Long-Term Successful Outcomes From Kidney Transplantation After Lung and Heart-Lung Transplantation

GENERAL THORACIC

Long-Term Successful Outcomes From Kidney Transplantation After Lung and Heart-Lung Transplantation Shinji Otani, MD, PhD, Bronwyn J. Levvey, RN, BEd Studies, Glen P. Westall, FRACP, PhD, Miranda Paraskeva, FRACP, Helen Whitford, FRACP, Trevor Williams, FRACP, MD, David C. McGiffin, FRACS, Rowan Walker, FRACP, MD, Solomon Menahem, FRACP, PhD, and Gregory I. Snell, FRACP, MD Lung Transplant Service, Department of Allergy, Immunology and Respiratory Medicine; and Departments of Cardiothoracic Surgery and Renal Medicine, The Alfred Hospital, Melbourne, Victoria, Australia

Background. Renal dysfunction is common after lung and heart-lung transplantation (Tx), and it limits the recipient’s survival and quality of life. This study analyzed the outcomes of simultaneous and late kidney Tx following lung and heart-lung Tx. Methods. From a single-center retrospective chart review of 1031 lung and heart-lung Tx recipients, we identified 13 simultaneous or late kidney Tx cases in 12 patients. Results. Three patients underwent simultaneous deceased donor lung and kidney Tx. Eight patients underwent lung and heart-lung Tx, followed by nine living donor kidney Tx (including one ABO-incompatible Tx). One additional patient underwent a late deceased donor kidney Tx following heart-lung Tx. The median time from lung and heart-lung Tx to later kidney Tx was 127 (interquartile range [IQR], 23 to 263) months. Three patients died, 1 of sepsis, 1 of multiple organ failure, and 1

of transplant coronary disease. At a median follow-up of 33 (IQR, 10 to 51) months, 9 patients are alive and well. Eight patients required dialysis before kidney Tx for a median time of 14 months (IQR, 5 to 49). Kidney graft loss occurred in 1 patient at 51 months. After kidney Tx, dialysis was necessary in association with acute allograft dysfunction in 2 patients. No acute kidney rejection has been detected in any patient. Treatable acute lung rejection was seen in 1 patient. Well-preserved pulmonary function was noted in recipients of late kidney Tx. Conclusions. Simultaneous kidney Tx and late deceased donor kidney Tx have challenges in the setting of lung Tx. By contrast, late living related kidney Tx after lung Tx is associated with excellent long-term survival and acceptable kidney and lung allograft function.

R

particularly poorly tolerated in the lung allograft; the inability of the denervated graft to autoregulate blood flow and the absence of functional lymphatic system to drain away excess alveolar fluid are noted. In the presence of LTx immunosuppressants and in the setting of a fluid-retaining lung allograft, traditional intermittent peritoneal or hemodialysis is very poorly tolerated [1, 3]. With these morbidity and mortality issues in mind, it is appropriate therefore to consider the following: (1) simultaneous LTx and KTx, in which the pre-LTx renal reserve is so limited that peri-LTx AKI, CKD, and longterm dialysis are very likely outcomes; and (2) late KTx after LTx, in which where CKD and long-term dialysis are required. The literature focusing on these KTx and LTx scenarios is limited but instructive (Table 1) [4–13]. In terms of simultaneous KTx and LTx, high waiting list mortality is noted in the absence of Tx, and although post-Tx 5-year survival is similar to that seen with LTx alone, it is inferior to survival with KTx alone [13]. Similarly, in LTx recipients with CKD, survival is higher with late KTx than being on a KTx waiting list [4, 8]. Having achieved LTx and KTx, the recipients’ survival is then

enal failure is a common complication in recipients of nonrenal organ transplantation (Tx) [1]. Indeed, renal dysfunction develops in 55% of adult recipients of lung Tx (LTx) and in 45% of adult recipients of heart-lung Tx (HLTx) in the first 5 years after Tx [2]. These data include 3.2% and 2.2% requiring maintenance dialysis and 0.7% and 1.1% requiring subsequent kidney Tx (KTx) among LTx and HLTx recipients, respectively [2]. The clinical impact of acute kidney injury (AKI), chronic kidney disease (CKD), and dialysis on a post-LTx or HLTx recipient are complex and significant. Alterations to key, but potentially nephrotoxic, immunosuppressants may allow recovery of some renal function, but that comes at the expense of potentially facilitating chronic lung allograft dysfunction and even lung allograft loss. Fluid retention associated with renal failure is Accepted for publication Nov 17, 2014. Address correspondence to Dr Snell, Lung Transplant Service, Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, 55 Commercial Rd, Melbourne, VIC 3004, Australia; e-mail: [email protected].

Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier

(Ann Thorac Surg 2015;99:1032–9) Ó 2015 by The Society of Thoracic Surgeons

0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.11.023

Ann Thorac Surg 2015;99:1032–9

OTANI ET AL KIDNEY TRANSPLANTATION AFTER LUNG/HEART-LUNG TRANSPLANTATION

Abbreviations and Acronyms AKI CKD CNI FEV1

= = = =

FVC HLTx KTx LTx

= = = =

acute kidney injury chronic kidney disease calcineurin-inhibitor forced expiratory volume in 1 second forced vital capacity heart-lung transplantation kidney transplantation lung transplantation

Patients and Methods We performed a single-center retrospective chart review of all 1031 patients who underwent LTx and HLTx between March 1990 and March 2014. We identified 13 simultaneous or late KTx cases in 12 recipients (1.2%). All patients had been comanaged by the Lung Transplant Service and the Department of the Renal Medicine at The Alfred Hospital in Melbourne, Australia. We analyzed patients’ demographics, type of donation, complications, and clinical outcomes including lung and renal allograft function. The study was approved by The Alfred Hospital Ethics Committee. Lung and heart-lung donor assessment, matching, procurement, preservation, and implantation were performed according to routine protocolized techniques [14].

Patients received a standard triple immunosuppressant regimen consisting of prednisolone (0.3 mg/kg in the first month, reducing to 0.1 mg/kg beyond the first year), azathioprine (1.5 mg/kg)/mycophenolate (1 g), and tacrolimus (trough level 10 to 12 ng/mL in first 6 months, 8 to 10 ng/mL between 6 and 12 months, and 4 to 8 ng/mL thereafter)/cyclosporine (trough level 225 to 300 mg/L in the first 3 months, 190 to 260 mg/L between 3 and 12 months, and 150 to 225 mg/L thereafter). Immunosuppression was tailored depending on rejection history, infection, bone marrow suppression, and renal impairment. Induction therapy with the interleukin-2 (IL-2) receptor blocker basiliximab was given as a calcineurin-inhibitor (CNI) sparing agent to patients who were identified before Tx as being at higher risk of developing AKI. CNI reduction or elimination, everolimus, antihypertensives, and cholesterol-lowering agents were instituted (as indicated) for increasing renal impairment and CKD [15]. To monitor lung allograft performance, pulmonary function testing, including forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), were completed serially on each patient, at least monthly in the first 2 years after LTx, with testing every 1 to 3 months indefinitely thereafter. Surveillance bronchoscopy and transbronchial biopsies were performed at 2 weeks and at 1, 2, 3, 6, and 12 months, or if clinically indicated [16]. Intermittent hemodialysis potential KTx recipient assessments, donor assessments, donor organ retrieval, and KTx surgical procedures were carried out according to standard KTx protocols. Immunosuppression was determined in consultation with the LTx team and included anti-CD25 induction (day 0 and day 4), CNI (tacrolimus or cyclosporine), an antiproliferative agent (mycophenolate or azathioprine), and corticosteroids (prednisolone). In the case of a potential simultaneous LTx and KTx, prior approval to prioritize the cadaveric kidney with the same donor lungs was sought from the Victoria and Tasmanian Transplant Advisory Committee. Donor recipient matching included a negative T-cell cytotoxic crossmatch

Table 1. Previous Literature Related to Kidney and Lung/Heart-Lung Transplantation First Author [Reference] Wolf [13] Cassuto [4] Srinivas [11] Lonze [8] Mason [9] Rosenberger [10] Tarnow [12] Ishani [6] Jayasena [7] Coopersmith [5]

Year

Type of KTx

No. Lung/ Heart-Lung Recipients

No. Living Donors

No. Deceased Donors

Source

2013 2010 2010 2009 2007 2007 2006 2002 2001 2001

Simultaneous KTx Late KTx Late KTx Late KTx Late KTx Late KTx Late KTx Late KTx Late KTx Late KTx

18 170 N/A 210 4 2 8 9 2 7

0 98 (59%) 144 N/A N/A N/A N/A N/A N/A

18 72 (41%) 66 N/A N/A N/A N/A N/A N/A

UNOS UNOS SRTR UNOS Single-center Single-center Single-center Single-center Single-center Single-center

KTx ¼ kidney transplantation; Network for Organ Sharing.

