Preventing PD Peritonitis: What's the Evidence?

Peritoneal dialysis associated peritonitis is the second commonest cause of death among PD patients (35/1000 years) and the most common cause of treatment failure. It confers a CV risk of 7 times normal for 6 months following the bacteremia, so we need to remain ever vigilant when dealing with PD patient, and its worth refreshing our knowledge on how to prevent this feared complication. There is a paucity of high quality evidence for many of the most fundamental questions in PD. Such is the lack of evidence, the International Society for Peritoneal Dialysis (ISPD) have issued a consensus document where they state they are unable to issue formal guidelines.

The best resources I have found on the topic are a Kidney International supplement from 2006, and the ISPD document already mentioned. In the first instance, which patients are at risk of developing peritonitis? The best described risk factors are hypoalbuminemia (similar to the association in haemodialysis patients), Staph aureus  carriage at inception of dialysis (HR 1.53), initiation of PD early after catheter insertion (HR 0.98/day), PD after transplant failure (HR 2.18), lower hemoglobin (HR 0.88/gram/l), faster PD transport rates (HR 2.92) and previous peritonitis. A special risk group to consider are those PD patients undergoing invasive procedures such as endoscopy or IUD insertion. There is evidence that antibiotic prophylaxis using cephalosporins may help reduce peritonitis rates.

The cornerstone of peritonitis prevention is minimizing contamination risk with effective hand washing and immaculate exchange technique. Specialized nurse-led training is key. If peritonitis occurs, retraining and re-education are the most important interventions. Home visits by PD nurses can cut recurrence rates in half, and should be performed where possible. A Cochrane review could find no RCT data to support any particular insertion technique, catheter type, number of cuffs or positioning. It demonstrated that of all catheter-related interventions designed to prevent peritonitis in PD, only disconnect (twin-bag and Y-set) systems have been proved to be effective. Topical antibiotic prophylaxis is a standard of care and there are multiple RCTs demonstrating the efficacy of mupirocin cream application at the exit site. Ointment is to be avoided as it can erode the catheter polymer.  In contrast, nasal mupirocin is more difficult to justify. Cochrane point out that while there is trial data that nasal mupirocin reduces exit-site/tunnel infection, it has no effect on peritonitis rates. Preoperative intravenous prophylaxis reduces early peritonitis but not exit-site/tunnel infection. 

Recent published trials in the area of antimicrobial prophylaxis have been disappointing. They include the Honeypot study, discussed previously on RFN, which demonstrated the application of honey to exit sites approximately doubled the risk of developing peritonitis in diabetic patients. The MP3 study published in JASN in 2012 found polysporin to increase rates of fungal exit site infections without any improvement in primary outcomes of exit site infection or peritonitis. Finally, a special mention goes to cats, who are responsible for at least 25 case reports of pastuerella peritonitis, as well as an assortment of other bugs. Not to be outdone, rodents feature  in the case reports also, coining the term “hamster bite peritonitis” caused by pastuerella aerogenes.

In summary, technique and continuing re-education are of fundamental importance, as are topical antibiotics to prevent exit site infection.  Beyond this, trial data are severely lacking and local opinion and consensus must guide practice.

Authored by Eoin O'Sullivan

Hemodialysis vs. Peritoneal Dialysis

My attention was caught by the recent article in CJASN which compared the mortality of peritoneal dialysis (PD) and hemodialysis (HD) patients in the first 2 years of dialysis therapy. When comparing survival outcomes of PD and HD patients, the data we have so far is based on observational studies. A randomized controlled study has never been successfully completed because of difficulties in randomization. The only randomized study so far - the NECOSAD study (Netherlands) managed to randomize only 5% of the eligible subjects3.  

