Randomized clinical trial of non-antibiotic prophylaxis with d-Mannose plus Proanthocyanidins vs. Proanthocyanidins alone for urinary tract infections and asymptomatic bacteriuria in de novo kidney transplant recipients: The Manotras study.

BACKGROUND: Studies analyzing non-antibiotic alternatives in kidney transplant UTI's are lacking. d-Mannose, a simple sugar, inhibits bacterial attachment to the urothelium, as does Proanthocyanidins; both could act as a synergic strategy preventing UTI; nonetheless their efficacy and safety have not been evaluated in kidney transplant population yet. METHODS: This is a pilot prospective, double-blind randomized trial. Sixty de novo kidney transplant recipients were randomized (1:1) to receive a prophylactic strategy based on a 24-h prolonged release formulation of d-Mannose plus Proanthocyanidins vs. Proanthocyanidins (PAC) alone. The supplements were taken for the first 3 months after kidney transplant and then followed up for 3 months as well. The main objective of the study was to search if the addition of Mannose to PAC alone reduced the incidence of UTI and/or asymptomatic bacteriuria in the first 6 months post-transplantation. RESULTS: 27% of patients experienced one UTI episode (cystitis or pyelonephritis) while asymptomatic bacteriuria was very common (57%). Incidences according UTI type or AB were: 7% vs. 4% for cystitis episode (p 0.3), 4% vs. 5% for pyelonephritis (p 0.5) and 17% vs. 14% for asymptomatic bacteriuria (p 0.4) for patients in the Mannose+PAC group vs. PAC group respectively. The most frequent bacteria isolated in both groups was Escherichia coli (28% of all episodes), UTI or AB due to E. coli was not different according to study group (30% vs. 23% for Mannose+PAC vs. PAC alone p 0.37). CONCLUSIONS: Non-antibiotic therapy is an unmet need to prevent UTI after kidney transplantation; however, the use of d-Mannose plus PAC does not seem capable to prevent it.

Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis.

Parietal epithelial cells (PECs) are kidney progenitor cells with similarities to a bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become activated and contribute to extracellular matrix deposition. Colony stimulating factor-1 (CSF-1), a hematopoietic growth factor, acts via its specific receptor, CSF-1R, and has been implicated in several glomerular diseases, although its role on PEC activation is unknown. Here, we found that CSF-1R was upregulated in PECs and podocytes in biopsies from patients with FSGS. Through in vitro studies, PECs were found to constitutively express CSF-1R. Incubation with CSF-1 induced CSF-1R upregulation and significant transcriptional regulation of genes involved in pathways associated with PEC activation. Specifically, CSF-1/CSF-1R activated the ERK1/2 signaling pathway and upregulated CD44 in PECs, while both ERK and CSF-1R inhibitors reduced CD44 expression. Functional studies showed that CSF-1 induced PEC proliferation and migration, while reducing the differentiation of PECs into podocytes. These results were validated in the Adriamycin-induced FSGS experimental mouse model. Importantly, treatment with either the CSF-1R-specific inhibitor GW2580 or Ki20227 provided a robust therapeutic effect. Thus, we provide evidence of the role of the CSF-1/CSF-1R pathway in PEC activation in FSGS, paving the way for future clinical studies investigating the therapeutic effect of CSF-1R inhibitors on patients with FSGS.

Sphenoparietal Sinus Transposition: Operative Technique for Optimizing Pretemporal Posterior Circulation Access While Preserving the Sylvian Venous Complex.

