Evaluation of Bone Mineral Metabolism After Liver Transplantation by Bone Mineral Densitometry and Biochemical Markers

AimThis study aimed to evaluate the course of bone and mineral metabolism after liver transplantation (LT) in patients with chronic liver disease.MethodsOne hundred four patients who had undergone LT and had a minimum of 6 months of follow-up after LT were included in this prospective cohort study. The following parameters were evaluated for each patient: preoperative and postoperative (postoperative day [POD]30, POD90, POD180) osteocalcin, bone-specific alkaline phosphatase (BALP), type 1 collagen, beta-C-terminal end telopeptide (β-CTx), vitamin D, parathyroid hormone (PTH), ALP, calcium, phosphate, sedimentation, and bone mineral densitometer scores (L2, L4, L total, and F total). The parameters were compared in terms of sex, presence of liver tumor (hepatocellular carcinoma [HCC; n = 19] vs non-HCC [n = 85]), and presence of autoimmune liver disease (autoimmune liver disease [ALD; n = 8] vs non-ALD [n = 96]).ResultsThe median age of the patients (n = 81 men and n = 23 women) was 52 years (95% CI, 50-56). There was a significant change in the defined time intervals in parameters such as osteocalcin (P < .001), BALP (P < .001), β-CTx (P < .001), vitamin D (P < .001), PTH (P < .001), ALP (P = .001), calcium (P < .001), phosphate (P = .001), L2 (P = .038), L total (P = .026), and F total (P < .001) scores. There was a significant difference in POD90 ALP (P = .033), POD180 calcium (P = .011), POD180 phosphate (P = .011), preoperative sedimentation (P = .032), and POD180 F total (P = .013) scores between both sexes. There was a significant difference in POD180 osteocalcin (P = .023), POD180 β-CTx (P = .017), and preOP calcium (P = .003) among the HCC and non-HCC groups. Furthermore, we found significant differences in preoperative ALP (P = .008), preoperative sedimentation (P = .019), POD90 (P = .037) and POD180 L2 (P = .005) scores, preoperative (P = .049) and POD180 L4 (P = .017), and POD180 L total (P = .010) and F total (P = .022) scores between the patients with and without ALD.ConclusionThis study shows that the bone and mineral metabolism of the LT recipients was negatively affected after LT. In addition, we showed that bone and mineral metabolism was more prominent in patients with HCC, and bone mineral density scores were higher in patients with ALD.     

Changes in Bone Mineral Density After Kidney Transplantation

Background

Numerous studies have shown that osteoporosis is common in kidney transplant recipients. However, the change in bone mineral density after kidney transplantation (KT) is not fully understood.

Evaluation of Long-Term Kidney Function Following Orthotopic Heart Transplantation

IntroductionAcute impairment of kidney function in patients with heart failure and heart transplantation is a frequent condition. However, the impact of the transplant on long-term kidney function remains controversial.MethodsThis study describes a cohort of patients who received a heart transplant in a reference hospital between 2005 and 2019. Glomerular filtration rate during follow-up was calculated at 0, 6,12, 24, and 60 months using the Cockcroft-Gault and MDRD (modification of diet in renal disease study) equations. To identify changes we compared glomerular filtration rate (GFR) at baseline with measurements over time after heart transplantation, using a paired t test and a longitudinal model of Generalized Estimating Equations (GEE).ResultsForty-four patients were included. The mean of baseline GFR was 67.9 ± 1.3 mL/min. A triple immunosuppressive therapy scheme was used with cyclosporine/tacrolimus, mycophenolate mofetil, and steroid, with progressive dose reduction. After adjusting for multiple variables, we found no reduction of GFR over time with the GEE model. There was no significant difference in GFR using Cockcroft-Gault equation at 6 (mean difference [MD] 4.46; confidence interval [CI] –2.1 to 11.09; P = 0.18), 12 (MD 1.65, CI -4.5 to 7.82; P = 0.59), 36 (MD 0.69; CI –6.04 to 7.43; P = 0.83), and 60 months (MD 0.62; CI –5.5 to 6.79; P = 0.83). Similar findings were found using MDRD equation.ConclusionsThere is no significant GFR decline between the time of heart transplantation and a follow-up at 60 months. New studies are needed to evaluate changes in renal function beyond this timeframe.     

