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15. Srisawat N, Murugan R, Lee M, Kong L, Carter M, Angus DC, Kellum JA; Genetic, Inflammatory Markers of Sepsis Study Investigators: Plasma neutrophil gelatinase-associated lipocalin predicts recovery from acute kidney injury following community-acquired pneumonia. Kidney Int 80:545–552, 2011 16. Taman M, Liu Y, Tolbert E, Dworkin LD: Increase urinary hepatocyte growth factor excretion in human acute renal failure. Clin Nephrol 48:241–245, 1997 17. Luk CC, Chow KM, Kwok JS, Kwan BC, Chan MH, Lai KB, Lai FM, Wang G, Li PK, Szeto CC: Urinary biomarkers for the prediction of reversibility in acute-on-chronic renal failure. Dis Markers 34:179–185, 2013 18. Vaidya VS, Waikar SS, Ferguson MA, Collings FB, Sunderland K, Gioules C, Bradwin G, Matsouaka R, Betensky RA, Curhan GC, Bonventre JV: Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl Sci 1:200–208, 2008 19. Kwon O, Ahn K, Zhang B, Lockwood T, Dhamija R, Anderson D, Saqib N: Simultaneous monitoring of multiple urinary cytokines may predict renal and patient outcome in ischemic AKI. Ren Fail 32:699– 708, 2010 20. Hall IE, Yarlagadda SG, Coca SG, Wang Z, Doshi M, Devarajan P, Han WK, Marcus RJ, Parikh CR: IL-18 and urinary NGAL predict dialysis and graft recovery after kidney transplantation. J Am Soc Nephrol 21:189–197, 2010 21. Kusaka M, Iwamatsu F, Kuroyanagi Y, Nakaya M, Ichino M, Marubashi S, Nagano H, Shiroki R, Kurahashi H, Hoshinaga K: Serum neutrophil gelatinase associated lipocalin during the early postoperative period predicts the recovery of graft function after kidney transplantation from donors after cardiac death. J Urol 187:2261–2267, 2012 22. Schmidt IM, Hall IE, Kale S, Lee S, He CH, Lee Y, Chupp GL, Moeckel GW, Lee CG, Elias JA, Parikh CR, Cantley LG: Chitinase-like protein Brp-39/YKL-40 modulates the renal response to ischemic injury and predicts delayed allograft function. J Am Soc Nephrol 24:309–319, 2013 23. Belcher JM, Sanyal AJ, Peixoto AJ, Perazella MA, Lim J, ThiessenPhilbrook H, Ansari N, Coca SG, Garcia-Tsao G, Parikh CR, fortheTRIBE-AKIConsortium: Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology 2013 Dec 21 [Epub ahead of print] 24. Aregger F, Uehlinger DE, Witowski J, Brunisholz RA, Hunziker P, Frey FJ, Jorres A: Identification of IGFBP-7 by urinary proteomics as a novel prognostic marker in early acute kidney injury. Kidney Int 2013 Sep 25 [Epub ahead of print]
4. Palevsky PM, O’Connor TZ, Chertow GM, Crowley ST, Zhang JH, Kellum JA; US Department of Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network: Intensity of renal replacement therapy in acute kidney injury: perspective from within the Acute Renal Failure Trial Network Study. Crit Care 13:310, 2009 5. Bagshaw SM, Berthiaume LR, Delaney A, Bellomo R: Continuous versus intermittent renal replacement therapy for critically ill patients with acute kidney injury: a meta-analysis. Crit Care Med 36:610–617, 2008 6. Heung M, Chawla LS: Predicting progression to chronic kidney disease after recovery from acute kidney injury. Curr Opin Nephrol Hypertens 21:628–634, 2012 7. Mohan S, Huff E, Wish J, Lilly M, Chen SC, McClellan WM; Fistula First Breakthrough Initiative Data Committee: Recovery of renal function among ESRD patients in the US medicare program. PLoS ONE 8:e83447, 2013 8. Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Straaten HO, Ronco C, Kellum JA: Discontinuation of continuous renal replacement therapy: a post hoc analysis of a prospective multicenter observational study. Crit Care Med 37:2576–2582, 2009 9. Chawla LS, Amdur RL, Amodeo S, Kimmel PL, Palant CE: The severity of acute kidney injury predicts progression to chronic kidney disease. Kidney Int 79:1361–1369, 2011 10. Schmitt R, Coca S, Kanbay M, Tinetti ME, Cantley LG, Parikh CR: Recovery of kidney function after acute kidney injury in the elderly: a systematic review and meta-analysis. Am J Kidney Dis 52:262–271, 2008 11. Kawarazaki H, Uchino S, Tokuhira N, Ohnuma T, Namba Y, Katayama S, Toki N, Takeda K, Yasuda H, Izawa J, Uji M, Nagata I, Group JCT: Who may not benefit from continuous renal replacement therapy in acute kidney injury? Hemodial Int 17: 624–632, 2013 12. Heung M, Wolfgram DF, Kommareddi M, Hu Y, Song PX, Ojo AO: Fluid overload at initiation of renal replacement therapy is associated with lack of renal recovery in patients with acute kidney injury. Nephrol Dial Transplant 27:956–961, 2012 13. Srisawat N, Wen X, Lee M, Kong L, Elder M, Carter M, Unruh M, Finkel K, Vijayan A, Ramkumar M, Paganini E, Singbartl K, Palevsky PM, Kellum JA: Urinary biomarkers and renal recovery in critically ill patients with renal support. Clin J Am Soc Nephrol 6:1815– 1823, 2011 14. Nejat M, Pickering JW, Devarajan P, Bonventre JV, Edelstein CL, Walker RJ, Endre ZH: Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney Int 81:1254–1262, 2012
