INTRODUCTION

The prevalence of CKD in India is 17.2% with end stage renal disease (ESRD) being 0.8%¹. Hemodialysis (HD) is an important modality in the treatment of chronic renal failure. Patients undergoing chronic HD require a placement of permanent vascular access which is superficial and has little resistance with optimum flow.^2-6 Native arteriovenous fistula , arteriovenous shunts – AV grafts and tunneled double lumen catheters are various access which can be used for hemodialysis.^2-6 As central venous catheters and grafts have high infection and thrombosis rates ,AV fistula is the preferred access.⁷

Alexis Carrel first introduced  the three-point end-to-end- and a side-to-side-anastomosis in 1912, a milestone and still used today . Brescia and Cimino introduced native arteriovenous fistula for hemodialysis in 1966 ⁸. Hemodialysis access survival rates are longer with native A-V fistula than A-V grafts. ⁹ Native A-V fistulas are associated with lower infection rate than A-V grafts and percutaneous catheters. ¹⁰

There are different types of native arteriovenous fistula – Radial-cephalic, Brachial-cephalic or brachial-basilic. They can be differentiated on the basis of type of anastomosis – side to side, end to side and end to end. The most commonly used is radial-cephalic end to side.  Before we can use the A-V fistula it requires some time for structural modification of vein .It results in arterialization of vein as a result of turbulent flow after which it can be used for cannulation for hemodialysis.¹¹

Patients on hemodialysis have reduced physical exercise. Exercise maintains blood pressure and oxidative stress and also improves arterial compliance, cardio-vascular profile ,  cardiac and left ventricular function.¹² The National Kidney Foundation Disease outcome quality initiative 2006 guidelines recommend regular forearm exercise post-operatively to aid in maturation of A-V fistula.¹³Although a definitive conclusion regarding post-operative exercise is still awaited from studies , but some studies show that regular fore-arm exercise improve vein diameter and thus help in maturation of A-V fistula . ⁹

It has been shown that local physical exercise in patients with end-stage renal disease may have a beneficial effect on forearm arteries and veins ¹⁴, and that intermittent compression of the upper arm veins alone improved the diameter of forearm veins ¹⁵.An intensive exercise program may improve fistula maturation via increasing the luminal diameter of vein and may permit early use of arteriovenous fistula.⁹ Along with that regular handgrip training increases the diameters of forearm vessels. It also improves endothelium-dependent vasodilatation.^{17, 18}

 A simple, incremental resistance, exercise-training program has been found to cause a significant increase in the size of the cephalic vein commonly used in the creation of an arteriovenous fistula. The increase in size and resultant probable increase in blood flow may theoretically accelerate the maturation of native arteriovenous fistulae, thereby lessening the morbidity associated with vascular access.¹⁸

There have been only a few studies for evaluation of influence of exercise on functioning, maturation and success of A-V fistula surgery. So we are going to conduct a study in which we will evaluate both pre-operative and post – operative effect of exercise on overall outcome of A-V fistula surgery. 

PURPOSE OF STUDY-

1. The arteriovenous fistula is considered to be the gold standard form of access for haemodialysis patients. ^2-6 Better strategies are needed to promote AVF creation and maturation. Therefore, interventions aimed at enhancing fistula maturation are warranted.

2. However, there is no evidence for handgrip exercise resulting in improvement in AV fistula surgery outcome. Therefore, the purpose of this study is to find whether handgrip exercise performed before and after the surgery results in the improvement of the outcome of Arteriovenous fistula surgery in CKD patients (pre-dialysis patients). ¹⁶ 

PROCEDURE

 PRE-OPERATIVE WORKUP: Patients attending vascular access clinic for creation of arteriovenous fistula for the purpose of haemodialysis will be recruited under the study protocol.

History of risk factors will be taken – Diabetes mellitus , Hypertension , peripheral vascular disease , Congestive cardiac failure , previous surgery in neck or chest , PICC(Peripherally inserted central catheter) , Central line insertion(temporary or perm catheter) , previous failed attempt at AV fistula and site and complications of previous AVF/ catheters .

