efecte de la patologia de l'artÈria nutrÍcia sobre la maduraciÓ i funciÓ de … ·...

Ramon Roca-Tey MD, PhD.

Membre de la Junta Directiva de la Vascular Access Society (VAS)

Coordinador del "Grupo Español Multidisciplinar del Acceso Vascular" (GEMAV)

Coordinador del Grupo de trabajo del acceso vascular de la Sociedad Española de Nefrología (SEN)

Coordinador del Grup de treball d’Accés Vascular de la Sociedad Catalana de Nefrología (SCN)

Membre del Grupo de trabajo de Nefrología Diagnóstica e Intervencionista de la SEN (grup promotor)

EFECTE DE LA PATOLOGIA DE

L'ARTÈRIA NUTRÍCIA SOBRE

LA MADURACIÓ I FUNCIÓ

DE LA FÍSTULA

Conflicte d'interessos: cap

Desè aniversari

Grup d'Accés Vascular

2008-2018

Vicent Esteve Joan Feixas

Néstor Fontseré Fredzzia Graterol

Jose Ibeas Joaquim Martínez

Manel Ramírez de Arellano Diego Sandoval

Ramon Sans Irati Tapia

Ramon Roca-Tey (coordinador)

Hospital de Bellvitge Hospital Clínic de Barcelona

Hospital de Figueres Hospital Germans Trías i Pujol de Badalona

Hospital de Mollet Hospital Parc Taulí de Sabadell

Fundació Puigvert Hospital de Terrassa

Hospital de Vic

PRINCIPALS ACTIVITATS DEL GRUP

1.Reunions: com mínim, 2 cada any.

2.Presentació de casos clínics durant

cada reunió.

3.Organitzar Cursos i Jornades sobre

l'accés vascular.

4.Promoure estudis (multicèntrics)

18-12-2014 23-11-2017

2015

2016

Kidney Int 2007; 72: 665-666

Taló d'Aquil·les: punt vulnerable i feble d’una persona

Copyright ©2007 American Society of Nephrology

Allon, M. Clin J Am Soc Nephrol 2007;2:786-800

The “fistula hurdle”

Rate of primary AVF failure (%):

Overall: 23 (n=7,393 AVFs)

Lower-arm: 28 (n=1,447 AVFs)

Upper-arm: 20 (n=1,586 AVFs)

(p<0.001)

Am J Kidney Dis 2014; 63(3):464-478

Ibeas J, Roca-Tey R, Vallespín J, Moreno T, Moñux G, Martí-Monrós A, et al, por el Grupo Español Multidisciplinar del

Acceso Vascular (GEMAV). GUÍA CLÍNICA ESPAÑOLA DEL ACCESO VASCULAR PARA HEMODIÁLISIS.

Nefrologia 2017; 37(Supl 1): 1-177.

INDICADOR: FALLO PRECOZ CAPÍTULO ESTÁNDAR

2017 (%)

Fístula radiocefálica 2

< 35

Fístula proximal (arteria humeral) 2

< 25

- One third of cases of vascular access dysfunction were related to feeding artery stenosis.

- We described 3 different patterns of radial artery stenosis.

Causes of primary AVF failure (lesiones identified)

Arterial dilatation may be a key step in maturation

Since the artery is generally narrower than the vein, the artery is the

chief source of vascular resistance in a new fistula.

Arteriovenous fistula maturation requires dilatation of the anastomosed artery and vein

Acute arterial pressure drop

Increase in feeding artery blood flow rate at short-term

Increase in arterial wall shear stress (WSS)

Vascular endothelium: releasing nitric oxide and other endothelium-dependent

relaxing factors

Feeding artery dilatation: neutralize the increased WSS flow-mediated

Increase in feeding artery internal diameter: reduce the WSS back to pre-AVF levels

The WSS gradually returned toward normal.

Creation of arteriovenous anastomosis (AVF)

Increase in feeding artery diameter and blood flow rate

Individual changes in blood flow rate of the brachial artery of the 18 patients at five time points.

549 % !!! (56.2 ± 20.0 vs 365.0 ± 129.3 ml/min)

Seminars in Dialysis —Vol 18, No 3 (May–June) 2005 pp. 243–246

Schematic of a vessel. The white layer shows smooth endothelial cells; the purple layer smooth muscle cells; 𝜌 shows direction of pressure; 𝜏 shows direction of wall shear stress. Figure reprinted by permission from Macmillian Publishers Ltd.: Nature Reviews Molecular Cell Biology, 10, 2009.

