Renal Failure Stages, Treatment, and Outcomes

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Would it surprise you to know that 37 million adults in the United States are living with chronic kidney disease (CKD), and most don’t even know it (1)? Would it also surprise you to know that there currently is no cure for chronic kidney disease? How then do these 37 million adults living with this disease function in their daily lives?

The answer is that most of the diagnosed are undergoing some type of renal replacement therapy. Renal replacement therapy (RRT) is an umbrella term that includes various treatment options for CKD patients. Even though this disease is so widespread, unless a person knows someone on dialysis or they have experienced it personally, they usually do not know anything about renal failure. This course offers an overview of renal failure and its’ causes, discusses the different options currently available to End-Stage Renal Disease (ESRD) patients, and discusses the pros and cons of each. 

Introduction

According to the Centers for Disease Control and Prevention (CDC), about 37 million adults in the United States, or 14% of the adult population, have chronic kidney disease (CKD) [1]. Estimates are that more than one in seven U.S. adults, equating to about 35.5 million people, have CKD, with 90% unaware of the condition [1][3].  

Furthermore, about one in three adults with severe CKD are unaware of their diagnosis. The prevalence of CKD varies by age, sex, and race/ethnicity; CKD is more common in individuals aged 65 years or older (34%) compared to those aged 45–64 years (12%) and 18–44 years (6%) [1]. Females are more affected by CKD (14%) than males (12%) [1]. Among racial and ethnic groups, non-Hispanic Black adults have a higher prevalence (20%) compared to non-Hispanic Asian adults (14%) and non-Hispanic White adults (12%), with Hispanic adults also showing a prevalence rate of 14% [1].  

Despite these statistics, a sizable portion of those with reduced kidney function, including 40% of those with a notable decrease and one-third of those with severe CKD, remain undiagnosed [2]. CKD occurs when damage to kidneys occurs over time, impairing their ability to perform these critical functions [3]. Moreover, CKD accelerates the risk of additional health complications, including heart disease and stroke [4]. Often, the progression of CKD is slow, with few symptoms in the initial stages, leading to its classification into five stages to facilitate treatment planning [5]. 

The kidneys play an integral role in preserving health, crucial for activating hormones, stabilizing blood's key molecules, and removing toxins, ranking them just behind the liver in toxin elimination importance [6][8]. The kidney contains millions of nephrons with filtering glomeruli that send fluid through the ureters, bladder, and urethra for excretion, or through the renal vein for return to the body [12]. Key functions include filtering natural waste and surplus water, supporting red blood cell production, balancing essential minerals, regulating blood pressure, and promoting bone health [7][8].  

With 20% to 25% of the heart's output flowing through them, the kidneys filter blood up to 60 times daily [9]. They eliminate a range of metabolic byproducts like ammonia, urea, uric acid, and creatinine, along with hemoglobin breakdown products, hormone byproducts, liver-processed water-soluble toxins, and excrete industrial substances such as heavy metals and synthetic chemicals [7][8]. They also remove excess intake of nutrients or dietary elements, including salt, vitamin C, and B vitamins [7][8]. 

Chronic kidney disease (CKD) has become a significant cause of mortality and morbidity in the 21st century, with its prevalence exacerbated by increasing rates of risk factors including obesity and diabetes mellitus. In 2017, CKD affected 843.6 million individuals across the globe [2]. While mortality rates for those with end-stage kidney disease (ESKD) have seen a decline, studies from the Global Burden of Disease (GBD) indicate that CKD ranks as a leading cause of death worldwide [10]. As such, early detection, monitoring, and treatment of CKD, alongside the implementation of preventive and therapeutic strategies on a global scale, are essential.  

Overview of Kidney Anatomy and Function 

The kidneys are bean-shaped organs situated in the retroperitoneal space. [11] They weigh between 150 to 200 g in males and 120 to 135 g in females. Their dimensions are 10 to 12 cm in length, 5 to 7 cm in width, and 3 to 5 cm in thickness, like a closed fist [11].   

The right kidney is lower than the left due to the liver’s position [12]. The adrenal glands are located on top of each kidney. Blood with excess fluid and waste products enters the kidney through the renal artery.  

Renal Failure Stages 

Health care professionals evaluate kidney health through blood and urine analysis. Blood tests assessing the glomerular filtration rate (GFR) reflect the efficiency of the kidneys in filtering waste from the bloodstream [14].  

Urine tests assess the albumin to creatinine ratio (ACR), focusing on the presence of the protein albumin, produced by the liver [14]. Albumin plays a crucial role in preventing fluid leakage from blood vessels and transporting various substances throughout the body [14]. Albumin should remain in the blood, with minimal amounts passing into the urine if the kidneys are working.  