Is Acute Peritoneal Dialysis Feasible for Treatment of Hospital-Acquired Acute Kidney Injury? Chang Yin Chionh* and Dinna N. Cruz† *Division of Renal Medicine, Changi General Hospital, Singapore, and †Division of NephrologyHypertension, Department of Medicine, University of California, San Diego, California
There has been a recent increase in interest in the use of peritoneal dialysis (PD) in acute kidney injury (AKI) (1,2). Although extracorporeal blood purification (EBP) is more commonly employed for supportive therapy in AKI worldwide, a recent sys-
tematic review demonstrated no significant differences in outcomes between PD and EBP (3). Because of its technical simplicity, PD is more widely used in resource-limited areas and is often the only form of dialysis available (4,5). In such areas, community-acquired AKI tended to feature more prominently, such as AKI due to diarrheal and other tropical diseases (including malaria, leptospirosis, and dengue), snake bites, and nephrotoxic drugs (5). In the urban and developed setting, hospital-acquired AKI is more commonly reported (6). Indeed the majority of AKI studies from high-income countries have focused on AKI in the hospital and intensive care unit (ICU).
Address correspondence to: Dinna N. Cruz, MD, MPH, Division of Nephrology-Hypertension, University of California, San Diego, 200 West Arbor Drive #8409, San Diego, CA 92103-8409, Tel.: (619) 471-0753, Fax: (619) 471-0754, or e-mail: [email protected]. Seminars in Dialysis—Vol 27, No 3 (May–June) 2014 pp. 239–242 DOI: 10.1111/sdi.12209 © 2014 Wiley Periodicals, Inc. 239
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While the definitions are not standardized, hospital-acquired AKI is recognized when the consensus AKI criteria (7–9) are met during hospitalization after one or more renal insults. Common causes of hospital-acquired AKI include volume depletion, sepsis, postsurgery AKI, radiocontrast media and drug-induced AKI (10). This article will review the experience with PD for AKI in this setting.
particularly in the context of hospital-acquired AKI. In one RCT, 120 patients with AKI referred to their nephrology service after hospital admission was randomized to treatment with PD or daily hemodialysis (13). Of the 120 patients, 77.4% required ICU care and 44.5% were septic. The RCT demonstrated no differences in mortality, but noted a significantly shorter time to renal recovery, with PD patients requiring an average of 5.5 days of dialysis dependence, as opposed to 7.5 days for hemodialysis. Another RCT randomized ICU patients with AKI to PD with continuous veno-venous hemodiafiltration (CVVHDF) looking primarily at solute control (correction of uremia, electrolyte and acid-base disorders), as well as correction of fluid overload (14). Urea and creatinine clearances, as well as control of fluid overload, were significantly better with CVVHDF than PD; however, correction of acidosis was better with PD. PD and CVVHDF were comparable with respect to correction of hyperkalemia and hemodynamic disturbances, although the cost of consumables for CVVHDF was more than twice that of PD. Sepsis is a common cause of AKI in the hospital setting. Observational studies including septic patients with AKI have reported successful treatment of hospital-acquired AKI with PD. Techniques to achieve a high dialysis dose with high volume PD have been utilized to enhance clearance in hypercatabolic patients with AKI(15). The investigators were able to deliver a weekly Kt/V of 3.56 0.68 which achieved a level of metabolic control desired in a group of predominantly septic patients. In a small study of 20 patients, adequate metabolic control was also achieved using a lower PD dose, and correction of acidosis was more rapid with bicarbonate-based rather than lactate-based solutions (16). Subset analysis of comparative studies including septic patients found no differences in outcomes between PD and EBP, although there is significant heterogeneity between the studies (Fig. 1). Although one RCT conducted in Vietnam favored EBP over PD, most patients in the study had malaria, which is regarded as a community-related AKI (17). In addition, such poor outcomes in patients with malaria were not seen in more recent studies (18). Data on the use of PD in AKI related to trauma or surgery are based on much older studies. Cameron and colleagues described successful use of PD to manage uremia in the postsurgery setting (19), while others described the applicability of PD in critical trauma (20). Hadidy et al. retrospectively reviewed 102 patients, majority of them having had trauma or surgery, and the patients who received PD did as well as those on hemodialysis (21). Two recent studies that included a small proportion of surgical patients reported no differences in outcomes with either PD or EBP (Fig. 1) (13,22). While no technical difficulties were reported, the studies did not include patients with major abdominal trauma or surgery.
