Immunosuppressive treatment results in patients with primary IgA nephropathy in Turkiye; the data from TSN-GOLD working group.

BACKGROUND: Immunoglobulin A (IgA) nephropathy (IgAN) treatment consists of maximal supportive care and, for high-risk individuals, immunosuppressive treatment (IST). There are conflicting results regarding IST. Therefore, we aimed to investigate IST results among IgAN patients in Turkiye. METHOD: The data of 1656 IgAN patients in the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases Study Group were analyzed. A total of 408 primary IgAN patients treated with IST (65.4% male, mean age 38.4 ± 12.5 years, follow-up 30 (3-218) months) were included and divided into two groups according to treatment protocols (isolated corticosteroid [CS] 70.6% and combined IST 29.4%). Treatment responses, associated factors were analyzed. RESULTS: Remission (66.7% partial, 33.7% complete) was achieved in 74.7% of patients. Baseline systolic blood pressure, mean arterial pressure, and proteinuria levels were lower in responsives. Remission was achieved at significantly higher rates in the CS group (78% vs. 66.7%, p = 0.016). Partial remission was the prominent remission type. The remission rate was significantly higher among patients with segmental sclerosis compared to those without (60.4% vs. 49%, p = 0.047). In the multivariate analysis, MEST-C S1 (HR 1.43, 95% CI 1.08-1.89, p = 0.013), MEST-C T1 (HR 0.68, 95% CI 0.51-0.91, p = 0.008) and combined IST (HR 0.66, 95% CI 0.49-0.91, p = 0.009) were found to be significant regarding remission. CONCLUSION: CS can significantly improve remission in high-risk Turkish IgAN patients, despite the reliance on non-quantitative endpoints for favorable renal outcomes. Key predictors of remission include baseline proteinuria and specific histological markers. It is crucial to carefully weigh the risks and benefits of immunosuppressive therapy for these patients.

Clinical and histopathological characteristics of primary focal segmental glomerulosclerosis in Turkish adults.

The data regarding primary FSGS (pFSGS) from different parts of the world differ. While the prevalence of pFSGS has been increasing in Western countries like the USA, it follows an inconsistent trend in Europe and Asia and a decreasing trend in Far Eastern countries such as China in the last two decades. There are undetermined factors to explain those national and geographic discrepancies. Herein, we aimed to reveal the current prevalence with clinical and histopathological characteristics of pFSGS in Turkish adults. This study includes the biopsy-proven pFSGS patients data recorded between 2009 and 2019, obtained from the national multicenter primary glomerulonephritis registry system of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database. 850 of the 3875 primer glomerulonephritis patients(21.9%) have pFSGS. The mean age is 40.5 ± 14.2 and 435 (51.2%) of patients are male. Nephrotic syndrome is the most common biopsy indication (59.2%). 32.6% of patients have hematuria, 15.2% have leukocyturia and 7.8% have both. Serum creatinine, albumin, and proteinuria are 1.0 mg/dL (IQR = 0.7-1.4) mg/dl, 3.4 ± 0.9 g/dl, 3400 mg/day(IQR, 1774-5740), respectively. Females have lower mean arterial pressure (- 2.2 mmHg), higher eGFR (+ 10.0 mL/min/1.73 m2), and BMI (+ 1.6 kg/m2) than males. Thickened basal membrane(76.6%) and mesangial proliferation (53.5%) on light microscopy are the major findings after segmental sclerosis. IgM (32.7%) and C3 (32.9%) depositions are the most common findings on immunofluorescence microscopy. IgM positivity is related to lower eGFR, serum albumin, and higher proteinuria. The prevalence of pFSGS is stable although slightly increasing in Turkish adults. The characteristics of the patients are similar to those seen in Western countries.

Could mesangial C3 deposition be an independent prognostic marker in immunoglobulin A nephropathy?

