Comparison of Caudal Block and Sacral Erector Spina Block for Postoperative Analgesia Following Pediatric Circumcision: A Double-Blind, Randomized Controlled Trial.

INTRODUCTION: Caudal block (CB) and erector spina plane block (ESPB) has been shown to provide effective postoperative analgesia following circumcision. Our aim was to compare the analgesic efficacy of sacral ESPB and CB, as well as the time to first analgesic requirement and postoperative complications. METHODS: Patients aged 1-7 years in the ASA I-II group, who were scheduled for circumcision were included in the study. Blocks were performed under general anesthesia before the operation. Postoperative pain was evaluated using the Face, Legs, Activity, Cry and Consolability (FLACC) scores. Analgesic requirements in the first 24 hours postsurgery, the time of first analgesia requirement, and postoperative complications were recorded. RESULTS: A total number of 150 patients were included in the study. In the CB group urinary retention was observed. No side effects were observed in the sacral ESPB group. The 4th and 6th hour postoperative FLACC scores were lower in the ESP group. The number of analgesic consumption in the first 24 hours postsurgery was significantly lower in the ESPB group (p <0.001). CONCLUSION: Based on our results, sacral ESPB performed with ultrasonography is a simple and safe regional anesthesia method that can be used to provide effective postoperative analgesia for circumcision.

Effects of Long-term Administration of Inhaled Lavender During Hemodialysis on Patients' Invasive Pain, Anxiety, and Comfort During Cannulation: A Single-blind Randomized Controlled Trial.

Context: Although a number of studies have shown that lavender administered via inhalation can decrease the invasive pain and anxiety experienced by hemodialysis (HD) patients during cannulation, the evaluation has mostly been on the short-term effectiveness of lavender oil. Also, no study has evaluated the effects of lavender on comfort level. Objective: The study aimed to investigate the long-term effectiveness of lavender oil, when administered via an inhaler during HD sessions, on a patient's experience of invasive pain, anxiety, and comfort during access to the fistula. Design: The research team designed a prospective, single-blind, randomized, controlled clinical trial. Setting: The study took place in an HD unit of a public hospital in Kirklareli, Turkey. Participants: Participants were 24 patients receiving HD in the unit between January and March 2021. Intervention: Participants were randomly assigned to the intervention or control group. Pure lavender essence was diluted with sweet almond oil at a ratio of 1:10. Before the cannulation procedure at 12 HD sessions, three drops of a 1:10 mixture were placed on sterile gauze and held at a distance of about 10 cm from the participant's nose to ensure its inhalation before the fistula puncture with the needle. No extra procedure was performed for the control group. Outcome Measures: Participants completed a visual analogue scale (VAS) right after puncture of the fistula during each HD session. The STAI and HD Comfort Scale were scored at baseline prior to the first HD session and postintervention at the twelfth HD session. Results: The VAS (P < .001) and state anxiety scores (P = .027) were significantly lower in the intervention group than in the control group at all time points, except at baseline. The comfort scale in the intervention group was significantly higher than that in the control group (P < .05). Conclusions: Lavender aromatherapy could be a good option for reducing the pain, anxiety, and discomfort level of HD patients.

The association of profilin-1 levels with survival in chronic kidney disease.

BACKGROUND: Profilin-1 is a ubiquitous, actin-binding protein that plays an important role in the regulation of actin polymerization and cytoskeleton remodelling and contributes to vascular dysfunction. We conducted this study to investigate the association of serum profilin-1 levels with fatal and nonfatal CVE in a cohort of patients with stage 1-5 CKD. MATERIALS AND METHODS: Serum concentrations of profilin-1 levels were determined by enzyme-linked immunosorbent assay. Endothelium-dependent vasodilatation (flow-mediated dilatation [FMD]) and endothelium-independent vasodilatation (nitroglycerine-mediated dilatation [NMD]) of the brachial artery were assessed noninvasively, using high-resolution ultrasound. RESULTS: Both fatal and nonfatal CVE were significantly higher in patients with high profilin-1 levels. Kaplan-Meier survival curves showed that patients with profilin-1 below the median value (114 pg/mL) had higher cumulative survival compared with patients who had profilin-1 levels above the median value (log-rank test, P < .001). CONCLUSIONS: This is the first study that demonstrates the serum profilin-1 is independently associated with endothelial dysfunction, cardiovascular events and survival in patients with CKD.

Osteoprotegerin in Chronic Kidney Disease: Associations with Vascular Damage and Cardiovascular Events.