Pathophysiology of Hospital-Acquired AKI Are there major differences in the pathophysiology of AKI which requires different approaches in their management? Very often, community-acquired AKI and hospital-acquired AKI have similar underlying pathophysiologic mechanisms. These include intravascular volume depletion, ischemia/reperfusion injury related to hypotension or circulatory shock (e.g. hemorrhagic shock, dehydration), or direct tubulo-toxic effects of various drugs or poisons. In such situations, the differences in outcomes between community-acquired and hospital-acquired AKI are often due to differences in timing of supportive therapy initiation. There exist theoretical postulates that some forms of hospital-acquired AKI have different underlying mechanisms of injury. In septic AKI, proinflammatory cytokines have been postulated to be the main trigger for the sepsis cascade resulting in AKI. In contrast, an immunologic-related mechanism has been demonstrated in cardio-renal syndromes (11). While there are many studies addressing the cytokine theory using continuous renal replacement therapy, only a few studies have utilized PD. The peritoneal membrane has pores large enough to theoretically allow clearance of these molecules. A study in infants after cardio-pulmonary bypass surgery demonstrated effective clearance of IL-6 and IL-8 using PD, although the clearance was superior with ultrafiltration (12). PD for AKI in Specific Populations In a systematic review of 24 studies (n = 1556 patients), no differences were found in mortality outcomes between PD and EBP for AKI (pooled OR 1.11, 95% CI 0.66–1.88) (3). However, there were multiple etiologies for AKI in each of the studies, and no study specifically identified hospitalacquired AKI. Pooled analysis of studies which included patients who were likely to have developed AKI in the hospital, such as postsurgical, ICU and septic patients revealed no significant differences in mortality outcomes between PD and EBP. Fig. 1 shows subgroup analyses for studies including patients with sepsis, in the ICU, and postsurgery or trauma. A few of these studies merit further discussion. There have been only a few randomized controlled trials (RCT) that compared PD with EBP, 240
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Fig. 1. Comparison of peritoneal dialysis (PD) with extra-corporeal blood purification (EBP) in studies which included (A) Septic patients, (B) Intensive care unit (ICU) patients, (C) Post-surgical or trauma patients. Odds ratio with 95% confidence intervals (CI) was calculated using the Mantel-Haenszel (M-H) random-effects model. Chow et al. described two study cohorts 10 years apart and data were analyzed separately, represented as (A) and (B).
Performing PD for AKI
bags and makeshift connections may be necessary in resource-poor settings. There is no convincing evidence that automated PD is safer or more effective than manual exchanges. In patients with shock or liver failure, bicarbonate containing solutions may be preferable to lactate, especially in the setting of metabolic acidosis. As noted above, correction of metabolic acidosis was more rapid with bicarbonate compared to lactate-based PD solutions, although hard clinical outcomes were comparable (16). During the initial 24 hours of therapy, short cycle times (e.g. 1–2 hours) may be necessary to correct fluid overload, hyperkalemia, and/or metabolic acidosis. Thereafter, the cycle time may be increased to 4–6 hours depending on the clinical circumstances. The optimal dose of PD for AKI is unclear, resulting in ambiguity among practitioners (26). A single center study, targeting a weekly Kt/V urea of 3.5, demonstrated comparable outcomes for PD and daily HD (13). However, other studies have shown good outcomes using lower doses (27,28). Extrapolating from data on EBP, targeting a weekly KT/V of 2.1 may represent a minimum clearance standard (29). Higher small solute clearances may be necessary in hypercatabolic AKI patients.
