J Nephrol DOI 10.1007/s40620-015-0187-z
ORIGINAL ARTICLE
The risk of acute kidney injury with transjugular intrahepatic portosystemic shunts John Danziger • Laxmi Thummalakunta Rachel Nelson • Salomao Faintuch
•
Received: 16 December 2014 / Accepted: 25 February 2015 Ó Italian Society of Nephrology 2015
Abstract Transjugular intrahepatic portosystemic shunts (TIPS) have been used for almost 40 years as a safe and effective alternative to surgical shunts, mostly in the setting of portal hypertension. Well described procedural complications include hepatic encephalopathy, hemorrhage, liver infarction and failure. The risk of post procedural acute kidney injury (AKI) associated with intraprocedural intravenous contrast administration has not been evaluated. Using a retrospective chart review of all consecutive patients undergoing a TIPS procedure as part of routine clinical care between 2001 and 2011, we examined whether the volume of administered intravenous contrast was associated with AKI. Of 163 patients who had a TIPS procedure, 16 % developed AKI as defined by a 0.3 mg/dl increase in serum creatinine within 48 h of the procedure. In adjusted analysis, a 50 ml increase of intravenous contrast was associated with a 1.27 (95 % CI 1.01–1.60), p = 0.04 increased risk of AKI. Baseline serum creatinine was also associated with post procedural AKI; a 0.1 mg/dl increase in creatinine was associated with a 1.17 (1.04–1.31), p = 0.008 risk. In patients with underlying kidney dysfunction, a 50 ml increase of intravenous contrast was associated with a 1.63 (1.20–2.31), p = 0.003 adjusted risk of AKI. In conclusion, intravenous contrast administered during a TIPS procedure is associated with an
J. Danziger (&) R. Nelson Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 185 Pilgrim Road, Farr 8, Boston, MA 02215, USA e-mail: [email protected] L. Thummalakunta S. Faintuch Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
increased risk of AKI, particularly in patients with impaired renal function at baseline. Keywords Acute kidney injury Cirrhosis Contrast nephropathy TIPS Portal hypertension Ascites
Introduction Transjugular intrahepatic portosystemic shunts (TIPS) involves creation of a low-resistance channel between the hepatic vein and the intrahepatic portion of the portal vein using angiographic techniques. First introduced in 1969 for the control of variceal bleeding due to portal hypertension [1], its indications have been expanded to include refractory ascites, hepatic hydrothorax, Budd–Chiari syndrome, hepatic veno-occlusive disease, and hepatorenal syndrome [2–6]. Although TIPS is less invasive than surgical shunt placement, it has been associated with complications, including encephalopathy, bleeding, liver failure, hemolytic anemia, and infection [7–9]. Acute kidney injury (AKI) was noted as an infrequent (2 %) complication of the TIPS procedure [10], although not observed in more recent studies [11]. Although intravenous contrast likely has less risk of renal injury than intraarterial contrast [12], given an increased susceptibility to renal injury among cirrhotic patients, likely due to a combination of underlying renal dysfunction, low renal perfusion, and comorbidities [13, 14], we hypothesized that the amount of intravenous contrast could cause renal injury. Using all consecutive inpatient TIPS procedure performed over a 10 year period at our institution, we examined whether the volume of intravenous contrast was associated with AKI in patients undergoing a TIPS procedure as part of routine care.
123
J Nephrol
Methods All consecutive patients who underwent a TIPS procedure in the Department of Radiology at Beth Israel Medical Center between January 2001 and October 2011 were included. Electronic medical records and procedure notes were reviewed to extract demographic and clinical information. Baseline serum creatinine was obtained immediately prior to the procedure, and follow up serum creatinine measurements were obtained within 24–48 h post procedure. Preprocedure and lowest recorded systolic blood pressure were obtained from review of procedure nursing notes. Contrast volume and whether an intra-procedure paracentesis was performed were recorded. Institutional Review Board approval was obtained prior to study initiation. Primary outcome and exposure AKI was defined as a 0.3 mg/dl serum creatinine increase from baseline within 48 h of the TIPS procedure, in keeping with standard clinical definitions [15]. The primary exposure was the amount of administered contrast volume, defined continuously and in quartiles. In a secondary analysis, we examined the risk of contrast exposure with more significant renal injury, as defined by a serum increase of 0.5 mg/dl. Statistical analysis Baseline characteristics are presented per contrast quartiles. Multi-variable analysis was used to clarify the association between contrast exposure and AKI. Age, baseline and lowest procedural systolic blood pressure, albumin, and baseline serum creatinine were included as continuous variables, and gender and intraprocedural paracentesis as binary variables. For the eight patients missing complete covariate documentation (seven missing serum albumin measurement, one missing baseline blood pressure), age
and gender imputation was used. Contrast exposure was included in quartiles, using the lowest quartile as reference, as well as a continuous variable. In order to evaluate whether baseline renal function modified the association between contrast exposure and post procedural AKI, a multiplicative interaction term between the cohort median baseline serum creatinine and contrast, defined continuously, was examined. All analyses were done with JMP Pro 10 (Cary, NC).