Most of the observational studies looking at survival had methodological limitations like suboptimal adjustment for modality switch over time (PD patients more likely to switch to HD), inability to account for time-varying confounding by laboratory values and inappropriate adjustment for the differential longitudinal censorship of transplantation across modalities (PD patients more likely to get a transplant). While analyzing such time-varying covariates which are simultaneously confounders as well as predictors of outcome and subsequent exposure, traditional methods like logistic or proportional hazards regression are biased and hence they pose unique analytical challenges. Hence a new statistical model – a Marginal Structural Model (MSM) which employs  inverse probability weights (IPWs) to determine the effects of these time varying covariates on the primary outcome (which was survival  in this study) was utilized  in this study. In order to adjust for the effect of each dialysis modality and censorship from transplantation, a combination of inverse probability of treatment weights (IPTWs) and inverse probability of censoring weights (IPCWs) was used. The IPTW (or IPCW) will have estimated probabilities of treatment (or censorship) using baseline covariates as the numerator and estimated probabilities of treatment (or censorship) using baseline and time-dependent covariates as the denominator. The MSM helped to derive meaningful survival data, adjusting for the above mentioned confounders

The study used information from two large databases viz. USRDS and Da Vita, providing a large cohort of almost 24000 incident dialysis patients. Separate analysis was conducted using a Kaplan–Meier survival curve, cox proportional hazards and the MSM model. A 48% greater survival for incident PD patients at 2 years was found using the MSM model. These findings were in contrast to findings in other studies in the past which showed either no difference in survival or marginal survival advantage especially in the first year for PD compared to HD5. Additionally, a comparison between the cox model and the MSM   demonstrated that the time-dependent confounders determined the difference in survival. Changes in modality during the first 2 years of dialysis affected the survival patterns over time and the reason for this trend is not completely understood at this point. This study supports greater use of PD in the treatment of ESRD patients especially in US where less than 8% of prevalent patients with ESRD are on PD.A comprehensive dialysis modality education program should be encouraged to expand the practice of PD.

See these two previous posts on the debate between PD and HD.

Posted by Bijin Thajudeen

Retroperitoneal leak in PD patient

Ultrafiltration failure is a frequent clinical problem in PD patients. The most common etiologies are: fast peritoneal membrane transport, loss of peritoneal surface membrane and high lymphatic absorption. Mechanical and anatomical etiologies are occasionally seen.

Rule of 4's is used to diagnose membrane ultrafiltration failure: less than 400ml UF using 4.25% bag after 4 hours.

Sudden onset of ultrafiltration failure may occur in the setting of peritoneal leakage. Though sometimes associated with localized subcutaneous edema, it is generally difficult to detect clinically. Retroperitoneal leakage is likely to arise from a tear or a gap in the peritoneum precipitated by an increase in intra-abdominal pressure associated with walking, coughing, straining, or using a high instilled volume (2.5 L or 3 L). Red flags may include history of hernia, pleuroperitoneal communication and large infusion volumes. The acute onset of ultrafiltration failure is another suggestive finding.

Best diagnostic modality is MRI (PD fluid can be used as constrast medium).



Management: involves interruption of PD. But few reports have achieved success by using fast cycles (1hour/exchanges x8) twice a week and leaving abdominal cavity empty between sessions for 4-8 weeks.

Home Dialysis University

The dates and locations for this year's Home Dialysis University for Fellows have been released. This is a series of courses on home HD and PD aimed at graduating fellows that is sponsored by the ISPD. You can check out the RFN review of the course here and our twitter feed from it here under #HomeDialysisU. The 4 locations are Charlotte, Dallas, Denver and Chicago and they are going to take place once a month from February to May.

The site for the fellows version is here. There is a similar course run for practicing renal physicians although this is starting in just 2 days in New Orleans. The website for the non-fellow's version is here. 

Conference Review: Home Dialysis University

It doesn't take much to get me to take a trip to San Diego so when the opportunity came up to attend this year's Home Dialysis University conference I booked my flight.  Having lived in San Diego for many years prior to moving to the Bay Area I took the opportunity to both check out this great conference and stay and visit with old friends.

The conference (formerly known as Peritoneal Dialysis University) now has significant content going over home hemodialysis therapies with much of this being delivered by Brent Miller who was one of the FHN daily investigators and part of the ongoing FREEDOM study.

The conference registration and up to $350 in hotel and travel are covered for fellows by a grant from the International Society of Peritoneal Dialysis.  The conference and accommodations were at the Westgate Hotel in the Gaslamp district.  Great location and high marks for tasty breakfast, lunch and frequent snacks (all at no additional cost!)

Conference size was small, under 20 people so lots of opportunity to interact with the faculty and other attendees. Also a short conference, one full day and two half days.