Appropriate patient selection and PD technique, as well as center experience, are important determinants of the feasibility and success of PD as a therapy for AKI. Where other EBP modalities are easily available, PD would probably be more appropriate for patients with only one or two organ failures. Patients with multiple organ failure, previous midline surgical scars or high risk of peritoneal adhesions may be more appropriately managed with EBP. On the other hand, patients with advanced CKD who have superimposed AKI could potentially be well-served by PD. In the event of a delay in, or lack of, significant renal recovery, it may facilitate the transition to outpatient peritoneal dialysis (23). Flexible peritoneal catheters are preferred and should ideally be used where resources and expertise exist, in view of lower incidence of peritoneal fluid leakage and infection (24). Prophylactic antibiotics prior to insertion of the PD catheter have been associated with a significant reduction in the incidence of peritonitis (25). A closed fluid delivery system with Y connection is also ideal to minimize infection, although it is recognized that spiking of 241
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Due to the high glucose concentration in PD fluid, there is concern regarding hyperglycemia with acute PD. The incidence of this complication is generally poorly reported in studies (3). However, in the randomized trial comparing PD to daily hemodialysis, glucose levels were similar between the two modalities (13). No patient had uncontrolled hyperglycemia in either group. Hyperglycemia can be treated with insulin subcutaneously, intravenously, or by adding it to the peritoneal fluid. There is no evidence to support the superiority of any particular approach. In AKI, the exposure to high glucose concentration is expected to be short-term. There are no data on its long-term consequences. Lastly, peritonitis is an important complication of PD. Its diagnosis may be challenging when dwell times are short. Nevertheless, a daily PD fluid leukocyte count may be useful for peritonitis surveillance. Diagnosis and treatment should be based on existing ISPD guidelines (30), in the absence of specific guidelines for acute PD.
8.
9. 10. 11.
12.
13.
14.
15.
16.
Is Acute Peritoneal Dialysis Feasible for Treatment of Hospital-Acquired AKI?
17.
To answer the question, there is no evidence to indicate inferiority of PD for management of hospital-acquired AKI. As such, PD should be considered a viable modality option. The feasibility and success of PD for AKI depends on appropriate patient selection, proper PD technique, and center experience. While expert practice recommendations exist for EBP, none currently exist for PD, resulting in variability in practice (26). The International Society of Peritoneal Dialysis is developing consensus guidelines to address this knowledge gap.
18. 19. 20.
21.
22.
23.
24.
References
25. 1. Blake PG: A renaissance for PD in acute kidney injury. Perit Dial Int 32(3):237, 2012 2. Yeates K, Cruz DN, Finkelstein FO: Re-examination of the role of peritoneal dialysis to treat patients with acute kidney injury. Perit Dial Int 32(3):238–241, 2012 3. Chionh CY, Soni SS, Finkelstein FO, Ronco C, Cruz DN: Use of peritoneal dialysis in AKI: A systematic review. Clin J Am Soc Nephrol 8(10):1649–1660, 2013 4. Jha V, Parameswaran S: Community-acquired acute kidney injury in tropical countries. Nat Rev Nephrol 9(5):278–290, 2013 5. Lameire NH, Bagga A, Cruz D, De Maeseneer J, Endre Z, Kellum JA, Liu KD, Mehta RL, Pannu N, Van Biesen W, Vanholder R: Acute kidney injury: An increasing global concern. Lancet 382(9887):170– 179, 2013 6. Lameire N, Van Biesen W, Vanholder R: The changing epidemiology of acute renal failure. Nat Clin Pract Nephrol 2(7):364–377, 2006 7. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P: Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: The Second International Consen-
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sus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8(4):R204–R212, 2004 Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A: Acute Kidney Injury Network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care 11(2):R31, 2007 Group KDIGOKAKIW: KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2:138, 2012 Nash K, Hafeez A, Hou S: Hospital-acquired renal insufficiency. Am J Kidney Dis 39(5):930–936, 2002 Virzi GM, Torregrossa R, Cruz DN, Chionh CY, de Cal M, Soni SS, Dominici M, Vescovo G, Rosner MH, Ronco C: Cardiorenal syndrome type 1 may be immunologically mediated: A pilot evaluation of monocyte apoptosis. Cardiorenal Med 2(1):33–42, 2012 Dittrich S, Aktuerk D, Seitz S, Mehwald P, Schulte-Monting J, Schlensak C, Kececioglu D: Effects of ultrafiltration and