Acutely (1 day following a RCF placement), mean shear stress increased by 475% and brachial artery internal diameter by 15%

IMPACT OF RADIAL ARTERY (RA) LESIONS ON RADIOCEPHALIC FISTULA (RCF) FUNCTION FOR HEMODIALYSIS (HD).

HISTOLOGIC STUDY OF 37 PATIENTS.

R. Roca-Tey, R. Bordes, A. Rivas *, R. Samon, O. Ibrik, I. Giménez, R. Martínez-Cercós, J. Viladoms. Departments of Nephrology, Pathology & Vascular Surgery, Hospital de Mollet.

* CETIR Centre Mèdic, Barcelona, Spain

Roca-Tey R. Repercusión de la patología de la arteria nutricia sobre la función del acceso vascular. Simposio SEN (Sevilla, 16-10-2011): “Estudio histológico del acceso vascular para hemodiálisis”

VARIABLE RESULT Gender: % (n): Male / Female 86.5 (32) / 13.5 (5)

Mean age (years) 64.9±13.2 (33-86)

Primary renal disease: % (n) Diabetic nephropathy

Polycystic kidney disease Glomerular disease

Hypertensive Vascular disease

Interstitial disease Amyloidosis

Unknown

21.6 (8) 13.5 (5) 10.8 (4) 10.8 (4) 8.1 (3) 5.4 (2) 2.7 (1) 27 (10)

Peripheral vascular disease: % (n) 10.8 (4) Coronary artery disease: % (n) 18.9 (7) Cerebrovascular disease: % (n) 5.4 (2)

At least one comorbidity other than diabetes: % (n) 21.6 (8) Already on chronic HD: % (n) 45.9 (17)

Mean time on HD (months) 6.1 ± 17.6 (0.5-74) RCF side: % (n): Left / Right 70.3 (26) / 29.7 (11)

Laboratory parameters/data

Calcium (mg/dl) Phosphorus (mg/dl)

Intact parathyroid hormone (ug/ml) Calcium x phosphorus product

8.6 ± 1.1 5.4 ± 1.2

300.4 ± 196.6 46.1 ± 10.9

Clinical characteristics of 37 included patients


Vascular assessment during the procedure by the surgeon and

radial artery evaluation by the pathologist

VARIABLE RESULT Vascular assessment by the surgeon

Radial artery Diameter: % (n): Normal / Reduced Findings: % (n): Normal / Pathology

Cephalic vein Diameter: % (n): Normal / Reduced Findings: % (n): Normal / Disease *

Thrill after releasing the clamps : % (n): Normal / Weak

94.6 (35) / 5.4 (2) 73 (27) / 27 (10)

91.9 (34) / 8.1 (3) 86.5 (32) / 13.5 (5) 81.1 (30) / 18.9 (7)

Radial artery evaluation by the pathologist

Findings: % (n): Normal / Pathology

Morphometric analysis (mm) ** Thickness of the intima layer (IT) Thickness of the media layer (MT)

Intima-media thickness (IMT)

70.3 (26) / 29.7 (11)

0.11 ± 0.22 (0.02-1.02) 0.39 ± 0.16 (0.20-0.90) 0.50 ± 0.38 (0.22-1.92)

* Lesions of needling. ** N =36

Nº 2. 47 años. PQR. QA= 1,471 ml/min (HE, 100x)

Nº 14. 72 años. DM. QA= 602 ml/min (HE, 100x)


Comparative analysis between patients with histological radial artery pathology and patients with healthy radial artery

VARIABLE Histological RA pathology

Healthy RA p

N 11 25 ˗ Gender: % (n): Male / Female 90.9 (10) / 9.1 (1) 84 (21) / 16 (4) 1

Mean age (years) 69.4±11.5 62.4 ±13.4 0,14 Diabetic nephropathy: % (n) 36.4 (4) 16 (4) 0.21

At least one comorbidity other than diabetes: % (n) 27.3 (3) 16 (4) 0.65

Already on chronic HD: % (n) 54.5 (6) 40 (10) 0,48 Mean time on HD (months) 2.8 ±3.5 1.2 ±0.6 0.23

Mean calcium (mg/dl) 8.4 ±0.7 8.7 ±1.3 0.41 Mean phosphorus (mg/dl) 5.5 ±1.0 5.4 ±1.3 0.61

Mean parathyroid hormone (ug/ml) 279.4 ±118.7 322.0 ±219.9 0.74 Mean Ca x P 46.3 ±9.4 46.4 ±11.9 0.84

