Editorials
Treatment of Diabetic Nephropathy: Changing Landscapes and New Horizons
Until the early 19th century, diabetes mellitus (DM) was regarded as a disease of the kidney, in which one of the signs was that of an increase in the volume of urine and wasting. Only after the identification of glucose in blood and urine in the late 18th century was it recognized as a metabolic disorder. It was noted in parallel that patients with DM may show presence of coagulable urine containing albumin as a sign of kidney disease. After the advent of availability of insulin in the early 1920s, which led to increased survival, diabetic nephropathy became more apparent.A New Therapeutic Era in the Management of Diabetic Kidney Disease
Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease (ESKD) worldwide. After 2 decades of negative trials, in the last few years there has been a major and welcome shift in the therapeutic options to treat DKD. Nephrologists will be in the forefront of implementation of these new therapies as well as in the education of their colleagues and patients on the benefits and possible side effects of these novel therapies.The Ultrasound-Augmented Physical Exam for Nephrologists: Beyond the Kidney
Recent developments in handheld ultrasound technology, including cloud-based image archiving, artificial intelligence–enhanced image guidance, and the development of the capacitive micromachined ultrasound transducer—a microchip alternative to conventional piezoelectrics—are driving down the cost of ultrasound devices and facilitating image acquisition for novice learners. These technologic adaptations lower the barrier for entry and accelerate an already burgeoning trend of adoption of point-of-care ultrasound (POCUS) among medical providers.Home Hemodialysis
This special issue of ACKD on home hemodialysis (HHD) represents a timely reflection on the state of HHD in the United States. President Trump's executive order of July 2019 (Advancing American Kidney Health Initiative) laid out an ambitious agenda for expanding the use of home dialysis and preemptive kidney transplantation in the United States. This issue is a compendium of articles that are wide in their breadth and scope, representing an attempt to address a variety of issues involved in implementing such a complex and difficult task.Dialysis: Please Try This at Home!
Yes, in 2021, we are able to say that the quality of life and freedom to do the things we love can be possible while on dialysis. A special mention to the photograph on the cover of this issue dedicated to home hemodialysis (see credits in the issue), which exemplifies that.Nephrology Critical Care: A Darwinian Evolution
While hospitals across the nation continue to expand their capacity to care for critically ill patients, the practice of medicine in the intensive care unit (ICU) has evolved from being solo intensivist-driven to a multidisciplinary care model. The latter involves a myriad of clinicians as well as pharmacists, physical therapists, nutritionists, and subspecialists that usher a diverse and complementary expertise.1 Among many subspecialists in the ICU, the nephrologist serves as an invaluable asset in many commonly encountered conditions, including electrolyte/acid-base derangements and most notably acute kidney injury (AKI).COVID-19 and the Kidney Community: Coalescing in Crisis
The coronavirus disease 2019 (COVID-19) pandemic has led to significant changes to the practice of kidney medicine. The ability to provide acute dialysis is strained due to high rates of acute kidney injury (AKI), which occurs in up to 30% to 40% of hospitalized patients. The presence of AKI in the setting of COVID-19 is associated with high morbidity and mortality.1 Figure 1 illustrates various manifestations of COVID-19 in the kidney. The need for social distancing has resulted in a shift to outpatient telemedicine for many patients with kidney disease.Reenvisioning the Adult Nephrology Workforce: The Future of Kidney Care in the United States
The cover image in this issue of Advances in Chronic Kidney Disease illustrates the various components (pieces) that make up the nephrology workforce. Although our nephrology community strives to complete this puzzle, these pieces are dynamic and constantly evolving. It is up to our community to react to changes in kidney care to ensure our workforce is able to provide optimal care for patients with kidney disease.Future of Nephrology Workforce: Reimagining Educational Value
The definition of this term states “people engaged in or available for work in any enterprise or company”. Should we be satisfied in simply creating the future workforce? Or should we redefine in how we even articulate what the future of our profession may look like? Should we not be raising the bar to say that we want to nurture the next generation of compassionate and astute clinicians, scientists, and leaders? If so, then we need to reimagine how to do that and tread with caution as we pass on the knowledge to that generation.Dialysis Access: The Future Is Already Here
At the time of this writing, we are in the midst of a full-blown pandemic – the likes of which none of us have seen in our lifetimes. It is in times such as these that our profession and the care of our patients is seen through an unfiltered lens. The American Society of Diagnostic and Interventional Nephrology and the Vascular Access Society of the Americas in an effort to protect the mainstay of our patients' access to adequate dialytic care came together to publish a joint statement in March of 2020 sharing that maintaining dialysis accesses “will be instrumental in maintaining health and survival for patients with end-stage kidney disease (ESKD) as well as protecting hospitals from an eventual wave of high urgency/emergency procedures to deal with lost dialysis accesses.” Dialysis access truly is the lifeline of our patients – the infamous “Achilles Heel,” and in these dire times, our patients' need for a reliable, low-risk access becomes blatantly obvious.Interventional Nephrology: What, Who, Why?
