Chronic Kidney Disease—A Common and Serious Complication After Intestinal Transplantation Gustaf Herlenius,1,5 Mattias Fa¨gerlind,1 Marie Krantz,2 Johan Mo¨lne,3 Michael Olausson,1 Markus Ga¨bel,1 Vanda Friman,4 Mihai Oltean,1 and Styrbjo¨rn Friman1 Background. Chronic kidney disease after organ transplantation is a serious complication that negatively impacts on long-term patient survival. We describe long-term renal function after intestinal transplantation by serial measurements of glomerular filtration rates (GFR) with 51Chromium EDTA clearance. Materials and Methods. Ten patients with at least 6 months survival form the basis of this report. Glomerular filtration rate measurements were performed at baseline, 3 months posttransplantation, and yearly thereafter. Median follow-up time for the cohort was 1.5 years (0.5–7.8 years). Tacrolimus (Prograf) was discontinued in four patients because of impaired renal function. These four patients were switched to sirolimus (Rapamune) at 11, 18, 24, and 40 months posttransplantation. Results. Median baseline GFR was 67 (22–114) mL/min/1.73 m2. In the adult patients, GFR 3 months posttransplantation had decreased to 50% of the baseline. At 1 year, median GFR in the adult patients was reduced by 72% (n⫽5). Two patients developed renal failure within the first year and required hemodialysis. One of the pediatric patients fully recovered her renal function, the second pediatric patient lost 20% of her baseline GFR at 6 months posttransplantation. Glomerular filtration rate calculated with the modified diet in renal disease formula consistently overestimated GFR by approximately 30% compared with measured GFR. Conclusion. Chronic kidney disease and renal failure are common after intestinal transplantation. These two factors significantly contribute to poor long-term survival rates. Measurements of GFR may help to identify those individuals at risk for developing chronic kidney disease to implement renal sparing strategies. Keywords: Intestinal transplantation, Renal toxicity, Chronic kidney disease, Glomerular filtration rate, Calcineurin inhibitors. (Transplantation 2008;86: 108–113)
enal dysfunction has emerged as a significant complication in solid organ transplantation. Long-term calcineurin inhibitor based immunosuppression is considered to be a major contributing factor in the development of chronic kidney disease (CKD). There is a 4-fold increase in mortality when CKD is present after solid organ transplantation (1). Despite improvements and encouraging results, transplantation of the intestine continues to be a major challenge. Factors such as renal dysfunction that may have an influence on long-term outcome need to be more clearly defined. There are only a few reports that include descriptions of renal function after intestinal transplantation (2, 3). Existing reports rely on calculated glomerular filtration rates (GFR), which use formulas that have not been validated for recipients of intestinal transplants or for patients with intestinal failure
R
This work was presented at the Xth International Small Bowel Transplantation Symposium held in Los Angeles, CA on September 6th– 8th, 2007. 1 Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, Go¨teborg, Sweden. 2 Department of Pediatrics, HRH Queen Silvia Children’s Hospital, Go¨teborg, Sweden. 3 Department of Pathology, Sahlgrenska University Hospital, Go¨teborg, Sweden. 4 Department of Infectious Diseases, Sahlgrenska University Hospital, Go¨teborg, Sweden. 5 Address correspondence to: Gustaf Herlenius, M.D., Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, 41345 Go¨teborg, Sweden. E-mail:
[email protected] Received 19 November 2007. Revision requested 19 December 2007. Accepted 10 March 2008. Copyright © 2008 by Lippincott Williams & Wilkins ISSN 0041-1337/08/8601-108 DOI: 10.1097/TP.0b013e31817613f8
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(IF) and advanced liver disease. These formulas may therefore inaccurately assess renal impairment in solid organ transplant recipients (4, 5). In the present study, we report on long-term renal function after intestinal transplantation through serial measurements of the GFR. The primary objectives of this study were to describe the progression of renal dysfunction after intestinal transplantation and to identify those clinical events that may have had an impact on renal function.
