Introductory Chapter: Chronic Kidney Disease – Introductive Overview and Current Issues

Abstract

Chronic Kidney Disease is reported as a “Kidney damage for ≥3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR or GFR”. Chronic Kidney Disease is a progressive condition and it has a significant negative impact on general population morbidity of and quality of life (Qol). The increase of Chronic Kidney Disease prevalence throughout the world is becoming a challenge for two main reasons: first of all, it will require in the next future an improvement of resources available to face the number of patients who’ll need medical assistance; secondarily, it will cause an increase of the costs for publich healthcare systems. Patients suffering from Chronic Kidney Disease have generically an increase risk to death and complications associated with this condition which causes over 1 million of deaths per year in the world. Basing on epidemiological data provided by the most important studies, Chronic Kidney Disease is expected to become one of the most prevalent conditions in industrial and rural countries and one of the most important causes of death. Strategies for prevention, improvement of therapeutic options to delay disease progression, and new perspectives that could replace the invasive methods today available to treat end stage renal disease are warranted to improve patients’ quality of life, wellness of population and to provide a favourable impact on public healthcare systems.

1. Introduction

Chronic kidney disease (CKD) is reported as a “kidney damage for ≥3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR” [1]. Chronic kidney disease has been classified into five different stages based on disease severity from mild condition to the end-stage renal disease (ESRD), which represents a status of complete renal failure and requires replacement therapy (dialysis or kidney transplantation) [2]. Chronic kidney disease may be the consequence of many pathologic conditions from genetic disorders to malformative alterations, inflammatory, degenerative, immunologic, metabolic, toxic, and oncologic pathologies. However, despite the numerous and various etiopathogenetic factors that can lead to CKD, a large part of patients suffering from this disorder are affected by blood hypertension and diabetes, which are two of the most prevalent pathologic conditions in the world. Lifestyle changes, especially regarding dietetic aspects, smoke abuse, and pollution, have hardly increase the risk to develop dysmetabolic, cardiovascular, and oncologic pathologies that are also often responsible for CKD. As a consequence, the prevalence and incidence of CKD are continuously increasing during the time and medical assistance for patients will become a challenge in the next years. New strategies for disease prevention to improve therapeutical options that can delay its progression, and new perspectives that could replace the invasive methods to treat ESRD are warranted to improve patients’ quality of life, wellness of population, and to provide a favorable impact on public healthcare systems, being in most countries a significant economic burden to manage CKD patients and substantial inequity for them in access to medical services.