Evaluation of Cinacalcet HCl Treatment After Kidney Transplantation

Background

Hyperparathyroidism often remains or develops after kidney transplantation. Vitamin D sterol used as treatment for an elevated parathyroid hormone (PTH) level and associated bone disease may be contraindicated due to hypercalcemia. The calcimimetic cinacalcet HCl (cinacalcet), which lowers PTH and calcium (Ca) in chronic kidney disease patients, may represent an alternate therapeutic modality.

Methods

This multicenter, retrospective, observational study examined 41 kidney transplant patients receiving cinacalcet for ≥3 months starting ≥3 months posttransplantation. Levels of intact PTH, Ca, and phosphorus (P) were examined during the assessment phase (3-6 months after initiation).

Results

Median PTH decreased 21.8% during the assessment phase (P < .001), with 32.5% of patients exhibiting a ≥30% decrease in PTH from baseline. Median Ca decreased 6.8% (P < .0001). Median serum P rose 10.0% (P = .0124), but remained within normal limits. The estimated glomerular filtration rate was stable throughout the study.

Conclusions

Cinacalcet may be useful for the treatment of hyperparathyroidism after kidney transplantation. Randomized, prospectively designed clinical trials are required to confirm these results.     

Long-Term Outcomes in Kidney Transplantation From Expanded-Criteria Donors After Circulatory Death

The number of recipients waiting for a transplant is increasing. In Japan, there is more frequent use of organs from expanded-criteria donors (ECDs) after circulatory death. We retrospectively analyzed long-term outcomes of kidney transplantation (KT) from expanded-criteria donation after circulatory death (DCD). From 1995 to 2013, 97 cases of KT from DCD donors were performed in our department. Death-censored graft survival rates of ECD kidneys (n = 50) versus standard-criteria deceased-donor (SCD) kidneys (n = 47) for 1, 5, and 10 years after transplantation were 84.0% vs 97.9%, 74.8% vs 95.6%, and 70.2% vs 81.8%, respectively. No significant difference was found between the 2 groups (P = .102). Kidneys from donors with a history of hypertension (HTN) and cerebrovascular events (CVE) and contribution from older donors had significantly lower 10-year graft survival rates (P values of .010, .036, and .050, respectively). Cox proportional hazard regression analyses showed donor age to be significantly associated with long-term graft survival independently from other factors. These results suggest that ECD kidneys remain an acceptable alternative to dialysis under certain conditions. Increased donor age was a significant risk factor determining long-term graft function. Moreover, comorbidities of HTN and CVE could become significant risk factors, especially in older donors.     

FK-506对肾移植术后患者糖代谢的影响

目的观察肾移植术后应用他克莫司（FK-506）对患者糖代谢的影响。方法按知情同意将107例无糖尿病痛史的肾移植患者分为FK-506组（38例），术后应用FK-506；环孢素A（CsA）组（69例），术后应用CsA。对两组患者的血糖和OGTT进行定时、动态监测。比较两组高血糖及肾移植后糖尿病（PTDM）发生率。结果FK-506组11例（28．95％）出现高血糖，其中8例（21.05％）确诊为PTDM；CsA组8例（11．59％）出现高血糖，其中5例（7．25％）确诊为PTDM。FK-506组高血糖发生率显著高于CsA组（P〈0．05），但两组PTDM发生率比较，差异无显著性意义（P〉0．05）。结论FK-506有高血糖的不良反应，护理时应对血糖进行严密监测以早发现、早治疗。     

FK-506对肾移植术后患者糖代谢的影响

目的 观察肾移植术后应用他克莫司(FK-506)对患者糖代谢的影响.方法 按知情同意将107例无糖尿病病史的肾移植患者分为FK-506组(38例),术后应用FK-506;环孢素A(CsA)组(69例),术后应用CsA.对两组患者的血糖和OGTT进行定时、动态监测.比较两组高血糖及肾移植后糖尿病(PTDM)发生率.结果 FK-506组11例(28.95%)出现高血糖,其中8例(21.05%)确诊为PTDM;CsA组8例(11.59%)出现高血糖,其中5例(7.25%)确诊为PTDM.FK-506组高血糖发生率显著高于CsA组(P＜0.05),但两组PTDM发生率比较,差异无显著性意义(P＞0.05).结论 FK-506有高血糖的不良反应,护理时应对血糖进行严密监测以早发现、早治疗.     

