Outcomes of bisphosphonate therapy in kidney transplant recipients: a systematic review and meta‐analysis

Mineral and bone disorders that precede kidney transplantation are exacerbated in the post‐transplant setting by tertiary hyperparathyroidism and immunosuppressive regimens. Bone mineral density (BMD) decreases following transplantation, leading to increased fracture risk. The effect of bisphosphonates on fracture is unknown. The aim of this study was to update estimates of change in BMD and fracture rates in bisphosphonate‐treated kidney transplant recipients through meta‐analysis. Studies comparing bisphosphonate therapy to standard of care were included if follow‐up duration was more than 6 months. We performed random‐effects meta‐analysis to determine the effect of bisphosphonates on lumbar spine and femoral neck BMD and fracture rates. Bisphosphonates improved femoral neck and lumbar spine BMD compared with controls (0.055 g/cm², 95% CI 0.012–0.099 and 0.053 g/cm², 95% CI 0.032–0.074, respectively) without adversely affecting serum creatinine or calcium. This corresponded to an unweighted improvement in BMD of 6.0% and 7.4%, respectively. There was no difference in fracture incidence in the two groups. Bisphosphonate therapy in kidney transplant recipients is associated with a statistically significant improvement in BMD at the lumbar spine and femoral neck. There was no difference in fracture incidence. Bisphosphonates did not adversely affect allograft dysfunction or serum calcium levels.     

Underweight and obesity increase the risk of mortality after lung transplantation: a systematic review and meta‐analysis

Many studies have found an association between abnormal body mass index (BMI) and poor outcomes among lung transplant recipients. We performed a systematic review and meta‐analysis to identify outcomes associated with an abnormal pretransplant BMI after lung transplantation (LTx). The MEDLINE and EMBASE databases were searched from inception to May 2015 with focus on original observational studies with post‐transplant survival data in candidates with abnormal BMI (underweight, overweight, or obese). We performed meta‐analyses examining survival and primary graft dysfunction after LTx. We identified 866 citations; 13 observational cohort studies involving 40 742 participants met our inclusion criteria for systematic review. Seven of the 13 were included in the meta‐analysis. There was a significant risk of mortality after LTx in candidates with underweight and obesity (underweight versus normal, relative risk [RR] 1.36, 95% confidence interval [CI] 1.11–1.66, I² = 0%; obesity vs. normal, RR 1.90, 95% CI 1.45–2.56, I² = 0%; overweight vs. normal, RR 1.36, 95% CI 1.11–1.66, I² = 0). There was also a significant risk of primary graft dysfunction in obese (RR 1.92, 95% CI 1.39–2.65, I² = 0%) and overweight (RR 1.72, 95% CI, 1.32–2.24, I² = 0%) candidates. Lung transplant candidates who are underweight or obese have a higher risk of post‐transplant mortality than recipients with a normal BMI.     

Bisphosphonates for the Prevention of Fractures in Osteogenesis Imperfecta: Meta‐Analysis of Placebo‐Controlled Trials

Bisphosphonates are widely used off‐label in the treatment of patients with osteogenesis imperfecta (OI) with the intention of reducing the risk of fracture. Although there is strong evidence that bisphosphonates increase bone mineral density in osteogenesis imperfecta, the effects on fracture occurrence have been inconsistent. The aim of this study was to gain a better insight into the effects of bisphosphonate therapy on fracture risk in patients with osteogenesis imperfecta by conducting a meta‐analysis of randomized controlled trials in which fractures were a reported endpoint. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials in which the effects of bisphosphonates on fracture risk in osteogenesis imperfecta were compared with placebo and conducted a meta‐analysis of these studies using standard methods. Heterogeneity was assessed using the I² statistic. Six eligible studies were identified involving 424 subjects with 751 patient‐years of follow‐up. The proportion of patients who experienced a fracture was not significantly reduced by bisphosphonate therapy (Relative Risk [RR] = 0.83 [95% confidence interval 0.69–1.01], p = 0.06) with no heterogeneity between studies (I² = 0). The fracture rate was reduced by bisphosphonate treatment when all studies were considered (RR = 0.71 [0.52–0.96], p = 0.02), but with considerable heterogeneity (I² = 36%) explained by one study where a small number of patients in the placebo group experienced a large number of fractures. When this study was excluded, the effects of bisphosphonates on fracture rate was not significant (RR = 0.79 [0.61–1.02], p = 0.07, I² = 0%). We conclude that the effects of bisphosphonates on fracture prevention in osteogenesis imperfecta are inconclusive. Adequately powered trials with a fracture endpoint are needed to further investigate the risks and benefits of bisphosphonates in this condition. © 2014 American Society for Bone and Mineral Research.     

