Impact of transplant nephrectomy on peak PRA levels and outcome after kidney re-transplantation

AIM: To determine the impact of transplant nephrectomy on peak panel reactive antibody (PRA) levels, patient and graft survival in kidney re-transplants.METHODS: From 1969 to 2006, a total of 609 kidney re-transplantations were performed at the University of Freiburg and the Campus Benjamin Franklin of the University of Berlin. Patients with PRA levels above (5%) before first kidney transplantation were excluded from further analysis (n = 304). Patients with graft nephrectomy (n = 245, NE+) were retrospectively compared to 60 kidney re-transplants without prior graft nephrectomy (NE-).RESULTS: Peak PRA levels between the first and the second transplantation were higher in patients undergoing graft nephrectomy (P = 0.098), whereas the last PRA levels before the second kidney transplantation did not differ between the groups. Age adjusted survival for the second kidney graft, censored for death with functioning graft, were comparable in both groups. Waiting time between first and second transplantation did not influence the graft survival significantly in the group that underwent nephrectomy. In contrast, patients without nephrectomy experienced better graft survival rates when re-transplantation was performed within one year after graft loss (P = 0.033). Age adjusted patient survival rates at 1 and 5 years were 94.1% and 86.3% vs 83.1% and 75.4% group NE+ and NE-, respectively (P < 0.01).CONCLUSION: Transplant nephrectomy leads to a temporary increase in PRA levels that normalize before kidney re-transplantation. In patients without nephrectomy of a non-viable kidney graft timing of re-transplantation significantly influences graft survival after a second transplantation. Most importantly, transplant nephrectomy is associated with a significantly longer patient survival.     

Long-term outcome of ketoconazole and tacrolimus co-administration in kidney transplant patients

AIM: To study the long-term outcome of ketoconazole and tacrolimus combination in kidney transplant recipients.METHODS: From 2006 to 2010, ketoconazole was given in 199 patients and was continued for at least 1 year or until graft failure (Group 1), while 149 patients did not receive any ketoconazole (Group 2). A combination of tacrolimus, mycophenolate and steroid was used as maintenance therapy. High risk patients received basiliximab induction.RESULTS: Basic demographic data was similar between the 2 groups. The 5-year cumulative incidence of biopsy-confirmed and clinically-treated acute rejection was significantly higher in Group 1 than in Group 2 (34% vs 18%, P = 0.01). The 5-year Kaplan-Meier estimated graft survival (74.3% vs 76.4%, P = 0.58) and patient survival (87.8% vs 87.5%, P = 0.93) were not different between the 2 groups. Multivariable analyses identified ketoconazole usage as an independent risk of acute rejection (HR = 2.33, 95%CI: 1.33-4.07; P = 0.003) while tacrolimus dose in the 2^nd month was protective (HR = 0.89, 95%CI: 0.75-0.96; P = 0.041).CONCLUSION: Co-administration of ketoconazole and tacrolimus is associated with significantly higher incidence of acute rejection in kidney transplant recipients.     

Single vs dual (en bloc) kidney transplants from donors ≤ 5 years of age: A single center experience

AIM: To compare outcomes between single and dual en bloc (EB) kidney transplants (KT) from small pediatric donors.METHODS: Monocentric nonprospective review of KTs from pediatric donors ≤ 5 years of age. Dual EB KT was defined as keeping both donor kidneys attached to the inferior vena cava and aorta, which were then used as venous and arterial conduits for the subsequent transplant into a single recipient. Donor age was less useful than either donor weight or kidney size in decision-making for kidney utilization as kidneys from donors < 8 kg or kidneys < 6 cm in length were not transplanted. Post-transplant management strategies were standardized in all patients.RESULTS: From 2002-2015, 59 KTs were performed including 34 dual EB and 25 single KTs. Mean age of donors (17 mo vs 38 mo, P < 0.001), mean weight (11.0 kg vs 17.4 kg, P = 0.046) and male donors (50% vs 84%, P = 0.01) were lower in the dual EB compared to the single KT group, respectively. Mean cold ischemia time (21 h), kidney donor profile index (KDPI; 73% vs 62%) and levels of serum creatinine (SCr, 0.37 mg/dL vs 0.49 mg/dL, all P = NS) were comparable in the dual EB and single KT groups, respectively. Actuarial graft and patient survival rates at 5-years follow-up were comparable. There was one case of thrombosis resulting in graft loss in each group. Delayed graft function incidence (12% dual EB vs 20% single KT, P = NS) was slightly lower in dual EB KT recipients. Initial duration of hospital stay (mean 5.4 d vs 5.6 d) and the one-year incidences of acute rejection (6% vs 16%), operative complications (3% vs 4%), and major infection were comparable in the dual EB and single KT groups, respectively (all P = NS). Mean 12 mo SCr and abbreviated MDRD levels were 1.17 mg/dL vs 1.35 mg/dL and 72.5 mL/min per 1.73 m² vs 60.5 mL/min per 1.73 m² (both P = NS) in the dual EB and single KT groups, respectively.CONCLUSION: By transplanting kidneys from young pediatric donors into adult recipients, one can effectively expand the limited donor pool and achieve excellent medium-term outcomes.     