peritoneal dialysis on proinflammatory cytokines during cardiopulmonary bypass surgery in newborns and infants. Eur J Cardiothorac Surg 25(6):935–940, 2004 Gabriel DP, Caramori JT, Martim LC, Barretti P, Balbi AL: High volume peritoneal dialysis vs daily hemodialysis: A randomized, controlled trial in patients with acute kidney injury. Kidney Int Suppl 108: S87–S93, 2008 George J, Varma S, Kumar S, Thomas J, Gopi S, Pisharody R: Comparing continuous venovenous hemodiafiltration and peritoneal dialysis in critically ill patients with acute kidney injury: A pilot study. Perit Dial Int 31(4):422–429, 2011 Ponce D, Berbel MN, Regina de Goes C, Almeida CT, Balbi AL: High-volume peritoneal dialysis in acute kidney injury: Indications and limitations. Clin J Am Soc Nephrol 7(6):887–894, 2011 Thongboonkerd V, Lumlertgul D, Supajatura V: Better correction of metabolic acidosis, blood pressure control, and phagocytosis with bicarbonate compared to lactate solution in acute peritoneal dialysis. Artif Organs 25(2):99–108, 2001 Phu NH, Hien TT, Mai NT, Chau TT, Chuong LV, Loc PP, Winearls C, Farrar J, White N, Day N: Hemofiltration and peritoneal dialysis in infection-associated acute renal failure in Vietnam. N Engl J Med 347 (12):895–902, 2002 Mishra SK, Mahanta KC: Peritoneal dialysis in patients with malaria and acute kidney injury. Perit Dial Int 32(6):656–659, 2012 Cameron JS, Ogg C, Trounce JR: Peritoneal dialysis in hypercatabolic acute renal failure. Lancet 1(7501):1188–1191, 1967 Howdieshell TR, Blalock WE, Bowen PA, Hawkins ML, Hess C: Management of post-traumatic acute renal failure with peritoneal dialysis. Am Surg 58(6):378–382, 1992 Hadidy S, Asfari R, Shammaa MZ, Hanifi MI: Acute renal failure among a Syrian population. Incidence, aetiology, treatment and outcome. Int Urol Nephrol 21(5):455–461, 1989 Mahajan S, Tiwari S, Bhowmik D, Agarwal SK, Tiwari SC, Dash SC: Factors affecting the outcome of acute renal failure among the elderly population in India: A hospital based study. Int Urol Nephrol 38 (2):391–396, 2006 Povlsen JV, Ivarsen P: How to start the late referred ESRD patient urgently on chronic APD. Nephrol Dial Transplant 21(Suppl 2):ii56– ii59, 2006 Wong SN, Geary DF: Comparison of temporary and permanent catheters for acute peritoneal dialysis. Arch Dis Child 63(7):827–831, 1988 Strippoli GF, Tong A, Johnson D, Schena FP, Craig JC: Antimicrobial agents for preventing peritonitis in peritoneal dialysis patients. Cochrane Database Syst Rev (4):CD004679, 2004 Gaiao S, Finkelstein FO, de Cal M, Ronco C, Cruz DN: Acute kidney injury: are we biased against peritoneal dialysis? Perit Dial Int 32 (3):351–355, 2012 Kilonzo KG, Ghosh S, Temu SA, Maro V, Callegari J, Carter M, Handelman G, Finkelstein FO, Levin N, Yeates K: Outcome of acute peritoneal dialysis in northern Tanzania. Perit Dial Int 32(3):261–266, 2012 Chitalia VC, Almeida AF, Rai H, Bapat M, Chitalia KV, Acharya VN, Khanna R: Is peritoneal dialysis adequate for hypercatabolic acute renal failure in developing countries? Kidney Int 61(2):747–757, 2002 Chionh CY, Ronco C, Finkelstein FO, Soni SS, Cruz DN: Acute peritoneal dialysis: what is the ‘adequate’ dose for acute kidney injury? Nephrol Dial Transplant 25(10):3155–3160, 2010 Li PK, Szeto CC, Piraino B, Bernardini J, Figueiredo AE, Gupta A, Johnson DW, Kuijper EJ, Lye WC, Salzer W, Schaefer F, Struijk DG: Peritoneal dialysis-related infections recommendations: 2010 update. Perit Dial Int 30(4):393–423, 2010
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15. Srisawat N, Murugan R, Lee M, Kong L, Carter M, Angus DC, Kellum JA; Genetic, Inflammatory Markers of Sepsis Study Investigators: Plasma neutrophil gelatinase-associated lipocalin predicts recovery from acute kidney injury following community-acquired pneumonia. Kidney Int 80:545–552, 2011 16. Taman M, Liu Y, Tolbert E, Dworkin LD: Increase urinary hepatocyte growth factor excretion in human acute renal failure. Clin Nephrol 48:241–245, 1997 17. Luk CC, Chow KM, Kwok JS, Kwan BC, Chan MH, Lai KB, Lai FM, Wang G, Li PK, Szeto CC: Urinary biomarkers for the prediction of reversibility in acute-on-chronic renal failure. Dis Markers 34:179–185, 2013 18. Vaidya VS, Waikar SS, Ferguson MA, Collings FB, Sunderland K, Gioules C, Bradwin G, Matsouaka R, Betensky RA, Curhan GC, Bonventre JV: Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl Sci 1:200–208, 2008 19. Kwon O, Ahn K, Zhang B, Lockwood T, Dhamija R, Anderson D, Saqib N: Simultaneous monitoring of multiple urinary cytokines may predict renal and patient outcome in ischemic AKI. Ren Fail 32:699– 708, 2010 20. Hall IE, Yarlagadda SG, Coca SG, Wang Z, Doshi M, Devarajan P, Han WK, Marcus RJ, Parikh CR: IL-18 and urinary NGAL predict dialysis and graft recovery after kidney transplantation. J Am Soc Nephrol 