Bisphosphonates for prevention of osteopenia in kidney-transplant recipients: a systematic review of randomized controlled trials

Summary

We conducted a systematic review of randomized controlled trials (RCTs) of bisphosphonates for the prevention of osteopenia in kidney-transplant recipients. Bisphosphonates improved bone mineral density at the lumbar spine and femoral neck after 12 months. However, additional well-designed RCTs are required to determine the optimal treatment strategy.Osteopenic–osteoporotic syndrome is a bone complication of renal transplantation. Bisphosphonates, calcitonin, and vitamin D analogs may be used to prevent or treat osteoporosis or bone loss after renal transplantation. However, there is currently no widely recognized strategy for the prevention of corticosteroid-induced osteoporosis. This study aims to assess the available evidence to guide the targeted use of bisphosphonates for reducing osteoporosis and bone loss in renal-transplant recipients. We searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE for randomized controlled trials of bisphosphonates for osteoporosis or bone loss after renal transplantation. A total of 352 abstracts were identified, of which 55 were considered for evaluation and 9 were included in the final analysis. The primary outcome measure was change in the bone mineral density (BMD) of the lumbar spine and femoral neck after 12 months. Data extraction was performed independently by two investigators. BMD at the lumbar spine was improved after treatment with bisphosphonates [9 trials; 418 patients; weighted mean difference (WMD), 0.61; 95 % confidence interval (CI), 0.16–1.06]. Eight trials (406 patients) that reported changes in BMD at the femoral neck also showed improved outcomes after treatment with bisphosphonates (WMD, 0.06; 95 % CI, 0.03–0.09). Bisphosphonates improve BMD at the lumbar spine and femoral neck after 12 months in renal-transplant recipients.

     

The effectiveness and safety of rituximab as induction therapy in ABO-compatible non-sensitized renal transplantation: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background: The objective of this systematic review and meta-analysis was to evaluate the effectiveness and safety of rituximab as induction therapy in ABO-compatible, non-sensitized renal transplantation. Methods: A literature search for randomized controlled trials (RCTs) was performed from inception through February 2015. Studies that reported relative risks or hazard ratios comparing the risks of biopsy-proven acute rejection (BPAR), graft loss, leukopenia, infection or mortality in ABO-compatible, non-sensitized renal transplant recipients who received rituximab as induction therapy versus controls were included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. Results: Four RCTs with 480 patients were included in the meta-analysis. Pooled RR of BPAR in recipients with rituximab induction was 0.90 (95% CI 0.50–1.60). Compared to placebo, the risk of BPAR in rituximab group was 0.76 (95% CI 0.51–1.14, I²?=?0). The risk of leukopenia was increased in rituximab group with the pooled RR of 8.22 (95% CI 2.08–32.47). There were no statistical differences in the risks of infection, graft loss and mortality at 3–6 months after transplantation with pool RRs of 1.02 (95% CI 0.85–1.21), 0.55 (95% CI 0.21–1.48) and 0.58 (95% CI 0.17–1.99), respectively. Conclusion: This meta-analysis demonstrated insignificant reduced risks of BPAR, graft loss or mortality among in ABO-compatible, non-sensitized renal transplant recipients with rituximab induction. Although rituximab induction significantly increases risk of leukopenia, it appears to be safe with no significant risk of infection.     

