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

ObjectiveThe 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.MethodsIn 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.ResultsThe 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).ConclusionsESRD 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

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Phosphorus control in peritoneal dialysis patients

PubMedID: 18379539Hyperphosphatemia is independently associated with an increased risk of death among dialysis patients. In this study, we have assessed the status of phosphate control and its clinical and laboratory associations in a large international group of patients on chronic peritoneal dialysis (PD) treatment. This cross-sectional multicenter study was carried out in 24 centers in three different countries (Canada, Greece, and Turkey) among 530 PD patients (235 women, 295 men) with a mean±s.d. age of 55±16 years and mean duration of PD of 33±25 months. Serum calcium (Ca2+), ionized Ca2+, phosphate, intact parathyroid hormone (iPTH), 25-hydroxy vitamin D3, 1,25-dihydroxy vitamin D3, total alkaline phosphatase, and bone alkaline phosphatase concentrations were investigated, along with adequacy parameters such as Kt/V, weekly creatinine clearance, and daily urine output. Mean Kt/V was 2.3±0.65, weekly creatinine clearance 78.5±76.6 l, and daily urine output 550±603 ml day-1. Fifty-five percent of patients had a urine volume of &lt;400 ml day -1. Mean serum phosphorus level was 4.9±1.3 mg per 100 ml, serum Ca2+ 9.4±1.07 mg per 100 ml, iPTH 267±356 pg ml-1, ionized Ca2+ 1.08±0.32 mg per 100 ml, calcium phosphorus (Ca × P) product 39±19 mg2dl-2, 25(OH)D3 8.3±9.3 ng ml-1, 1,25(OH) 2D3 9.7±6.7 pg ml-1, total alkaline phosphatase 170±178 U l-1, and bone alkaline phosphatase 71±108 U l-1. While 14% of patients were hypophosphatemic, with a serum phosphorus level lower than 3.5 mg per 100 ml, most patients (307 patients, 58%) had a serum phosphate level between 3.5 and 5.5 mg per 100 ml. Serum phosphorus level was 5.5 mg per 100 ml or greater in 28% (149) of patients. Serum Ca2+ level was ?9.5 mg per 100 ml in 250 patients (49%), between 8.5 and 9.5 mg per 100 ml in 214 patients (40%), and lower than 8.5 mg per 100 ml in 66 patients (12%). Ca × P product was &gt;55 mg 2dl-2 in 136 patients (26%) and lower than 55 mg 2dl-2 in 394 patients (74%). Serum phosphorus levels were positively correlated with serum albumin (P&lt;0.027) and iPTH (P=0.001), and negatively correlated with age (P&lt;0.033). Serum phosphorus was also statistically different (P = 0.013) in the older age group (&gt;65 years) compared to younger patients; mean levels were 5.1±1.4 and 4.5±1.1 mg per 100 ml, respectively, in the two groups. In our study, among 530 PD patients, accepted uremic-normal limits of serum phosphorus control was achieved in 58%, Ca × P in 73%, serum Ca2+ in 53%, and iPTH levels in 24% of subjects. Our results show that chronic PD, when combined with dietary measures and use of phosphate binders, is associated with satisfactory serum phosporus control in the majority of patients. © 2008 International Society of Nephrology

C-Terminal Fragment of Agrin (CAF): A Novel Marker for Progression of Kidney Disease in Type 2 Diabetics

BACKGROUND Diabetes is the leading cause of CKD in the developed world. C-terminal fragment of agrin (CAF) is a novel kidney function and injury biomarker. We investigated whether serum CAF predicts progression of kidney disease in type 2 diabetics. METHODS Serum CAF levels were measured in 71 elderly patients with diabetic nephropathy using a newly developed commercial ELISA kit (Neurotune®). Estimated glomerular filtration rate (eGFR) and proteinuria in spot urine were assessed at baseline and after 12 months follow up. The presence of end stage renal disease (ESRD) was evaluated after 24 months follow-up. Correlation and logistic regression analyses were carried out to explore the associations of serum CAF levels with GFR, proteinuria, GFR loss and incident ESRD. Renal handling of CAF was tested in neurotrypsin-deficient mice injected with recombinant CAF. RESULTS We found a strong association of serum CAF levels with eGFR and a direct association with proteinuria both at baseline (r = 0.698, p<0.001 and r = 0. 287, p = 0.02) as well as after 12 months follow-up (r = 0.677, p<0.001 and r = 0.449, p<0.001), respectively. Furthermore, in multivariate analysis, serum CAF levels predicted eGFR decline at 12 months follow-up after adjusting for known risk factors (eGFR, baseline proteinuria) [OR (95%CI) = 4.2 (1.2-14.5), p = 0.024]. In mice, injected CAF was detected in endocytic vesicles of the proximal tubule. CONCLUSION Serum CAF levels reflect renal function and are highly associated with eGFR and proteinuria at several time points. Serum CAF was able to predict subsequent loss of renal function irrespective of baseline proteinuria in diabetic nephropathy. CAF is likely removed from circulation by glomerular filtration and subsequent endocytosis in the proximal tubule. These findings may open new possibilities for clinical trial design, since serum CAF levels may be used as a selection tool to monitor kidney function in high-risk patients with diabetic nephropathy

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-OGraph 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 &lt; 0.001; 81.5 ± 11.8 versus 78 ± 11.9 mmHg, P &lt; 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 &lt; 0.05; 9.6 ± 2.3 versus 9.4 ± 2.3 m/s, P &lt; 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. © The Author 2015. Published by Oxford University Press

Anthropometric, clinical and biochemical characteristics of patients with TD2M and CKD with stable (or increased) and with decreased GFR at one year follow-up.

<p>Continuous variables are presented as mean (S.D.) or median (interquartile range, IQR).</p><p>^a<i>P</i> values of Mann-Whitney <i>U</i> or one-way ANOVA test for differences of variables among patients with stable or decreased eGFR at one year follow-up.</p><p>* Statistical significance at the 0.05 level (two-tailed).</p><p>BMI, body mass index; HbA1c, glycosylated hemoglobin A1c; RAAS blockade, use of medicines affecting renin–angiotensin system; Crea T0, serum creatinine levels at timepoint 0 (baseline); Crea T1, serum creatinine levels at timepoint 1 (12 months); eGFR T0, estimated GFR assessed by the CKD-EPI formula at timepoint 0 (baseline); eGFR T1, estimated GFR assessed by the CKD-EPI formula at timepoint 1 (12 months); PU T0, Proteinuria assessed by protein to creatinine ratio at timepoint 0 (baseline); PU T1, Proteinuria assessed by protein to creatinine ratio at timepoint 1 (12 months); ΔGFR T0-T1, Algebric difference between eGFR at timepoint 1 and eGFR at timepoint 0; ΔPU T0-T1, Algebric difference between Proteinuria at timepoint 1 (12 months) and Proteinuria at timepoint 0 (baseline); ESRD, progression to end stage renal disease; Total-CAF, serum levels of C-terminal agrin fragment; Decreased GFR, patients with loss of eGFR ≥ 1 ml/min/1.73m² during the 12 month follow-up.</p><p>Anthropometric, clinical and biochemical characteristics of patients with TD2M and CKD with stable (or increased) and with decreased GFR at one year follow-up.</p