Renal function outcomes following liver transplantation and combined liver-kidney transplantation

Acute renal failure (ARF) is common immediately after orthotopic liver transplantation (OLT), whereas the incidences of chronic kidney disease (CKD) and end-stage renal disease increase with time. Introduction of the Model for End-stage Liver Disease (MELD) score-intended to prioritize patients with more-severe pretransplantation liver disease in general, and worse pretransplantation renal function in particular-for the allocation of liver grafts led to concerns about compromised patient and allograft survival and increased incidence of postoperative ARF and CKD. Nonetheless, it has been suggested that early OLT of candidates with baseline renal dysfunction improves post-transplantation renal outcomes. For OLT candidates with mild to moderate chronic renal impairment or recent-onset ARF, the decision of whether to perform OLT alone or combined liver-kidney transplantation (CLKT) can be challenging because no single factor has been shown to be predictive of the degree of renal function recovery or CKD progression following successful OLT. In this article, we provide an overview of the literature on renal function outcomes following OLT and CLKT, share our perspectives on the potential predictors of renal dysfunction or nonrecovery of renal function after OLT, and present United Network for Organ Sharing data on patient and allograft outcomes in CLKT recipients in the pre-MELD and post-MELD eras. Mechanisms that might underlie immunological protection of kidney grafts by liver allografts are also discussed.     

Impact of Dialysis and Older Age on Survival after Liver Transplantation

Because creatinine is heavily weighed in the MELD (model for end-stage liver disease) score, we sought to determine the impact of MELD-based organ allocation on outcomes after transplantation in the pre- and post-MELD eras, focusing on recipients over age 65 on dialysis prior to transplant. A total of 20 196 patients from the UNOS database were analyzed. Comparing the pre-MELD to MELD era, there was a 41% increase in patients on dialysis (p<0.0001), and a 117% increase in combined liver/kidney transplants (p<0.0001). In the pre-MELD era, 1-year patient survival in recipients greater and less than age 65 on dialysis who received liver transplant alone was 56.8% and 76.4%, respectively (p=0.13). In the MELD era these rates were 50.7% and 77.8% (p=0.04). In the pre-MELD era, 1-year patient survival in recipients greater and less than age 65 on dialysis who underwent combined liver/kidney transplantation was 25.0% and 83.2%, respectively (p=0.0002). In the MELD era, these rates were 67.0% and 82.5% (p=0.18). In conclusion, a greater proportion of patients in the MELD era are on dialysis prior to transplant, and more receive combined liver/kidney transplants compared with the pre-MELD era. Candidates over age 65 who are on dialysis at the time of transplant have decreased survival after isolated liver transplantation.     

The development of proteinuria and focal-segmental glomerulosclerosis in recipients of pediatric donor kidneys

Several reports in animals, and sporadic case reports in humans, have suggested that kidneys with decreased nephron mass may be more susceptible to the development of focal-segmental glomerosclerosis. This prompted a reexamination of our previously reported group of pediatric donor-adult recipient renal transplant combinations. Data were analyzed from 31 adult recipients who had received renal transplants from cadaver pediatric donors (less than 6 years) with graft function for greater than 6 months and no evidence of chronic rejection. These were compared with a control group transplanted during the same period with adult donor kidneys. Immunosuppression consisted of azathioprine/prednisone or quadruple therapy in 16 and 15 patients respectively. End-stage renal disease (ESRD) was secondary to chronic glomerulonephritis (n = 9), diabetes mellitus (n = 6), polycystic kidney disease (n = 5), and miscellaneous causes (n = 11). Twenty patients had radiographic documentation of renal hypertrophy posttransplant. All patients had serial 24-hr urinalysis for protein and creatinine after transplantation during periods of stable renal function. Ten patients had renal biopsies performed at a mean time from transplant to biopsy of 10.4 +/- 1.6 months. Seven recipients had biopsies that revealed glomerulosclerosis at 13 +/- 6 months posttransplant. Protein excretion and serum creatinine in these patients were significantly higher than in control patients (1.6 +/- 0.37 vs. 0.49 +/- 0.15 g/24 hr and 1.96 +/- 0.11 vs. 1.64 +/- 0.09 mg%; P less than 0.03 and P less than 0.01, respectively). Only 3 of 25 control adult donor recipients developed proteinuria greater than 0.8 g/24 hr within 2 years of transplantation vs. 15/31 pediatric donor recipients. No correlations with the etiology of ESRD, age (greater than or less than 40 years), weight, sex, diabetes, hypertension, or the number of acute rejection episodes could be found. Our data suggest that adult recipients of pediatric donor renal transplants may be at greater risk for the development of glomerulosclerosis than those recipients receiving adult donor kidneys.     