MATERIALS AND METHODS Thirteen intestinal transplants have been performed at our institution since October 1998 (Table 1). Eleven of the patients received multivisceral (MV) grafts (10 adults and 1 child), one adult patient received a combined liver and intestinal graft (LIT), and one child received an isolated intestinal graft. Six patients have died. Three of these deaths occurred less than 6 months posttransplantation; these patients were excluded from this analysis. The causes of these early deaths were posttransplant lymphoproliferative disease, deep fungal infection, and multiple organ failure. The 10 patients with a posttransplantation survival of at least 6 months form the basis of this report. Median follow-up time for the cohort was 1.5 years (0.5–7.8 years). Median age at transplantation was 42 years (4 – 67 years) (Table 2). For three of the patients, transplantation was deemed necessary because of neuroendocrine pancreatic tumors (NEPT) with hepatic metastases. The remaining seven patients experienced IF with varying degrees of hepatic fibrosis and portal hypertension. Four of the patients were hospitalized at the time of the transplantation. All donors were blood group identical except in one case when an MV graft from a donor belonging to a compatible Transplantation • Volume 86, Number 1, July 15, 2008
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TABLE 1.
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Results after intestinal transplantation—survival, causes of death, and renal status in 13 patients
No.
Sex
Age
Diagnosis
Graft
Time of death (mo)
Cause of death
Survival (yr)
CKD
RRT
1 2 3 4 5 6 7 8 9 10 11 12 13
F M M F M F M F F M F F F
4 42 44 56 38 58 27 40 67 44 37 24 4
SD/ESLD NEPT NEPT SBS/ESLD NEPT NEPT SBS/ESLD SBS/ESLD CIPO NEPT SBS/ESLD CIPO HD
MV MV MV LIT MV MV MV MV⫹K MV MV MV⫹K MV I
— 4 — 40 2 27 1 — — — 11 — —
— PTLD — Hemorrhage Infection Recurrence MOF — — — Sepsis — —
9.3 0.25 8 3.5 0.2 2.3 0.1 4.3 3.8 3.8 0.9 1.1 1
⫺ ⫺ ⫹ ⫹ ⫺ ⫹
⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫹ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺
⫹ ⫺ ⫹ ⫹ ⫹ ⫺
SD, secretory diarrhea; ESLD, end stage liver disease; NEPT, neuroendocrine pancreatic tumor; SBS, short bowel syndrome; CIPO, chronic intestinal pseudo obstruction; HD, Hirschsprung’s disease; MV, multivisceral; LIT, combined liver and intestine; K, kidney graft; I, isolated intestinal graft; PTLD, post transplant lymphoproliferative disease; MOF, multiple organic failure; CKD, chronic kidney disease; RRT, renal replacement therapy.
TABLE 2. Demographics, diagnosis, type of intestinal graft, and long-term follow-up of renal function in 10 patients with GFR measurements No.
Sex
Age
Diagnosis
Graft
GFR follow-up (yr)
Baseline GFR
GFR at end of follow-up
% change GFR
RRT
1 2 3 4 5 6 7 8 9 10
F M F F F F M F F F
4 44 56 58 40 67 44 37 24 4
SD/ESLD NEPT SBS/ESLD NEPT SBS/ESLD CIPO NEPT SBS/ESLD CIPO HD
MV MV LIT MV MV⫹K MV MV MV⫹K MV I
7.8 5.2 3.4 0.5 3.5 0.5 2.0 0.9 0.8 0.7
22 94 73 114 41 61 93 42 85 46
102 15 21 9 20 8 30 15 32 35
⫹360 ⫺84 ⫺71 ⫺90 ⫺51 ⫺86 ⫺68 ⫺64 ⫺62 ⫺20
No No No Yes No Yes No No No No
Baseline GFR, GFR pretransplantation; % change GFR, percentual loss/gain of GFR compared with baseline value; SD, secretory diarrhea; ESLD, end stage liver disease; NEPT, neuroendocrine pancreatic tumor; SBS, short bowel syndrome; CIPO, chronic intestinal pseudo obstruction; HD, Hirschsprung’s disease; MV, multivisceral; LIT, combined liver and intestine; K, kidney graft; I, isolated intestinal graft.
