Advances in Peritoneal Dialysis, Vol. 29, 2013

Hepatorenal Syndrome Treated for Eight Months

Elliot Charen,1 Kobena Dadzie,1 Nijal Sheth,1 Hira Siktel,1 with Continuous-Flow Alan Dubrow,1 Nikolas Harbord,1 James Winchester,1 Claudio Ronco,2 Richard Amerling1 Peritoneal Dialysis

The case documented here represents the longest Hypotension was managed with a combination course of continuous-flow peritoneal dialysis (PD) of blood transfusions, albumin, and vasopressors. reported in the literature. A 61-year-old man with The acute kidney injury (AKI) initially responded hepatorenal syndrome type 1 and ascites presented to resuscitative measures as listed, but then oliguria with hypotension and bright red blood per rectum and acidemia worsened, with creatinine increasing and was found to be in acute renal failure with severe to 8.65 mg/dL. The patient became more obtunded; anemia. Continuous-flow PD was initiated, and the the anasarca worsened, including reaccumulation of patient improved clinically. The patient died of a the ascites post paracentesis; and the patient became jejunal bleed 8 months later, before discharge. Acute dyspneic at rest. PD or continuous-flow PD is a viable alternative in By the 5th hospital day, palliative care was con- the setting of hemodynamic instability and ascites, sulted because of the poor prognosis of hepatorenal can be used as a chronic modality, and addresses syndrome and the patient’s ineligibility for liver trans- many of the weaknesses of continuous ambulatory plantation secondary to alcohol abuse. The renal team and automated PD. discussed the risks and possible benefits of peritoneal dialysis (PD) and continuous-flow PD (CFPD) with Key words the family, who agreed to a trial. On hospital day 12, a Continuous-flow peritoneal dialysis, acute kidney dual-lumen Ronco PD catheter (Figure 1) was placed injury, hepatorenal syndrome at bedside, and 8 L ascites was drained. The patient required intravenous albumin and Case description dopamine infusion to support his blood pressure. On A 61-year-old man with alcoholic cirrhosis, chronic hospital day 13, standard acute PD was initiated (with kidney disease (baseline creatinine 3 months before dopamine infusion) using 4 exchanges of 1.5% dex- admission: 1.5 mg/dL), and tophaceous gout presented trose solution. With a daily net negative fluid balance with hypotension and bright red blood per rectum. He of 4 – 7 L, a combination of albumin, blood transfu- denied recent use of alcohol and nonsteroidal anti- sions, saline, and dopamine were needed. On hospital inflammatory drugs. Physical exam revealed hypo- day 21, dopamine was switched to midodrine, and the tension, altered mental status, tense ascites, anasarca, patient was transferred to the general medical ward. spider angiomata of the abdomen, large tophi of both Serum albumin was consistently below 1.8 g/dL. upper extremities, muscle wasting, and cachexia. Because of persistent hypotension after 24 days Laboratory data on admission were significant of intermittent PD, CFPD was started once radio- for creatinine 5.24 mg/dL and hemoglobin 5.6 g/dL. graphic verification had been obtained that the dif- Paracentesis was negative for spontaneous bacterial fuser portion of the Ronco catheter was located in the peritonitis, and 4.6 L ascites were drained. Upper peritoneal cavity. A Fresenius 2008H hemodialysis endoscopy demonstrated no evidence of bleeding or machine with a F180NR dialyzer was used in continu- varices, only chronic gastritis. ous renal replacement therapy mode to dialyze ascites

with a peritoneal fluid flow (Qp) of 300 mL/min and From: 1Division of Nephrology and Hypertension, Beth a dialysate flow of 500 mL/min. The ascitic fluid was Israel Medical Center, New York, New York, U.S.A., and dialyzed against a standard dialysate with 2.5 mEq/L 2Nephrology Division, San Bortolo Hospital, Vicenza, Italy. Ca and 4.0 mEq/L K. During each session, 2 – 4 L Charen et al. 39

