Nephrology Hypertension

Peritoneal Dialysis: Principles and Peritoneal Physiology

Does this patient have an adequate peritoneal membrane for dialysis?

Peritoneal dialysis is a commonly used form of renal replacement therapy worldwide, although less frequently utilized in the United States (around 7% of prevalent dialysis patients). Two major variations of peritoneal dialysis are commonly used:

  • Continous ambulatory peritoneal dialysis (CAPD): The patient performs exchanges manually three to four times per day.

  • Automated peritoneal dialysis (APD):An automated cycler performs multiple nightime exchanges. At the end of this time the patient either instills fluid in the abdomen for a daytime dwell- continuous cycling peritoneal dialysis (CCPD) or leaves no dialysate in the abdomen for the daytime- nocturnal intermittent peritoneal dialysis (NIPD). NIPD is probably not suitable for patients with minimal residual kidney function (RKF).

Other important goals for a PD patient are to normalize acid-base abnormalities, bone and mineral metabolism abnormalities, blood pressure, nutritional status, and functional status.

Ultrafiltration failure is clinically recognized as the inability to maintain normal fluid homeostasis. While peripheral and pulmonary edema are specific findings of volume overload, more sensitive signs include hypertension and weight gain. In the evaluation of volume overload, the provider must assess contributing factors such as dietary sodium excess, non-compliance with medications or with the dialysis regimen, episodes of hyperglycemia (which remove osmotic stimulus for water removal), and decreased residual kidney function.

Difficulty with ultrafiltration may be associated with dialysate leaks. Leaks can occur into the pleural space (hydrothorax), abdominal wall (causing localized edema), or into a hernia. Due to sequestration of fluid and increased lymphatic absorption, ultrafiltration is decreased.

A rare condition, encapsulating peritoneal sclerosis (EPS) may present with ultrafiltration failure. The patient may also have symptoms of uremia (due to inadequate solute removal), nausea/vomiting, decreased appetite, and weight loss.

Soon after an episode of peritonitis, a decrease in drain volume can be detected in many patients. This may explain the correlation between peritonitis and a high rate of cardiovascular events.

What tests to perform?

Assessment of peritoneal membrane

Peritoneal equilibration test (PET)

After overnight dwell, 2 liters of 2.5% dextrose solution is instilled and dwells for 4 hours. At time 0, 2 hrs, and 4 hours, samples of dialysate urea, glucose, sodium, and creatinine are measured along with serum values at 2 hours. One can then calculate the ratio of dialysate/plasma (D/P) creatinine and the ratio of dialysate glucose at 4 hrs to time 0 (D/Do glucose).

Patients who have rapid absorption of glucose and/or rapid removal of creatinine are classified as rapid (or high) transporters while patients who have slow equilibration of urea, creatinine, and dextrose are slow transporters. Using published nomograms, patients can be classified in one of four categories: High, High-Average, Low-Average, and Low transporters.

PET allows the provider to tailor a dialysis prescription to the patient's peritoneal characteristics. In general, fast transporters will have better ultrafiltration with shorter exchanges and usually are treated with CCPD or NIPD. Should perform 1st PET 4 - 6 weeks after initiating dialysis as it may be inaccurate immediately after starting PD. Similarly, a PET should not be performed within one month of an episode of peritonitis. A PET only needs to be repeated for a clinical change. There is no role for routine monitoring of transport status.

Modified Peritoneal equilibration test

  • Performed in the same manner as PET but 4.25% dextrose solution is used instead of 2.5% dextrose.

  • Useful in diagnosing ultrafiltration failure which is defined as net UF less than 400 ml after a 4 hour dwell.

  • In general, solute transport type correlates well with 2.5% dextrose PET.

  • Often patients with UF failure are rapid transporters; if so, dialysis prescription can be modified to shorten dwell times.

  • In patients with average transport status, one must rule out dialysate leaks and catheter malposition.

  • In patients with low transport status, patients may also have evidence of low solute removal (uremic symptoms). Conditions such as encapsulating peitoneal sclerosis (EPS) and abdominal adhesions may be associated with this profile. Continuing peritoneal dialysis in these patients is very challenging.

Dialysate and urine collection for urea

  • Based on 24 hour collection of urine and sample of drained dialysate over 24 hours.