Impact of steroid maintenance on the outcomes in first-time deceased donor kidney transplant recipients: Analysis by induction type

AIM: To analyze the impact of steroid maintenance on the outcomes in kidney transplant recipients stratified by induction agent received.METHODS: Patients who underwent first-time deceased donor kidney transplantation between 2000 and 2008 after receiving induction therapy with rabbit-antithymocyte globulin (r-ATG), alemtuzumab or an interleukin-2 receptor blocker (IL-2B) and discharged on a calcineurin inhibitor (CNI)/mycophenolate mofetil (MMF)-regimen along with or without steroids were identified from the Organ Procurement and Transplant Network/United Network of Organ Sharing database. For each induction type, adjusted overall and death-censored graft as well as patient survivals were compared between patients discharged on steroid vs no steroid. Among r-ATG induced patients, analysis was repeated after splitting the group into low and high immune risk groups.RESULTS: Among the 37217 patients included in the analysis, 17863 received r-ATG (steroid = 13001, no-steroid = 4862), 3028 alemtuzumab (steroid = 852, no-steroid = 2176) and 16326 IL-2B (steroid = 15008, no-steroid = 1318). Adjusted overall graft survival was inferior (HR = 1.16, 95%CI: 1.06-1.27, P = 0.002) with similar death-censored graft survival (HR = 0.99, 95%CI: 0.86-1.14, P = 0.86) for steroid vs no-steroid groups in r-ATG induced patients. Both adjusted overall and death-censored graft survivals for steroid vs no-steroid groups were similar in alemtuzumab (HR = 0.92, 95%CI: 0.73-1.15, P = 0.47 and HR = 0.87, 95%CI: 0.62-1.22, P = 0.43 respectively) and IL-2B (HR = 1.05, 95%CI: 0.91-1.21, P = 0.48 and HR = 0.94, 95%CI: 0.75-1.18, P = 0.60 respectively) induced groups. Adjusted patient survivals were inferior for steroid vs no-steroid groups in r-ATG induced (HR = 1.31, 95%CI: 1.15-1.49, P < 0.001) but similar in alemtuzumab (HR = 1.02, 95%CI: 0.75-1.38, P = 0.92) and IL-2B (HR = 1.17, 95%CI: 0.97-1.40, P = 0.10) induced patients. Among the r-ATG induced group there were 4346 patients in the low immune risk and 13517 patients in the high immune risk group. Adjusted overall graft survivals were inferior for steroid vs no steroid groups in both low immune (HR = 1.34, 95%CI: 1.09-1.64, P = 0.001) and high immune (HR = 1.18, 95%CI: 1.07-1.30, P = 0.005) risk groups. Adjusted death-censored graft survivals for steroid vs no steroid groups were similar in both low (HR = 1.06, 95%CI: 0.78-1.45, P = 0.70) and high (HR = 1.04, 95%CI: 0.98-1.20, P = 0.60) immune risk groups. Adjusted patient survivals were inferior for steroid vs no steroid groups in both low immune (HR = 1.54, 95%CI: 1.18-2.02, P < 0.001) and high immune (HR = 1.32, 95%CI: 1.16-1.51, P = 0.002) risk groups. Overall, there were significantly higher deaths from infections and cardiovascular causes in patients maintained on steroids.CONCLUSION: Our study showed an association between steroid addition to a CNI/MMF-maintenance regimen and increased death with functioning graft in patients receiving r-ATG induction for first-time deceased donor kidney transplantation.     

Role of steroid maintenance in sensitized kidney transplant recipients

AIM: To evaluate whether there is a threshold sensitization level beyond which benefits of chronic steroid maintenance (CSM) emerge.METHODS: Using Organ Procurement and Transplant Network/United Network of Organ Sharing database, we compared the adjusted graft and patient survivals for CSM vs early steroid withdrawal (ESW) among patients who underwent deceased-donor kidney (DDK) transplantation from 2000 to 2008 who were stratified by peak-panel reactive antibody (peak-PRA) titers (0%-30%, 31%-60% and > 60%). All patients received perioperative induction therapy and maintenance immunosuppression based on calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF).RESULTS: The study included 42851 patients. In the 0%-30% peak-PRA class, adjusted over-all graft-failure (HR 1.11, 95%CI: 1.03-1.20, P = 0.009) and patient-death (HR 1.29, 95%CI: 1.16-1.43, P < 0.001) risks were higher and death-censored graft-failure risk (HR 1.06, 95%CI: 0.98-1.14, P = 0.16) similar for CSM (n = 25218) vs ESW (n = 7399). Over-all (HR 1.04, 95%CI: 0.85-1.28, P = 0.70) and death-censored (HR 0.97, 95%CI: 0.78-1.21, P = 0.81) graft-failure risks were similar and patient-death risk (HR 1.39, 95%CI: 1.03-1.87, P = 0.03) higher for CSM (n = 3495) vs ESW (n = 850) groups for 31%-60% peak-PRA class. In the > 60% peak-PRA class, adjusted overall graft-failure (HR 0.90, 95%CI: 0.76-1.08, P = 0.25) and patient-death (HR 0.92, 95%CI: 0.71-1.17, P = 0.47) risks were similar and death-censored graft-failure risk lower (HR 0.84, 95%CI: 0.71-0.99, P = 0.04) for CSM (n = 4966) vs ESW (n = 923).CONCLUSION: In DDK transplant recipients who underwent perioperative induction and CNI/MMF maintenance, CSM appears to be associated with increased risk for death with functioning graft in minimally-sensitized patients and improved death-censored graft survival in highly-sensitized patients.     