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is a common primary glomerulonephropathy. There is evidence that mesangial C3 deposition plays a role in the development of the disease. The aim of this study was to examine the effect of C3 deposition on the prognosis of IgAN patients. METHOD: The study included 1135 patients with biopsy-confirmed IgAN from the database of the Turkish Nephrology Association Glomerular Diseases Working Group (TSN-GOLD). Patients were excluded from the study if they were aged < 18 or > 75 years or if C3 staining had not been performed in the immunofluorescent analysis. C3 deposition was defined as an immunofluorescence intensity of C3 ≥ 2 + within the mesangium. The primary endpoints were the development of end-stage renal disease, a 30% decrease in glomerular filtration rate compared to the basal value or an elevation in proteinuria to a nephrotic level (3.5 gr/day). RESULTS: Mesangial C3 deposition was observed in 603 (53.1%) patients. No statistically significant difference was found at baseline between the groups with and without mesangial C3 deposition, as for age, sex, BMI, proteinuria level, or the presence of hypertension. In the follow-up period with a mean duration of 78 months, no significant difference was found between the two groups regarding the primary endpoints (p = 0.43). A significant correlation between C3 deposition and segmental glomerulosclerosis (S1) according to the Oxford MEST-C classification was found (p = 0.001). CONCLUSION: Although a correlation was observed between mesangial C3 deposition and the S1 MEST-C classification, mesangial C3 deposition was not a prognostic factor in IgAN.

Comparison of focal segmental glomerulosclerosis and other primary glomerulonephrites in terms of parameters of hepatic steatosis and metabolic syndrome.

PURPOSE: The increasing frequency of coexistence of focal segmental glomerulosclerosis (FSGS) and obesity-associated glomerulopathy and the relationship between metabolic syndrome components and chronic kidney disease have been demonstrated in studies. Based on this information, in this study, we aimed to compare FSGS and other primary glomerulonephritis diagnoses in terms of parameters of metabolic syndrome and hepatic steatosis. MATERIALS AND METHODS: In our study, the data of 44 patients who were diagnosed FSGS through kidney biopsy and 38 patients with any other primary glomerulonephritis diagnoses in our nephrology clinic were retrospectively analyzed. Patients were divided into two groups: FSGS and other primary glomerulonephritis diagnoses, and they were examined in terms of their demographic data, laboratory parameters, body composition measurements, and the presence of hepatic steatosis, as shown using liver ultrasonography. RESULTS: In the comparative analysis of patients with FSGS and other primary glomerulonephritis diagnoses, with the increase in age increased the risk of FSGS by 1.12 times, the increase in BMI ​​increased the risk of FSGS by 1.67 times, while with the decrease in waist circumference decreased the risk of FSGS by ​​0.88 times, the decrease in HbA1c decreased the risk of FSGS by ​​0.12 times, and the presence of hepatic steatosis increased the risk of FSGS by 20.24 times. CONCLUSION: The presence of hepatic steatosis, an increase in waist circumference and BMI values, which are body components favoring obesity, and an increase in HbA1c, which is a marker for hyperglycemia and insulin resistance, are greater risk factors for the development of FSGS compared with other primary glomerulonephritis diagnoses.

Demographic, clinical and laboratory characteristics of adult-onset minimal change disease in Turkey: Turkish Society of Nephrology-Glomerular Diseases (TSN-GOLD) Working Group.