These 2 words can mean different things from a patient's or a provider's perspective. For the patient, it is a “lifeline” to undergo a life-sustaining treatment, day after day, and lack of an optimal access can literally be a death sentence. Whether be it lack of achieving or maintaining the vascular access.O Complement, Where Aren't Thou
The innate immune system represents the oldest arm of mammalian host defense, of which the complement cascade is of paramount importance. Complement serves several roles, including direct cellular killing, tagging of foreign and self-debris for cell-mediated clearance, and modulation of the adaptive immune response. The Human Genome Organization Gene Nomenclature Committee recognizes 56 proteins within the complement pathway. Given this complexity, most medical students and clinicians devote little time to understanding the intricacies of the cascade.Poisoning, Toxicology, and the Nephrologist
In 2017, the American Association of Poison Control Centers reported more than 2.1 million human toxic exposures across the United States. In fact, toxic exposures with serious outcomes have increased every year since 2000.1 Although the 3208 resulting or related deaths were far fewer than the total referrals and interventions, concerns remain. Most reported exposures were due to a few classes of prescription medications (analgesics, sedative/hypnotics, antipsychotics, antidepressants) or readily available cleaning or personal care products.Toxicology and Kidney: Not so Innocent Bystander
Patients are exposed to numerous prescribed and over-the-counter medications. Unfortunately, drugs remain a relatively common cause of acute and chronic kidney injury. By some estimates, up to 1-in-3 cases of acute kidney injury (AKI) can be attributed to the effect of prescribed drugs and endogenous/exogenous toxins. However, establishing causality in drug-induced kidney disease is challenging and requires knowledge of the biological plausibility of the agent, mechanism of injury, time course, and assessment of competing risk factors.Advances in Chronic Kidney Disease as Syntopicon
Advances in Chronic Kidney Disease began its life under the aegis of Allen R. Nissenson as the first Editor-in-Chief of Advances in Renal Replacement Therapy.1 Dr. Nissenson's expressed desire was for A-R-R-T to become the “art” of renal replacement therapy. He explicitly stated this aspiration, echoing the enthusiastic prose of Dr. Seuss, in his inaugural editorial in April 1994, “The ARRT of Uremia Therapy.”1 Instrumental to the journal's conception was much the effort of Garabed Eknoyan—a long-time advisor-contributor to the National Kidney Foundation in so many ways.Cardiovascular Calcifications Among Patients With Uremia: Answers to Hard Questions
A 56-year-old woman with long-standing history of diabetes mellitus and end-stage renal disease is evaluated for severely painful indurations covering both thighs. She is obese and has been on warfarin therapy for atrial fibrillation. A skin biopsy obtained from the indurated area demonstrates calcifications involving subcutaneous arterioles and adjacent adipocytes. A diagnosis of uremic calciphylaxis is made. Prior radiological examinations demonstrate diffuse arterial and valvular calcifications involving coronary, mesenteric, carotid, femoral and aortic beds, and mitral and tricuspid valves.Lupus Nephritis: Breaking the Lull
Systemic lupus erythematosus (SLE) has a prevalence of 241 per 100,000 people in the United States.1 Young women are disproportionately affected and disease burden is highest in blacks and lowest in whites in studies that report data by race.1 Up to 75% of SLE patients will develop kidney disease, which is often asymptomatic and detected only by urinalysis. Pathologic classification of lupus nephritis (LN) is based on the location and degree of glomerular involvement coupled with the activity and chronicity of histologic changes.Lupus Nephritis: How Far Have We Come, and Where Are We Headed?