Perioperative effects of high doses of intraoperative thymoglobulin induction in liver transplantation

AIM: To describe our single-centre experience in liver transplantation(LT) with the infusion of high perioperative thymoglobulin doses. The optimal dosage and timing of thymoglobulin~ [antithymocyte globulin(ATG)] administration during LT remains controversial. Cytokine release syndrome, haemolytic anaemia, thrombocytopenia, neutropenia, fever and serum sickness are potential adverse effects associated with ATG infusion.METHODS: Between December 2009 and December 2010, 16 adultnon- randomized patients( ATG group), receiving a liver graft from a deceased donor, received an intraoperative infusion(4-6 h infusion) of thymoglobulin(3 mg/kg, ATG: Thymoglobuline~). These patients were compared(case control approach) with 16 patients who had a liver transplant without ATG treatment(control group) to evaluate the possible effects of intraoperative ATG infusion. The matching parameters were: Sex, recipient age(± 5 years), LT indication including viral status, MELD score(± 5 points), international normalized ratio and platelet count(as close as possible). The exclusion criteria for both groups included the following: Multi-organ or living donor transplant, immunosuppressive therapy before transplantation, contraindications to the administrationof any thymocyte globulin, human immunodeficiency virus seropositivity, thrombocytopenia [platelet 50000/μL] or leukopenia [white blood cells 1000/μL]. The perioperative side effects(haemodynamic alterations, core temperature variations, colloids and crystalloids requirements, and surgical time) possibly related to ATG infusion and the thromboelastographic(TEG) evaluation of the ATG effects on coagulation, blood loss and blood product transfusion were analysed during the operation and the first three postoperative days.RESULTS: Intraoperative ATG administration was associated with longer surgical procedures [560 ± 88 min vs 480 ± 83 min(control group), P = 0.013], an intraoperative core temperature more than 37 ℃(50% of ATG patients vs 6.2% of control patients, P = 0.015), major intraoperative blood loss [3953 ± 3126 mL vs 1419 ± 940 m L(control group), P = 0.05], higher red blood cell [2092 ± 1856 mL ATG group vs 472 ± 632 mL(control group), P = 0.02], fresh frozen plasma [671 ± 1125 mL vs 143 ± 349 mL(control group), P = 0.015], and platelet [374 ± 537 mL vs 15.6 ± 62.5 mL(control group), P = 0.017] transfusion, and a higher requirement for catecholamines(0.08 ± 0.07 μg/kg per minutes vs 0.01 ± 0.38 μg/kg per minutes, respectively, in the ATG and control groups) for haemodynamic support. The TEG tracings changed to a straight line during ATG infusion(preanhepatic and anhepatic phases) in 81% of the patients from the ATG group compared to 6.25% from the control group(P 0.001). Patients from the ATG group compared to controls had higher post-op core temperatures(38 ℃± 1.0 ℃ vs 37.3 ℃± 0.5 ℃; P = 0.02), an increased need of noradrenaline(43.7% vs 6.25%, P = 0.037), received more platelet transfusions(31.5% vs 0%, P = 0.04) and required continuous renal replacement therapy(4 ATG patients vs none in the control group; P = 0.10). ATG infusion was considered the cause of a fatal anaphylactic shock and of a suspected adverse reaction that led to intravascular haemolysis and acute renal failure.CONCLUSION: The side effects and the coagulation imbalance observed in patients receiving a high dosage of ATG suggest caution in the use of thymoglobulin during LT.     

Kinin B2 receptor does not exert renoprotective effects on mice with glycerol-induced rhabdomyolysis