Results Of 163 patients undergoing a TIPS procedure, the mean volume of administered contrast was 202 (±99.3) ml. Ioversol 320 was used in 93 % of cases, with iodixanol 320 used in the remainder. When stratified by quartiles (Table 1), those patients who received more contrast tended to be younger, male, and with lower baseline serum creatinine measurement, but were similar in hemodynamics, serum albumin, and use of concurrent paracentesis to those receiving less contrast. 26 (16 %) developed AKI, as defined by a 0.3 mg/dl creatinine increase from baseline. Both baseline renal function and the amount of contrast were significantly associated with the risk of AKI in adjusted analyses. Each 50 ml increment of contrast was associated with a 1.27 (95 % CI 1.01–1.60), p = 0.04 increased risk of post procedural AKI (Table 2). Each 0.1 mg/dl increase of baseline serum creatinine was associated with a 1.17 (95 % CI 1.04–1.31, p = 0.008) adjusted risk of post procedure AKI. 67 (41.1 %) had a baseline creatinine less than 0.9 mg/ dl (Table 3), and tended to be younger, female, and received significantly more intravenous contrast during the TIPS procedure. The risk of AKI differed by baseline creatinine (multiplicative interaction in adjusted analysis p = 0.02), with 23 % developing AKI in the higher baseline creatinine group, compared to less than 6 % in the
Table 1 Baseline characteristics Baseline characteristics stratified by volume of contrast exposure \125 ml, N = 40 Age (years) Male, no. (%) Baseline SBP (mmHg) Lowest intraprocedural SBP (mmHg)
C125 to 175 ml, N = 40
61.8 (1.9)
60.0 (1.9)
28 (70.0)
35 (87.5)
C175 to 255 ml, N = 42 63.4 (1.8) 26 (61.9)
C255 ml, N = 41 57.8 (1.8) 26 (63.4)
121.3 (3.2)
123.8 (3.2)
126.3 (3.1)
125.1 (3.1)
p value 0.17 0.03 0.70
89.6 (2.0)
90.0 (2.0)
91.3 (2.0)
92.6 (2.0)
0.71
Serum albumin (g/dl)
2.6 (0.1)
2.6 (0.1)
2.8 (0.1)
2.6 (0.1)
0.42
Baseline creatinine (mg/dl)
1.1 (0.1)
1.0 (0.1)
1.1 (0.1)
0.9 (0.1)
0.07
Intraprocedural paracentesis, no. (%)
17 (42.5)
21 (52.5)
20 (47.6)
15 (36.6)
0.51
Mean (standard deviation) provided for continuous variables
123
J Nephrol Table 2 Risk of AKI according to amount of intravenous contrast AKI by contrast exposure \125 ml
C125 to 175 ml
C175 to 255 ml
C255 ml
Per 50 ml of contrast
Post procedure AKI, no. (%)
5 (12.5)
4 (10.0)
8 (19.1)
9 (22.0)
26 (15.9)
Adjusted risk of AKIa
(Ref.)
