JOURNAL OF RENAL NUTRITION AND METABOLISM (2015) 1: 19-21 Nutrition and Peritoneal Dialysis 19


image

REVIEW ARTICLE


How does Peritoneal Dialysis Work?

Nutritional Challenges in Peritoneal Dialysis

Anurag Singh

Consultant Nephrologist and Traansplant Physician Allahabad



P

P

eritoneal dialysis (PD) was first performed on humans by Ganter, in Germany, in the 1920s. The relative simplicity

of the technique, its low cost, and the facility with which it could be performed by the patient at home all contributed to its popularity.


Peritoneal Transport

Understanding of peritoneal transport has been greatly facilitated by the development of three-pore model for peritoneal capillary transport. It states that solute and water transport across the peritoneal capillary occurs through three different sets of pores. The smallest of these are known as ultraporres and have diameters of 4 to 6 Angstroms. They correspond to acquaporin I channels and transport only water and not solute. Small pores are abundant, have a diameter of 40 to 60 Angstroms, and correspond to clefts in the endothelium. They transport small solutes and water in proportion to their concentrations in serum. Large pores have diameter of 100 to 200 Angstroms and also correspond is clefts in the endothelium. These pores are much fewer in number and are responsible for the transport of macromolecules such as albumin. In standard glucose based PD, approximately half of peritoneal water transport is accounted for by small pores and the other half by ultrapores. Because the proportion of water transported by ultrapores is solute free the total ultrafiltrate in PD has a lower solute concentration than serum. This is the phenomenon of sieving.

The two cardinal requirements for dialysis are that solute be cleared and fluid be removed from the uremic patient. Three distinct peritoneal transport processes occur and


image

Address for correespondance:

Dr Anurag Singh

Consultant Nephrologist and Traansplant Physician Janakipuram Colony, Near AMA Blood Bank,

32/6, Stanley Road, Allahabad


determine the success of fluid removal and solute clearance. These three processes are diffusion, convective ultrafiltration, and peritoneal fluid absorption.


Diffusion

The key factor determining diffusion for the given solute is of course the concentration gradient. In renal failure, plasma to dialysate concentration gradient for solutes such as urea or creatinine is the focus. The other major factor determining solute diffusion is the ability of the membrane to transport the solute concerned. This is expressed as the mass transfer area coefficient (MTAC). The MTAC for a given solute depends on the effective peritoneal surface area, which in turn, is determined by the size and vascularity of the patient's peritoneal membrane. There may also be submesothelial matrix. At the start of a PD dwell, the concentration gradient is maximal and solute removal is fastest. As the dwell proceeds and the gradient decreases, transport slow down. More frequent drainage and replenishment of the cavity with fresh solution tends to keep the gradient greater and maximizes peritoneal transport. Smaller solutes have higher MTAC values than larger ones.


Fluid Removal

Ultrafiltration, or fluid removal, on PD in achieved by osmotic or oncotic forces, as distinct from the hydrostatic pressure gradients that are applied in hemodialysis. In standard PD, the osmotic gradient for glucose is the key determinant of fluid removal. It should be noted that any osmotic agent used in PD has a reflection coefficient. This expresses the degree to which that agent is retained in the peritoneal cavity and so can continue to apply its osmotic or oncotic pressure across the membrane. The closer the value is to 1.0, the better the agent is retained and the more sustained is the ultrafiltration. Although glucose has long been the mainstay of PD, it actually has a very low reflection coefficient of about 0.02 which theoretically implies non­ suitability of glucose as an osmotic agent for PD.

20

On the contrary, peritoneal solutions based on polyglucose agent, icodextrin, have approximately the same osmolarity as serum and so do not remove fluid by osmotic forces. However, the large icodextrin molecules have and oncotic effect analogous to that of albumin and remove fluid in this manner.


Fluid Absorption

During the course of a PD dwell, there is constant removal of fluid form the peritoneal cavity through the lymphatics back into the peritoneal circulation. This peritoneal lymphatic flow can be demonstrated by infusing a macromolecule such as dextran into the peritoneal cavity and measuring both its disappearance from the cavity and its appearance in the systemic circulation. It should be noted that overall solute removal depends on the combined contributions of diffusion and convection minus the effect of peritoneal fluid absorption.