2. Epidemiologic and socio-economic aspects

Epidemiologic aspects of CKD are important to understand how much this pathologic condition could have a negative socio-economic impact. Chronic kidney disease is highly represented in the general population, accounting more than 800 million individuals [3]. Furthermore, this disorder has presented a significant increase of incidence and prevalence in the last 10 years, and it is one of the most frequent causes of death [4]. Recent review studies, including rigorous metanalysis of epidemiological investigations performed on large populations, report a prevalence of CKD varying from 10.6 to 13.4% [5]. One of the most important characteristics of CKD, under a social point of view, is that patients affected by this condition have an increased risk to death that has been estimated from one to five times higher than general population. This specific risk increases with disease severity, being the most in subjects with renal failure undergoing dialysis [5]. Patients suffering from CKD need continuous medical assistance since early stages of condition to advanced ones. General clinical status worsens with progression of CKD requiring laboratory tests to assess kidney function, imaging of urinary tract, and cardiovascular assessment. Nutritional restrictions, medical pharmacological treatment, or invasive therapies (i.e., peritoneal or extracorporeal hemodialysis) are differently provided basing on the CKD stage. As a consequence, patients’ quality of life (QoL) proportionally decreases either due to clinical conditions related to the renal disorder or also due to the need of recurrent diagnostic and therapeutic interventions. Most important studies on patients with CKD show that QoL falls with disease progression, especially in patients with significant comorbidities such as diabetes, and that it is particularly compromised in those undergoing dialysis [6]. The same studies assess that renal transplantation has the most favorable impact on QoL of CKD patients if compared with all the other treatments available for ESRD because it provides the most valuable functional ability [7]. During the last years, the incidence and prevalence increase of CKD have presented the same epidemiological trend shown by blood hypertension and diabetes, which have been identified as the main responsible for CKD [8]. Blood hypertension still represents the principal cardiovascular risk factor [8], and therefore, CKD significantly worsens the cardiovascular risk of individuals, independently from sex and age, but proportionally to stage disorder. Large epidemiological surveys show that CKD can be considered one of the most important causes of death throughout the world [8]. There is still somewhat controversy about epidemiological findings of CKD because the studies during the time have used different methods for its definition and classification [9]. However, there is a common scientific agreement that the burden of CKD is considerable, taking into account also direct and indirect costs of population needing diagnostic assessments, medical treatments, and replacement therapy (hemodialysis, peritoneal dialysis, and renal transplantation), whose number has been estimated approximately between 4902 and 7083 million people [10]. All these data and considerations should enforce the need of a general awareness about this pathologic condition and the possible future evolution in terms of incidence, prevalence, impact on Qol, and economic burden, especially considering aging of population, which directly correlates to functional kidney impairment. Some studies have provided data about the estimation of the increase of nephropathic population in the next years. In European countries, a number of people with CKD over 100 million are expected [10]. This will surely induce the governments, sanitary systems, and social services to develop more prevention strategies to reduce the impact of CKD on the world population and will prompt medical research to improve nephroprotective measures and therapeutic options, aiming to limit the number of patients who will need replacement therapies.