The presence of protein in the urine signals a potential compromise in kidney filtration capacity [13][14]. The GFR is the primary measure of kidney function, quantified in milliliters per minute based on how plasma substances filter through the glomerulus. Creatinine, a waste product found in blood, serves as the standard endogenous marker for evaluating glomerular function, with its clearance rate providing an estimate of GFR [13]. 

Chronic Kidney Disease (CKD) – classified into five renal failure stages based on GFR [5]. 

Detecting chronic kidney disease (CKD) in its earlier stages can slow its progression, extending kidney function [15]. In 2019, the Kidney Disease: Improving Global Outcomes (KDIGO) conference focused on “Early Identification and Intervention in CKD” explored various approaches to enhance the early detection and management of chronic kidney disease (CKD) [15]. They advocated for targeted CKD screening among populations with prevalent and significant risk factors to identify individuals at increased risk of CKD progression and cardiovascular incidents who would benefit from established treatment protocols.  

Early consultation with a nephrologist upon recognizing symptoms of renal failure enables the initiation of treatment sooner, helping patients to avoid the disease’s progression. However, many patients postpone seeking medical care when symptoms worsen, leading to uremia—accumulation of toxins in the blood [16]. Symptoms of uremia include confusion, loss of appetite, nausea, and diarrhea, and some patients may develop ‘uremic frost,’ a condition where uremic toxins crystallize on the skin [16][17].  

Awareness of renal failure is under 10% in Stages 1-3, increasing at Stage 4, as symptoms become more apparent [18]. In Stage 5 Renal Failure, known as end-stage renal disease (ESRD), patients require permanent renal replacement therapy, or dialysis. The urgent need for dialysis forces patients to start treatment without sufficient preparation. About 50% of dialysis initiations may be suboptimal, leaving patients unprepared for the psychological adjustments required, thereby increasing their risk of stress, anxiety, and depression [27]. 

Acute Versus Chronic Renal Failure 

Kidney damage can manifest as either acute or chronic conditions. A rapid onset characterizes acute kidney injury (AKI), where the kidneys lose the ability to function, often as a response to physical injury, toxic substance exposure, infections, or a temporary reduction in blood flow [19]. In cases of AKI, there is an expectation for the kidneys to recover normal function after addressing the immediate cause healing has occurred [20]. 

Chronic kidney disease (CKD) develops over a period and is irreversible [20]. It falls under the broader category of acute kidney diseases and disorders (AKD), encompassing conditions where there is a gradual reduction in kidney performance or sustained kidney issues [20]. This often results in the irreversible destruction of kidney cells and nephrons progressing to chronic kidney disease (CKD) [20].  

Lifestyle factors play a significant role in the onset of CKD, with uncontrolled diabetes and high blood pressure being the leading causes [21]. Other factors contributing to CKD include long-term use of specific drugs (such as NSAIDs, heroin, and certain antibiotics), recurring infections (for example, urinary tract infections and glomerulonephritis), inherited conditions like polycystic kidney disease, and the presence of kidney stones [22]. In some instances, an event causing AKI may result in permanent kidney damage if the organs do not recover within 90 days, at which point the condition receives classification as chronic kidney disease (CKD) [23].  

Types of Dialysis 

Dialysis serves as a substitute for kidney functions, with hemodialysis and peritoneal dialysis being the primary methods. These techniques employ a semi-permeable membrane to filter out waste, toxins, and residual fluids from the body [24][25].  

These membranes permit the passage of small molecules and fluids through their pores, restricting larger molecules [24][25]. During dialysis, substances including urea and selected electrolytes (sodium, potassium, magnesium, calcium, and phosphorus), which are present in excessive amounts in the blood, pass through this membrane [25][26]. 

Meanwhile, blood cells, due to their larger size, remain in the bloodstream. Unlike the constant operation of healthy kidneys, dialysis can only mimic a portion of renal function, regardless of the frequency or efficiency of the treatments [25]. 

Hemodialysis 

Hemodialysis remains the primary form of renal replacement therapy, leveraging a dialysis machine equipped with a pump designed to emulate the cardiac function of circulating blood throughout the organism [28]. To facilitate access to the vascular system implanted accesses are employed to bridge an artery and a vein.  

The primary access types include arteriovenous fistulas (AVFs), arteriovenous grafts (AVGs), and central venous catheters (CVCs), with AVFs being the most favored due to their employment of the patient's native arterial and venous system [29]. AVGs utilize synthetic materials to form the arterial-venous connection, representing permanent solutions [30]. CVCs are less desirable due to elevated risks of infection and thrombosis and positioning the catheter's tip within the heart's right atrium. CVCs are viewed as interim solutions pending the establishment of permanent access [31]. For patients lacking suitable vasculature for permanent access, CVCs may represent a final alternative.  

