Recurrence of Idiopathic Membranous Nephropathy in the Kidney Allograft: A Systematic Review.

INTRODUCTION: The recurrence of idiopathic membranous nephropathy (iMN) after kidney transplantation is common, although its exact clinical significance remains unclear. This systematic review aims to elucidate the effects of iMN recurrence on graft survival. MATERIALS AND METHODS: A literature search was performed by systematically searching Medline, Scopus, Web of Science, and Google Scholar from inception. Cohort studies examining iMN recurrence after kidney transplantation were deemed eligible. Meta-analysis was performed by fitting random-effects models. RESULTS: Twelve (12) articles published from 1995 to 2016 reporting on 139 transplant patients with recurrent iMN were included. The median time of the diagnosis of recurrent iMN was 18 months during follow-up from 35 to 120 months. Risk factors for iMN recurrence in the renal allograft are a positive serum test for anti-PLA2R antibodies pretransplant, female sex, younger age, high proteinuria pretransplant, the longest interval from initial disease to end-stage chronic kidney disease, and the combination of alleles HLA DQA1 05:01 and HLA DQB1 02:01. In the pretransplant period, 37 (26.61%) patients had a positive serum test and 18 (12.94%) patients had a positive biopsy stain for anti-PLA2R antibodies. The sensitivity of the pretransplant positive serum test for these antibodies ranges from 57% to 85.30% and the specificity is 85.10-100%. A total of 81.80% of patients who received rituximab as treatment for iMN recurrence achieved complete and partial remission, while 18.20% had no response to treatment. iMN recurrence was not associated with significantly different rates of graft loss (odds ratio = 1.03, 95% CI: 0.52-2.04, p = 0.524, I2 = 0.00%). Recurrence of iMN was not associated with increased risk of graft loss independently of whether patients were treated with rituximab (OR: 0.98, 95% CI: 0.39-2.50, I2: 0%) or not (OR: 1.22, 95% CI: 0.58-2.59, I2: 3.8%). Patients with iMN recurrence who achieved remission had significantly reduced risk of graft loss (OR: 0.14, 95% CI: 0.03 to 0.73). CONCLUSION: The main outcome from this systematic review is that there is no statistically significant difference in graft survival in patients with iMN recurrence compared to those without recurrence in long-term follow-up. The achievement of remission is associated with significantly reduced risk of graft loss.

Results of a hemodialysis vascular access routine ultrasound surveillance protocol and frequency of surveillance guided pre-emptive access maintenance interventions.

BACKGROUND: To evaluate the implementation of routine surveillance using ultrasound on hemodialysis vascular access (VA) outcomes and determine the number and frequency of corrective, surveillance-guided procedures performed. METHODS: Multicenter, prospective, observational study that includes consecutive hemodialysis patients receiving therapy from native arteriovenous fistulae (AVF) or grafts (AVG). Participants were assigned to a routine VA Color Doppler ultrasound surveillance (DUS) protocol from January 2019 to December 2021. Patients were referred for corrective procedures (endovascular or surgical) based on clinical or DUS findings (pre-emptive procedures; PEP). Primary endpoint was the estimation of primary unassisted (PUP) and secondary patency (SP) rates. Secondary endpoints were the determination of the number and frequency of PEP and VA survival rates. RESULTS: In total, 223 patients with 243 VA (192 AVF and 51 AVG) were included. Access PUP and SP rates were 83% and 93% at 12 months, 75% and 88% at 24 months, and 72% and 83% at 36 months follow-up. Autologous fistulae PUP and SP were 89% and 96% at 12 months, 81% and 93% at 24 months, and 80% and 89% at 36 months, respectively. Graft PUP and SP were 56% and 80% at 12 months, 44% and 65% at 24 months, and 39% and 54% at 36 months, respectively. In total, 56 corrective procedures (38/56 PEP; 65.5%) were performed (0.13 procedures/year), of which 34 were in AVF patients (0.09 procedures/year) and 22 in AVG patients (0.40 procedures/year). Overall, 33 VA losses occurred (0.06 failures/year), 17 in AVF (0.04 failures/year), and 16 in AVG patients (0.20 failures/year). CONCLUSION: The use of DUS resulted in the timely diagnosis of dysfunction, satisfactory overall VA survival, and patency rates, with a low PEP frequency. Randomized controlled trials are required to establish the value of DUS surveillance on access patency and whether DUS-guided interventions could improve VA outcomes.

Dialysis Patients Respond Adequately to Influenza Vaccination Irrespective of Dialysis Modality and Chronic Inflammation.