N/A ¼ not available/applicable;

SRTR ¼ Scientific Registry of Transplant Recipients;

UNOS ¼ United

GENERAL THORACIC

almost entirely connected to the function and outcomes associated with the lung allograft. Surprisingly, there is minimal published information on the merits of deceased versus living-related KTx in the LTx setting. We have reviewed our single-institutional experience of LTx/HLTx and KTx. This case series confirms a significant evolution in strategic approach over time that provides confirmatory and novel data to assist in the management of this troublesome post-LTx problem.

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IPF ¼ Cr ¼ serum creatinine; DM ¼ diabetes; F ¼ female; HLTx ¼ heart-lung transplantation; HT ¼ hypertension; LAM ¼ lymphangioleiomyomatosis; LTx ¼ lung transplantation; M ¼ male; MOF ¼ multiorgan failure.

Deceased IPF BLTx M 59 Simultaneous KTx 3

BLTx ¼ bilateral lung transplantation; CF ¼ cystic fibrosis; idiopathic pulmonary fibrosis; KTx ¼ kidney transplantation;

. . 151

124

6 mo: alive and well

3 mo: died of MOF 2 y 9 mo: alive and well . 1.5 20 . 580 131

DM Angiolipomas, nephrectomy HT, acute tubular necrosis Deceased Deceased CF LAM BLTx BLTx F F 17 47 Simultaneous KTx 1 Simultaneous KTx 2

Gender Case

40 131

Clinical Outcome/ Complications Dialysis Pre-KTx (mo) Latest Cr (mmol/L) Pre-KTx Cr (mmol/L) KTx Indication KTx Donor HLTx/ LTx Indication

Three patients underwent simultaneous deceased donor LTx and KTx because of cystic fibrosis and diabetes, lymphangioleiomyomatosis and angiolipomas (after a previous left nephrectomy), and pulmonary fibrosis and hypertension after sepsis-related acute tubular necrosis (see Table 2). Eight patients (congenital heart disease, n ¼ 2; cystic fibrosis, n ¼ 5; pulmonary fibrosis, n ¼ 1) underwent thoracic Tx (LTx, n ¼ 4, or HLTx, n ¼ 4), followed by 9 patients who underwent elective living donor KTx (including one from an ABO-incompatible parent) (Table 3). One additional patient with congenital heart disease underwent a late deceased donor KTx after HLTx (Case number 5). The indication for late KTx was CNI toxicity/hypertension (n ¼ 7; cyclosporine n ¼ 5, tacrolimus n ¼ 2) alone or in combination with diabetes (n ¼ 3), nephrolithiasis (n ¼ 2), immunoglobulin A nephropathy (n ¼ 1), BK virus nephropathy (n ¼ 1), poststreptococcal glomerulonephritis (n ¼ 1), and focal segmental glomerulosclerosis and angiolipomas (n ¼ 1). The median time from LTx/HLTx to later KTx was 127 (interquartile range [IQR], 23 to 263) months. Three patients died secondary to urosepsis (day 72), multiple organ failure (iatrogenic hemorrhage from heparin overdose, day 95), and transplant coronary arterial disease (157 months) (n ¼ 1 each) (Fig 1). At a median follow-up of 33 (10 to 51) months, 9 patients are currently alive and well. Kidney graft loss occurred in 1 patient via BK viremic nephropathy at 51 months; it required re-KTx, which was successful. Eight patients had undergone dialysis before KTx for a median time of 14 months (IQR, 5 to 49). After KTx, dialysis was necessary in 2 patients: perioperatively in a patient with simultaneous LTx/KTx and in 1 patient with late HLTx who had a complicated ureteric anastomosis. Plasmapheresis was performed twice in 1 patient after an ABO-incompatible KTx. No acute kidney rejection has been detected. One patient experienced ureterovesicular stenosis and was successfully treated by endovascular

HLTx/ LTx

Results

Age (KTx) (y)

and avoidance of higher titer specific anti–human leukocyte antigen (anti-HLA) antibodies (determined by Luminex, Bio-Strategy, Campbellfield, Australia). The timing of living-related KTx after LTx depended on the degree of tolerance and medical risk of dialysis, the physical condition and state of the potential recipient, and surgical organization factors. In the case of the ABOincompatible KTx (case number 8; Table 2), ABOantibody-depleting repeat plasmapheresis (Spectra Optia, TerumoBCT, Tokyo, Japan) was undertaken 6, 4, 2, and 1 days before and on the day of KTx and up to 5 days after KTx. Prednisolone dose and CNI trough levels were tapered significantly beyond the first 3 months. Surveillance/renal biopsies were not undertaken unless clinically indicated. Renal allograft function was monitored with sequential serum creatinine estimations at increasing intervals over time (daily initially and eventually every 3 months indefinitely).