Progressive Chronic Kidney Disease After Pediatric Lung Transplantation

The development of chronic kidney disease (CKD) was evaluated in a large cohort of pediatric lung transplant recipients. Retrospective chart review identified 125 patients undergoing first lung transplant at St. Louis Children's Hospital and surviving 1 year. Mean age at transplant was 10.3 +/- 0.55 years, while mean time after transplant was 4.9 years. Serum creatinine nearly doubled from baseline 0.48 mg/dL +/- 0.02 (n = 125) to 0.87 mg/dL +/- 0.04 (n = 120) at 1 year, and tripled to 1.39 mg/dL +/- 0.15 (n = 23) by 7 years after transplant. The glomerular filtration rate (GFR), as estimated by the Schwartz formula, decreased from baseline 163 +/- 5.9 mL/min/1.73 m(2) (n = 109) to 88 +/- 2.5 (n = 104), reaching 69 +/- 9.0 (n = 6) by 10 years (p < 0.01). Seven patients developed end-stage kidney disease, and by 5 years after transplant, 38% of patients reached GFR < 60 mL/min. Older age at transplant and primary diagnosis of cystic fibrosis (CF) were both associated with decreased renal survival by Kaplan-Meier (KM) analysis. In summary, pediatric lung transplant recipients experience significant loss of renal function over time, as observed in other solid organ transplant recipients, and is most dramatic in adolescents.     

Model for End-stage Liver Disease Can Predict Very Early Outcome After Liver Transplantation

Postoperative Model for End-stage Liver Disease (MELD) values have never been assessed to predict very early (<1 week) death after liver transplantation (OLT). We retrospectively reviewed 275 consecutive OLTs performed in 252 recipients reported in a prospective database. We calculated the MELD score (pre-MELD) and consecutive postoperative MELD (post-MELD) scores computed daily during the first postoperative week and on days 15 and 30 after OLT. Post-MELD scores from nonsurviving recipients displayed on a scatterplot of immediate probability of death were adjusted to the best goodness-of-fit curve, and, finally, depicted graphically as a receiver operating characteristic (ROC) curve. Nonsurviving recipients showed higher post-MELD scores: day 1: 23.5 versus 16.6 (P = .05); day 3: 25.1 versus 12.5 (P = .000); day 5: 25.7 versus 11.8 (P = .000); and day 7: 22.1 versus 10.2 (P = .000). Overall comparisons were performed using a time-dependent general linear regression model, revealing higher post-MELD scores for nonsurviving recipients, irrespective of postoperative time (P = .002). The best goodness-of-fit curve was displayed when adjusting to a theoretical exponential regression curve calculated as follows: Probability of dying within the first week (%) = 3.36 × e^{0.079 × (post-MELD)} (r = .89; P = .000). The area under the ROC curve was 0.783 (95% confidence interval, 0.630-0.935; P = .001). The model had a positive predictive value of 82.3%, a negative predictive value of 33.1%, and an accuracy of 79.2%. In conclusion, this study corroborated the suggestion that the MELD score may serve as a reliable tool to assess very early death after OLT.     

