The Clinical Significance of Salusins in Systemic Sclerosis-A Cross-Sectional Study.

Background: Systemic sclerosis (SSc) is a connective tissue disease manifesting with progressive fibrosis of the skin and internal organs. Its pathogenesis is strictly associated with vascular disfunction and damage. Salusin-α and salusin-ß, endogenous peptides regulating secretion of pro-inflammatory cytokines and vascular smooth muscle proliferation, may potentially play a role in SSc pathogenesis. Objectives: The aim of this study was to assess the concentration of salusins in sera of patients with SSc and healthy controls and to evaluate correlations between the salusins levels and selected clinical parameters within the study group. Materials and methods: 48 patients with SSc (44 women; mean age, 56.4, standard deviation, 11.4) and 25 adult healthy volunteers (25 women; mean age, 55.2, standard deviation, 11.2) were enrolled. All patients with SSc were treated with vasodilators and twenty-seven of them (56%) also received immunosuppressive therapy. Results: Circulating salusin-α was significantly elevated in patients with SSc in comparison to healthy controls (U = 350.5, p = 0.004). Patients with SSc receiving immunosuppression had higher serum salusin-α concentrations compared with those without immunosuppressive therapy (U = 176.0, p = 0.026). No correlation was observed between salusins concentrations and skin or internal organ involvement parameters. Conclusions: Salusin-α, a bioactive peptide mitigating the endothelial disfunction, was elevated in patients with systemic sclerosis receiving vasodilators and immunosuppressants. Increased salusin-α concertation may be associated with the initiation of atheroprotective processes in patients with SSc managed pharmacologically, which requires verification in future studies.

CYP3A5 Expressor Genotype of the Transplanted Kidney Increases the Risk of Preterm Graft Loss and Acute Rejection.

INTRODUCTION: Tacrolimus is metabolized mainly in the liver by the CYP3A enzyme family, with a particularly well-documented role of CYP3A5. CYP3A5 is also expressed in the renal tissue and is present in the transplanted kidney. To date, the association between donor CYP3A5 polymorphisms and transplant outcome remains poorly understood. The aim of this study was to assess the effect of donor CYP3A5 expression on early and long-term transplant outcomes. METHODS: A retrospective cohort study including 207 patients who received kidney grafts from 110 deceased donors was conducted at a single Central European Center. Tissue samples from all donors were studied for CYP3A5 single-nucleotide polymorphism (rs776746). Death-censored graft loss within 5-year follow-up, acute rejection occurrence, and kidney function, measured using serum creatinine and MDRD eGFR, were compared between groups of patients with allografts from rs776746 carriers (CYP3A5 expressors) and noncarriers (CYP3A5 nonexpressors). RESULTS: Recipients who received kidneys from CYP3A5 expressors (n = 24) were at significantly higher risk of death-censored graft loss within 5-year follow-up (adjusted HR, 95% CI: 6.82, 2.01-23.12; p = 0.002) and acute rejection within the 1st posttransplant year (adjusted OR, 95% CI: 4.62, 1.67-12.77; p = 0.003) than those who did not (n = 183). The median time to loss of function was 1.93 [IQR; 0.77-3.19] years. CONCLUSIONS: Donor CYP3A5 expressor status is associated with worse renal graft survival and a higher risk of acute rejection. Determination of donor CYP3A5 genotype is a potentially useful tool that may improve kidney transplant outcomes.

Peritoneal dialysis catheter removal at the time or after kidney transplantation: a systematic review and meta-analysis.