Ann Thorac Surg 2015;99:1032–9

Dialysis Post-KTx (mo)

OTANI ET AL KIDNEY TRANSPLANTATION AFTER LUNG/HEART-LUNG TRANSPLANTATION

Table 2. Patient Characteristics and Clinical Information: Simultaneous Kidney Transplantation and Lung/Heart-Lung Transplantation

GENERAL THORACIC

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Table 3. Patient Characteristics and Clinical Information: Late Kidney Transplantation After Lung/Heart-Lung Transplantation

Case

46

M

HLTx

CHD

151

55

M

HLTx

CHD

263

53

M

HLTx

IPF

107

Late KTx 3 Late KTx 4

32 29

M M

BLTx BLTx

CF CF

47 72

Late KTx 5 Late KTx 6

39 27

M M

HLTx BLTx

CHD CF

204 98

Late KTx 7

37

M

HLTx

CHD

213

Late KTx 8

35

F

BLTx

CF

23

Late KTx 9

21

F

HLTx

CF

91

KTx Donor Living related (mother) Living related (brother-in-law) Living related (wife)

KTx Indication

Clinical Follow-Up/ Complications

CNI (CyA)

894

.

8

.

BK viremia nephropathy CNI (CyA)

770

95

61

.

410

205

37

.

450 764

99 194

. .

. .

157 mo: died of transplant coronary disease 125 mo: alive and well 110 mo: alive and well

446 834

293 100

94 .

0.5 .

2 mo: died of sepsis 49 mo: alive and well

418

109

5

.

45 mo: alive and well

526

80

1

894

72

5

Pheresis for ABOi .

11 mo: alive and well, acute lung rejection 10 mo: alive and well

Living related (father) CNI (CyA) Living related (mother) Recurrent FSGS (sirolimus) Deceased CNI (CyA) Living related (father) IgA nephropathy, nephrolithiasis, DM Living related CNI (CyA) (dizygotic twin) Living related Poststreptococcal (mother, ABOi) GN, DM, CNI (Tac) Living related (mother)

Pre-KTx Latest Dialysis Dialysis Cr Cr Pre-KTx Post-KTx (mmol/L) (mmol/L) (mo) (mo)

Nephrolithiasis, DM, CNI (Tac)

51 mo: kidney graft loss 16 mo: alive and well

ABOi ¼ ABO-incompatible donor; BLTx ¼ bilateral lung transplantation; CF ¼ cystic fibrosis; CHD ¼ congenital heart disease; CNI ¼ calcineurin inhibitor toxicity; Cr ¼ serum creatinine; CyA ¼ cyclosporine; DM ¼ diabetes; F ¼ female; FSGS ¼ focal segmental glomerulosclerosis; GN ¼ glomerulonephritis; HLTx ¼ heart-lung transplantation; IgA ¼ immunoglobulin A; IPF ¼ idiopathic pulmonary fibrosis; KTx ¼ kidney transplantation; LAM ¼ lymphangioleiomyomatosis; LTx ¼ lung transplantation; M ¼ male; Tac ¼ tacrolimus.

OTANI ET AL KIDNEY TRANSPLANTATION AFTER LUNG/HEART-LUNG TRANSPLANTATION

Late KTx 1 (first KTx) Late KTx 1 (second KTx) Late KTx 2

Age HLTx/ Time From LTx HLTx/LTx (KTx) HLTx/ (y) Gender LTx Indication (mo)

1035

GENERAL THORACIC

GENERAL THORACIC

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OTANI ET AL KIDNEY TRANSPLANTATION AFTER LUNG/HEART-LUNG TRANSPLANTATION

Fig 1. Survival curve after kidney transplantation (KTx; simultaneous kidney-lung transplantation and late kidney transplantation after lung transplantation).

stenting 4 months after KTx. The median creatinine is 115 (IQR, 110 to 120) mmol/L at 1 year (n ¼ 6) and 116 (IQR, 111 to 123) mmol/L at 5 years (n ¼ 3) after KTx, respectively (Fig 2). Acute lung rejection was seen in 1 patient at 3 months after late KTx and was successfully treated by pulsed intravenous corticosteroid. In the 9 patients who underwent late KTx after LTx/HLTx, the median FEV1 and FVC were 2.2 (IQR, 1.6 to 2.8) L and 2.3 (IQR, 1.4 to 2.8) L during the 6 months before late KTx and 2.9 (IQR, 2.7 to 4.2) L and 3.3 (IQR, 2.9 to 4.4) L during 6 months after late KTx, respectively (n ¼ 9) (Fig 3).