Of all the organ domains involved in systemic lupus erythematosus (SLE), renal disease is associated with the greatest morbidity and mortality. Relative age-adjusted mortality in SLE patients with renal disease compared to those without is greater at every level of renal involvement and stage of CKD.1,2 Recent data show decreased trends in the burden of end-stage renal disease (ESRD) due to lupus nephritis (LN) in the United States. However, greater than 50% of SLE patients will develop LN and an unacceptably high number (up to 44% of patients with class III or IV LN) progress to ESRD by 15 years requiring renal replacement therapy in the form of dialysis or kidney transplant.Erythropoiesis-Stimulating Agents and Cancer: Myth or Truth
Erythropoiesis-stimulating agents (ESAs) have been implicated in causing cancer progression. This belief has been largely based on trials in the early 2000s of ESA use in malignancy with high hemoglobin (Hgb) targets and large ESA doses to attain the targets. More recent trials using ESA doses with Hgb targets similar to current goal levels in CKD have not confirmed this increased risk of cancer progression for most malignancies.Anemia Treatment After 30 Years of Erythropoietic Stimulating Agents: No Longer Business as Usual?
The publication date of this issue of ACKD, July-August 2019, is almost exactly 30 years after the approval by the Food and Drug Administration (FDA) of epoetin alfa in June 1989. There has been considerable evolution in the treatment of anemia in patients with CKD since that time despite the fact that erythropoietic stimulating agents (ESAs) remain the mainstay of that therapy. In the 1990s, we discovered the necessity of adequate iron supplementation to achieve the targeted erythropoietic response to ESAs.Eradicating the Viral Triad in Hemodialysis Units
In this issue of Advances in Chronic Kidney Diseases, Dr James Novak as Guest Editor has curated a collection of manuscripts from a cadre of nephrologists whose curiosity includes the viral nephropathies. The authors present a well-researched group of articles that comprehensively review the vast majority of contemporary viral disorders with which most nephrologists will engage at some point in their careers. However, the bulk of nephrologists will be concerned with 3 viruses more than others, hepatitis C virus (HCV), hepatitis B virus (HBV), and the human immunodeficiency virus-1 (HIV).Warning: Kidney Virus Detected
The variety of genes on the planet in viruses exceeds, or is likely to exceed, that in all of the rest of life combined. —Edward O. Wilson In 1993, the number of viruses that infected vertebrates, specifically mammals, was estimated at 1,000,000 and 320,000, respectively.1 By 2012, 219 human virus species had been identified, with 3–4 novel viruses projected to emerge each year from mammalian and avian reservoirs.2 Advances in genetics during the past few decades have facilitated the detection of more and more occult viruses, previously unrecognized within the human genome, the accumulation of which is collectively known as the human virome.Dr. Conn Lives on: Insights Into Screening and Genetics of Primary Aldosteronism
This issue of Advances in Chronic Kidney Disease features an old standard, hypertension. This topic is reviewed periodically. This time, Dr. Kausik Umanath has taken up the gauntlet to press forward our collective mission to diagnose and treat this most fundamental medical problem early, accurately, and efficiently. In this issue, the variegation of the pathophysiology of hypertension will be revealed along with its treatments. In Dr. Umanath's Guest Editorial, you will see a glimpse of what is contained within, but first, a story.Hypertension: A Common but Complex Condition
Hypertension is a common condition known to cause significant cardiovascular events including death, stroke, and heart failure.1,2 Our understanding of the pathogenesis and optimal approaches to therapy has evolved tremendously over the past 50 years.3 Despite these advances, only 50% of individuals achieve blood pressure control according to National Health and Nutrition Examination Surveys 2015-2016 data.4 Hypertension remains a significant global health problem, and in this issue of Advances in Chronic Kidney Disease, we have put together a set of manuscripts covering several key issues in both the pathogenesis and management of hypertension.The Many Faces of Infection in CKD: Evolving Paradigms, Insights, and Novel Therapies
In 1961, Schreiner was the first to note unique susceptibility to infection among patients with kidney failure.1 It was assumed that general debility from chronic uremia increased the risk of infection; thus, it was postulated that reversal of the uremic state would reduce the risk of infection.2 Unfortunately, kidney replacement therapy has not reduced the problem of infection; it has only changed the paradigm.3 Dialysis superimposes myriad new problems onto patients already suffering relentless deterioration from underlying multisystem disease and poor wound healing.Hemodialysis Catheter Device Protection: Damned if We Do; Patients Are Damned if We Don't