Donor structural and functional parameters are independent predictors of renal function at 3 months

INTRODUCTION: Epidemiological studies have shown that demographic, clinical, and histological donor characteristics influence renal function after transplantation, but whether these variables are independent predictors has not been established. The aim of this study was to evaluate the relative contribution of different donor variables on glomerular filtration rates (GFRs) at 3 months. PATIENTS AND METHODS: We analyzed single renal transplants performed at our center from January 2000 to July 2004. Donor variables included age, gender, weight and height, cause of death, duration of brain death, serum creatinine at admission and preprocurement, history of arterial hypertension or diabetes mellitus, and smoking habit. Donor chronic damage score was calculated in preimplantation biopsies as was the addition of interstitial fibrosis, fibrous intimal thickening, and glomerulosclerosis (<10% = 0, >10% = 1). Donor and recipient GFRs were calculated according to the Cockroft-Gault formula. RESULTS: We analyzed 202 transplants obtained from 113 deceased donors. A renal biopsy was available in 111 transplants. Recipient GFR at 3 months correlated negatively with donor age (R = -0.32, P < .01) and donor chronic damage score (R = 0.32, P < .01). GFR was lower among recipients of female versus male donors (50 +/- 15 vs 60 +/- 20 mL/min; P < .01). Donor cerebrovascular accident death (53 +/- 19 vs 63 +/- 19 mL/min; P < .01) and hypertension (48 +/- 16 vs 59 +/- 20 mL/min; P < .01) were also associated with lower GFR at 3 months. There was a positive correlation between GFR at admission, GFR preprocurement, and GFR at 3 months (R = 0.32 and R = 0.18 respectively; P < .01). Stepwise regression analysis included chronic damage score, GFR at admission, and donor gender but not donor age as independent predictors of GFR at 3 months (R = 0.50; P < .01). CONCLUSION: Donor structural and functional parameters are independent predictors of renal function at 3 months.     

De novo malignancies after kidney and liver transplantations: experience on 582 consecutive cases

De novo malignancies after transplantation are a growing problem of solid organ transplant recipients, due to longer survival follow-up under chronic immunosuppression. The aim of this study was to analyze a population of 582 consecutive kidney (n = 382) and liver (n = 202) transplant recipients, who survived at least 12 months after transplantation, at a single transplant center for the development of de novo cancers. The incidence of de novo malignancies was 7% after both renal and liver transplantation. The median elapsed time from transplant to the diagnosis of de novo malignancy was 45 months (range 3 to 220) months for kidney and 37 months (range 12 to 101 months) for liver transplants. Skin cancers were the most common within renal recipients, while gastroenteric cancers were more frequently encountered in liver transplants. Oropharyngeal and upper digestive tract tumors were always associated with a history of chronic alcohol consumption in liver recipients. Liver transplant recipients treated for acute rejection had a worse cancer prognosis than patients without rejection 1- and 2-year survivals 83% and 63% versus 36% and 17% (P = .026). The estimated 1- and 2-year survival rates for all types of de novo malignancies were 79% and 66%, including 64% and 51% for solid organ tumors versus 89% and 89% for skin cancers and posttransplant lymphoproliferative disorder (PTLD) (P = .17) in renal transplants and 70% and 42%, including 57% and 28% for solid organ tumors versus 85% and 64% for skin cancers and PTLD (P = .43) in liver transplants respectively.     