Comment A common clinical problem after LTx/HLTx is the development of AKI and CKD, traditionally attributed to CNI toxicity [3, 17]. Although we try hard to prevent significant renal impairment after LTx (Table 4), irreversible CKD ultimately requires consideration of renal

Fig 2. Changes in serum creatinine after kidney transplantation at 1, 2, and 5 years.

Ann Thorac Surg 2015;99:1032–9

Fig 3. Changes in spirometry 6 months before and 6 months after kidney transplantation (KTx). (FEV1 ¼ forced expiratory volume in 1 second; FVC ¼ forced vital capacity.)

replacement therapy. This case series demonstrates that simultaneous LTx and KTx, or LTx and late KTx, are viable approaches to this problem. Indeed, an added KTx in these LTx cases has significantly extended lives, wellpreserved lung function, and improved quality of life. Historically, the reasonable glomerular filtration rate cutoff of 50 mL/min per 1.73 m2 has been used for preLTx evaluation, with limited supporting evidence [18]. Only untreatable advanced dysfunction of another major organ is included as a contraindication for LTx in international LTx guidelines [19]. Alternatively, multiorgan Tx can be considered in highly selected cases. Although there is limited literature with only a small number of cases described, simultaneous LTx/KTx from deceased donors has been shown to provide acceptable outcomes to those in need of combined Tx procedures, as experienced by the 3 cases in the current series. In 2013, Wolf and associates reported the entire United Network for Organ Sharing experience of 18 simultaneous LTx and KTx recipients’ cases and noted that 1-year and 5-year post-Tx survival in these 18 patients was 66.7% and 51.6%, respectively; this survival was comparable to that with LTx alone, but poorer than that with KTx alone [13]. Additionally, the wait-list survival at 1 and 3 years for simultaneous LTx and KTx was 65% and 52%, respectively, similar to survival among patients awaiting LTx alone [13]. These authors note acceptable results for these few individuals, but they raise ethical questions about the utility of using a kidney from a deceased donor that would have a better outcome in any other single KTx or simultaneous KTx/heart or liver Tx situation. By contrast, survival is noted to be increased by 53% to 54% after late KTx after LTx, when compared with remaining on the waiting list for a deceased KTx donor [4, 8]. A waiting time of many years for a deceased KTx/ HLTx donor is clearly disadvantageous for LTx recipients, with long-term dialysis on immunosuppression associated with serious morbidity and mortality [3]. Our Case number 5 (see Table 3) made it to a late KTx 94 months after starting dialysis but succumbed to sepsis only weeks later. The remaining patients in the current series have

Ann Thorac Surg 2015;99:1032–9

OTANI ET AL KIDNEY TRANSPLANTATION AFTER LUNG/HEART-LUNG TRANSPLANTATION

Table 4. Lessons Learned to Optimize Renal Function After LTx and Manage Renal Replacement When Needed

CNI ¼ calcineurin inhibitor; LTx ¼ lung transplantation.

KTx ¼ kidney transplantation;

done well. Subsequent survival is mostly dependent on the functional outcomes of LTx, rather than the performance of the renal allograft. Death with a functioning kidney accounted for 80% 5 years after the late KTx [4]. Indeed, 5-year death-censored renal graft survival in later KTx after LTx was compatible with the matched control of KTx recipients without previous LTx (84% versus 87%) [8]. Again, this brings up the ethical question of the appropriate use of a deceased donor kidney, by noting that the median patient survival of 4.2 years is exactly half that of a KTx alone [3]. Recognizing this concept then gives currency to actively targeting extended-criteria renal donors for the late KTx after LTx population [3]. Late living related donor KTx after LTx can provide optimal timing without allocation concerns. Five-year death-censored renal graft survival is compatible with matched control of KTx recipients without previous LTx (89% versus 91%), and this is better than results from the use of deceased donors (84%) [8]. Consistent with this finding, Cassuto and associates also showed a 70% increase in 5-year adjusted survival benefit when comparing living donor KTx after LTx with deceased donor KTx [4]. Outcomes using living donor KTx after LTx in the current study were favorable and consistent with this strategy. Just as the short waiting time could explain part of the advantage of living donor KTx compared with deceased donor KTx [20], the preemptive approach, with KTx before starting dialysis, is also recommended [3, 17, 21, 22]. Additionally, ABO-incompatible Tx may be a viable option where the pool of living donors is limited and a paired-kidney exchange is not practical, as in our Case number 8 (see Table 3). This is the first such ABOincompatible postthoracic Tx described and has proved very successful. ABO-incompatible Tx is becoming more accepted with favorable outcomes that are compatible with conventional ABO-compatible Tx, especially for