Vascular injury and dysfunction contribute to cardiovascular disease, the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor receptor superfamily that has been linked to atherogenesis and endothelial dysfunction. Elevated circulating OPG levels predict future cardiovascular events (CVE). Our aim was to evaluate the determinants of circulating OPG levels, to investigate the relationship between OPG and markers of vascular damage and to test whether OPG improves risk stratification for future CVE beyond traditional and renal-specific risk factors in a CKD population. 291 patients with CKD stage 1-5 not on dialysis were included in the study. In the multivariate analysis, OPG was a significant predictor for flow-mediated dilatation, but not for carotid intima media thickness levels. During follow-up (median 36 months, IQR = 32-42 months), 87 patients had CVE. In the Cox survival analysis, OPG levels were independently associated with CVE even after adjustment for traditional and renal-specific cardiovascular risk factors. The addition of OPG to a model based on commonly used cardiovascular factors significantly improved the reclassification abilities of the model for predicting CVE. We show for the first time that OPG improves risk stratification for CVE in a non-dialysis CKD population, above and beyond a model with established traditional and renal-specific cardiovascular risk factors, including estimated glomerular filtration rate and fibroblast growth factor 23.

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.

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.

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.

Soluble TWEAK plasma levels increase after renal transplantation and associate with the improvement of endothelial function.

BACKGROUND: Soluble TWEAK (sTWEAK) and asymmetric dimethyl arginine (ADMA) concentrations have been associated with endothelial function in patients with chronic kidney disease (CKD). We tested the hypothesis that the improvement in endothelial function observed after renal transplantation is directly linked to the normalization of both sTWEAK and ADMA. MATERIALS AND METHODS: One hundred and seventy-five kidney transplant recipients (71% men; 31·6 ± 9·4 years) were studied immediately before and on the 180th day post-transplantation. At each visit, blood samples were taken to assess circulating levels of sTWEAK and ADMA. Brachial artery endothelium-dependent vasodilatation (FMD) assessments were also performed. RESULTS: Renal transplantation was followed by an improvement in FMD. This improvement was paralleled by an increase in sTWEAK and a reduction in ADMA after transplantation (P < 0·001 for all). Cross-sectionally, both molecules associated with FMD before as well as after transplantation (P < 0·001 for all). Longitudinally, the changes observed in sTWEAK (ß = 0·26, P < 0·001) and ADMA (ß = -0·44, P < 0·001) levels were independently associated with the improvement of FMD (r(2)  = 0·30). CONCLUSIONS: Renal transplantation is followed by an improvement of FMD that is independently associated with the normalization of both sTWEAK and ADMA concentrations. We identify two surrogate biomarkers of endothelial function with potential as therapeutic targets.

Longitudinal analysis of vascular function and biomarkers of metabolic bone disorders before and after renal transplantation.

BACKGROUND/AIMS: The role of chronic kidney disease-mineral bone disorder (CKD-MBD) reversibility in the amelioration of vascular function and in the reduction of the risk for cardiovascular events after renal transplantation is still unknown. METHODS: We investigated the longitudinal relationship between the main biomarkers of CKD-MBD and the evolution of vascular function [flow-mediated dilatation (FMD)] after transplantation in a series of 161 patients with kidney failure maintained on chronic dialysis (5D-CKD). RESULTS: Before transplantation, FMD in patients was markedly lower (-40%, p < 0.001) than in well-matched healthy subjects and increased by 27% after transplantation (p = 0.001). Fibroblast growth factor 23 (FGF23), 25-hydroxy-vitamin D (25OHVD) and serum phosphate (p < 0.01) were independently associated with simultaneous changes in FMD. Changes in classical risk factors and in risk factors related to CKD like the glomerular filtration rate, serum albumin, C-reactive protein and insulin resistance failed to independently explain the variability in FMD changes after transplantation. CONCLUSION: Endothelium-dependent vasodilatation improves after kidney transplantation, which is parallel to the dramatic fall in FGF23, the reduction in serum phosphorus and the increase in 25OHVD levels. If these associations are causal, a part of decline in cardiovascular risk after transplantation is related to partial resolution of CKD-MBD.