John Burkart from Wake Forest gives a great lecture on how PD and HD work in terms of small and other solute clearance and reviews the uses and limitations of Kt/V.  He also gives a very practical lecture on the financial considerations related to home dialysis.  Anjali Saxena (one of my attendings who is the PD director down at the Stanford affiliated Santa Clara Valley Medical Center) covers PD access issues, the challenges that face the long-term PD patient and the infrastructure requirements for starting your own home unit.  Joanne Bargman from Toronto does some great case based discussions surrounding commonly encountered PD issues.

One of the highlights is the hands-on demonstration session were home dialysis RNs actually do a walk through with a PD cycler and a NxStage machine. Very informative.

An area where many fellows unfortunately have limited exposure is the nuances of the dialysis prescription writing for the NxStage system.  Brent Miller gives a really nice talk going over the details of this.  Lots of nice compare and contrast examples to conventional HD to put things in a more familiar context.

At least as of this writing, they haven't announced when the 2013 fellows conferences are going to be held so stay tuned to their website for dates.  In past years they've had sessions in several locations on several different dates so hopefully you'll find something that will fit your schedule.

I again tried my best to keep up a solid twitter feed of interesting points for RFN which you can find here with all the tweets indexed under #HomeDialysisU.

Honey for the Achilles Heel

In the PD literature, peritonitis has been referred to as an Achilles’ heel because it could lead to catheter removal and PD treatment failure. Topical antibiotics have been used for prevention of an exit site infection (ESI) which may precede and lead to peritonitis.

For this purpose, most centers use mupirocin as their first choice. It has reduced the ESI significantly, but mupirocin-resistant S. aureus and P. aeruginosa ESI have emerged. Then came gentamicin which is superior to mupirocin. However, gentamicin-resistant P. aeruginosa has already been reported… How can we break this cycle?

FOOD was the bright idea! Not any food but a very specific sweet treat – honey. Honey has been applied to wounds since ancient times, but only recently have we come to understand its antibacterial properties: acidity (pH 3-4), high osmolarity (3000 mOsm/kg), H₂O₂, methyl glyoxal, bee defensin-1, etc. In vitro, honey killed bacteria including MRSA, β-lactamase producing E. Coli, ciprofloxacin-resistant P. aeruginosa and VRE! Because of its multiple antibacterial mechanisms, there is a low likelihood that bacteria will gain resistance.

But does it work in vivo? It has been shown that honey heals wounds and maintains sterility. Then, an Australian and New Zealand group tested standardized antibacterial honey (Medihoney) for HD catheter-associated infections and its effectiveness was comparable to mupirocin.

Now the same group is conducting the HONEYPOT study to see its efficacy in reducing the risk of PD infection. This is one of the initiatives to improve the PD technique survival in the region which is lower than in other parts of the world.

The results of the HONEYPOT study are pending, but it would be exciting if honey is proven to be an effective alternative prophylaxis with less chance of bacterial resistance. Penicillin was discovered from fungi. Gentamicin is synthesized by bacteria. Maybe it’s time to ask for honey bees for help.

Posted by Tomoki Tsukahara

Bury it!

One of the issues that we come across repeatedly in the clinic is the timing of access insertion. We all want to avoid the use of catheters and so we refer patients early (when possible) for fistula formation. This is a bigger problem when your patient wants to start PD. You don’t want the patient to have the catheter placed too early because then they will be unnecessarily exposed to the risk of infection. At the same time, you don’t want to wait too long and get to the stage where the patient requires urgent HD (and often, once they start HD it is difficult to make the transition to PD). I saw a patient in the clinic a few weeks ago that fits this bill perfectly. He is an otherwise healthy man in his 60s who has a very active life and a full-time job. His creatinine had been stable for 2-3 years but climbed rapidly earlier this year and we thought he would need to start soon. However, his creatinine stabilized again and he is feeling well so we have him in a holding pattern with regard to the PD catheter insertion. Our surgeon suggested implanting a buried PD catheter, a technique that he has just started doing in our institution.