living donor KTx [23]. Importantly, because living donor KTx is elective and scheduled, strategies to deplete antiABO titers can be practicably instituted and monitored. Living donor KTx also has ethical considerations related to potential donor risk, with the Organ Procurement and Transplantation Network reporting a mortality of living kidney donors of 0.03% [24] and other authors noting a risk for perioperative complication of 3% to 30% [25]. A decrease in kidney function as a long-term consequence in living donors was also proven [26]. Constant awareness of the mortality and morbidity of living donation should never be forgotten. Some studies have suggested the possibility of less acute and chronic rejection in simultaneous multiple organ Tx compared with single organ Tx [27–31]. Although no such relationship has previously been found for allograft rejection in simultaneous LTx and KTx recipients, the low number of rejection events in the current study is at least consistent with this suggestion. Our study notes a mild effect on LTx lung function with a modest improvement of 0.1 L in FEV1 and 0.4 L in FVC after KTx. A few studies have described the effects of KTx on lung function in the non-LTx setting [32–36]. Guleria and colleagues reported mild improvements in symptoms of dyspnea, respiratory muscle function, FEV1, and FVC after 90 days of KTx in 29 recipients with a normal chest x-ray film and no chest disease [35]. Well-preserved lung function in the current study contributes to prolonged survival with acceptable quality-of-life. In conclusion, simultaneous and late deceased donor KTx procedures are clinically and ethically challenging for LTx and HLTx recipients with CKD. However, late living related KTx is a reasonable late option and is associated with excellent long-term survival and acceptable kidney and lung allograft function. We now recognize the best outcomes are obtained where the KTx is preemptive or at least where pre-KTx dialysis period is not extended. KTx from extended-criteria deceased donors and KTx from ABO-incompatible living donors are also options to reduce the risk of waiting list mortality. We wish to thank the Margaret Pratt and Lilley Foundations for their support in preparing this manuscript.

References 1. Ojo AO, Held PJ, Port FK, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003;349: 931–40. 2. Yusen RD, Christie JD, Edwards LB, et al. The Registry of the International Society for Heart and Lung Transplantation: thirtieth adult lung and heart-lung transplant report—2013; focus theme: age. J Heart Lung Transplant 2013;32:965–78. 3. Bloom RD, Doyle AM. Kidney disease after heart and lung transplantation. Am J Transplant 2006;6:671–9. 4. Cassuto JR, Reese PP, Sonnad S, et al. Wait list death and survival benefit of kidney transplantation among nonrenal transplant recipients. Am J Transplant 2010;10:2502–11.

GENERAL THORACIC

Preemptive to optimize renal dysfunction risk factors:  Optimal salt and water intake (particularly in cystic fibrosis during summer)  Optimal management of diabetes, hypertension, and hypercholesterolemia  Avoid nonsteroidal antiinflammatory drugs and aspirin Reactive when creatinine rises:  Minimize/cease all nephrotoxic agents immediately perioperatively  Specifically reduce CNI and increase mycophenolate or cease CNI and introduce everolimus Specific renal replacement:  Avoid dialysis with preemptive KTx  Avoid peritoneal dialysis (particularly in cystic fibrosis)  Minimize dialysis time  Engage family for living-related KTx, even ABO-incompatible family members

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INVITED COMMENTARY Traditionally, renal failure in the setting of lung transplantation has been an ominous condition associated with poor survival. This is due to the exquisite sensitivity of the transplanted lung to shifts in volume status. Fluid retention associated with renal impairment is poorly tolerated in the lung allograft due to inability of the denervated graft to autoregulate blood flow and the lack of a functional lymphatic system within the transplanted lung to

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remove excess alveolar fluid. These factors, combined with further postoperative immunosuppressive drug toxicity to the kidney days to months after lung transplantation, may necessitate some patients to undergo dialysis. Both peritoneal and hemodialysis have been shown to be poorly tolerated in lung transplant recipients [1]. For these reasons, most experienced transplant surgeons avoid performing lung transplants in patients who

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