AIM: To investigate a potential protective role of the kinin B₂ receptor in a glycerol-induced rhabdomyolysis mouse model.METHODS: We separated 28 C57Bl/6 male mice into 4 groups: untreated WT animals, untreated B₂ knockout mice, glycerol-treated WT and glycerol-treated B₂ knockout mice. Glycerol-treated animals received one intramuscular injections of glycerol solution (50% v/v, 7 mL/kg). After 48 h, urine and blood samples were collected to measure creatinine and urea levels. Additionally, kidney samples were extracted for histological evaluation, and the mRNA expression levels of kinin B1 and B2 receptors and inflammatory mediators were measured by real-time polymerase chain reaction.RESULTS: Serum creatinine and urea levels showed differences between untreated wild-type and glycerol-treated wild-type mice (0.66 ± 0.04 vs 2.61 ± 0.53 mg/dL, P < 0.01; and 33.51 ± 2.08 vs 330.2 ± 77.7 mg/dL, P < 0.005), and between untreated B₂ knockout mice and glycerol-treated knockout mice (0.56 ± 0.03 vs 2.23 ± 0.87 mg/dL, P < 0.05; and 42.49 ± 3.2 vs 327.2 ± 58.4 mg/dL, P < 0.01), but there was no difference between the glycerol-treated wild-type and glycerol-treated knockout mice. Glycerol was able to induce a striking increase in kinin B₂ receptor expression (> 30 times, 31.34 ± 8.9) in kidney. Animals injected with glycerol had a higher degree of tubular injury than untreated animals. Wild-type and knockout mice treated with glycerol intramuscularly present kidney injury, with impairment in renal function. However, B₂ knockout mice treated with glycerol did not show a different phenotype regarding kidney injury markers, when compared to the wild-type glycerol-treated group.CONCLUSION: We conclude that the kinin B₂ receptor does not have a protective role in renal injury.     

Effect of ureteric stents on urological infection and graft function following renal transplantation

AIM: To compare urological infections in patients with or without stents following transplantation and to determine the effect of such infections on graft function.METHODS: All 285 recipients of kidney transplantation at our centre between 2006 and 2010 were included in the study. Detailed information including stent use and transplant function was collected prospectively and analysed retrospectively. The diagnosis of urinary tract infection was made on the basis of compatible symptoms supported by urinalysis and/or microbiological culture. Graft function, estimated glomerular filtration rate and creatinine at 6 mo and 12 mo, immediate graft function and infection rates were compared between those with a stent or without a stent.RESULTS: Overall, 196 (183 during initial procedure, 13 at reoperation) patients were stented following transplantation. The overall urine leak rate was 4.3% (12/277) with no difference between those with or without stents - 7/183 vs 5/102, P = 0.746. Overall, 54% (99/183) of stented patients developed a urological infection compared to 38.1% (32/84) of those without stents (P = 0.0151). All 18 major urological infections occurred in those with stents. The use of stent (Wald χ² = 5.505, P = 0.019) and diabetes mellitus (Wald χ² = 5.197, P = 0.023) were found to have significant influence on urological infection rates on multivariate analysis. There were no deaths or graft losses due to infection. Stenting was associated with poorer transplant function at 12 mo.CONCLUSION: Stents increase the risks of urological infections and have a detrimental effect on early to medium term renal transplant function.     

A retrospective Aliskiren and Losartan study in non-diabetic chronic kidney disease

AIM: To assess the efficacy of combined Aliskiren and Losartan vs high dose Losartan and Aliskiren alone in chronic kidney disease (CKD).METHODS: This is a retrospective study of 143 patients with non-diabetic CKD comparing combined Aliskiren (150 mg/d) with Losartan (100 mg/d) therapy vs High dose Angiotensin receptor blockers (ARB) (Losartan 200 mg/d) and the third group Aliskiren (150 mg/d) alone. This study involved only patient medical records. Entry criteria included those patients who had been treated with the above drugs for at least 36 mo within the 5 years period; other criteria included proteinuria of 1 g or more and or CKD Stage 3 at the start of the 36 mo period. The study utilised primary renal end points of estimated Glomerular Filtration Rate (eGFR) < 15 mL/min or end stage renal failure.RESULTS: Patients treated with high dose ARB compared to the other two treatment groups had significantly less proteinuria at the end of 36 mo (P < 0.007). All 3 groups had significant reduction of proteinuria (P < 0.043, P < 0.001). Total urinary protein was significantly different between the 3 groups over the 3-year study period (P = 0.008), but not eGFR. The changes in eGFR from baseline to each year were not significantly different between the 3 therapeutic groups (P < 0.119). There were no significant differences in the systolic and diastolic blood pressure between the 3 drug groups throughout the 3 years. The incidence of hyperkalemia (> 5.5 mmol/L) was 14.2% (7/49) in the Combined Aliskiren and ARB group, 8.7% (4/46) in the Aliskiren alone group and 6.3% (3/48) in the High dose ARB group (P < 0.001).CONCLUSION: This study in non-diabetic CKD patients showed that Combination therapy with Aliskiren and ARB was effective but was not safe as it was associated with a high prevalence of hyperkalaemia.     

Disseminated paracoccidioidomycosis in a liver transplant patient

Paracoccidioidomycosis is an endemic systemic mycosis caused by Paracoccidioides brasiliensis complex and P. lutzii. It is a rare disease in non-HIV-induced immunosuppressed individuals. In organ transplant recipients, it is more frequently associated with immunosuppression after kidney transplantation. In a liver transplant patient, only one case has been published in the literature to date. The present report comprises the case of a 47-year-old female patient with disseminated skin lesions associated with signs and symptoms of systemic involvement of paracoccidioidomycosis that manifested one year after liver transplantation and under an immunosuppression regimen with tacrolimus and mycophenolate mofetil.     

