Kidney Failure Risk Equation predictive tool to improve predialysis patient management?

Abstract

The Kidney Failure Risk Equation (KFRE) is a predictive tool that estimates the risk of progression to end-stage renal disease (ESKD) in patients with chronic kidney disease (CKD). This study evaluated the systematic implementation of KFRE in our nephrology center to improve the management of pre-dialysis patients. Through the analysis of 100 patients followed in the pre-dialysis pathway in the last 36 months, we observed a significant reduction in the initiation of dialysis in late referral mode, a lower use of temporary central venous catheters and an increase in timely preparation of vascular or peritoneal access. The comparison with historical pre-implementation data (2017-2020) highlighted an improvement in clinical organization and patient awareness in the choice of dialysis modality. The KFRE has proven to be a valid tool for risk stratification, optimizing the timing of renal replacement therapy and improving the allocation of healthcare resources. The integration of KFRE into clinical practice could represent a step towards precision nephrology, promoting more informed and personalized therapeutic decisions.

Keywords: KFRE, CKD, vascular access, peritoneal access

Introduction

Kidney Failure Risk Equation (KFRE) is a predictive tool that estimates the risk of progression to end-stage kidney disease (ESKD) in patients with chronic kidney disease (CKD). It represents a system validated by nephrology specialists to provide better personalized management of patients and evaluate the appropriate moment to plan the timing of starting renal function replacement treatment by planning all preparatory interventions (setting up vascular access/peritoneal catheter or pre-emptive kidney transplant). KFRE calculates risk over a 2- or 5-year period using 4 key variables, commonly available in medical records: age (in years), sex (male or female), eGFR (estimated glomerular filtration rate, expressed in mL/min/1.73 m²), UACR (urine albumin/creatinine ratio, expressed in mg/g). The calculation of the KFRE is based on a mathematical equation that uses the values ​​of the variables indicated above. Equation details include specific coefficients for each variable (e.g., age, gender, eGFR, and UACR). The result is expressed as a percentage chance of developing kidney failure within 2 to 5 years.  To facilitate the calculation, there are online calculators and tools integrated into clinical software on platforms that only require the entry of the 4 variables to quickly provide the result.  Ukidney’s KFRE calculator offers a useful interface to enter the required data and obtain a risk estimate [1]. Results can be interpreted as low risk (<5%) with minimal likelihood of progression to renal failure; intermediate risk (5%-20%) patients who may require intensive monitoring and management; high risk (>20%) active planning for dialysis or transplant, with priority in clinical management. The calculator also includes a table that classifies patients by eGFR categories (G1: eGFR ≥90 (Normal or High), G2: eGFR 60-89 (Slightly Reduced), G3a: eGFR 45-59 (Slightly-Moderately Reduced), G3b: eGFR 30-44 (Moderately-Severely Reduced), G4: eGFR 15-29 (Severely reduced), G5: eGFR <15 (Renal insufficiency) ) and albuminuria levels (A1: <30 mg/g (Normal or slightly increased), A2: 30-299 mg/g (Moderately increased), A3: ≥300 mg/g (Severely increased) (Figure 1). A possible alternative to the traditional UKidney calculator is the calculator https://kidneyfailurerisk.com which can offer more advanced options with an eight variable version (calcium, phosphorus, bicarbonates, albumin) with better risk stratification and more accurate planning. Certainly UKidney is an easy calculator to use in daily outpatient practice.

Figure 1. GFR categories and risk of kidney disease progression.
Figure 1. GFR categories and risk of kidney disease progression.

The KFRE uses few but relevant clinical parameters, making risk calculation quick and easy. It allows you to estimate the progression of CKD so you can initiate preventative treatments and plan renal replacement options before the onset of ESKD. This can motivate the patient to follow medical recommendations, adopt a healthy lifestyle and reduce risk factors. Despite the reliability of the KFRE, it has some limitations. The cohorts used for its validation may not represent all populations, limiting accuracy in some ethnic groups or in patients with significant comorbidities. The availability and quality of data influence the accuracy of the score. For example, ACR is not always measured in patients with CKD; exclusion of some risk factors: variables such as the presence of diabetes or hypertension are not directly included in the model, even if they influence the risk of CKD progression [2].

The study by Ingwiller et al. validated the effectiveness of the 40% threshold of 2-year risk calculated with the renal failure risk equation (KFRE) for planning vascular access in patients with chronic kidney disease (CKD). The research, conducted on a retrospective French cohort, compared the KFRE model with the traditional criterion of estimated glomerular filtration rate (eGFR < 15 mL/min/1.73 m²), demonstrating a better predictive capacity of the 8-variable model compared to the 4-variable one. The results indicate that the use of the 40% threshold of the KFRE guarantees personalized support in the management of patients with CKD by optimizing the time for the packaging of arteriovenous fistulas and the risk of starting dialysis with a central venous catheter [3].

