Clinical Background: Clinical infections and its most severe forms sepsis and septic shock are commonly associated with changes in kidney function. This acute kidney injury (AKI) is associated with increased risk of morbidity and mortality in hospitalized patients. Epidemiology: Recent standardized, separate consensus definitions of sepsis and AKI have informed the epidemiology of these 2 distinct processes. While there is no consensus definition specific to sepsis-associated AKI, several studies have utilized the combined definitions of these two syndromes to identify those patients at the highest risk for adverse outcomes. Challenges: Prevention of sepsis-associated AKI is difficult in part because patients will often present for medical care with the sepsis-associated AKI already clinically apparent. Additionally, for those that do not have AKI on presentation the ability to detect injury early is limited by the imperfect current gold standard biomarkers serum creatinine and urine output. Prevention and Treatment: Despite these challenges, there has been increased investigation of novel biomarkers of AKI. Additionally, there has been intense investigation into the ideal care of patients with sepsis, AKI as well as sepsis-associated AKI. While there are limited specific therapeutic options outside of antibiotics for infections, several studies have investigated the use of care bundles to treat these syndromes. While there is continued investigation into novel therapeutics and the use of dialysis and extracorporeal modalities, these trials have failed to revolutionize clinical care. This review summarizes the current state of sepsis-associated AKI care and discusses strategies to improve care.

Snakebite-related acute kidney injury (AKI) is mainly caused by bites from the Viperidae family which are common snakes worldwide. It is a frequent and potentially fatal clinical complication. Coagulation abnormalities are usually present and are most likely to contribute to AKI development. A better comprehension of AKI pathogenesis following the toxicsyndrome may improve patient management by primary healthcare providers, allowing earlier diagnosis and treatment. This chapter highlights the main studies about snakevenom-related AKI, the most common snakes around the world, and the respective mechanisms of AKI.

Clinical Background: Cancer therapeutics (for both solid and hematological malignancies) have evolved over the last two decades, from traditional chemotherapies to novel treatments. A better supportive care, older patients with comorbidities who receive multiple chemotherapeutic and pharmacological regimens, multiple CT scans with contrast agents, and new therapeutic options are also increasing the number of cancer patients who can develop acute kidney injury (AKI) or chronic kidney disease (CKD). Challenges: Targeted therapies and immunotherapies, which harness the body's own immune system to fight cancer cells have led to improved survival in cancer patients, yet all are associated with many organ toxicities. Renal toxicity is mainly represented by acute tubular-interstitial damage, glomerular lesions, thrombotic microangiopathy, tumor lysis, proteinuria, arterial hypertension, AKI, CKD, and secondary fluid/electrolyte disturbances. On the other hand, it is important to consider how the presence of CKD, AKI, and other renal disorders may affect treatment options for the oncologists and patient's outcome. All these features require a specialized approach. Prevention and Treatment: A new evolving field, namely Onconephrology, has emerged during the last few years, including the broad spectrum of renal disorders that can arise in patients with cancer. Nephrologists have become an indispensable part of the multidisciplinary cancer care teams, but a clear and updated knowledge of solid and hematological malignancies, always new anticancer therapies, and their relationships with kidney function is essential to ensure the highest quality of care. In this chapter, we summarize the principal aspects of this new field of Nephrology.

Clinical Background: Nephrotoxic acute kidney injury or toxin-related acute kidney injury (ToxAKI) is a relevant and relatively common category of kidney damage. Exogenous toxins and venomous animals with epidemiologic variations across the world are some nephrotoxic agents. Epidemiology: The epidemiologic features of the toxic agent-related acute kidney injury are associated with different culture, biodiversity of the tropics, and economic status. It seems economic status is the major factor which defines the etiology of ToxAKI. In developing countries, the AKI is commonly associated with self-poisonings by pesticides and herbicides, while developed countries often notify poisonings due to antibiotics, nonsteroidal anti-inflammatory drugs, immunosuppressants (such as methotrexate), and iodinated contrast media. Moreover, envenoming due to snakes, spiders, and scorpions is more frequent in tropical regions. Challenge: Poisoned patients are more susceptible to renal impairment associated with renal replacement therapy and death. Prevention and Treatment: Preventing patient exposure and performing early diagnosis are crucial to beat the main causes of ToxAKI and further complications. Renal replacement therapy may be necessary to manage the patient, and it is associated with poor prognosis and death. According to each poisoning profile, specific measures are suggested. School-base interventions, early identification, treatment, and care of people with mental and substance use disorders, reducing access to chemical agents, making parents aware of the hazards of accidental poisoning in children, and maintaining fully functional poison control centers are vital actions too.