PURPOSE: In our study, diagnostic and demographic characteristics of patients diagnosed with minimal change disease (MCD) by biopsy, clinical and laboratory findings in our country were investigated. METHODS: Data were obtained from the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group database. Demographic characteristics, indications for biopsy, diagnosis of the glomerular diseases, comorbidities, laboratory and biopsy findings of all patients were recorded. The data presented are cross-sectional and includes application data for the biopsy period. RESULTS: Of 3875 patients, 233 patients with MCD (median age 35.0 years) were included in the study, which constitutes 6.0% of the total glomerulonephritis database. Renal biopsy was performed in 196 (84.1%) patients due to nephrotic syndrome. Median serum creatinine was 0.7 (0.6-1.0) mg/dl, mean eGFR was 104 ± 33 ml/min/1.73 m2 and median proteinuria 6000 mg/day. The number of patients under the age of 40 years was 139 (59.7%) (Group A), and the number of patients aged 40 years and over was 94 (40.3%) (Group B). Compared to Group A, global sclerotic glomeruli (24 vs. 43, p < 0.001) interstitial inflammation (15 vs. 34, p < 0.001), interstitial fibrosis (20 vs. 31, p = 0.001, vascular changes (10 vs. 25, p < 0.001) and tubular atrophy (18 vs. 30, p < 0.001) were found to be significantly higher in Group B. There was no difference in immunofluorescent staining properties between the two groups. CONCLUSION: Our data are generally compatible with the literature. Chronic histopathological changes were more common in patients aged 40 years and older than younger patients. Studies investigating the effects of these different features on renal survival are needed.

Impact of hospital-acquired acute kidney injury on Covid-19 outcomes in patients with and without chronic kidney disease: a multicenter retrospective cohort study

Background/aim: Hospital-acquired acute kidney injury (HA-AKI) may commonly develop in Covid-19 patients and is expected to have higher mortality. There is little comparative data investigating the effect of HA-AKI on mortality of chronic kidney disease (CKD) patients and a control group of general population suffering from Covid-19. Materials and methods: HA-AKI development was assessed in a group of stage 3­5 CKD patients and control group without CKD among adult patients hospitalized for Covid-19. The role of AKI development on the outcome (in-hospital mortality and admission to the intensive care unit [ICU]) of patients with and without CKD was compared. Results: Among 621 hospitalized patients (age 60 [IQR: 47­73]), women: 44.1%), AKI developed in 32.5% of the patients, as stage 1 in 84.2%, stage 2 in 8.4%, and stage 3 in 7.4%. AKI developed in 48.0 % of CKD patients, whereas it developed in 17.6% of patients without CKD. CKD patients with HA-AKI had the highest mortality rate of 41.1% compared to 14.3% of patients with HA-AKI but no CKD (p < 0.001). However, patients with AKI+non-CKD had similar rates of ICU admission, mechanical ventilation, and death rate to patients with CKD without AKI. Adjusted mortality risks of the AKI+non-CKD group (HR: 9.0, 95% CI: 1.9­44.2) and AKI+CKD group (HR: 7.9, 95% CI: 1.9­33.3) were significantly higher than that of the non-AKI+non-CKD group. Conclusion: AKI frequently develops in hospitalized patients due to Covid-19 and is associated with high mortality. HA-AKI has worse outcomes whether it develops in patients with or without CKD, but the worst outcome was seen in AKI+CKD patients.

The Collapsing Variant of Focal Segmental Glomerulosclerosis (FSGS) Secondary to Sarcoidosis, A Very Rare Case.

Sarcoidosis is a multisystemic granulomatous disease of unknown etiology. Renal involvement in sarcoidosis patients is occurred, but the incidence and prevalence is uncertain. The most common renal involvement of systemic sarcoidosis is nephrocalcinosis and interstitial nephritis. After sarcoidosis was diagnosed in a 31-year-old male patient, we performed a renal biopsy because of nephrotic range proteinuria and renal dysfunction. The collapsing variant of focal segmental glomerulosclerosis (FSGS) secondary to sarcoidosis was diagnosed by kidney biopsy.

Chronic kidney disease predicts poor outcomes of COVID-19 patients.