A study conducted by Grams et al. evaluated the potential application of the KFRE using CKD-EPI 2021 for eGFR estimation, incorporating cardiovascular comorbidities as a variable. The analysis, based on data from 59 cohorts and 312,000 patients, compared this approach with the standard model and highlighted that KFRE shows high specificity in patients with eGFR < 45 ml/min/1.73 m² and in elderly. The model showed significant results in elderly patients with eGFR 45–59 ml/min/1.73m² especially in a long-term horizon. However, the integration of new variables did not bring significant improvements in the prediction of development of end-stage renal disease [4]. An external validation study conducted by Gallego-Valcarce et al. examined the effectiveness of KFRE and Grams predictive models in determining the risk of kidney failure and mortality in a cohort of Spanish patients with advanced (stage 4) chronic kidney disease (CKD). The analysis involved 339 patients followed for up to 5 years. Both models demonstrated excellent discrimination for renal failure, with AUCs ranging from 0.823 to 0.897. Furthermore, the Grams model provided reliable estimates of mortality before renal failure, with AUCs of 0.708 and 0.744 for the 2- and 4-year periods, respectively. Although both models showed adequate calibration for renal failure, the Grams model tended to overestimate mortality risk.

These results confirm the usefulness of predictive models in supporting personalized clinical decisions for patients with advanced CKD in Southern Europe [5]. The study conducted by Whitlock et al. validated the KFRE in a Manitoba population highlighting a high predictive capacity in the development of kidney failure in the following five years. A cohort of 1512 patients CKD stages three, four and five was examined. The analysis showed that KFRE is more specific than eGFR in discriminating high-risk patients with an area under the curve (AUC) of 0.90 compared to 0.78 for eGFR. Using a 5-year risk threshold of 3%, the KFRE achieved a sensitivity of 97% and a specificity of 62% for identifying high-risk patients. This study reiterates the importance of integrating KFRE in the management of patients with chronic renal failure by providing support to the nephrologist’s clinical decisions and optimizing resources [6]. The study conducted by Chu et al. evaluated the usefulness of KFRE together with eGFR in predicting the time to develop the stage of end-stage chronic renal failure in patients with advanced CKD. 1641 patients in outpatient follow-up in the United States were considered and the results showed that KFRE has a high specificity (C-statistic: 0.862; 95% CI: 0.838–0.889) in estimating the timing of dialysis initiation or kidney transplant eligibility. The results showed that KFRE was more accurate than eGFR in temporally estimating renal failure progression in patients with eGFR ≥20 mL/min/1.73m², while it showed no benefit in patients with advanced CKD eGFR ≤15 mL/min/1.73m² or KFRE risk >40%.

These findings suggest that KFRE can improve clinical decision planning, such as vascular access preparation, and provide patients with more intuitive and precise prognostic information [7]. The use of the KFRE as a tool to improve vascular access (VA) planning in patients with advanced chronic kidney disease has received increasing attention. Marques da Silva et al. have highlighted how the addition of a KFRE threshold ≥ 40% to the traditional criterion of eGFR < 20 mL/min/1.73m² can significantly improve the adequacy in the creation of arteriovenous fistulas or grafts (AVF/G). In their studies, the adoption of this combination allowed to increase the proportion of patients starting dialysis with AVF/G, while reducing unnecessary interventions. Furthermore, a retrospective study highlighted that a KFRE cut-off ≥ 20% has high sensitivity and specificity (72.8% and 78.4% respectively) for predicting the need for dialysis within two years. These results highlight the potential of the KFRE as a complementary tool to optimize the management of patients with CKD, suggesting the need for further validation in different population cohorts [8]. The study evaluated the use of KFRE in vascular access planning in patients with CKD. 256 patients with advanced CKD who underwent arteriovenous fistula or preemptive transplantation between 2018 and 2019 were retrospectively analyzed. The use of the KFRE proved accurate in predicting the need for the start of renal replacement therapy within two years. Patients with KFRE > 20% showed a significantly increased risk of initiating dialysis (HR 9.2; 95% CI: 5.06–16.60; p < 0.001) and a shorter mean time between vascular access creation and initiation of dialysis (10.8 ± 9.4 months vs 15.6 ± 10.3 months; p < 0.001). Even in patients with eGFR <20 mL/min/1.73m², KFRE >20% remained a significant predictor of dialysis initiation within 2 years (HR 6.61; 95% CI: 3.49–12.52; p < 0.001). These results suggest that KFRE can be used to identify patients with higher priority for vascular access creation in patients with eGFR <20 mL/min/1.73m² combined with KFRE >20% [9]. KFRE represents a fundamental predictive tool for risk stratification in patients with chronic kidney disease.