(1) Background: Chronic inflammation and suboptimal immune responses to vaccinations are considered to be aspects of immune dysregulation in patients that are undergoing dialysis. The present study aimed to evaluate immune responses in hemodialysis (HD) and online hemodiafiltration (OL-HDF) patients to a seasonal inactivated quadrivalent influenza vaccine (IQIV). (2) Methods: We enrolled 172 chronic dialysis patients (87 on HD and 85 on OL-HDF) and 18 control subjects without chronic kidney disease in a prospective, cross-sectional cohort study. Participants were vaccinated with a seasonal IQIV, and antibody titers using the hemagglutination inhibition (HI) assay were determined before vaccination (month 0) and 1, 3, and 6 months thereafter. Demographics and inflammatory markers (CRP, IL-6, IL-1ß) were recorded at month 0. The primary endpoints were the rates of seroresponse (SR), defined as a four-fold increase in the HI titer, and seroprotection (SP), defined as HI titer ≥ 1/40 throughout the study period. Statistical analyses were conducted in R (version 3.6.3) statistical software. The differences between groups were analyzed using chi-square and t-test analyses for dichotomous and continuous variables, respectively. To identify independent determinants of SR and SP, generalized linear models were built with response or protection per virus strain as the dependent variable and group, age, sex, time (month 0, 1, 3, 6), diabetes, IL-6, dialysis vintage, HD access, and HDF volume as independent explanatory variables. (3) Results: SR and SP rates were similar between control subjects, and dialysis patients were not affected by dialysis modality. SP rates were high (> 70%) at the beginning of the study and practically reached 100% after vaccination in all study groups. These results applied to all four virus strains that were included in the IQIV. IL-6 levels significantly differed between study groups, with HD patients displaying the highest values, but this did not affect SP rates. (4) Conclusions: Dialysis patients respond to influenza immunization adequately and similarly to the general population. Thus, annual vaccination policies should be encouraged in dialysis units. OL-HDF reduces chronic inflammation; however, this has no impact on SR rates.

The Prognostic Role of Automated Office Blood Pressure Measurement in Hypertensive Patients with Chronic Kidney Disease.

BACKGROUND: The aim of this study was to evaluate the prognostic value of automated office blood pressure (AOBP) measurement in patients with hypertension and chronic kidney disease (CKD) stage 3-5 not on dialysis. METHODS: At baseline, 140 patients were recruited, and blood pressure (BP) measurements with 3 different methods, namely, office blood pressure (OBP), AOBP, and ambulatory blood pressure measurement (ABPM), were recorded. All patients were prospectively followed for a median period of 3.4 years. The primary outcome of this study was a composite outcome of cardiovascular (CV) events (both fatal and nonfatal) or a doubling of serum creatine or progression to end-stage kidney disease (ESKD), whichever occurred first. RESULTS: At baseline, the median age of patients was 65.2 years; 36.4% had diabetes; 21.4% had a history of CV disease; the mean of estimated glomerular filtration rate (eGFR) was 33 mL/min/1.73 m2; and the means of OBP, AOBP, and daytime ABPM were 151/84 mm Hg, 134/77 mm Hg, and 132/77 mm Hg, respectively. During the follow-up, 18 patients had a CV event, and 37 patients had a renal event. In the univariate cox regression analysis, systolic AOBP was found to be predictive of the primary outcome (HR per 1 mm Hg increase in BP, 1.019, 95% CI 1.003-1.035), and after adjustment for eGFR, smoking status, diabetes, and a history of CV disease and systolic and diastolic AOBP were also found to be predictive of the primary outcome (HR per 1 mm Hg increase in BP, 1.017, 95% CI 1.002-1.032 and 1.033, 95% CI 1.009-1.058, respectively). CONCLUSIONS: In patients with CKD, AOBP appears to be prognostic of CV risk or risk for kidney disease progression and could, therefore, be considered a reliable means for recording BP in the office setting.

Myasthenia gravis genome-wide association study implicates AGRN as a risk locus.

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disorder affecting the neuromuscular junction (NMJ). Here, we investigate the genetic architecture of MG via a genome-wide association study (GWAS) of the largest MG data set analysed to date. METHODS: We performed GWAS meta-analysis integrating three different data sets (total of 1401 cases and 3508 controls). We carried out human leucocyte antigen (HLA) fine-mapping, gene-based and tissue enrichment analyses and investigated genetic correlation with 13 other autoimmune disorders as well as pleiotropy across MG and correlated disorders. RESULTS: We confirmed the previously reported MG association with TNFRSF11A (rs4369774; p=1.09×10-13, OR=1.4). Furthermore, gene-based analysis revealed AGRN as a novel MG susceptibility gene. HLA fine-mapping pointed to two independent MG loci: HLA-DRB1 and HLA-B. MG onset-specific analysis reveals differences in the genetic architecture of early-onset MG (EOMG) versus late-onset MG (LOMG). Furthermore, we find MG to be genetically correlated with type 1 diabetes (T1D), rheumatoid arthritis (RA), late-onset vitiligo and autoimmune thyroid disease (ATD). Cross-disorder meta-analysis reveals multiple risk loci that appear pleiotropic across MG and correlated disorders. DISCUSSION: Our gene-based analysis identifies AGRN as a novel MG susceptibility gene, implicating for the first time a locus encoding a protein (agrin) that is directly relevant to NMJ activation. Mutations in AGRN have been found to underlie congenital myasthenic syndrome. Our results are also consistent with previous studies highlighting the role of HLA and TNFRSF11A in MG aetiology and the different risk genes in EOMG versus LOMG. Finally, we uncover the genetic correlation of MG with T1D, RA, ATD and late-onset vitiligo, pointing to shared underlying genetic mechanisms.