RA diameter *: % (n): Normal / Reduced 100 (11) / 0 (0) 92 (23) / 8 (2) 1 RA findings *: % (n): Normal / Pathology 18.2 (2) / 81.8 (9) 100 (25) / 0 (0) 0.0001 CV diameter *: % (n): Normal / Reduced 81.8 (9) / 18.2 (2) 96 (24) / 4 (1) 0.22 CV findings *: % (n): Normal / Disease 90.9 (10) / 9.1 (1) 88 (22) / 12 (3) 1

Thrill after releasing the clamps *: % (n): Normal / Weak 72.7 (8) / 27.3 (3) 88 (22) / 12 (3) 0.34 Mean IT of RA (mm) 0.22 ±0.38 0.05 ±0.03 0.13

Mean MT of RA (mm) 0.54 ± 0.19 0.33 ±0.09 0.01 Mean IMT of RA (mm) 0.76 ± 0.39 0.39 ±0.10 < 0.001 Failed RCF: % (n) ** 36.4 (4) 16 (4) 0.21

Mean QAof RCF (ml/min) 771.7 ± 395.2 1282.4 ± 477.9 0.007 Mean primary unassisted RCF patency (months) 32.1 ±11.7 49.5 ± 6.5 0.064

*Obtained by gross examination. ** The ninth failed RCF didn't have histological lesions but not was considered healthy because it had lesions at gross examination.


*Obtained by gross examination. ** The ninth failed RCF didn't have histological lesions but not was considered healthy because it had lesions at gross examination.

Comparative analysis between patients with microscopic radial artery calcifications and patients with healthy radial artery

VARIABLE Microscopic RA calcifications

Healthy RA p

N 9 25 ˗ Gender: % (n): Male / Female 100 (9) / 0 (0) 84 (21) / 16 (4) 0.55

Mean age (years) 66.7 ±10.9 62.4 ±13.4 0,39 Diabetic nephropathy: % (n) 44.4 (4) 16 (4) 0.16

At least one comorbidity other than diabetes: % (n) 22.2 (2) 16 (4) 0.64

Already on chronic HD: % (n) 66.7 (6) 40 (10) 0,25 Mean time on HD (months) 2.8 ±3.5 1.2 ±0.6 0.23

Mean calcium (mg/dl) 8.5 ±0.7 8.7 ±1.3 0.61 Mean phosphorus (mg/dl) 5.4 ±1.1 5.4 ±1.3 0.82

Mean parathyroid hormone (ug/ml) 273.1 ±131.6 322.0 ±219.9 0.76 Mean Ca x P 45.9 ±9.7 46.4 ±11.9 0.95

RA diameter *: % (n): Normal / Reduced 100 (9) / 0 (0) 92 (23) / 8 (2) 1 RA findings *: % (n): Normal / Pathology 11.1 (1) / 88.9 (8) 100 (25) / 0 (0) 0.0002 CV diameter *: % (n): Normal / Reduced 77.8 (7) / 22.2 (2) 96 (24) / 4 (1) 0.16 CV findings *: % (n): Normal / Disease 88.9 (8) / 11.1 (1) 88 (22) / 12 (3) 1

Thrill after releasing the clamps *: % (n): Normal / Weak 66.7 (6) / 33.3 (3) 88 (22) / 12 (3) 0.30 Mean IT of RA (mm) 0.15 ±0.32 0.05 ±0.03 0.28

Mean MT of RA (mm) 0.58± 0.18 0.33 ±0.09 <0.001 Mean IMT of RA (mm) 0.73± 0.37 0.39 ±0.10 0.001 Failed RCF: % (n) ** 44.4 (4) 16 (4) 0.16

Mean QAof RCF (ml/min) 662.0± 265.9 1282.4 ± 477.9 0.005 Mean primary unassisted RCF patency (months) 33.7±12.3 49.5 ± 6.5 0.040

Observational prospective study comparing patency rates of RCFs in ESRD diabetics who had Mönckeberg radial artery disease by plain two-dimensional radiography (calcified [C] group, n=39) were compared with those obtained in ESRD diabetics who had healthy, noncalcified vessels before RCF construction (healthy [H] group, n=33).