Oxidative Stress in Alopecia Areata: A Case–Control Study

Background

Increased reactive oxygen species (ROS) and lipid peroxidation are seen in many dermatologic disorders, including atopic dermatitis, psoriasis, vitiligo, acne vulgaris, pemphigus vulgaris, and lichen planus. In alopecia areata (AA), there is increased production of ROS from perifollicular inflammatory cells.

Objective

The aim of this study was to determine the oxidative stress index (OSI) and lipid peroxidation by studying serum total oxidant capacity (TOC), total antioxidant capacity (TAC), and malondialdehyde (MDA) values in AA patients.

Methods

The study included 35 AA patients and a control group consisting of 30 age- and sex-matched healthy volunteers. The serum TOC, TAC, and MDA values were measured, and the OSIs were calculated and compared in both groups.

Results

The mean serum TOC (p < 0.001), MDA (p < 0.001), and OSI (p < 0.001) values were found to be significantly higher in AA patients than in the control group. The mean serum TAC value was significantly lower (p < 0.05) in cases than in controls. Significantly higher MDA (p < 0.001), TOC (p < 0.001), and OSI values (p < 0.001) and lower TAC values (p < 0.01) were found in severe AA than in mild or moderate AA.

Conclusion

The demonstrated results confirmed the presence of oxidative stress and lipid peroxidation in AA. Whether these changes play a role in disease pathogenesis or result from the inflammatory process requires further investigation.     

Rituximab or plasmapheresis for prevention of recurrent focal segmental glomerulosclerosis after kidney transplantation: A systematic review and meta-analysis

BACKGROUNDFocal segmental glomerulosclerosis (FSGS) is one of the most common glomerular diseases leading to renal failure. FSGS has a high risk of recurrence after kidney transplantation. Prevention of recurrent FSGS using rituximab and/or plasmapheresis has been evaluated in multiple small studies with conflicting results. AIMTo assess the risk of recurrence of FSGS after transplantation using prophylactic rituximab with or without plasmapheresis, and plasmapheresis alone compared to the standard treatment group without preventive therapy.METHODSThis meta-analysis and systematic review were performed by first conducting a literature search of the MEDLINE, EMBASE, and Cochrane databases, from inception through March 2021; search terms included ‘FSGS,’ ’steroid-resistant nephrotic syndrome’, ‘rituximab,’ and ‘plasmapheresis,’. We identified studies that assessed the risk of post-transplant FSGS after use of rituximab with or without plasmapheresis, or plasmapheresis alone. Inclusion criteria were: Original, published, randomized controlled trials or cohort studies (either prospective or retrospective), case–control, or cross-sectional studies; inclusion of odds ratio, relative risk, and standardized incidence ratio with 95% confidence intervals (CI), or sufficient raw data to calculate these ratios; and subjects without interventions (controls) being used as comparators in cohort and cross-sectional studies. Effect estimates from individual studies were extracted and combined using a random effects model.RESULTSEleven studies, with a total of 399 kidney transplant recipients with FSGS, evaluated the use of rituximab with or without plasmapheresis; thirteen studies, with a total of 571 kidney transplant recipients with FSGS, evaluated plasmapheresis alone. Post-transplant FSGS recurred relatively early. There was no significant difference in recurrence between the group that received rituximab (with or without plasmapheresis) and the standard treatment group, with a pooled risk ratio of 0.82 (95%CI: 0.47-1.45, I² = 65%). Similarly, plasmapheresis alone was not associated with any significant difference in FSGS recurrence when compared with no plasmapheresis; the pooled risk ratio was 0.85 (95%CI: 0.60-1.21, I² = 23%). Subgroup analyses in the pediatric and adult groups did not yield a significant difference in recurrence risk. We also reviewed and analyzed post-transplant outcomes including timing of recurrence and graft survival.CONCLUSIONOverall, the use of rituximab with or without plasmapheresis, or plasmapheresis alone, is not associated with a lower risk of FSGS recurrence after kidney transplantation. Future studies are required to assess the effectiveness of rituximab with or without plasmapheresis among specific patient subgroups with high-risk for FSGS recurrence.     

Residual urinary output in high body mass index individuals on chronic hemodialysis: A disregarded life vest?