Examination of artery and vein – Brachial artery, radial artery and ulnar artery pulses palpability, arterial wall hardening/plaques, compressibility of vein, patency of palmar arch, dilated collateral veins over chest/breast and upper arm, Scars of previous central line insertions in the neck, Scars of PICC line in arm or forearm, Multiple sites of vein prick scars / localized thickening or phlebitis and sites available for creation of vascular access is assessed.

Investigations that will be performed – Investigations like kidney function test will be done. USG Doppler will be preformed 8 weeks before the surgery, on the day of surgery and 8 weeks after creation of AV fistula.

Patients will be allocated to one of the three groups- Patients in group A will be given routine pre-operative teaching and care of AV fistula. Patients in group B will be asked to do handgrip exercise (without tourniquet at arm) for 8 weeks after AV fistula surgery.

OPERATIVE PROCEDURE – Depending on the site most suitable for creation of AV fistula – Radio cephalic, Brachiocephalic or Brachiobasilic fistula will be created.

POST-OPERATIVELY- Post operatively patient will be started on antibiotics and analgesics depending on cases to case basis as per the requirement of the patient. They will be followed in the post operative period according to pre-determined parameters provided in the Performa.

Success of fistula in terms of its use successfully for dialysis at the end of two months will be assessed and successful maturation of fistula will be assessed via USG Doppler at the end of 8 weeks.

 REVIEW OF LITERATURE –

            The basis for management of chronic renal failure patients is hemodialysis initially.¹⁹ Hemodialysis requires placement of a permanent vascular access which should provide safe and effective withdrawal of blood and return of blood via extracorporeal circuit. ²⁰ The fundamental forms of chronic vascular access available are native arteriovenous fistula, arteriovenous grafts and double lumen catheters. Of these, the native AVF is preferred for long-term hemodialysis vascular access since it has low morbidity, superior primary patency rates, lowest rates of thrombosis, longer duration of action, lower infection rates, lower need of secondary interventions and low cost .^2-6

The National Kidney Foundation Kidney Disease Quality Outcomes Initiative (NKF-KDOQI) clinical practice guidelines suggest a goal prevalence rate for successful native AVF of 65 percent ⁷. NKF-K/DOQI 2006 defines vascular access functional when – flow is >600ml / min, vein diameter is >0.6 cm ,  it has depth < 0.6 cm and it has clearly defined margins. According to NKF-KDOQI Practice Guidelines, the order of preference for the creation of AVF is radial-cephalic, brachial-cephalic, and then brachial-basilic transposition .²³

 There are still difficulties in both pre-operative and post-operative periods regarding A-V fistula surgeries. Overly aggressive attempts to increase AVF prevalence in patients with suboptimal anatomy leads to reduced maturation rates, and a longer duration of dialysis catheter use ⁸. Post-operatively primary causes for fistula abandonment are –failure to mature (27%), thrombosis (17%), post operative steal syndrome (1%) etc . Primary endpoint for every fistula surgery is maturation / fistula functional maturation. The maturation can be assessed on physical examination as well as on post-operative USG Doppler if needed. On USG Doppler maturation is defined by adequate vein dilation (Depth < 6mm, diameter >6mm). ²¹

Fistula maturation depends on several changes involving the vein such as increased rate of blood flow, increased vein diameter, and increased visibility of the vein. Successful fistula creation results in easy cannulation within 90 days of placement and adequate blood flow to support dialysis.²²

Vessel diameter is an important predictor of functional maturity of a fistula . ²³ The artery and vein intraluminal diameter are very important before construction of an A-V fistula ²⁴, because it is known that atherosclerotic and/or smaller arteries and small-sized cephalic veins are mostly responsible for the primary failure of arteriovenous fistula construction ²⁵. In previous studies vein diameter was found to have major predictor of fistula maturation. ²⁶ In Lauvao et al (2009) showed that vein diameter of size four or more are significant predictor for maturation of fistula. (p<0.0002).  ²⁶   Due to lack of adequate size vein in the forearm or arm, AV fistula surgery is often associated with higher failure rate

Adequate blood flow volume is also an essential requirement for proper hemodialysis. For functional maturation a flow rate of 350-400 ml/min may be needed for atleast 4 hours.