Variants in clock genes could be associated with lower risk of type 2 diabetes in an elderly Greek population.

OBJECTIVES: Recent evidence has linked circadian rhythm dysregulation to an increased risk of metabolic disorders. This study explores a potential association between variation in genes regulating the endogenous circadian timing system (clock genes) and the risk of type 2 diabetes (T2D) in a sample of Greek elderly people. STUDY DESIGN: Variants within and upstream or downstream of PPARA, PPARD, CLOCK/TMEM165, PER1, PER2 and PER3 genes were genotyped in 716 individuals with T2D (A) and 569 normoglycemic controls (B), and allele frequencies were compared between the groups in a case control study design. MAIN OUTCOME MEASURES: Samples were genotyped on Illumina Human PsychArray. Permutation test analysis was implemented to determine statistical significance. To avoid the possibility of subjects with prediabetes being included in the control group, people with HbA1c <5.7% and fasting glucose <100 mg/dl comprised group C (n = 393), for whom a separate analysis was performed (secondary analysis). RESULTS: A protective role against T2D was identified for 14 variants in the PPARA gene. The rs7291444, rs36125344, rs6008384 in PKDREJ, located upstream of PPARA, and rs2859389 in UTS2, located upstream of PER3, demonstrated a protective role against T2D in both analyses. In contrast, rs6744132, located between HES6 and PER2, was positively correlated with T2D risk. Only in the secondary analysis, rs2278637 in VAMP2, located downstream of PER1, and rs11943456 in CLOCK/TMEM165 were found to confer protection against T2D. In a recessive model analysis of all groups, PPARD variants exhibited a protective role against disease. CONCLUSIONS: Our findings suggest a possible implication of clock genes in T2D susceptibility. Further studies are needed to clarify the mechanisms that connect circadian rhythm dysfunction and T2D pathogenesis.

Genetic variation in CARD8, a gene coding for an NLRP3 inflammasome-associated protein, alters the genetic risk for diabetic nephropathy in the context of type 2 diabetes mellitus.

BACKGROUND: Approximately one third of type 2 diabetes mellitus (T2DM) cases present with diabetic nephropathy (DN), the leading cause of end-stage renal disease. Inflammation plays an important role in T2DM disease and DN pathogenesis. NLRP3 inflammasomes are complexes that regulate interleukin-1B (IL-1B) and IL-18 secretion, both involved in inflammatory responses. Activation of NLRP3 is associated with DN onset and progression. Here, we explore whether DN is associated with variants in genes encoding key members of the NLRP3 inflammasome pathway. METHODS: Using genome-wide association data, we performed a pilot case-control association study, between 101 DN-T2DM and 185 non-DN-T2DM cases from the Hellenic population across six NLRP3 inflammasome pathway genes. RESULTS: Three common CARD8 variants confer decreased risk for DN, namely rs11665831 (OR = 0.62, p = 0.016), rs11083925 (OR = 0.65, p = 0.021), and rs2043211 (OR = 0.66, p = 0.026), independent of sex or co-inheritance with an IL-1B variant. CONCLUSION: CARD8 acts as an NLRP3, NF-κB and caspase-1 inhibitor; perhaps, alterations in the cross-talk between CARD8, NF-κB, and NLRP3, which could affect the pro-inflammatory environment in T2DM, render diabetic carriers of certain common CARD8 variants potentially less likely to develop T2DM-related pro-inflammatory responses followed by DN. These preliminary, yet novel, observations will require validation in larger cohorts from several ethnic groups.

Reversed connection of cuffed, tunneled, dual-lumen catheters with increased blood flow rate maintains the adequacy of delivered dialysis despite the higher access recirculation.