PURPOSE: The recent outbreak of COVID-19 rapidly spread worldwide. Comorbid diseases are determinants of the severity of COVID-19 infection and mortality. The aim of this study was to explore the potential association between chronic kidney disease (CKD) and the severity of COVID-19 infection. METHODS: The study included 609 consecutive adult patients (male: 54.52%, mean age: 59.23 ± 15.55 years) hospitalized with the diagnosis of COVID-19 in a tertiary level hospital. Data were collected from the electronic health records of the hospital. The patients were separated into two groups: Group I included COVID-19-positive patients with CKD stage 1-2, and Group II included COVID-19-positive with CKD stage 3-5. The relationships were examined between CKD stage, laboratory parameters and mortality. RESULTS: Significant differences were determined between the groups in respect of the inflammation parameters and the parameters used in prognosis. In Group II, statistically significantly higher rates were determined of comorbid diseases [hypertension (p < 0.001) and diabetes mellitus (p < 0.001), acute kidney injury (AKI), which was found to be associated with mortality (p < 0.001), and mortality (p < 0.001)]. In multivariate regression analysis, CKD stage 3-5, AKI, male gender, hypertension, DM and malignancy were found to be significant independent variables increasing mortality. CONCLUSION: The prevelance of CKD stage 3-5 on admission is associated with a high risk of in-hospital mortality in patients with COVID-19. Close follow-up can be recommended for patients with a reduced glomerular filtration rate (GFR).

Novel 2'-alkoxymethyl substituted klavuzon derivatives as inhibitors of Topo I and CRM1.

In this work, 2'-alkoxymethyl substituted klavuzon derivatives were prepared starting from 2-methyl-1-naphthoic acid in eight steps. Anticancer potencies of the synthesized compounds were evaluated by performing MTT cell viability test over cancerous and healthy pancreatic cell lines, along with CRM1 inhibitory properties in HeLa cells by immunostaining and Topo I inhibition properties by supercoiled DNA relaxation assay. Their cytotoxic activities were also presented in hepatocellular carcinoma cells (HuH-7) derived 3D spheroids. Among the tested klavuzon derivatives, isobutoxymethyl substituted klavuzon showed the highest selectivity of cytotoxic activity against pancreatic cancer cell line. They showed potent Topo I inhibition while their CRM1 inhibitory properties somehow diminished compared to 4'-alkylsubstituted klavuzons. The most cytotoxic 2'-methoxymethyl derivative inhibited the growth of the spheroids derived from HuH-7 cell lines and PI staining exhibited time and concentration dependent cell death in 3D spheroids.

Serum neutrophil gelatinase-associated lipocalin is associated with cardiovascular events in patients with chronic kidney disease.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin family best known as a novel and early marker of acute kidney injury (AKI). Recent data suggest that NGQueryAL is not only a marker of AKI, but also an important player in the vascular remodeling, atherosclerotic plaque stability and thrombus formation. We conducted this study to investigate the association of serum NGAL levels with fatal and composite (fatal and non-fatal) cardiovascular events (CVE) in a cohort of patients with stage 1-5 CKD. METHODS: This was an observational cohort study in which serum NGAL was obtained from 298 CKD (stages 1-5) patients. Fatal and composite CVE were recorded for a median 41 months. We examined alteration of serum NGAL through CKD groups as well as association with inflammatory markers. We also performed a Cox regression analysis to determine the association of NGAL with predefined clinical outcomes. RESULTS: The median value of NGAL was 50.5 ng/mL (IR 47.6-54.9 ng/mL), and higher NGAL values were recorded in diabetic patients. In a multiple linear regression model, including all univariate associates of NGAL, only log eGFR, log hs-CRP and log HDL cholesterol maintained an independent association with log NGAL. During the observational period, 30 patients died due to cardiovascular causes and 69 non-fatal CVE were registered. In the fully adjusted model, we observed a 2.08-fold increase in the risk of fatal CVE and a 1.50-fold increase in the risk of fatal and non-fatal CVE for each increment of 1 SD in log NGAL values. CONCLUSIONS: This is the first study that shows that serum NGAL is associated with cardiovascular events (fatal and non-fatal) in patients with CKD, independently of traditional risk factors, renal function and inflammation.