In this issue of Advances in Chronic Kidney Disease, Guest Editor Mohanram Narayanan, MD, reinvigorates the prior theme of infections in kidney patients. Infections are frequent in nephrology patients and often deadly. Each of Dr. Narayanan's authors pointedly contributes his/her wisdom to the infection theme. So, before reading more, please read each article carefully to enhance your practical working knowledge on behalf of your patients.Leadership in Nephrology: Vital to the Future of Our Profession
When surveyed in 2016 by the Renal Physicians Association, young nephrologists expressed surprise at the speed and manner in which nephrology as a field was changing and “the unique opportunity for leadership” inherent to the profession. The notable concern for a “lack of physician leadership” was balanced by the general sentiment that nephrologists are “uniquely positioned to lead” the way in providing innovation to chronic health care management.Leadership as Tribal Leader
In this final 2018 issue of Advances in Chronic Kidney Disease, our Guest Editor Rebecca Schmidt takes the lead on leadership. She has compiled a series of articles that compress 2 important and sometimes nebulous concepts into digestible format with the assistance of her contributing authors. Each article adds to the others to provide a roadmap to establishing a successful career in medicine and specifically nephrology.A Tale of Two Failures: A Guide to Shared Decision-Making for Heart and Renal Failure
Heart failure and kidney disease are common and rapidly growing conditions in the United States. It is estimated that there are currently 6.5 million adults in the United States1 and 23 million adults worldwide who suffer from heart failure.2 Approximately 30 million Americans have evidence of chronic kidney disease (CKD).3 The presence of either condition is associated with a higher morbidity and mortality than the general population. Approximately 40% of patients with end-stage renal disease (ESRD) have heart failure.Cardiorenal Syndrome: A Call to Action for a Pressing Medical Issue
Thomas Lewis used the term “cardiorenal” in his lecture titled “Paroxysmal Dyspnoea in Cardiorenal Patients” in which he discussed his clinical observations on patients with dyspnea related to advanced heart and kidney disease (referred to as cardiac and uremic asthma in the lecture).1 However, researchers in the 19th and early 20th century had already noted the interactions between the heart and the kidney and performed eloquent experiments highlighting the impact of venous congestion on kidney function.It Is Really Time for Ammonium Measurement
In this issue of Advances in CKD, Guest Editors, Jose A. Arruda and Daniel Batlle, have assembled an A-list of clinician-scientists to review the old and new concepts of renal tubular acidosis (RTA). In an era in which dialysis and CKD dominate nephrology clinical practice, is it not nice to encounter something different every now and then? A low-serum venous total CO2 (referred to as bicarbonate, hereafter), of which the etiology is not readily apparent, is one of the many respites for acid-base mavens of nephrology.Renal Tubular Acidosis and the Nephrology Teaching Paradigm
The renal tubular acidosis (RTA) syndromes, while relatively rare, are of great interest among students of pathophysiology because they offer a model of disease in which the biochemical, physiologic, molecular, and, in some cases, genetic basis of its pathogenesis can be examined.1 Understanding the mechanisms causing RTA also offers a paradigm for nephrology teaching. Practicing physicians as well as adult and pediatric nephrologists in the academic setting who teach trainees at all levels ought to have a solid understanding of the RTA syndromes.Diabetes and the Kidney: Sweet Dreams
A spoonful of sugar makes the medicine go down. —Robert B. Sherman, Richard M. Sherman; 1964 With apologies to Julie Andrews, a spoonful of sugar might be considered child abuse in this modern era of diabetes and obesity. As of 2015, more than 700 million adults worldwide have diabetes or impaired glucose tolerance, and about half of these are unaware of the diagnosis.1 Almost certainly, the glut of type 2 diabetes has been fueled by the expanding obesity epidemic (pun intended). In the United States, the prevalence of obesity tripled from 13% in 1960 to 38% in 2014.Diabetic Kidney Disease (c. 2018)
Diabetes has become a global pandemic that rivals almost any other that has come before it. In the year 2015, 415 million people in the world were living with diabetes, and by the year 2040, that number is projected to rise to 642 million. Most of these people, 95%, have type 2 diabetes. More sobering, there is no evidence that the steadily upward trend in diabetes frequency will abate despite unequivocal evidence that type 2 diabetes is largely preventable, especially by healthy lifestyle choices.Disturbances in Acid-Base, Potassium, and Sodium Balance in Patients With CKD: New Insights and Novel Therapies
The kidney plays a critical role in the regulation of acid-base, potassium, and sodium balance, a role that can be compromised by a decrease in kidney function caused by CKD (defined as an eGFR < 60 mL/min/1.73 m2). Because of the high prevalence of type II diabetes and hypertension, progressive damage to the kidney resulting in CKD is increasingly common in the world's population. Furthermore, it is likely that the prevalence of CKD will only increase as the population ages.Hyperkalemia: Inpatient PaniK