Clinical Background: As a result of modern industrialization, air pollution has become a potential contributor to global burden of noncommunicable diseases, such as cardiovascular disease, respiratory disease, and kidney disease. Epidemiology: Emerging epidemiological evidence has demonstrated that exposure to ambient air pollution is associated with an increased risk for the development and progression of chronic kidney disease (CKD) and CKD-related mortality. Exposure to PM2.5, even at relatively low concentrations, is a risk factor for a lower estimated glomerular filtration rate and a faster decline in glomerular filtration rate. It has been estimated that the global burden of CKD attributable to PM2.5 is 6.95 million incident cases of CKD per year. Low- and middle-income countries in the Eastern Mediterranean and South-East Asia regions experienced the highest urban air pollution levels, thus facing a heavier burden of related disease. Challenges: Despite a growing awareness of kidney damage related to air pollution, large gaps still exist between the exact toxicological effect of particles on the kidney and the increasing prevalence of air pollution-related kidney diseases. Considering the geographic variation of air pollution, more longitudinal studies in different parts of the world are urgently needed, especially in those most affected countries. Prevention and Treatment: Air pollution control should be regarded as a high priority in urban plan and policy making. Actions are required to narrow gaps in knowledge and clean air, thus preventing air pollution-related kidney disease.

Clinical Background: Poly- and perfluorinated compound (PFCS) pollution has been found to be the driver of different diseases, including glucose intolerance, hyperlipidemia, thyroid diseases, gestational diabetes mellitus and hypertension, testicular and genitourinary cancer, as well as impaired kidney function. This review focuses on the renal effects of PFCS, intending to clarify their occurrence and pathogenetic mechanisms. Epidemiology: Between October 31st, 2017, and March 31st, 2020, most frequently analyzed PFCS were perfluorooctane sulfonate, perfluorooctanoic acid, sodium perfluoro-1-hexanesulfonate, perfluoro-n-nonanoic acid, and perfluoro-n-decanoic acid. Unfortunately, the novel replacement compounds (e.g., perfluoroether carboxylic acid) are unregulated, and they are not under study. PFCS are linked with an impaired kidney function: the kidney is a target of PFCS because it is involved in their excretion. Inter- and intra-species variations exist and affect PFCS pharmacokinetics, leading to different risk profiles of adverse effects, even at similar exposures, and influencing the risk of renal damage in case of concomitant exposure to PFCS and some heavy metals. Challenges, Prevention and Treatment: In the last 20 years, much effort has been made to stop the PFCS production in Europe and USA. However, human exposure remains persistently high due to PFCS long half-life, the large-scale production in some countries and the unregulated novel compounds. This context makes further studies mandatory to understand the pathogenetic mechanisms of old and new PFCS and the effective strategies to remove PFCS from the human blood in the most affected areas of the world.