Bisphosphonates and bone fractures in long-term kidney transplant recipients

BACKGROUND: There is little information on the role of bisphosphonates and bone mineral density (BMD) measurements for the follow-up and management of bone loss and fractures in long-term kidney transplant recipients. METHODS: To address this question, we retrospectively studied 554 patients who had two BMD measurements after the first year posttransplant and compared outcomes in patients treated, or not with bisphosphonates between the two BMD assessments. Kaplan-Meier survival and stepwise Cox regression analyses were performed to examine fracture-free survival rates and the risk-factors associated with fractures. RESULTS: The average time (+/-SE) between transplant and the first BMD was 1.2+/-0.05 years. The time interval between the two BMD measurements was 2.5+/-0.05 years. There were 239 and 315 patients in the no-bisphosphonate and bisphosphonate groups, respectively. Treatment was associated with significant preservation of bone loss at the femoral neck (HR 1.56, 95% CI 1.21-2.06, P=0.0007). However, there was no association between bone loss at the femoral neck and fractures regardless of bisphosphonate therapy. Stepwise Cox regression analyses showed that type-1 diabetes, baseline femoral neck T-score, interleukin-2 receptor blockade, and proteinuria (HR 2.02, 0.69, 0.4, 1.23 respectively, P<0.01), but not bisphosphonates, were associated with the risk of fracture. CONCLUSIONS: Bisphosphonates may prevent bone loss in long-term kidney transplant recipients. However, these data suggest a limited role for the initiation of therapy after the first posttransplant year to prevent fractures.     

Clinical predictors of incipient vertebral fractures and bone mineral density in kidney transplant patients

Purpose

Kidney transplant recipients are prone to metabolic bone diseases and consequent fractures. This study aimed to evaluate the incidence of incipient vertebral fractures, osteopenia, osteoporosis, and the clinical factors associated with incipient vertebral fractures in a group of kidney transplant patients.

Methods

Two hundred sixty-four patients (F/M 124/140, 45.3 ± 13 years) who had undergone kidney transplantation in tertiary care centers were included. Vertebral fractures were assessed semiquantitatively using conventional thoracolumbar lateral radiography in 202 of the patients.

Results

Vertebral fractures were observed in 56.4% (n = 114) of the study group. The frequency of osteoporosis was 20.0% (53 of 264 patients), and osteopenia was 35.6% (94 of 264 patients). Bone mineral density (BMD) levels were in the normal range in 40.3% (n = 46) of the subjects with vertebral fractures. It was in the osteoporotic range in 20.1% (n = 23) and the osteopenic range in 40.3% (n = 46). Vertebral fractures were associated with age, duration of hemodialysis, BMI, and femoral neck Z score (R² 37.8%, p = 0.027).

Conclusion

As incipient vertebral fractures can be observed in patients with normal BMD levels in kidney transplant recipients, conventional X-ray screening for vertebral fractures may be beneficial for a proper therapy decision of metabolic bone disease in kidney transplant recipients.

     

Hypothermic Machine Perfusion Versus Static Cold Storage in Deceased Donor Kidney Transplantation: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Static cold storage (SCS) and hypothermic machine perfusion (HMP) are two primary options for renal allograft preservation. Compared with SCS, HMP decreased the incidence of delayed graft function (DGF) and protected graft function. However, more evidence is still needed to prove the advantages of the HMP. In this study, the outcomes of kidney grafts from the two preservation methods were compared by conducting a systematic review and meta‐analysis. Randomized controlled trials (RCTs) comparing the effect of hypothermic machine perfusion and static cold storage in deceased donor kidney transplantation were identified through searches of the MEDLINE, EMBASE, and Cochrane databases between January 1, 1980 and December 30, 2017. The primary endpoints were delayed graft function and graft survival. Secondary endpoints included primary non‐function (PNF), graft renal function, duration of DGF, acute rejection, postoperative hospital stay and patient survival. Summary effects were calculated as risk ratio (RR) with 95% confidence interval (CI) or mean difference (MD) with 95% confidence intervals (CI). A total of 13 RCTs were included, including 2048 kidney transplant recipients. The results indicated that compared with SCS, HMP decreased the incidence of DGF (RR 0.78, 95% CI 0.69–0.87, P < 0.0001), and improved the graft survival at 3 years (RR 1.06, 95% CI 1.02–1.11, P = 0.009). There was no significant difference in other endpoints. HMP might be a more desirable method of preservation for kidney grafts. The long‐term outcomes of kidney allografts stored by hypothermic machine perfusion still need to be further investigated.     