The role of plasma triglyceride/high-density lipoprotein cholesterol ratio to predict cardiovascular outcomes in chronic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) risk is substantially increased in subjects with chronic kidney disease (CKD). The Triglycerides (TG) to High-Density Lipoprotein Cholesterol (HDL-C) ratio is an indirect measure of insulin resistance and an independent predictor of cardiovascular risk. No study to date has been performed to evaluate whether the TG/HDL-C ratio predicts CVD risk in patients with CKD. METHODS: A total of 197 patients (age 53±12 years) with CKD Stages 1 to 5, were enrolled in this longitudinal, observational, retrospective study. TG/HDL-C ratio, HOMA-IR indexes, serum asymmetric dimethyl arginine (ADMA), high sensitivity C-reactive protein (CRP), parathyroid hormone (PTH), calcium, phosphorous, estimated glomerular filtration rate (eGFR), and albumin levels were measured. Flow mediated vasodilatation (FMD) of the brachial artery was assessed by using high-resolution ultrasonography. RESULTS: A total of 11 cardiovascular (CV) deaths and 43 nonfatal CV events were registered in a mean follow-up period of 30 (range 9 to 35) months. Subjects with TG/HDL-C ratios above the median values (>3.29) had significantly higher plasma ADMA, PTH, and phosphorous levels (p=0.04, p=0.02, p=0.01 respectively) and lower eGFR and FMD values (p=0.03, p<0.001 respectively). The TG/HDL-C ratio was an independent determinant of FMD (ß=-0.25 p=0.02) along with TG, HDL-C, hsCRP, serum albumin, phosphate levels, systolic blood pressure, PTH, eGFR and the presence of diabetes mellitus. The TG/HDL-C ratio was also a significant independent determinant of cardiovascular outcomes [HR: 1.36 (1.11-1.67) (p=0.003)] along with plasma ADMA levels [HR: 1.31 (1.13-1.52) (p<0.001)] and a history of diabetes mellitus [HR: 4.82 (2.80-8.37) (p<0.001)]. CONCLUSION: This study demonstrates that the elevated TG/HDL-C ratio predicts poor CVD outcome in subjects with CKD. Being a simple, inexpensive, and reproducible marker of CVD risk, the TG/HDL-C ratio may emerge as a novel and reliable indicator among the many well-established markers of CVD risk in CKD. SYSTEMATIC REVIEW REGISTRATION: Clinical trial registration number and date: NCT02113462 / 10-04-2014.

A longitudinal study of inflammation, CKD-mineral bone disorder, and carotid atherosclerosis after renal transplantation.

BACKGROUND AND OBJECTIVES: The role of reversibility of nontraditional risk factors, like inflammation and CKD-mineral bone disorder, in the reduction of cardiovascular risk after renal transplantation is still scarcely defined. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The longitudinal relationship between C-reactive protein, CKD-mineral bone disorder biomarkers, and intima media thickness was investigated in a series of 178 patients (age=32±10 years) with stage 5 CKD maintained on chronic dialysis who underwent echo-color Doppler studies of the carotid arteries before and after renal transplantation. Smokers and patients with diabetes were excluded from the study. In all patients, immunosuppression was performed by a standard regimen on the basis of calcineurin inhibitors. Healthy controls were specifically selected to match the age and sex distribution of the patients. Biochemical and intima media thickness assessments were repeated 6 months after transplantation. RESULTS: Before transplantation, intima media thickness in patients with stage 5 CKD on dialysis (average=0.9±0.2 mm) was higher (P<0.001) than in well matched healthy controls (0.6±0.1 mm) and reduced substantially (-22%; 95% confidence interval, -24% to -20%) after transplantation (P=0.001). GFR (multivariable-adjusted ß=0.23; P<0.001), C-reactive protein (ß=0.15; P<0.001), and fibroblast growth factor 23 (ß=0.28; P<0.001) were the strongest independent correlates of intima media thickness before transplantation. Similarly, longitudinal changes in the same biomarkers were the sole independent correlates of simultaneous changes in intima media thickness (C-reactive protein: ß=0.25; fibroblast growth factor 23: ß=0.26; P<0.001 for both) after renal transplantation. The evolution of intima media thickness after transplantation was largely independent of classic risk factors, including BP, LDL cholesterol, and insulin resistance, as measured by homeostatic model assessment. CONCLUSIONS: Intima media thickness improves after renal transplantation. Such an improvement associates with parallel changes in serum C-reactive protein and fibroblast growth factor 23. These observations are in keeping with the hypothesis that the decline in cardiovascular risk after transplantation, in part, depends on partial resolution of nontraditional cardiovascular risk factors, like inflammation and CKD-mineral bone disorder.