PURPOSE: An increasing number of patients treated with peritoneal dialysis eventually undergo kidney transplantation. Owing to opposing reports, we aimed to find evidence about the best time for peritoneal dialysis catheter removal in transplant patients. METHODS: We conducted a systematic review and random effects meta-analysis of non-randomized studies of intervention comparing patients with peritoneal dialysis catheters left in place or removed during kidney transplantation in regard to the need for dialysis and occurrence of catheter-related complications. We searched (last update on 8 December 2021) PubMed, Embase, Scopus, and Web of Science for eligible studies. ROBINS-I tool and funnel plot asymmetry analysis were used to assess the quality of included articles. RESULTS: Eight observational studies were evaluated. Five of them, which involved 338 patients, were included in a meta-analysis. All were at moderate to serious risk of bias. The odds of needing dialysis are more than twice as high for patients with peritoneal dialysis catheters left in situ (pooled odds ratio, 2.21; 95% confidence interval [CI], 1.03 to 4.73; I2 = 0%). No statistically significant difference was noted when adult and pediatric subgroups were compared (Q = 0.13, P = .720). More individuals with catheters left in place required dialysis (pooled prevalence, 20.9%; 95% CI, 13.6 to 30.7%; I2 = 59% vs. 12.4%; 95% CI, 5.6 to 25.2%; I2 = 0%) and experienced catheter-related infections. CONCLUSION: Available evidence is scarce. Unless new data from a randomized controlled trial are available, the dilemma of peritoneal dialysis catheter removal cannot be solved. TRIAL REGISTRATION: PROSPERO Protocol ID: CRD42020207707.

Donor CYP3A5 Expression Decreases Renal Transplantation Outcomes in White Renal Transplant Recipients.

BACKGROUND After renal transplantation, immunosuppressants should be administered to prevent organ rejection and prolong graft survival. One of them is tacrolimus, which is metabolized by the CYP3A enzyme family. The variability of the CYP3A5 gene in renal transplant recipients has been previously studied for its correlation with acute rejection and allogeneic kidney function. CYP3A5 enzyme is also present in the renal tissue, and its relevance has not yet been extensively investigated. This study aimed to evaluate the effect of donor and recipient CYP3A5 expression status on early and long-term transplant outcomes. MATERIAL AND METHODS Single-nucleotide polymorphism in CYP3A5 (rs776746) was analyzed in 95 kidney transplant recipients and their grafts. The effect of donor and recipient genotypes on the primary endpoint, which was the loss of the renal graft over 5-year follow-up, was assessed. The secondary endpoints were biopsy-proven acute rejection, proteinuria, delayed graft function, and renal function. RESULTS Patients who received a CYP3A5*1 allele-carrying kidney (n=16) were at greater risk of graft loss (adjusted hazard ratio, 95% CI: 10.61, 2.28-49.42, P=.003) than those with the CYP3A5*3/*3 genotype (n=79). Renal CYP3A5 expression was also a predictor of acute rejection between the 2nd and 12th post-transplant months (adjusted odds ratio, 95% CI: 4.36; 1.08-17.6, P=.038) and proteinuria at different time intervals. No effect of the recipient CYP3A5 genotype was observed. CONCLUSIONS The donor CYP3A5 genotype is associated with inferior transplantation outcomes. Local renal tacrolimus metabolism is a potential target for improving long-term transplantation outcomes.

Renal Cyp3a5-Expressing Genotype Decreases Tacrolimus-to-Dose Ratio in Small Cohort of Renal Transplant Recipients-Preliminary Report.