A study conducted at Johns Hopkins Medicine demonstrated that the integration of the KFRE into computerized medical records increases the sensitivity of the nephrologist regarding the specific risk of progression of kidney disease. However, to date its use remains limited and variable and influenced by factors such as access to laboratory data, understanding of risk thresholds and the sensitivity of medical and nursing staff. It has been observed that the use of KFRE is fundamental for crucial decisions for the evolution of chronic kidney disease, promoting awareness of both healthcare personnel and patients for the choice of timing for planning the dialysis modality and with all the consequent actions such as the preparation of the vascular access or the positioning of the peritoneal catheter or the possible candidacy for pre-emptive kidney transplantation. Experience suggests that targeted training of healthcare personnel together with standardization of guidelines could amplify the use of KFRE by improving the clinical management of high-risk patients [10].  The use of the KFRE could also be extended to general practitioners through integration into electronic medical records, increasing awareness of each patient’s risk. This would help improve the appropriateness of referrals to nephrologists and support shared decision-making regarding the initiation of dialysis, ultimately contributing to optimized management of CKD.

International validation of this tool has shown that the four-variable KFRE (age, sex, eGFR, urinary albumin-creatinine ratio) is particularly effective in short-term prediction of progression to end-stage renal disease. However, KFRE adoption varies significantly across national contexts, highlighting the need for specific adaptations to reflect local peculiarities, including demographic patterns and clinical practices. In Italy, the integration of KFRE could improve the efficiency of the healthcare system, reducing unnecessary referrals and concentrating resources on high-risk patients, in line with the principles of personalized and sustainable medicine [11]. Management of CKD requires accurate prediction of the risk of progression to ESKD to optimize educational strategies and clinical interventions. Recent studies have shown that the KFRE represents a valid and calibrated tool for estimating the 2- and 5-year risk of ESKD, exceeding intuitive estimates by nephrologists in terms of accuracy and precision. Unfortunately, the adoption of KFRE in daily clinical practice is still limited, resulting in many patients starting dialysis in late referral. Greater sensitivity of the KFRE model in medical practice suggests a potential use to identify high-risk patients with the initiation of timely treatment and with adequate programming of the dialysis modality most suitable for the patient (hemodialysis with creation of arteriovenous fistula for dialysis or peritoneal catheter) and a possible reduction in the use of temporary central venous catheters in the initiation of renal replacement therapy. These results highlight the importance of integrating standardized predictive tools such as the KFRE into healthcare policies to improve the management of patients with CKD [12].

 

Materials and Methods

Over the past 36 months, our nephrology center has implemented the systematic use of the KFRE in predialysis clinics to improve the management of patients with advanced CKD. The study involved a total of 100 patients followed in the predialysis process, in which the application of the KFRE guided clinical decisions relating to the timing of starting renal replacement therapy. KFRE was calculated using eight variables: age (years), sex (male/female), eGFR (estimated glomerular filtration rate according to CKD-EPI), UACR (urinary albumin-creatinine ratio in mg/dl), serum calcium level (mg/dl), serum bicarbonate (mEq/L), serum albumin (g/dl). The values ​​obtained made it possible to stratify the individual risk of progression towards end-stage renal disease (ESKD) and to plan all preparatory interventions for the start of dialysis. The calculation of the KFRE was carried out using the equation available on the official Kidney Failure Risk Equation website [1]. The main indicators analyzed in the study were: the reduction in the proportion of patients who started dialysis in late referral mode (i.e. with insufficient or no preparation before starting renal replacement treatment), the decrease in the use of temporary central venous catheters as the first access for hemodialysis, the increase in patient awareness in the choice of dialysis method (peritoneal dialysis or hemodialysis), thanks to a more structured education path, the increase in the percentage of patients with a native vascular access or with a peritoneal catheter packaged in adequate times before the start of dialysis.

 

Results

The collected data were analyzed retrospectively, comparing the results obtained with the historical pre-implementation data of the KFRE. In the three-year period 2017-2020, out of a total of 92 patients followed in predialysis clinics, 25% (23 patients) started dialysis with a temporary central venous catheter, 21.7% (20 patients) with a peritoneal catheter before starting dialysis, 38% (35 patients) with an arteriovenous fistula and 15.2% (14 patients) with a tunneled central venous catheter. In the three-year period 2021-2024, following the implementation of the KFRE, out of a total of 100 patients, only 5% (5 patients) started dialysis with a temporary central venous catheter, 35% (35 patients) with a peritoneal catheter before starting dialysis, 50% (50 patients) with an arteriovenous fistula and 10% (10 patients) with a tunneled central venous catheter (tCVC).

Figure 2. Types of dialysis access in two periods.
Figure 2. Types of dialysis access in two periods.

