < 0.001) than at the first session of MCO dialyzers. CONCLUSION: The decline in circulating levels of several middle and large uremic toxins including VEGF following hemodialysis was more pronounced when using MCO membranes as compared to high-flux membranes while their effect on inflammatory molecules was similar.

Unexpectedly High Prevalence of Low Alpha-Galactosidase A Enzyme Activity in Patients with Focal Segmental Glomerulosclerosis

OBJECTIVES: Fabry disease (FD) is a rare disease associated with sphingolipid accumulation. Sphingolipids are components of plasma membranes that are important in podocyte function and accumulate in various glomerular diseases such as focal segmental glomerulosclerosis (FSGS). Both FD and FSGS can cause podocyte damage and are classified as podocytopathies. In this respect, FD and FSGS share the same pathophysiologic pathways. Previous screening studies have shown that a significant proportion of end-stage renal disease (ESRD) patients receiving hemodialysis (HD) have unsuspected FD, and the prevalence of low alpha-galactosidase A (αGLA) enzyme activity in these patients is higher than that in the normal population. We aimed to compare αGLA enzyme activity in patients with biopsy-proven FSGS and ESRD receiving HD. METHODS: The records of 232 patients [62 FSGS (F/M: 33/29); 170 HD (M/F: 93/79)] were evaluated retrospectively. The screening was performed based on the αGLA enzyme activity on a dried blood spot, with the confirmation of plasma LysoGb3 levels, and the known GLA mutations were tested in patients with low enzyme activities. The two groups were compared using these parameters. RESULTS: The mean level of αGLA enzyme activity was found to be lower in FSGS patients than in the HD group (2.88±1.2 μmol/L/h versus 3.79±1.9 μmol/L/h, p<0.001). There was no significant relationship between the two groups with regard to the plasma LysoGb3 levels (2.2±1.22 ng/ml versus 1.7±0.66 ng/ml, p: 0.4). In the analysis of GLA mutations, a D313Y mutation [C(937G>T) in exon p] was found in one patient from the FSGS group. CONCLUSIONS: We found that αGAL activity in patients with FSGS is lower than that in patients undergoing HD. The low enzyme activity in patients with FSGS may be explained by considering the similar pathogenesis of FSGS and FD, which may also lead to sphingolipid deposition and podocyte injury.

Pentraxin-2 is associated with renal fibrosis in patients undergoing renal biopsy

OBJECTIVES: Progressive renal disease is characterized by histological changes in the kidney and fibrosis is a common outcome. Renal biopsy is the only diagnostic tool to evaluate these histopathological changes. Pentraxin-2 (PTX-2) is an anti-inflammatory constitutive plasma protein associated with the innate immune system. Recently, as a biomarker, the circulating level of PTX-2 is shown to be decreased in chronic fibrotic diseases. In this study, we aimed to investigate the relationship between renal fibrosis severity and serum PTX-2 levels in patients undergoing renal biopsy. METHODS: This cross-sectional study included 45 patients and 16 healthy individuals (HIs). The severity of renal fibrosis was evaluated according to the Banff and Sethi scoring systems by the same pathologist. PTX-2 was measured by an enzyme-linked immunosorbent assay and compared with the demographical, clinical, biochemical, and histopathological data of the patients and HIs. RESULTS: PTX-2 levels were lower in the biopsy group than in the HI group (p=0.12). Patients with moderate renal fibrosis had significantly lower serum PTX-2 levels than those in patients with minimal and mild fibrosis (p=0.017 and p=0.010, respectively). PTX-2 concentrations were correlated with serum albumin (r=0.30, p=0.016), and were negatively correlated with serum creatinine levels (rho=-0.42, p=0.01) and body mass index (r=-0.32, p=0.011). CONCLUSIONS: The results indicated that PTX-2 levels are significantly lower in patients with renal fibrosis than HIs, and declining further in patients with severe fibrosis.