blood group was used (“O” to “A”). Median cold ischemia time was 8.1 hr (4.5–10.2). Definition of Chronic Kidney Disease and Glomerular Filtration Rates Measurements Severe chronic kidney disease was defined in accordance with the United States National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines as a GFR below 30 mL/min/1.73 m2. Renal failure was defined as the requirement for renal replacement therapy (RRT) as chronic dialysis or kidney transplantation. All the patients were followed-up with 51Chromium EDTA clearance using the previously reported method (6). Glomerular filtration rates measurements were performed at the time of listing for transplantation, at 3 months posttransplantation, and yearly thereafter. Additional measurements were performed as needed, when persistent rise in serum creatinine evidenced a deterioration of renal function or, if any other signs of declining renal function were present. Glomer-
ular filtration rates measurements were performed using the Chromium EDTA clearance method. Calculation of GFR was performed with the modified diet in renal disease (MDRD) formula in its abbreviated form (7). 51
GFR ⫽ 186 ⫻ serum creatinine (mg/dL)⫺1.154 ⫻ age (years)⫺0.203 ⫻ 0.7422 (if female) Screening for proteinuria with urine dispsticks was performed on a weekly basis during the first 3 months after transplantation and monthly thereafter. Patients with a positive dipstick test underwent confirmation of proteinuria by quantitative measurement as “spot” urine samples or timed urine collection (overnight or 24 hr). Surgical Technique The MV grafts included the liver, stomach, pancreaticoduodenal complex, and small intestine. In one case the spleen
110 was included in the graft and two patients received a kidney en bloc with the MV graft. The LIT graft included the liver, duodenum, pancreatic head, and the small intestine. Arterial inflow to the MV and LIT grafts was achieved by anastomosis of a donor aortic conduit to the infrarenal aorta except in two cases where the aortic conduit was anastomosed end to side to the left common iliac artery because of extensive retroperitoneal fibrosis. Venous outflow from the graft was achieved by a side to side cavo-caval anastomosis in all MV and LIT cases. Portosystemic venous drainage of the isolated intestinal graft to the inferior vena cava was used. Ileostomas were left in all cases for endoscopic intestinal graft surveillance. Preemptive Combined Renal and Multivisceral Transplantation Because of a low baseline GFR (41 and 42 mL/min/1.73 m2, respectively) a preemptive renal transplantation was performed on two patients. A kidney was transplanted en bloc and orthotopically with the MV graft. The ureter of the kidney graft was anastomosed in an end to end fashion to the native ureter. The cause of the pretransplantation renal dysfunction in these two patients was considered to be multifactorial and secondary to repetitive septic episodes aggravated by cholestatic liver disease and chronic dehydration. The two pediatric patients presented with a low baseline GFR but did not receive a kidney transplant. The first child presented with severe end-stage liver disease and was considered to have a hepatorenal syndrome. Her renal function was expected to improve after the successful transplantation of a liver in the MV graft. The second child was born with only one kidney. A simultaneous intestinal and kidney transplant was initially considered but this strategy was abandoned because of the presence of a reduced abdominal cavity that would have impeded the simultaneous transplantation of intestine and kidney. Immunosuppression Two main immunosuppressive protocols have been used since the initiation of our program in 1998. Tacrolimus (Tac; Prograf) has been the mainstay of therapy in both protocols. From 1998 to 2003, Tac in combination with steroids and the interleukin-2 receptor antagonist daclizumab (Zenapax) were used. Twelve-hour trough levels for Tac in this protocol was 15 to 20 ng/mL throughout the first 3 months posttransplantation and thereafter tapered to 10 ng/mL. After 2003, antithymocyte globulin (Fresenius) induction with Tac monotherapy in a steroid-free protocol has been used as described by the Pittsburgh group (8). Target levels of Tac were 10 ng/mL during the first 6 months after transplantation and thereafter tapered to approximately 5 ng/mL by the end of the first year posttransplantation. Rejection was treated with a steroid bolus and thereafter the steroids were quickly tapered. Steroid resistant rejection episodes were treated with OKT-3 (Orthoclone). Tacrolimus Discontinuation In those cases where a rapid and persisting decline in the renal function was present Tac was discontinued and replaced with sirolimus (Rapamune). Before switching immunosuppressors, an upper gastrointestinal endoscopy and an ileoscopy were performed to rule out a subclinical rejection episode. Sirolimus was initiated with a loading dose of 10 mg daily for 2 days and thereafter the dose was adjusted to main-