Risk factors for the development of vertebral fractures after percutaneous vertebroplasty

We have recently observed an increased risk for vertebral fractures (VF) in a randomized controlled trial comparing the analgesic effect of vertebroplasty (VP) versus conservative treatment in symptomatic VF. The aim of the present study was to evaluate the risk factors related to the development of VF after VP in these patients. We evaluated risk factors including age, gender, bone mineral density, the number, type, and severity of vertebral deformities at baseline, the number of vertebral bodies treated, the presence and location of disk cement leakage, bone remodeling (determining bone turnover markers) and 25 hydroxyvitamin D [25(OH)D] levels at baseline in all patients. Twenty‐nine radiologically new VF were observed in 17 of 57 patients undergoing VP, 72% adjacent to the VP. Patients developing VF after VP showed an increased prevalence of 25(OH)D deficiency (<20 ng/mL) and higher P1NP values. The principal factor related to the development of VF after VP in multivariate analysis was 25(OH)D levels < 20 ng/mL (RR, 15.47; 95% CI, 2.99–79.86, p < 0.0001), whereas age >80 years (RR, 3.20; 95% CI, 1.70–6.03, p = 0.0007) and glucocorticoid therapy (RR, 3.64; 95% CI, 1.61–8.26, p = 0.0055) constituted the principal factors in the overall study population. Increased risk of VF after VP was also associated with cement leakage into the inferior disk (RR, 6.14; 95% CI, 1.65–22.78, p = 0.044) and more than one vertebral body treated during VP (RR, 4.19; 95% CI, 1.03–34.3, p = 0.044). In conclusion, nearly 30% of patients with osteoporotic VF treated with VP had a new VF after the procedure. Age, especially >80 years, the presence of inferior disk cement leakage after the procedure, the number of cemented vertebrae, and low 25(OH)D serum levels were related to the development of new VF in these patients, with the latter indicating the need to correct vitamin D deficiency prior to performing VP.     

Prevention and treatment of glucocorticoid-induced osteoporosis with active vitamin D<Subscript>3</Subscript> analogues: a review with meta-analysis of randomized controlled trials including organ transplantation studies

The aim of this review with meta-analysis was to determine if there is a rationale to use activated forms of vitamin D₃ to treat or prevent glucocorticoid-induced osteoporosis, and to compare the effect of active vitamin D₃ metabolites with that of other anti-osteoporosis therapies. We performed a systemic search using MEDLINE/PubMed (1966–2003). Animal studies and clinical trials involving humans with data on therapy to treat or prevent glucocorticoid-induced osteoporosis with active vitamin D₃ analogues were included. Animal studies and basic research studies with active vitamin D₃ were reviewed (qualitative review). Meta-analysis (quantitative review) on clinical trials (including organ transplantation studies) was performed with percent change in lumbar spine bone mineral density or bone mineral content as the primary outcome measure; the secondary outcome measure was incidence of vertebral fractures. Fifty-four articles were found. Animal and basic research studies showed that active vitamin D₃ analogues can inhibit bone loss during treatment with glucocorticoids. Concerning the effect on bone mineral density, the pooled effect size of active vitamin D₃ analogues compared with no treatment, placebo, plain vitamin D₃ and/or calcium was 0.35 (95% confidence interval (CI) 0.18, 0.52). Compared with bisphosphonates, the pooled effect size was –1.03 (95% CI –1.71, –0.36). The pooled estimate of the relative risk for vertebral fractures of active vitamin D₃ analogues compared with no treatment, placebo, plain vitamin D₃ and/or calcium was 0.56 (95% CI 0.34, 0.92) and compared with bisphosphonates it was 1.20 (95% CI 0.32, 4.55). Active vitamin D₃ analogues not only preserve bone during glucocorticoid therapy more effectively than no treatment, placebo, plain vitamin D₃ and/or calcium, but are also more effective in decreasing the risk of vertebral fractures. Bisphosphonates, however, are more effective in preserving bone and decreasing the risk of vertebral fractures than active vitamin D₃ analogues.     