21:189–197, 2010 21. Kusaka M, Iwamatsu F, Kuroyanagi Y, Nakaya M, Ichino M, Marubashi S, Nagano H, Shiroki R, Kurahashi H, Hoshinaga K: Serum neutrophil gelatinase associated lipocalin during the early postoperative period predicts the recovery of graft function after kidney transplantation from donors after cardiac death. J Urol 187:2261–2267, 2012 22. Schmidt IM, Hall IE, Kale S, Lee S, He CH, Lee Y, Chupp GL, Moeckel GW, Lee CG, Elias JA, Parikh CR, Cantley LG: Chitinase-like protein Brp-39/YKL-40 modulates the renal response to ischemic injury and predicts delayed allograft function. J Am Soc Nephrol 24:309–319, 2013 23. Belcher JM, Sanyal AJ, Peixoto AJ, Perazella MA, Lim J, ThiessenPhilbrook H, Ansari N, Coca SG, Garcia-Tsao G, Parikh CR, fortheTRIBE-AKIConsortium: Kidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury. Hepatology 2013 Dec 21 [Epub ahead of print] 24. Aregger F, Uehlinger DE, Witowski J, Brunisholz RA, Hunziker P, Frey FJ, Jorres A: Identification of IGFBP-7 by urinary proteomics as a novel prognostic marker in early acute kidney injury. Kidney Int 2013 Sep 25 [Epub ahead of print]
4. Palevsky PM, O’Connor TZ, Chertow GM, Crowley ST, Zhang JH, Kellum JA; US Department of Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network: Intensity of renal replacement therapy in acute kidney injury: perspective from within the Acute Renal Failure Trial Network Study. Crit Care 13:310, 2009 5. Bagshaw SM, Berthiaume LR, Delaney A, Bellomo R: Continuous versus intermittent renal replacement therapy for critically ill patients with acute kidney injury: a meta-analysis. Crit Care Med 36:610–617, 2008 6. Heung M, Chawla LS: Predicting progression to chronic kidney disease after recovery from acute kidney injury. Curr Opin Nephrol Hypertens 21:628–634, 2012 7. Mohan S, Huff E, Wish J, Lilly M, Chen SC, McClellan WM; Fistula First Breakthrough Initiative Data Committee: Recovery of renal function among ESRD patients in the US medicare program. PLoS ONE 8:e83447, 2013 8. Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Straaten HO, Ronco C, Kellum JA: Discontinuation of continuous renal replacement therapy: a post hoc analysis of a prospective multicenter observational study. Crit Care Med 37:2576–2582, 2009 9. Chawla LS, Amdur RL, Amodeo S, Kimmel PL, Palant CE: The severity of acute kidney injury predicts progression to chronic kidney disease. Kidney Int 79:1361–1369, 2011 10. Schmitt R, Coca S, Kanbay M, Tinetti ME, Cantley LG, Parikh CR: Recovery of kidney function after acute kidney injury in the elderly: a systematic review and meta-analysis. Am J Kidney Dis 52:262–271, 2008 11. Kawarazaki H, Uchino S, Tokuhira N, Ohnuma T, Namba Y, Katayama S, Toki N, Takeda K, Yasuda H, Izawa J, Uji M, Nagata I, Group JCT: Who may not benefit from continuous renal replacement therapy in acute kidney injury? Hemodial Int 17: 624–632, 2013 12. Heung M, Wolfgram DF, Kommareddi M, Hu Y, Song PX, Ojo AO: Fluid overload at initiation of renal replacement therapy is associated with lack of renal recovery in patients with acute kidney injury. Nephrol Dial Transplant 27:956–961, 2012 13. Srisawat N, Wen X, Lee M, Kong L, Elder M, Carter M, Unruh M, Finkel K, Vijayan A, Ramkumar M, Paganini E, Singbartl K, Palevsky PM, Kellum JA: Urinary biomarkers and renal recovery in critically ill patients with renal support. Clin J Am Soc Nephrol 6:1815– 1823, 2011 14. Nejat M, Pickering JW, Devarajan P, Bonventre JV, Edelstein CL, Walker RJ, Endre ZH: Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney Int 81:1254–1262, 2012
Is Acute Peritoneal Dialysis Feasible for Treatment of Hospital-Acquired Acute Kidney Injury? Chang Yin Chionh* and Dinna N. Cruz† *Division of Renal Medicine, Changi General Hospital, Singapore, and †Division of NephrologyHypertension, Department of Medicine, University of California, San Diego, California
There has been a recent increase in interest in the use of peritoneal dialysis (PD) in acute kidney injury (AKI) (1,2). Although extracorporeal blood purification (EBP) is more commonly employed for supportive therapy in AKI worldwide, a recent sys-
tematic review demonstrated no significant differences in outcomes between PD and EBP (3). Because of its technical simplicity, PD is more widely used in resource-limited areas and is often the only form of dialysis available (4,5). In such areas, community-acquired AKI tended to feature more prominently, such as AKI due to diarrheal and other tropical diseases (including malaria, leptospirosis, and dengue), snake bites, and nephrotoxic drugs (5). In the urban and developed setting, hospital-acquired AKI is more commonly reported (6). Indeed the majority of AKI studies from high-income countries have focused on AKI in the hospital and intensive care unit (ICU).
