Effect of balloon angioplasty in femoropopliteal arteries assessed by intravascular ultrasound

Objective:To study the effects of balloon angioplasty (PTA) of the femoropopliteal artery with intravascular ultrasound (IVUS).Materials and methods:Corresponding IVUS cross-sections (n = 1033) obtained before and after PTA from 115 procedures were analysed. Vascular damage including plaque rupture, dissection and media rupture was assessed. Free lumen area (FLA), media-bounded area (MBA) and plaque area (PLA) were measured.Results:After PTA vascular damage was seen at the target site in 83 (72%) arteries: plaque rupture in 30 (26%), dissection in 66 (57%) and media rupture in 20 (17%) arteries. The FLA increased from 5.4 ± 3.4 mm2 to 14.1 ± 5.0 mm2 (p<0.001), MBA increased from 26.9 ± 10.0 mm2 to 32.9 ± 10.7 mm2 (p<0.001) and PLA decreased from 21.6 ± 8.5 mm2 to 18.8 ± 8.0 mm2 (p<0.001). The increase in MBA accounted for 68% of lumen gain. The frequency of vascular damage and the relative contribution of MBA increase and PLA decrease to luminal gain were not different in procedures with balloon diameter ≤ 5 mm and ≥ 6 mm.Conclusions:Vascular damage is common following PTA. Lumen gain is mainly due to vessel expansion and, to a lesser extent, to a decrease in plaque area

Deficiency of functional mannose-binding lectin is not associated with infections in patients with systemic lupus erythematosus

Infection imposes a serious burden on patients with systemic lupus erythematosus (SLE). The increased infection rate in SLE patients has been attributed in part to defects of immune defence. Recently, the lectin pathway of complement activation has also been suggested to play a role in the occurrence of infections in SLE. In previous studies, SLE patients homozygous for mannose-binding lectin (MBL) variant alleles were at an increased risk of acquiring serious infections in comparison with patients who were heterozygous or homozygous for the normal allele. This association suggests a correlation between functional MBL level and occurrence of infections in SLE patients. We therefore investigated the biological activity of MBL and its relationship with the occurrence of infections in patients with SLE. Demographic and clinical data were collected in 103 patients with SLE. Functional MBL serum levels and MBL-induced C4 deposition were measured by enzyme-linked immunosorbent assay using mannan as coat and an MBL- or C4b-specific monoclonal antibody. The complete MBL-dependent pathway activity was determined by using an assay that measures the complete MBL pathway activity in serum, starting with binding of MBL to mannan, and was detected with a specific monoclonal antibody against C5b-9. Charts were systematically reviewed to obtain information on documented infections since diagnosis of SLE. Major infections were defined as infections requiring hospital admission and intravenous administration of antibiotics. In total, 115 infections since diagnosis of lupus, including 42 major infections, were documented in the 103 SLE patients (mean age 41 ± 13 years, mean disease duration 7 ± 4 years). The percentage of SLE patients with severe MBL deficiency was similar to that in 100 healthy controls: 13% versus 14%, respectively. Although deposition of C4 to mannan and MBL pathway activity were reduced in 21% and 43% of 103 SLE patients, respectively, neither functional MBL serum levels nor MBL pathway activity was associated with infections or major infections in regression analyses. In conclusion, SLE patients frequently suffer from infections, but deficiency of functional MBL does not confer additional risk

A case of severe chlorite poisoning successfully treated with early administration of methylene blue, renal replacement therapy, and red blood cell transfusion:case report

The case of a 55-year-old man who attempted suicide by ingesting <100 mL of 28% sodium chlorite solution is presented. On arrival in the intensive care unit, the patient appeared cyanotic with lowered consciousness and displayed anuria and chocolate brown serum.Initial laboratory tests revealed 40% of methemoglobin. The formation of methemoglobin was effectively treated with methylene blue (10% after 29 hours).To remove the toxin, and because of the anuric acute renal failure, the patient received renal replacement therapy. Despite these therapeutic measures, the patient developed hemolytic anemia and disseminated intravascular coagulation, which were treated with red blood cell transfusion and intermittent hemodialysis. These interventions led to the improvement of his condition and the patient eventually fully recovered. Patient gave written informed consent.This is the third known case of chlorite poisoning that has been reported. Based upon this case, we suggest the management of sodium chlorite poisoning to comprise the early administration of methylene blue, in addition to renal replacement therapy and transfusion of red blood cells

