Evaluation of arteriovenous fistula maturation and early prediction of clinical eligibility, using ultrasound: The Fistula Maturation Evaluation (FAME) Study.

INTRODUCTION: The study of time-related alterations of ultrasound-determined parameters during maturation, and the assessment of time to hemodynamic maturation, enabling early prediction of clinical eligibility, of hemodialysis autologous arteriovenous fistulae (AVF). METHODS: This is an observational, prospective, study of only AVF-eligible patients referred for access creation, from 02/2019 to 02/2022 (ClinicalTrials.gov identifier: NCT0473687). Brachial artery diameter (dBA), access flow volume (FV), non-augmented efferent vein diameter (dEV), resistivity index (RI), and efferent vein total wall thickness (tEV), were assessed by ultrasound. Measurements were conducted daily in the first week and repeated on days 14, 21, 30, 60, and 90, postoperatively. The primary endpoint included the documentation of serial changes of flow and structural parameters related to AVF maturation in the first 90 days of the post-operative period and maturation early prediction. Secondary endpoints included the determination of factors affecting maturation. RESULTS: One hundred one participants (mean age, 67 ± 6 years; 76 males) were enrolled. Average dBA and FV reached maximum on day 60 (5.64 ± 0.85 mm) and 90 (1.172 ± 617 mL/min), respectively. Day 7 values of dBA (5.48 ± 0.73 mm) and FV (1.039 ± 531 mL/min) did not alter significantly during the follow-up period. Parameters indicative of clinical functionality, dEV (5.82 ± 0.90 mm) and tEV (0.493 ± 0.10 mm), reached approximately 90% of maximum (6.66 ± 1.42 mm and 0.526 ± 0.11 mm), by day 14. RI reached minimum on day 30 (0.46 ± 0.09), without significant changes after day 2 (0.48 ± 0.09, p = 0.284). A significant correlation was identified, between day 7 FV and day 60 dEV (r = 0.40, p = 0.0002). A FV cut-off value ⩾657.51 mL/min, on day 7, predicted successful fistula maturation with 85% sensitivity and 100% specificity. Multivariate analysis identified female gender, age >75, diabetes, and wrist access as independent predictors of decreased values of maturation parameters. CONCLUSION: Hemodynamic maturation is completed by the first postoperative week, while AVF is clinically functional, by the second. FV can be used for early prediction of maturation.

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.

Lower serum magnesium is a predictor of left ventricular hypertrophy in patients on dialysis.

PURPOSE: Left ventricular hypertrophy (LVH) represents one of the main risk factors for cardiovascular mortality in dialysis patients. Low serum magnesium Mg is related with increased mortality in general and dialysis population. Aim of our study was to evaluate the association of Mg with LVH and cardiac geometry in dialysis patients. METHODS: Hemodialysis (HD) and peritoneal dialysis (PD) patients from nine nephrology departments were included. Echocardiographic LVH was defined by LV mass index > 95 g/m2 in women and > 115 g/m2 in men. Four LV geometric patterns were defined: normal, concentric remodeling, eccentric LVH and concentric LVH. Demographic and laboratory data were collected. RESULTS: 133 patients (68 HD, 65 PD) with a median age of 63 years (IQR 52-74) were studied. Mg correlated positively with creatinine, HDL and negatively with CRP levels and BMI. There were no significant differences in Mg between the modality groups. 80 patients presented LVH (43 HD and 37 PD patients). Patients with LVH were older (median age 68 vs 55 years, p < 0.001), with higher BMI (median 26.9 vs 24.7 kg/m2, p = 0.009), had a history of PVD or CAD (55% vs 30.2%, p = 0.003), had higher pulse pressure (median 60 vs 50, p = 0.017), MIS score (median 5 vs 4, p = 0.011), lower albumin (median 3.5 vs 3.8 g/dl, p = 0.011) and Mg levels (median 2.1 vs 2.4 mg/dl, p < 0.001). In univariate analysis age, CVD comorbidities, pulse pressure, CRP, BMI, albumin, Mg, MIS and use of b-blockers or calcium blockers were LVH predictors. In multivariate analysis, Mg was an independent predictor of LVH, adjusted for age, MIS and b-blockers. Considering LV geometry, lower Mg levels were mainly correlated with concentric LVH. CONCLUSION: Low serum magnesium levels seem to be an independent factor for LVH in hemodialysis and peritoneal dialysis patients.

Novel and Founder Pathogenic Variants in X-Linked Alport Syndrome Families in Greece.