Ramipril lowers plasma FGF-23 in patients with diabetic nephropathy.

BACKGROUND/AIMS: Ramipril attenuates renal Fibroblast growth factor-23 (FGF-23) expression, ameliorates proteinuria and normalizes serum phosphate in the diabetic Zucker rat with progressive renal disease suggesting that the renoprotective effect by this drug may be in part due to a FGF-23-lowering effect of angiotensin-converting enzyme (ACE) inhibition. METHODS: In this nonrandomized study, we tested whether ACE-inhibition reduces circulating FGF-23 in type-2 diabetics with stage-1 chronic kidney disease (CKD) and proteinuria. Intact FGF-23, the eGFR, proteinuria and the endothelium-dependent flow-mediated (FMD) response to ischemia and other parameters were measured at baseline and after 12-weeks of treatment with ramipril (n = 68) or amlodipine (n = 32). RESULTS: Blood Pressure (BP) fell to a similar extent (p < 0.001) in the two groups. However, 24 h proteinuria and the FMD improved more (both p < 0.01) in ramipril-treated patients than in amlodipine-treated patients. Changes in proteinuria (r = 0.47) and in FMD (r = -0.49) by ramipril were closely associated (p < 0.001) with simultaneous changes in FGF-23 and this link was confirmed in multiple regression analyses. In these analyses, the relationship between FMD and proteinuria changes attained statistical significance (p < 0.01) only in a model excluding FGF-23 suggesting that endothelial dysfunction and FGF-23 share a common pathway conducive to renal damage. CONCLUSION: Findings in this study contribute to generate the hypothesis that FGF-23 may be implicated in proteinuria and in endothelial dysfunction in diabetic nephropathy (clinicaltrials.gov (NCT01738945)).

Mitral annular calcification and the serum osteocalcin level in patients with chronic kidney disease.

OBJECTIVE: To determine the relationships between inflammatory mediators, mitral annular calcification (MAC), and osteocalcin in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: Echocardiographic data for 60 patients diagnosed as CKD were retrospectively evaluated. The patients were divided into 2 groups; patients with MAC (MAC+ group) and patients without MAC (MAC- group). The relationships between biochemical markers-including osteocalcin-and MAC were evaluated. RESULTS: The study included 19 female and 41 male patients. In all, 29 patients were MAC+ and 31 were MAC-. High-sensitive C-reactive protein (hsCRP) and osteocalcin levels were significantly higher in the MAC+ group (p < 0.05). The eGFR was lower, serum calcitonin (we could not obtain calcitonin data for 15 patients), Ca, PO4, CaxPO4, the erythrocyte sedimentation rate, red cell distribution width, the neutrophil/Lymphocyte rate, and PTH were higher in the MAC+ group; however, the differences between the groups were not significant (p > 0.05). The mitral E/A ratio, mitral peak Ea velocity, tricuspid E/A ratio, hsCRP, and the osteocalcin level were strongly correlated with MAC. Multivariate logistic regression analysis showed that only the osteocalcin level and mitral E/A ratio were independent variables, each with an independent effect on MAC. CONCLUSION: CKD patients in the MAC+ group had higher osteocalcin levels than those in the MAC- group, and left ventricular diastolic dysfunction was more common in the MAC+ group.