Diastolic blood pressure variability in 24 hour-ABPM and outcomes of chronic kidney disease
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BACKGROUND: Blood pressure variability (BPV) has been associated with increased morbidity and mortality. There are a few studies that reported worse outcomes of chronic kidney disease (CKD) with greater visit-to-visit BPV (VVV), but data with ambulatory blood pressure monitoring (ABPM) is scarce. MATERIALS AND METHODS: Ambulatory hypertensive CKD (stage 2 - 4) patients (> 18 years old) with complete 24 hours of ABPM study (SpaceLabs), who were followed up between January 2012 and December 2016, were retrospectively analyzed for the baseline characteristics and outcomes of CKD. Coefficient of variation (CV) in diastolic blood pressure (DBP) was used as an index of BPV. RESULTS: Data of 191 patients (mean age 59.7 ± 12.4 years, 54.9% males, 42.1% diabetic, mean eGFR-EPI (Chronic Kidney Disease Epidemiology Collaboration) 51.7 ± 22.0 mL/min/1.73m2, mean follow-up 26.2 ± 10.4 months) were available for the analysis. On multivariate linear regression analysis, greater DBP-CV was associated with slower decline in eGFR-EPI per year (B -0.648, p = 0.000). Likewise, the hazard ratio (HR) for dialysis inception (occurred in 9.4%) was found significantly lower with increasing DBP-CV in unadjusted and fully adjusted Cox models (HR 0.730, 95% CI 0.618 - 0.861, p = 0.000, and HR 0.678, 95% CI 0.526 - 0.874, p = 0.003, respectively). CONCLUSION: These findings suggest that DBP variability in 24-hour ABPM may be a good prognostic factor for the outcomes of CKD. Further studies are needed to determine the impact of 24-hour ABPM BPV on CKD progression and its differences from VVV.
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Encapsulated peritoneal sclerosis: a single center, retrospective analysis of clinical manifestations, risk factors and prognosis.

BACKGROUND: Encapsulated peritoneal sclerosis (EPS) is a multifactorial chronic intra-abdominal inflammatory disorder affecting the peritoneum diffusely. The aim of this study was to evaluate the rates of EPS in our peritoneal dialysis (PD) population, to perform a general assessment of the clinical presentation and to determine the outcome of affected patients and risk factors. METHODS: The medical records of consecutive 384 patients who started PD therapy between January 2001 and November 2016 were evaluated. Socio-demographic characteristics, comorbidities, PD therapy details and infectious complications were recorded. Medical records were examined to make sure that the cases met the ISPD criteria for EPS diagnosis including clinical features and either radiological and/or histopathological confirmation. Patients diagnosed with EPS were identified, and the incidence, clinical presentation, treatments and recent status of the patients were reviewed. Factors that might be associated with EPS formation and mortality were investigated. RESULTS: Two hundred one of 384 patients were female, mean age was 45.9±15.6 years and mean PD follow up time were 42.6±35 months. EPS was developed in 26 patients and EPS development rate was 6.7%. PD follow-up period and duration of hypertonic solution usage were longer in patients with EPS (P<0.001 and P=0.017 respectively). Patients with and without EPS were similar in terms of modality (P=0.21) but treatment duration with APD modality was longer in patients with EPS (P<0.001). The PD follow-up period was found to be a predictor of EPS formation (P<0.001, RR:1.034 [95% CI: 1.020-1.047]). Age (P<0.001, RR:1.039 (95% CI: 1.024-1.053) and use of hypertonic dialysis solution (P=0.007, RR:0.979 (95% CI: 0.965-0.994)) were the factors affecting survival in EPS patients. CONCLUSIONS: EPS is a relatively rare but fatal complication of peritoneal dialysis and extension of PD duration is a risk for EPS formation. Younger age and usage of hypertonic dialysis solution affects mortality in patients with EPS.

Aldosterone Resistance Due to Tacrolimus: A Case Report.