BACKGROUND: Transsylvian approaches are a cornerstone of complex cranial operations, with wide applicability across cerebrovascular, skull base, and neuro-oncology operations. Deep lesions, especially those involving the basilar apex, midbrain, or interpeduncular fossa, require wide exposures that may be inhibited by the presence of a large complex of superficial sylvian veins (SSV) draining into the sphenoparietal sinus. This report describes technical and clinical aspects of the sphenoparietal sinus transposition (SPST) technique. METHODS: Technical case report of the SPST technique, including a step-by-step neuroanatomic description, overview of common indications, clinical pearls and pitfalls, and illustrative case examples. RESULTS: Once the benefits of proceeding with SPST have been established, the maneuver is initiated with 2 stepwise dural incisions: an incision from lateral to medial along the lateral margin of the lesser sphenoid wing, followed by an orthogonal cut across the temporal pole down the middle fossa floor. The pretemporal dura is peeled off the lateral wall of the cavernous sinus, allowing mobilization of the SSV complex and temporal pole posteriorly without disrupting or straining the connection point at the sphenoparietal sinus. Illustrative case examples include a clip reconstruction of a basilar apex aneurysm for which earlier endovascular treatment had failed and microsurgical resection of a peduncular cavernous malformation. CONCLUSIONS: SPST is a simple but versatile technique with important applications in complex cranial surgery. By mobilizing the SSV complex together with its dural attachment, the transsylvian corridor can be markedly widened, allowing access to the basilar apex region and ventral midbrain.

Collapsing Glomerulonephritis in a Kidney Transplant Recipient after mRNA SARS-CoV-2 Vaccination.

With the vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), studies are describing cases of glomerulonephritis arising after vaccination. We present the first case of a kidney transplant patient who, after mRNA vaccination against SARS-CoV-2, developed nephrotic proteinuria and renal dysfunction, with a biopsy diagnostic of collapsing glomerulonephritis. No other triggers for this glomerulonephritis were identified. Antibodies against the spike protein were negative, but the patient developed a specific T-cell response. The close time between vaccination and the proteinuria suggests a possible determinant role of vaccination. We should be aware of nephropathies appearing after COVID-19 vaccination in kidney transplant recipients also.

Molecular Mechanisms of Kidney Injury and Repair.

Chronic kidney disease (CKD) will become the fifth global cause of death by 2040, thus emphasizing the need to better understand the molecular mechanisms of damage and regeneration in the kidney. CKD predisposes to acute kidney injury (AKI) which, in turn, promotes CKD progression. This implies that CKD or the AKI-to-CKD transition are associated with dysfunctional kidney repair mechanisms. Current therapeutic options slow CKD progression but fail to treat or accelerate recovery from AKI and are unable to promote kidney regeneration. Unraveling the cellular and molecular mechanisms involved in kidney injury and repair, including the failure of this process, may provide novel biomarkers and therapeutic tools. We now review the contribution of different molecular and cellular events to the AKI-to-CKD transition, focusing on the role of macrophages in kidney injury, the different forms of regulated cell death and necroinflammation, cellular senescence and the senescence-associated secretory phenotype (SAPS), polyploidization, and podocyte injury and activation of parietal epithelial cells. Next, we discuss key contributors to repair of kidney injury and opportunities for their therapeutic manipulation, with a focus on resident renal progenitor cells, stem cells and their reparative secretome, certain macrophage subphenotypes within the M2 phenotype and senescent cell clearance.

Obesity in Renal Transplantation.

BACKGROUND: Data from the WHO show an increasing rate of overweight and obesity in general population in the last decades. This increase in obesity also affects population with end-stage renal disease (ESRD) and kidney transplant (KT) candidates. SUMMARY: In this review, we focused on how obesity impacts on KT stages: access to KT and outcomes of KT candidates; how to reduce weight and its consequences; short and long-term outcomes in obese recipients and the impact of weight variations; and the implications of obesity in living donor KT. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials until November 30, 2020. We selected systematic reviews and meta-analyses and randomized clinical trials. When no such reports were found for a topic, observational studies were included in the assessment. Key Messages: Although obesity is a risk factor to present worst outcomes after KT, several studies have demonstrated a survival benefit compared to patients who continue on dialysis. There is a need for a public health campaign to raise awareness in KT candidates and to highlight the importance of self-care, increasing exercise, healthy diet, and weight loss.