Weak Expression of Terminal Complement in Active Antibody-Mediated Rejection of the Kidney

BACKGROUND: The role of the complement system in antibody-mediated rejection (ABMR) is insufficiently understood. We aimed to investigate the role of local and systemic complement activation in active (aABMR). We quantified complement activation markers, C3, C3d, and C5b-9 in plasma of aABMR, and acute T-cell mediated rejection (aTCMR), and non-rejection kidney transplant recipients. Intra-renal complement markers were analyzed as C4d, C3d, C5b-9, and CD59 deposition. We examined in vitro complement activation and CD59 expression on renal endothelial cells upon incubation with human leukocyte antigen antibodies. METHODS: We included 50 kidney transplant recipients, who we histopathologically classified as aABMR (n=17), aTCMR (n=18), and non-rejection patients (n=15). RESULTS: Complement activation in plasma did not differ across groups. C3d and C4d deposition were discriminative for aABMR diagnosis. Particularly, C3d deposition was stronger in glomerular (P<0,01), and peritubular capillaries (P<0,05) comparing aABMR to aTCMR rejection and non-rejection biopsies. In contrast to C3d, C5b-9 was only mildly expressed across all groups. For C5b-9, no significant difference between aABMR and non-rejection biopsies regarding peritubular and glomerular C5b-9 deposition was evident. We replicated these findings in vitro using renal endothelial cells and found complement pathway activation with C4d and C3d, but without terminal C5b-9 deposition. Complement regulator CD59 was variably present in biopsies and constitutively expressed on renal endothelial cells in vitro. CONCLUSION: Our results indicate that terminal complement might only play a minor role in late aABMR, possibly indicating the need to re-evaluate the applicability of terminal complement inhibitors as treatment for aABMR

CUBN as a Novel Locus for End-Stage Renal Disease: Insights from Renal Transplantation

Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage renal disease (ESRD) and proteinuria. First, a total of 1142 patients with ESRD, admitted for renal transplantation, and 1186 donors were genotyped for SNPs rs7918972 and rs1801239 (case-control study). The rs7918972 minor allele frequency (MAF) was higher in ESRD patients comparing to kidney donors, implicating an increased risk for ESRD (OR 1.39, p = 0.0004) in native kidneys. Second, after transplantation recipients were followed for 5.8 [3.8–9.2] years (longitudinal study) documenting ESRD in transplanted kidneys – graft failure (GF). During post-transplant follow-up 92 (9.6%) cases of death-censored GF occurred. Donor rs7918972 MAF, representing genotype of the transplanted kidney, was 16.3% in GF vs 10.7% in cases with functioning graft. Consistently, a multivariate Cox regression analysis showed that donor rs7918972 is a predictor of GF, although statistical significance was not reached (HR 1.53, p = 0.055). There was no association of recipient rs7918972 with GF. Rs1801239 was not associated with ESRD or GF. In line with an association with the outcome, donor rs7918972 was associated with elevated proteinuria levels cross-sectionally at 1 year after transplantation. Thus, we identified CUBN rs7918972 as a novel risk variant for renal function loss in two independent settings: ESRD in native kidneys and GF in transplanted kidneys

Gastrointestinal tuberculosis following renal transplantation accompanied with septic shock and acute respiratory distress syndrome:A survival case presentation