PURPOSE: Reversing the connection mode of permanent dual-lumen dialysis catheters results in higher access recirculation that may compromise the dialysis adequacy. The purpose of this study is to investigate the effect of reversed-connected dialysis with a higher versus a standard blood flow rate (Qb) on adequacy parameters and access recirculation. MATERIALS AND METHODS: In a cross-over design, 46 prevalent dialysis patients with a properly functioning cuffed, tunneled, dual-lumen catheter were evaluated in three consecutive mid-week dialysis sessions. At baseline, participants were evaluated under standardized conditions (correct connection, Qb = 300 ml/min). In Phase A, dialysis was performed with reversed connection and Qb = 300 ml/min. In Phase B, dialysis was performed with reversed connection and Qb = 400 ml/min. The sequence of evaluations (Phase A and B or vise verse) was randomized. All other dialysis-related parameters were unchanged in all three occasions. RESULTS: As expected, compared with baseline, reversed-connected dialysis in Phase A resulted in lower URR and spKt/V, and in a higher recirculation rate. Compared with baseline, reversed-connected dialysis with a higher Qb in Phase B resulted in an even higher recirculation rate, but the parameters of dialysis adequacy were not different. Increase in Qb from 300 to 400 ml/min resulted in an improvement of the dialysis adequacy (URR: 64.1 ± 7.8% vs. 70.6 ± 8.2%, P < 0.001; spKt/V: 1.22 ± 0.3 vs. 1.45 ± 0.3, P < 0.001) despite the higher recirculation rate. CONCLUSION: This study suggests that reversed-connected dialysis with increasing Qb maintains the adequacy of the delivered dialysis despite the compensatory increase in recirculation.

Glomerular expression of matrix metalloproteinases in systemic lupus erythematosus in association with activity index and renal function.

PURPOSE: The aim of this study was to examine the expression of matrix metalloproteinases (MMPs) MMP-1, MMP-2, MMP-3, MMP-9, and their specific tissue inhibitor TIMP-1 in kidney biopsies of patients with lupus nephritis (LN) and to investigate the relationship between MMPs, activity index, and renal function at the time of kidney biopsy. METHODS: We performed immunohistochemistry with monoclonal antibodies against MMP-1, MMP-2, MMP-3, MMP-9, and TIMP-1 in 58 kidney-biopsy specimens with LN (according to the 2004 ISN/RPS classification) and eight specimens from normal kidney tissue. We used clinical data of 36 patients at the time of kidney biopsy to evaluate the association between MMPs expression and renal function. RESULTS: We found increased MMP-1, MMP-2, and MMP-3 expression in LN glomeruli and a significant correlation with the activity features, with higher activity index score and worse renal function (p < .001). In particular, we have noticed a significant correlation of MMP-1 with leukocyte influx (OR:16.5 95%CI 4.3-62.5 p < .001), and MMP-3 with glomerular hypercellularity (OR:18.6 95%CI 4.8-72.8 p < .001). Moreover, we found a strong correlation of MMP-2 expression with fibrinoid necrosis and cellular crescents formation (OR:17.1 95%CI 4.3-67.7 p < .001). CONCLUSIONS: MMP expression in renal biopsy of patients with LN is increased and directly related to a highly active inflammatory response. Moreover, stronger MMP expression is associated with higher activity index and a more profound renal dysfunction.

Endovascular Repair of an Inadvertent Right Vertebral Artery Rupture during Dialysis Catheter Insertion.

Central venous (CV) catheterization is not only an invaluable diagnostic modality but also an essential therapeutic tool for the treating physician, enabling rapid and reliable intravenous administration of drugs and fluids, providing venous access to patients undergoing long-term continuous or repeated intravenous treatment such as chemotherapy, or it can be used for hemodialysis in patients suffering from acute or chronic renal disease. On the other hand, CV catheterization can lead to a wide range of life-threatening complications for the patient especially if left untreated or become late-diagnosed. In particular, arterial injuries are among the most feared complications that require early clinical suspicion for prompt diagnosis and management. We report the case of a 79-year-old female dialysis patient who suffered from a vertebral artery (VA) injury complicated by a herald bleeding on the third postintervention day after an internal jugular vein dialysis catheter replacement. The patient initially presented neurological signs of a stroke and urgently treated endovascularly after immediate diagnosis of VA rupture was made. Imaging techniques are evidence-based tools that help minimize these mechanical complications, including inadvertent arterial puncture and therefore should be practiced and taught in training programs to avoid the potentially devastating consequences of CV catheterization.

Association of ALOX12 gene polymorphism with all-cause and cardiovascular mortality in diabetic nephropathy.