1.13 (0.24–5.15)
1.93 (0.53–7.71)
3.77 (1.01–16.5)
1.27 (1.01–1.60)
p = 0.87
p = 0.32
p = 0.05
p = 0.04
a
Adjusted for age, gender, baseline SBP, lowest intraprocedural SBP, serum albumin, baseline creatinine, and intraprocedural paracentesis
Table 3 Characteristics according to baseline renal function Baseline creatinine \ 0.9 mg/dl, N = 67 Age (years) Male, no. (%) Baseline SBP (mmHg) Lowest intraprocedural SBP (mmHg)
57.7 (1.4) 50 (74.6)
Baseline creatinine C 0.9 md/dl, N = 96 62.8 (1.2) 66 (69.4) 125.7 (2.0)
0.20
94.0 (1.5)
89.1 (1.3)
0.02
2.6 (0.1)
2.7 (0.05)
Intraprocedural paracentesis, performed, no. (%)
25 (36.8)
48 (50.0)
Post procedure AKI, no. (%)
0.006 0.002
121.6 (2.4)
Serum albumin (g/dl) Administered contrast (ml)
p value
228.9 (11.9) 4 (5.9)
184.2 (9.9) 22 (22.9)
0.31 0.09 0.004 0.002
Mean (standard deviation) provided for continuous variables
lower group. In adjusted analysis of those with a baseline creatinine C0.9 mg/dl, each 50 ml of administered contrast was associated with a 1.63 (1.20–2.31), p = 0.003 risk of AKI, whereas in those with a baseline creatinine less than 0.9 mg/dl, contrast volume was not significantly associated with AKI (p = 0.65). Thirteen (8 %) of the patients had a serum creatinine that increased by 0.5 mg/dl within 48 h of the procedure. In unadjusted analysis, a 50 ml increment of contrast was associated with a 1.39 (0.08–1.75, p = 0.06) increased risk of this secondary outcome. Multiplicative interaction terms between contrast volume and serum albumin, as well as concurrent paracentesis, were both nonsignificant (p [ 0.05). In adjusted analysis, the type of contrast (ioversol versus iodixanol) was not a significant predictor of AKI (p = 0.9) and a multiplicative interaction term between contrast type and volume was similarly nonsignficant (p = 0.6).
Discussion In our single center experience of patients undergoing routine TIPS procedures, 16 % of patients developed AKI. A 50 ml increase of intravenous contrast administered during the procedure was associated with an almost 30 % increased risk of post procedural AKI, and 0.1 mg/dl increase in baseline serum creatinine was associated 17 % increased risk. The risk of contrast associated AKI was significantly
greater in those with baseline kidney dysfunction. We could not detect an effect of contrast volume on risk of AKI in those with lower baseline serum creatinine, although the analysis was underpowered given the smaller number of individuals in this subgroup. Our findings are in keeping with a growing literature that suggests total contrast dose [16] and patient susceptibility [17, 18] are important determinants of the risk of contrast induced renal injury. We found a significantly higher incidence of renal injury than reported with computed tomography (ranging 4–11 %) [19, 20], perhaps due to a combination of larger contrast volumes in the TIPS procedure, underlying renal susceptibility in cirrhosis, and disparate definitions of AKI amongst the studies. Given the marked cachexia and muscle loss associated with liver disease, serum creatinine measurements likely under represent the degree of renal dysfunction, and our median reported creatinine of 0.9 mg/ dl likely reflects significant baseline dysfunction. In addition, the ‘‘low flow’’ state of cirrhosis, a consequence of splenic vasodilation and portal venous shunting, decreases renal perfusion, and may increase the susceptibility to contrast, in a manner similar to volume depletion as a known risk factor for contrast nephropathy in the general population. Whether the use of preprocedural saline volume expansion, as has become standard for patients at high risk of contrast nephropathy [21], might be applicable to the TIPS procedure is not known. The type of contrast agent has traditionally been thought to contribute to the risk of AKI, due to the specific
123
J Nephrol
properties of the contrast medium, including osmlolality and viscosity [22, 23]. The majority of patients in our study received ioversol 320, with a osmolality of 290 mOsm/kg and a viscosity of 11.4 mPa s at 37 °C. In adjusted analysis, the type of contrast was not a significant predictor of AKI, nor was a multiplicative interaction term between contrast volume and type. However, given experimental evidence that the hyperosmolality of contrast media contributes to tubule damage, our small study, not powered to address the risk of a particular agent, should be interpreted with caution. Our analysis has several important limitations. There is no consensus on defining AKI in patients with underlying liver disease and no information whether the episodes of AKI in the cirrhotic patients will have similar long term deleterious effects as in the general population. In addition, we could not determine the indication for the TIPS procedure in patients. Finally, we did not have long term follow up regarding recoverability of renal function.
Conclusion Our study raises the awareness of kidney injury as a risk for the TIPS procedure, particularly in those with underlying kidney disease. More importantly, our study suggests that even small increments of intravenous contrast increase the risk of renal injury, and encourage minimizing the amount of intraprocedural contrast. Acknowledgments Dr. Danziger is supported by a Normon S. Coplon Extramural Grant from Satellite Healthcare. Conflict of interest
No author has a conflict of interest.
Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
References 1. Rosch J, Hanafee W, Snow H, Barenfus M, Gray R (1971) Transjugular intrahepatic portacaval shunt. An experimental work. Am J Surg 121(5):588–592 2. Corso R, Intotero M, Solcia M, Castoldi MC, Rampoldi A (2008) Treatment of Budd-Chiari syndrome with transjugular intrahepatic portosystemic shunt (TIPS). Radiol Med (Torino) 113(5):727–738 3. Panagiotou I, Kelekis DA, Karatza C, Nikolaou V, Mouyia V, Brountzos EN (2007) Treatment of Budd-Chiari syndrome by transjugular intrahepatic portosystemic shunt. Hepatogastroenterology 54(78):1813–1816 4. Watanabe H, Shinzawa H, Saito T et al (2000) Successful emergency treatment with a transjugular intrahepatic portosystemic shunt for life-threatening Budd-Chiari syndrome with portal thrombotic obstruction. Hepatogastroenterology 47(33):839–841
123
5. Peltzer MY, Ring EJ, LaBerge JM, Haskal ZJ, Radosevich PM, Gordon RL (1993) Treatment of Budd-Chiari syndrome with a transjugular intrahepatic portosystemic shunt. J Vasc Interv Radiol JVIR 4(2):263–267 6. Boyer TD, Haskal ZJ, American Association for the Study of Liver Diseases (2010) The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension: update 2009. Hepatology 51(1):306 7. Colombato L (2007) The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension. J Clin Gastroenterol 41(Suppl 3):S344–S351 8. Huonker M, Schumacher YO, Ochs A, Sorichter S, Keul J, Rossle M (1999) Cardiac function and haemodynamics in alcoholic cirrhosis and effects of the transjugular intrahepatic portosystemic stent shunt. Gut 44(5):743–748 9. Sanyal AJ, Freedman AM, Purdum PP, Shiffman ML, Luketic VA (1996) The hematologic consequences of transjugular intrahepatic portosystemic shunts. Hepatology 23(1):32–39 10. Haskal ZJ, Martin L, Cardella JF et al (2003) Quality improvement guidelines for transjugular intrahepatic portosystemic shunts. J Vasc Interv Radiol JVIR 14(9 Pt 2):S265–S270 11. Qin JP, Jiang MD, Tang W et al (2013) Clinical effects and complications of TIPS for portal hypertension due to cirrhosis: a single center. World J Gastroenterol WJG 19(44):8085–8092 12. Dong M, Jiao Z, Liu T, Guo F, Li G (2012) Effect of administration route on the renal safety of contrast agents: a meta-analysis of randomized controlled trials. J Nephrol 25(3):290–301 13. Schrier RW, Shchekochikhin D, Gines P (2012) Renal failure in cirrhosis: prerenal azotemia, hepatorenal syndrome and acute tubular necrosis. Nephrol Dial Transplant Off Pub Eur Dial Transpl Assoc Eur Ren Assoc 27(7):2625–2628 14. Gines P, Schrier RW (2009) Renal failure in cirrhosis. New Engl J Med 361(13):1279–1290 15. Mehta RL, Kellum JA, Shah SV et al (2007) Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11(2):R31 16. Yu J, Mehran R (2012) ‘‘CIN’’ no more: the use of contrast volume to e-GFR ratio to predict and prevent contrast-induced acute kidney injury. Catheter Cardiovasc Interv Off J Soc Cardiac Angiogr Interv 79(7):1201–1202 17. Davenport MS, Khalatbari S, Cohan RH, Dillman JR, Myles JD, Ellis JH (2013) Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material: risk stratification by using estimated glomerular filtration rate. Radiology 268(3):719–728 18. Mehran R, Nikolsky E (2006) Contrast-induced nephropathy: definition, epidemiology, and patients at risk. Kidney Int Suppl 100:S11–S15 19. Weisbord SD, Mor MK, Resnick AL, Hartwig KC, Palevsky PM, Fine MJ (2008) Incidence and outcomes of contrast-induced AKI following computed tomography. Clin J Am Soc Nephrol CJASN 3(5):1274–1281 20. Mitchell AM, Jones AE, Tumlin JA, Kline JA (2010) Incidence of contrast-induced nephropathy after contrast-enhanced computed tomography in the outpatient setting. Clin J Am Soc Nephrol CJASN 5(1):4–9 21. Mueller C, Buerkle G, Buettner HJ et al (2002) Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 162(3):329–336 22. Bucher AM, De Cecco CN, Schoepf UJ et al (2014) Is contrast medium osmolality a causal factor for contrast-induced nephropathy? Biomed Res Int 2014:931413 23. Andreucci M, Faga T, Pisani A, Sabbatini M, Michael A (2014) Acute kidney injury by radiographic contrast media: pathogenesis and prevention. Biomed Res Int 2014:362725
ORIGINAL ARTICLE
The risk of acute kidney injury with transjugular intrahepatic portosystemic shunts John Danziger • Laxmi Thummalakunta Rachel Nelson • Salomao Faintuch
•
Received: 16 December 2014 / Accepted: 25 February 2015 Ó Italian Society of Nephrology 2015