 

Discussion

The KFRE not only helps nephrologists predict the progression of chronic kidney disease, but also provides important decision support for planning arteriovenous fistula (AVF) packaging. The indication and timing for starting an AVF are crucial in the management of patients approaching dialysis, and the KFRE allows for more informed decisions in this regard [13]. Using parameters such as eGFR and albuminuria, the KFRE provides a clear estimate of the 2- or 5-year risk of end-stage renal disease (ESRD). In patients with high short-term risk (for example, greater than 20% at two years), it is recommended to consider AVF packaging early to be ready for the possible start of dialysis. Intermediate-risk patients can benefit from gradual and monitored preparation, allowing nephrologists to schedule AVF packaging only when necessary, avoiding premature invasive procedures [14]. Timely packaging of the AVF, guided by the KFRE, reduces the risk of complications and the possibility of depending on temporary catheters, which increase the risk of infections and other associated complications [15]. The KFRE allows nephrologists to intervene at the right time, when the risk of progression is high but not yet critical. In patients with a very low risk of rapidly progressing to dialysis, KFRE allows us to avoid early packaging of the AVF, which may be unnecessary. This saves costs and avoids unnecessary interventions for the patient. Together with other clinical parameters (such as the rate of decline of GFR and the patient’s age), the KFRE provides a basis for more precisely establishing the timing of the AVF, particularly useful for elderly patients or those with comorbidities, for whom an invasive intervention could pose greater risks [16]. Nephrologists can make more informed, risk-based decisions regarding AVF packaging. This helps reduce complications, optimize resources and improve the quality of care, ensuring that each patient receives the intervention at the right time. From here it follows that it is possible to stratify patients at different risk: high risk (e.g. >20% at 2 years): consider packaging the AVF quickly, with close monitoring; moderate risk (e.g. 10-20% at 2 years): frequent monitoring, with evaluation for packaging AVF if risk increases; low risk (<10% at 2 years): no immediate need to prepare the AVF; the patient can be followed up with regular follow-ups [17].

If the KFRE demonstrates a good level of accuracy, it could represent a useful tool to support the nephrologist in decisions regarding the management of patients with CKD. The integration of KFRE into clinical practice could facilitate risk stratification, optimize the timing of replacement therapies and improve the management of healthcare resources. The KFRE could also help reduce the anxiety of CKD patients by providing a more realistic prediction of the risk of disease progression. The validation of the KFRE is the first step towards personalized medicine in the management of CKD with better quality of care and efficient management of resources.  The integration of KFRE in the daily work of nephrology specialists will be able to promote the development of precision nephrology at the service of patient health and the sustainability of the system. Furthermore, the validation of the KFRE could increase patients’ motivation to follow medical recommendations by adopting a healthy lifestyle aimed at reducing risk factors.

 

Conclusion

In this study was documented that the implementation data of the KFRE notoriously reduced the percentage of patients who had started dialysis with a temporary central venous catheter, in comparison to the before KFRE implementation period.

 

Bibliography

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PD catheters: evolution towards optimal design

Abstract

The first peritoneal accesses were devices that had been used in other fields (general surgery, urology, or gynecology) for flush or irrigate: trocars, rubber catheters, and sump drains. The majority of cases were treated with the continuous flow technique; rubber catheters tor inflow and sump drains for outflow were commonly used. These early devices, used for short-term peritoneal dialysis, were plagued with multiple complications, such as pressure on intestines of rigid tubes, plugging of openings, leakage of fluid around the access, and difficulties in fixation of the tube on the abdominal wall. In the late 1940s, after World War II, multiple peritoneal accesses were tried, and first accesses specifically tor peritoneal dialysis were designed. In the 1950s and particularly 1960s new access features solved most of the problems and eliminated most complications of peritoneal dialysis performed in the supine position. The invention of silicone rubber catheter with polyester cuff(s) was a greatest breakthrough in peritoneal dialysis access development. Unfortunately, none of the currently used catheters is trouble free; poor dialysate drainage, pericatheter leaks, exit site and tunnel infections, and recurrent peritonitis episodes are frequently encountered. Therefore, there is an incessant search for new technological solutions, including new shapes of intraperitoneal and intramural catheter segments, and new catheter materials are tried.

Keywords: Peritoneal access, Abdominal drains, Cannulas, Catheters, Peritoneal lavage, Peritoneal irrigation, Peritoneal dialysis.

This paper will present a brief history of peritoneal access development and describe the designs of most commonly used devices. More complete history (seven times longer) has been described in my previous paper published in 2006 (1). For more details one can go to this paper.

Celsus in his treatise, De Medicina, written about 30 AD, described the drainage of fluid from the peritoneal cavity using a hollow cane stalks (in Latin canna – hence the name cannula) introduced after the incision of the abdominal wall. Since the 17th century the tube, usually metal, was introduced on trocar. In surgery the cannulas were used to flush (lavare), to hydrate or irrigate (irrigare) for bladder, gall, pleura, and peritoneum. Cannulas were also called probes or catheters (from Greek καθιεναιto send down, to introduce). For almost two centuries there were no publications on peritoneal dialysis in humans; however, the properties of peritoneum were studied in animals. Georg Wegner, from the University of Berlin, perfused the peritoneal cavity of rabbits. For the access he used a cannula with multiple side perforations that was introduced into the peritoneal cavity on the right side and exited on the left. He noted that hypotonic solutions were absorbed and hypertonic solutions increased in volume (2). Putnam from John Hopkins University, Baltimore, Maryland, USA, repeated many previous experiments and determined that the peritoneum behaves like a semi-permeable membrane (3).