PURPOSE: Cardiovascular (CV) events are the first cause of death in patients with chronic renal disease (CKD) and in patients with type 2 diabetes mellitus (DM2). The combination of CKD and DM2 elevates the risk of both cardiovascular disease (CVD) and death in this high-risk population. Besides traditional risk factors, such as dyslipidemia, smoking, obesity, and carotid atherosclerosis, novel factors are under investigation such as genetic polymorphisms. Lipoxygenases (LOXs) and their genes are of critical importance in oxidative stress, inflammation, and atherosclerosis. The aim of the study is to clarify a potential ALOX12 role in CVD presence and progress of diabetic patients in different stages of nephropathy. METHODS: We studied 145 patients with a documented history of DM2 for at least 10 years and diabetic nephropathy (DN), mean age 68 ± 9 years, body mass index 31 ± 5 kg/m2, and different stages of renal disease, depending on glomerular filtration rate. The sample population consisted of two groups: 108 DM2 patients with DN in all five stages of CKD and 37 DM2 patients as controls. Anthropometric and clinical characteristics, interview for history of previous CV event, and assessment of carotid intima-media thickness (cIMT) were recorded at baseline. All patients were genotyped for ALOX12 polymorphisms with focus on rs14309. Genotypes (AA, AG, and GG) were evaluated for any possible role in CVD, and grouping was performed on A genotype, which is the dominant model. All participants were followed over a period of 7 years, and the end points studied were all-cause mortality, CV mortality, and CV events. CV events were defined as myocardial infarction (MI), stroke, or peripheral artery disease. RESULTS: The GG genotype has been significantly associated with cIMT levels above 0.86 mm and with history of MI. Regarding the presence of an atherosclerotic plaque in either carotid artery, no significant association was found when the genotypes were assessed on their own. After grouping, though, GG genotype revealed a significant association between carotid plaque formation and atheromatosis. Kaplan-Meier analysis revealed that ALOX12 gene GG genotype predicted all-cause mortality, CV mortality, and CV events. Similarly, when AA and AG genotypes were grouped, Kaplan-Meier analysis showed that patients with GG genotype presented an even more significant higher all-cause mortality, CV mortality, and CV events compared with AA and AG genotypes combined. After adjustment for several traditional risk factors, multivariate Cox proportional hazard analysis showed that patients with the GG genotype had a significant higher risk of all-cause mortality, a threefold increase in CV mortality, and a twofold increased risk for CV events compared to patients with the AA or the AG genotype. CONCLUSION: ALOX12 rs14309 GG genotype expression was found to be significantly associated with MI, higher cIMT, increased CV events, CV, and overall mortality. This phenomenon could be partially explained by the increased platelet proaggregatory activity of AA products and the control they exert in thrombotic occurrence and plaque formation.

Matrix Gla protein T-138C polymorphism is associated with carotid intima media thickness and predicts mortality in patients with diabetic nephropathy.

AIMS: We sought to determine the predictive value of Matrix Gla Protein MGP T-138C polymorphism in relation to all-cause mortality, cardiovascular mortality and cardiovascular events in patients with diabetic nephropathy (DN). METHODS: MGP T-138C polymorphism was assessed in 40 diabetic patients without nephropathy and 118 patients at different stages of DN, including patients on hemodialysis. Measurement of carotid intima-media thickness (cIMT) was performed using real-time B-mode ultrasonography. Plasma levels of dephoshorylated uncarboxylated Matrix Gla Protein (dp-ucMGP) were determined in a subgroup of 67 patients by ELISA. Mortality and cardiovascular events were assessed during a 7year follow-up. RESULTS: TT homozygotes for the MGP T-138C polymorphism had higher values of cIMT compared to combined TC and CC genotypes (P=0.006) whereas no association was observed between cIMT and dp-ucMGP levels. MGP T-138C polymorphism was a strong independent predictor of cIMT (P<0.0001), after adjustment for several well-known atherosclerosis risk factors. Patients with TT genotype presented a significantly higher all-cause and cardiovascular mortality risk compared to patients with TC and CC genotypes (P=0.01 and P=0.04 respectively), after adjustment for several traditional risk factors. CONCLUSIONS: MGP T-138C polymorphism is a strong and independent predictor of increased cIMT as well as all-cause and cardiovascular mortality in DN patients.

Comparison of standard forearm prosthetic loop grafts to composite semiloop forearm grafts ("semi-grafts") in hemodialysis patients: A prospective study.

INTRODUCTION: To prospectively assess the performance of composite semiloop antebrachial grafts ("semi-grafts," SGs) in hemodialysis patients. METHODS: Eighty-five patients who received 67 loop antebrachial grafts (LG-group) and 25 antebrachial semigrafts (SG-group) were enrolled. SGs were defined as those originating from the brachial artery and anastomosed with the proximal mature mid-antebrachial cephalic vein. Cephalic vein length should be at least 10 cm in length and of ≥5 mm in diameter for inclusion in the SG-group. LG-group included all possible outflow vein options of minimum diameter 3 mm. Kaplan-Meier statistics was used for comparison of groups. FINDINGS: Main indication for a SG was a failing radiocephalic fistula with extensive distal cephalic vein stenosis not amenable to correction or failed after endovascular repair or requiring long interposition grafting. The mean follow-up period was 20.16 ± 22.6 and 29.6 ± 36.7 months for the LG- and SG-group, respectively (P = 0.14). Forty-two patients died during the follow-up. Primary patency (up to first intervention or failure) at 6 and 12 months for LG- vs. SG-group was 93.9% vs. 83.7% and 47% vs. 55.8% (P = 0.08). Secondary patency (up to abandonment) was 58.2% vs. 61.1% and 36% vs. 45.8% at 12 and 24 months (P = 0.18). Mortality at 48 months was 22.4% (LG-group) and 24% (SG-group) (P = 0.9). DISCUSSION: There was a trend toward better primary and secondary patency rates for the SGs especially in the long-term. This is a valuable option in selected patients that access surgeons and nephrologists should be aware of.