Although more common with tacrolimus, it is known that calcineurin inhibitors may induce the development of electrolyte disorders such as hyponatremia and hyperkalemia by causing a hyporeninemic hypoaldosteronism-like syndrome. We present a 32-year-old female renal transplant patient who admitted to clinic with hyponatremia and hyperkalemia. Normal anion gap metabolic acidosis and renal tubular dysfunction were detected and after other reasons were excluded, it was considered as electrolyte disorder due to tacrolimus. No response was detected after tacrolimus conversion to everolimus and considering tubular dysfunction due to aldosterone resistance, we initiated fludrocortisone therapy and electrolyte disorders rapidly improved. Fludrocortisone therapy should be considered when hyponatremia and/or hyperkalemia due to tacrolimus are detected in renal transplant patients.

Frequency of Polyneuropathy in Patients on Long Term Peritoneal Dialysis Treatment.

INTRODUCTION: Uremic polyneuropathy is very common among patients with Chronic Kidney Disease (CKD). The patients have electrophysiologic signs of impaired nerve function, although a lower percentage of patients are symptomatic. Electrophysiological parameters are quantitative indices of Polyneuropathy (PNP) severity. AIM: To assess the frequency of PNP in patients on long term Peritoneal Dialysis (PD) treatment. MATERIALS AND METHODS: Twenty three PD patients were analysed, who were receiving dialysis for at least five years and the study population divided into two groups according to duration of PD treatment. Group 1 consisted of the patients who were dialysed for at least 10 years and Group 2 consisted of patients who were dialysed for five to nine years. Patients who switched from Haemodialysis (HD) to PD and patients with coexisting diseases that could lead to disturbances in nerve conduction were excluded from the study. PNP was diagnosed when slowing of Nerve Conduction Velocity (NCV) and/or lengthening of distal latencies and/or decrease in amplitude of muscle action potential were present in two or more nerves and longer F wave response was present in one or two nerves. Carpal Tunnel Syndrome (CTS) was diagnosed if slowing of NCV and/or decrease in amplitude of muscle action potential and/or lenghening of distal latency of either sensory or motor median nerve present. RESULTS: PNP was observed in 17 of the patients {73.9%; Group 1 (n=10) and Group 2 (n=7)}. Mixed type sensory motor neuropathy was diagnosed in nine patients from Group 1 and five patients from Group 2; one patient from Group 1 had demyelinating PNP affecting motor and sensory nerves; one patient from Group 2 had axonal PNP affecting motor and sensory nerves. From Group 1, two patients had CTS related to PNP and one patient had CTS without PNP. The results of motor conductivity testing showed lower conduction velocity for left popliteal nerve in Group 1 and Group 2 patients (13.85±2.17 ms, 4.80±1.11 ms, p=0.01). In both groups, mean motor and sensory latency, amplitude and velocity of other nerves were not found to be significantly different (p>0.05). CONCLUSION: PNP is a common complication in long term PD patients. Over five years of treatment, frequency of PNP and CTS do not increase with duration of dialysis.

[Femoral hemodialysis catheter-related bacteremia due to Globicatella sanguinis: challenges in species identification]. / Femoral hemodiyaliz kateteri ile iliskili Globicatella sanguinis bakteremisi: tür düzeyinde tanimlamada karsilasilan sorunlar.