Comparison of calcium acetate and sevelamer on vascular function and fibroblast growth factor 23 in CKD patients: a randomized clinical trial.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) is a marker of endothelial dysfunction and atherosclerotic complications in patients with chronic kidney disease (CKD). Because previous studies suggested that sevelamer may exert effects on FGF-23 level and endothelial function independently of its phosphate-lowering action, we tested the effect of sevelamer versus calcium acetate on vascular function and FGF-23 levels. STUDY DESIGN: Randomized prospective open-label trial. SETTING & PARTICIPANTS: Patients with stage 4 CKD with hyperphosphatemia (n = 100). INTERVENTION: An 8-week intervention with sevelamer (n = 47) and calcium acetate (n = 53). OUTCOMES: The primary study outcome was change in flow-mediated vasodilatation in the forearm. The secondary outcome was change in FGF-23 levels. RESULTS: Serum phosphate levels decreased in both treatment arms (P < 0.001), but more markedly in the sevelamer group (P < 0.001). Flow-mediated vasodilatation increased from 6.1% to 7.1% (P < 0.001) in sevelamer-treated patients, whereas it was unchanged in the calcium-acetate group (6.0% vs 6.0%). In a combined analysis, treatment-induced changes in flow-mediated vasodilatation were (P < 0.001) associated with simultaneous changes in FGF-23 levels (-27.1% [-33.2% to -8.8%] for the sevelamer group; 3.5% [-8.4% to 12.1%] for the calcium acetate group), as well as with C-reactive protein and fetuin A levels. These relationships were confirmed in multiple regression analysis adjusting for changes in serum phosphate levels and other factors. LIMITATIONS: Unblinded randomized controlled study that cannot establish mechanisms of effect. CONCLUSIONS: In hyperphosphatemic patients with stage 4 CKD, treatment with phosphate lowering induces measurable improvements in flow-mediated vasodilatation. Furthermore, independently of serum phosphate level, FGF-23 level changes induced by phosphate binders are associated with simultaneous changes in flow-mediated vasodilatation. These observations are compatible with the hypothesis that FGF-23 may contribute to vascular dysfunction in this population.

Relationship between serum magnesium levels and cardiovascular events in chronic kidney disease patients.

BACKGROUND: Magnesium is an essential ion for all living cells because over 300 enzymes require the presence of magnesium for their catalytic action. To date, no group has evaluated magnesium as a cardiovascular risk factor in chronic kidney disease (CKD) subjects, in which closely interrelated factors and potential confounders such as endothelial dysfunction, insulin resistance (the homeostasis model assessment (HOMA) index) and inflammation (expressed as serum C-reactive protein (CRP) levels) were also considered. METHODS: Between March 2006 and December 2010, 283 CKD patients were followed up for time-to-event analysis until the occurrence of fatal or nonfatal cardiovascular events. Endothelium-dependent vasodilatation (flow-mediated dilatation; FMD) and endothelium-independent vasodilatation (nitroglycerin-mediated dilatation) of the brachial artery were assessed noninvasively using high-resolution ultrasound. RESULTS: From the univariate analysis of FMD, it appears that a higher magnesium level is associated with less endothelial dysfunction. When a multivariate analysis was performed, magnesium and estimated glomerular filtration rates (eGFR) maintained a strong positive correlation with FMD, supporting the hypothesis that higher levels of magnesium may protect against endothelial damage. In univariate Cox proportional hazards models, FMD, magnesium, high sensitivity CRP, the HOMA index, eGFR, comorbid diabetes, hypertension, smoking status, systolic blood pressure, serum phosphate and intact parathormone emerged as significant predictors for cardiovascular outcomes. Kaplan-Meier curves showed significantly higher cardiovascular mortality rates in CKD patients whose serum magnesium levels were below 2.05 mg/dl. CONCLUSIONS: This observational cohort study showed that magnesium may be an independent predictor of future cardiovascular outcomes and is the first study demonstrating such a role in etiologically diagnosed CKD patients, across different stages.

Effect of the arterial needle bevel position on puncture pain and postremoval bleeding time in hemodialysis patients: A self-controlled, single-blind study.

AIM: This study aimed to investigate the effect of the bevel orientation (facing upwards or downwards towards the skin) of the needle inserted into the arterial limb of the arteriovenous fistula (AVF) on puncture pain and postremoval bleeding time. METHODS: This study, using a single-blind crossover design, was conducted on 35 maintenance hemodialysis patients who had been dialyzed for at least 6 months and in whom blood access was via an AVF. AVF cannulation was performed with the needle bevel pointing upward in the first six sessions and the needle bevel pointing downwards (towards the skin) in the subsequent six sessions. Needles were always inserted in the direction of blood flow. At each dialysis session, cannulation pain was measured using a visual analog scale (VAS), and the bleeding time at the end of dialysis after needle removal was recorded. FINDINGS: The VAS score and postremoval bleeding time were lower when the needle bevel pointed downwards towards the skin during insertion (P < 0.05). DISCUSSION: Insertion of the needle with the bevel pointed downward decreased puncture pain during cannulation and bleeding time postdialysis on needle removal.