Comparison of multiple fluid status assessment methods in patients on chronic hemodialysis.

PURPOSE: Control of hydration status is an important constituent of adequate and efficient hemodialysis (HD) treatment. Nevertheless, there are no precise clinical indices for early recognition of small changes in fluid status of patients undergoing chronic hemodialysis therapy. This study aimed to evaluate and compare the widely used and reliable method of indexed inferior vena cava diameter (IVCDi) with established and more recently available techniques (bioelectrical impedance analysis [BIA], continuous blood volume monitoring [Crit-line], and the B-line score [BLS] with lung ultrasonography) for estimating the hydration status of patients on HD. METHODS: Fifty-three patients undergoing chronic HD thrice weekly were included in the study. Evaluation of hydration status methods (IVCDi, BLS, BIA, and Crit-line) was performed thrice weekly before and after HD. Receiver operating characteristic curve analysis was performed to evaluate the discriminative power of (methods) the BLS, BIA, and Crit-line for predicting over- and underhydration of patients, as determined by the reference method, IVCDi. RESULTS: BLS showed the most promising results in predicting overhydration, as determined by IVCDi, compared with BIA and Crit-line and presented a sensitivity of 77% and specificity of 74%. The accuracy of the BLS was higher than that of BIA (0.81 vs. 0.71, p = 0.032) and Crit-line (0.61, p = 0.001). BLS also showed more promising results in predicting underhydration, as determined by IVCDi, than BIA and Crit-line and presented a sensitivity of 78% and a specificity of 73%. The accuracy of the BLS was higher than that of BIA (0.83 vs. 0.76, p = 0.035) and Crit-line (0.50, p < 0.001). CONCLUSIONS: The BLS is a useful and easily performed technique that has recently become available for accurate evaluation of dry weight and fluid status in patients with end-stage renal disease undergoing chronic HD. This method might help recognize asymptomatic lung congestion in these patients.

Association of Plasma Adiponectin and Oxidized Low-Density Lipoprotein with Carotid Intima-Media Thickness in Diabetic Nephropathy.

AIMS: We sought to determine the association between levels of adiponectin and oxidized low-density lipoprotein (ox-LDL) in patients with diabetic nephropathy as well as their effect on carotid intima-media thickness (cIMT). METHODS: Adiponectin and ox-LDL were determined in 25 diabetic patients without nephropathy and 94 patients at different stages of diabetic nephropathy including subjects on hemodialysis. cIMT was measured using real-time B-mode ultrasonography. RESULTS: Plasma adiponectin levels increased significantly with severity of diabetic nephropathy (P = 0.002), on the contrary to ox-LDL which decreased with disease severity (P < 0.001). cIMT was significantly higher at late stages of diabetic nephropathy compared with early stages (P = 0.022). Adiponectin was a significant negative predictor of ox-LDL levels (ß = -5.45, P = 0.023), independently of confounding factors. There was no significant correlation between cIMT and adiponectin or ox-LDL either in the total sample population or according to disease staging. Cluster analysis showed that patients with the highest cIMT values, highest levels of adiponectin, and lowest levels of ox-LDL were included in one cluster and all assigned to stage 5 of diabetic nephropathy. CONCLUSIONS: There was no significant association between adiponectin or ox-LDL and cIMT and, therefore, other factors affecting this surrogate marker of cardiovascular disease in diabetic nephropathy should be sought.

Ambulatory aortic blood pressure, wave reflections and pulse wave velocity are elevated during the third in comparison to the second interdialytic day of the long interval in chronic haemodialysis patients.

