Early Allograft Dysfunction After Liver Transplantation Is Associated With Short- and Long-Term Kidney Function Impairment.

Early allograft dysfunction (EAD) after liver transplantation (LT) is related to ischemia-reperfusion injury and may lead to a systemic inflammatory response and extrahepatic organ dysfunction. We evaluated the effect of EAD on new-onset acute kidney injury (AKI) requiring renal replacement therapy within the first month and end-stage renal disease (ESRD) within the first year post-LT in 1325 primary LT recipients. EAD developed in 358 (27%) of recipients. Seventy-one (5.6%) recipients developed AKI and 38 (2.9%) developed ESRD. Compared with those without EAD, recipients with EAD had a higher risk of AKI and ESRD (4% vs. 9% and 2% vs. 6%, respectively, p < 0.001 for both). Multivariate logistic regression analysis showed an independent relationship between EAD and AKI as well as ESRD (odds ratio 3.5, 95% confidence interval 1.9-6.4, and odds ratio 3.1, 95% confidence interval 11.9-91.2, respectively). Patients who experienced both EAD and AKI had inferior 1-, 3-, 5-, and 10-year patient and graft survival compared with those with either EAD or AKI alone, while those who had neither AKI nor EAD had the best outcomes (p < 0.001). Post-LT EAD is a risk factor for both AKI and ESRD and should be considered a target for future intervention to reduce post-LT short- and long-term renal dysfunction.

Antithymocyte globulin induction and rapid steroid taper leads to excellent results in kidney transplantation with donation after cardiac death donors: importance of rejection and delayed graft function.

Recipients of primary transplants from donation after cardiac death (DCD) donors (n = 40) performed from January 2005 to December 2009 were retrospectively reviewed and compared with recipients of primary transplants from donation after brain death (DBD) donors (n = 142). Patients received rabbit antithymocyte globulin induction and rapid steroid taper (RST; steroids stopped 5 days after surgery). Maintenance immunosuppression included tacrolimus and mycophenolate mofetil. Protocol kidney biopsies, creatinine (Cr), and measured glomerular filtration rate (mGFR; determined by cold iothalamate or 24-h creatinine clearance) were obtained at 1, 4, 12, and 24 months. Kidney biopsies for cause were conducted for unexplained elevated Cr, decline in mGFR, or new proteinuria. Biopsies were graded for rejection according to the Banff criteria. Graft survival at 3 years was 90.0% for DCD recipients and 86.6% for DBD recipients (P = NS). Rejection of any grade diagnosed on any biopsy through the first 2 years occurred in 18 DCD (45%) and 50 DBD (35%) recipients. Rejection of a grade more than Banff borderline occurred in 12.5% DCD and 12.7% DBD recipients. At 2 years, the mean ± SEM Cr and mGFR for DCD recipients with rejection were 1.8 ± 0.29 mg/dL and 59.2 ± 8.5 mL/min versus 1.3 ± 0.11 mg/dL and 67.0 ± 7.8 ml/min for those without rejection. For DBD recipients with rejection, Cr and mGFR at 2 years were 1.7 ± 0.12 mg/dL and 54.0 ± 4.4 mL/min versus 1.4 ± 0.11 mg/dL and 66.6 ± 3.3 ml/min for those without rejection (P = NS). Comparing DCD to DBD, there was no statistical difference in mean Cr or mGFR outcomes. Regardless of group, grafts with delayed graft function had lower 3-year survival. DCD primary kidney transplant recipients treated with rabbit antithymocyte induction and RST have short-term graft survival and function equivalent to DBD recipients. RST appears to be acceptable immunosuppression for DCD recipients.

Kidney allocation to liver transplant candidates with renal failure of undetermined etiology: role of percutaneous renal biopsy.