BACKGROUND: Previous reports have established that patient CYP3A5 allelic variability may be the most important genetic contributor to interindividual variation in tacrolimus exposure in renal transplant recipients. However, CYP3A5 protein is expressed in the allogenic kidney. The aim of this study was to investigate the role of the renal CYP3A5 genotype in tacrolimus concentration-to-dose ratio within 3 years posttransplant. METHODS: A retrospective cohort study of 90 renal transplant recipients and their donors evaluated the effect of the CYP3A5 single-nucleotide polymorphism (rs776746) on tacrolimus exposure. The area under the curve for tacrolimus concentration-to-dose ratio within 3-year follow-up was calculated and compared in kidneys carrying at least 1 CYP3A5*1 allele and those carrying the CYP3A5*3/*3 genotype. RESULTS: A significant effect of CYP3A5 expression on tacrolimus exposure was observed in both donors (mean ± SD: 23.8 ± 7.9 vs 32.6 ± 7.4 ng/mL/mg, respectively; P < .001) and recipients (mean ± SD: 27.1 ± 8.0 vs 32.2 ± 7.9 ng/mL/mg, respectively; P = .034) and was lower when CYP3A5 enzyme occurred. Thus, new groups were formed: the group in which at least 1 of the pairs, donor or recipient, had a CYP3A5 expressing allele (n = 23) had lower exposure to tacrolimus compared with nonexpressors (n = 67; mean ± SD: 26.2 ± 7.6 vs 33.2 ± 7.4 ng/mL/mg, respectively; P < .001). CONCLUSION: Intrarenal metabolism of tacrolimus may affect both local and systemic drug exposure. Nonexpressors receiving kidneys with the CYP3A5*1 allele may benefit from higher tacrolimus doses to hasten achievement of target drug concentrations.

Single-center experience with perioperative antibiotic prophylaxis and surgical site infections in kidney transplant recipients.

BACKGROUND: Infections in kidney transplant recipients are particularly challenging owing to the immunosuppressive treatment, usually long history of chronic illness, comorbidities and prior exposures to antibiotics. Among the most common complications early after surgery are surgical site infections. The aim of this study was to identify risk factors and evaluate epidemiological data regarding surgical site infections. Moreover, we were able to compare the current results with historical data from our institution when different perioperative antibiotic prophylaxis was practiced. METHODS: We conducted a retrospective case-control study in a group of 254 deceased donor renal graft recipients transplanted in a single Central European institution. We evaluated epidemiological findings and resistance patterns of pathogens causing surgical site infections. We used multivariable logistic regression to determine risk factors for surgical site infections. RESULTS: We revealed no differences in baseline characteristics between patients with and without surgical site infections. Ten surgical site infections (3.9%) were diagnosed (six superficial incisional, two deep incisional, and two organ/space). Eight species (19 strains) were identified, most of which were multi-drug resistant (63%). The most common was extended-spectrum ß-lactamase producing Klebsiella pneumoniae (26%). We showed that statistically significant differences were present between reoperated and non-reoperated patients (adjusted odds ratio: 6.963, 95% confidence interval 1.523-31.842, P = .012). CONCLUSIONS: Reoperation is an individual risk factor for surgical site infection after kidney transplantation. According to our experience, cefazolin-based prophylaxis can be safe and is associated with relatively low prevalence of surgical site infections.

Local, non-systemic, and minimally invasive therapies for calcinosis cutis: a systematic review.

Calcinosis cutis is a deposition of calcium in the skin and subcutaneous tissue, often accompanied by pain, reduced mobility, and chronic infections. Limited evidence is available about the feasibility and efficacy of therapies alternative to systemic treatment and surgical excision, both of which often lead to unsatisfactory results or complications. We conducted a systematic review to evaluate the efficacy and safety of topical and intralesional sodium thiosulfate, extracorporeal shock-wave lithotripsy (ESWL), and laser for calcinosis cutis. PubMed, Embase, and Web of Science were searched. Reports of calciphylaxis and treatment combined with systemic medications were excluded. A total of 40 studies including 136 patients were analysed. Partial or complete remission after monotherapy was observed in 64% to 81% of cases. Self-applied topical sodium thiosulfate required patient's adherence (mean treatment duration, 4.9 months; range 2-24). Laser therapy enabled complete remission of microcalcifications after a single procedure (57%; 12/21). ESWL and intralesional sodium thiosulfate injections decreased calcinosis-associated pain (median reduction in VAS score, 3; range 0-9 and 1; range 0-5, respectively). The most common adverse event was scarring and hyperkeratosis, observed after CO2 laser (56%; 10/18). Intralesional sodium thiosulfate injections caused transient pain in over 11% of patients. Recurrences within the follow-up were rare (2%; 3/136). This study provides an overview of minimally invasive and local therapies that in selected cases might transcend conventional treatment. The limitation of this study is the poor level of evidence, which emerges mainly from non-randomized studies at high risk of bias.

