Toxic Nephropathies of the Tubulointerstitium: Core Curriculum 2024.

Toxic nephropathies are a clinically common group of disorders characterized by toxin-induced renal injury that can affect the glomerulus, vasculature, or tubulointerstitium. Various endogenous (eg, myoglobin, hemoglobin, monoclonal light chains, and lysozymes) and exogenous toxins (eg, therapeutic drugs, herbal medications, heavy metals, radiocontrast, intoxicants, and environmental exposures) have been implicated. The kidney's primary role of metabolism and excretion of substances via glomerular filtration and tubular secretion increases its susceptibility to their adverse effects. The structure, dose, metabolic handling, and excretory pathway of the drug/toxin through the kidney determines its nephrotoxic risk. Patient characteristics that impact risk include genetic determinants of drug metabolism, transport and excretion, immune response genes, and comorbid conditions. Clinical manifestations depend on site and severity of renal injury. Toxin-induced tubulointerstitial injury often presents as a decline in renal function and/or solute transport defects and renal solute wasting. Injury is often reversible with limited toxin exposure; however, irreversible renal injury can occur with prolonged exposure. In this Core Curriculum, we will focus on discussing mechanisms of common toxin-induced tubulointerstitial renal injury and review their causes, clinical presentations, diagnosis, and management.

Assessment of a hemodialysis E-curriculum in postgraduate nephrology education: A pilot mixed methods study.

BACKGROUND: Online educational modules support asynchronous E-learning and offer several advantages. This multi-institutional pilot study describes the experience among nephrology trainees, of using a faculty-developed interactive E-curriculum in hemodialysis (HD) and examines its impact on learner knowledge and satisfaction. STUDY DESIGN: A sequential mixed method design was developed for curriculum assessment, using a survey tool and 1 : 1 interview. SETTING AND PARTICIPANTS: Current or recent (within past 2 years) nephrology fellows from four U.S. training programs. MATERIALS AND METHODS: After curriculum completion, a 6-item survey was administered to all conveniently sampled participants followed by a 1 : 1 interview of a sampled subset. Quantitative and qualitative data were analyzed using descriptive statistics and thematic analysis, respectively. RESULTS: 25 participants (18 Yale and 7 non-Yale) were recruited. All participants filled a 6-item Qualtrics survey after curriculum completion; 12/25 were interviewed. The majority were 1st (11/25) or 2nd year (8/25) nephrology fellows. Most self-identified as visual (11/25) or kinesthetic (11/25) learners. 100% participants agreed to the ease of use and clinical applicability of the E-modules; 100% found the animated videos and self-assessment sections valuable. On a scale of 1 (not comfortable at all) to 5 (very comfortable), respondents rated their perceived level of knowledge in 6 key competency areas. Means were 2.2 (range: 2.08 - 2.6) pre-intervention and 4.1 (range: 4.0 - 4.32) post-intervention, representing a significant increase (p-value = 0.0001). Animated videos were the most desired feature of the curriculum. Standardization, repetition, a controlled learning environment, and flexibility were identified as key advantages of an E-curriculum. Need for a self-motivated learner and lack of collaborative learning were its limitations. CONCLUSION: Our study highlights the effectiveness of an asynchronous E-curriculum in promoting active learning in nephrology and provides a framework for E-curricula development. Further study is needed to assess its impact on changes in learner attitude and patient outcomes.

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.

A hemodialysis curriculum for nephrology fellows using a blended learning approach: best of both worlds?

A comprehensive, hands-on hemodialysis curriculum during nephrology training is necessary for effective learning and optimal patient care. Traditional instructive approaches are unable to fully meet the needs of the digitally inclined learner and are limited by time constraints and increasing clinical workload. Internet based learning (E-learning) is becoming increasingly popular in medical education and nephrology and gaining even greater relevance in the COVID era. However, it presents technical challenges and may create an environment of social isolation. A 'blended learning approach' combines E-learning with traditional methods of teaching and offers advantages over either approach alone. We have designed and implemented a formalized hemodialysis curriculum at our institution that is based on blended learning, utilizing faculty-created E-learning tools combined with traditional pedagogical methods (bed-side and classroom). The web-based tools discuss hemodialysis adequacy, principles of urea transport, hemodialysis access examination and access complications. These tools are open access and structured around the science of cognitive learning using animation, interactivity, self-assessment and immediate feedback features. They have been viewed by a wide audience of nephrologists, dialysis nurses as well as medicine house-staff and have received strong validation in a post-test survey. The online tools have supported a 'flipped classroom' instructive model and our blended curriculum has been successfully used for nephrology fellow training at our institution. Incorporating faculty designed/approved E-learning tools to create a 'blended' nephrology curriculum for trainees at various levels of medical education, can help streamline active and time-efficient learning, with the goal of improving learner engagement, knowledge acquisition and academic curiosity in the field.