Pregnancy After Kidney Transplantation

BackgroundPregnancy after kidney transplantation is an uncommon event. In addition to the risk to the child and the mother, pregnancy has a certain risk for the transplanted kidney.MethodsWe made a retrospective analysis of pregnancy and kidney function over a 49-year period in women with transplanted kidneys monitored at the National Transplant Centre, University Medical Centre Ljubljana, Ljubljana, Slovenia.ResultsWe analyzed 22 pregnancies in 18 women (26-39 years old) 78 ± 37 months after transplantation. Serum creatinine before conception was 92 ± 26 μmol/L; 3 years after delivery, it was 117 ± 67 μmol/L. There were no rejections during pregnancy. Three rejections occurred in the first 9 months after delivery. The median duration of pregnancies was 37 weeks. Preeclampsia occurred in 4 women and severe eclampsia occurred in 2 women. In 19 cases, delivery was by caesarean section. One child was born with trisomy of chromosome 21 and 3 children were born with minor congenital anomalies.ConclusionsRenal function and proteinuria did not deteriorate 3 years after pregnancy, even after 2 pregnancies. Rejections in the early post-pregnancy period were common. Preeclampsia was more frequent than in the average population. The incidence of major congenital anomalies was comparable to that seen in pregnant women without immunosuppression.     

Contrast-Enhanced Ultrasonography in the Early Period After Kidney Transplantation Predicts Long-Term Allograft Function

IntroductionReal-time contrast-enhanced sonography (CES) can assess microvascular tissue perfusion using gas-filled microbubbles. The purpose of the study was to evaluate the feasibility of early CES in predicting long-term kidney allograft function in comparison to color Doppler ultrasonography (CDUS).MethodsWe prospectively studied 68 consecutive kidney transplant recipients using CES and conventional CDUS investigation 1 week after transplantation. Transplant tissue perfusion imaging was performed by low-power imaging during intravenous administration of the sonocontrast SonoVue. Renal tissue perfusion was assessed quantitatively using flash replenishment kinetics of microbubbles to estimate renal blood flow (RBF). The obtained sonography values were correlated with clinical data 1 week up to 1 year after transplantation.ResultsIn contrast with conventional CDUS resistive indices, RBF estimated by CES 1 week posttransplantation significantly correlated with kidney function after 1 year (r = 0.67; P < .001). Determination of RBF by CES revealed a significant correlation with donor age but not recipient age, whereas conventional CDUS resistive index was significantly correlated to recipient age (r = 0.54; P < .001) but not donor age. Furthermore RBF was associated with vascular fibrosis and intimal thickening of the engraftment biopsies.ConclusionThis is the first prospective study demonstrating the prognostic value of CES early after kidney transplantation. In contrast with CDUS, CES reveals information about kidney allograft perfusion independent of recipient vascular compliance.     

Recurrent Glomerulonephritis After Kidney Transplantation

Thirty to fifty percent of kidney transplant recipients have glomerular diseases as the underlying causes of end-stage renal failure. While recurrence of glomerulonephritis is an important cause of late renal allograft failure, the risk factors for recurrence are largely unknown or imprecise and prediction remains difficult. Recurrent disease usually presents with similar manifestations as the native disease. With regard to treatment of recurrent glomerular disease in the renal allograft, plasma exchange may be effective in reducing proteinuria in patients with early recurrence of focal and segmental glomerulosclerosis, but immunosuppressive therapy is generally ineffective in the prevention or treatment of recurrent disease. General supportive measures including strict blood pressure control and inhibition or blockade of the rennin-angiotensin pathway are helpful in retarding the rate of deterioration in renal allograft function. Despite the risk of recurrence, kidney transplantation following primary glomerulonephritides enjoys graft and patient survival rates comparable to other causes of end-stage renal failure. With a few exceptions, living related renal transplantation is not contraindicated in view of the favorable outcome and the donor shortage. This review discusses commonly encountered recurrent glomerulonephritides, with special emphasis on the influence of post-transplant prophylactic immunosuppression and emerging treatments.     

