- Email: [email protected]
Peritoneal dialysis: The state of the art in Europe
Of Nephrology and Nephrologists Spotlighting new and provocative developments in world nephrology and featuring nephrologists who occupy leadership roles
Manuel Martı´nez-Maldonado, MD Editor-at-Large
Peritoneal Dialysis: The State of the Art in Europe Claudio Ronco, MD
E
UROPE’S metamorphosis from a conglomeration of autonomous nations into a community of countries is bringing medical practice in closer association with the economy and the politics of the region. Although economic and political differences among European countries still exist, the strategy for the treatment of uremia has become unified through the efforts of the European Dialysis and Transplant Association (EDTA) to establish a patient registry and uniform guidelines for the treatment of end-stage renal disease (ESRD). The provision of peritoneal dialysis (PD) as a therapeutic alternative to ESRD patients is now viewed as an ethical obligation, particularly because it is a superior therapy under specific circumstances. PERITONEAL DIALYSIS AND HEMODIALYSIS AS THERAPY FOR UREMIA
The ESRD patient must be kept informed of the potentially progressive nature of renal failure. The need for renal replacement therapy should not come as a surprise, and the patient must be aware that the choices include hemodialysis, PD, and transplantation. In addition to serving the patient’s medical needs, the availability of choices optimizes the allocation of resources and, in recent years, has reduced the unfettered growth of costly hemodialysis programs. PD has reduced the use of hospital-based hemodialysis units, but, being a self-care treatment, it requires absolute commitment by the patient, continuous support from the family, and a clear understanding by all involved of the limitations of the technique. Nevertheless, to ensure the offering of treatment choices to patients, the training of the renal team members must continue so that pro-hemodialysis bias does not cloud the indications for PD. l
PERITONEAL DIALYSIS SYSTEM
The PD system comprises the microvasculature, the mesothelium, and the peritoneal cavity. Controversy exists as to the limiting role of the microvasculature in PD. The ‘‘nearest capillary hypothesis’’ suggests that the capillaries closest to the mesothelial cells participate in the exchanges; the rest of the capillaries represent a reserve for solute exchange. In this view, the diffusion of molecules from blood to dialysis fluid depends on the thickness of the peritoneal interstitium, which is the key determinant of peritoneal transport. Reduced permeability results from damage of the capillaries closest to the mesothelium; excessive permeability may occur if interstitial thickness is reduced or if capillaries proliferate in the vicinity of the mesothelial barrier. Mesothelial cells synthesize various chemical mediators that may be involved in the sclerosing process of the peritoneal membrane that frequently accompanies PD. Another component, intra-abdominal pressure, correlates with the speed of the exchanges and the size of the filling volume. Calculation of fluid tidal volumes has increased the possibility of reaching adequacy targets in PD prescription. Flows and dwell times can be predetermined and achieved thanks to manual exchange procedures or to special cyclers or exchange devices. TREATMENT ADEQUACY, PRESCRIPTION, AND OUTCOME
Early studies in continuous ambulatory peritoneal dialysis (CAPD) suggested that adequacy was achieved by weekly Kt/V values of 1.7. To guarantee low mortality and morbidity in ESRD, target values for Kt/V of 2.0 to 2.2 and weekly creatinine clearance of 60 to 66 L have been
American Journal of Kidney Diseases, Vol 33, No 3 (March), 1999: pp l-lii
OF NEPHROLOGY AND NEPHROLOGISTS
Prof Dr Claudio Ronco Department of Nephrology St Bortolo Hospital Vicenza, Italy
T
HE GREAT Renaissance painter Andrea Mategna was born between Padua and Vicenza—possibly in Isola de Carturo—in the Veneto region of northern Italy. Claudio Ronco was born in a small town near Vicenza and has spent his life going from Vicenza to Padua and back. The young Ronco, who was at the top of his class when he received his doctorate in medicine and surgery, was educated in the classics in Padua and must have been influenced by the city’s illustrious medical past. Being on top became a habit. While training in adult and pediatric nephrology, Ronco received the highest scholastic distinctions. Today he is the director of the hemodialysis and peritoneal dialysis program at St Bortolo Hospital in Vicenza and professor of nephrology at his alma mater, the University of Padua. He also is in charge of the hemodialysis and critical care nephrology teaching program in the university’s postgraduate school. Taking his cues from the spirit of his Renaissance heritage, Professor Ronco is a dynamic and tireless
suggested for CAPD and NPD, respectively (DOQI 1997). Adequacy in Europe has always included great attention to the clinical condition of the patient, to the maintenance of residual renal function, and to nutritional status. These have been considered more critical than urea kinetics. Dietary protein intake correlates with dialysis efficiency in a nonlinear fashion that displays a plateau after a certain increase in weekly Kt/V. Thus, a minimum efficiency should be reached in patients to guarantee freedom from uremic symptoms and thus ensure good appetite and nutrition. Adequacy is viewed as control of dry body weight, blood pressure and acidosis, optimal calcium-phosphate balance, and a good state of physical rehabilitation. The frequency of visits to the physician (the MDt/P index: Medical Doctor visits ⫻ time/patient) stresses the greater usefulness of clinical condition evaluation over the use of adequacy software.