Abstract Transjugular intrahepatic portosystemic shunts (TIPS) have been used for almost 40 years as a safe and effective alternative to surgical shunts, mostly in the setting of portal hypertension. Well described procedural complications include hepatic encephalopathy, hemorrhage, liver infarction and failure. The risk of post procedural acute kidney injury (AKI) associated with intraprocedural intravenous contrast administration has not been evaluated. Using a retrospective chart review of all consecutive patients undergoing a TIPS procedure as part of routine clinical care between 2001 and 2011, we examined whether the volume of administered intravenous contrast was associated with AKI. Of 163 patients who had a TIPS procedure, 16 % developed AKI as defined by a 0.3 mg/dl increase in serum creatinine within 48 h of the procedure. In adjusted analysis, a 50 ml increase of intravenous contrast was associated with a 1.27 (95 % CI 1.01–1.60), p = 0.04 increased risk of AKI. Baseline serum creatinine was also associated with post procedural AKI; a 0.1 mg/dl increase in creatinine was associated with a 1.17 (1.04–1.31), p = 0.008 risk. In patients with underlying kidney dysfunction, a 50 ml increase of intravenous contrast was associated with a 1.63 (1.20–2.31), p = 0.003 adjusted risk of AKI. In conclusion, intravenous contrast administered during a TIPS procedure is associated with an
J. Danziger (&) R. Nelson Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 185 Pilgrim Road, Farr 8, Boston, MA 02215, USA e-mail: [email protected] L. Thummalakunta S. Faintuch Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
increased risk of AKI, particularly in patients with impaired renal function at baseline. Keywords Acute kidney injury Cirrhosis Contrast nephropathy TIPS Portal hypertension Ascites
Introduction Transjugular intrahepatic portosystemic shunts (TIPS) involves creation of a low-resistance channel between the hepatic vein and the intrahepatic portion of the portal vein using angiographic techniques. First introduced in 1969 for the control of variceal bleeding due to portal hypertension [1], its indications have been expanded to include refractory ascites, hepatic hydrothorax, Budd–Chiari syndrome, hepatic veno-occlusive disease, and hepatorenal syndrome [2–6]. Although TIPS is less invasive than surgical shunt placement, it has been associated with complications, including encephalopathy, bleeding, liver failure, hemolytic anemia, and infection [7–9]. Acute kidney injury (AKI) was noted as an infrequent (2 %) complication of the TIPS procedure [10], although not observed in more recent studies [11]. Although intravenous contrast likely has less risk of renal injury than intraarterial contrast [12], given an increased susceptibility to renal injury among cirrhotic patients, likely due to a combination of underlying renal dysfunction, low renal perfusion, and comorbidities [13, 14], we hypothesized that the amount of intravenous contrast could cause renal injury. Using all consecutive inpatient TIPS procedure performed over a 10 year period at our institution, we examined whether the volume of intravenous contrast was associated with AKI in patients undergoing a TIPS procedure as part of routine care.
123
J Nephrol
Methods All consecutive patients who underwent a TIPS procedure in the Department of Radiology at Beth Israel Medical Center between January 2001 and October 2011 were included. Electronic medical records and procedure notes were reviewed to extract demographic and clinical information. Baseline serum creatinine was obtained immediately prior to the procedure, and follow up serum creatinine measurements were obtained within 24–48 h post procedure. Preprocedure and lowest recorded systolic blood pressure were obtained from review of procedure nursing notes. Contrast volume and whether an intra-procedure paracentesis was performed were recorded. Institutional Review Board approval was obtained prior to study initiation. Primary outcome and exposure AKI was defined as a 0.3 mg/dl serum creatinine increase from baseline within 48 h of the TIPS procedure, in keeping with standard clinical definitions [15]. The primary exposure was the amount of administered contrast volume, defined continuously and in quartiles. In a secondary analysis, we examined the risk of contrast exposure with more significant renal injury, as defined by a serum increase of 0.5 mg/dl. Statistical analysis Baseline characteristics are presented per contrast quartiles. Multi-variable analysis was used to clarify the association between contrast exposure and AKI. Age, baseline and lowest procedural systolic blood pressure, albumin, and baseline serum creatinine were included as continuous variables, and gender and intraprocedural paracentesis as binary variables. For the eight patients missing complete covariate documentation (seven missing serum albumin measurement, one missing baseline blood pressure), age
and gender imputation was used. Contrast exposure was included in quartiles, using the lowest quartile as reference, as well as a continuous variable. In order to evaluate whether baseline renal function modified the association between contrast exposure and post procedural AKI, a multiplicative interaction term between the cohort median baseline serum creatinine and contrast, defined continuously, was examined. All analyses were done with JMP Pro 10 (Cary, NC).