Radiocephalic fistula (RCF) outcomes

J Vasc Surg 2014;60:462-70

VARIABLE SUCCESSFUL RCF FAILED RCF p

N: % (n) 75.7 (28) 24.3 (9) ˗ Gender: % (n): Male / Female 82.1 (23) / 17.9 (5) 100 (9) / 0 (0) 0.30

Mean age (years) 63.6 ±13.1 69.2 ±12.9 0.27 Diabetic nephropathy: % (n) 17.9 (5) 33.3 (3) 0.37

At least one comorbidity other than diabetes: % (n) 21.4 (6) 22.2 (2) 1 Already on chronic HD: % (n) 35.7 (10) 77.8 (7) 0.052

Mean time on HD (months) 2.0±2.8 11.7±27.4 0.42 Mean calcium (mg/dl) 8.6±1.2 8.9±1.0 0.22

Mean phosphorus (mg/dl) 5.5 ±1.2 4.9±1.3 0.18 Mean parathyroid hormone (ug/ml) 336.0±206.2 192.1±112.9 0.06

Mean Ca x P 46.9±10.6 43.7±12.1 0.41 RA diameter *: % (n): Normal / Reduced 96.4 (27) / 3.6 (1) 88.9 (8) / 11.1 (1) 0.43 RA findings *: % (n): Normal / Pathology 78.6 (22) / 21.4 (6) 55.6 (5) / 44.4 (4) 0.17

CV diameter *: % (n): Normal / Reduced 96.4 (27) / 3.6 (1) 77.8 (7) / 22.2 (2) 0.14 CV findings *: % (n): Normal / Disease 92.9 (26) / 7.1 (2) 66.7 (6) / 33.3 (3) 0.08

Thrill after releasing the clamps *: % (n): Normal / Weak 89.3 (25) / 10.7 (3) 55.6 (5) / 44.4 (4) 0.045 Histological RA pathology: % (n) 25.0 (7) 44.4 (4) 0.40

Microscopic RA calcification: % (n) 17.8 (5) 44.4 (4) 0.18 Mean IT of RA (mm) 0.08 ± 0.19 0.15 ± 0.31 0.88

Mean MT of RA (mm) 0.36 ±0.15 0.48 ± 0.15 0.03 Mean IMT of RA (mm) 0.45 ±0.23 0.64 ± 0.39 0.07


Comparative analysis between patients with successful and failed RCF

*Obtained at gross examination

Tiempo (meses)

Supe

rviv

enci

a ac

umul

ada

MT < 0,40 mm: 54,2 ± 7,1 (n = 20)

p = 0,010

MT ≥ 0,40 mm: 12,5 ± 3,8 (n = 16)

Primary unassisted RCF patency


Relationship between radial artery IMT value and AVF failure

The IMT value in the failed group (n=14) was thicker than that in the patent group

(n=24) (0.46±0.08 mm vs 0.40±0.09 mm, p=0.032)

The IMT value correlated significantly with the AVF failure (r=0.358, p=0.027)

Comparison of AVF patency rate between patients with IMT ≥500 um (n=26) and <500 um (n=64)

Young Ok Kim et al

p=0.017

The frequency of AVF nonmaturation was similar between patients with or without preexisting arterial microcalcification The structural abnormalities seen in the native vessels used to create an AVF correlate poorly with the functional vascular properties that result in AVF nonmaturation

Of 127 study AVFs, 39 (31%)

failed to mature.

The frequency of AVF

nonmaturation was similar for

patients in the 4 categories of

arterial microcalcification

p=0.9 for comparison of patients in the 4 groups

Am J Kidney Dis 2015; 66(1):84-90

Preoperative arterial and venous diameters duplex ultrasound groups of functioning and non-functioning arteriovenous fistulas

Preoperative Sonographic Measurements by Fistula Outcome

J Ultrasound Med 23:161–168, 2004

The same vascular surgeon created all fistulas and took all diameter measurements.

Pre-anastomosis artery and vein diameters were measured with intraluminal probes during surgery

Characteristics of matured and failed fistula groups

It seems likely that low arterial elasticity

(preoperative measurement on the day of

surgery by tonometer technique)

promotes AVF maturation failure (6/26)

by impairing arterial dilatation

Fistulas that matured generally had a higher small artery elasticity index than fistulas that failed.

Solid symbols indicate mean ± SE.

Low arterial elasticity is an important factor in fistula maturation failure

Year: 1990 Number of accesses: 434 AVF vs AVG (%): 93 Failing-to-mature AVF (%): 10

In children who have small arterial diameter, AVF can

usually be created successfully

Importance of arterial dilatation on AVF maturation

Microsurgery instruments (1: scissors, 2: Vickers-Owen needle holder, 3: Dumont forceps, 4 and 5: Acland clamps) Surgical microscope

Demographic and comorbidity factors Distribution of patients for radial artery diameters

All patients were pre-operatively examined by both clinical and ultrasound examinations. The criterion for a distal access creation was the presence of arterial and venous vessels with no sign of stenosis. Ultrasound evidence of radial artery calcification did not preclude its use for access creation. No thrombosis occurred within the initial 24 h. The early failure rate was 14% (4 out of 28 patients) because thrombosis >1 week after surgery (n=1 on Day 14) and lack of maturation (patent but unfunctional AVF) at Week 4 after surgery (n=3).