 So the maturation of an A-V fistula is an important part in a fistula surgery .²⁶ Lack of maturation of AV fistula (i.e. inadequate flow rate and/or lack of adequate luminal diameter) may result in failure of AVF surgery or late dialysis suitability.

Aerobic exercise has been reported to improve vascular flow and venous compliance.  Various types of handgrip and softball exercises have been described for local physical training in end stage renal disease patients. ²⁸   Oder et al (2003) showed significant increase in diameter of vein ranging from 3.8% to 25% in his study (p<0.0001). ²⁷  Similarly Sangwon kong et al (2014) compared both handgrip as well as soft ball exercises and found that both handgrip as well as soft ball exercises were increasing the vein diameter significantly(7.0+/- 1.3mm and 7.4+/- 1.2mm respectively) .³⁰

The only randomized control trial assessing the effect of progressive handgrip training on arteriovenous fistula showed small effect on change of venous diameter. ³⁰ Similarly other studies also show that hand grip exercises increases vein size and diameter.

Sangwon kong et al (2014)  showed that both hand grip and soft ball exercises were increasing blood flow volume through the fistula(861.5 ml and 575. 8 ml respectively).²⁸

It has been shown that local physical exercise in patients with end-stage renal disease may have a beneficial effect on forearm arteries and veins ¹³, and that intermittent compression of the upper arm veins alone improved the diameter of forearm veins. ¹⁴ An intensive exercise program may improve fistula maturation via increasing the diameter of vein and may permit early use of arteriovenous fistula. ³¹

A controlled exercise program in post operative period increases maturation rate of arteriovenous fistula. ¹⁶

Studies have shown that hand squeezing exercise program also result in acute dilatation of arteriovenous fistula and they do recommend that exercise should be continued in post operative period. ³¹

However there is lack of evidence about the benefit of preoperative hand exercise in improving the outcome of arteriovenous fistula surgery. It is known that regular handgrip training increases the diameters of forearm vessels. It also improves endothelium-dependent vasodilatation.^{27 , 30}. A simple, incremental resistance, exercise-training program has been found to cause a significant increase in the size of the cephalic vein commonly used in the creation of an arteriovenous fistula. The increase in size and resultant probable increase in blood flow may theoretically accelerate the maturation of native arteriovenous fistulae, thereby lessening the morbidity associated with vascular access.³⁶

These changes point to the possible beneficial effects of daily handgrip training in chronic renal failure patients before arteriovenous fistula construction.

BIBLIOGRAPHY –

1.       Epidemiology and risk factors of chronic kidney disease in India - results from the SEEK (Screening and Early Evaluation of Kidney Disease) study. Singh AK, Farag YM, Mittal BV, Subramanian KK, Reddy SR, Acharya VN, Almeida AF, Channakeshavamurthy A, Ballal HS, P G, Issacs R, Jasuja S, Kirpalani AL, Kher V, Modi GK, Nainan G, Prakash J, Rana DS, Sreedhara R, Sinha DK, V SB, Sunder S, Sharma RK, Seetharam S, Raju TR, Rajapurkar MM . BMC Nephrol. 2013 May 28; 14():114

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3.       Ascher E, Gade P, Hingorani A, et al. Changes in the practice of angioaccess surgery: impact of dialysis outcome and quality initiative recommendations. J Vasc Surg 2000; 31:84.

4.       Allon M, Robbin ML. Increasing arteriovenous fistulas in hemodialysis patients: problems and solutions. Kidney Int 2002; 62:1109.

5.       Dixon BS, Novak L, Fangman J. Hemodialysis vascular access survival: upper-arm native arteriovenous fistula. Am J Kidney Dis 2002; 39:92.

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8.       History of vascular access for haemodialysis.   Klaus Konner

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10.   Cost-effectiveness of Vascular Access for Haemodialysis: Arteriovenous Fistulas Versus Arteriovenous Grafts .  J.J.P.M. Leermakers, A.S. Bode, A. Vaidya, S.M.A.A. Evers, J.H.M. Tordoir^, 

11.   Hemodialysis vascular access survival: upper-arm native arteriovenous fistula.Dixon BS, Novak L, Fangman J SO , Am J Kidney Dis. 2002;39(1):92. 