Attitudes Toward Organ, Tissue, and Vascularized Composite Allograft (VCA) Donation and Transplantation: A Survey of United States Military Veterans.

BACKGROUND: There are 20 million living US armed forces veterans; however, the organ donation attitudes of veterans have not been examined. METHODS: Over a 17-month period, a convenience sample of 1517 veterans in New England completed a survey to assess attitudes about organ, tissue, and vascularized composite allograft (VCA) donation. RESULTS: Most veterans (96%) supported the donation of organs and tissue for transplantation, and 59% were registered as an organ and tissue donor. Being younger (adjusted odds ratio [aOR]: 0.960.970.98; P = 0.01), female (aOR: 1.061.462.03; P = 0.02), non-Hispanic white (aOR: 1.302.073.30; P = 0.01), Hispanic (aOR: 1.282.434.61; P = 0.01), and having more trust that the transplant process is fair and equal (aOR: 1.191.401.65; P = 0.01) were predictive of donor registration. Also, most veterans were willing to donate their face (57%), hands/arms (81%), legs (81%), penis (men: 61%), and uterus (women: 76%) at time of death; donation willingness was higher for upper and lower limbs than for face or genitourinary organs (P < 0.001). Those unwilling to donate VCA organs expressed concerns about identity loss, psychological discomfort of self and others, body integrity, funeral presentation, and religious beliefs. Most (54%) felt that VCA donation should require permission of legal next-of-kin at the time of one's death, even if the decedent was a registered donor. CONCLUSIONS: There is a high level of support for organ, tissue, and VCA transplantation and donation among veterans, despite limited educational campaigns targeting this population. There is high potential among veterans to further increase donor registry enrollment and raise awareness about VCA benefits for severely injured service members.

Resistant Hypertension Updated Guidelines.

PURPOSE OF REVIEW: To discuss the current definition as well as recommendations for diagnosis and treatment of resistant hypertension (RH) based on the 2018 American Heart Association (AHA) guidelines and recent literature. RECENT FINDINGS: RH is defined as uncontrolled blood pressure (BP) on ≥ 3 anti-hypertensives, one of which should be a diuretic, prescribed at maximally tolerated doses and appropriate dosing frequency. The diagnosis of RH requires exclusion of white coat effect and medication non-adherence, underscoring the importance of out-of-office BP measurements. Secondary causes of hypertension must be excluded in all patients with RH. A step-wise approach to treatment focusing on lifestyle modifications and medication optimization can be effective in > 50% of the patients with RH. Device-based interventional therapies for RH are currently investigational. Out-of-office BP measurements are central to the diagnosis of RH. Medication optimization is successful in most patients. Further studies are needed to define the role of device-based interventions.

The Role of PET Scanning in the Evaluation of Patients With Kidney Disease.

Patients with underlying kidney disease are often required to undergo imaging for a variety of purposes including diagnosis and prognosis. A test that is being increasingly used with for this group of patients is the positron emission test (PET) scan. In addition, combining the nuclear medicine technique (PET) with computed tomography scan allows additional imaging advantages over either alone. These imaging modalities are commonly used for a number of extrarenal indications (ie, cancer, coronary artery disease, central nervous system disease, infectious diseases, and others). They have also been used for diagnosis of acute tubulointerstitial nephritis, evaluation and management of retroperitoneal fibrosis, identifying infection within kidney and liver cysts, and distinguishing complex kidney cysts from kidney cancer in patients with underlying CKD. We will review PET scan utility in patients with kidney disease.

We Avoid Antibiotic Lock Solutions due to Fear of Antibiotic Resistance.