The feasibility, value and risk of percutaneous renal biopsy (PRB) in liver transplant candidates with renal failure are unknown. PRB was performed on 44 liver transplant candidates with renal failure of undetermined etiology and glomerular filtration rate (GFR) <40 mL/min/1.73 m(2) (n = 37) or on renal replacement therapy (RRT) (n = 7). Patients with >or=30% interstitial fibrosis (IF), >or=40% global glomerulosclerosis (gGS) and/or diffuse glomerulonephritis were approved for simultaneous-liver-kidney (SLK) transplantation. Prebiopsy GFR, urinary sodium indices, dependency on RRT and kidney size were comparable between 27 liver-transplant-alone (LTA) and 17 SLK candidates and did not relate to the biopsy diagnosis. The interobserver agreement for the degree of IF or gGS was moderate-to-excellent. After a mean of 78 +/- 67 days, 16 and 8 patients received LTA and SLK transplants. All five LTA recipients on RRT recovered kidney function after transplantation and serum creatinine was comparable between LTA and SLK recipients at last follow-up. Biopsy complications developed in 13, of these, five required intervention. PRB is feasible in liver transplant candidates with renal failure and provides reproducible histological information that does not relate to the pretransplant clinical data. Randomized studies are needed to determine if PRB can direct kidney allocation in this challenging group of liver transplant candidates.

Continued influence of preoperative renal function on outcome of orthotopic liver transplant (OLTX) in the US: where will MELD lead us?

Renal function is a component of the Model for End Stage Liver Disease (MELD), We queried the 1999-2004 OPTN/UNOS database to determine whether preoperative renal function remained an important determinant of survival in primary deceased donor liver transplant alone patients (DDLTA) or primary combined kidney liver transplant patients (KLTX). We examined preoperative creatinine, renal replacement therapy (RRT), incidence of KLTX, and patient survival in the 34 months before and after introduction of MELD and performed a multivariate Cox regression analysis of time to death. Preoperative renal function is an independent predictor of survival in DDLTA but not in KLTX. When compared to DDLTA with a preoperative serum creatinine of 0-0.99 mg/dL, patients with serum creatinine from 1-1.99 mg/dL, >2.0 mg/dL, those requiring RRT, and those receiving KLTX had a relative risk of death following transplant of 1.11, 1.58, 1.77, and 1.44 respectively. KLTX requiring RRT had better survival than DDLTA requiring RRT. Since introduction of MELD, KLTX, preoperative creatinine, and number of patients requiring preoperative RRT have increased. Despite this, patient survival following orthotopic liver transplant (OLTX) in the 34 months after introduction of MELD is not different than prior to introduction of MELD.

Renal replacement therapy and orthotopic liver transplantation: the role of continuous veno-venous hemodialysis.

BACKGROUND: The need for renal replacement therapy (RRT) either before or after orthotopic liver transplant (OLTX) has been reported to be a poor prognostic indicator for survival. Use of continuous veno-venous hemodialysis (CVVHD) for RRT has been reported in three series of OLTX patients with high 90-day mortality rates of 57-60%. We have examined our patient population to determine the effect of necessity and type of RRT on patient survival after OLTX. METHODS: We analyzed 1535 OLTX that were performed at our institution from 1985 through 1999, 1037 from 1985 to 1995 (period I) and 498 from 1996 to 1999 (period II). Combined liver-kidney transplants were excluded from analysis. Hospital dialysis unit records and a prospectively maintained database on all OLTX patients served as the source of data. Patients were classified into groups defined on whether or not they received RRT, when they received RRT, and the type of RRT. Groups were compared for preoperative intensive care unit status, time on the waiting list, laboratory variables, 90-day postoperative mortality, 1-year patient survival, and absolute survival. RESULTS: Use of RRT increased from 8.29% in period I to 12.45% in period II, along with increased median waiting times. In period I, patients receiving preoperative RRT had a 90-day mortality (0%) and a 1-year survival (89.5%) almost identical to those patients who never required RRT (1.7% and 90.6%). Patients who developed acute renal failure postoperatively requiring RRT, however, had a 90-day mortality of 28.6% and a 1-year survival of 55%. In period II, patients requiring RRT had a 90-day mortality of 39.7% and a 1-year actuarial survival of 54.5% compared with 6.9% and 88.6% in patients never requiring RRT. Patients treated with CVVHD had a 90-day mortality of 42% compared with 25% in patients treated with hemodialysis alone. However, patients receiving CVVHD both pre- and postoperatively had a 90-day mortality of 27.7% vs. 50% in those patients who only received CVVHD postoperatively. Patients who developed acute renal failure postoperatively, which required RRT, regardless of therapy, had a 1-year survival of only 41.0% compared with a 1-year survival of 73.6% in those patients started on RRT preoperatively, P=0.03. CONCLUSIONS: The need for RRT has increased along with waiting time in OLTX patients. Patients developing the need for RRT postoperatively have an increased 90-day mortality and lower 1-year survival with the highest being present in patients receiving CVVHD, which was started postoperatively. These findings may reflect a trend toward a sicker population awaiting OLTX and emphasize the negative impact of renal failure on survival after OLTX.