Alport syndrome (AS) is the most frequent monogenic inherited glomerulopathy and is also genetically and clinically heterogeneous. It is caused by semi-dominant pathogenic variants in the X-linked COL4A5 (NM_000495.5) gene or recessive variants in the COL4A3/COL4A4 (NM_000091.4/NM_000092.4) genes. The disease manifests in early childhood with persistent microhematuria and can progress to proteinuria and kidney failure in adolescence or early adulthood if left untreated. On biopsy, pathognomonic features include alternate thinning, thickening and lamellation of the glomerular basement membrane (GBM), in the presence of podocyte foot process effacement. Although previous studies indicate a prevalence of AS of about 1/50,000, a recent publication reported a predicted rate of pathogenic COL4A5 variants of 1/2320. We herewith present 98 patients (40 M/58 F) from 26 Greek families. We are selectively presenting the families segregating the X-linked form of AS with pathogenic variants in the COL4A5 gene. We found 21 different pathogenic variants, 12 novel: eight glycine and one proline substitutions in the collagenous domain, one cysteine substitution in the NC1 domain, two premature termination of translation codons, three splicing variants, one 5-bp insertion/frameshift variant, one indel-frameshift variant and four gross deletions. Notably, patients in six families we describe here and three families we reported previously, carried the COL4A5-p.G624D substitution, a founder defect encountered all over Europe which is hypomorphic with mostly milder symptomatology. Importantly, on several occasions, the correct genetic diagnosis reclassified patients as patients with AS, leading to termination of previous immunosuppressive/cyclosporine A therapy and a switch to angiotensin converting enzyme inhibitors (ACEi). With the understanding that all 98 patients span a wide range of ages from infancy to late adulthood, 15 patients (11 M/4 F) reached kidney failure and 11 (10 M/1 F) received a transplant. The prospects of avoiding lengthy diagnostic investigations and erroneous medications, and the advantage of delaying kidney failure with very early administration of renin-angiotensin-aldosterone system (RAAS) blockade, highlights the importance of timely documentation of AS by genetic diagnosis.

VOLume flow assistance for optimizing outcomes of dysfunctional autologous arteriovenous fistula Angioplasty: the VOLA Pilot Study.

OBJECTIVES: To investigate the feasibility of VF-assisted angioplasty (VFA) in dysfunctional AVF using sequential intraprocedural duplex ultrasound (DUS), to utilize intraprocedural VF as a quantifiable, functional endpoint in endovascular treatment. METHODS: This prospective study included 20 consecutive patients (23 lesions; 16 men; mean age 67 ± 16 years) with dysfunctional AVF undergoing fluoroscopically guided balloon angioplasty between June 2019 and May 2020. Primary endpoints were quantification of outcome using sequential DUS VF analysis following each dilation, 6-month target lesion re-intervention (TLR)-free rate, standard technical success, procedural success (achievement of a postprocedural VF value equal (or 10% less) or superior to the baseline steady-state access), and correlation between procedural success and TLR-free rate. Secondary endpoints included 6-month lesion late lumen loss (LLL), correlation between balloon diameter used and intraprocedural VF values, and correlation between VF and LLL at 6 months follow-up. RESULTS: Mean VF increase was 168.5% ± 102.5% (range: 24.24-493.33%). Procedural success was 80% (16/20 cases). VFA improved procedural success by 20% (4/20 cases) compared to standard assessment (< 30% residual stenosis and palpable thrill). TLR-free rate was 78.3% and 67.3% at 6 and 12 months. Significantly less TLR was noted in cases of procedural success (82.4% vs. 66.7% 6 months; p = 0.041). Unweighted linear regression showed a significant positive relationship between diameter of balloon and VF (146.9 ± 42.3 mL/min VF gain per mm of balloon diameter; p = 0.001, R2 = 0.23) and a significant negative relationship between LLL and VF decline at follow-up (102.0 ± 34.6 mL/min loss per mm of LLL; p = 0.01, R2 = 0.35). Optimal VF cutoff value and percentile increase to predict access failure were 720 mL/min (sensitivity 58.3%, specificity 71.4%) and 153% (sensitivity 66.7%, specificity 85.7%), respectively. CONCLUSION: Intraprocedural VF assessment could be used to optimize AVF angioplasty. KEY POINTS: • A newly proposed functional endpoint of angioplasty in dysfunctional dialysis fistula was evaluated and angioplasty outcome was quantified using volume flow (VF) assessment with sequential intraprocedural DUS. • Intraprocedural VF assessment improved immediate procedural success; increased balloon diameter was correlated with VF gain and late lumen loss with VF decline. • Intraprocedural VF values ≥ to baseline steady-state values were correlated with less re-interventions.

Relationship between depression, clinical and biochemical parameters in patients undergoing haemodialysis.

In this paper, we investigated the incidence of depression and its relation to clinical, laboratory parameters and sleep disorders in 45 haemodialysis (HD) patients. They were divided into two groups. Group A (n = 29) had no depression, whereas Group B (n = 16) had clinically assessed depression. Subjects were compared in terms of socioeconomic, clinical, laboratory parameters and presence of sleep disorders. Groups were matched for age, sex, family status, education, self-esteem, coffee and alcohol consumption, psychiatric history, time on HD and laboratory (serum urea, creatinine, electrolytes, iron, albumin and lipids) parameters. Group B demonstrated significantly lower haemoglobin levels (11.13 ± 1.69 and 12.23 ± 1.31 g/dl, respectively; p < 0.01) and higher C-Reactive Protein (CRP) levels (1.82 ± 1.73 and 0.83 ± 0.6 mg/dl, respectively; p < 0.005) compared to Group A. Additionally, strong correlation was observed when Hamilton Depression Scale scores were related to haemoglobin (r =-0.30, p < 0.05), CRP (r = 0.38, p < 0.001) and AIS scores (r = 0.54, p < 0.0001). In conclusion, depression seems to be related to high CRP, low haemoglobin levels and sleep disorders.