Hemodialysis catheter-related bacteremia (CRB) is the most common complication associated with catheter use in dialysis patients and portends a high morbidity and mortality. Current CDC and KDIGO guidelines recommend treating CRBs with systemic antibiotics in conjunction with catheter replacement, although the latter has limitations. Antibiotic lock solutions (ABLs) are very effective in both prevention and treatment of CRBs in hemodialysis patients and may be a preferred alternative to catheter replacement especially in patients where catheter salvage is a priority. Previous smaller observational studies have raised concerns of a potential increase in antibiotic resistance associated with the widespread use of ABLs. Review of the recent literature does not support this claim.

We Hold Antihypertensives Prior To Dialysis.

Hypertension is the most common complication of end-stage renal disease and chronic hemodialysis and yet, only a third of these patients have adequately controlled blood pressures. Pathogenesis of hypertension in this population is complex and multifactorial and therefore poses numerous treatment challenges. Furthermore, it is common practice among nephrologists to withhold antihypertensives prior to a hemodialysis procedure due to concerns for intradialytic hypotension (IDH). Intradialytic hypertension (ID-HTN) is an increasingly recognized phenomenon and although less common than IDH, portends poor cardiovascular prognosis as well as reflects higher hypertension burden in the dialysis population. Withholding antihypertensives prior to dialysis routinely in patients may worsen interdialytic blood pressure control as well as increase the prevalence of euvolemic ID-HTN. It may also increase the risk of cardiac arrhythmias and further compromise hemodynamic stability during dialysis. In such situations, predialysis administration of antihypertensive is appropriate and necessary and drug choice should be based on the patient's comorbidities, pharmacokinetics of the drug and its dialyzability.

Drug-induced acute interstitial nephritis: pathology, pathogenesis, and treatment.

Drug-induced acute interstitial nephritis (DAIN) is a common cause of acute kidney injury and often presents as an unexplained rise in serum creatinine level. Kidney biopsy is therefore frequently required to make a definitive diagnosis. The hallmark pathologic features of DAIN are interstitial edema, interstitial inflammation, and tubulitis with a predominance of CD4+ T lymphocytes and mononuclear cells, with variable numbers of eosinophils. This is a result of a type B idiosyncratic non-immunoglobulin-E-mediated immune reaction marked by cell-mediated immune injury to the renal tubulointerstitium. The drug becomes immunogenic via various mechanisms such as haptenization, antigen mimicry, and neo-antigen formation. Renal interstitial dendritic cells, and renal tubular epithelial cells play an important role in further propagating this immunologic injury. Acute DAIN can progress within days to weeks to a chronic form triggered by fibroblast activation and manifested as interstitial fibrosis and tubular atrophy. The mainstay of treatment of DAIN is discontinuation of the offending drug. Incomplete renal recovery is seen in one-third of the patients and depends on the duration of injury prior to diagnosis. Use of steroids for treatment of DAIN makes biological sense, but lack of randomized controlled trials and conflicting data from retrospective studies makes the approach unclear. Positive effects include faster recovery of kidney function, more complete recovery with less chronic kidney disease, and reduced need for chronic dialysis. Therefore, it seems reasonable to employ corticosteroids in patients that do not rapidly improve 3 to 5 days following discontinuation of the offending agent.

A mutation in the mouse Chd2 chromatin remodeling enzyme results in a complex renal phenotype.

BACKGROUND AND AIMS: Glomerular diseases are the third leading cause of kidney failure worldwide, behind only diabetes and hypertension. The molecular mechanisms underlying the cause of glomerular diseases are still largely unknown. The identification and characterization of new molecules associated with glomerular function should provide new insights into understanding the diverse group of glomerular diseases. The Chd2 protein belongs to a family of enzymes involved in ATP-dependent chromatin remodeling, suggesting that it likely functions as an epigenetic regulator of gene expression via the modification of chromatin structure. METHODS: In this study, we present a detailed histomorphologic characterization of mice containing a mutation in the chromodomain helicase DNA-binding protein 2 (Chd2). RESULTS: We show that Chd2-mutant mice present with glomerulopathy, proteinuria, and significantly impaired kidney function. Additionally, serum analysis revealed decreased hemoglobin and hematocrit levels in Chd2-mutant mice, suggesting that the glomerulopathy observed in these mice is associated with anemia. CONCLUSION: Collectively, the data suggest a role for the Chd2 protein in the maintenance of kidney function.