Results Of 163 patients undergoing a TIPS procedure, the mean volume of administered contrast was 202 (±99.3) ml. Ioversol 320 was used in 93 % of cases, with iodixanol 320 used in the remainder. When stratified by quartiles (Table 1), those patients who received more contrast tended to be younger, male, and with lower baseline serum creatinine measurement, but were similar in hemodynamics, serum albumin, and use of concurrent paracentesis to those receiving less contrast. 26 (16 %) developed AKI, as defined by a 0.3 mg/dl creatinine increase from baseline. Both baseline renal function and the amount of contrast were significantly associated with the risk of AKI in adjusted analyses. Each 50 ml increment of contrast was associated with a 1.27 (95 % CI 1.01–1.60), p = 0.04 increased risk of post procedural AKI (Table 2). Each 0.1 mg/dl increase of baseline serum creatinine was associated with a 1.17 (95 % CI 1.04–1.31, p = 0.008) adjusted risk of post procedure AKI. 67 (41.1 %) had a baseline creatinine less than 0.9 mg/ dl (Table 3), and tended to be younger, female, and received significantly more intravenous contrast during the TIPS procedure. The risk of AKI differed by baseline creatinine (multiplicative interaction in adjusted analysis p = 0.02), with 23 % developing AKI in the higher baseline creatinine group, compared to less than 6 % in the
Table 1 Baseline characteristics Baseline characteristics stratified by volume of contrast exposure \125 ml, N = 40 Age (years) Male, no. (%) Baseline SBP (mmHg) Lowest intraprocedural SBP (mmHg)
C125 to 175 ml, N = 40
61.8 (1.9)
60.0 (1.9)
28 (70.0)
35 (87.5)
C175 to 255 ml, N = 42 63.4 (1.8) 26 (61.9)
C255 ml, N = 41 57.8 (1.8) 26 (63.4)
121.3 (3.2)
123.8 (3.2)
126.3 (3.1)
125.1 (3.1)
p value 0.17 0.03 0.70
89.6 (2.0)
90.0 (2.0)
91.3 (2.0)
92.6 (2.0)
0.71
Serum albumin (g/dl)
2.6 (0.1)
2.6 (0.1)
2.8 (0.1)
2.6 (0.1)
0.42
Baseline creatinine (mg/dl)
1.1 (0.1)
1.0 (0.1)
1.1 (0.1)
0.9 (0.1)
0.07
Intraprocedural paracentesis, no. (%)
17 (42.5)
21 (52.5)
20 (47.6)
15 (36.6)
0.51
Mean (standard deviation) provided for continuous variables
123
J Nephrol Table 2 Risk of AKI according to amount of intravenous contrast AKI by contrast exposure \125 ml
C125 to 175 ml
C175 to 255 ml
C255 ml
Per 50 ml of contrast
Post procedure AKI, no. (%)
5 (12.5)
4 (10.0)
8 (19.1)
9 (22.0)
26 (15.9)
Adjusted risk of AKIa
(Ref.)