li
investigator and clinician. As a result of his interest in biomaterials, hydraulics, engineering, and instrumentation, he introduced to Italy the use of continuous hemofiltration and was responsible for the first use of the technique in neonates. Professor Ronco is a popular speaker at countless meetings and congresses. He has authored close to 330 journal publications and 12 books. It is rare to pick up a nephrology journal in which his name does not appear in the editorial board members listings. His pioneering contributions to the use of replacement therapy in different medical settings has led to visiting professorships at important institutions around the world. His leadership skills have placed him on the council of the Italian Society of Nephrology, the European Society of Artificial Organs, and the International Society for Peritoneal Dialysis. A world leader in renal replacement therapy, he is particularly proud of the time—one whole year over a period of a decade—he spent in Juan Bosch’s unit at George Washington University, in Washington, DC. Never idle, Claudio Ronco goes skiing in the Dolomites and sailing in Lake Garda with his son, a medical student, and his admiring wife Paola. In his talks, Professor Ronco’s quest to meld engineering and medicine becomes so intense that one would conclude that’s the only subject in his mind. Nevertheless, given the chance, he confesses that what he would really like to do is open a small restaurant and show off his culinary skills . . . when he retires, of course! —Manuel Martı´nez-Maldonado, MD
PD maintains residual renal function for a longer time and appears preferable as initial renal replacement therapy. Correction for comorbid conditions reveals that patient survival is not different between PD and hemodialysis. Nevertheless, PD technical failure of 50% at 5 years is much higher than in hemodialysis. The differences among programs conducting PD usually relate to technical survival, which in turn is probably the best index of quality of dialysis and in determining outcomes. Technical failures include peritonitis and inadequacy of dialysis from loss of ultrafiltration capacity. Frequent episodes of peritonitis in the early phases of PD should lead to discontinuation of the modality. The long-term outcome depends on the maintenance of the peritoneal membrane capacity for solute clearances and ultrafiltration. Nonbiocompatible PD solutions can adversely affect these characteristics, and
lii
OF NEPHROLOGY AND NEPHROLOGISTS
their use should be abandoned in favor of newer and safer solutions. NEW PERITONEAL DIALYSIS SOLUTIONS
A survey of EDTA nephrologists and nephrology nurses indicated that ultrafiltration loss was felt to be induced by glucose and glucosederived products. Other problems of biocompatibility were felt to be generated by lactate and the inflammatory action of acidic solutions. The ideal solution would have a different osmotic agent, be lactate free, and made pH neutral with bicarbonate. Ongoing studies aimed at achieving these objectives should provide results soon, particularly the efficacy of bicarbonate-buffered PD solutions. Morphological (vacuolar degeneration, loss of microvilli, and so forth) and functional (phosphatidylcholine secretion and lubricating activity) changes are less evident in human peritoneal cells in culture incubated in solutions in which lactate is replaced by bicarbonate. Early results of a large European trial using commercially available bicarbonate-buffered solutions are promising in maintaining long-term peritoneal membrane function. Substitution of glucose by other osmotic agents is more difficult, but recent studies with icodextrins, glycerol, and amino acids seem to be promising. Polyglucose solutions have limited osmotic efficiency in shortdwell exchanges, increase plasma levels of maltose and maltotriose, and may block the reticuloendothelial system. Advantages of polyglucose solutions include their iso-osmotic composition, reduced intake of calories per milliliter of ultrafiltrate, minimal or absent insulin response, and sustained ultrafiltration in long-dwell exchanges. Amino acid solutions have limited osmotic efficiency and clinical tolerance, and increase the chances of acidosis. The concurrent development of new biomaterials (polyolefines) for PD bags that produce fewer plastic residuals and other products after the sterilization procedures may further contribute to the long-term preserva-