The use of liver grafts from donors with bacterial meningitis

BACKGROUND: The shortage of suitable donors for transplantation is a worldwide problem. The use of cadaveric donors with bacterial meningitis may be associated with an increased risk of sepsis. We report the results of orthotopic liver transplantation (OLT) from 33 such donors between 1989 and 1999. METHODS: The hospital records of recipients from cadaveric donors with meningitis (study group) were retrospectively reviewed and compared with matched recipients from cadaveric donors dying from causes other than meningitis (recipient-matched control group). RESULTS: A total of 34 recipients underwent 21 whole, 10 reduced, and 3 split liver transplants from 33 cadaveric donor livers with bacterial meningitis. The donor meningitis pathogens were Neisseria meningitidis (n=14), Streptococcus pneumoniae (n=4), Haemophilus influenzae (n=1), Streptococcus species (n=2), and unknown (n=12). Twenty-seven patients had an elective OLT and seven patients had an emergency OLT. Adequate antimicrobial therapy before organ procurement and after transplant was administrated. The mean posttransplant follow-up was 37 months (range: 1 day-106 months). There was no difference in recipient and graft survival rates between the study and the recipient-matched groups. In the study group, there were no infectious complications caused by the meningeal pathogens. Overall patient survival rates were 79%, 76%, 72%, and 72% at 1, 6, 12, and 60 months, respectively. Graft survival was 77%, 70%, 65%, and 65% at 1, 6, 12, and 60 months, respectively. The survival rate in elective cases was significantly better than emergency cases (P<0.05). CONCLUSION: Liver transplantation from donors with bacterial meningitis is a safe procedure provided both donors and recipients receive adequate antimicrobial therapy.     

Recovery of decreased ability of peripheral-blood mononuclear cells from chronic renal failure to produce interleukin-1 alpha and beta after renal transplantation

The ability of cultured peripheral-blood mononuclear cells (PBMC) to release interleukin-1 alpha and beta (IL-1 alpha, IL-1 beta) in response to concanavalin A (con A) was investigated in patients with chronic renal failure (CRF) and in renal transplant recipients. Mean IL-1 alpha level released by PBMC of healthy subjects (n = 42), CRF patients (n = 42), or transplants 2 months after operation (n = 69) was 152 +/- 103, 110 +/- 80, or 154 +/- 87 pg/5 x 10(5) cells/ml culture, respectively. IL-1 alpha release from PBMC of recipients 2 months after renal transplantation was significantly higher than that of CRF patients (p less than 0.05). Mean IL-1 beta level released by PBMC of healthy subjects (n = 34), CRF (n = 30), or transplants (n = 55) was 223 +/- 159, 135 +/- 129, or 276 +/- 155 pg/5 x 10(5) cells, respectively. Similar to IL-1 alpha, the level in CRF was significantly lower than that in healthy subjects (p less than 0.05). A time course study indicated that the ability of PBMC from transplants to release IL-1 alpha and beta promptly decreased following the operation, possibly owing to prednisolone and ciclosporin immunosuppressive therapy. However, after maintaining a low level for 2-3 weeks, IL-1 release from PBMC gradually increased thereafter. The results were consistent with known characteristics of decreased immunity in CRF states, and further suggested that the decreased ability of PBMC to release IL-1 alpha and beta in response to con A in CRF patients is recovered 2 months after renal transplantation.     

Mild hyperhomocysteinemia is not associated with cardiac allograft coronary disease

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for coronary disease and elevated plasma homocysteine levels have been documented in heart transplant recipients. The aim of this study was to test the hypothesis that homocysteine levels are associated with presence or absence of transplant coronary artery disease. METHODS: Forty-three non-smoking adults were recruited, all of whom had received a heart transplant between 2 and 7 yr previously. All 43 had blood drawn for fasting homocysteine level on the day of presentation. All patients had undergone diagnostic coronary angiography within the past 6 months. RESULTS: For all patients, the average fasting plasma homocysteine level was 17.0+/-SD 6.6 micromol/L with a range from 6.0 to 36.9 micromol/L. Twenty-six patients (60%) had fasting plasma homocysteine levels above 15.0 micromol/L. On the basis of arteriography, patients were categorized as those with angiographically normal (n=22) or abnormal (n=21) coronary arteries. There was no difference in the mean plasma homocysteine level comparing patients with angiographically normal (17.2+/-SD 7.0 micromol/L) to those with abnormal (16.8+/-SD 6.2 micromol/L) coronary arteries. Plasma homocysteine levels increased with increasing plasma creatinine levels (r=0.63, p<0.0001) and with decreasing vitamin B6 levels (r=-0.56, p<0.0001). CONCLUSIONS: Mild hyperhomocysteinemia is a consistent finding among heart transplant recipients. This finding was not associated with transplant coronary artery disease in our patients. The combination of renal dysfunction and vitamin B6 deficiency may explain the unusual prevalence of hyperhomocysteinemia in heart transplant recipients.     