Low triiodothyronine alters flow-mediated vasodilatation in advanced nondiabetic kidney disease.

BACKGROUND/AIMS: Subclinical or frank hypothyroidism is causally implicated in endothelial dysfunction. Since the plasma concentration of the active form of thyroid hormone, triiodothyronine (T3), is reduced in chronic kidney disease (CKD), where endothelial function is frequently altered, low T3 may be a factor implicated in this disturbance in CKD patients. METHODS: We investigated the relationship between flow-mediated vasodilatation (FMD) and thyroid hormones in a series of 217 nondiabetic patients with stage 3-4 CKD. RESULTS: The plasma concentration of free T3 (fT3) was closely associated with FMD (r = 0.38; p < 0.001). fT3 was also inversely associated with hemoglobin (r = -0.41; p < 0.001), systolic pressure (r = -0.28; p < 0.001) and the plasma concentration of the endogenous inhibitor of NO synthase, asymmetric dimethylarginine (ADMA; r = -0.18; p = 0.007). However, adjustment for ADMA markedly attenuated the fT3-FMD link, a phenomenon suggesting that raised plasma ADMA, possibly driven by low fT3, at least in part mediates the adverse effects of low T3 on endothelial function in CKD. CONCLUSIONS: Low T3 in patients with moderate-to-severe CKD is a marker of endothelial dysfunction. This study sets a solid rationale for designing specific intervention studies aimed at clarifying the nature (causal or not causal) of the endothelial function-T3 link in CKD.

Vascular health, systemic inflammation and progressive reduction in kidney function; clinical determinants and impact on cardiovascular outcomes.

INTRODUCTION: Systemic inflammation, endothelial dysfunction and arterial thickening contribute to the elevated cardiovascular risk of dialysis patients. However, the course of these derangements and their relative contribution to the cardiovascular risk of nondialysed chronic kidney disease (CKD) are scarcely investigated. METHODS: Flow-mediated dilatation (FMD) and intima-media thickness (IMT) were assessed in 304 nondialysed CKD patients Stages 1-5 (mean age 46 ± 12 years, 158 men), together with routine biochemical measurements, C-reactive protein (CRP) and insulin resistance. Patients were then followed for time-to-event analysis of cardiovascular outcomes (fatal and nonfatal). RESULTS: CRP and IMT increased, while FMD decreased in parallel with estimated glomerular filtration rate (eGFR) decline (P < 0.001 for all). CRP and intact parathormone, as well as eGFR, appeared as strong determinants of FMD and IMT in multivariate analyses. After a median follow-up of 41 (range 6-46) months, 30 fatal and 59 nonfatal cardiovascular events occurred. In univariate analysis, FMD, IMT and CRP were significant predictors of outcome. In a multivariate Cox model excluding IMT, both FMD [hazard ratios 0.52 (95% confidence intervals 0.37-0.73) per %] and CRP [1.07 (1.03-1.11) per mg/L] predicted cardiovascular outcomes independently of confounders. In a model excluding FMD, only CRP (and not IMT) was a significant predictor. CONCLUSIONS: Endothelial dysfunction, arterial thickening and inflammation occur in parallel with the decline in eGFR, contributing to the increased cardiovascular risk of nondialysed CKD. Our results support the use of FMD over IMT measurements to monitor nondialysed CKD patients at risk.

Diffuse alveolar hemorrhage as an unusual presentation of systemic lupus erythematosus.

Diffuse alveolar hemorrhage (DAH) is rarely seen in patients with systemic lupus erythematosus (SLE), often associated with a poor outcome. It almost affects young women and it is an unusual initial manifestation of SLE. We report a case of SLE presenting with DAH. The patient was a male. He had no history of photosensitivity, malar rash, discoid rash, arthritis, and oral ulcer. Antinuclear antibody, and anti-double stranded DNA (dsDNA) were positive with very high titers, and serum complement levels (C3, C4) were low. He also had renal dysfunction and pericardial effusion. He was diagnosed as DAH due to SLE. He had to undergo hemodialysis for several weeks. DAH and renal dysfunction were improved with intensive treatment including corticosteroid, cyclophosphamide, and mycophenolate mophetil.

FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease.