12.   The effects of progressive handgrip training on arteriovenous fistula maturation in   chronic kidney disease – a pilot randomised controlled trial . Junglee, N, Law, B, Bigwood, B, William, Jibani, M, Macdonald ,Ysbyty Gwynedd Hospital, Bangor General Hospital, Bangor University, North Wales

13.   National Kidney Foundation, Inc . K/DOQI Guidelines – Updates 2006.

14.   Rus RR, Ponikvar R, Kenda R, Buturović-Ponikvar J. Effect of local physical training on the forearm arteries and veins in patients with end-stage renal disease. Blood Purif 2003; 21: 389–94.

15.   Rus RR, Ponikvar R, Kenda R, Buturović-Ponikvar J. Effect of intermittent compression of upper arm veins on forearm vessels in patients with end-stage renal disease. Hemodialysis Int .

16.   Effects of Handgrip Training and Intermittent Compression of Upper Arm Veins on Forearm Vessels in Patients With End-stage Renal Failure . Rina Rus, Rafael Ponikvar,Rajko B Kenda, Jadranka Buturović-Ponikvar

17.   Effect of Local Physical Training on the Forearm Arteries and Veins in Patients with End-Stage Renal Disease . Rus R.R Â· Ponikvar· Kenda R.B. Buturović-Ponikvar J. Departments of Pediatric Nephrology and Nephrology, University Medical Centre, Ljubljana, Slovenia

18.   Isometric exercise increases the size of forearm veins in patients with chronic renal failure. Leaf DA, MacRae HS, Grant E, Kraut J.

19.   The National Service Framework for Renal Services Part 1: Dialysis and Transplantation, Department of Health, London, UK, January 2004. 

20. Atkins D, Best D, Briss PA et al. Grading quality of evidence and strength of recommendations. BMJ 2004; 328:1490.

21.   . J Nephrol. 2002 Nov-Dec;15 Suppl 6:S28-32.Vascular access in the 21st century.  Konner   

22.   Vascular Access for Hemodialysis - How to Maintain in Clinical Practice Hossam Elwakeel and Khaled Elalf

23.   Vein diameter is the major predictor of fistula maturation .Lannery S. Lauvao, MD, Daniel M. Ihnat, MD, Kaoru R. Goshima, MD, LeAnn Chavez, MD,Angelika C. Gruessner, MS, PhD, and Joseph L. Mills Sr, MD, Tucson, Ariz

24.   Malovrh M. Approach to patients with end-stage renal disease who need an arteriovenous fistula. Nephrol Dial Transplant 2003;18: v50–52.

25.   Wong V, Ward R, Taylor J, Selvakumar S, How TV, Bakran A. Factors associated with early failure of arteriovenous fistulae for haemodialysis access. Eur J Vasc Endovasc Surg 1996;12: 207–13.

26.   J Nephrol. 2002 Nov-Dec;15 Suppl 6:S28-32.Vascular access in the 21st century.  Konner   

27.   The Effect of Two Different Hand Exercises on Grip Strength, Forearm Circumference, and Vascular Maturation in Patients Who Underwent Arteriovenous Fistula Surgery Sangwon Kong, MD1 , Kyung Soo Lee, MD1 , Junho Kim, MD1 , Seong Ho Jang, MD2

28.   Effect of Exercise on the Diameter of Arteriovenous Fistulae in Hemodialysis Patients.

29.   The effects of progressive handgrip training on arteriovenous fistula maturation in chronic kidney disease – a pilot randomised controlled trial .junglee, n¹, law, b³, bigwood, b², williams, d², jibani, m², macdonald, j² ³

30.   Effect of Local Physical Training on the Forearm Arteries and Veins in Patients with End-Stage Renal Disease . Rus R.R.^a Â· Ponikvar R.^b Â· Kenda R.B.^a Â· Buturović-Ponikvar J.^b Departments of ^aPediatric Nephrology and ^bNephrology, University Medical Centre, Ljubljana, Slovenia

31.   Effect of Exercise on the Diameter of Arteriovenous Fistula in Hemodialysis         Patients . Terrence f. oder, victoria teodorescu, and jaime uribarri.