Journal of Renal Nutrition and Metabolism Vol 2 No 3 July-September- 2016 Ultrafiltration Failure 16

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Article


Approach To A Patient With Ultrafiltration Failure


1Behera Manas Ranjanl and 'Gupta Amit

'Post Doctoral Fellow , 'Professor, Department of Nephrology,

Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow. Uttar Pradesh.


Key Words: Peritoneal Dialysis, Ultrafiltration Failure, Peritoneal Equilibrium Test



Ultrafiltration failure (UFF) is major factor deciding technique survival in peritoneal dialysis (PD) patients . It is a major complication after long duration of PD. All patients with decreased ultrafiltration and/or edema are not ultrafiltration failure (UFF). UFF is a peritoneal membrane defined clinical situation. Hence, prior to diagnosing UFF, other causes to be rule out (Table-I). Three essential features ofultrafiltration failure (UFF) are

  1. Always implies peritoneal membrane dysfunction.

  2. Presence of features of volume overloads i.e. edema, breathlessness and etc.

  3. Ultrafiltration volume < 400ml by modified peritoneal equilibrium test (PET).

Table 1 (Causes ofvolume overload other than UFF)

Hyperglycemia (especially diabetic patients)

Poor patient compliance to salt and water Poor patient compliance to PD prescriptions Inappropriate bag selection Inappropriate prescription as per PET test Unable to use Icodextrin based PD solution.

Catheter malfunction - migration (X ray-KUB), inflow and outflow issues Abdominal leak - pericatheter leak, parietal leak, leak into pleura and genital wall Peritoneal Equilibrium Test (PET)

It is a indirect method to monitor peritoneal membrane transport function, that can be used in clinical practice routinely. It has good correlation with MTAC, which is difficult to measure in clinical practice. It measures combined effect of diffusion and ultrafiltration. It uses equilibrated ratio between dialysate and plasma for urea, creatinine and sodium. It depends on molecular weight of solute, peritoneal membrane permeability and effective peritoneal surface area but co-relates poorly with body weight.

Standard Peritoneal Equilibrium Test Verses Modified Peritoneal Equilibrium Test

Standard PET test uses 2.5% 2L dextrose while modified peritoneal equilibrium test uses 4.25% 2L dextrose. Former is used for characterized solute transport of membrane while later can also be used for diagnosed ultrafiltration failure.

Method

It involves dwell of required strength of dextrose based


PD solution for 4 hour and dialysate sample taken at 0, 2 and 4 hr and plasma sample taken at 2 hr. Sample is analysed for urea, creatinine and sodium. Equilibrated ratio is calculated between dialysate and plasma (DIP) and plotted against Twardoski PET chart to characterized different types of transporter. But, usually 4th hour equilibrated DIP Cr is used to characterized transporter status. Ratio of dialysate glucose at 4th hour to O hour (DIDO G) and total volume of ultrafiltration is also calculated.

Types Peritoneal Transporters Four types oftransporter

1 High Transporters have high intrinsic membrane permeability to solutes and have larger effective surface area. Hence, they achieve rapid equilibrium for urea, creatinine and glucose. Later responsible for rapid loss of osmotic gradient, due absorption of glucose from PD fluid. Thus, high transporters have the highest DIP Creatinine, DIP Urea, and D/P Na values but have low net ultrafiltration and DIDO G values. They frequently have hypoalbuminemia due to protein lossin dialysate. They dialyze well but ultrafiltrate poorly. Hence, they do better with short dwell regimens e.g.APD or higher strength and Icodextrin-based PD fluid.

  1. Low transporters have lower membrane permeability andhavelesser effective surface area. Equilibrium achieved for solutes slow and incomplete. Thus, they have lowest DIP Creatinine, DIP Urea, and DIP Na values but have good net ultrafiltration and high DIDO G values. Serum albumin is relatively higher. They do better with long dwell and/or high volume regimens like CAPD.

  2. High and low average transporters -Values for DIP Creatinine, DIP Urea, DIP Na and DIDO G values lies in between the high and lowtransporters.

Four types of ultrafiltration failure

  1. Type 1UFF (UFF with High transporter is mostcommon cause of UFF. It is due to rapid loss of osmotic gradient due to absorption of glucose. It isusually developed after long duration of peritoneal dialysis, typically 3 years or more. Probable mechanism is due to increase in effective surface area secondarily to increasevascularity. Uremia, high glucose load, glucose degraded products, advanced glycosylated end products, low pH of peritoneal dialysis (PD) fluid, recurrent peritonitis and during acute episode of peritonitis are presumed etiology. Continuous exposures

    Journal of Renal Nutrition and Metabolism Vol 2 No 3 July-September- 2016 Ultrafiltration Failure 17

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    to bio-incompatible PD fluids causes peritoneal membrane inflammation leading to fibrosis and neovascularisation of eritoneal membrane. Epithelial mesenchymal t r a n s i t i o n (EMT) of mesothelial cells is central to above process. Transforming growth factor-P (TGF-P) and vascular endothelial growth factor (VEGF) by MCs can induce EMT. They have thicker peritoneal membrane than those with preserved ultrafiltration function.