Safety and efficacy of hepatitis A vaccination in liver transplantation recipients

OBJECTIVE: Vaccination against hepatitis A (HAV) has been shown to be safe and effective in healthy subjects and in patients with chronic liver disease (CLD). The safety and efficacy of HAV vaccines in liver transplant (OLT) recipients have not been established. The objective of this study is to assess the safety and efficacy of inactivated hepatitis A vaccine in OLT recipients. METHODS: Thirty-seven HAV seronegative OLT recipients were enrolled. Patients received two doses of vaccine 6 months apart. Postvaccination IgG anti-HAV were determined at 1, 6, and 7 months after the first vaccine dose. Side effects were monitored for 3 days after each vaccination shot. An unvaccinated control group (45 patients) was followed for evidence of seroconversion. Seroconversion rate was also compared with those reported in healthy patients and in patients with chronic liver disease. RESULTS: Testing was available for all the cases at 1 month, and for 26 and 23 patients at 6 and 7 months, respectively. Only 3 of 37 patients (8%) had seroconversion at 1 month. At 6- and 7-month time points, 5 of 26 (19%) and 6 of the 23 (26%) patients had seroconversion, respectively. Vaccine responders had higher total white blood cell count and lymphocyte count and were further out from transplant compared with nonresponders. None of the unvaccinated patients had seroconversion over the follow-up time. Seroconversion rates in OLT recipients were significantly lower than that reported in healthy individuals (P=0.001) or in pre-OLT patients with CLD (P=0.001). All patients tolerated the vaccine well. CONCLUSIONS: HAV vaccination is safe in OLT recipient. Efficacy of HAV vaccination in OLT recipients, as measured by a commercially available enzyme immunoassay, is low and alternative strategies should be developed to improve response rate.     

Renal insufficiency after liver transplantation in the MELD era compared to the pre-MELD era

Abstract:  Because the model for end-stage liver disease (MELD) system for liver allocation gives priority to patients with a higher creatinine, and because pre-transplant renal function is one determinant of post-transplant renal function, this study compares the burden of renal insufficiency in the pre-MELD and MELD eras. Two hundred and elven patients, at our institution, transplanted in the pre-MELD era, were compared to 143 in the MELD era. The GFR (mL/min/1.73 m²) was significantly higher in the MELD cohort than the pre-MELD cohort at time of transplant, discharge, and 12 months post-transplant (95.5 vs. 85.3, p = 0.039; 90.4 vs. 77.4, p = 0.002; 66.8 vs. 60.3, p = 0.026). There was no difference between the two groups in time to renal failure. There was a higher rate of sirolimus use in the MELD era (27% vs. 18%: p = 0.042) and a slightly higher use of kidney–liver transplant in the MELD era (p = 0.056). We did not identify greater renal insufficiency in the MELD era. There was greater renal function in the MELD era at time of transplant, discharge and month 12. Potential explanations include: absence of an increase in renal insufficiency prior to transplant in the MELD era, greater use of renal sparing immunotherapy and growing use of kidney–liver transplant.     

Can the renal transplant patient be really considered as a patient with chronic renal insufficiency?

To assess if the renal transplant patient can really be considered as a patient with chronic renal insufficiency, disease progression and outcomes were compared in both groups. At the same stage of chronic kidney disease (CKD), the deterioration of renal function was slower and graft survival was longer in renal transplant patients. Despite slower rates of kidney function decline, overall patient survival was similar between the two groups. Interestingly, stage 3 adjusted mortality rates were greater in kidney transplant recipients, most likely because of the disease burden (history of end-stage renal disease in renal transplant recipients) and immunosuppression. The three major causes of mortality in transplant patients (cardiovascular, infectious and malignant) may present with specific characteristics in transplant patients. Renal transplantation is thus a specific form of CKD, controlled by 3 factors, a single kidney, immunosuppression and the burden of the disease. The general application of the KDOQI and KDIGO guidelines to kidney transplant recipients requires therefore further evaluation.     