For this technique, the catheter is buried subcutaneously at the time of insertion. Then, when the patient is ready to start dialysis, the subcutaneous portion is externalized and the catheter can be used straight away. This can be done in the dialysis clinic and does not require a trip to the OR. Thus, a catheter can be inserted months (or even years) prior to use and the problem of timing is dealt with very elegantly. Recently, a paper was published which described the experience of the University of Denver where they have been using this technique as standard since 2000. In total, 134 catheters were implanted in that time. The period prior to externalization varied between 2 and 788 days with an average of 40 days. There was no relationship between catheter embedment time and the risk of catheter failure. 90% of catheters worked immediately and of the remaining 13 catheters, 12 were easily corrected laparascopically. Only 1 patient failed this technique and required transition to HD. This seems like a great technique and I look forward to seeing the results here over the next few months.

See also this earlier paper in KI about the experience with the use of buried catheters in Ottawa.

PD or HD post cardiac surgery?

A few months back I was covering the inpatient consult service when one of our patients on peritoneal dialysis came in for an elective combined aortic valve replacement and coronary artery bypass grafting. She had recently switched over from in-center HD to PD and still had a functional arteriovenous graft in place. The surgery went well and the patient came out of the operating room to the cardiac critical care unit.

 As I sat reviewing the chart my attending posed the following question "So is it reasonable to continue PD here in the unit or should we switch over to HD until she's extubated and clinically improving?"

Would the increased intra-abdominal pressure from PD lead to prolonged intubation time? Given the manipulation of the thoracic cavity was there a higher risk of dialysate leak through the diaphragm? Would we be able to provide adequate clearance and ultrafiltration with PD? Would the infection risk be higher for PD given the relative unfamiliarity of the nursing staff?

A recent article in Peritoneal Dialysis International comparing perioperative outcomes in patients on PD and HD post cardiac surgery sheds some light on the situation. In the study the Southern California Permanente Group at Los Angeles Medical Center looked back at 15 years of CABG and cardiac valve replacement surgeries in ESRD patients and compared a variety of outcomes between 36 patients on PD and 76 on HD.

There were no reported significant differences between the two groups at baseline including age, dialysis vintage, presence of diabetes, type of surgery and Charlson comorbidity index.  The only statistically significant difference in terms of outcomes was a slightly longer median length of stay in the cardiac surgical unit for HD patients (4 vs 2 days) though the median total hospital length of stay between the two groups was no different (PD 9.5 days, HD 10 days).

There was trend towards more infections in the HD group (19% vs 6%) but this did not reach statistical significance. Median intubation time was the same between groups.  Survival perioperatively (defined as during the hospital stay or within 30 days of operation) and at one and two years was similar between groups (PD 89%, 81%, 69%, HD 90%, 78%, 66%).

Conversion of PD patients to HD occurred in just 6% percent of patients. One for dialysate leak and another for uncontrolled azotemia.  CRRT was needed in 1 HD patient due to hemodynamic instability.

The study doesn't answer the question of whether converting a patient on PD to HD or CRRT might improve outcomes but it does provide reassurance that PD patients don't have an excessive risk of dialysate leak or inability to achieve adequate clearance and ultrafiltration.  It also shows that in general outcomes post cardiac surgery between PD and HD patients are similar.

In our patient we continued peritoneal dialysis using an automated cycler without difficulty.  Over the weekend the covering team changed to HD via the arteriovenous graft over concern that PD might lead to a dialysate leak.  Unfortunately the patient tolerated HD poorly with episodes of hypotension so we transitioned back to PD when we came back on.  The rest of her hospitalization was without incident.

Entrapment

An 18 year-old girl with end stage renal disease secondary to focal segmental glomerular sclerosis had a double cuff flex neck peritoneal dialysis (PD) catheter uneventfully inserted in order to begin dialysis. Ten days after this procedure, following successful post-operative catheter flushes, she presented with new, intermittent, sharp, right-sided abdominal pain with catheter flushes. Over the next week, she went on to experience progressive peritoneal filling difficulties that required curtailing planned treatments. She was otherwise asymptomatic and, when not on dialysis, reported feeling well. An abdominal x-ray revealed that her catheter had migrated into the right flank, and her dialysis treatments did not improve after recombinant tissue plasminogen activator or an intensified bowel regimen. Her PD catheter was capped, and she was instructed to present for surgical repositioning of the catheter the following day.