End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment.

BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.

Gastrointestinal tuberculosis in renal transplantation: a case report and review.

The pattern of tuberculosis has changed and in recent years: extrapulmonary tuberculosis has become more common, especially in immuno-compromised individuals. A case of primary intestinal tuberculosis in a patient with kidney transplant is reported. The patient presented with persistent fever and right-sided abdominal pain. Histopathology of colonic tissue showed granulomatous inflammation containing acid fast bacilli, and culture of the tissue grew Mycobacterium tuberculosis. Clinical improvement occurred after institution of appropriate anti-tubercular treatment.

Stability of long-term renal function in heart transplant patients treated with induction therapy and low-dose cyclosporine.

Long-term renal function was evaluated in heart transplant recipients who were treated with antilymphocyte globulin induction therapy and low-dose cyclosporine therapy. Although an initial 16% drop in the glomerular filtration rate occurred, long-term follow-up revealed stability of renal function. Four-year patient survival was 77.6%. Use of induction therapy with low-dose cyclosporine may preserve renal function without compromising long-term patient survival.

Simultaneous heart and kidney transplantation: a report of three cases and review of the literature.

Three cases of combined heart and kidney transplantation are presented. All three patients suffered from end-stage kidney disease, one chronic glomerulonephritis, two diabetic nephropathy. Ages of the patients were 22, 30, and 39 years, respectively. Two of the patients had the diagnosis of dilated cardiomyopathy and the third had ischemic heart disease. Patient follow-up is from 6 to 30 months. None of the patients have had a heart rejection and only one has had a kidney rejection. Cardiac and renal function remain excellent in all three patients. Glomerular filtration rates range from 53 to 77 ml/min. These three cases are compared with other reported cases in the literature. Combined heart and kidney transplantation may be of benefit in selected persons.

Race and liver transplantation.

Little is known about the effect of race on the outcome of liver transplantation. We retrospectively reviewed a series of 358 recipients of orthotopic liver transplants to address this issue. Black recipients were underrepresented compared with the general population (6% of transplant recipients vs 12% of the population). Black recipients appeared sicker when presenting for transplantation, as evidenced by a higher priority score and a significantly greater incidence of acute and fulminant presentation. Despite this, black recipients had survival rates following transplantation that were not significantly different from those of white recipients; the 1-, 2-, and 3-year actuarial survival rates of blacks were 89.6%, 68.3%, and 68.3%, respectively, while the actuarial survival rates of whites at the same periods were 86%, 82.4%, and 78.6%, respectively. We conclude that blacks can have an outcome equal to whites following liver transplantation but they are underrepresented compared with the general population.

Calcium acetate, an effective phosphorus binder in patients with renal failure.

Calcium salts are increasingly used as phosphorus binders in patients with chronic renal failure. Calcium carbonate is the principal salt presently utilized, however, other calcium salts may be more effective and safer phosphorus binders. Theoretical calculations, in vitro experiments, and in vivo studies in normal subjects have shown calcium acetate to be a more effective phosphorus binder than other calcium salts. This salt has not previously been studied in patients with chronic renal failure. We used a one-meal gastrointestinal balance technique to measure phosphorus absorption, calcium absorption and phosphorus binding in six patients with chronic renal failure. Calcium acetate was compared with calcium carbonate and placebo. Equivalent doses (50 mEq Ca++) of calcium acetate bound more than twice as much phosphorus (106 +/- 23 mg) as calcium carbonate (43 +/- 39 mg) P less than 0.05. When phosphorus binding was factored for calcium absorption, calcium acetate bound 0.44 mEq HPO4 =/mEq absorbed Ca++ compared with 0.16 mEq HPO4 = bound/mEq Ca++ absorbed with calcium carbonate. More efficient phosphorus binding permits serum phosphorus concentration to be controlled with lower doses of calcium salts. The higher phosphorus binding/calcium absorption ratio coupled with a lower dose indicates that less calcium will be absorbed when calcium acetate is used for phosphorus control. Markedly positive calcium balance, hypercalcemia and ectopic calcification should be less likely to occur with this drug than other calcium salts.