We have evaluated the results of RCFs (created with microsurgery along with preventive haemostasis) in a subset of patients with a radial artery internal diameter below the lower limit (<1.6 mm) proposed by the guidelines as a predictor of poor outcome

Vachharajani T. "Unassisted" evaluation of access dysfunction (eyes, ears, and fingers).

ASDIN 2014 Scientific Meeting, Phoenix, Arizona (21-02-2014).

PHYSICAL AVF EXAMINATION

Predictors of a well-functioning AVF: thrill

Thrill is a palpable vibration of AVF

(“buzz”) related to flow. When present, it

indicates that there is flow within the AVF

Thrill = surrogate variable of flow

Prospective study to determine clinical and ultrasound intra-operative factors related to 1-month AVF thrombosis in ESRD patients

N = 111 autogenous end-to-side AVF (39.6% RCF)

Primary AVF failure: 15.3%

After final anastomosis creation: pulse 100%, thrill 83.8%.

Following skin closure: audible bruit 73.0 %.

- Intra-operative absence of bruit following skin closure could predict 1-month AVF

thrombosis (S: 70.6%) better than absence of thrill after anastomosis creation (S:

35.3%).

- Intra-operative feeding artery flow: significantly lower for thrombosed versus

patent AVF at 1 month follow-up (137.7 versus 457.1 ml/min)

J Vasc Surg 2008;48: 167-72

Prospective cohort study to determine the value of intraoperative blood flow measurement with respect to AVF short-term outcome (n=109)

Comparison of

demographic features,

surgical findings, vessel

diameters and comorbid

conditions in 58 patients

with non-functioning

(n = 12) and functioning

(n = 46) RCAVF

OBJECTIVE To evaluate whether preoperative functional properties of arteries predict postoperative AVF measurements

Preoperative vascular function tests (VFTs) that assess the capacity of the brachial artery to dilate

- Flow-mediated dilation (FMD): measures the increase in brachial artery diameter in response to a sudden increase in blood flow and partly depends on the ability of the endothelium to release the endogenous vasodilator nitric oxide. - Nitroglycerin-mediated dilation (NMD): measures the intrinsic ability of the arterial media to respond directly to an exogenous nitric oxide donor and is, therefore, independent of a functional endothelium

J Am Soc Nephrol 27: 3788–3795, 2016

Preoperative NMD and FMD positively associated with changes in 6-week AVF blood

flow development rate and diameter, suggesting that native functional arterial

properties affect AVF development

Association of 6-week AVF flow rate and diameter with preoperative predictor VFT variables controlled for AVF location, preoperative ultrasound features, and baseline demographics

J Am Soc Nephrol 27: 3788–3795, 2016

CURRENT PATIENT WITH CHRONIC KIDNEY DISEASE AGE / DIABETES / CARDIOVASCULAR COMORBIDITIES

Feeding artery involvement: increased medial thickening

HIGH RISK OF PRIMARY AVF FAILURE

Creation of AVF anastomosis

Increased arterial stiffness

Decreased arterial elasticity (compliance): impaired ability to respon to vasoconstricitive or vasodilatadory stimuli

Decreased flow-mediated dilatation

1) L'èxit en la maduració de la fístula no està determinat exclusivament

pel diàmetre de l'artèria nutrícia.

2) Les propietats funcionals de l'artèria nutrícia poden contribuir al fracàs de maduració de

la fístula fins i tot quan el seu diàmetre es adequat.

3) Una vegada feta la anastomosi arteriovenosa, el increment del flux i la dilatació arterials

son factors clau per la maduració de la fístula.

4) La presencia de microcalcificacions de la arteria aferent no implica necessariament el

fracàs en la maduració de la fístula però pot limitar el seu flux i disminuir la seva

supervivència primària

5) El gruix preexistent de la paret de la artèria nutrícia i el flux intraoperarori de la fístula

semblen variables predictives de la maduració i la supervivència primària de la fístula.

Take home messages

I + D El dispositiu VasQ

El dispositiu HeRO

efecte de la patologia de l'artÈria nutrÍcia sobre la maduraciÓ i funciÓ de … ·...

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