In the operating room, the peritoneal catheter was found to be in the right lower quadrant as expected and initially appeared to be surrounded by only inflamed omental remnants. Further dissection of the omentum away from the catheter, however, revealed multiple dense adhesions, including a small loop of bowel and a markedly inflamed appendix, encircling the PD catheter. These adhesions were lysed, freeing the PD catheter from the appendix. After a pause to discuss these findings with her mother, the surgeon proceeded to perform a previously unplanned appendectomy. The PD catheter was relocated to the pelvis and flushed with ease.

This case highlights a rare but previously documented cause of PD catheter obstruction: appendiceal entrapment. However, this case has a few significant differences from the literature. First, and most notably, the patient’s pathologically-confirmed appendicitis did not present with signs or symptoms consistent with this disease (fever, localized abdominal pain, elevated WBC). Catheter obstruction and malposition were our only clues, and even en route to the OR, both the medical and surgical teams believed this to be a simple case of catheter malposition, perhaps with an element of omental adherence. Second, this case questions the current literature’s suggested management of surgical peritonitis, which centers around catheter removal and dialysis interruption. HS’s catheter was left in, and her pain, catheter flows, and dialysis treatments dramatically improved post-operatively. Perhaps the most important lesson that I take away from this case, though, is to quickly consider the more rare surgical causes of PD catheter obstruction and even peritonitis when conventional medical treatments fail.

Posted by Matt O'Rourke

Dialysis care in Bangladesh

Although diabetes and hypertension rates in developing countries is rising to match that seen in developed regions, care for patients with end-stage renal disease is still a nascent field.


I recently visited Dhaka, Bangladesh. I was able to visit 2 dialysis units there, one sponsored by a charity and another that was part of the National Kidney Hospital in Dhaka. The National Kidney Hospital in Dhaka is a major referral center for care for patients with acute kidney injury from other hospitals, and has one of the largest outpatient dialysis units (with 30-40 dialysis machines functioning at one time). My understanding is that less 10,000 patients are undergoing some form of dialysis or living with a transplant in the country.


It was so interesting to learn how dialysis is run in Dhaka. Nephrologists I met there mentioned that they take care of about 100 patients who are outpatients. Cost of dialysis in this particular unit is subsidized by the government, at about $8-10 per treatment. But most patients are only able to afford two times per week treatment, and it was excruciating to hear that nearly 80-90% “withdraw” from dialysis in 5-6 months as their families’ resources are depleted. In the charity unit I visited they had only had a handful of patients undertake dialysis for more than 1 year.


Typical dialysis prescription in Dhaka:
Access: fistula
Blood flow: 250 ml/min
Dialystate flow: 500 ml/min
Dialyzer: F6, fresinius machine
Length of time: 4hrs, typically 2x/wk


Most of the patients I saw were young or middle aged, much younger than the average US patient. The nephrologists mentioned that glomerulonephritis is the most common diagnosis among the outpatient dialysis patients in their unit, but I wonder if glomerulonephritis is indeed the most common cause of ESRD there or it’s simply that patients with diabetic ESRD are older and their families chose not to pursue dialysis treatment. Rates of diabetes in Bangladesh are estimated to be about 5-6% of the adult population, not too too far from the 11% rate usually seen in the US.


The financial constraints are even tighter for those not lucky enough to get one of the subsidized dialysis spots; in the private units, dialysis costs close to $40 per treatment. Again you can see how this may be completely cost prohibitive in a country where 50% of the population lives on less than $2 per day.


Peritoneal dialysis is not widely available. Only living renal transplants are performed; one of the largest centers is the National Kidney Hospital which performs1-2 transplants per week. The cost of a transplant is $3000 for the surgery and post op care. Not surprisingly, there was a recent scandal related to an “organ trafficking” ring that had reportedly gotten 200 poor people to sell their kidneys on the cheap.


The nephrologists I met were very committed and extremely well trained. It was really touching to see how proud they were of their work, from setting up the water facilities to getting research projects up and going.