Serum sclerostin and adverse outcomes in nondialyzed chronic kidney disease patients.

BACKGROUND: The chronic kidney disease (CKD)-mineral and bone disorder (MBD) syndrome is an important contributor to the CKD-associated cardiovascular disease and high mortality rates. Sclerostin, a protein synthesized in osteocytes, is a potent downregulator of bone metabolism and a novel candidate for the bone-vascular axis in CKD patients. We tested whether serum sclerostin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population. METHODS: Serum sclerostin was obtained from 173 CKD (stage 3-5) and 47 control patients, and its concentration was correlated with estimated glomerular filtration rate and to mineral and vascular abnormalities that are present in the CKD evolution. All-cause mortality and CVEs were also analyzed in relation to serum sclerostin values. RESULTS: Patients with CKD showed higher sclerostin levels (median 63.5 pmol/L vs 52 pmol/L, P < .001) than controls, with values progressively higher across the CKD stages. In univariate analysis, serum sclerostin concentrations were correlated with gender, estimated glomerular filtration rate, flow-mediated dilatation, and endothelium-independent vasodilatation as markers of endothelial dysfunction and with different serum CKD-MBD-associated parameters. However, in multivariate analysis, only gender, fibroblast growth factor-23, phosphate, flow-mediated dilatation, and cholesterol remained significantly associated with sclerostin levels. During the observational period, there were 19 deaths and 50 CVEs. In survival analysis, different sclerostin levels were associated with all-cause mortality and CVEs in these patients. CONCLUSIONS: This is the first study that shows that serum sclerostin values are associated, even after multiple adjustments, with fatal and nonfatal CVEs in a nondialyzed CKD population.

Plasma endocan levels associate with inflammation, vascular abnormalities, cardiovascular events, and survival in chronic kidney disease.

Plasma endocan levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. There are currently no data on endocan in patients with chronic kidney disease (CKD). Therefore, we measured plasma endocan in 251 patients with CKD (stage 1-5) and 60 control individuals. Plasma endocan concentrations correlated with estimated glomerular filtration rate (eGFR), different markers of inflammation (pentraxin 3 and high-sensitivity C-reactive protein), and vascular abnormalities (flow-mediated vasodilation (FMV) and carotid intima media thickness (CIMT)). All-cause mortality and cardiovascular events (CVE) were also analyzed with respect to plasma endocan. Patients with CKD showed significantly increased plasma endocan (4.7 [IQR 1.9-9.4] compared with controls [IQR 1.1-1.5] ng/ml), with values progressively higher across stages of CKD. On univariate analysis, plasma endocan concentrations correlated negatively with eGFR and FMV, but positively with both markers of inflammation and CIMT. However, on multivariate analysis only high-sensitivity C-reactive protein, FMV, and CIMT remained significantly associated with plasma endocan. On Cox survival analysis, endocan levels were associated with all-cause mortality and CVE in these patients. Thus, plasma endocan increases in the presence of decreasing eGFR and influences all-cause mortality and CVE in patients with CKD independent of traditional and nontraditional risk factors.

Endothelial function in patients with familial Mediterranean fever-related amyloidosis and association with cardiovascular events.

