Allograft tissue under the microscope: only the beginning.

PURPOSE OF REVIEW: To review novel modalities for interrogating a kidney allograft biopsy to complement the current Banff schema. RECENT FINDINGS: Newer approaches of Artificial Intelligence (AI), Machine Learning (ML), digital pathology including Ex Vivo Microscopy, evaluation of the biopsy gene expression using bulk, single cell, and spatial transcriptomics and spatial proteomics are now available for tissue interrogation. SUMMARY: Banff Schema of classification of allograft histology has standardized reporting of tissue pathology internationally greatly impacting clinical care and research. Inherent sampling error of biopsies, and lack of automated morphometric analysis with ordinal outputs limit its performance in prognostication of allograft health. Over the last decade, there has been an explosion of newer methods of evaluation of allograft tissue under the microscope. Digital pathology along with the application of AI and ML algorithms could revolutionize histopathological analyses. Novel molecular diagnostics such as spatially resolved single cell transcriptomics are identifying newer mechanisms underlying the pathologic diagnosis to delineate pathways of immunological activation, tissue injury, repair, and regeneration in allograft tissues. While these techniques are the future of tissue analysis, costs and complex logistics currently limit their clinical use.

Update on Renal Sympathetic Denervation for the Treatment of Hypertension.

PURPOSE OF REVIEW: Hypertension is a leading risk factor for all-cause mortality in adults; however, medication non-adherence and intolerance present an enormous treatment challenge. Given the critical role of renal sympathetic nerves in neurogenic control of blood pressure and pathophysiology of hypertension, renal sympathetic denervation (RDN) has been explored as a therapeutic strategy in hypertension treatment over the last 15 years. In this review, we will discuss the role of renal sympathetic nerves in the pathophysiology of hypertension, provide an update on the available evidence regarding the short- and long-term safety and effectiveness of RDN in the treatment of hypertension, and consider its future perspectives. RECENT FINDINGS: RDN is a percutaneous endovascular catheter-based neuromodulation approach that enables ablation of renal sympathetic nerve fibers within the adventitial layer of the renal arteries using radiofrequency (most extensively studied), ultrasound energy, or neurolytics (e.g., alcohol). In the last decade, advancements in procedural techniques and well-designed sham-controlled trials utilizing 24-h ambulatory blood pressure measurements have demonstrated that RDN has an excellent safety profile and results in a modest reduction of blood pressure, in a wide range of hypertensive phenotypes (mild to resistant), irrespective of antihypertensive drug use and this effect is sustained over a 3-year period. Superiority of a particular RDN modality has not been yet established. Despite strong evidence demonstrating efficacy and safety of RDN, current data does not support its use as a primary approach in the treatment of hypertension due to its modest treatment effect and concerns around long-term sustainability. Perhaps the best utility of RDN is in hypertensives intolerant to antihypertensive medications or as an adjunct to aldosterone antagonists in the management of resistant hypertension. Patient selection will be critical to demonstrate a meaningful benefit of RDN. Future well-designed studies are necessary to determine predictors and measures of response to RDN, long-term efficacy given question of renal nerve regeneration, comparison of available technologies, safety in patients with advanced kidney disease, and improvement in patient quality of life measures.

Life-threatening hypertriglyceridemia-induced pancreatitis related to alectinib successfully treated by plasmapheresis: A review of the literature on metabolic toxicities associated with anaplastic lymphoma kinase inhibitors.