In this issue, Guest Editor Jeffrey Kraut determined to “go back to the basics” of nephrology and assembled an august group of authors whose expertise spans the gamut of electrolytes and acid-base disorders. The table of contents represents a carefully curated compilation of articles, each of which is a minireview and state-of-the-art appraisal of the literature on a particular topic. In alignment with this familiar group of topics, I have chosen to concentrate on inpatient hyperkalemia. Rather than opining on the panoply of potassium abundance disorders, I devote my time and yours to matters of all things done wrong when confronted with inpatient hyperkalemia, a common finding that evokes a “PaniK” disorder.Acute Kidney Injury: A Paradigm in Quality and Patient Safety
The first contemporary description of the syndrome of acute tubular necrosis (synonymously used with the clinical diagnosis of acute kidney injury) was reported by Drs. Bywaters and Beal.1 That specific case was a clinical description of a young woman who had suffered crush injuries during the “London Blitz,” with the probably cause of ATN resulting from a combination of ischemic injury and rhabdomyolysis. It turns out that there have been prior historical references hinting toward nephrotoxic injury.The AKI Clinic for Fragile Patients
The recent terrorist attack in Manchester, England, at a pop “musical” concert1 represents a somber reminder of the London Blitz—the “lightning war”—prosecuted by Hitler against Great Britain during World War II. The dome of the church on the cover illustration, provided by Guest Editor, Charuhas Thakar, represents the hope of the Londoners who survived the protracted bombing that lasted 9 months, and our own hope that an effective resolution to the abject, lawless acts of violence by fanatical and radical terrorists comes soon.Prophylactic Hemodialysis for Protection Against Gadolinium-Induced Nephrogenic Systemic Fibrosis: A Doll's House
No doubt you, like I, have been informed by your radiologist that your advanced CKD or ESRD patient “must undergo hemodialysis” to prevent gadolinium-based contrast agent (GBCA)-induced nephrogenic systemic fibrosis (NSF) following a magnetic resonance imaging (MRI) study. Few disorders in nephrology have generated more excitement and fear than this devastating dermatologic disorder, first described in 2001 as a case series of 13 patients originally discovered in 1997 at the Sharp Clinic.1 This disfiguring and disabling skin-scarring disorder, formerly labeled as nephrogenic fibrosing dermopathy, is attributed to the deposition of gadolinium chelates in the skin and other organs, hence, the “systemic” term.Scared to the Marrow: Pitfalls and Pearls in Renal Imaging
Medical science can only flourish when it is conducted in alignment with society's interests. We value the health of our patients and want to ensure the safety of our diagnostic procedures. Often the quality and value of these procedures are increased with intravascular contrast. Common contrast materials include iodinated contrast (useful in too many X-ray-enhanced examinations to list) and gadolinium-based contrast for nuclear magnetic resonance imaging.The Renal Tubulointerstitium
The renal tubulointerstitium is an often underappreciated compartment of the kidney but of great importance in acute kidney disease and CKD. As early as the 1970s, Bohle and colleagues1 recognized that kidney function did not correlate well with the severity of glomerular disease but rather with the relative interstitial volume. We now know that the microenvironment encompassing the tubulointerstitium is composed of tubular epithelial cells, interstitial cells, peritubular capillary endothelium, pericytes, and extracellular matrix, which have complex structural and functional relationships.The Tubulointerstitium: Dark Matter
Relegated to a less glamorous position than the glomerulonephritides, the tubulointerstitial compartment or tubulointerstitium of the kidney has been the dark matter of the kidney universe.1 In the same fashion that dark matter predominates over atomic matter, the tubulointerstitium does so over the glomerular compartment. In fact, dark matter and the tubulointerstitium hold their respective universes together. In this issue, some of the mysteries of kidney dark matter are revealed by Cynthia Nast and the authors she has enlisted.A Fundamental Theorem of Telehealth
In 2009, Friedman proposed the Fundamental Theorem of Informatics,1 which stipulates that a person working in partnership with an information resource (eg, an informatics system such as a computer) is “better” than that same person unassisted (Fig 1A). Similarly, Friedman described what informatics is not, explaining that informatics is more about people than technology (Fig 1B). Current advances in the use of health care informatics for the treatment of chronic illness have expanded into the realm of telehealth, and Friedman's theorem can be equally applied to its intent.Nephrology and Telehealth: Now? or Now!