Decreased survival in liver transplant patients requiring chronic dialysis: a Canadian experience

BACKGROUND: Chronic kidney disease is associated with increased mortality among nonrenal organ transplant recipients. End-stage renal disease (ESRD) is a serious complication after orthotopic liver transplantation (OLT). It is unclear if the outcomes of these individuals are different from nontransplant patients requiring dialysis or a kidney transplant. METHODS: We report the incidence of ESRD in OLT recipients and compare their outcomes to matched dialysis controls. We analyzed 4186 patients who received an OLT in Canada between January 1981 and December 2002 and 228 matched, nontransplant, chronic dialysis controls. RESULTS: The incidence of ESRD after OLT was 2.9% (n=120). The unadjusted mortality rate for those who required chronic dialysis was 49.2% compared with 26.8% in those who did not develop kidney failure (P<0.0001). The survival of OLT recipients on dialysis was lower than the matched chronic dialysis cohort (log-rank test, P=0.01). A kidney transplant was performed in 24% of the OLT recipients and 21% of the matched dialysis cohort, and their overall survival was similar. The OLT patients who remained on dialysis had a significantly lower survival when compared with matched dialysis patients who did not receive a kidney transplant (log-rank test, P=0.0002). CONCLUSIONS: Mortality was greater for OLT recipients on dialysis than would be expected from a matched, nontransplant, dialysis cohort. Kidney transplantation may abrogate some of this increased mortality risk.     

Incidence, treatment, and outcome of recurrent focal segmental glomerulosclerosis posttransplantation in 42 allografts in children--a single-center experience

Steroid-resistant FSGS and its recurrence posttransplantation are predominantly seen in children. We report on the largest pediatric transplant population for FSGS with similar numbers of azathioprine- and cyclosporine-treated patients analyzed for recurrence. Of 70 patients with idiopathic FSGS identified over the years 1974-1989, 49 progressed to end-stage renal disease and 28 received 42 transplants (17 live-related donors, 25 cadaveric). Seventeen patients each received one transplant, 9 patients each received two transplants, and one patient each received three and four transplants. The mean age at diagnosis of FSGS was 9.1 +/- 4.2 years, the mean duration of FSGS prior to reaching ESRD was 2.2 +/- 1.3 years, and the mean duration on dialysis prior to transplantation was 9.7 +/- 6.3 months. Primary nonfunction was observed in 2 transplants; in the remaining 40 transplants, 6 recurrences were noted (15%). Recurrences were noted in four AZA and prednisone (n = 22) and two CsA and prednisone (n = 18) recipients. Risk factors analyzed for recurrence included race, age at FSGS, histological and clinical severity of FSGS, classification of FSGS, duration of disease, interval on dialysis, multiple transplants, and HLA matching. Only age at onset of FSGS was predictive of recurrence. The incidence of recurrence was higher in children less than or equal to 6 years of age compared with those over 6 years (P less than .05). All 4 patients receiving AZA and prednisone went on to lose their grafts due to recurrence. Recurrent proteinuria in the 2 CsA and prednisone recipients was controlled by gradually increasing the CsA dose from 15 mg/kg/day to 27 and 35 mg/kg/day. Remission of the nephrotic syndrome was induced within 60 days in both patients. Presently, both grafts are functioning 24 and 16 months posttransplant with serum creatinines of 0.9 and 0.5 mg/dl, respectively. We conclude that recurrence is predominantly seen in very young children and occurs even under CsA immunosuppression. High-dose CsA may control the recurrent proteinuria--however, the long-term outcome of such intense therapy is not known.     