INTRODUCTION: Actionable mutations are tested as standard of care for all new metastatic non-small cell lung cancers. Tumors harboring an anaplastic lymphoma kinase mutation respond to tyrosine kinase inhibitors targeting anaplastic lymphoma kinase pathway. Patients are monitored for common adverse effects, although we occasionally encounter unexpected side effects. CASE REPORT: A 52-year-old male presented with a right hilar lung mass, and workup revealed a stage IIIA adenocarcinoma. He underwent treatment with concurrent chemoradiation; however, disease recurred one year later with a right hilar mass and contralateral mediastinal lymphadenopathy, biopsy of which resulted positive for adenocarcinoma. Molecular analysis showed anaplastic lymphoma kinase rearrangement and alectinib was started. Six months into therapy, he presented with hematochezia, nausea, and epigastric pain and was diagnosed with acute pancreatitis. Triglyceride level resulted above the measurable level at >5680mg/dL, thought to be the inciting event of pancreatitis.Management and outcome: Despite treatment with intravenous hydration, insulin infusion, and antibiotics, he decompensated with development of respiratory failure, shock requiring intensive care. Therapeutic plasmapheresis was initiated due to persistently elevated triglyceride. Following the third plasmapheresis, triglyceride level decreased to 359 mg/dL. With aggressive multidisciplinary management, he made a complete recovery. Follow-up imaging studies at three and six months show a stable mass-like abnormality in the right hilum without evidence of disease progression. DISCUSSION: Prior to starting alectinib, our patient's triglyceride level was 420 mg/dL. While he consumed alcohol, he had no other traditional risk factor. To our knowledge, this is the first reported case of hypertriglyceridemia-induced acute pancreatitis related to treatment with an anaplastic lymphoma kinase inhibitor.

Pregnancy in Chronic Kidney Disease: Acute Kidney Injury in Pregnant Women and Management of Chronic Kidney Disease in the Pregnant Patient.

Women pursue pregnancy with comorbidities such as hypertension and kidney disease, necessitating primary care physicians to remain up to date with current clinical practice. Hypertensive disorders of pregnancy pose risks to the pregnancy and to the woman in the short and long term. These risks and their management are detailed in this review. Normally, pregnancy is associated with hemodynamic and kidney-specific changes. Here the authors discuss these changes and review the impact and management of pregnancy-related acute kidney injury, chronic kidney disease, and dialysis in pregnant patients. Kidney transplant recipients may experience return of fertility and require counseling to improve outcomes.

Donor-Recipient Non-HLA Variants, Mismatches and Renal Allograft Outcomes: Evolving Paradigms.

Despite significant improvement in the rates of acute allograft rejection, proportionate improvements in kidney allograft longevity have not been realized, and are a source of intense research efforts. Emerging translational data and natural history studies suggest a role for anti-donor immune mechanisms in a majority of cases of allograft loss without patient death, even when overt evidence of acute rejection is not identified. At the level of the donor and recipient genome, differences in highly polymorphic HLA genes are routinely evaluated between donor and recipient pairs as part of organ allocation process, and utilized for patient-tailored induction and maintenance immunosuppression. However, a growing body of data have characterized specific variants in donor and recipient genes, outside of HLA loci, that induce phenotypic changes in donor organs or the recipient immune system, impacting transplant outcomes. Newer mechanisms for "mismatches" in these non-HLA loci have also been proposed during donor-recipient genome interactions with transplantation. Here, we review important recent data evaluating the role of non-HLA genetic loci and genome-wide donor-recipient mismatches in kidney allograft outcomes.

Talaromycosis in a Patient on Nintedanib for Interstitial Lung Disease.

Talaromycosis is a fungal infection caused by Talaromyces sp. that is predominantly prevalent in patients with acquired immunodeficiency syndrome in the United States. It is also rarely seen in other individuals who are otherwise immunosuppressed. With the advent of immunotherapy and increasing usage of these novel agents in treating several conditions, the prevalence of talaromycosis may increase, especially in people from endemic regions who might harbor a dormant infection. Clinical presentation is non-specific with respiratory symptoms such as shortness of breath, cough, or even fever that can delay the diagnosis. Little is known about the exact pathogenesis of the condition, and management is largely based on anecdotal evidence and small-sized studies. We present the case of an individual on nintedanib, a tyrosine kinase inhibitor that blocks fibroblast growth factor receptor and used for the treatment of interstitial lung disease, who was diagnosed with talaromycosis.

Overexpression of the BCL2 gene in a Sertoli-Leydig cell tumor of the ovary: a pathologic and cytogenetic study.

A case of virilizing ovarian Sertoli-Leydig cell tumor overexpressing the BCL2 gene and including a novel clonal chromosomal rearrangement of chromosome 18, der(5)t(5;18)(p13;q12),+6,+12, der(18)r(5;18)(p15.3p13;p11.3q12) is described. Further studies of these rare tumors are necessary to ascertain the significance of the findings.