Georg Ganter from Würzburg, Germany, is commonly credited with the first peritoneal dialysis in humans for the purpose of treatment of uremia. In his paper from 1923 (4) Ganter described several experiments of peritoneal dialysis in guinea pigs, where he infused normal saline into the peritoneal cavity and drained it after a short period of time. His first attempt of sodium chloride infusion into serous cavity was done in Greiswald, Germany, in 1918. In a patient with terminal uremia he drained 3/4 liters of effusate from the right pleural space and replaced it with normal saline. He did not drain the solution, but observed improvement in the patient’s condition. In the same paper he reported on two cases of normal saline infusion into the peritoneal cavity; in the first case with bilateral ureteral obstruction due to uterine carcinoma, he infused 1½ liters of normal saline, in the second case he infused “3 liters of normal saline to a diabetic patient, who lay totally unconscious in coma; the patient’s condition improved temporarily so the relatives could communicate with him”. In all cases he used a needle commonly used at that time for abdominal and pleural punctures. In patients, he did not drain the fluid as he did in guinea pigs, so it was not dialysis as we understand it now; however, there was some dialysis into the saline solution. In his paper he speculated on the possibility of using two punction needles for simultaneous infusion and drainage of the rinsing fluid.

Rosenak from Budapest, working as a volunteer in Bonn, and Siwon, from the Surgery Department at the University of Bonn, Germany, performed several experiments on continuous dialysis in nephrectomized dogs in 1926 (5). They inserted two glass cannulas through laparotomy. The inflow cannula tip was placed below the liver, the outflow in the Douglas cavity. Simple glass tubes, used in early experiments, were frequently obstructed so they decided to provide “cannulas with flask shape, multi-perforated, sprinkling can rose-like tips”. These were manufactured by Geissler from Bonn. If the cannula became obstructed despite this modification, they performed omentectomy before inserting new cannulas.

The first continuous flow peritoneal dialyses in humans with acute renal failure caused by poisoning with mercury bichloride were performed in two patients by Balazs and Rosenak from St. Rochus Hospital in Budapest, Hungary in 1934 (6). For peritoneal access they used glass cannulas distended globularly at the tip and having multiple holes (similar to those used previously by Rosenak and Siwon (5) or cannulas made of fine wire. The inflow cannula was introduced between the liver and the diaphragm, the outflow cannula was inserted into the Douglas cavity. Both cannulas were introduced by laparotomy under local and light ethyl chlorine anesthesia. In the first patient the continuous dialysis lasted 1/2 hour and 12 liters of 4.2% glucose were used, in the second patient 19 liters of 0.8% saline were used during 1½ hours of continuous dialysis. Both patients died.

The first case of a patient who survived after peritoneal lavage for the treatment of uremia in April, 1937, was reported by Wear, Sisk, and Trinkle from the Wisconsin General Hospital, Madison, Wisconsin, USA (7). “The procedure was carried out by morphine and nembutal anesthesia. A standard gall bladder trochar was introduced in the upper abdomen. The trochar introduced into the lower abdomen was modified by placing numerous small holes in the distal third to avoid occlusion of a single opening by the omentum and intestine. From an insulated reservoir the fluid was introduced into upper cannula. The lower cannula was attached to rubber tubing which hung dependent to a bottle on the floor and acted as syphon”. The authors used the procedure in five cases, but only one patient survived. This was a case of reflex anuria superimposed on obstructive uropathy due to kidney and bladder stones. In spite of urethral catheterization the patient’s condition deteriorated and continuous peritoneal lavage with Locke-Ringer’s solution was performed. No details of the amount of fluid were given. After the lavage, the urine output gradually increased and the bladder stone was successfully removed. It is difficult to say whether the single peritoneal lavage was important for patient’s survival. The authors treated four more patients with continuous peritoneal lavage, using up to 33 L of fluid for a session, but none survived.