AIM: To assess residual diuresis and diverse variables according to body mass index (BMI).METHODS: Cross-sectional study (n = 57), with 3 groups. Group A: BMI < 25, n = 22; Group B: BMI 25-30, n = 15; Group C: BMI > 30, n = 20. Diuresis, hematocrit, albumin, C-reactive protein, Malnutrition inflammatory score, Pro-BNP, Troponin T, leptin and insulin levels are expressed as median and ranges (r).RESULTS: Albumin (g/dL): GA vs GC, 3.70 (r2.20-4.90) vs 3.85 (r3.40-4.90), P = 0.02. Diuresis (mL/d): GA 690 (r0-1780); GB 660 (r60-1800); GC 840 (r40-2840). Diuresis GA vs GC, P = 0.01. Leptin (ng/mL): GA vs GC, 3.81 (r0.78-69.60) vs GC, 32.80 (r0.78-124.50), P < 0.001. Insulin (µU/mL): GA vs GB, 7 (r2-44) vs 11.50 (r4-38), P = 0.02; GA vs GC, 7 (r2-44) vs 19.5 (r5-155), P = 0.0001. Troponin T and Pro-BNP levels were not different. Significant correlations: GC, Insulin-UF: ρ = 0.53; P = 0.03; TroponinT-diuresis: ρ = -0.48, P < 0.05; Pro-BNP-diuresis: ρ = -0.39, P < 0.01; Troponin T-ProBNP: ρ = 0.77, P < 0.0001; albumin-Troponin T: ρ = -0.66, P < 0.0001; albumin-ProBNP: ρ = -0.44, P < 0.05.CONCLUSION: High BMI associated positively with higher diuresis and albuminemia, and negatively with TropT and Pro-BNP. High BMI-associated better survival may be explained by better urinary output, lowering cardiovascular stress.     

Pericytes synthesize renin

AIM: To investigate renin expression in pericytes during normal kidney development and after deletion of angiotensinogen, the precursor for all angiotensins.METHODS: We examined the distribution of renin expressing cells by immunoshistochemistry in the interstitial compartment of wild type (WT) and angiotensinogen deficient (AGT -/-) mice at different developmental stages from embryonic day 18 (E18: WT, n = 4; AGT -/-, n = 5) and at day 1 (P1: WT, n = 5; AGT -/-, n = 5), 5 (P5: WT, n = 7; AGT -/-, n = 8), 10 (P10: WT, n = 3; AGT -/-, n = 5), 21 (P21: WT, n = 7; AGT -/-, n = 5), 45 (P45: WT, n = 3; AGT -/-, n = 3), and 70 (P70: WT, n = 2; AGT -/-, n = 2) of postnatal life. We quantified the number of pericytes positive for renin at all the developmental stages mentioned above and compared the results of AGT -/- mice to their WT counterparts.RESULTS: In WT mice, renal interstitial pericytes synthesize renin in early life supporting a lineage relationship with renin cells in the vasculature. The number of pericytes positive for renin per area of 0.32 mm² (density) in WT mice was maintained from fetal life till weaning age (E18 = 4.25 ± 0.63, P1 = 3.75 ± 0.48, P5 = 3.75 ± 0.48, P10 = 4 ± 0.71, P21 = 3.8 ± 0.58) and markedly decreased in adult life (P45 = 1.2 ± 0.37, P70 = 0.8 ± 0.20). On the other hand, in AGT -/- mice the density of pericytes expressing renin was not significantly different from WT mice at E18 and P1: E18 = 5.75 ± 0.50 vs 4.25 ± 0.63 (P = 0.106), P1 = 9.25 ± 3.50 vs 3.75 ± 0.48 (P = 0.175) but significantly increased from P5 till P70: P5 = 38.25 ± 5 vs 3.75 ± 0.48 (P = 0.0004), P10 = 173 ± 7.50 vs 4 ± 0.70 (P = 5.24567 × 10^-7), P21 = 83 ± 6.70 vs 3.8 ± 0.58 (P = 2.97358 × 10^-6), P45 = 49 ± 3.50 vs 1.2 ± 0.37 (P = 8.18274 x 10^-7) and P70 = 17.8 ± 2.30 vs 0.8 ± 0.20 (P = 3.51151 × 10^-5). The AGT -/- mice showed a marked increase in the number of pericytes per field studied starting from P5, reaching its peak at P10, and then a gradually decreasing until P70.CONCLUSION: Interstitial pericytes synthesize renin during development and the number of renin-expressing pericytes increases in response to a homeostatic threat imposed early in life such as lack of angiotensinogen.     

Combination cryotherapy and intralesional corticosteroid versus steroid monotherapy in the treatment of keloids

Background

Keloids are common and have significant negative effects on quality of life. There is a need for more effective treatment approaches for keloids.

Aims

We investigated treatment outcomes of intralesional triamcinolone acetonide (IL TAC) compared with combination IL TAC and cryotherapy, including changes in pruritus, pain, and keloid size.

Patients/Methods

We performed a prospective study of patients referred to one provider who treated patients with combination therapy and compared them to a historic control cohort treated with IL TAC alone. All patients were seen at Thomas Jefferson University between 2019 and 2021. Patient demographics, location of keloids, and inciting events were recorded. Pruritus and pain scores were self-reported by patients using a 10-point Likert scale administered as standard of care. Changes in keloid size were denoted as “No change,” “up to 50% decrease,” “more than 50% decrease,” and “completely flattened.”

