Risks for donors associated with living kidney donation: meta-analysis.

BACKGROUND: Living kidney donation risk is likely to differ according to donor's demographics. We aimed to analyse the effects of age, sex, body mass index (BMI) and ethnicity. METHODS: A systematic review and meta-analysis was undertaken of the effects of preoperative patient characteristics on donor kidney function outcomes, surgical complications, and hypertension. RESULTS: 5129 studies were identified, of which 31 met the inclusion criteria, mainly from the USA and Europe. The estimated glomerular filtration rate (eGFR) in donors aged over 60 years was a mean of 9.54 ml per min per 1.73 m2 lower than that of younger donors (P < 0.001). Female donors had higher relative short- and long-term survival. BMI of over 30 kg/m2 was found to significantly lower the donor's eGFR 1 year after donation: the eGFR of obese donors was lower than that of non-obese patients by a mean of -2.70 (95 per cent c.i. -3.24 to -2.15) ml per min per 1.73 m2 (P < 0.001). Obesity was also associated with higher blood pressure both before and 1 year after donation, and a higher level of proteinuria, but had no impact on operative complications. In the long term, African donors were more likely to develop end-stage renal disease than Caucasians. CONCLUSION: Obesity and male sex were associated with inferior outcomes. Older donors (aged over 60 years) have a larger eGFR decline than younger donors, and African donors have a higher incidence of ESRD than Caucasians.

How good is a living donor? Systematic review and meta-analysis of the effect of donor demographics on post kidney transplant outcomes.

BACKGROUND AND AIMS: Living donor kidneys are considered the best quality organs. In the attempt to expand the donor pool, the donor's age, sex and body mass index (BMI) might be considered as potential determinants of the kidney transplant outcomes, and thus guide recipient selection. We aimed to investigate the effects of donor demographics on kidney function, graft and recipient survival, delayed graft function (DGF) and acute rejection (AR). METHODS: Systematic review and meta-analysis. EMBASE, MEDLINE, Web of Science, BIOSIS, CABI, SciELO and Cochrane were searched using algorithms. NHBLI tools were used for risk of bias assessment. Mean difference (MD), standardized mean difference (SMD), and risk ratio (RR) were calculated in Revman 5.4 RESULTS: Altogether, 5129 studies were identified by the search algorithm; 47 studies met the inclusion criteria and were analyzed. No significant difference in recipient 1-year survival was found between recipients of donors aged < 50 vs donors aged > 50 (RR = 0.65 95% CI: 0.1-4.1), and recipients of donors aged < 60 vs donors aged > 60 (RR = 0.81 95% CI: 0.3-2.3). Graft survival was significantly higher in recipients of grafts from donors aged < 60. Risk of AR (RR = 0.62 95% CI: 0.5-0.8) and DGF (RR = 0.28 95% CI: 0.1-0.9) were significantly lower in recipients of grafts from donors aged < 60. One-year serum creatinine was significantly lower in recipients from donors aged < 60 years compared to donors aged > 60 years (MD = 0.3 mg/dl 95% CI: 0.1-0.9), although there was high heterogeneity. Recipients of grafts from male donors had lower 1-year serum creatinine (MD = 0.12 mg/dl 95% CI: 0.2-0.1) and higher eGFR compared to recipients of female donors (p < 0.00001). Donor obesity increased the incidence of delayed graft function but not acute rejection (RR = 0.66 95% CI: 0.32-1.34). CONCLUSIONS: Older donor age was associated with worse post-transplant outcomes and recipients of male donors had better 1-year eGFR. Donor obesity affects the incidence of delayed graft function, but not the incidence of acute rejection in recipients.

Nannizziopsis Immune Reconstitution Inflammatory Syndrome in a Patient with HIV: First Reported Case.

We describe the case of a 35-year-old HIV-positive male of African origin diagnosed with neurotoxoplasmosis and a Nannizziopsis spp. cavitating pulmonary lesion unmasking immune reconstitution inflammatory syndrome (IRIS). The patient presented with headache, left hemiparesis and confusion. MRI of the brain showed two space-occupying lesions in the right basal ganglia and left parietal lobe typical for neurotoxoplasmosis. The patient tested positive for HIV and had advanced CD4 lymphopenia. After commencement of antiretroviral treatment, a CT scan of the chest showed a cavitating lesion in the right upper lobe. The diagnosis of Nannizziopsis spp. fungal infection was confirmed by DNA sequencing on a bronchial wash sample. The patient achieved complete recovery with antiretroviral therapy, standard neurotoxoplasmosis treatment and antifungal treatment with voriconazole for 12 weeks. LEARNING POINTS: AIDS patients at risk of multiple concomitant opportunistic infections present a significant diagnostic challenge.Unusual pathologies should also be considered in addition to the most common opportunistic pathogens, especially in the context of immune reconstitution inflammatory syndrome.