Studies in animals show that fibroblast growth factor (FGF)-23 interferes with vascular reactivity induced by the nitric oxide (NO) system. To investigate the relationship between circulating FGF-23 levels and the response of forearm blood flow to ischemia (flow-mediated vasodilatation, FMD) and nitroglycerin, we tested 183 patients with stage 3-4 chronic kidney disease (CKD). None of them had cardiovascular complications or were taking drugs interfering with vascular function. Patients with FGF-23 levels above the median had significantly lower glomerular filtration rate, FMD, and fetuin-A levels (an anti-inflammatory molecule and potent inhibitor of calcification). They also had higher proteinuria and phosphate levels when compared to patients whose FGF-23 levels were below the median. The response to nitroglycerin was not different between the two groups. Multiple regression analysis showed that the relationship between FGF-23 and FMD was only modestly sensitive to adjustment for classical risk factors, biomarkers of bone mineral metabolism, high-sensitivity C-reactive protein, and homeostatic model assessment index. Adjustment for asymmetrical dimethyl arginine (ADMA) weakened the strength of this link; however, it remained highly significant. There was no independent association between FGF-23 and nitroglycerin. Thus, attenuation of FMD by ADMA suggests that this endogenous inhibitor of NO synthase may, in part, mediate the vascular effects of FGF-23 in patients with CKD.

Predictors of carotid artery intima-media thickness in chronic kidney disease and kidney transplant patients without overt cardiovascular disease.

BACKGROUND/AIMS: Carotid intima-media thickness (IMT) assessed using ultrasonography is a widely used marker of atherosclerosis. In the largest study to date of IMT and chronic kidney disease (CKD), we assessed correlates of IMT in CKD patients with a wide range of renal dysfunction, and also investigated what happens to IMT following renal transplantation. METHODS: We studied 406 patients with different stages of nondiabetic CKD (50% males, 46 +/- 12 years), and 58 kidney transplant recipients (27 +/- 6 years), testing relationships between IMT, assessed by ultrasonography, and selected biomarkers. RESULTS: Despite a lack of overt CVD, patients had significantly higher IMT as compared to controls (0.9 [0.7-1.0] vs. 0.6 [0.4-0.7] mm; p > 0.001). Furthermore, in multivariate analysis IMT was independently associated with CKD stage, mean arterial pressure (MAP) and calcium-phosphate product, but not with Framingham risk factors. Following kidney transplantation, IMT decreased rapidly, reaching levels comparable to those in the controls within 90 days. In a time-dependent multivariate analysis, this decrease was predicted by changes in GFR, MAP, and uric acid levels. CONCLUSION: Our data does not exclude IMT as a predictor of mortality in CKD, but suggests that other etiologies than atherosclerosis may be more important in determining IMT levels in the population with CKD.

Reduced proteinuria using ramipril in diabetic CKD stage 1 decreases circulating cell death receptor activators concurrently with ADMA. A novel pathophysiological pathway?

BACKGROUND: Renin-angiotensin system (RAS) blockade improves proteinuria and the endothelial functions in diabetic nephropathy. Plasma asymmetric dimethylarginine (ADMA), abundant in the cell than in the plasma, is also improved by RAS blockage. We hypothesized that RAS blockade may reduce ADMA by reducing injurious cell death. METHODS: In a hypothesis-generating study, we assessed circulating levels of apoptotic signalling peptides in incident chronic kidney disease (CKD) stage 1 patients (aged >18 years with diabetes mellitus type 2 as the only cause of nephropathy) not previously prescribed statins or RAS blockade. Ninety-three (29 M, 47 ± 5 years) patients with CKD 1 diabetic nephropathy and 38 healthy subjects (20 M, 47 ± 5 years) were enrolled. Ramipril was given (5 mg daily for 12 weeks), and circulating ADMA, soluble Fas (sFas), myostatin and endothelial function [flow-mediated vasodilation (FMD); ultrasound)] were measured. RESULTS: After the study, ADMA, sFas, myostatin, insulin resistance, high-sensitive C-reactive protein (hsCRP), estimated glomerular filtration rate (eGFR), blood pressure and proteinuria levels were decreased, and FMD and serum albumin levels increased (P < 0.05 for all). ADMA and sFas levels were independently related to FMD levels both before (rho = -0.33; P < 0.005 and rho = -0.26; P < 0.02, respectively) and after (rho = -0.39; P < 0.001 and rho = -0.28; P < 0.002, respectively) ramipril treatment. Changes in sFas and ADMA were related to the change in FMD (-0.32; P > 0.004 and -0.31; P < 0.004, respectively). CONCLUSION: A reduction of proteinuria in CKD 1 diabetic kidney disease is accompanied by lower circulating sFas, myostatin and ADMA, suggesting that increased cell death may contribute to ADMA formation and endothelial dysfunction in diabetic CKD.