Results

While both treatments produced a significant reduction in mean pruritus and pain scores, there was no difference between the two treatment groups (p = 0.3933 and p = 0.2123, respectively). A greater percentage of keloids in the combination therapy group had a post-treatment size difference greater than 50% compared with those in the IL TAC only treatment group (p = 0.0021). In the subgroup of pubic keloids, all lesions treated with combination IL TAC and cryotherapy responded remarkably well to treatment.

Conclusions

While both IL TAC and IL TAC with cryotherapy were effective at reducing pruritus and pain, combination therapy was more effective in reducing keloid size, specifically for pubic keloids.     

El uso de productos no específicos es insuficiente para prevenir la aparición de las estrías gravídicas: Evaluación del impacto en la calidad de vida tras la utilización de productos antiestrías durante el embarazo

Introduction

Striae are superficial linear depressions of the skin caused by fibroblast dysfunction, which frequently occur during pregnancy. Their aesthetic effects negatively affect the quality of many patients and is a source of stress. The aim of this study was to evaluate the prevalence of pre-pregnancy stretch marks, the incidence of striae gravidarum, their relationship with the use or non-use of products to try to prevent and/ or reduce them, and their impact on quality of life.

Material and Methods

We performed an observational, epidemiological, prospective, open study that included consecutive women who were attending a midwife consultation for pregnancy confirmation or prenatal care. The study included three visits: baseline, follow-up (20 weeks of pregnancy) and final visit (10 days postpartum). During the visits, anthropometric characteristics, the presence and cause of stretch marks, impact of stretch marks on quality of life, severity of the stretch marks and the use of products to prevent or reduce them were recorded, along with the type of product used (“Velastisa^®”, “other anti-striae products” and “moisturizers or non-specific products”).

Results

The sample included 321 women, with a mean (SD) age of 30.9 (5.04) years, of whom 227 were followed up. The prevalence of pre-pregnancy stretch marks was 90%. The overall incidence of stretch marks during pregnancy was 37.9%. The incidence of striae gravidarum was significantly lower in women that used anti-striae products at least until week 20 than in those not using these products (29.9% vs 45.4%; p<0.05; OR: 1.9 [95% CI:1.1-3.4]) and in those who used moisturizers or non-specific products (29.9% vs. 46.7%; p<0.01; OR: 2.1 [95% CI:1.2-3.6]). The severity of striae was lower among women who used anti-striae products than among those who used moisturizers or non-specific products in the visit at week 20 [1.19 (0.69) vs 1.42 (0.75); p<0.05] and in the final visit [1.22 (0.72) vs. 1.52 (0.83); p<0.05]. The maximum severity of stretch marks during the study was higher among users of moisturizers and non-specific products than among those who used anti-striae products [mean: 0.77 (0.95) vs. 0.46 (0.78); p<0.05] and especially among those using Velastisa^® anti-striae cream [0.77 (0.95) vs 0.41 (0.69); p<0.05].

Conclusions

The use of anti-striae products, at least until week 20 of gestation, compared with the use of moisturizers or non-specific products, reduces the incidence of striae gravidarum and the severity of new stretch marks improves dermatology-related quality life the end of pregnancy. Thus, we conclude that the use of non-specific products insufficient to prevent development of marks that the use of anti-striae products is recommended.     

Findings on intraprocedural non-contrast computed tomographic imaging following hepatic artery embolization are associated with development of contrast-induced nephropathy

BACKGROUNDContrast-induced nephropathy (CIN) is a reversible form of acute kidney injury that occurs within 48-72 h of exposure to intravascular contrast material. CIN is the third leading cause of hospital-acquired acute kidney injury and accounts for 12% of such cases. Risk factors for CIN development can be divided into patient- and procedure-related. The former includes pre-existing chronic renal insufficiency and diabetes mellitus. The latter includes high contrast volume and repeated exposure over 72 h. The incidence of CIN is relatively low (up to 5%) in patients with intact renal function. However, in patients with known chronic renal insufficiency, the incidence can reach up to 27%.AIMTo examine the association between renal enhancement pattern on non-contrast enhanced computed tomographic (CT) images obtained immediately following hepatic artery embolization with development of CIN.METHODSRetrospective review of all patients who underwent hepatic artery embolization between 01/2010 and 01/2011 (n = 162) was performed. Patients without intraprocedural CT imaging (n = 51), combined embolization/ablation (n = 6) and those with chronic kidney disease (n = 21) were excluded. The study group comprised of 84 patients with 106 procedures. CIN was defined as 25% increase above baseline serum creatinine or absolute increase ≥ 0.5 mg/dL within 72 h post-embolization. Post-embolization CT was reviewed for renal enhancement patterns and presence of renal artery calcifications. The association between non-contrast CT findings and CIN development was examined by Fisher’s Exact Test.RESULTSCIN occurred in 11/106 (10.3%) procedures (Group A, n = 10). The renal enhancement pattern in patients who did not experience CIN (Group B, n = 74 with 95/106 procedures) was late excretory in 93/95 (98%) and early excretory (EE) in 2/95 (2%). However, in Group A, there was a significantly higher rate of EE pattern (6/11, 55%) compared to late excretory pattern (5/11) (P < 0.001). A significantly higher percentage of patients that developed CIN had renal artery calcifications (6/11 vs 20/95, 55% vs 21%, P = 0.02).CONCLUSIONA hyperdense renal parenchyma relative to surrounding skeletal muscle (EE pattern) and presence of renal artery calcifications on immediate post-HAE non-contrast CT images in patients with low risk for CIN are independently associated with CIN development.     