The Impact of Recipient Demographics on Outcomes from Living Donor Kidneys: Systematic Review and Meta-Analysis.

Background and Aims: Recipient demographics affect outcomes after kidney transplantation. The aim of this study was to assess, for kidneys retrieved from living donors, the effect of recipient sex, ethnicity, and body mass index (BMI) on delayed graft function (DGF) and one-year graft function, incidence of acute rejection (AR), and recipient and graft survivals. Methods: A systematic review and meta-analysis was performed. EMBASE and MEDLINE databases were searched using algorithms through Ovid. Web of Science collection, BIOSIS, CABI, Korean Journal database, Russian Science Citation Index, and SciELO were searched through Web of Science. Cochrane database was also searched. Risk of bias was assessed using the NHBLI tools. Data analysis was performed using Revman 5.4. Mean difference (MD) and risk ratio (RR) were used in analysis. Results: A total of 5129 studies were identified; 24 studies met the inclusion criteria and were analysed. Female recipients were found to have a significantly lower serum creatinine 1-year-post renal transplantation (MD: -0.24 mg/dL 95%CI: -0.18 to -0.29 p < 0.01) compared to male recipients. No significant difference in survival between male and female recipients nor between Caucasians and Africans was observed (p = 0.08). However, Caucasian recipients had a higher 1-year graft survival compared to African recipients (95% CI 0.52-0.98) with also a lower incidence of DGF (RR = 0.63 p < 0.01) and AR (RR = 0.55 p < 0.01). Recipient obesity (BMI > 30) was found to have no effect on 1-year recipient (p = 0.28) and graft survival (p = 0.93) compared to non-obese recipients although non-obese recipients had a lower rate of DGF (RR = 0.65 p < 0.01) and AR (RR = 0.81 p < 0.01) compared to obese recipients. Conclusions: Gender mismatch between male recipients and female donors has negative impact on graft survival. African ethnicity and obesity do not to influence recipient and graft survival but negatively affect DGF and AR rates.

The Effect of a Single Bout of Continuous Aerobic Exercise on Glucose, Insulin and Glucagon Concentrations Compared to Resting Conditions in Healthy Adults: A Systematic Review, Meta-Analysis and Meta-Regression.

BACKGROUND: Elevated glucose and insulin levels are major risk factors in the development of cardiometabolic disease. Aerobic exercise is widely recommended to improve glycaemic control, yet its acute effect on glycaemia and glucoregulatory hormones has not been systematically reviewed and analysed in healthy adults. OBJECTIVE: To determine the effect of a single bout of continuous aerobic exercise on circulating glucose, insulin, and glucagon concentrations in healthy adults. METHODS: CENTRAL, CINAHL, Embase, Global Health, HMIC, Medline, PubMed, PsycINFO, ScienceDirect, Scopus and Web of Science databases were searched from inception to May 2020. Papers were included if they reported a randomised, crossover study measuring glucose and/or insulin and/or glucagon concentrations before and immediately after a single bout of continuous aerobic exercise (≥ 30 min) compared to a time-matched, resting control arm in healthy adults. The risk of bias and quality of evidence were assessed using the Cochrane Risk of Bias Tool and GRADE approach, respectively. Random-effects meta-analyses were performed for glucose, insulin, and glucagon. Sub-group meta-analyses and meta-regression were performed for categorical (metabolic state [postprandial or fasted], exercise mode [cycle ergometer or treadmill]) and continuous (age, body mass index, % males, maximal aerobic capacity, exercise duration, exercise intensity) covariates, respectively. RESULTS: 42 papers (51 studies) were considered eligible: glucose (45 studies, 391 participants), insulin (38 studies, 377 participants) and glucagon (5 studies, 47 participants). Acute aerobic exercise had no significant effect on glucose concentrations (mean difference: - 0.05 mmol/L; 95% CI, - 0.22 to 0.13 mmol/L; P = 0.589; I2: 91.08%, large heterogeneity; moderate-quality evidence). Acute aerobic exercise significantly decreased insulin concentrations (mean difference: - 18.07 pmol/L; 95% CI, - 30.47 to - 5.66 pmol/L; P = 0.004; I2: 95.39%, large heterogeneity; moderate-quality evidence) and significantly increased glucagon concentrations (mean difference: 24.60 ng/L; 95% CI, 16.25 to 32.95 ng/L; P < 0.001; I2: 79.36%, large heterogeneity; moderate-quality evidence). Sub-group meta-analyses identified that metabolic state modified glucose and insulin responses, in which aerobic exercise significantly decreased glucose (mean difference: - 0.27 mmol/L; 95% CI, - 0.55 to - 0.00 mmol/L; P = 0.049; I2: 89.72%, large heterogeneity) and insulin (mean difference: - 42.63 pmol/L; 95% CI, - 66.18 to - 19.09 pmol/L; P < 0.001; I2: 81.29%, large heterogeneity) concentrations in the postprandial but not fasted state. Meta-regression revealed that the glucose concentrations were also moderated by exercise duration and maximal aerobic capacity. CONCLUSIONS: Acute aerobic exercise performed in the postprandial state decreases glucose and insulin concentrations in healthy adults. Acute aerobic exercise also increases glucagon concentrations irrespective of metabolic state. Therefore, aerobic exercise undertaken in the postprandial state is an effective strategy to improve acute glycaemic control in healthy adults, supporting the role of aerobic exercise in reducing cardiometabolic disease incidence. PROSPERO REGISTRATION NUMBER: CRD42020191345.