Expression of TGFbeta-1 and Type I TGFbeta-receptor on sequential biopsies of renal transplants with chronic allograft nephropathy

The aim of this study was to determine the expression of transforming growth factor-beta (TGFbeta)-1 and type I TGFbeta-receptor on sequential biopsies from renal transplants with and without chronic allograft nephropathy. Twenty-four renal transplant recipients entered the study. They underwent sequential biopsies performed before (T1: 1.44 +/- 1.2 months) and 6 months after (T2: 15.96 +/- 7.2 months) transplantation. Lesions were graded according to the criteria of the Banff classification. C4d was detected by fluorescence microscopy. Immunohistochemistry was performed in order to identify cells expressing TGFbeta-1 and type I TGFbeta-receptor. In normal renal tissue (n = 4), TGFbeta-1 is expressed by tubular epithelial cells and endothelial cells lining glomerular and peritubular capillaries, whereas type 1 TGFbeta-receptor is expressed by tubular epithelial cells and smooth muscle cells in the media of arteries. In recipients with chronic allograft nephropathy (group 1, n = 14), diffuse epithelial expression of both molecules was found in more patients at T2 than at T1 (42.8% vs 21.4%). In contrast, this pattern of expression remained stable or decreased over time in recipients with long-term normal transplants (group 2, n = 10). Furthermore, type 1 TGFbeta-receptor was detected on the smooth muscle cells of arteries in 12/14 (85.7%) of recipients in group 1 and only in 4/9 (44.4%) of recipients in group 2. No relationship was noticed with regard to C4d deposits. These data suggest that the synthesis of TGFbeta-1 and type I TGFbeta-receptor increases over time in recipients developing chronic allograft nephropathy. Further studies are in progress in order to quantify mRNA of both molecules with real-time polymerase chain reaction.     

Potential effects of 1,25-dihydroxyvitamin D3 in renal transplant recipients

Besides its effects on bone metabolism, calcitriol has an important immunomodulatory effect, which may be protective for a renal allograft. Therefore, we evaluated the effects of oral calcitriol administration in renal transplant recipients. One hundred ten renal transplant recipients (78 men, 32 women) of mean age 35.2 +/- 11.4 years and mean posttransplantation follow-up of 50.7 +/- 22.9 months were entered into the study. Patients in group 1 (n = 57) received calcitriol therapy and patients in group 2 (n = 53) did not. The mean start of calcitriol therapy was 22.4 +/- 19.1 months posttransplantation. We restrospectively collected pretransplantation and posttransplantation laboratory and clinical data as well as creatinine levels before and after the initiation of calcitriol therapy at 6-month intervals for 2 successive years. There were no significant differences in terms of age, gender, immunosuppression, bone mineral densitometry, and follow-up. Our results showed that patients in group 1 had lower pretransplantation and postransplantation body mass index (P < .03; P < .03, respectively), lower posttransplantation third year parathyroid hormone levels (P < .02), and lower requirements for pulse steroid doses (P < .04). Using Friedman repeated measures variance test to analyze the effect of calcitriol, the increase in creatinine levels was significantly lower in group 1 (P < .04). There was no significant difference between follow-up time and calcitriol dose (P > .05). In conclusion, calcitriol therapy may reduce the rate of loss of renal function among patients receiving renal transplants.     

Renal histological lesions and outcome in liver transplant recipients

Tsapenko M, El‐Zoghby ZM, Sethi S. Renal histological lesions and outcome in liver transplant recipients.
Clin Transplant 2012: 26: E48–E54.
© 2011 John Wiley & Sons A/S. Abstract: Background: Chronic kidney disease in liver transplant (OLT) recipients is often attributed to calcineurin inhibitors (CNI) toxicity, but little is known about the spectrum of their renal histological lesions. Methods: Between 1988 and 2008, 1698 OLTs were performed in our center. We retrospectively analyzed clinical and histological data on 23 recipients (1.4%) referred for kidney biopsy (KB). Results: Median age at OLT was 50.2 yr, 65.2% were men, 30.4% had hepatitis C, and 95.7% were given CNI. KB was performed 6.9 yr (median) post‐OLT. Median creatinine was 1 mg/dL pre‐OLT and 2.2 mg/dL at KB. Main pathological diagnoses were focal segmental and global glomerulosclerosis (n = 8, 34.8%), glomerular diseases (7, 30.4%), CNI toxicity (2, 8.7%), and diabetic nephropathy (2, 8.7%). Moderate/severe interstitial fibrosis, tubular atrophy, arteriosclerosis, and hyalinosis were present in 47.8%, 43.5%, 60.9%, and 56.5%, respectively. Twelve patients (52.5%) reached end‐stage renal disease (ESRD) and 17 (73.9%) died. Death was more common among those reaching ESRD, but the difference was not significant (83.3% vs. 63.6%, p = 0.37). Conclusion: Renal histology is variable and not limited to CNI toxicity in OLT recipients referred for KB. Whether management based on KB findings can directly improve outcomes remains unclear.     