Background: Post-transplant tuberculosis (PTTB) is a serious opportunistic infection in renal graft recipients with a 30-70 fold higher incidence compared to the general population. PTTB occurs most frequently within the first years after transplantation, manifesting as pulmonary or disseminated TB. Gastrointestinal TB (GITB) is a rare and potentially lethal manifestation of PTTB and may show delayed onset in renal transplant recipients due to the use of lower doses of immunosuppressants. Further, non-specificity of symptoms and the common occurrence of GI disorders in transplant recipients may delay diagnosis of GITB. Case presentation: Here we report a rare survival case of isolated GITB in a renal transplant recipient, occurring seven years after transplantation. The patient's condition was complicated by severe sepsis with positive blood culture Staphylococcus haemolyticus, septic shock, multiple organ failure including acute respiratory distress syndrome (ARDS) and acute renal failure, requiring mechanical ventilation, vasopressor circulatory support and intermittent hemodialysis. Furthermore, nosocomial infections such as invasive aspergillosis and Pseudomonas aeruginosa occurred during hospitalization. Antituberculosis therapy (rifampicin, isoniazid, ethambutol and pyrazinamide) was initiated upon Mycobacterium confirmation. Moreover, treatment with voriconazole due to the Aspergillus flavus and meropenem due to the Pseudomonas aeruginosa was initiated, the former necessitating discontinuation of rifampicin. After 34 days, the patient was weaned from mechanical ventilation and was discharged to the pulmonary ward, followed by complete recovery. Conclusion: This case offers a guideline for the clinical management towards survival of GITB in transplant patients, complicated by septic shock and multiple organ failure, including acute renal injury and ARDS

Effect of balloon angioplasty in femoropopliteal arteries assessed by intravascular ultrasound

Objective: To study the effects of balloon angioplasty (PTA) of the femoropopliteal artery with intravascular ultrasound (IVUS). Materials and methods: Corresponding IVUS cross-sections (n = 1033) obtained before and after PTA from 115 procedures were analysed. Vascular damage including plaque rupture, dissection and media rupture was assessed. Free lumen area (FLA), media-bounded area (MBA) and plaque area (PLA) were measured. Results: After PTA vascular damage was seen at the target site in 83 (72%) arteries: plaque rupture in 30 (26%), dissection in 66 (57%) and media rupture in 20 (17%) arteries. The FLA increased from 5.4 ± 3.4 mm2 to 14.1 ± 5.0 mm2 (p < 0.001), MBA increased from 26.9 ± 10.0 mm2 to 32.9 ± 10.7 mm2 (p < 0.001) and PLA decreased from 21.6 ± 8.5 mm2 to 18.8 ± 8.0 mm2 (p < 0.001). The increase in MBA accounted for 68% of lumen gain. The frequency of vascular damage and the relative contribution of MBA increase and PLA decrease to luminal gain were not different in procedures with balloon diameter ≤ 5 mm and ≤ 6 mm. Conclusions: Vascular damage is common following PTA. Lumen gain is mainly due to vessel expansion and, to a lesser extent, to a decrease in plaque area

Functional Studies on Primary Tubular Epithelial Cells Indicate a Tumor Suppressor Role of SETD2 in Clear Cell Renal Cell Carcinoma

SET domain-containing 2 (SETD2) is responsible for the trimethylation of histone H3 lysine36 (H3K36me3) and is one of the genes most frequently mutated in clear cell renal cell carcinoma (ccRCC). It is located at 3p21, one copy of which is lost in the majority of ccRCC tumors, suggesting that SETD2 might function as a tumor suppressor gene. However, the manner in which loss of SETD2 contributes to ccRCC development has not been studied in renal primary tubular epithelial cells (PTECs). Therefore, we studied the consequences of SETD2 knockdown through lentiviral shRNA in human PTECs. Consistent with its known function, SETD2 knockdown (SETD-KD) led to loss of H3K36me3 in PTECs. In contrast to SETD2 wild-type PTECs, which have a limited proliferation capacity; the SETD2-KD PTECs continued to proliferate. The expression profiles of SETD2-KD PTECs showed a large overlap with the expression profile of early-passage, proliferating PTECs, whereas nonproliferating PTECs showed a significantly different expression profile. Gene set enrichment analysis revealed a significant enrichment of E2F targets in SETD2-KD and proliferating PTECs as compared with nonproliferating PTECs and in proliferating PTEC compared with SETD2-KD. The SETD2-KD PTECs maintained low expression of CDKN2A and high expression of E2F1, whereas their levels changed with continuing passages in untreated PTECs. In contrast to the nonproliferating PTECs, SETD2-KD PTECs showed no β-galactosidase staining, confirming the protection against senescence. Our results indicate that SETD2 inactivation enables PTECs to bypass the senescence barrier, facilitating a malignant transformation toward ccRCC

Erratum to: Strong predictive value of mannose-binding lectin levels for cardiovascular risk of hemodialysis patients

Nephrolog