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tain 12-hr trough levels of 5 to 10 ng/mL. The prednisolone dose was temporarily increased to 10 mg daily during the switch procedure and was then tapered. Infection Prophylaxis Meropenem (Meronem) and Vancomycin (Vancomycin) were used as broad-spectrum antibacterial prophylaxis. The two were initiated preoperatively and continued for the first 5 postoperative days. Antifungal prophylaxis consisted of liposomal amphotericin B (AmBisome) at 1 to 1.5 mg/kg/day or caspofungin (Cancidas) initial bolus of 70 mg preoperatively and thereafter 50 mg daily. A cytomegalovirus prophylaxis gancyclovir (Cymevene) was given intravenously during the first 6 months posttransplantation. All drugs were given at a dosage adjusted according to renal function. For the adults, Pneumocystis jiroveci prophylaxis was administered once a month during the first 6 months of posttransplantation with inhalations of pentamidine (Pentacarinat). The children received trimehoprim and sulfametoxazole (Bactrim) for the first year posttransplantation. Antibacterial and cytomegalovirus prophylaxis were usually reinitiated when an acute rejection episode was diagnosed and treated. Infectious Episodes Patient records were retrospectively reviewed for clinically relevant infectious episodes, based on clinical presentation, systemic inflammatory response, positive bacteriology or polymerase chain reaction in blood or tissues, immunohistochemistry and pertinent radiologic and endoscopic examinations. Emergent Surgical Procedures These were defined as any major urgent abdominal reoperation performed after transplantation. The indicators usually included hemorrhaging, abdominal compartment syndrome, intraabdominal abscess, intestinal perforations, or other life-threatening conditions.
RESULTS Baseline Renal Function The Median Baseline GFR for the Whole Cohort (n⫽10) was 67 (22–114) mL/min/1.73 m2. None of the patients were on hemodialysis before transplantation. The median baseline GFR for the group with IF (n⫽7) was 42 mL (22–73 mL) with three also experiencing a hepatorenal syndrome. In the group with NEPT (n⫽3) the median baseline GFR was 94 mL (93–114). The two pediatric patients had compromised renal function before transplantation because of hepatorenal syndrome and unilateral renal agenesia. Their GFR levels were 22 and 46 mL/min/1.73 m2, respectively. Measured Glomerular Filtration Rate Levels Posttransplantation Glomerular filtration rates after transplantation decreased in all the adult patients (Fig. 1). Median GFR at 3 months posttransplantation for the whole cohort (n⫽10) was 32 mL (15– 44) representing approximately a 50% decrease from the baseline. Of the five adult patients with a follow-up of 1 year or more after transplantation, median GFR had declined by 70% to 22 mL (18 – 40). Four of these five patients also presented with CKD because of a GFR below 30 mL.
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111
120
mls/min/BSA
100 80 60 40 20
5
4. 5
4
3. 5
3
2. 5
2
1. 5
1
0. 5
PRE
0
Years post transplantation
FIGURE 1. GFR pre- and post intestinal transplantations. The pediatric patient with normalized renal function is illustrated by the thick broken line.
Two patients required RRT within the first year. One of these patients received a kidney transplant after 2 years. Of the two pediatric patients, one normalized her renal function from a baseline of 22 mL. Eight years after her transplantation her GFR had increased to 102 mL. The other pediatric patient received an isolated intestinal graft and her GFR declined 20% during the 6 months after transplantation. Median GFR and Tac trough levels posttransplantation are represented in Table 3. Comparison of Glomerular Filtration Rates Measured with Chromium EDTA and Calculated by the Modified Diet in Renal Disease Formula In four adult patients measured and calculated GFR was compared. The calculated GFR by the MDRD formula was persistently 30% above the measured values for the duration of the 2-year follow-up period (Fig. 2).
TABLE 3. levels
Median (range) Time
GFR (mL/min/1.73 m2)
Tac (ng/mL)
n
Pretransplant Day 7 Day 90 1 yr
67 (22–114) — 32 (15–44) 22 (18–40)
— 18 (3–30) 12 (6–26) 7 (5–15)
10 10 10 6
mls/min/1. 73 m2
50 39
30
31
32 25
27
GFR MDRD
10 0 1 year
Infections Infectious episodes were frequent. A total of 60 episodes were recorded. The majority (84%) occurred within the first 6 months after transplantation. Approximately 19% of these episodes were related to central intravenous catheters and 20% originated in the gastrointestinal tract. Respiratory infections accounted for 27%. Bacterial (68%), viral (17%), fungal (11%), and combined bacterial and fungal (4%) agents were the most common. One patient died of bacterial pneumonia and sepsis.