The Effect of Preservation Temperature on Liver, Kidney, and Pancreas Tissue ATP in Animal and Preclinical Human Models.

The recent advances in machine perfusion (MP) technology involve settings ranging between hypothermic, subnormothermic, and normothermic temperatures. Tissue level adenosine triphosphate (ATP) is a long-established marker of viability and functionality and is universal for all organs. In the midst of a growing number of complex clinical parameters for the quality assessment of graft prior to transplantation, a revisit of ATP may shed light on the underlying reconditioning mechanisms of different perfusion temperatures in the form of restoration of metabolic and energy status. This article aims to review and critically analyse animal and preclinical human studies (discarded grafts) during MP of three abdominal organs (liver, kidney, and pancreas) in which ATP was a primary endpoint. A selective review of recent novel reconditioning approaches relevant to mitigation of graft ischaemia-reperfusion injury via MP and for different perfusion temperatures was also conducted. With a current reiterated interest for oxygenation during MP, a re-introduction of tissue ATP levels may be valuable for graft viability assessment prior to transplantation. Further studies may help delineate the benefits of selective perfusion temperatures on organs viability.

Machine Perfusion for Abdominal Organ Preservation: A Systematic Review of Kidney and Liver Human Grafts.

INTRODUCTION: To match the current organ demand with organ availability from the donor pool, there has been a shift towards acceptance of extended criteria donors (ECD), often associated with longer ischemic times. Novel dynamic preservation techniques as hypothermic or normothermic machine perfusion (MP) are increasingly adopted, particularly for organs from ECDs. In this study, we compared the viability and incidence of reperfusion injury in kidneys and livers preserved with MP versus Static Cold Storage (SCS). METHODS: Systematic review and meta-analysis with a search performed between February and March 2019. MEDLINE, EMBASE and Transplant Library were searched via OvidSP. The Cochrane Library and The Cochrane Central Register of Controlled Trials (CENTRAL) were also searched. English language filter was applied. RESULTS: the systematic search generated 10,585 studies, finally leading to a total of 30 papers for meta-analysis of kidneys and livers. Hypothermic MP (HMP) statistically significantly lowered the incidence of primary nonfunction (PMN, p = 0.003) and delayed graft function (DGF, p < 0.00001) in kidneys compared to SCS, but not its duration. No difference was also noted for serum creatinine or eGFR post-transplantation, but overall kidneys preserved with HMP had a significantly longer one-year graft survival (OR: 1.61 95% CI: 1.02 to 2.53, p = 0.04). Differently from kidneys where the graft survival was affected, there was no significant difference in primary non function (PNF) for livers stored using SCS for those preserved by HMP and NMP. Machine perfusion demonstrated superior outcomes in early allograft dysfunction and post transplantation AST levels compared to SCS, but however, only HMP was able to significantly decrease serum bilirubin and biliary stricture incidence compared to SCS. CONCLUSIONS: MP improves DGF and one-year graft survival in kidney transplantation; it appears to mitigate early allograft dysfunction in livers, but more studies are needed to prove its potential superiority in relation to PNF in livers.