Relation between insomnia mood disorders and clinical and biochemical parameters in patients undergoing chronic hemodialysis.

BACKGROUND: Sleep disturbances are usually the outcome of a complex interplay between intrinsic factors and environmental influences. Aim of this study was to investigate the incidence of insomnia and to assess its relation to clinical and laboratory parameters in hemodialysis patients. METHODS: Using Athens Insomnia Scale (AIS), sleeping profile of 45 subjects (32 male, 13 female, mean age 59+/-16.2 years) was evaluated. According to AIS, patients were divided into two groups. Group A comprised 32 patients with score 0-9 (absence of sleep disorders), whereas group B included 13 patients scoring higher than 9 (clinically assessed disorder). Subjects were compared in terms of socioeconomic, clinical, laboratory parameters and presence of depression (assessed by Hamilton Depression Scale, HAMD). RESULTS: No significant difference was observed with respect to age, sex, family status, education, self-esteem, coffee and alcohol consumption, time in hemodialysis and laboratory parameters. Group B demonstrated significantly lower albumin levels (3.65+/-0.38 and 3.9+/-0.24 g/dL respectively, p<0.01), higher CRP levels (1.88+/-1.9 and 0.92+/-0.64 mg/dL respectively, p<0.01) and exhibited depression (HAMD score 13.4+/-6.4 and 7.8+/-5.9 respectively, p<0.005). Moreover, significant correlation was observed when AIS scores were related to albumin (r=-0.29, p< 0.05), CRP (r=0.38, p<0.01) and HAMD scores (r=0.54, p<0.0001). CONCLUSIONS: Sleep disorders are common in hemodialysis patients. They seem to be related to high CRP and low albumin levels and demonstrate strong correlation to mood disorders, which are equally common to such patients.

Metformin-associated lactic acidosis treated with continuous renal replacement therapy.

INTRODUCTION: Lactic acidosis is an infrequent complication of metformin therapy for diabetes mellitus. The presence of clinical conditions, such as renal failure, increases the risk of metformin-associated lactic acidosis (MALA). We present a case of lactic acidosis in a patient with diabetes treated with metformin, complicated by acute renal failure in preexisting chronic nephropathy. CASE SUMMARY: A 70-year-old white male, weighing 77 kg, with diabetes mellitus, coronary heart disease, congestive heart failure (New York Heart Association class III), moderate essential hypertension (stage 2), and renal dysfunction (serum urea, 90 mg/dL; serum creatinine, 1.5 mg/dL; creatinine clearance, 49.8 mL/min/1.73 m2) presented to the emergency department of the General Hospital of Rhodes (Rhodes, Greece), complaining of malaise, respiratory distress, myalgias, disorientation, abdominal discomfort, and increasing somnolence of insidious onset. The patient's regimen included isosorbide mononitrate 60 mg QD, furosemide 40 mg QD, quinapril 20 mg QD, and metformin 850 mg TID. Before this hospitalization, he had received a 2-week course of oral diclofenac sodium 25 mg TID for low back pain. Preliminary laboratory evaluation found leukocytosis (27,300/mm3), severe renal failure (serum urea, 215 mg/dL; serum creatinine, 7.4 mg/dL; calculated creatinine clearance, 10.1 mL/min/1.73 m2), and a high anion gap metabolic acidosis (pH, 6.95; anion gap, 33 mEq/L) in arterial blood gas analysis. His medical and drug history, the clinical and laboratory findings, and the determination of lactate in samples of plasma (7.8 mEq/L), aroused the suspicion of MALA. The Naranjo algorithm scores for metformin and diclofenac sodium were 6 and 7, respectively. The patient received a single session of bicarbonate-buffered continuous venovenous hemodiafiltration (CWHDF) that lasted 16 hours. Ultimately, he was stabilized, and progressive restoration of acid-base balance and renal function was observed. DISCUSSION: We suspect that lactic acidosis may have been related to the use of metformin, the presence of heart and renal failure (contributing to metformin toxicity), and previous use of diclofenac sodium. CVVHDF has an advantage over conventional intermittent hemodialysis in that it corrects acidosis and removes lactate and metformin without risk of hypernatremia or fluid overload. CONCLUSIONS: MALA should be strongly suspected in diabetic patients presenting with high anion gap metabolic acidosis and increased serum lactate level. In the case described, prompt recognition of lactic acidosis and early application of bicarbonate-buffered CVVHDF produced successful results.