  • Dialysis dose is typically quantified by the removal of urea (Kt/V urea). The daily peritoneal Kt urea is calculated by multiplying D/P urea by 24 hour drain volume. To normalize for urea distribution volume (V), Kt urea is divided by V which can be calculated through many methods (such as Watson method). Finally, to arrive at the weekly Kt/V (std Kt/V) the daily Kt/V is multiplied by 7. To calculate urine Kt/V, U/P urea is multiplied by 24 hour urine volume and divided by V. The renal Kt/V is multiplied by 7 as well. The renal Kt/V and peritoneal Kt/V can then be added together to give the total Kt/V result.

  • In patients who rely on residual kidney function to achieve the minimum acceptable weekly Kt/V urea of 1.7, urine collection should be done every two months; dialysate collection and urine collection is otherwise typically done every four months.

  • Observational studies have suggested that higher Kt/V urea values are correlated with decreased mortality. The early studies did not separate renal urea removal from dialysate urea removal. Subsequent analysis of large cohorts, such as CANUSA, have demonstrated that the presence of residual kidney function is far more important to survival than peritoneal urea removal.

  • Three randomized studies have compared different targets of solute removal in PD patients

    • ADEMEX (Mexico): Achieved peritoneal Kt/V 2.2 vs 1.8. No difference in mortality or hospitalizations were seen although more patients withdrew from the low dose group due to uremia.

    • Lo WK et al (Hong Kong): Patients randomized to three total (renal + peritoneal) Kt/V targets-1.5 to 1.7, 1.7 to 2.0, and > 2.0. Study demonstrated no difference in survival or hospitalizations but patients in the lowest dose group have worse anemia and higher erythropoetin requirements.

    • Mak et al (Hong Kong): Patients on CAPD randomized to extra exchange or no change. Achieved peritoneal Kt/V was 1.56 vs 1.92. There was no difference in serum albumin but higher dose group had fewer hospitalizations.

  • Most national and international guidelines recommend achieving total Kt/V urea of 1.7

Abdominal X- ray/Peritoneography

  • Plain abdominal X-rays are performed to evaluate malposition of the peritoneal catheter.

  • Normal position of catheter is in pelvic gutter.

  • In patients with normal inflow of dialysate but problems with outflow, the most common underlying cause is constipation. However, if symptoms do not improve after resumption of normal bowel movements, abdominal X-ray should be done to assess catheter position.

  • For peritoneography, initial X ray is taken, then 100-200 ml non-inoic contrast is mixed into 2L dialysate bag and instilled in patient. The patient changes positions to mix dialysate and a repeat X ray is taken.

  • Can be used to diagnose an entrapped catheter or peritoneal leak.

Abdominal computed tomography scan

  • Can be used to evaluate the presence of dialysate leaks. Contrast injection as per peritoneography can help delineate the leak.

  • Abdominal computed tomography (CT) scan can also be used when EPS is suspected. Typical imaging findings include peritoneal calcifications, thick-walled "cocoon" encasing the intestines, and bowel dilatation.

How should patients with ultrafiltration failure be managed?

Patients with inadequate solute removal/uremia

  • If patient is not receiving 24 hours of dliaysis (NIPD), 1st step should be addition of dialysate during previous dry periods.

  • An increase in exchange number will usually provide a significant increase in small solute clearance. Care must be exercised, however, to avoid multiple, rapid, hypertonic exchanges to prevent "sodium sieving" with ensuing hypernatremia.

  • Increases in dwell volumes are usually well-tolerated and will also provide benefit.

  • Patients with ultrafiltration failure (High transporters)

    • CCPD may offer an advantage over CAPD as it will provide more frequent exchanges.

    • Icodextrin should be used for long dwell (at least 8 hours).

    • Increase in urinary volume with diuretics (if possible) may be helpful.

Patients with ultrafiltration failure (Average transport)

  • If workup demonstrates leak into hernia, surgical repair is warranted.

  • Patients with hydrothorax should have PD temporarily suspended; if pleural effusion recurs with re-initiation, pleurodesis can be attempted.

  • In patients without leaks or catheter problems, should combine methods used in high transporters (icodextrin, shorter dwells, diuretics).

Patients with ultrafiltration failure (Low transport)

  • This is the most rare situation. First, one should ensure that the patient does not have a baseline low transport status and a new complication (such as dialysate leak). Assuming that is not the case, this situation typically represents severe damage to the peritoneal membrane.