Address correspondence to: Dinna N. Cruz, MD, MPH, Division of Nephrology-Hypertension, University of California, San Diego, 200 West Arbor Drive #8409, San Diego, CA 92103-8409, Tel.: (619) 471-0753, Fax: (619) 471-0754, or e-mail: [email protected]. Seminars in Dialysis—Vol 27, No 3 (May–June) 2014 pp. 239–242 DOI: 10.1111/sdi.12209 © 2014 Wiley Periodicals, Inc. 239
240
Chionh and Cruz
While the definitions are not standardized, hospital-acquired AKI is recognized when the consensus AKI criteria (7–9) are met during hospitalization after one or more renal insults. Common causes of hospital-acquired AKI include volume depletion, sepsis, postsurgery AKI, radiocontrast media and drug-induced AKI (10). This article will review the experience with PD for AKI in this setting.
particularly in the context of hospital-acquired AKI. In one RCT, 120 patients with AKI referred to their nephrology service after hospital admission was randomized to treatment with PD or daily hemodialysis (13). Of the 120 patients, 77.4% required ICU care and 44.5% were septic. The RCT demonstrated no differences in mortality, but noted a significantly shorter time to renal recovery, with PD patients requiring an average of 5.5 days of dialysis dependence, as opposed to 7.5 days for hemodialysis. Another RCT randomized ICU patients with AKI to PD with continuous veno-venous hemodiafiltration (CVVHDF) looking primarily at solute control (correction of uremia, electrolyte and acid-base disorders), as well as correction of fluid overload (14). Urea and creatinine clearances, as well as control of fluid overload, were significantly better with CVVHDF than PD; however, correction of acidosis was better with PD. PD and CVVHDF were comparable with respect to correction of hyperkalemia and hemodynamic disturbances, although the cost of consumables for CVVHDF was more than twice that of PD. Sepsis is a common cause of AKI in the hospital setting. Observational studies including septic patients with AKI have reported successful treatment of hospital-acquired AKI with PD. Techniques to achieve a high dialysis dose with high volume PD have been utilized to enhance clearance in hypercatabolic patients with AKI(15). The investigators were able to deliver a weekly Kt/V of 3.56 0.68 which achieved a level of metabolic control desired in a group of predominantly septic patients. In a small study of 20 patients, adequate metabolic control was also achieved using a lower PD dose, and correction of acidosis was more rapid with bicarbonate-based rather than lactate-based solutions (16). Subset analysis of comparative studies including septic patients found no differences in outcomes between PD and EBP, although there is significant heterogeneity between the studies (Fig. 1). Although one RCT conducted in Vietnam favored EBP over PD, most patients in the study had malaria, which is regarded as a community-related AKI (17). In addition, such poor outcomes in patients with malaria were not seen in more recent studies (18). Data on the use of PD in AKI related to trauma or surgery are based on much older studies. Cameron and colleagues described successful use of PD to manage uremia in the postsurgery setting (19), while others described the applicability of PD in critical trauma (20). Hadidy et al. retrospectively reviewed 102 patients, majority of them having had trauma or surgery, and the patients who received PD did as well as those on hemodialysis (21). Two recent studies that included a small proportion of surgical patients reported no differences in outcomes with either PD or EBP (Fig. 1) (13,22). While no technical difficulties were reported, the studies did not include patients with major abdominal trauma or surgery.