tion of the peritoneal membrane by reducing inflammation and sclerosis. DEVICES AND TECHNIQUES
The PD prescription is aimed at maximal efficiency of small-molecule clearances and ultrafiltration to achieve good clinical tolerance, good nutritional intake, and maximal patient compliance to therapeutic schedules. Different forms of automated peritoneal dialysis (APD) are frequently prescribed as sole therapy or in conjunction with long-dwell exchanges of CAPD. Different cyclers permit additional long-dwell exchanges in APD for patients with low peritoneal membrane permeability, whereas short, rapid exchanges are performed nightly in patients with medium-to-high permeability. Compliance and the adequacy parameters can be monitored by computerized programs or by manual methods so that the validity of the prescription can be assessed throughout life and modifications in prescription and treatment schedule introduced as needed. New exchange devices and monitoring equipment are available to meet the technical requirements imposed by these new therapeutic schedules. The use of the Y set, for example, has represented a milestone in this field. CONCLUSION
In Europe, PD is considered as suitable as hemodialysis for renal replacement therapy, with transplantation as the ultimate treatment. The therapy of uremia is viewed as more than a simple measurement of Kt/V. Dialysis adequacy includes clinical assessment and evaluation of the degree of rehabilitation, both of which temper the decisions for changes in treatment schedule and intensity of therapy. The newest technological innovations have greatly improved the monitoring of compliance and adequacy use. The next frontier, the development of improved biocompatible solutions, is the subject of intense research.
Manuel Martı´nez-Maldonado, MD Editor-at-Large
Peritoneal Dialysis: The State of the Art in Europe Claudio Ronco, MD
E
UROPE’S metamorphosis from a conglomeration of autonomous nations into a community of countries is bringing medical practice in closer association with the economy and the politics of the region. Although economic and political differences among European countries still exist, the strategy for the treatment of uremia has become unified through the efforts of the European Dialysis and Transplant Association (EDTA) to establish a patient registry and uniform guidelines for the treatment of end-stage renal disease (ESRD). The provision of peritoneal dialysis (PD) as a therapeutic alternative to ESRD patients is now viewed as an ethical obligation, particularly because it is a superior therapy under specific circumstances. PERITONEAL DIALYSIS AND HEMODIALYSIS AS THERAPY FOR UREMIA
The ESRD patient must be kept informed of the potentially progressive nature of renal failure. The need for renal replacement therapy should not come as a surprise, and the patient must be aware that the choices include hemodialysis, PD, and transplantation. In addition to serving the patient’s medical needs, the availability of choices optimizes the allocation of resources and, in recent years, has reduced the unfettered growth of costly hemodialysis programs. PD has reduced the use of hospital-based hemodialysis units, but, being a self-care treatment, it requires absolute commitment by the patient, continuous support from the family, and a clear understanding by all involved of the limitations of the technique. Nevertheless, to ensure the offering of treatment choices to patients, the training of the renal team members must continue so that pro-hemodialysis bias does not cloud the indications for PD. l