OBJECTIVES: Secondary amyloidosis is the most important complication of FMF and endothelial function is more severely impaired. Elevated asymmetric dimethyl arginine (ADMA) may mediate the excess cardiovascular disease (CVD) risk of this group. We aimed to compare endothelial function characteristics, including ADMA, in patients with FMF-related amyloidosis and primary glomerulopathies and to define risk factors for a CVD event. METHODS: We undertook a cross-sectional study with prospective follow-up including consecutive patients with FMF-related amyloidosis (n = 98) or other non-diabetic glomerulopathies (n = 102). All patients had nephrotic-range proteinuria and normal glomerular filtration rate. Flow-mediated dilatation (FMD) was assessed and ADMA levels, CRP and pentraxin 3 (PTX3) were determined. Patients were followed for cardiovascular events. RESULTS: Amyloidosis patients secondary to FMF showed higher levels of ADMA, CRP and PTX3 and lower FMD as compared with patients with other glomerulopathies. Cardiovascular events (n = 54) were registered during 3 years of follow-up. Increased ADMA levels and lower FMD were observed in patients with cardiovascular risk in both groups, but especially in individuals with amyloidosis. CONCLUSION: Patients with FMF-related amyloidosis have increased CVD event risk, probably related to the high ADMA levels, elevated inflammatory markers and decreased FMD measures observed in these patients.

Monocyte count/HDL cholesterol ratio and cardiovascular events in patients with chronic kidney disease.

BACKGROUND AND AIM: Previous studies showed that renal dysfunction was associated with both a reduction in serum high-density lipoprotein (HDL) cholesterol concentration and increased circulating monocyte count. We aimed to investigate the effect of circulating monocyte to serum HDL cholesterol ratio (M/H ratio) on fatal and composite cardiovascular events, in an observational cohort study of chronic kidney disease (CKD) patients. MATERIALS AND METHODS: A total of 340 subjects with stage 1-5 CKD were followed for a mean follow-up period of 33 (range 2-44) months and assessed for fatal and nonfatal CV events. M/H ratio was calculated for all patients. All-cause mortality and CVE were also analyzed in relation to M/H ratio. RESULTS: Monocyte/HDL cholesterol ratio was negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.43, P < 0.001). Notably, both fatal and combined fatal and nonfatal cardiovascular events were more common in patients having a M/H ratio in the third tertile was associated with a hazard ratio of 2.24 and 4.91, respectively, for fatal and composite cardiovascular events compared to being in the first tertile. CONCLUSION: Monocyte/HDL cholesterol ratio was increased with decreasing eGFR in predialytic CKD patients. Most importantly, we report for the first time that an increased M/H ratio was cross-sectionally associated with a worse cardiovascular profile and arose as independent predictors of major cardiovascular events during follow-up.

Red cell distribution width is independently related to endothelial dysfunction in patients with chronic kidney disease.

BACKGROUND: Red cell distribution width (RDW) is a measure of erythrocyte size variability and has been shown as an independent predictor of mortality. The aim of this article was to evaluate the association of RDW with endothelial dysfunction in patients with chronic kidney disease (CKD). METHODS: Patients with 1 to 5 stages of CKD were included in the study. Endothelial function was assessed with flow-mediated dilatation (FMD). Estimated glomerular filtration rate (eGFR) and carotid intima media thickness (CIMT) were determined. Clinicodemographic characteristics, biochemical values, complete blood counts, ferritin, C-reactive protein (CRP) and cholesterol levels were recorded. Spearman's correlation was used to determine correlates of RDW. Multivariate linear regression model was used to assess independent associates of FMD. RESULTS: Overall, 367 patients with CKD 1 to 5 were included in the study. RDW showed a significant increase from stage 1 to stage 5 CKD. Median RDW was 13.5. Patients with RDW values higher than median had significantly lower hemoglobin, eGFR and FMD values and higher CIMT and CRP values compared with patients who had RDW values below median. RDW showed a significant positive correlation with the presence of diabetes mellitus, CIMT and CRP, whereas a significant negative correlation with eGFR, ferritin and FMD. Multivariate analysis showed independent predictors of FMD as RDW, presence of diabetes, hemoglobin, eGFR, CRP, and serum albumin. CONCLUSIONS: Multivariate regression model revealed RDW as a significant predictor of FMD independent of major confounding factors, such as diabetes, inflammation, anemia and kidney function in CKD.