Pathophysiology of Hospital-Acquired AKI Are there major differences in the pathophysiology of AKI which requires different approaches in their management? Very often, community-acquired AKI and hospital-acquired AKI have similar underlying pathophysiologic mechanisms. These include intravascular volume depletion, ischemia/reperfusion injury related to hypotension or circulatory shock (e.g. hemorrhagic shock, dehydration), or direct tubulo-toxic effects of various drugs or poisons. In such situations, the differences in outcomes between community-acquired and hospital-acquired AKI are often due to differences in timing of supportive therapy initiation. There exist theoretical postulates that some forms of hospital-acquired AKI have different underlying mechanisms of injury. In septic AKI, proinflammatory cytokines have been postulated to be the main trigger for the sepsis cascade resulting in AKI. In contrast, an immunologic-related mechanism has been demonstrated in cardio-renal syndromes (11). While there are many studies addressing the cytokine theory using continuous renal replacement therapy, only a few studies have utilized PD. The peritoneal membrane has pores large enough to theoretically allow clearance of these molecules. A study in infants after cardio-pulmonary bypass surgery demonstrated effective clearance of IL-6 and IL-8 using PD, although the clearance was superior with ultrafiltration (12). PD for AKI in Specific Populations In a systematic review of 24 studies (n = 1556 patients), no differences were found in mortality outcomes between PD and EBP for AKI (pooled OR 1.11, 95% CI 0.66–1.88) (3). However, there were multiple etiologies for AKI in each of the studies, and no study specifically identified hospitalacquired AKI. Pooled analysis of studies which included patients who were likely to have developed AKI in the hospital, such as postsurgical, ICU and septic patients revealed no significant differences in mortality outcomes between PD and EBP. Fig. 1 shows subgroup analyses for studies including patients with sepsis, in the ICU, and postsurgery or trauma. A few of these studies merit further discussion. There have been only a few randomized controlled trials (RCT) that compared PD with EBP, 240
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Fig. 1. Comparison of peritoneal dialysis (PD) with extra-corporeal blood purification (EBP) in studies which included (A) Septic patients, (B) Intensive care unit (ICU) patients, (C) Post-surgical or trauma patients. Odds ratio with 95% confidence intervals (CI) was calculated using the Mantel-Haenszel (M-H) random-effects model. Chow et al. described two study cohorts 10 years apart and data were analyzed separately, represented as (A) and (B).
Performing PD for AKI
bags and makeshift connections may be necessary in resource-poor settings. There is no convincing evidence that automated PD is safer or more effective than manual exchanges. In patients with shock or liver failure, bicarbonate containing solutions may be preferable to lactate, especially in the setting of metabolic acidosis. As noted above, correction of metabolic acidosis was more rapid with bicarbonate compared to lactate-based PD solutions, although hard clinical outcomes were comparable (16). During the initial 24 hours of therapy, short cycle times (e.g. 1–2 hours) may be necessary to correct fluid overload, hyperkalemia, and/or metabolic acidosis. Thereafter, the cycle time may be increased to 4–6 hours depending on the clinical circumstances. The optimal dose of PD for AKI is unclear, resulting in ambiguity among practitioners (26). A single center study, targeting a weekly Kt/V urea of 3.5, demonstrated comparable outcomes for PD and daily HD (13). However, other studies have shown good outcomes using lower doses (27,28). Extrapolating from data on EBP, targeting a weekly KT/V of 2.1 may represent a minimum clearance standard (29). Higher small solute clearances may be necessary in hypercatabolic AKI patients.
Appropriate patient selection and PD technique, as well as center experience, are important determinants of the feasibility and success of PD as a therapy for AKI. Where other EBP modalities are easily available, PD would probably be more appropriate for patients with only one or two organ failures. Patients with multiple organ failure, previous midline surgical scars or high risk of peritoneal adhesions may be more appropriately managed with EBP. On the other hand, patients with advanced CKD who have superimposed AKI could potentially be well-served by PD. In the event of a delay in, or lack of, significant renal recovery, it may facilitate the transition to outpatient peritoneal dialysis (23). Flexible peritoneal catheters are preferred and should ideally be used where resources and expertise exist, in view of lower incidence of peritoneal fluid leakage and infection (24). Prophylactic antibiotics prior to insertion of the PD catheter have been associated with a significant reduction in the incidence of peritonitis (25). A closed fluid delivery system with Y connection is also ideal to minimize infection, although it is recognized that spiking of 241
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Due to the high glucose concentration in PD fluid, there is concern regarding hyperglycemia with acute PD. The incidence of this complication is generally poorly reported in studies (3). However, in the randomized trial comparing PD to daily hemodialysis, glucose levels were similar between the two modalities (13). No patient had uncontrolled hyperglycemia in either group. Hyperglycemia can be treated with insulin subcutaneously, intravenously, or by adding it to the peritoneal fluid. There is no evidence to support the superiority of any particular approach. In AKI, the exposure to high glucose concentration is expected to be short-term. There are no data on its long-term consequences. Lastly, peritonitis is an important complication of PD. Its diagnosis may be challenging when dwell times are short. Nevertheless, a daily PD fluid leukocyte count may be useful for peritonitis surveillance. Diagnosis and treatment should be based on existing ISPD guidelines (30), in the absence of specific guidelines for acute PD.
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Is Acute Peritoneal Dialysis Feasible for Treatment of Hospital-Acquired AKI?
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To answer the question, there is no evidence to indicate inferiority of PD for management of hospital-acquired AKI. As such, PD should be considered a viable modality option. The feasibility and success of PD for AKI depends on appropriate patient selection, proper PD technique, and center experience. While expert practice recommendations exist for EBP, none currently exist for PD, resulting in variability in practice (26). The International Society of Peritoneal Dialysis is developing consensus guidelines to address this knowledge gap.
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References
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