  2. Type 2 UFF (UFF with Low transporter)characterized by decreased soluteclearance and ultrafiltration. Decreased surface area due to adhesion and scaring after severe peritonitis and other intra-abdominal complications. It is caused by TGF-P causing epithelial mesenchymal transition, submesothelial and obliterative vasculopathy.

  3. UFF with Normal transporter {high average and low average) can be either due to increased lymphatic absorption of peritoneal fluid (type 3) or due to aquaporin deficiency. Former is diagnosed by rate of reabsorption of Types Of Ultrafiltration Failure dextran 70 from peritoneal cavity.Later is diagnosed by comparing changes in dialysate odium after a dwell of 30-60mins with 4.25 and 1.5% dextrose respectively. Aquaporin deficiency leads to impaired initial fall in dialysate sodium with 4.25% dextrose and difference in dialysate sodium < Smmol/1between 4.25% and 1.5% dextrose at 30-60mins. Aquaporine-1 found in peritoneal membrane mediates 50% of ultrafiltration . Aquaporin transport water but not sodium (sodium sieving),responsible for initial fall in dialysate sodium by 5- lOmmol/l with 4.25% dextrose dwell, that doesn't occurs in aquaporin deficiency. Free water clearance is less than 26% of total Aquaporin deficiency is not quantitative, rather it is a functional defect.

    Management OfUltrafiltration Failure

    1. General measures - Diabetic patients are at high risk of developing u ncont rolled blood sugar, due to absorption of glucosefrom peritoneal dialysis fluid. Even some patients with normal or impaired blood sugar become overt diabetic after starting peritoneal dialysis. blood sugar leads to loss of osmotic gradient and ultrafiltration failure. Using higher strength or decreasing dwell time will not solve the issue, rather it may aggravate. Hence, diabetic patients should be subjected to intense sugar monitoring .Non-diabetic should also be subjected to routine screening. Excess salt intake can lead to volume overload secondary to increase thirst. Hence, salt (< 3gm/day) and water restriction is essential, especially those with no residual renal function . Non-adherence to per itoneal dialysis prescription is important cause of volume overload and should be suspected in alpatients. They usually do less no of exchanges or uses low strength bags. It can be confirmed in interrogating patients and relative. They usually have good Kt/V, still serum urea and creatinine are remains high. During prescribing PD prescription PET results should

      always be considered. Managing high transporter with long dwell (CAPD) or low transporter with short dwell can lead to decreased ultrafiltration. Using higher strength bag or Icodextrin can solve issue of low ultrafiltration especially in high transporter and those on APD. Catheter malfunction like migration, nicking and omental wrap should be excluded prior to diagnosis of ultrafiltration failure. All patients with decreased ultrafiltration should be subjected to X-ray KUB and chest. X- ray KUB can diagnose catheter migration and nicking. It can be managed by better bowel preparation. If any mechanical cause, other than constipation, is suspected, should be managed surgically. X-chest can suspect any pleura-peritoneal shunt leading to hydrothorax and decreased ultrafiltration . Leak into parietal and genital organ can be suspected clinically and by USG. Suspected case of any leak can be confirmed by CT or peritoneal scintigraphy using Technetium- labeled albumin colloid {5 mCi). These are usually managed conservatively with rest to peritoneum or low volume supine dwell or surgical closure of tract.

    2. Type 1 UFF - can be managed with short dwell (APD). Icodextrin is an attractive option for these patients. It is neither absorbed across peritoneal membrane nor metabolized. It is slowly taken up in lymphatic. Hence osmotic gradient maintained up to 10-12 hour. Temporary cessation of peritoneal dialysis may improve outcome by restingperitoneum .

    3. Type 2 UFF usually managed by transfer to hemodialysis unless has significant residual renal functions.


    4. UFF with normal transporter are managed by general such as decrease salt and water, diuretics, short dwell and Icodextrin is particularly useful in aquaporin deficiency as it induces ultrafiltration by non-aquaporin chanel.After all patient regarding blood sugar monitoring, low salt diet, compliance to PD prescription and regarding change of strength of bag isan essential step in managing decreased ultrafiltration.

      PREVENTIVE MEASURES

      Some interventions have shown to retard progression to UFF.

      1. Asepsis to prevent peritonitis, early treatment of peritonitis and timely catheter removal in refractory peritonitis may help.

      2. Use of renin - angiotensin - aldosterone axis blockers retard progression of UFF significantly by retarding angiogenesis .

      3. Biocompatible PD fluids like Icodextrin or amino-acid based PD fluid and Glucose containing pH-neutral low GDP PD flu id retard prog ressio n to UF F as the i r biocompatible nature, less GDP formation that prevent inflammation, angiogenesis and fibrosis.