BACKGROUND: Increased arterial stiffness and aortic blood pressure (BP) are independent predictors of cardiovascular outcomes in end-stage renal disease. The 3-day interdialytic interval is associated with elevated risk of cardiovascular morbidity and mortality in haemodialysis. This study investigated differences in ambulatory aortic BP and arterial stiffness between the second and third day of the long interdialytic interval. METHODS: Ambulatory BP monitoring with Mobil-O-Graph monitor (IEM, Stolberg, Germany) was performed in 55 haemodialysis patients during a 3-day interval. Mobil-O-Graph records oscillometric brachial BP and pulse waves and calculates aortic BP and augmentation index (AIx) as measure of wave reflections, and pulse wave velocity (PWV) as measure of arterial stiffness. RESULTS: Ambulatory aortic systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher during the third versus second interdialytic day (123.6 ± 17.0 versus 118.5 ± 17.1 mmHg, P < 0.001; 81.5 ± 11.8 versus 78 ± 11.9 mmHg, P < 0.001, respectively). Similar differences were noted for brachial BP. Ambulatory AIx and PWV were also significantly increased during the third versus second day (30.5 ± 9.9 versus 28.8 ± 9.9%, P < 0.05; 9.6 ± 2.3 versus 9.4 ± 2.3 m/s, P < 0.001, respectively). Differences between Days 2 and 3 remained significant when day-time and night-time periods were compared separately. Aortic SBP and DBP, AIx and PWV showed gradual increases from the end of dialysis session onwards. Interdialytic weight gain was a strong determinant of the increase in the above parameters. CONCLUSIONS: This study showed significantly higher ambulatory aortic BP, AIx and PWV levels during the third compared with the second interdialytic day. These findings support a novel pathway for increased cardiovascular risk during the third interdialytic day in haemodialysis.

Subcutaneous and total fat at L4-L5 and subcutaneous, visceral and total fat at L3-L4 are important contributors of fasting and postprandial adiponectin levels.

OBJECTIVES: Insulin resistance and central obesity have been implicated in the pathogenesis of hypoadiponectinemia in obesity. The aim of this study is to evaluate circulating post-prandial adiponectin in relation to glucose and insulin metabolism, indexes of insulin resistance and sensitivity and, indexes of body fat accumulation and distribution in obese men. METHODS: Twenty-eight non-diabetic men underwent an OGTT followed by an oral fat load and were studied at baseline and for 5 h post-prandially for serum adiponectin, glucose and insulin. Insulin resistance was estimated by Homeostasis model assessment (HOMA) and insulin sensitivity by Matsuda index. Body fat accumulation and distribution were evaluated by anthropometric indexes and multiple slices MRI of the abdomen and hip. RESULTS: Adiponectin was negatively correlated to insulin levels. Fasting and area under the curve (AUC) adiponectin levels were negatively correlated to HOMA (both p < 0.01) and positively to Matsuda index (both p < 0.05). Negative correlations between fasting adiponectin and total fat (r = -0.408, p < 0.05), AUC adiponectin and subcutaneous, visceral and total fat (r = -0.375, -0.413 and -0.475 respectively, all p < 0.05) at L3-L4 were found, and negative correlations between fasting adiponectin and subcutaneous (r = -0.402, p < 0.05) and total fat (r = -0.491, p < 0.05) and between AUC adiponectin and subcutaneous and total fat (r = -0.506 and -0.547, respectively, both p < 0.01) were present at L4-L5. CONCLUSIONS: Circulating adiponectin is inversely correlated to both visceral and subcutaneous fat in non-diabetic men, implying that both compartments are important for adiponectin levels. The best correlation is found at measurement site L4-L5.

Correlation of pre-existing radial artery macrocalcifications with late patency of primary radiocephalic fistulas in diabetic hemodialysis patients.

OBJECTIVE: The aim of this study was to evaluate the impact of pre-existing radial artery macrocalcification (Mönckeberg type of arteriosclerosis) on patency rates of radiocephalic fistulas (RCFs) in diabetic end-stage renal disease (ESRD) patients undergoing hemodialysis. METHODS: In this observational prospective study, the long-term patency rates (primary outcome measures) of RCFs in ESRD diabetics who had Mönckeberg radial (±brachial) artery disease (calcified [C] group) were compared with those obtained in ESRD diabetics who had healthy, noncalcified vessels before RCF construction (healthy [H] group). Vessel calcification was assessed by plain two-dimensional radiography. For inclusion in the C-group, uniform linear railroad track-type macrocalcifications of at least 6 cm in length, in the medial wall of the radial artery ipsilateral to RCF creation, were required. Patients were included in the H-group if the radial artery ipsilateral to the RCF creation was free of any macrocalcification, of either intima or media type. Any intimal-like plaque with irregular and patchy distribution was an exclusion criterion for both groups. Patients in both groups also were required to have suitable upper limb vascular anatomy on the basis of ultrasound imaging before RCF creation (cephalic vein of minimum diameter of 1.6 mm, without stenosis or thrombosis in all outflow areas, and radial artery of minimum diameter of 1.5 mm, without proximal hemodynamically significant stenosis). Secondary outcome measures included all-cause mortality. Kaplan-Meier statistics were used for comparison between groups. RESULTS: The arm radiograph at the site of possible fistula construction showed abnormality in 39 patients (C-group, 47 RCFs), whereas 33 patients had noncalcified ("healthy") vascular anatomy (H-group, 40 RCFs). Mean duration of the diabetic disease at the time of RCF creation was 8.9 ± 5.6 years (range, 2-25 years) for the H-group and 14 ± 9.9 years (range, 1-40 years) for the C-group (P = .018). The mean follow-up period for H-group and C-group was 51.9 ± 35.9 months (range, 0.1-126 months) and 26.1 ± 31.6 months (range, 0.1-144 months), respectively (P = .0006). Forty-four patients died during the follow-up period. Primary patency rates at 12, 24, 36, and 48 months for C-group vs H-group were 50.2% vs 80%, 36.5% vs 72.3%, 32.4% vs 67.9%, and 29.1% vs 59.3% (P = .0019). Respective values for secondary patency rates were 52.4% vs 87.5%, 40.9% vs 82.4%, 36.6% vs 78.1%, and 33.2% vs 72.8% (P = .00064). Patient survival rates at 24 and 48 months were 56.1% and 46.4% for C-group and 92.4% and 67.4% for H-group, respectively (P = .05). CONCLUSIONS: ESRD diabetics with radial artery Mönckeberg calcifications receiving RCFs had worse late clinical outcomes compared with ESRD diabetics with healthy distal arm vessels receiving the same access. The long-term benefit of RCFs may be lost in diabetics with extensively calcified vessels, and preferably the brachial artery should be used instead.