Incidence and risk factors for early renal dysfunction after liver transplantation

AIM: To determine renal dysfunction post liver transplantation, its incidence and risk factors in patients from a Belgian University Hospital.METHODS: Orthotopic liver transplantations performed from January 2006 until September 2012 were retrospectively reviewed (n = 187). Patients with no renal replacement therapy (RRT) before transplantation were classified into four groups according to their highest creatinine plasma level during the first postoperative week. The first group had a peak creatinine level below 12 mg/L, the second group between 12 and 20 mg/L, the third group between 20 and 35 mg/L, and the fourth above 35 mg/L. In addition, patients who needed RRT during the first week after transplantation were also classified into the fourth group. Perioperative parameters were recorded as risk factors, namely age, sex, body mass index (BMI), length of preoperative hospital stay, prior bacterial infection within one month, preoperative ascites, preoperative treatment with β-blocker, angiotensin-converting enzyme inhibitor or non steroidal anti-inflammatory drugs, preoperative creatinine and bilirubin levels, donor status (cardiac death or brain death), postoperative lactate level, need for intraoperative vasopressive drugs, surgical revision, mechanical ventilation for more than 24 h, postoperative bilirubin and transaminase peak levels, postoperative hemoglobin level, amount of perioperative blood transfusions and type of immunosuppression. Univariate and multivariate analysis were performed using logistic ordinal regression method. Post hoc analysis of the hemostatic agent used was also done.RESULTS: There were 78 patients in group 1 (41.7%), 46 in group 2 (24.6%), 38 in group 3 (20.3%) and 25 in group 4 (13.4%). Twenty patients required RRT: 13 (7%) during the first week after transplantation. Using univariate analysis, the severity of renal dysfunction was correlated with presence of ascites and prior bacterial infection, preoperative bilirubin, urea and creatinine level, need for surgical revision, use of vasopressor, postoperative mechanical ventilation, postoperative bilirubin and urea, aspartate aminotransferase (ASAT), and hemoglobin levels and the need for transfusion. The multivariate analysis showed that BMI (OR = 1.1, P = 0.004), preoperative creatinine level (OR = 11.1, P < 0.0001), use of vasopressor (OR = 3.31, P = 0.0002), maximal postoperative bilirubin level (OR = 1.44, P = 0.044) and minimal postoperative hemoglobin level (OR = 0.059, P = 0.0005) were independent predictors of early post-liver transplantation renal dysfunction. Neither donor status nor ASAT levels had significant impact on early postoperative renal dysfunction in multivariate analysis. Absence of renal dysfunction (group 1) was also predicted by the intraoperative hemostatic agent used, independently of the extent of bleeding and of the preoperative creatinine level.CONCLUSION: More than half of receivers experienced some degree of early renal dysfunction after liver transplantation. Main predictors were preoperative renal dysfunction, postoperative anemia and vasopressor requirement.     

Evaluation of ex vivo melanogenic response to UVB,UVA, and visible light in facial melasma and unaffected adjacent skin

BackgroundThe independent role of solar radiation in the differential melanogenesis between melasma and adjacent skin is unknown.ObjectivesTo assess the melanogenic responses of skin with facial melasma and of the adjacent skin to UVB, UVA, and visible light, in an ex vivo model.MethodsThis was a quasi-experimental study involving 22 patients with melasma. Facial melasma and adjacent skin samples were collected and stored in DMEM medium, at room temperature. One fragment was placed under the protection from light, while another was exposed to UVB, UVA, and visible light (blue-violet component): 166 mJ/cm², 1.524 J/cm², and 40 J/cm², respectively. Subsequently, all samples were kept for 72 hours in a dark environment and stained by Fontana-Masson to assess basal layer pigmentation, dendrites, and melanin granulation.ResultsEffective melanogenesis was observed in the basal layer in melasma and in the normal adjacent skin after all irradiations (p < 0.01), with the following median increment: UVB (4.7% vs. 8.5%), UVA (9.5% vs. 9.9%), and visible light (6.8% vs. 11.7%), with no significant difference between anatomical sites. An increase in melanin granulation (coarser melanosomes) was observed only after irradiation with UVA and only in the skin with melasma (p = 0.05). An increase in the melanocyte dendrite count induced by UVB radiation was observed in both anatomical sites (p ≤ 0.05).Study limitationsUse of an ex vivo model, with independent irradiation regimes for UVB, UVA, and visible light.ConclusionsMelanogenesis induced by UVB, UVA, and visible light was observed both in melasma and in the adjacent skin. The morphological patterns suggest that different irradiations promote individualized responses on the skin with melasma.