Clinical Background and Epidemiology: Low physical activity is a common phenotype in individuals living with chronic kidney disease (CKD). It increases as renal function declines and is associated with adverse clinical outcomes and a poor quality of life (QOL). Both behavioral and disease-related factors contribute to the low physical activity levels in CKD. CKD has profound negative effects on skeletal muscle structure and function that are related to impairments in mitochondrial function, inflammation, oxidative stress, metabolic acidosis, and other uremia-related factors. These factors promote muscle protein catabolism and wasting, and impair strength, physical performance, and cardiorespiratory fitness. Moreover, the high burden of comorbid disease contributes to patient fatigue, fear of injury, and poor exercise self-efficacy. All of these factors reinforce patient's sedentary behavior, leading to a vicious cycle of disease and disability that further compromises their health and QOL. Data from both observational studies and exercise interventions indicate that increasing levels of physical activity may provide a range of benefits in CKD patients, including attenuating declines in renal function, and improving markers of physical function, cardiovascular disease risk, and QOL. Unfortunately, these results have not led to widespread implementation of exercise programs in CKD, and physical inactivity and poor physical function remain hallmarks of the disease worldwide. Challenges and Solutions: There are many frequently cited barriers to implementing exercise programs in CKD. These include: a lack of training and knowledge about physical activity/exercise prescriptions and interventions among health professionals; inadequate time to implement exercise programs due to other clinical responsibilities; a lack of specific funding and incentives to develop these programs; and a poor quality of the data demonstrating efficacy of exercise. Many CKD patients also are unmotivated to incorporate exercise into their daily lives due to time constraints, depression, and other comorbid diseases, and poor self-efficacy for exercise. Given these barriers, it is not surprising that physical activity/exercise programs have not become a component of standard of care for CKD patients. We discuss several potential solutions to address these barriers, including: (1) providing better education and training for healthcare professionals who provide exercise advise and counselling to individuals with CKD; (2) providing incentives to reimburse payers to develop and maintain exercise programs in CKD; and (3) providing more personalized approaches to exercise prescription and implementation of exercise programs that consider the unique circumstances of individual CKD patients. In summary, low physical activity levels in CKD patients result from a combination of many factors that adversely impact patient's health and QOL. Addressing this problem will require comprehensive intervention strategies that consider both the unique pathophysiology of CKD and the individual circumstances of those living with the disease.

Chronic kidney disease (CKD) is considered a public health problem and part of the growing burden of noncommunicable diseases. Many studies have searched for ways to reduce the risk of complications and death. One possible approach to modify the course of this disease is the adoption of healthy dietary habits. Previous studies have suggested that healthy dietary patterns, such as the Dietary Approaches to Stop Hypertension (DASH), the Mediterranean diet, the vegetarian diet, and a diet adhering to the Healthy Eating Index, are associated with improved renal health. In this chapter, we reviewed the scientific literature and presented the potential role of dietary patterns in the prevention of CKD, contributing to dietary strategies for promoting kidney health. We found that nutritional planning plays an important role in kidney health maintenance and in the protection of kidneys from further damage. The DASH, Mediterranean, and vegetarian dietary patterns can be viable strategies for CKD prevention. However, individualized nutritional monitoring is necessary for individuals with overt kidney disease. Randomized, controlled, and prospective studies focusing on nutritional interventions applied to renal patients undergoing conservative and dialytic treatment and to the general population are necessary to assess habits that can prevent the occurrence and worsening of kidney disease.

Digital health is an area that emerges from the association between health needs and technological solutions. With the growing access of people to the internet and the ease of acquiring equipment that allows internet connection, we are observing an exponential increase in the strategies that use technology to connect patients and healthcare providers. Telenephrology is a channel of communication that facilitates the access to the nephrologist for both primary care physicians and patients and has been implemented in several countries. Applications for smartphones are frequently used by both patients and healthcare providers, and these tools are changing the way we practice nephrology and medicine in general. Social networks emerge as an important way of communicating between healthcare professionals and patients and a source of connection for people with the same interests. Artificial intelligence, big data, and other technological solutions, including wearable devices that measure and monitor different health parameters, are revolutionizing healthcare and the field of nephrology. Implantable devices are in development, including devices to monitor electrolytes in dialysis patients, systems to track medication intake, wearables to monitor exercises, monitoring of blood pressure, heart rate, arrhythmia, and peripheral oxy-hemoglobin saturation, among others. The wearable artificial kidney, a device which would perform renal function during ambulation and social activities outside of the hospital, has been under investigation for many years. In this chapter, we highlight the most recent advances in digital health applied to nephrology.

Clinical Background: Kidney transplantation (KT) is the best treatment for most patients with end-stage kidney disease (ESKD), providing better survival and quality of life and lower cost when compared to dialysis. Epidemiology: Despite robust evidence showing the superiority of KT over dialysis, a significant percentage of ESKD patients worldwide do not access this treatment. Challenges: Barriers resulting in inequalities and inequities in access to KT involves chronic kidney disease (CKD) diagnosis and management, including difficulties in accessing dialysis therapy before KT; suboptimal referral and enlistment to KT; and imbalance between supply and demand for organs. Low socioeconomic status has an important role in that scenario. Prevention and Treatment: Strategies to minimize disparities in access to KT involve public policies to ensure access to CKD diagnosis and treatment, health education, continuous training of health providers, infrastructure, and allocation policies.