1.13 (0.24–5.15)
1.93 (0.53–7.71)
3.77 (1.01–16.5)
1.27 (1.01–1.60)
p = 0.87
p = 0.32
p = 0.05
p = 0.04
a
Adjusted for age, gender, baseline SBP, lowest intraprocedural SBP, serum albumin, baseline creatinine, and intraprocedural paracentesis
Table 3 Characteristics according to baseline renal function Baseline creatinine \ 0.9 mg/dl, N = 67 Age (years) Male, no. (%) Baseline SBP (mmHg) Lowest intraprocedural SBP (mmHg)
57.7 (1.4) 50 (74.6)
Baseline creatinine C 0.9 md/dl, N = 96 62.8 (1.2) 66 (69.4) 125.7 (2.0)
0.20
94.0 (1.5)
89.1 (1.3)
0.02
2.6 (0.1)
2.7 (0.05)
Intraprocedural paracentesis, performed, no. (%)
25 (36.8)
48 (50.0)
Post procedure AKI, no. (%)
0.006 0.002
121.6 (2.4)
Serum albumin (g/dl) Administered contrast (ml)
p value
228.9 (11.9) 4 (5.9)
184.2 (9.9) 22 (22.9)
0.31 0.09 0.004 0.002
Mean (standard deviation) provided for continuous variables
lower group. In adjusted analysis of those with a baseline creatinine C0.9 mg/dl, each 50 ml of administered contrast was associated with a 1.63 (1.20–2.31), p = 0.003 risk of AKI, whereas in those with a baseline creatinine less than 0.9 mg/dl, contrast volume was not significantly associated with AKI (p = 0.65). Thirteen (8 %) of the patients had a serum creatinine that increased by 0.5 mg/dl within 48 h of the procedure. In unadjusted analysis, a 50 ml increment of contrast was associated with a 1.39 (0.08–1.75, p = 0.06) increased risk of this secondary outcome. Multiplicative interaction terms between contrast volume and serum albumin, as well as concurrent paracentesis, were both nonsignificant (p [ 0.05). In adjusted analysis, the type of contrast (ioversol versus iodixanol) was not a significant predictor of AKI (p = 0.9) and a multiplicative interaction term between contrast type and volume was similarly nonsignficant (p = 0.6).
Discussion In our single center experience of patients undergoing routine TIPS procedures, 16 % of patients developed AKI. A 50 ml increase of intravenous contrast administered during the procedure was associated with an almost 30 % increased risk of post procedural AKI, and 0.1 mg/dl increase in baseline serum creatinine was associated 17 % increased risk. The risk of contrast associated AKI was significantly
greater in those with baseline kidney dysfunction. We could not detect an effect of contrast volume on risk of AKI in those with lower baseline serum creatinine, although the analysis was underpowered given the smaller number of individuals in this subgroup. Our findings are in keeping with a growing literature that suggests total contrast dose [16] and patient susceptibility [17, 18] are important determinants of the risk of contrast induced renal injury. We found a significantly higher incidence of renal injury than reported with computed tomography (ranging 4–11 %) [19, 20], perhaps due to a combination of larger contrast volumes in the TIPS procedure, underlying renal susceptibility in cirrhosis, and disparate definitions of AKI amongst the studies. Given the marked cachexia and muscle loss associated with liver disease, serum creatinine measurements likely under represent the degree of renal dysfunction, and our median reported creatinine of 0.9 mg/ dl likely reflects significant baseline dysfunction. In addition, the ‘‘low flow’’ state of cirrhosis, a consequence of splenic vasodilation and portal venous shunting, decreases renal perfusion, and may increase the susceptibility to contrast, in a manner similar to volume depletion as a known risk factor for contrast nephropathy in the general population. Whether the use of preprocedural saline volume expansion, as has become standard for patients at high risk of contrast nephropathy [21], might be applicable to the TIPS procedure is not known. The type of contrast agent has traditionally been thought to contribute to the risk of AKI, due to the specific
123
J Nephrol
properties of the contrast medium, including osmlolality and viscosity [22, 23]. The majority of patients in our study received ioversol 320, with a osmolality of 290 mOsm/kg and a viscosity of 11.4 mPa s at 37 °C. In adjusted analysis, the type of contrast was not a significant predictor of AKI, nor was a multiplicative interaction term between contrast volume and type. However, given experimental evidence that the hyperosmolality of contrast media contributes to tubule damage, our small study, not powered to address the risk of a particular agent, should be interpreted with caution. Our analysis has several important limitations. There is no consensus on defining AKI in patients with underlying liver disease and no information whether the episodes of AKI in the cirrhotic patients will have similar long term deleterious effects as in the general population. In addition, we could not determine the indication for the TIPS procedure in patients. Finally, we did not have long term follow up regarding recoverability of renal function.
Conclusion Our study raises the awareness of kidney injury as a risk for the TIPS procedure, particularly in those with underlying kidney disease. More importantly, our study suggests that even small increments of intravenous contrast increase the risk of renal injury, and encourage minimizing the amount of intraprocedural contrast. Acknowledgments Dr. Danziger is supported by a Normon S. Coplon Extramural Grant from Satellite Healthcare. Conflict of interest
No author has a conflict of interest.
Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
References 1. Rosch J, Hanafee W, Snow H, Barenfus M, Gray R (1971) Transjugular intrahepatic portacaval shunt. An experimental work. Am J Surg 121(5):588–592 2. Corso R, Intotero M, Solcia M, Castoldi MC, Rampoldi A (2008) Treatment of Budd-Chiari syndrome with transjugular intrahepatic portosystemic shunt (TIPS). Radiol Med (Torino) 113(5):727–738 3. Panagiotou I, Kelekis DA, Karatza C, Nikolaou V, Mouyia V, Brountzos EN (2007) Treatment of Budd-Chiari syndrome by transjugular intrahepatic portosystemic shunt. Hepatogastroenterology 54(78):1813–1816 4. Watanabe H, Shinzawa H, Saito T et al (2000) Successful emergency treatment with a transjugular intrahepatic portosystemic shunt for life-threatening Budd-Chiari syndrome with portal thrombotic obstruction. Hepatogastroenterology 47(33):839–841
123
5. Peltzer MY, Ring EJ, LaBerge JM, Haskal ZJ, Radosevich PM, Gordon RL (1993) Treatment of Budd-Chiari syndrome with a transjugular intrahepatic portosystemic shunt. J Vasc Interv Radiol JVIR 4(2):263–267 6. Boyer TD, Haskal ZJ, American Association for the Study of Liver Diseases (2010) The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension: update 2009. Hepatology 51(1):306 7. Colombato L (2007) The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension. J Clin Gastroenterol 41(Suppl 3):S344–S351 8. Huonker M, Schumacher YO, Ochs A, Sorichter S, Keul J, Rossle M (1999) Cardiac function and haemodynamics in alcoholic cirrhosis and effects of the transjugular intrahepatic portosystemic stent shunt. Gut 44(5):743–748 9. Sanyal AJ, Freedman AM, Purdum PP, Shiffman ML, Luketic VA (1996) The hematologic consequences of transjugular intrahepatic portosystemic shunts. Hepatology 23(1):32–39 10. Haskal ZJ, Martin L, Cardella JF et al (2003) Quality improvement guidelines for transjugular intrahepatic portosystemic shunts. J Vasc Interv Radiol JVIR 14(9 Pt 2):S265–S270 11. Qin JP, Jiang MD, Tang W et al (2013) Clinical effects and complications of TIPS for portal hypertension due to cirrhosis: a single center. World J Gastroenterol WJG 19(44):8085–8092 12. Dong M, Jiao Z, Liu T, Guo F, Li G (2012) Effect of administration route on the renal safety of contrast agents: a meta-analysis of randomized controlled trials. J Nephrol 25(3):290–301 13. Schrier RW, Shchekochikhin D, Gines P (2012) Renal failure in cirrhosis: prerenal azotemia, hepatorenal syndrome and acute tubular necrosis. Nephrol Dial Transplant Off Pub Eur Dial Transpl Assoc Eur Ren Assoc 27(7):2625–2628 14. Gines P, Schrier RW (2009) Renal failure in cirrhosis. New Engl J Med 361(13):1279–1290 15. Mehta RL, Kellum JA, Shah SV et al (2007) Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11(2):R31 16. Yu J, Mehran R (2012) ‘‘CIN’’ no more: the use of contrast volume to e-GFR ratio to predict and prevent contrast-induced acute kidney injury. Catheter Cardiovasc Interv Off J Soc Cardiac Angiogr Interv 79(7):1201–1202 17. Davenport MS, Khalatbari S, Cohan RH, Dillman JR, Myles JD, Ellis JH (2013) Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material: risk stratification by using estimated glomerular filtration rate. Radiology 268(3):719–728 18. Mehran R, Nikolsky E (2006) Contrast-induced nephropathy: definition, epidemiology, and patients at risk. Kidney Int Suppl 100:S11–S15 19. Weisbord SD, Mor MK, Resnick AL, Hartwig KC, Palevsky PM, Fine MJ (2008) Incidence and outcomes of contrast-induced AKI following computed tomography. Clin J Am Soc Nephrol CJASN 3(5):1274–1281 20. Mitchell AM, Jones AE, Tumlin JA, Kline JA (2010) Incidence of contrast-induced nephropathy after contrast-enhanced computed tomography in the outpatient setting. Clin J Am Soc Nephrol CJASN 5(1):4–9 21. Mueller C, Buerkle G, Buettner HJ et al (2002) Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 162(3):329–336 22. Bucher AM, De Cecco CN, Schoepf UJ et al (2014) Is contrast medium osmolality a causal factor for contrast-induced nephropathy? Biomed Res Int 2014:931413 23. Andreucci M, Faga T, Pisani A, Sabbatini M, Michael A (2014) Acute kidney injury by radiographic contrast media: pathogenesis and prevention. Biomed Res Int 2014:362725