‘Failure to thrive’ on PD

A few months ago I took care of a patient who, having been on peritoneal dialysis for a number of years, was losing weight, had poor small solute clearances and worsening edema. We transitioned her over to HD for presumed membrane failure, but her nutritional status really did not improve. She continued to complain of nausea, vomiting and abdominal bloating - an abdominal CT gave us the answer. It showed loculated fluid collections, markedly thickened peritoneal membrane and tethering of the bowel in the centre of the abdomen (as in left image). The entire presentation was consistent with encapsulating peritoneal sclerosis (EPS) – a dreaded complication of long term PD.

EPS is quite rare, but has a high associated mortality (25-50%). It is relevant even for those of us who take care of few/no PD patients, as over half of all cases present after changing from PD to HD and it can even present post renal transplantation.
So what is EPS? Basically, it is an inflammatory condition, characterized by severe peritoneal fibrosis and thickening, leading to adhesions, small bowel obstruction and ascites formation. It occurs in between 0.5- 2.8% of PD patients and is seen primarily in patients who have been on PD for over 5 years, with risk increasing as time on dialysis increases (Up to 17% in those on PD over 15 years). However, there have been reported cases in patients on PD for less than 6 months. Frequently, patients have had recurrent episodes of peritonitis although again, this is not universal. Infection is thought to ‘prime’ the membrane for fibrotic change and may be a precipitating event.

The clinical presentation can be quite vague, so a high degree of suspicion is needed to make the diagnosis. Patients may present as ‘failing’ PD but EPS should be considered in any patient with persistent GI symptoms and declining nutritional status either while on PD or after transfer to HD. Commonest complaints include decreased appetite, early satiety, nausea and vomiting. Recurrent episodes of small bowel obstruction are seen in severe cases. In the right clinical setting, bloody dialysate (PD) or recurrent +/- bloody ascites (HD) may also point to EPS. Abdominal CT scanning can be helpful (as above). However, direct visualisation with laparoscopy and peritoneal biopsy are sometimes needed to confirm the diagnosis. Interesting reviews on the condition are here and here.


Martina McGrath MD

PD – causes of blood in the dialysate

A recent post got me thinking of the differential diagnosis of blood-stained peritoneal dialysis effluent. I thought it would be interesting to share some of the differentials and to remember that the Tenchkoff catheter can truly be a window to the abdominal cavity.

Blood-stained PD fluid can be dramatic and frightening for both patient and doctor alike. As little as 4-5mls of blood can be enough to cause grossly apparent colour changes in the fluid. A very succinct review can be found here.

Catheter related conditions

- Catheter insertion, manipulation and trauma/pulling of the external limb of the catheter can all cause local tissue damage at the peritoneal entry site, which could lead to blood staining.

- Insertion related trauma to intra-abdominal organs and/or vasculature can also cause more serious and more persistent bleeding. This may be reduced by laparoscopic assisted placement of catheters, which allows more direct visualization of the catheter during insertion. The risk of bleeding obviously increases if patients have significant adhesions and previous surgeries (often relative contraindications to successful PD anyway).

Menstruation

In female patients menses accounts for around one third of cases of haemoperitoneum associated with PD. This of course varies with age. The menstrual history is an important area to ask about during history taking from female PD patients. Ovulation can also result in haemoperitoneum.

Obstetric related

Lacerations of the gravid uterus by the PD catheter have been proposed as a possible rare cause for bloody PD fluid during pregnancy.

Other intra-abdominal organ pathology

Rupture cysts from ADPKD have been proposed to cause bloody PD fluid, despite their retroperitoneal location. It’s postulated that superficial cysts may form adhesions with the peritoneal cavity, allowing access after cyst rupture.

Liver and splenic lesions may cause bleeding into the peritoneal cavity – e.g. tumours, cysts, rupture and trauma. Bloody dialysate has rarely been reported after colonoscopy procedures also.

Surgery

Intra-abdominal surgery has been well recognized to lead to bloody PD fluid. The tendency to bleed may be enhanced by advanced uraemia and by the coexistence of any coagulopathies.

Of note gross haematuria is rare with infectious aetiologies of peritoneal disease. However, it is important to take advantage of the relative ease of acquiring a fluid sample when a PD patient presents with abdominal pathology. Remember that we can check for more than just white cells in a PD fluid sample – we can also look for red cells, amylase and abnormal cytology as just a few examples of additional tests. Putting all these clues together may lead us to an alternative and interesting diagnosis.