No papers on peritoneal lavage, irrigation or dialysis appeared during World War II, but the number of renal failure cases after war trauma must have accelerated research on renal replacement therapies. Seligman, Frank, and Fine from the Surgical Research Department, Beth Israel Hospital and the Department of Surgery, Harvard Medical School, Boston, Massachusetts, USA, performed a series of experiments on nephrectomized dogs to determine suitable peritoneal access, optimal flow of continuous flow peritoneal irrigation, and proper irrigation fluid. The access was a mushroom-tip type catheter inserted through an incision or whistle-tip (urethral catheter with a terminal opening as well as a lateral one) type inserted using a trocar. Both types had added perforations. Mushroom type catheters drained more effectively than the whistle-tip type catheters. “To help maintain patency of the irrigating catheters in long term experiments, omentectomy was performed at the time of nephrectomy”. “Ringer’s solution containing glucose, used in the early experiments, was changed later to Tyrode’s solution. In addition, the irrigation fluid contained sodium penicillin and sodium sulfadiazine for prophylaxis against infection, and the sodium salt of heparin in order to minimize the intraperitoneal formation of fibrin and adhesions” (8). The same group of authors reported the use of this method for treatment of patients. Four patients were presented at the meeting of the American Surgical Association, Hot Springs, Virginia, USA, April 2-4, 1946, by Jacob Fine and published in November 1946 (9). One patient with acute renal failure due to “parenchymatous injury to the kidneys from sulfathiazole administration” was also reported separately in more detail (10). The mushroom catheter and the sump drain were used in this case. The patient ultimately recovered kidney function. Although in the discussion the authors stated that “(w)e cannot state with finality that the patient would have died without peritoneal irrigation”, the severity of the case, fifteen days of oliguria/anuria, and improvement during peritoneal lavage seem to justify the assumption that this was the first patient who survived because of peritoneal dialysis. The report in JAMA of successful use of peritoneal irrigation in acute renal failure prompted others to implement this method.

The major problems encountered by clinicians treating patients with peritoneal irrigation were related to peritoneal access. Rosenak, working with Oppenheimer at the Mount Sinai Hospital in New York, New York, USA, in a paper published in Surgery in 1948 (11) listed the five most troublesome complications of peritoneal drains used for fluid outflow: “1) Rigidity of the tube with resulting pressure on the intestines, 2) Constant suction of contaminated air into the peritoneal cavity, 3) Occasional plugging of the small openings, 4) Leakage of lavage fluid into the dressing, which is a potential source of infection and which make exact determination of nitrogen output difficult, 5) Difficulties of proper fixation of the tube on the abdominal wall”. For the first time they developed a drain specifically for peritoneal dialysis. Made of stainless steel the tube provided a rigid extra-abdominal portion, but flexible intraperitoneal portion made of a spiral, stainless steel spring wire with a rounded tip. An adjustable plate was screwed to the outer portion of the steel tube and served for fixation to the abdominal wall by means of adhesive plaster. The straight inner tube was located inside the extra-abdominal rigid tube and extended about half an inch into the flexible intra-abdominal tube. This inner tube was fitted with a rubber tube connection for suction aspiration for fluid outflow. There was an air space between the inner and the outer tube which was connected with the right angle air inlet tube further connected with a glass funnel covered with several layers of sterile gauze. Because of this connection with air, no significant negative pressure could develop. The authors believed that this would prevent omentum from being drawn into interstices of the spring coil. The access was used in dog experiments and, according to the authors, performed satisfactorily. This peritoneal access was factory-built (Speedo Manufacturing Company, New York, New York, USA.) Compared to the sump drain, the access introduced two important improvements: flexible tube made of spiral wire instead of rigid network of cords and the plate for fixation to the abdominal wall.

By permission of Oppenheimer, a second version of the Rosenak-Oppenheimer access was described by Ferris and Odel from the Mayo Clinic, Rochester, Minnesota, USA (12). The improved version had two accesses, one for inflow and one for outflow. They found the inflow tube to be entirely satisfactory. However, they experienced considerable difficulty in fluid outflow, because the flexible steel spring appeared to be wound too tightly. They were also concerned with the foreign body reaction to metal and rubber tubes. Accordingly, they improved the Rosenak­Oppenheimer access by changing the intra-abdominal portion of the outer tube. Instead of the spring coil they used a polyvinyl tube with multiple perforations. This tubing was “sweated” into the stainless steel portion of the tube with acetone. The tips of the tubes were provided with plugs consisting of bendaloy completely encased in the polyvinyl. The tubes were weighted with these plugs to insure they would hang dependently in the peritoneal cavity. This was particularly important for the outflow tube to keep the tip in the true pelvis, the place of a fluid reservoir. Francis and Odel introduced two important ideas in their access: 1) use of plastic (polyvinyl) for the intra-abdominal segment of the access, and 2) use of weights to keep the tip of the tubing in the true pelvis. Both ideas were emulated later by other inventors.

Rapid progress in peritoneal dialysis was made in the 1950s. Grollman, from the Southwestern Medical School of the University of Texas, Dallas, Texas, USA, and his collaborators reported their experience with intermittent peritoneal lavage in nephrectomized dogs and 5 patients. The fluid was infused and drained from the peritoneal cavity through a single polyethylene tube placed through the anterior abdominal wall, “(a) trocar was inserted as in the routine removal of ascitic fluid, the stylet replaced with the polyethylene plastic tube, and the trocar removed” (13).