PERITONEAL DIALYSIS SYSTEM
The PD system comprises the microvasculature, the mesothelium, and the peritoneal cavity. Controversy exists as to the limiting role of the microvasculature in PD. The ‘‘nearest capillary hypothesis’’ suggests that the capillaries closest to the mesothelial cells participate in the exchanges; the rest of the capillaries represent a reserve for solute exchange. In this view, the diffusion of molecules from blood to dialysis fluid depends on the thickness of the peritoneal interstitium, which is the key determinant of peritoneal transport. Reduced permeability results from damage of the capillaries closest to the mesothelium; excessive permeability may occur if interstitial thickness is reduced or if capillaries proliferate in the vicinity of the mesothelial barrier. Mesothelial cells synthesize various chemical mediators that may be involved in the sclerosing process of the peritoneal membrane that frequently accompanies PD. Another component, intra-abdominal pressure, correlates with the speed of the exchanges and the size of the filling volume. Calculation of fluid tidal volumes has increased the possibility of reaching adequacy targets in PD prescription. Flows and dwell times can be predetermined and achieved thanks to manual exchange procedures or to special cyclers or exchange devices. TREATMENT ADEQUACY, PRESCRIPTION, AND OUTCOME
Early studies in continuous ambulatory peritoneal dialysis (CAPD) suggested that adequacy was achieved by weekly Kt/V values of 1.7. To guarantee low mortality and morbidity in ESRD, target values for Kt/V of 2.0 to 2.2 and weekly creatinine clearance of 60 to 66 L have been
American Journal of Kidney Diseases, Vol 33, No 3 (March), 1999: pp l-lii
OF NEPHROLOGY AND NEPHROLOGISTS
Prof Dr Claudio Ronco Department of Nephrology St Bortolo Hospital Vicenza, Italy
T
HE GREAT Renaissance painter Andrea Mategna was born between Padua and Vicenza—possibly in Isola de Carturo—in the Veneto region of northern Italy. Claudio Ronco was born in a small town near Vicenza and has spent his life going from Vicenza to Padua and back. The young Ronco, who was at the top of his class when he received his doctorate in medicine and surgery, was educated in the classics in Padua and must have been influenced by the city’s illustrious medical past. Being on top became a habit. While training in adult and pediatric nephrology, Ronco received the highest scholastic distinctions. Today he is the director of the hemodialysis and peritoneal dialysis program at St Bortolo Hospital in Vicenza and professor of nephrology at his alma mater, the University of Padua. He also is in charge of the hemodialysis and critical care nephrology teaching program in the university’s postgraduate school. Taking his cues from the spirit of his Renaissance heritage, Professor Ronco is a dynamic and tireless
suggested for CAPD and NPD, respectively (DOQI 1997). Adequacy in Europe has always included great attention to the clinical condition of the patient, to the maintenance of residual renal function, and to nutritional status. These have been considered more critical than urea kinetics. Dietary protein intake correlates with dialysis efficiency in a nonlinear fashion that displays a plateau after a certain increase in weekly Kt/V. Thus, a minimum efficiency should be reached in patients to guarantee freedom from uremic symptoms and thus ensure good appetite and nutrition. Adequacy is viewed as control of dry body weight, blood pressure and acidosis, optimal calcium-phosphate balance, and a good state of physical rehabilitation. The frequency of visits to the physician (the MDt/P index: Medical Doctor visits ⫻ time/patient) stresses the greater usefulness of clinical condition evaluation over the use of adequacy software.