figure 1 Ronco 15F peritoneal dialysis catheter with diffuser. Source: C. Ronco, reproduced with permission. ascites was removed by ultrafiltration (UF). Each to enhance clearance, but because of worsening session lasted 4 – 6 hours, and 4 – 6 sessions were symptomatic hypotension, hemodialysis was stopped. delivered per week. Clearances were calculated by Eight months into the hospital admission, the the Daugirdas equation using pre- and post-treatment patient developed recurrent gastrointestinal bleeding. blood chemistries (Table I). Sigmoidoscopy was negative, and a bleeding scan re- The patient improved clinically over several vealed a jejunal bleed. The bleeding proved refractory, weeks, with clearing of anasarca (20 kg net weight and the patient died 236 days after hospitalization. reduction), control of ascites and acidosis, and with- drawal of pressors. The CFPD was continued, with a Discussion few missed treatments because of melena, worsening anemia, and punctate leaks in the external portion of Review of CFPD the catheter near the Luer connector (fixed by trim- The principle of CFPD is to maximize transperitoneal ming the tubing and inserting a new Luer connector). solute transport by maintaining a constant infusion Four months into the admission, the patient devel- of solute-free dialysate. The process requires a dual- oped an elevated white blood cell count of 15.6×109/L, lumen catheter (or 2 catheters), and either large vol- but was asymptomatic. The cell count in his peritoneal umes of fresh, sterile dialysate (single-pass, used in fluid was 3060/μL with 85% neutrophils, and a cul- pediatric AKI), or external regeneration of dialysate ture grew Streptococcus mitis and S. oralis sensitive using a hemodialysis circuit or sorbent. to ceftriaxone. The white blood cell count in ascites Continuous-flow PD was first reported by Shina- decreased promptly with antibiotics. berger et al. in 1965, with urea clearances in the range The patient’s Kt/V urea averaged 0.25 per treat- 46 – 125 mL/min (1). Those authors used 2 peritoneal ment (Table I) with a mean urea clearance (KU) of catheters with 3 L sterile dialysate refreshed by an 46 mL/min. Mean creatinine clearance (KCr) was external Kiil dialyzer and a Qp in the range 120 – 44 mL/min, mean phosphorus clearance (KPh) was 300 mL/min. During the subsequent two decades, 52 mL/min, and mean uric acid clearance (KUric) was other groups (2–5) reported urea clearances of 30 – 47 mL/min (Table II). 50 mL/min using various means of peritoneal access. The patient remained cachectic, and sessions were Since the start of the 1990s, enhanced solute clear- increased to 6 hours. The KU declined after 6 – 8 ance with CFPD has been confirmed (6–9). There have months to a mean of 24 mL/min (Table I). The KCr also been improvements in catheter design to prevent was 21 mL/min, KPh was 17 mL/min, and KUric was “streaming”—that is, channeling of dialysate causing 22 mL/min (Table II). Seven months into the hospital a maldistribution of flow (10). The newer catheters admission, an attempt was made to add hemodialysis enhance intraperitoneal (IP) dialysate mixing and 40 Hepatorenal Syndrome Treated for Eight Months with CFPD table i Early and late treatment data for continuous-flow peritoneal dialysis

Treatment UF Weight (kg) Volume time Qp volume BUN (mg/dL) Urea KU Date Before After (L) (min) (mL/min) (L) Before After Kt/V (mL/min)

25 Apr 81.4 77 48.8 240 300 3961 27 23 0.25 50.88 26 Apr 79.4 77.6 47.6 240 300 1800 24 21 0.21 41.69 28 Apr 78 77.3 46.8 245 300 1000 27 23 0.21 40.11 30 Apr 78.8 77.3 47.3 240 300 1500 30 24 0.32 63.04 7 May 75 71.8 45.0 260 200 3200 48 41 0.24 41.54 17 May 69.9 66.7 41.9 260 300 3065 34 29 0.25 40.33 25 May 64 62 38.4 240 300 2007 31 26 0.25 40.00 Mean (early) 75 73 45 246 286 2362 32 27 0.25 45.37

20 Aug 55.1 54.6 33.1 300 300 4200 30 26 0.26 28.65 12 Oct 55.9 52.3 33.5 360 300 3700 47 44 0.17 15.84 17 Oct 55.7 52.3 33.4 360 300 2600 51 43 0.28 25.99 Mean (late) 56 53 33 340 300 3500 43 38 0.24 23.49

Qp = peritoneal fluid flow; UF = ultrafiltration; BUN = blood urea nitrogen; KU = urea clearance.

table ii Early and late treatment data for small solutes during continuous-flow peritoneal dialysis

Creatinine (mg/dL) KCr Phosphorus (mg/dL) KPh Uric acid (mg/dL) KUric Date Before After Kt/V (mL/min) Before After Kt/V (mL/min) Before After Kt/V (mL/min)

25 Apr 3.8 3.2 0.26 52.91 4.6 3.6 0.35 71.23 26 Apr 3.4 3.0 0.18 35.73 4.0 3.5 0.22 43.67 28 Apr 3.8 3.1 0.26 49.67 4.2 3.5 0.25 47.76 30 Apr 4.1 3.3 0.32 63.04 4.5 3.5 0.35 68.95 8.2 6.6 0.28 55.16 7 May 4.2 3.7 0.21 36.35 3.3 2.9 0.21 36.35 9 7.8 0.23 39.81 17 May 5.3 4.4 0.28 45.17 6.7 5.9 0.26 41.94 25 May 3.8 3.5 0.16 25.60 4.7 Mean (early) 44.07 51.65 47.48

20 Aug 4.6 4.1 0.22 24.24 5.3 5.1 0.13 14.33 6.9 6.1 0.24 26.45 17 Oct 4.5 4.1 0.20 18.57 5.7 5.1 0.21 19.50 6.1 5.6 0.18 16.71 Mean (late) 21.41 16.91 21.58