The next major progress was made in the late 1950s when Maxwell, Rockney, Kleeman and Twiss from the University of California in Los Angeles, California, USA, reported their experience with 76 peritoneal dialyses (14). Seemingly minor improvements in the technique provided major improvements in results. The catheter was introduced with a technique similar to that of Grollman et al (13) but the semirigid catheter was made of nylon (polyamide) instead of polyethylene, had rounded tip, and had numerous very tiny perforations (80 holes of 0.2 inch diameter (0.508 mm) instead of larger openings at the distal 3 inches. The authors believed that the use of nonirritating plastic prevented omentum and intestines from clinging to the catheter, and that the small diameter of perforations prevented particles of omental fat from plugging the catheter. They used a 17F Duke trocar set for insertion of the catheter. Two liters of solution, available in 1 L bottles, were warmed to body temperature, and connected through a Y-tubing to the catheter. The fluid dwelled in the catheter was manufactured by the Medical Development Corporation, Miami, Florida, USA. The catheter was introduced surgically under direct vision deep into the posterior pelvis or through a 22 G gallbladder trocar in the midline directly below the umbilicus. The drainage of fluid from the peritoneal cavity was markedly improved compared to sump drains, but leakage and pericatheter infections continued to plague the access.

The next major progress was made in the mid-1960s. Weston and Roberts made a small improvement by providing Maxwell catheter with a pointed stylet, thus eliminating the need of insertion through the cannula. A sharp stainless steel stylet (“three-sided trocar point”) inserted through the nylon catheter was used to penetrate the abdominal wall. As a result, the abdominal opening fitted snugly around the catheter, thereby preventing leakage (15). The stylet catheters soon became commercially available (Trocath) from Don Baxter Inc., Glendale, California, USA, and McGraw Laboratories, Milledgeville, Georgia, USA. Only local anesthesia was used for catheter insertion. Before catheter insertion the abdomen was filled with dialysis solution via a 14 or 15 gauge needle inserted through the linea alba below the umbilicus. Then a small incision was made in the skin, the catheter with the stylet was pierced through the abdominal wall.

However, the major progress was made by applying a silicone rubber as a material for peritoneal catheter. Silicon rubber was flexible so it did not press on the intestines, and was inert, not causing peritoneal membrane irritation. In 1964 a preliminary communication appeared in the Lancet describing the use of silicone rubber peritoneal catheter in two patients (16). Palmer, not satisfied with the available catheters, and Quinton, already successful in manufacturing silicone rubber shunts for hemodialysis (W.E. Quinton Instrument Co., Seattle, Washington, USA), developed a catheter, which is the prototype for currently used catheters. It was 84 cm long and had internal diameter of 2 mm. The intraperitoneal part of the catheter was coiled and had numerous perforations in the distal 23 cm. In the middle the catheter had a triflange step for locating in the deep fascia and the peritoneum.

In 1968, Henry Tenckhoff and H. Schechter from the University of Washington, Seattle, Washington, USA, published the results of their studies on a new catheter (17). Their catheter was an improved version of the Palmer catheter. An intraabdominal flange was replaced by a Dacron® felt cuff, which allowed tissue growth into it, fixing the catheter in the tunnel and restricting penetration of bacteria (Figure 1). A subcutaneous tunnel was shortened and a second, external cuff was used to decrease the length of the catheter sinus tract. The external cuff was not protruding through the skin, but was located just below the skin surface. To keep both exits (external and internal) down the intramural silicon tubing was bent. The intraperitoneal segment was open ended and the size of the side holes was optimized to 0.5 mm to prevent tissue suction. As mentioned above, the small diameter of side holes was recommended by Maxwell et al. (14) 19 years earlier. A shorter subcutaneous tunnel and a straight intraperitoneal segment facilitated catheter implantation at the bedside. To avoid excessive bleeding, the catheter was inserted through the midline. The initial results in six patients were excellent with 5 catheters functioning for 4-14 months.

The Tenckhoff catheter has become the gold standard of peritoneal access. Some of the original recommendations for catheter insertion such as an arcuate subcutaneous tunnel with downward directions of both intraperitoneal and external exits are still considered very important elements of catheter implantation. Few complications were reported in patients treated with periodic peritoneal dialysis in the supine position. However, in patients treated with continuous ambulatory peritoneal dialysis (CAPD), complications became more frequent, due to high intra-abdominal pressure in the upright position and numerous daily manipulations. The most common complications were: exit/tunnel infection, tip migration out of the true pelvis predisposing to obstruction, external cuff extrusion, pericatheter leak, and peritonitis.

To decrease the rate of tip migration modifications of Tenckhoff catheter were made in Toronto, Canada by Oreopoulos and his collaborators and manufactured as TWH (Toronto Western Hospital) catheter by Zellerman company (18). The intraperitoneal portion of the catheter was provided with three silicone discs. Six years later to prevent pericatheter leaks, from the same institution, a TWH-2 catheter was described (19). This catheter inserted through the rectus muscle had two Dacron cuffs, but the deep cuff was provided with a Dacron disc (flange) and a silicone ring (bead) at the deep cuff to create a better seal and prevent pericatheter leaks. The intraperitoneal portion was provided with two silicone discs (Figure 1).