Peritoneal Equilibration Test

The peritoneal equilibration test (PET), first described by Twardowski in 1987, is the standard test used in clinical practice to assess peritoneal transport. PET is primarily a measure of the effective surface area or vascularity of the patient's membrane, and so DIP Cr value differ between patients and increase during peritonitis.


Changes in Transport with Time on Peritoneal Dialysis

It has long been recognized that there is a tendency for peritoneal transport to alter with time on PD. It is associated with a decrease in ultrafiltration capacity, which leads to ultrafiltration failure in the worst affected patients. The associated phathology includes loss of the mesothelium, gross thickening of the subserosal matrix, hyalinosis and obliterate changes in postcapillary venules, and most significantly, neoangiogenesis within the peritoneal membrane. The latter change makes the membrane more vascular and explains why transport characteristics should increase and conversely, why glucose driven ultrafiltration might decrease. The most accepted, explanation for this is that the changes are related to cumulative exposure to bioincompatible PD solutions and in particular, to glucose and glucose degradation products (GDPs).


Nutrition and Peritoneal Dialysis

Malnutrition is a common finding in patients on PD, particularly in developing countries, and is directly co­ related with dialysis vintage. Malnutrition is evaluated with several variables, including serum albumin level, prealbumin level, lean body mass, total body nitrogen level, creatinine excretion, anthropometric indices, subjective global assessment and composite nutritional scores. Malnutrition has also been shown to be strongly associated with morbidity and monitoring of the nutritional status, clinicians must use multiple tools to measure provides a completed overview of protein energy nutritional status.

JOURNAL OF RENAL NUTRITION AND METABOLISM (2015) 1: 19-21


The cause of malnutrition in patients on PD is complex. Nutrient losses during dialysis, low nutrient intake, comorbid conditions, chronic inflammation, metabolic acidosis, loss of RKF, uncorrected uremia, and a variety of endocrine disorders have been shown to contribute to the decline in nutritional status. Patients with high peritoneal membrane permeability may be at higher risk for malnutrition when many of the factors just noted are present; however, studies on the association between peritoneal transport characteristics and nutritional status have yields contradictory results.

The causes of malnutrition in PD and hemodialysis are same. The only additional factor that contributes to loss of appetite in PD is the feeling of satiety and fullness because of PD solution (dialysate).


Nutritional Counseling and Nutrient Supplements

Nutritional counseling is considered the first line strategy of standard nutritional treatment to achieve adequate nutrient intake. According to the KDOQI clinical practice guidelines, the recommended daily energy intake for patients on maintenance PD is 35 kcal per kilogram of body weight per day for those younger than 60 years of age and 30 to 35 kcal/kg/day for those aged 60 years or older. Energy intake in patients on PD is the sum of dietary intake and the glucose absorbed from the dialysate which in turn is dependent on several factors such a peritoneal transport volume dwell time and glucose concentration. Energy from dialysate is about 20% of the total energy intake, corresponding to 3 to 13kcal/ kg/day.With regard to the dietary protein intake, no less than 1.2g/kg (> 50% or proteins with high biologic value) is the daily recommendation for adults on PD. However, protein and energy intake of PD patients has frequently been shown to be considerable lower than recommended.

Intensive nutritional support may be particularly valuable during episodes of peritonitis or other hypercatabolic illness. Nutritional counseling as an isolated measure, may maintain nutritional status despite a decrease in RKF and higher rates of systemic inflammation. Administration of oral nutritional supplements may contribute to improvement of nutritional status. Few controlled clinical trials have involved commercial supplements or dry egg albumin based supplements as a nutritional intervention. Major drawbacks with commercial oral nutrient supplements are the cost and difficulty to ensure sustained adherence, which may preclude their chronic and broad use.


Biocompatible Dialysates

Intraperitoneal amino acids increase nitrogen intake but have lesser effects on non laboratory based endpoints. Potential anti-inflammatory effects of bicarbonate based dialysis solutions, icodextrin and 1.1% amino acid based dialysis solutions include reduction of the incidence of peritonitis and prevention of the increase of dialysate IL-6 levels observed with the use of conventional PD solutions.