  • Generally, patients will have extensive adhesions or encapsulating peritoneal sclerosis.

  • Given the lack of both solute and fluid removal, continuing peritoneal dialysis is usually not possible.

What happens to patients with alterations in peritoneal membrane transport?

The normal peritoneal transport barrier

  • Composed of visceral peritoneum (80% surface area) and parietal peritoneum (20% surface area).

  • Osmotic movement of water out of capillaries occurs through aquaporin-1 channels and through interendothelial spaces filled with luminal glycocalyx.

  • Between capillaries and the peritoneal cavity lies smooth muscle cells and extracellular matrix which compose an additional barrier to filtration.

  • Ultrafiltration is mathematically represented by the following equation: Average UF rate (ml/min)= hydraulic conductivity (cm/min/mmHg) x total effective pore area (cm2) x [average osmotic pressure + net trans-membrane hydrostatic pressure - net oncotic pressure].

    • The net oncotic pressure depends on the solute reflection coefficient (σ). Ideally, a solute should have a σ value of 1. For aquaporin-1 channels, the σ value for glucose is 1; however, for the larger pores, the value is 0.05. For icodextrin, for the inter-endothelial pores, the σ value is 1.

  • Small solutes are primarliy removed by diffusion and somewhat removed by convection. Peritoneal concentrations of smaller molecules will equilibrate with plasma concentrations quicker than larger molecules. For instance, at 4 hours, on average, there is 90% equilibration with urea and 66% equilibration with creatinine.

  • Middle moecules (β2-microglobulin) are removed via convection in a time dependent manner. Longer dwells will increase middle molecule clearance.

Pathologic alterations in the peritoneal transport barrier

  • Peritonitis can cause increased vascularization and increased surface area leading to a higher transport status. Furthermore, new vessels may lack a glycocalyx which can further increase small solute transport.

  • Prolonged exposure to dextrose also seems to increase the effective peritoneal surface area as a result of neovascularization.

  • Long dialysis duration (> 6 years), repeated episodes of peritonitis, and intra-abdominal adhesions may lead to scarring of the peritoneum. Instead of a thin layer of smooth muscle cells between vessels and peritoneal cavity, there may be collagen deposition, fibroblasts and increased distance between capillaries and the peritoneal cavity.

Consequences of high transport status

  • In the past, observational studies of High transporters on CAPD revealed a higher mortality rate. With widespread usage of CCPD, High transport type does not appear to now be a risk factor for early mortality.

  • The majority of patients with a high transport status and inadequate ultrafiltration can be successfully treated with PD by shortening dwell times, using icodextrin, and diuretics.

Consequences of low transport status and ultrafiltration failure

  • Unless the patient has significant residual kidney function, continuation of peritoneal dialysis is usually not possible due to inadequate solute and volume removal.

How to utilize team care?

Surgery consultation should be obtained for patients with dialysate leaks/hernias and for patients with EPS.

PD nurses are indispensable as they provide frequent assessments of patients' clinical status, including weights, blood pressure readings, early symptoms of uremia. Also, as part of dialysis training, nurses instruct patients regarding catheter difficulties, problems with fluid removal, and weight monitoring. Nurses also help monitor residual kidney function frequently and instruct the patient on the importance of RKF.

Dietitians provide education to patient regarding dietary sodium reduction and fluid restriction to enable the patient to remain euvolemic

Social workers provide emotional support to the patient and caregivers, financial counseling and support, expertise in navigating insurance and medication assistance programs.

Are there clinical practice guidelines to inform decision making?

Peritoneal membrane functional characteristics

International Society for Peritoneal Dialysis

  • Small solute clearance (2006):

    • Adequacy should be assessed clinically (absence of uremic symptoms, blood pressure control, and acceptable anemia and mineral metabolism abnormalitie.

    • Although Kt/V should not be the main measure of adequacy, total Kt/V (peritoneal + renal) should be at least 1.7 at all times.

    • In patients on automated PD (NIPD or CCPD), weekly creatinine clearance > 45 L/wk./1.73 m2 should also be achieved.

    • In patients who rely on residual kidney function to maintain Kt/V 1.7, kidney function should be monitored every 1 - 2 months. Otherwise, it should be measured no less than every 4 - 6 months.

    • Continuous peritoneal dialysis is preferred, whenever possible.