35
20
3 months
Patients with Kidney Included in the Multivisceral Graft One patient is alive and off total parenteral nutrition 3 years postmultivisceral transplantation with a GFR that is stable approximately 23 mL. A renal scintigram performed 5 months posttransplantation demonstrated a normal accumulation and slow elimination of the isotope by the transplanted kidney (Fig. 3). The second patient died of sepsis secondary to bacterial pneumonia 11 months posttransplantation. Two months before death her GFR was 15 mL/min/1.73 m2. Administration of Antibacterial and Antifungal Drugs In most cases the duration of administration of antibiotic and antifungal drugs was prolonged because of the presence of infectious or rejection episodes. The median duration of treatment with meropenem was 19 days (11–50 days), for vancomycin 20 days (7–37 days), and antifungals 23 days (16 –38 days).
Median GFR and tacrolimus 12-hr trough
40
FIGURE 3. Renal scintigram performed 5 months posttransplantation in a patient with an en bloc multivisceral and renal transplantation. The kidney graft is located on the right and its image is superimposed with that of the native right kidney.
2 years
FIGURE 2. GFR measured with cromium EDTA and GFR calculated with the MDRD formula after intestinal transplantation in four adults.
Emergent Surgical Procedures Twenty-three abdominal reoperations were performed after transplantation in 9 of the 10 patients. Sixteen explorative laparotomies were necessary because of sepsis and for debridement of superficial necrosis of the pancreas. Other important indications for emergency laparotomies were revisions of the aortic graft caused by aneurysmatic dilation and stenosis. One native nephrectomy was also performed because of hydrone-
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FIGURE 4. Light microscopic image of a small artery showing myocyte vacuolation compatible with tacrolimus toxicity. Multiple myocytes show distinct vacuoles (arrows).
phrosis and recurring pyelonephritis. This patient was already in hemodialysis at the time of the nephrectomy. Tacrolimus Discontinuation and Switching to Rapamycin Because of Declining Renal Function Tacrolimus was discontinued in four adult patients because of impaired renal function and proteinuria (n⫽2). These patients were switched to sirolimus at 11, 18, 24, and 40 months posttransplantation. Biopsy of the native kidney in one of these patients showed signs of Tac toxicity (9) (Fig. 4). This patient eventually developed renal failure and required hemodialysis. Another patient died 3.5 years after transplantation of a retroperitoneal hemorrhage caused by an overdosage of low molecular weight heparin. Her GFR was 29 mL at the time of the switch (18 months posttransplantation) and at 6 months before her death it was 21 mL/min/1.73 m2. In the remaining two patients GFR levels have remained stable, 2 and 3 years after Tac discontinuation. Use of sirolimus did not complicate treatment and no rejection episodes were documented. Two patients developed hypercholesterolemia and thrombocytopenia. The drug was otherwise well tolerated.
DISCUSSION By serial measurements of the GFR with 51Chromium EDTA, we found that CKD and renal failure are frequent and serious complications that occur after intestinal transplantation. The median measured GFR decreased to 70% at 1-year posttransplantation. At 1 year after intestinal transplantation 80% of the adult patients developed CKD and one fifth of the patients developed renal failure requiring RRT. Publications related to renal dysfunction after intestinal transplantation are few and the ones that exist rely on creatinine-based formulas to calculate the GFR (3, 10, 11). The accuracy of these GFR calculations is challengeable, because the method consistently overestimates the GFR in patients with severe liver disease. Furthermore, in the period postliver transplantation, the MDRD and Cockcroft-Gault formulas underestimate the true GFR (4, 5, 12, 13). Another important consideration is that a calculated measurement of GFR has not been validated for patients with IF or recipients of
intestinal grafts. In this context, it is interesting to note that in our series the results of the calculated GFR was approximately 30% above the measured GFR values; this indicates that the MDRD formula overestimates the GFR in these conditions. The risk of developing renal dysfunction after transplantation of a nonrenal organ and, in particular, recipients of intestinal transplants have been addressed by other authors. Ojo et al. (1) observed that the 5-year risk of chronic renal failure (defined as a GFR of 29 mL/min/1.73 m2 or less) varied according to the type of organ transplanted—from 6.9% recipients of heart–lung transplants to 21.3% among recipients of intestinal transplants. One of the conclusions from this analysis was that the presence of chronic renal failure after transplantation of a nonrenal organ is associated with a 4-fold increase in the relative risk of death. Renal impairment is being seen more and more as a hazard for all solid organ recipients. Ueno et al. (10) analyzed data from 24 adult patients who received different types of intestinal transplants. With that analysis, the creatinine clearance calculated with the Cockcroft-Gault