JOURNAL OF RENAL NUTRITION AND METABOLISM (2015) 1: 19-21


Reversible Causes of Anorexia

Increasing the dosage of dialysis solution to correct anorexia is an approach often attempted, but not found to be effective in large randomized trials. Gastroparesis is a frequent complication in patients on PD, particularly but not exclusively among those with diabetes; correction of gastroparesis may increase dietary intake and reduce nausea and vomiting. The use of prokinetic agents (e.g; metoclopramide, erythromycin) has been reported to increase serum albumin concentration in hypoalbuminemic patients on dialysis with delayed gastric emptying.


Metabolic Acidosis

Because acidosis induces protein catabolism in ESRD, correction of acidosis or even induction of mild alkalosis by mean of oral alkali has been a measure to improve nutritional status. In a randomized trial conduced among patients on PD, oral sodium bicarbonate supplementation resulted in a significant increase in the plasma bicarbonate concentration along with improvements in some anthropometric measurements and nutritional status (evaluated by subjective global assessment); shorter hospitalization period and reduced morbidity.


Anabolic Hormones, Ghrelin, L-Carnitine

An anabolic strategy is to administer recombinant growth hormone. Its administration has been reported to be effective in improving nutritional parameters in short-term studies and seems to be particularly appealing for children; however its use in limited by cost and the development of hyperglycemia and other side effects. Similar results have been observed with the use of insulin-like growth factor- I. Ghrelin is a potent growth hormone secretagogue involved in the regulation of food ingestion and energy metabolism. Patients on PD seem to exhibit lower ghrelin concentrations than do either patients on hemodialysis or controls. Advanced chronic kidney disease is associated with

Nutrition and Peritoneal Dialysis 21

In the stable patient on PD without active peritonitis or other infection several conditions may be implicated in the origin of inflammation, including the use of bioincompatible dialysis solutions. Additional factors, such as rapid peritoneal membrane transport, have also residual renal function, and overhydration, have also been associated with inflammation. Some patients have rapid peritoneal transport and inflammation from the beginning of PD (frequently related to comorbidity and mortality) and others develop fast transport over time on PD (probably) as a result of exposure to bioincompatible dialysate but in rare cases, in association with inflammation). The interaction among uremia, malnutrition, cardiovascular disease and loss of residual renal and peritoneal membrane function, however, continues to be incompletely understood ..


Extracellular Fluid Volume Control

There is a strong association among fluid overload, cardiac natriuretic hormones, and proinflammatory cytokines. Adequate control of the extracellular fluid volume expansion may ameliorate the heightened inflammatory state observed in some patients on PD (particularly those with high transport rates).


Drug Treatment

Results of small studies indicate that agents such as thiazolidinediones and statins may have relevant anti­ inflammatory effects, but the effect is modest.


Residual Kidney Function and Peritoneal Dialysis

RKF has consistently been shown to have direct association with anorexia and dietary intake. Factors affecting RKF should be controlled. The presence of RKF in patients starting PD is associated with lower rates of peritonitis and peritonitis related mortality, which could be due in part to better immune function associated with RKF (either related to better control of uremia or other factors).

abnormal L-carnitine metabolism. Although results of some

studies have suggested that L-carnitine has an erythropoietin sparing effect in the management of anemia in patients on hemodialysis, data demonstrating a salutary effect of L-carnitine on nutritional status are insufficient. In the case of PD, it is currently unclear whether the abnormalities in L-carnitine metabolism have a role in the genesis or treatment of malnutrition.

Inflammation and Peritoneal Dialysis

Inflammation, which is related to atherosclerosis and malnutrition is marked by increased pro-inflammatory cytokines and acute phase reactants. It is present in 12% to 65% of patients with CKD even before they start dialysis and is aggravated with both PD and hemodialysis.

References

  1. Peritoneal Dialysis in CKD Peritoneal Dialysis (PD) (Guidelines PD 1.1-1.5) 30 July 2010)

  2. Peritoneal Dialysis in CKD Peritoneal Dialysis (PD) (Guidelines PD 2.1-2.4) 30 July 2010)

  3. Peritoneal Dialysis in CKD Peritoneal Dialysis (PD) (Guidelines PD 3.1- 3.3) 30 July 2010)

  4. NKF/ KDOQI Clinical Practice Guidelines for Nutrition in Chronic Renal Failure Guideline 16 Dietary protein Intake in chronic peritoneal dialysis 2000 AJKD Vol 35 No 6 Suppl 2 S42