The retrospective analysis of complication rates with Tenckhoff and Toronto Western Hospital catheters at the University of Missouri, Columbia, Missouri, USA, (20) showed that the lowest complication rates were with double cuff catheters implanted through the belly of the rectus muscle and with both internal and skin exits of the tunnel directed downward; however, the resulting arcuate tunnel led to frequent external cuff extrusions. To avoid this complication a permanent bend between cuffs was postulated and such a catheter was manufactured by Accurate Surgical Instruments, Toronto, Ontario, Canada. The catheter was dubbed “swan neck” because of its shape (20). Because of this design, catheters can be placed in an arcuate tunnel in an unstressed condition with both external and internal segments of the tunnel directed downward (Figure 2). The downward directed exit, two cuffs, and optimal sinus length reduce exit/tunnel infection rates. A permanent bend between the cuffs eliminates the silicone rubber resilience force or “shape memory”, which tends to extrude the external cuff. The downward peritoneal entrance tends to keep the tip in the true pelvis, reducing its migration. Similar to TWH-2 catheter Swan Neck Missouri (Figure 2) catheter has a flange and bead circumferentially surrounding the catheter below the internal cuff but the flange and bead are slanted approximately 45° relative to the axis of the catheter (Figure 3). This feature helps to maintain downward direction of the intraperitoneal segment. Insertion through the rectus muscle decreases pericatheter leaks. Lower exit/tunnel infection rates curtail peritonitis episodes. Finally, swan-neck catheters with a coiled intraperitoneal segment (Figure 2) minimize infusion and pressure pain. Slanted flange and curved intratunnel part requires different catheters for the right and left side (Figure 2). Swan neck catheters are designed to have an exit in the abdominal integument (swan-neck abdominal, Missouri, catheters) or in the chest (swan-neck presternal catheter – Figure 4).

The idea of a presternal exit location stemmed from several observations indicating that this location may decrease exit infections (21). The chest is a sturdy structure with minimal wall motion; the catheter exit located on the chest wall is subjected to minimal movements decreasing chances of trauma and contamination. Also, in patients with abdominal ostomies and in children with diapers, a chest exit location decreases chances of contamination. Moreover, a loose garment is usually worn on the chest and there is less external pressure on the exit. Clinical surgical experience indicates that wounds heal better after thoracic surgery than after abdominal surgery; this may be related to less chest mobility or some other reasons. Obese patients have higher exit site infection rates and a tendency to poor wound healing, particularly after abdominal surgery. The subcutaneous fat layer is several times thinner on the chest than on the abdomen. If fat thickness per se is responsible for quality of healing and susceptibility to infection then the chest location may be preferred for obese patients. The catheter is particularly useful in obese patients (BMI>35), patients with ostomies, children with gastrostomy tubes, diapers, and fecal incontinence, and patients who want to take tub baths without the risk of exit contamination. Many patients prefer a presternal catheter because of better body image.

To accommodate these principles, the swan-neck peritoneal catheter was modified to have an exit on the chest but preserving all advantages of the swan-neck Missouri coiled catheters; minimizing catheter obstruction, cuff extrusion, pericatheter dialysate leak and infusion pain The major differences from the swan-neck Missouri catheter are the length of the subcutaneous tunnel and three instead of two cuffs. The presternal peritoneal dialysis catheter is composed of two flexible (silicon rubber) tubes, which are connected end to end with a titanium connector in the tunnel (Figure 4).

In conclusion, technological evolution never ends. Many improvement of Tenckhoff catheter provided better results. Nevertheless, even today, almost five decades after first use, the Tenckhoff catheter in its original form is widely used catheter type. More information on peritoneal catheters and their implantation is available in the recent book chapter (22).

 

References

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  3. Putnam TJ. The living peritoneum as a dialyzing membrane. Am J Physiol 1923; 63: 548-65.
  4. Ganter G. Ueber die Beseitigung giftiger Stoffe aus dem Blute durch Dialyse (On the eliminaton of toxic substances from the blood by dialysis.) 1223; 70; 1478–80.
  5. Rosenak S, Siwon P. Experimentelle Untersuchungen über die peritoneale Ausscheidung harnpflichtiger Substanzen aus dem  Blute (Experimental  investigations on the peritoneal eliminationfrom the blood of substances normally excreted in urine). Mitteilungen aus den Grenzgebieten der Medizin und Chirurgie 1926; 39: 391-408.
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  10. Frank HA, Seligman AM, Fine J. Treatment of uremia after acute renal failure by peritoneal irrigation. JAMA 1946; 130: 703-5.
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  12. Ferris DO, Odel HM. An improved plastic tube for use in peritoneal lavage: Preliminary report. Proceedings of the Staff Meetings of the Mayo Clinic 1948; 23: 612-4.
  13. Grollman A, Turner LB, McLean JA. Intermittent peritoneal lavage in nephrectomized dogs and its application to the human being. Arch Intern Med 1951; 87: 379-90.
  14. Maxwell MH, Rockney RE, Kleeman CR, Twiss MR. Peritoneal dialysis. JAMA 1959; 170: 917-24.).
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