Cinacalcet versus standard treatment for chronic kidney disease: a systematic review and meta-analysis

Background: Chronic kidney disease-mineral and bone disorders (CKD-MBD) have been associated with poor health outcomes, including diminished quality and length of life. Standard management for CKD-MBD includes phosphate restricted diet, vitamin D and phosphate binders. Persistently elevated parathyroid hormone levels may require the addition of cinacalcet hydrochloride (cinacalcet), which sensitizes calcium receptors in the parathyroid gland.

Purpose: The objective of this systematic review is to compare, in patients with CKD-MBD the effect of cinacalcet versus standard treatment on patient-important outcomes, including parathyroidectomy, fractures, hospitalizations due to cardiovascular events, cardiovascular mortality, all-cause mortality, and intermediate outcomes, in particular Kidney Disease Outcome Quality Initiative targets.

Methods: Data sources included MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and Web of Science from 1996 to June 2015. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible trials. We calculated the effect estimates (risk ratios or mean differences) and 95% confidence intervals, as well as statistical measures of variability in results across studies using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate quality of evidence about estimates of effect on an outcome-by-outcome basis for all outcomes. We presented our results with a GRADE summary table.

Results: Twenty-four trials including 8311 CKD patients proved eligible. The results left considerable uncertainty regarding the impact of cinacalcet on reducing fractures (relative risk [RR] 0.59, 95% confidence interval [CI] 0.13–2.60; heterogeneity: p?=?0.03, I²=?78%; very low quality evidence), and indicated that cinacalcet did not reduce hospitalizations due to cardiovascular events (RR 0.93, 95% CI 0.85–1.02, moderate quality of evidence), cardiovascular mortality (RR 0.95, 95% CI 0.84–1.07; heterogeneity p=?0.61, high quality evidence) or all-cause mortality (RR 0.96, 95% CI 0.89–1.04; heterogeneity: p=?0.98, I²=?0%; moderate quality evidence). Cinacalcet reduced the need for parathyroidectomy (RR 0.30, 95% CI 0.22–0.42; heterogeneity: p=?0.70, I²=?0%; absolute effect 55 fewer per 1000 [95% CI 61 fewer to 45 fewer], high quality of evidence). The most common adverse event associated with cinacalcet therapy was gastrointestinal side effects. Cinacalcet increased nausea (RR 2.16, 95% CI 1.46–3.21, absolute effect 158 more per 1000 [95% CI 82 more to 302 more]) and vomiting (RR 2.15, 95% CI 1.66–2.80, absolute effect 63 more per 1000 [95% CI 109 more to 171 more]). Cinacalcet treatment increased the rate of hypocalcemia (RR 6.0, 95% CI 3.65–9.87; heterogeneity: p=?0.71, I²=?0%, absolute effect 20 more per 1000 [95% CI 11 more to 36 more], high quality of evidence).

Conclusions: In the hands of clinicians participating in these studies, cinacalcet decreased the rate of parathyroidectomy but had no influence on mortality. Patients and clinicians can trade of the benefit of fewer parathyroidectomies against the adverse effects.     