KCr = creatinine clearance; KPh = phosphorous clearance; KUric = uric acid clearance. contact with the peritoneal membrane. The Ronco Along with others, we have reported the success- dual-lumen catheter used in our patient has a thin- ful use of CFPD for AKI (12,13). We have also used walled silicone diffuser that is implanted in the upper CFPD in patients with refractory dialysis ascites (14). abdomen and that enables dialysate to exit from mul- Other potential applications include home dialysis and tiple pores, thus reducing trauma to the peritoneal walls a wearable artificial kidney device. and also improving IP mixing of the dialysate (11). The Our patient benefited from use of PD and CFPD second lumen is positioned inferiorly in the pelvis to for AKI leading to end-stage renal disease and minimize streaming. management of ascites. We were in the process of Charen et al. 41 preparing the patient for home CFPD, with the family the circuit would maintain that level, lower concentra- providing support. tions would likely be successful. The machine would need to balance internal UF with external UF to allow CFPD in AKI for gradual removal of the IP volume, a task that might Like standard acute PD, CFPD benefits patients with be accomplished using IP pressure monitors. AKI who are too hemodynamically unstable to tolerate The 2008K2 machines are designed for blood use intermittent hemodialysis, those for whom blood ac- and therefore require disabling of the optical blood- cess is unavailable, and those in whom anticoagulation sensing alarms. For patients with significant ascites is contraindicated (15,16). Our patient was extremely and volume overload, setting UF goals and checking unstable, with large fluid shifts and hypotension even weight before and after should suffice for manage- on standard acute PD. Those circumstances forced the ment. Our patient rarely had abdominal pain, because transition to CFPD, which was then maintained for the the IP volume was decreasing; however, the few times duration of his hospitalization. such pain occurred, it resolved with either a decrease

in the Qp or with the IP addition of normal saline. CFPD in dialysis ascites However, patients without significant hypervolemia Continuous-flow PD can be used in end-stage renal may suffer from volume depletion or failure of ascitic disease patients with dialysis ascites, obviating the recirculation (or both) as ascitic fluid is depleted (15). need for recurrent large-volume paracentesis. Dialy- Advantages of CFPD over standard PD include sis patients can accumulate ascites secondary to cir- removal of inefficiency from the fill–dwell–drain rhosis, heart failure, or previous PD (15). Repeated cycles (17), absence of glucose degradation prod- ascitic drainage causes continuous protein loss and ucts in the dialysate, improved biocompatibility of malnutrition; in contrast, the proteins are retained fluids (bicarbonate), minimal protein loss (18), and with CFPD (15). If ascitic fluid is circulated against lower cost of online production of dialysate from sterile, urea-free dialysate, then urea clearance lags purified water. by about 30 – 60 minutes depending on the volume of ascites and the efficiency of the extracorporeal Discussion circuit, because the external dialyzer must first Our patient presented with hepatorenal syndrome lower the urea level in the ascitic fluid to facilitate and AKI in the setting of a gastrointestinal bleed. transperitoneal urea transport (15). Another benefit He benefited from multiple applications of CFPD, of dialysis of ascites is that the proteins become including management of AKI, ascites, and daily concentrated as water exits the dialyzer membrane, dialysis. This case reinforces the potential for CFPD creating a favorable gradient for transperitoneal in such settings. Our patient survived and experienced UF (15). On chronic CFPD, our patient no longer improved functional status (he attended his daughter’s required vasopressors or intravenous saline sup- wedding) on chronic CFPD. However, he remained port, and we were easily able to maintain volume cachectic throughout the course of his hospitalization, homeostasis by UF of ascites. despite dietary measures and anabolic steroids. We attribute the cachexia to end-stage liver failure. The CFPD in daily home dialysis decrease in clearance over time was likely the result Obstacles to daily home CFPD include machine of membrane failure (19). The reduced urea clearance design and UF management. In patients who do not might still have been adequate if we had been able to generate ascites, several options for volume control extend treatment time to 8 – 10 hours, which was our are available. Diuretics can be used to maximize plan after discharge to home. natriuresis from the native kidneys in patients with There are still barriers to a successful home dialy- residual function. An overnight or day dwell with sis implementation, which this patient never had the hypertonic dextrose or icodextrin might be sufficient chance to experience. The Ronco catheter represents in some patients. a major advance in peritoneal access technology, and To incorporate volume management into a CFPD CFPD continues to address many of the weaknesses machine, the dextrose concentration in the external cir- of continuous ambulatory PD and automated PD. Cur- cuit would have to be boosted to 1% – 1.5%. Because rently, projects using CFPD technology to develop a 42 Hepatorenal Syndrome Treated for Eight Months with CFPD wearable artificial kidney are ongoing (20). 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