li
investigator and clinician. As a result of his interest in biomaterials, hydraulics, engineering, and instrumentation, he introduced to Italy the use of continuous hemofiltration and was responsible for the first use of the technique in neonates. Professor Ronco is a popular speaker at countless meetings and congresses. He has authored close to 330 journal publications and 12 books. It is rare to pick up a nephrology journal in which his name does not appear in the editorial board members listings. His pioneering contributions to the use of replacement therapy in different medical settings has led to visiting professorships at important institutions around the world. His leadership skills have placed him on the council of the Italian Society of Nephrology, the European Society of Artificial Organs, and the International Society for Peritoneal Dialysis. A world leader in renal replacement therapy, he is particularly proud of the time—one whole year over a period of a decade—he spent in Juan Bosch’s unit at George Washington University, in Washington, DC. Never idle, Claudio Ronco goes skiing in the Dolomites and sailing in Lake Garda with his son, a medical student, and his admiring wife Paola. In his talks, Professor Ronco’s quest to meld engineering and medicine becomes so intense that one would conclude that’s the only subject in his mind. Nevertheless, given the chance, he confesses that what he would really like to do is open a small restaurant and show off his culinary skills . . . when he retires, of course! —Manuel Martı´nez-Maldonado, MD
PD maintains residual renal function for a longer time and appears preferable as initial renal replacement therapy. Correction for comorbid conditions reveals that patient survival is not different between PD and hemodialysis. Nevertheless, PD technical failure of 50% at 5 years is much higher than in hemodialysis. The differences among programs conducting PD usually relate to technical survival, which in turn is probably the best index of quality of dialysis and in determining outcomes. Technical failures include peritonitis and inadequacy of dialysis from loss of ultrafiltration capacity. Frequent episodes of peritonitis in the early phases of PD should lead to discontinuation of the modality. The long-term outcome depends on the maintenance of the peritoneal membrane capacity for solute clearances and ultrafiltration. Nonbiocompatible PD solutions can adversely affect these characteristics, and
lii
OF NEPHROLOGY AND NEPHROLOGISTS
their use should be abandoned in favor of newer and safer solutions. NEW PERITONEAL DIALYSIS SOLUTIONS
A survey of EDTA nephrologists and nephrology nurses indicated that ultrafiltration loss was felt to be induced by glucose and glucosederived products. Other problems of biocompatibility were felt to be generated by lactate and the inflammatory action of acidic solutions. The ideal solution would have a different osmotic agent, be lactate free, and made pH neutral with bicarbonate. Ongoing studies aimed at achieving these objectives should provide results soon, particularly the efficacy of bicarbonate-buffered PD solutions. Morphological (vacuolar degeneration, loss of microvilli, and so forth) and functional (phosphatidylcholine secretion and lubricating activity) changes are less evident in human peritoneal cells in culture incubated in solutions in which lactate is replaced by bicarbonate. Early results of a large European trial using commercially available bicarbonate-buffered solutions are promising in maintaining long-term peritoneal membrane function. Substitution of glucose by other osmotic agents is more difficult, but recent studies with icodextrins, glycerol, and amino acids seem to be promising. Polyglucose solutions have limited osmotic efficiency in shortdwell exchanges, increase plasma levels of maltose and maltotriose, and may block the reticuloendothelial system. Advantages of polyglucose solutions include their iso-osmotic composition, reduced intake of calories per milliliter of ultrafiltrate, minimal or absent insulin response, and sustained ultrafiltration in long-dwell exchanges. Amino acid solutions have limited osmotic efficiency and clinical tolerance, and increase the chances of acidosis. The concurrent development of new biomaterials (polyolefines) for PD bags that produce fewer plastic residuals and other products after the sterilization procedures may further contribute to the long-term preserva-
tion of the peritoneal membrane by reducing inflammation and sclerosis. DEVICES AND TECHNIQUES
The PD prescription is aimed at maximal efficiency of small-molecule clearances and ultrafiltration to achieve good clinical tolerance, good nutritional intake, and maximal patient compliance to therapeutic schedules. Different forms of automated peritoneal dialysis (APD) are frequently prescribed as sole therapy or in conjunction with long-dwell exchanges of CAPD. Different cyclers permit additional long-dwell exchanges in APD for patients with low peritoneal membrane permeability, whereas short, rapid exchanges are performed nightly in patients with medium-to-high permeability. Compliance and the adequacy parameters can be monitored by computerized programs or by manual methods so that the validity of the prescription can be assessed throughout life and modifications in prescription and treatment schedule introduced as needed. New exchange devices and monitoring equipment are available to meet the technical requirements imposed by these new therapeutic schedules. The use of the Y set, for example, has represented a milestone in this field. CONCLUSION
In Europe, PD is considered as suitable as hemodialysis for renal replacement therapy, with transplantation as the ultimate treatment. The therapy of uremia is viewed as more than a simple measurement of Kt/V. Dialysis adequacy includes clinical assessment and evaluation of the degree of rehabilitation, both of which temper the decisions for changes in treatment schedule and intensity of therapy. The newest technological innovations have greatly improved the monitoring of compliance and adequacy use. The next frontier, the development of improved biocompatible solutions, is the subject of intense research.