Prophylactic intra-abdominal drainage following kidney transplantation: a systematic review and meta-analysis.

INTRODUCTION: An ongoing debate concerns the need for routine placement of prophylactic intra-abdominal drains following kidney transplantation. <br/><br/>Aim: We conducted a systematic review and meta-analysis to determine whether such an approach brings any advantages in the prevention of perirenal transplant fluid collection, surgical site infection, lymphocele, hematoma, urinoma, wound dehiscence, graft loss, and need for reoperation. <br/><br/>Methods: We conducted a random-effects meta-analysis of non-randomized studies of intervention comparing drained and drain-free adult renal graft recipients regarding perirenal transplant fluid collection and other wound complications. ROBINS-I tool and funnel plot asymmetry analysis were used to assess the risk of bias. <br/><br/>Results: Five studies at moderate to critical risk of bias were included. A total of 2094 renal graft recipients were evaluated. Our analysis revealed no significant differences between drained and drain-free patients regarding perirenal transplant fluid collection (pooled odds ratio [OR], 0.77; 95% confidence interval [CI], 0.28-2.17; I 2 = 72%), surgical site infection (OR, 1.64; 95% CI, 0.11-24.88; I 2 = 80%), lymphocele (OR, 0.61; 95% CI, 0.02-15.27; I 2 = 0%), hematoma (OR, 0.71; 95% CI, 0.12-3.99; I 2 = 71%), and wound dehiscence (OR, 0.75; 95% CI, 0.21-2.70; I 2 = 0%). There was insufficient data concerning urinoma, graft loss, and need for reoperation. <br/><br/>Conclusions: The available evidence is weak. Our findings show that the use of intra-abdominal drains after kidney transplantation seems to have neither beneficial nor harmful effects on perirenal transplant fluid collection and other wound complications. The present study does not support the routine placement of surgical drains after kidney transplantation. <i>In this systematic review and meta-analysis we summarize the most up-to-date evidence for and against the routine use of intra-abdominal drain following renal transplantation.</i>.

Outcomes of ex vivo liver resection and autotransplantation: A systematic review and meta-analysis.

BACKGROUND: Many patients with hepatic tumors cannot benefit from resection owing to the difficult anatomic sites of their lesions. Some of these patients might be eligible for ex vivo liver resection and autotransplantation. This procedure consists of complete hepatectomy, extracorporeal liver resection, and autotransplantation of the remnant liver. METHODS: Four databases were searched for studies reporting cases of ex vivo liver resection and autotransplantation. Outcomes of this procedure were evaluated by meta-analysis of proportions with random effects model and individual participant data analysis. RESULTS: Fifty-three studies were assessed. Meta-analysis revealed an R0 resection rate of 93.4% (95% confidence interval: 81.0-97.9%, I2 = 0%), a frequency of major surgical complications of 24.5% (95% confidence interval, 16.9-34.3%, I2 = 26%), a 30-day mortality of 9.5% (95% confidence interval: 5.9-14.9%, I2 = 0%), and a 1-year survival of 78.4% (95% confidence interval: 62.2-88.8%, I2 = 64%). We were able to obtain the individual participant data in 244 patients; R0 resection was achieved in 98.6%, with no obvious difference between analyzed subgroups. The 30-day mortality and 1-year survivals were 7.9% and 82.1%, respectively. For groups with malignant and nonmalignant tumors, the 30-day mortalities were 11.3% vs. 6.3% (P = .181), and 1-year survivals were 65.0% vs. 89.7% (P < .001). When comparing those with malignant versus those with nonmalignant lesions, major surgical complications occurred in 50.0% vs. 21.0%; P < .001). Regression analysis revealed that outcomes of patients with benign tumors were better compared with those with malignant tumors (1-year survival, odds ratio: 4.629; 95% confidence interval: 2.181-10.097, P < .001). CONCLUSION: Ex vivo liver resection and autotransplantation facilitates radical treatment in selected patients with conventionally unresectable hepatic tumors and normal liver function. The outcomes of treatment of malignant lesions appear to be less satisfactory.