Thrombotic Microangiopathy After Kidney Transplantation

Thrombotic microangiopathy (TMA) is a severe complication of kidney transplantation that often causes graft failure. TMA may occur de novo, often triggered by immunosuppressive drugs and acute antibody‐mediated rejection, or recur in patients with previous history of hemolytic uremic syndrome (HUS). Recurrent TMA is very rare in patients who had developed end‐stage renal failure following HUS caused by Shiga‐toxin producing E. scherichia coli, whereas disease recurrence is common in patients with atypical HUS (aHUS). The underlying genetic defect greatly impacts the risk of posttransplant recurrence in aHUS. Indeed recurrence is almost the rule in patients with mutations in genes encoding factor H or factor I, whereas patients with a mutation in membrane‐cofactor‐protein gene have a good transplant outcome. Prophylactic and therapeutic options for posttransplant TMA, including plasma therapy, combined kidney and liver transplantation and targeted complement inhibitors are discussed in this review.     

Multidrug-Resistance 1 Gene Single-Nucleotide Polymorphisms Do Not Influence Long-Term Graft Survival After Kidney Transplantation

Background

The single-nucleotide polymorphisms (SNPs) of the Multidrug resistance 1 (MDR1) gene have been associated with changes in the pharmacokinetics of cyclosporine (CsA) and tacrolimus (FK506). Our aim was investigate the influence of MDR1 SNPs on long-term graft survival in a population of kidney transplant recipients.

Methods

We retrospectively analyzed 154 patients; they were genotyped for the SNPs C1236T, G2677T/A, and C3435T and evaluated for the influence of those 3 SNPs on CsA or FK506 pharmacokinetics and on long-term graft survival.

Results

Thirty-one patients were wild-type for C1236T, G2677T/A, and C3435T polymorphisms (group A), 76 patients had ≥1 heterozygous mutations (group B), and 47 patients had ≥1 homozygous mutations (group C). CsA-receiving patients in group C needed a significantly higher oral dose than patients in groups B and A (P = .02). No differences in FK506 trough level nor in oral dose taken were observed in FK506-receiving patients. Kaplan-Meier analysis did not show survival differences in the 3 groups, and Cox proportional hazards model confirmed that the MDR1 SNPs did not represent a risk for graft loss.

Conclusions

Pretransplantation determination of MDR1 SNPs may be helpful to optimize the starting dose of CsA but can not predict long-term graft survival.     

Pregnancy Outcomes After Kidney Transplantation and Long-Term Evolution of Children: A Single Center Experience

BackgroundPregnancies in women who underwent kidney transplants are at high risk compared with the general population.MethodsIn this study, we aimed to retrospectively assess the obstetrical complications, delivery outcomes, and impact of pregnancy on kidney allograft function in a single-center cohort of kidney transplant recipients (KTRs). We provide data regarding the long-term evolution of children.ResultsThirty-two KTRs underwent a total of 57 pregnancies between 1994 and 2010. Fourteen pregnancies (24 %) did not survive caused by miscarriages (n = 9), stillborn (n = 1), ectopic pregnancies (n = 2), and medical abortion (n = 2). Live birth occurred in 76% of pregnancies. Delivery was by cesarean in 66%. The mean gestational age was 30.45 ± 11.3 weeks and 65% of newborns were premature. A low birth weight <2500g was noted in 46%. Obstetric complications were de novo hypertension in 4%, pre-eclampsia in 9%, and gestational diabetes in 2%. The 5- and 10-year post-delivery death-censored graft loss rates were 3.1% and 12.5%, respectively. Data on 21 children were collected via a self-questionnaire. After a median follow-up time of 17 years, they appeared in good medical and psychological health. None of them suffered from chronic disease (especially uronephrological condition) or was taking chronic medication.ConclusionsLong-term evolution of children born to women who underwent kidney transplants seems favorable. Pregnancies in KTRs are successful in two-thirds of cases but are at increased risk of prematurity, delivery by cesarean, and low birth weight.     