Resource utilization among kidney transplant recipients

BACKGROUND: Hospitalization consumes a significant portion of the end-stage renal disease (ESRD) program, which includes kidney transplant recipients. Identification of kidney transplant recipients at risk of increased resource utilization could lead to appropriate interventions to attenuate the complications related to kidney transplant, which may reduce resource utilization. METHODS: This retrospective cohort study of kidney transplant recipients was performed to identify risk factors for hospital utilization. The study population consisted of patients who received kidney transplant at our center between October 1990 and September 1999 and were followed in the outpatient clinic. RESULTS: Of the 220 patients, 171 (78%) were hospitalized during a median follow-up of 36 months. The number of hospitalizations, hospital days, and outpatient visits per patient-year at risk were 1.1, 6.3, and 21.6, respectively. Infection episodes were the leading cause of hospitalization. In a multivariate regression analysis, cytomegalovirus (CMV)-positive status of donor (RR 1.58; 95% CI 1.15, 2.18) and a higher number of hospital days during the transplant hospitalization (RR 1.10 per 7 days increase; 95% CI 1.03, 1.19) were associated with a higher risk of hospitalization, while higher serum albumin (RR 0.84 per 0.5 g/dL increase; 95% CI 0.73, 0.97), higher hematocrit (RR 0.95 per 1% increase; 95% CI 0.92, 0.98), higher glomerular filtration rate (GFR) (RR 0.91 per 10 mL/min/1.73 m2; 95% CI 0.85, 0.99), and an increased interval since transplant (RR 0.84 per 6 months increase; 95% CI 0.75, 0.93) were associated with a lower risk of hospitalization. CMV-positive status of the donor (RR 1.11; 95% CI 1.00, 1.21) and presence of cardiovascular disease (RR 1.12; 95% CI 1.00, 1.24) were associated with a higher risk of outpatient visits, while Caucasian race (RR 0.82; 95% CI 0.73, 0.94), higher serum albumin (RR 0.88 per 0.5 g/dL increase; 95% CI 0.84, 0.93), higher hematocrit (RR 0.96 per 1% increase; 95% CI 0.95, 0.97), and an increased interval since transplant (RR 0.79 per 6 months increase; 95% CI 0.76, 0.83) were associated with a lower risk of outpatient visits. CONCLUSION: Identification of risk factors associated with increase resource utilization among kidney transplant recipients could aid in the development of targeted interventions to improve clinical and economic outcomes.     

Vertebral augmentation plus short-segment fixation versus vertebral augmentation alone in Kümmell’s disease: a systematic review and meta-analysis

Osteoporotic vertebral compression fractures of the thoracolumbar spine can progress to Kümmell’s disease, an avascular vertebral osteonecrosis. Vertebral augmentation (VA)—vertebroplasty and/or kyphoplasty—is the main treatment modality, but additional short-segment fixation (SSF) has been recommended concomitant to VA. The aim is to compare clinical and radiological outcomes of VA?+?SSF versus VA alone. Systematic review, including comparative articles in Kümmell’s disease, was performed. This study assessed the following outcome measurements: visual analog scale (VAS), Oswestry Disability Index (ODI), anterior vertebral height (AVH), local kyphotic angle (LKA), operative time, blood loss, length of stay, and cement leakage. Six retrospective studies were included, with 126 patients in the VA?+?SSF group and 152 in VA alone. Pooled analysis showed the following: VAS, non-significant difference favoring VA?+?SSF: MD –0.61, 95% CI (–1.44, 0.23), I² 91%, p?=?0.15; ODI, non-significant difference favoring VA?+?SSF: MD –9.85, 95% CI (–19.63, –0.07), I² 96%, p?=?0.05; AVH, VA?+?SSF had a non-significant difference over VA alone: MD –3.21 mm, 95% CI (–7.55, 1.14), I² 92%, p?=?0.15; LKA, non-significant difference favoring VA?+?SSF: MD –0.85°, 95% CI (–5.10, 3.40), I² 95%, p?=?0.70. There were higher operative time, blood loss, and hospital length of stay for VA?+?SSF (p?<?0.05), but with lower cement leakage (p?<?0.05). VA?+?SFF and VA alone are effective treatment modalities in Kümmell’s disease. VA?+?SSF may provide superior long-term results in clinical and radiological outcomes but required a longer length of stay.

     

Effect of risedronate on bone in renal transplant recipients

Bisphosphonates may prevent or treat the bone loss promoted by the immunosuppressive regimens used in renal transplantation. Risedronate is a commonly used third-generation amino-bisphosphonate, but little is known about its effects on the bone health of renal transplant recipients. We randomly assigned 42 new living-donor kidney recipients to either 35 mg of risedronate weekly or placebo for 12 months. We obtained bone biopsies at the time of renal transplant and after 12 months of protocol treatment. Treatment with risedronate did not affect bone mineral density (BMD) in the overall cohort. In subgroup analyses, it tended to preserve BMD in female participants but did not significantly affect the BMD of male participants. Risedronate did associate with increased osteoid volume and trabecular thickness in male participants, however. There was no evidence for the development of adynamic bone disease. In summary, further study is needed before the use of prophylactic bisphosphonates to attenuate bone loss can be recommended in renal transplant recipients.     