In this issue of Advances in Chronic Kidney Disease, Clarissa Diamantidis, Andrew Narva, and colleagues provide examples of telehealth within the field of nephrology that are actively utilized today. They also offer descriptions of real-world approaches to the development and sustainability of such telehealth programs.One Isn't the Loneliest of Numbers: N-of-1 Trials
In this issue of Advances in Chronic Kidney Disease by Guest Editors, Donald Molony and Joshua Samuels, evidence-based medicine (EBM) once again comes to the fore. This issue represents an encore of sorts, reinvigorating many of the concepts which they promoted with their authors in Volume 19, Issue 1 of this journal, “Evidence-Based Nephrology.”Translation of Evidence Into Clinical Practice
Evidence-based medicine (EBM) emerges from the belief that delivery of care to patients will be more effective and efficient if decisions are based, as much as possible, on unbiased robust evidence regarding prognosis, etiology, diagnosis, and therapy/prevention. Although acknowledging a degree of uncertainty in every clinical decision, EBM has always challenged practitioners to pursue evidence to reduce uncertainty as much as possible. Application of only the most rigorous evidence can minimize the uncertainly inherent in medical decisions.Advanced CKD: Preparing for a Storm to Avoid a Disaster
Traditionally, advanced CKD is the stage when we try to prepare a patient for the possible need for renal replacement therapy (RRT). Our difficulty as clinicians in this preparation is multifold: all patients do not progress uniformly; an individual patient's trajectory of decline can hasten or slow; comorbidities may cause death before needing RRT; acute kidney injury may herald the need for more urgent initiation of dialysis; and patients may resist our treatment plans and tell us they are fine.Improving Transitions in CKD: Failure Mode
In this issue of ACKD, Maria DeVita with her collaborators summarize the important points to consider as patients transition from Stage 4 to Stage 5 CKD. The earlier transition from Stage 3A to Stage 3B portends enhanced cardiovascular risk, and these heart and vascular risks and overall mortality increase exponentially through Stages 4 and 5.1,2 The importance of safe navigation through the course of Stage 4 cannot be overemphasized. This is particularly relevant in terms of patient education and modality of renal replacement therapy.Intensive Care Unit Renal Replacement Therapy: Less Is More (or Better)
Acute kidney injury (AKI) is on every nephrologist's mind. Although it took some time for the transition to the nomenclature of CKD stages from chronic kidney failure, the rapid assimilation of “AKI” into the internal medicine vernacular has been relatively light speed. Now, AKI must be considered a cause of CKD, although not necessarily in the fashion of a 5/6 nephrectomy—an immediate cause of CKD that is accompanied by a tremendous degree of compensatory hypertrophy unseen in the human analogue.Changing Faces of Critical Care Nephrology
The intensive care unit is dynamic and constantly evolving. Four years ago, we devoted an issue to Critical Care for the Nephrologist. Since then, there has been sufficient change in the field to devote another issue of “Advances in Chronic Kidney Disease” to the topic of critical care nephrology, which we have called “Changing Faces of Critical Care Nephrology.”