The First Year Renal Function as a Predictor of Long-Term Graft Survival After Kidney Transplantation

This study examined the impact of graft function at the end of the first year after kidney transplantation on long-term graft survival. We analyzed the roles of serum creatinine (Scr) and other variables as predictors of graft survival among 235 adult kidney transplant patients. The subjects were divided into 3 groups according to their Scr at the end of the first year: group 1, Scr < 100 μmol/L; group 2, 100 μmol/L ≤ Scr ≤ 150 μmol/L; and group 3, Scr >150 μmol/L. The annual rate of graft loss of 0.7% (95% confidence interval [CI], 0.63-0.77) in group 1, was lower than those in group 2 (2.1%; 95% CI, 2.02-2.18; P < .0001) and group 3 (6%; 5.74-6.26; P < .0001). Regression analysis showed the role of recipient age at the time of operation, and Scr level at the end of the first year to be independent predictors of graft loss. Graft survival was not influenced by any other studied parameter, including donor age, year of procedure, warm ischemia time, history of acute tubular necrosis, and occurrence of an acute rejection episode. We conclude that the 1-year Scr value predicts long-term renal graft survival, representing a simple, practical tool to identify recipients with an high risk for late graft failure.     

Long-term Allograft Survival After Kidney Transplantation

BackgroundTechnical and medical advances over the past few years have produced an important increase in the functionality of renal allografts. The aim of this study was to identify the factors associated with allograft survival 15 years after transplantation in our series.MethodsA retrospective study of kidney transplantations was carried out at Reina Sofia Hospital in Cordoba from February 1979 to December 1997, with follow-up through June 2012. A subanalysis of the series was undertaken, and Kaplan-Meier analysis and Cox proportional hazards model regression used to achieve the main objective of the study.ResultsA total of 487 renal allografts with a mean follow-up of 114 months were studied, of which 37% (n = 180) survived for >15 years. Of the 180 patients, the main causes of graft failure were chronic allograft nephropathy in 29 (66%) and patient death in 13 (29.5%). Multivariate analysis identified the number of HLA mismatches (hazard ratio [HR] 1.25, 95% CI 1.01–1.56), panel reactive antibodies (HR 2.61, 95% CI 1.28–5.26), and delayed graft function (HR 11.25, 95% CI 1.33–95.28) as being significantly associated with graft loss after 15 years.ConclusionsThe high immunologic risk of the patients was independently associated with graft loss. Delayed graft function was the most important factor in the speed of graft failure beyond 15 years.     

Long-Term Results of Kidney Transplantation Between HLA-Identical Siblings

Long-term data on HLA-identical renal transplants are scarce, and the advantages of using cyclosporine (CsA) over azathioprine (AZA) have yet to be elucidated. In 68 recipients from HLA-identical donors (37 under AZA-steroids and 31 under CsA-steroids), we estimated the graft and patient survival to posttransplant 120 months, and compared the results between patients on different protocols. Episodes of rejection, causes of graft loss or patient death, and long-term complications were also compared retrospectively. The 10-year patient/graft survivals were comparable: 82.7/67.6% for the AZA and 78.4/63.5% for the CsA patients. The incidence of acute rejection during the first year after transplant was also comparable. We lost 25 grafts. The major causes of graft loss were patient death (7/13 in AZA and 5/12 in CsA patients) and chronic rejection (3/13 in AZA and 3/12 in CsA patients). Four grafts were lost due to poor compliance. We lost 12 patients due mostly to cerebrovascular disease and infections. There was no difference in the prevalence of complications between patients. In conclusion, the long-term outcome was excellent in this subgroup of transplant patients. We could not find any advantages of using CsA over AZA in these patients after a long-term follow-up. To achieve better results, continued attention should be paid to the prevention of poor compliance and complications. Received: June 5, 2000 / Accepted: September 26, 2000