Clinical manifestations and outcomes of coronavirus disease-19 in heart transplant recipients: a multicentre case series with a systematic review and meta-analysis

Available data on clinical presentation and mortality of coronavirus disease-2019 (COVID-19) in heart transplant (HT) recipients remain limited. We report a case series of laboratory-confirmed COVID-19 in 39 HT recipients from 3 French heart transplant centres (mean age 54.4 ± 14.8 years; 66.7% males). Hospital admission was required for 35 (89.7%) cases including 14/39 (35.9%) cases being admitted in intensive care unit. Immunosuppressive medications were reduced or discontinued in 74.4% of the patients. After a median follow-up of 54 (19–80) days, death and death or need for mechanical ventilation occurred in 25.6% and 33.3% of patients, respectively. Elevated C-reactive protein and lung involvement ≥50% on chest computed tomography (CT) at admission were associated with an increased risk of death or need for mechanical ventilation. Mortality rate from March to June in the entire 3-centre HT recipient cohort was 56% higher in 2020 compared to the time-matched 2019 cohort (2% vs. 1.28%, P = 0.15). In a meta-analysis including 4 studies, pre-existing diabetes mellitus (OR 3.60, 95% CI 1.43–9.06, I² = 0%, P = 0.006) and chronic kidney disease stage III or higher (OR 3.79, 95% CI 1.39–10.31, I² = 0%, P = 0.009) were associated with increased mortality. These findings highlight the aggressive clinical course of COVID-19 in HT recipients.     

Bisphosphonate treatment and risk of esophageal cancer: a meta-analysis of observational studies

Summary

The use of bisphosphonates and the risk of esophageal cancer have recently received increasing concern and related studies have yielded controversial results. The present meta-analysis of observational studies shows that no clear association between bisphosphonate treatment and risk of esophageal cancer was observed.

Introduction

Epidemiological evidence suggests that bisphosphonate treatment can increase the risk of esophageal cancer. However, data on this issue are unstable and controversial. We conducted a meta-analysis to provide a quantitative assessment of the association between use of bisphosphonates and risk of esophageal cancer.

Methods

We searched the Medline and Embase databases up to May 2012 to identify studies related to bisphosphonates and esophageal cancer. Summary effect estimates with 95 % confidence intervals (CI) were derived using a fixed or random effects model, depending on the heterogeneity of the included studies.

Results

Seven epidemiologic studies that consisted of four cohort studies and three case–control studies were included in this meta-analysis. In our primary analysis, bisphosphonate treatment was not associated with risk of esophageal cancer in both cohort studies [pooled relative risk (RR) 1.23, 95 % CI 0.79–1.92] and case–control studies [pooled odds ratio (OR) 1.24, 95 % CI 0.98–1.57]. Evidence for the presence of significant heterogeneity was found in cohort studies (p?=?0.009, I ²?=?74 %) but not in case–control studies (p?=?0.338, I ²?=?7.8 %). In our secondary analysis, no significant increased risk of esophageal cancer was found in alendronate users (pooled RR 1.08, 95 % CI 0.67–1.75 in cohort studies; pooled OR 1.16, 95 % CI 0.82–1.63 in case–control studies).

Conclusions

Based on current evidences, bisphosphonate treatment was not significantly associated with excess risk of esophageal cancer.     

Hospital readmissions following HLA‐incompatible live donor kidney transplantation: A multi‐center study

Thirty percent of kidney transplant recipients are readmitted in the first month posttransplantation. Those with donor‐specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22‐center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant‐matched controls and to waitlist‐only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Readmission risk was determined using multilevel, mixed‐effects Poisson regression. In the first month, ILDKTs had a 1.28‐fold higher readmission risk than compatible controls (95% confidence interval [CI] 1.13‐1.46; P < .001). Risk peaked at 6‐12 months (relative risk [RR] 1.67, 95% CI 1.49‐1.87; P < .001), attenuating by 24‐36 months (RR 1.24, 95% CI 1.10‐1.40; P < .001). ILDKTs had a 5.86‐fold higher readmission risk (95% CI 4.96‐6.92; P < .001) in the first month compared to waitlist‐only controls. At 12‐24 (RR 0.85, 95% CI 0.77‐0.95; P = .002) and 24‐36 months (RR 0.74, 95% CI 0.66‐0.84; P < .001), ILDKTs had a lower risk than waitlist‐only controls. These findings of ILDKTs having a higher readmission risk than compatible controls, but a lower readmission risk after the first year than waitlist‐only controls should be considered in regulatory/payment schemas and planning clinical care.     

Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis

Previous studies have reported inconsistent findings regarding the association between the use of selective serotonin reuptake inhibitors (SSRIs) and the risk of fracture. We identified relevant studies by searching three electronic databases (MEDLINE, EMBASE, and the Cochrane Library) from their inception to October 20, 2010. Two evaluators independently extracted data. Because of heterogeneity, we used random‐effects meta‐analysis to obtain pooled estimates of effect. We identified 12 studies: seven case‐control studies and five cohort studies. A meta‐analysis of these 12 observational studies showed that the overall risk of fracture was higher among people using SSRIs (adjusted odds ratio [OR] = 1.69, 95% confidence interval [CI] 1.51–1.90, I² = 89.9%). Subgroup analysis by adjusted number of key risk factors for osteoporotic fracture showed a greater increased fracture risk in those adjusted for fewer than four variables (adjusted OR = 1.83, 95% CI 1.57–2.13, I² = 88.0%) than those adjusted for four or more variables (adjusted OR = 1.38, 95% CI 1.27–1.49, I² = 46.1%). The pooled ORs anatomical site of fracture in the hip/femur, spine, and wrist/forearm were 2.06 (95% CI 1.84–2.30, I² = 62.3%), 1.34 (95% CI 1.13–1.59, I² = 48.5%), and 1.51 (95% CI 1.26–1.82, I² = 76.6%), respectively. Subgroup analysis by exposure duration revealed that the strength of the association decreased with a longer window of SSRI administration before the index date. The risk of fracture was greater within 6 weeks before the index date (adjusted OR = 3.83, 95% CI 1.96–7.49, I² = 41.5%) than 6 weeks or more (adjusted OR = 1.60, 95% CI 0.93–2.76, I² = 63.1%). Fracture risk associated with SSRI use may have a significant clinical impact. Clinicians should carefully consider bone mineral density screening before prescribing SSRIs and proper management for high‐risk populations. © 2012 American Society for Bone and Mineral Research.     

Comparison of outcomes of peritoneal dialysis between patients after failed kidney transplant and transplant-naïve patients: a meta-analysis of observational studies

PurposeThe influence of prior failed kidney transplants on outcomes of peritoneal dialysis (PD) is unclear. Thus, we conducted a systematic review and meta-analysis to compare the outcomes of patients initiating PD after a failed kidney transplant with those initiating PD without a prior history of kidney transplantation.MethodsWe searched PubMed, Embase, CENTRAL, and Google Scholar databases from inception until 25 November 2020. Our meta-analysis considered the absolute number of events of mortality, technical failures, and patients with peritonitis, and we also pooled multi-variable adjusted hazard ratios (HR).ResultsWe included 12 retrospective studies. For absolute number of events, our analysis indicated no statistically significant difference in technique failure [RR, 1.14; 95% CI, 0.80–1.61; I²=52%; p = 0.48], number of patients with peritonitis [RR, 1.13; 95% CI, 0.97–1.32; I²=5%; p = 0.11] and mortality [RR, 1.00; 95% CI, 0.67–1.50; I²=63%; p = 0.99] between the study groups. The pooled analysis of adjusted HRs indicated no statistically significant difference in the risk of technique failure [HR, 1.25; 95% CI, 0.88–1.78; I²=79%; p = 0.22], peritonitis [HR, 1.04; 95% CI, 0.72–1.50; I²=76%; p = 0.85] and mortality [HR, 1.24; 95% CI, 0.77–2.00; I²=66%; p = 0.38] between the study groups.ConclusionPatients with kidney transplant failure initiating PD do not have an increased risk of mortality, technique failure, or peritonitis as compared to transplant-naïve patients initiating PD. Further studies are needed to evaluate the impact of prior and ongoing immunosuppression on PD outcomes.