How Early Postoperative Urinary Tract Infections Affect Renal Graft Function at 1-Year Follow-up.

BACKGROUND: Urinary tract infection (UTI) occurs in 21% of kidney recipients within the first 3 months after transplantation (KTx). It is associated with impaired graft function. Ureteral stent placement increases the occurrence of UTIs. The aim of this study was to assess the correlation between double-J placement, UTI incidence, and graft function. MATERIAL AND METHODS: We conducted an observational study in 753 patients transplanted between 2010 and 2017 in compliance with the Helsinki Congress and the Istanbul Declaration. Recipients with preserved graft function at the 1-year follow-up were included. Medical records were searched for intraoperative double-J placement, UTI incidence, and estimated glomerular filtration rate (eGFR) on the 30th and 360th days post-transplant. Pretransplant hypothetical estimated GFR (heGFR) of each donor was calculated from donors' age and physiological age-dependent loss of functional nephrons. Spearman's correlation and linear regression analyses were applied. P < .05 was considered significant. RESULTS: UTIs occurred in 239 (31.8%) patients. On the 30th day after KTx, eGFR was significantly lower in the UTI group (median, 39.5 vs 43.2; P < .01). A similar pattern was seen 1 year after KTx (47.5 vs 54.2; P < .01). Urinary stents were placed in 213 (28.3%) patients. UTIs occurred in 92 (43.2%) of them and in 147 (27.2%) of nonstented patients (odds ratio: 2; 95% confidence interval [CI], 1.5-2.8; P < .01). Median donor heGFR was 105.8 mL/min/1.73 m2, whereas median donor Modification of Diet in Renal Disease (MDRD) GFR was 64.2 mL/min/1.73 m2. A moderate correlation between age-adjusted heGFR and 1-year transplant function (r = .47) was noted. CONCLUSIONS: UTIs in the early post-transplant period decreased 1-year eGFR by 4 to 5 mL/min/1.73 m2. UTIs occurred twice as often when a urinary stent was placed.

Early Postoperative Complications and Outcomes of Kidney Transplantation in Moderately Obese Patients.

BACKGROUND: Obese renal transplant recipients (body mass index [BMI] ≥30 kg/m2) are at risk of delayed graft function and postoperative complications, such as infections or delayed wound healing. There is also a tendency to exclude extremely obese patients from transplantation (KTx). Nonetheless, no association between obesity and increased mortality has been reported. The aim of this study is to evaluate the effect of BMI on the most common surgical and infectious complications after KTx. MATERIALS AND METHODS: An observational study in 872 patients transplanted from 2010-2017 was conducted. Median BMI was 24.6 (13.9-34.3), and 8.3% of the group was obese. Patient records were searched for early postoperative complications: lymphocele or hematoma (>33 mL), urinary leakage, or urinary tract infection (UTI). Mann-Whitney U and χ2 or Fisher exact tests were used. P < .05 was considered statistically significant. The study complies with the Helsinki Congress and the Istanbul Declaration. RESULTS: Renal primary nonfunction was observed in 1.4% (12/872) of patients. Surgical or infectious complications occurred in 52.7% (453/860) of patients. No correlation between BMI and complication rate was noted. Complications were observed in 56.9% (41/72) of obese vs 52.3% (412/788) of nonobese patients (P = .448), including lymphocele in 15.3% vs 16.4% (P = .810), hematoma in 22.2% vs 19.2% (P = .530), urinary leakage in 1.4% vs 4.6% (P = .203), and UTI in 31.9% vs 32.9% (P = .873), respectively. CONCLUSIONS: Recipient's BMI has no significant association with the most common surgical complications after KTx. There is no need to delay KTx in moderately obese patients.