Validation of a new risk score to predict contrast-induced nephropathy after percutaneous coronary intervention.

Contrast-induced nephropathy (CIN) is a frequent, potentially lethal complication of percutaneous coronary interventions (PCIs). We prospectively validated the diagnostic performance of a simple CIN risk score in a large multicenter international cohort of patients who underwent PCI. About 2,882 consecutive patients treated with elective or urgent PCI were enrolled. A simple CIN risk score was calculated for all patients by allocating points according to a prespecified scale (pre-existing renal disease = 2; metformin use = 2; previous PCI = 1; peripheral arterial disease = 2; and injected volume of contrast medium ≥300 ml = 1). CIN was defined as an increase, compared with baseline, of serum creatinine by ≥25%, or by ≥0.5 mg/dl, 48 hours after PCI. CIN occurred in 15.7% of the study population. The predictive accuracy of the CIN risk score was good (c-statistic 0.741, 95% confidence interval 0.713 to 0.769). Receiver-operating characteristic analysis identified a score of ≥3 as having the best diagnostic accuracy. Examination of the performance of the proposed risk score using different definitions of CIN yielded a robust predictive ability. The score exhibited good discrimination (area under the curve ≥0.700) across all predefined subgroups of the study population. Compared with 2 previously published risk scores for CIN, our score demonstrated higher discriminative ability and resulted in a net reclassification improvement and an integrated discrimination improvement (p <0.001). In conclusion, the new risk score can easily be applied in the setting of urgent or elective PCI, allows for robust risk assessment and offers the potential to improve the peri-interventional management of patients at risk for CIN.

Differential effect of baseline adiponectin on all-cause mortality in hemodialysis patients depending on initial body mass index. Long-term follow-up data of 4.5 years.

OBJECTIVES: We sought to investigate the interaction of adiponectin levels and body mass index (BMI) for predicting all-cause mortality in a cohort of hemodialysis (HD) patients. DESIGN: Longitudinal, observational cohort study. SETTING: HD unit. SUBJECTS: Sixty patients (mean age: 64 ± 13 years, 39 men) with end-stage renal disease on maintenance HD followed up for 4.5 years represented the prospective study cohort. INTERVENTION: Associations between baseline plasma adiponectin levels and initial BMI with all-cause mortality were assessed taking into account the assumption of nonlinear correlations. The association between adiponectin, BMI, and serum levels of interleukin-10 (IL-10) and interleukin-6 (IL-6) with survival was determined cross-sectionally. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: Nonlinear survival modeling showed that there was a U-shaped association of BMI with all-cause mortality, whereas there was an inverse U-shaped association for plasma adiponectin levels. Using a BMI of 24 kg/m(2) as a cutoff, an interaction effect of BMI on the association between adiponectin and mortality was observed (P = .045). In participants with BMI ≥ 24 kg/m(2), each 15 µg/mL increase in plasma adiponectin levels was associated with a decreased hazard of death (hazard ratio: 0.57, 95% CI: 0.32 to 0.99) in unadjusted analysis. In HD patients with BMI < 24 kg/m(2), no significant association was observed between adiponectin and mortality (P = .989). Cross-sectional analysis showed that in the subgroup of patients in whom the protective effect of adiponectin was observed (BMI ≥ 24 kg/m(2)), a positive linear association existed between adiponectin and IL-10 levels (r = 0.345, P = .027) as well as a negative association with IL-6 levels (r = -0.322, P = .040). No association was observed in patients with BMI < 24 kg/m(2), neither with IL-10 nor with IL-6. CONCLUSIONS: Obesity possibly modifies the effect of adiponectin on all-cause mortality in HD patients, thus explaining the published conflicting results in recent literature regarding the association of plasma adiponectin levels and mortality in chronic kidney disease patients.