formula decreased to 43% of the pretransplant value after 2 years. A separate analysis of the nine patients who received MV grafts was not reported. Our data parallel their experience but, the difference in magnitude in the decline of renal function between our series and theirs is significant. Our cohort lost 70% of their renal function after the first year with a similar immunosuppressive regimen and target Tac trough levels. One possible explanation for this discrepancy could be the different methods used to estimate GFR levels. In another article by the same group (3), the experience with a pediatric population (n⫽36) was different from the adult population. The renal function dropped initially but recovered to remain above 100 mL/min after the first year after transplantation. One of our two pediatric patients normalized her renal function to approximately 100% of the expected value for her age. The second had one kidney remaining. That kidney had a reduced function. Despite these two factors, 6 months after transplantation this child had a GFR only 20% below the baseline value. Based on the data from the Miami group and our own series, it seems that children’s renal function can return to relatively normal levels after transplantation. This finding correlates well with the reported experiences with renal function in children after liver transplantation. Only a few pediatric recipients have their renal dysfunction progress to CKD (14, 15). However, long-term changes in renal function need to be studied; life expectancy and future long-term exposure to calcineurin inhibitors are important factors to consider especially in the setting of intestinal transplantation where high levels of Tac are required for a successful outcome. Target trough levels of 20 ng/mL are not unusual during the first months of posttransplantation. In fact, the median Tac levels in our population was 18 ng/mL at day 7. These levels are substantially higher than those required for transplantation of other organs. Furthermore, the cumulative Tac level after intestinal transplantation has been described as a predictor of renal dysfunction both in the adult and pediatric population (10, 11). Unfortunately, because of the small numbers in our series a similar analysis was not feasible. We were however able to histologically confirm the presence of calcineurin toxicity from a renal biopsy of one of our patients. This finding led us to consider using sirolimus instead of Tac. Sirolimus or my-
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cophenolate, as part of a renal sparing regimen, has been described in the context of liver transplantation as a safe alternative (16 –18). We found that sirolimus was safe and well tolerated. Despite the evidence of calcineurin toxicity as a causative factor in renal failure, our data suggest a multifactorial cause related to several major abdominal surgical procedures performed after transplantation, repetitive infectious episodes, and prolonged treatments with nephrotoxic drugs. Our data also give some insight into the complexity of the management of these patients and the severity of their underlying diseases. However, few patients do not permit any factorial analysis. Our rationale for performing a preemptive renal transplantation was based on the recognition that nephrotoxic immunosuppressive therapy will lead to a significant decrease in glomerular filtration capacity—sometimes in the range of 30% to 40% (1). This strategy seems to be a successful one considering that one of the recipients still have a functioning renal graft 31⁄2 years after transplantation. The second patient died of sepsis after 11 months; the renal graft was functioning. We believe that the decision to perform a combined intestinal and kidney transplant should be reserved for those cases where renal dysfunction is not secondary to reversible causes such as acute tubular necrosis or hepatorenal syndrome. In our experience, it was difficult to establish the exact cause of the renal dysfunction before transplantation; the cause was multifactorial and secondary to chronic dehydration, multiple septic insults, severe liver disease, and drug nephrotoxicity. This is particularly interesting considering the marked differences in baseline GFR between the group with IF and the one with NEPT (42 mL and 94 mL, respectively). The patients with IF had a history of severe liver disease, septic episodes, the permanent need for total parenteral nutrition, fluid and electrolyte disturbances. These features were absent for those with NEPT. With regards to this group of NEPT patients it is important to mention that in the event of tumor recurrence posttransplantation somatostatin receptor-mediated radiotherapy is initiated with Lutetium octreotide, an agent that is notoriously nephrotoxic. Thus, the initiation of somatostatin receptor-mediated radiotherapy in these patients may precipitate the development of CKD and, in the worst of cases, the need for RRT. In conclusion, CKD after intestinal transplantation is becoming a significant factor that may have an adverse effect on long-term survival and quality of life. To obtain an accurate assessment of renal function, frequent direct measure-
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