In this case, catheter-related bacteremia due to Globicatella sanguinis in a 43 years old female patient undergoing hemodialysis with the diagnosis of diabetic nephropathy was presented and the methods in the laboratory diagnosis of the rare opportunistic pathogen, Globicatella cins, were nvestigated. A set of peripheral blood cultures and simultaneous catheter culture was obtained from the patient in third of May 2016. Biochemical tests, Phoenix (Becton Dickinson, USA) and MicroScan (Beckman Coulter, USA) automated systems and matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF MS) based Microflex MS (Bruker, Daltonics, Germany) and VITEK MS (database v2.0) (bioMérieux, France) systems were used for the identification of the cultured bacteria. Partial 16S rDNA sequencing was done by using specific p8FPL 5'-AGT TTG ATC ATG GCT CAG-3' and p806R 5'-GGA CTA CCA GGG TAT CTA AT-3' primers. Minimal inhibitory concentrations (MICs) for vancomycin, erythromycin, imipenem, cefotaxime and benzypenicillin were determined by agar gradient method. The blood and catheter cultures yielded the same type of bacterial colonies. Alfa-hemolytic, catalase negative colonies observed on blood agar plates after an over night incubation yielded gram-positive cocci on Gram staining. In Sisli Hamidiye Etfal Hospital, the isolate was identifed as G.sulfidifaciens (score value > 2) by Bruker MS system and as G.sanguinis by Phoenix automated system. In Inönü University, the isolate could not be identified by Microscan automated system while VITEK MS named the isolate as 99.9% G.sanguinis and 98.3% G.sulfidifaciens. The 16S rDNA sequencing identifed the isolate as 100% G.sanguinis (GenBank accessionno. KJ680157.1). The MIC values were 0.38 µg/ml, 1.5 µg/ml, 0.38 µg/ml, > 32 µg/ml and 64 µg/ml for vancomycin, eryrthromycin, imipenem, cefotaxime and benzylpenicillin, respectively. The patient was diagnosed as catheter-related bacteremia and vancomycin (1 x 1 g IV/72 h) was used for up to 10 days. No fever and bacterial growth in cultures were present in her control visits. As G.sanguinis is not among the commonly encountered pathogens and due to difficulties in laboratory diagnosis, it may be missedor mis-identified in clinical laboratories. BD Phoenix and Bruker MS data bases lack G.sulfidifaciens and G.sanguinis, respectively, while the Globicatella genus is not present in MicroScan database. The increased number of medical implementations and the increasing number of immunosuppressed patient populations in recenty ears will lead to the emergence of rare bacteria. Increasing the diagnostic power of clinical microbiology laboratories by conventional and molecular methods and renewal of the databases of commercial identification systems by expanding the pathogen spectrum are significantly important for the prevention and control of infections caused by these agents.

Serum VEGF-C levels as a candidate biomarker of hypervolemia in chronic kidney disease.

Attaining and maintaining optimal "dry weight" is one of the principal goals during maintenance hemodialysis (MHD). Recent studies have shown a close relationship between Na load and serum vascular endothelial growth factor-C (VEGF-C) levels; thus, we aimed to investigate the role of VEGF-C as a candidate biomarker of hypervolemia. Physical examination, basic laboratory tests, N-terminal pro b-type natriuretic peptide (NT-ProBNP), echocardiography, and bioimpedance spectroscopy data of 3 groups of study subjects (euvolemic MHD patients, healthy controls, and hypervolemic chronic kidney disease [CKD] patients) were analyzed. Research data for MHD patients were obtained both before the first and after the last hemodialysis (HD) sessions of the week. Data of 10 subjects from each study groups were included in the analysis. Serum VEGF-C levels were significantly higher in hypervolemic CKD versus in MHD patients both before the first and after the last HD sessions (P = .004 and P = .000, respectively). Healthy controls had serum VEGF-C levels similar to and higher than MHD patients before the first and after the last HD sessions of the week (P = .327 and P = .021, respectively). VEGF-C levels were correlated with bioimpedance spectroscopy results (r 0.659, P = .000) and edema (r 0.494, P =0.006), but not with ejection fraction (EF) (r -0.251, P = .134), blood pressures (systolic r 0.037, P = 0.824, diastolic r -0.067, P = .691), and NT-ProBNP (r -0.047, P = .773). These findings suggest that serum VEGF-C levels could be a potential new biomarker of hypervolemia. The lack of correlation between VEGF-C and EF may hold a promise to eliminate this common confounder. Further studies are needed to define the clinical utility of VEGF-C in volume management.