3. Current issues of chronic kidney disease

After the beginning of the new century, we have assisted to significant changes under epidemiological point of view regarding health status [11]. World population is continuously aging and chronic pathologic conditions are getting even more prevalent proportionally to this phenomenon. Particularly, a consistent decrease of diseases than can be transmitted has been associated with a severe increase of risk factors of chronic non-transmissible pathologies [12]. In this scenario, CKD has presented, as above mentioned, a significant increase of incidence and prevalence, and the identification of risk factors and their treatment is the most important action to adopt aiming to reduce the CKD burden. Various levels of intervention can be applied to reach this goal. Nutrition campaigns, that today can be delivered also by social media, to reduce dysmetabolic syndromes (dyslipidemia, diabetes), obesity, and smoking (which are strongly associated to cardiovascular risk) should be supported, and educational strategies should be developed since the first years of school to limit also the onset of the same disorders in the pediatrics and adolescents [13]. All these strategies have the goal to reduce the number of people suffering from chronic diseases, including CKD, and can contribute to lower the socio-economic impact of this condition on public healthcare. The strongest effort regarding prevention should be focused on diabetes and blood hypertension, which result to be the principal risk factors for CKD in all countries. Unfortunately, promotion of these preventive actions is difficult to achieve with the same efficacy in all the countries being these initiatives directly under the control of different governments. However, various experiences with campaigns of screening and prevention performed in different countries on adult and young people (middle school) have shown to be feasible and to increase awareness of population, among the public and policymakers [14, 15, 16]. Very important studies confirm that screening and prevention programs can prevent CKD and that in those countries that adopted and implemented management strategies the incidence of ESRD has been reduced [17]. These experiences should convince about the utility of prevention programs to limit the impact on the population of chronic pathologic conditions, requiring in the future more economic investments. In fact, early detection of chronic conditions is often based on the identification of biological markers as predictors of disease and that have high costs if widely investigated on large populations. One of the most important aspects that can prompt the governments and public healthcare systems to face the clinical and socio-economic impact of CKD is represented by the costs that this chronic disease requires for diagnosis and treatment of patients. Some studies report that almost 70–80% of sanitary resources of public healthcare are spent to manage chronic diseases [17]. Specific data from European countries estimate annual costs at about 700 billion euro that are comprehensive of direct costs (for diagnostic and therapeutic procedures) but mostly of the indirect ones (absence from work, nutritional support, and psychological care) [18]. In particular, in patients for CKD, it has been shown that these costs are directly correlated with disease progression reaching about 52,000 euros/patient per year in those undergoing hemodialysis. Therefore, prevention strategies and rigorous therapeutic approach should be adopted to strongly reduce the rate of patients undergoing replacement therapies, offering people with CKD better QoL and hardly reducing costs for public healthcare. Recent improvements on pathophysiology of CKD have contributed to develop better therapeutic options to manage conservative treatment. In addition to the well-known and commonly used pharmacologic treatments (as ACE inhibitors and angiotensin receptor antagonists or sartans) [19], new drugs are today available with renoprotective effects. Glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter 2 inhibitors represent a new frontier as glucose-lowering agents for diabetic CKD, having a significant renoprotective effect that can slow the disease progression and delay the need of replacement therapy [20, 21]. Additionally, in specific disorders, such as in Lupus Nephritis, biological agents (belimumab, obinutuzumab, anifrolumab, et al.) have shown to provide renoprotective effects by modulating self-antigens or by dual immunosuppressive and antiproteinuric effects (voclosporin) [22]. Furthermore, it has been shown that in lupus nephritis sodium-glucose cotransporter 2 inhibitors alleviate podocyte damage, therefore, producing renoprotective effects [23]. Some interesting perspectives are also under investigation for patients suffering from polycystic kidney disease. In fact, new randomized clinical trials are going to assess the efficacy of new molecules acting on specific pathophysiological pathways and sphingolipids, and preliminary data suggest that in the future, the prognosis of these patients could improve [24]. These evidences induce to consider that in the future, the chance to lower the incidence and prevalence at least of ESRD can be considered realistic, and the use of these new pharmacologic options should theoretically have a lower economic impact if compared with that associated with replacement treatments. The efforts of governments and health systems should be focused on screening, prevention, health education, and research in order to reduce as much as possible the epidemiological trend toward growth of the population affected by CKD. On the other side, scientific societies have the responsibility to implement research in this field and disseminate knowledge on recent therapeutic advances to protect renal function. Although it is still far from real-life application, a very promising solution will probably income in the next 10 years for patients with ESRD needing replacement treatment and could be represented by the bionic kidney. This device is under pre-clinical assessment and it consists of an implantable system and a bioreactor. The bionic kidney is capable of functioning as a filter for the blood and to maintain the plasmatic homeostasis, but at the moment research is still far from clinical applications in humans, while preliminary data on animals have already published [25]. At the present, kidney transplant still represents the best solution for patients with renal failure. The number of kidney transplanted patients in the world has reported over 25,000 in 2022, and this number is expected to be larger from data under revision of 2023 considering the increasing number of donor nephrectomies (from living kidney donors) [26]. New surgical devices, especially robot-assisted procedures, have contributed to improve patients’ compliance versus this type of surgery because less invasive. Furthermore, a better awareness of population about the need of kidney donation has hardly contributed to relief many patients from dialysis. The hope is that in the next years, all the efforts to reduce CKD incidence will help also to reduce the request of renal transplants, lowering the number of single-kidney individuals due to a donor nephrectomy.

4. Conclusion

Epidemiological and socio-economic data estimate a worrying growth of the population affected by CKD in the world, with consequent increase of mortality risk associated with this pathology, reduction of quality of life, and a significant economic impact on healthcare systems. Various scientific evidences show that this trend could be slowed down by screening and prevention programs and by the use of new therapeutic resources today available to protect kidney function. More than being a nephrological problem, nephroprotection has become a public health issue as the etiopathogenetic factors associated with it are represented by the most widespread chronic diseases, such as diabetes and hypertension, which are often related to malnutrition, especially overweight and obesity. For this reason, all institutions should be involved in programs intended to reduce the impact of CKD, including schools, responsible for very important educational aspects.