Estimated donor glomerular filtration rate is the most important donor characteristic predicting graft function in recipients of kidneys from live donors

We hypothesized that predictors of outcome in live donor transplants were likely to differ significantly from deceased donor transplants, in which cold ischaemia time, cause of donor death and other donor factors are the most important predictors. The primary aim was to explore the independent predictors of graft function in recipients of live donor kidneys (LDK). Our secondary aim was to determine which donor characteristics are the most useful predictors. A retrospective analysis was undertaken of all patients receiving live donor (n = 206) renal transplants at our institution between 31 May 1994 and 15 October 2002. Twelve patients were excluded from the analysis. Follow-up was completed on all patients until graft loss, death or 22 November 2003. We explored predictors of Nankivell glomerular filtration rate (GFR) at 6 months by multivariate linear regression. In the 194 patients studied, the mean recipient 6-month Nankivell GFR was 59 +/- 15 ml/min/1.73 m(2). Independent predictors of recipient GFR in at 6 months were donor Cockcroft-Gault GFR (CrCl; beta 0.16; CI 0.13 to 0.29; P < 0.0001), steroid resistant rejection (beta-6.07; CI -12.05 to -0.09; P = 0.006) and delayed graft function (DGF) (beta-10.0; CI -19.52 to -0.49; P = 0.039). Renal function in an LDK transplant recipients is predicted by donor GFR, episodes of steroid resistant rejection and DGF. Importantly, donor Cockcroft-Gault GFR is the most important characteristic for predicting the recipient renal function.     

Acute renal failure in the first 100 orthotopic liver transplant patients in Southern Iran

Postoperative acute renal failure is a frequent and serious medical complication following orthotopic liver transplant. Here, we report our experiences with liver transplant recipients who developed acute renal failure in the early period following orthotopic liver transplant. Among 100 liver transplants performed between April 1993 and January 2004, we retrospectively analyzed 91 patients (mean age, 29.9 +/- 14.0 years) who had undergone orthotopic liver transplant. The underlying causes of liver failure were cryptogenic liver cirrhosis (n=27), viral hepatitis (n= 21) (hepatitis-B-related liver cirrhosis [n=13], hepatitis-C-related liver cirrhosis [n=7], and hepatitis-B- and C-related liver cirrhosis [n=1]), autoimmune hepatitis (n=18), Wilson's disease (n=10), primary sclerosing cholangitis (n=8), biliary atresia (n=3), Budd-Chiari syndrome (n=2), and primary biliary cirrhosis (n=2). The immunosuppressive regimen included mycophenolate mofetil (azathioprine for 10 patients), cyclosporine, and steroids. Six patients received a combination of tacrolimus and steroids. Ten patients (10.9%) experienced acute renal failure, 7 (70%) were men, and none of them required renal replacement therapy and/or died. Four patients were diagnosed as having cryptogenic liver cirrhosis; 2 with hepatitis-C-related liver cirrhosis, 2 with autoimmune liver cirrhosis; 1 with primary biliary cirrhosis; and 1 hepatitis-B-related liver cirrhosis. Six patients were Child-Pugh's classification C, and the others were B. The rate of postoperative acute renal failure in our patients was relatively low when compared with other series, and our outcomes were good.