    • Attention should be paid to both urine volume and ultrafiltration volume.

    • For patients with signs and symptoms of underdialysis, a trial of increased dialytic dose should be attempted even if Kt/V urea is above minimal target.

Ultrafiltration Failure (2000):

  • A systematic and thorough evaluation of fluid status should be undertaken to ensure euvolemia and normotension in PD patients. In the absence of valid, objective studies to determine volume status, clinical judgment remains best guide.

  • In the evaluation of causes of fluid overload, screening for reversible causes, such as dietary indiscretion and noncompliance, problems in prescription design, and mechanical problems is imperative

  • Evaluation of peritoneal membrane related causes of fluid overload begins with evaluation of UF response to an effective osmotic challenge and then an evaluation of small solute transport profile.

  • Evaluation of peritoneal membrane function is best done with modified PET (4.25% glucose). A net UF > 400 ml after a 4 hour dwell rules out alterations in peritoneal function as the principle factor in fluid overload.

  • For patients with UF < 400 ml and high transport status, APD and icodextrin for long dwell are recommended therapeutic approaches.

  • For patients with UF <400 ml who are functionally anephric with low transport status, transfer to HD is usually required. However, if some degree of RKF is present, maintenance on PD may be feasible.

  • Patients with a net UF less than 400 ml and low-average, average, or high-average transport profiles may have mechanical problems, high peritoneal absorption rates, or aquaporin deficiency.

National Kidney Foundation/K-DOQI (2006)

  • For patients with RKF (> 100 ml/day urine volume), minimal total Kt/V urea should be 1.7. Renal Kt/V should be measured every 2 months and total Kt/V every 4 months.

  • For patients without RKF, the minimal peritoneal Kt/V should be 1.7. Kt/V should be measured every 4 months.

  • Each facility should monitor dialysate drain volume, RKF, and blood pressure on a monthly basis. To optimize extracellular fluid volume, one should consider dietary sodium and water restriction, use of diuretics in patients with RKF, and optimzation of dialysis prescription to achieve ultrafiltration.

What is the evidence?

"Clinical practice guidelines for peritoneal dialysis adequacy". Am J Kidney Dis. vol. 48. 2006. pp. S98-129.

Bargman, JM, Thorpe, KE, Churchill, DN. "Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanlaysis of the CANUSA study". J Am Soc Nephrol. vol. 12. 2001. pp. 2158-2162.

Flessner, MF. "Peritoneal ultrafiltration: physiology and failure". Contrib Nephrol. vol. 163. 2009. pp. 7-14.

Lo, WK, Bargman, JM, Burkart, J, Krediet, RT, Pollock, C, Kawanishi, H, Blske, PG. "Guideline on targets for solute and fluid removal in adult patients on chronic peritoneal dialysis". Perit Dial Int. vol. 26. 2006. pp. 520-522.

Lo, WK, Ho, YW, Li, CS, Wong, KS, Chan, TM, Yu, AW, Ng, FS, Cheng, IK. "Effect of Kt/V on survival and clinical outcome in CAPD patients in a randomized prospective study". Kidney Int. vol. 64. 2003. pp. 649-656.

Mak, SK, Wong, PN, Lo, KY, Tong, GM, Fung, LH, Wong, AK. "Randomized prospective study of the effect of increased dialytic dose on nutritional and clinical outcome in continuous ambulatory peritoneal dialysis patients". Am J Kidney Dis. vol. 36. 2000. pp. 105-114.

Mujais, S, Nolph, K, Gokal, R, Blake, P, Burkart, J, Coles, G, Kawaguchi, Y, Kawanishi, H, Korbet, S, Krediet, R, Lindholm, B, Oreopoulos, D, Rippe, B, Selgas, R. "Evaluation and management of ultrafiltration problems in peritoneal dialysis. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis". Perit Dial Int. vol. 20. 2000. pp. S5-21.

Paniagua, R, Amato, D, Vonesh, E, Correa-Rotter, R, Ramos, A, Moran, J, Mujais, S. "Effects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial". J Am Soc Nephrol. vol. 13. 2002. pp. 1307-1320.

Twardowski, ZJ, Nolph, KO, Khanna, R, Prowant, BF, Ryan, LP, Moore, HL, Nielsen, MP. "Peritoneal Equilibration Test". Peritoneal Dialysis International. vol. 7. 1987. pp. 138-148.

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