The operational mechanism of AVFs and AVGs necessitates the insertion of two large-bore needles into the access point to facilitate blood flow into the dialysis circuit, which houses a dialyzer (artificial kidney) [32]. Myriad semi-permeable microtubules line the interior of the dialyzer that permits blood passage in one direction and a specially formulated dialysate—comprising ultrapure water produced via reverse osmosis (RO), sodium bicarbonate, and an acid solution enriched with electrolytes like sodium, potassium, calcium, and magnesium—in the reverse [33].  

This setup generates a pressure differential, enabling diffusion and osmosis within the dialyzer to aid the body in achieving homeostasis by expelling waste, toxins, and superfluous fluid [33]. Post-filtration, the effluent discharges into a drain, while the purified blood is reintroduced into the patient's circulation through the second needle. 

Peritoneal Dialysis 

Peritoneal dialysis involves the surgical insertion of a catheter into the patient's abdomen, facilitating the inflow and outflow of fluid within the peritoneal space [34]. The peritoneum, a semi-permeable membrane, acts as the filtration barrier in this process [34]. During treatment, the introduction of a dialysis solution rich in dextrose occurs into the peritoneal cavity, drawing waste, toxins, and excess fluid from the bloodstream across the peritoneum [34].  

After a designated period known as the dwell time, this fluid, now containing the filtered waste products (referred to as the effluent), drains away through the catheter [34]. The procedure, or exchange, repeats several times based on the individual's remaining kidney function and laboratory values, which are indicative of their stage of renal failure. Unlike hemodialysis, this method does not require vascular access, thereby eliminating the need for needles. 

Treatment Goals 

The primary objectives of dialysis treatments are to compensate for the loss of renal function and restore equilibrium within the body [32]. Achieving and maintaining fluid balance is vital, making precise patient weight measurements critical. Estimated dry weight serves as a reference for regulating fluid extraction during outpatient hemodialysis treatments [35]. Nephrologists determine an estimated dry weight (EDW) for each patient, representing their optimal weight minus any excess fluid [35].  

Dialysis machines receive precise calibration to extract fluid to align the patient's weight with their EDW by the treatment's conclusion. Inaccuracies in fluid removal or its rate can result in complications like hypervolemia, characterized by symptoms such as shortness of breath, pneumonia, edema, congestive heart failure, pulmonary edema, and hypertension. Hypovolemia is another complication manifesting as cardiac issues, hypotension, nausea, vomiting, cramps, and dizziness [28]. Fluid imbalance and infection are leading causes of hospitalization among patients with end-stage renal disease (ESRD) [36]. 

Another crucial aim of dialysis is waste elimination and electrolyte regulation, often measured through clearance or adequacy metrics. Several factors influence clearance, including the semi-permeable membrane's size, treatment duration and frequency, membrane exposure duration, access functionality, dialysate concentration, and the effectiveness of anticoagulants or thrombolytics [28]. A more concentrated dialysate enhances clearance, but concentrated solutions may harm the peritoneal membrane or cause red blood cell crenation in hemodialysis [28]. 

To simulate various kidney functions including hormone regulation and infection prevention, patients receive medications during dialysis sessions. These include erythropoietin-stimulating agents (ESAs) and iron to promote healthy red blood cell production, vitamin D for calcium absorption, and protein supplements to increase albumin levels, aiding in fluid shift to the vascular space for elimination [37].  

In addition, heparin prevents blood clotting, thrombolytics address catheter clots, and IV antibiotics combat infections [38]. Vaccinations against Hepatitis B, influenza, pneumonia, and Covid-19 protected against infectious diseases [38]. Phosphorus binders enhance calcium absorption by limiting phosphorus intake during meals [38]. 

Treatment Goals 

Dialysis Settings  

Both hemodialysis and peritoneal dialysis offer administration flexibility in various settings, including hospitals, outpatient facilities, or the comfort of a patient's home. Hemodialysis requires electricity for the dialysis and reverse osmosis (RO) machines, as well as a water source for producing RO water [39].  

Depending on the specific equipment used, patients have the mobility to travel with their dialysis supplies and perform their treatments outside of dialysis centers. In contrast, peritoneal dialysis does not necessitate electricity or a clinic location secondary to a manual option that operates on gravity alone [39]. Regardless of the dialysis method selected or the location of treatment, maintaining strict infection control practices is critical. 

Dialysis supplies are sterile upon packaging and must remain uncontaminated upon opening to prevent the introduction of microbes into the bloodstream or peritoneal cavity [40]. Between 2017 and 2020, adults undergoing dialysis were at a 100-fold increased risk of experiencing a staphylococcus bloodstream infection compared to adults who were not on dialysis [40]. Employing aseptic techniques is essential to reduce the risk of infection and/or cross-contamination. 

Incenter Hemodialysis 

In the United States, the outpatient hemodialysis clinic is the most prevalent venue for dialysis, with thousands of such facilities nationwide [41]. Patient care technicians (PCTs) and licensed practical nurses (LPNs), supervised by registered nurses, deliver direct patient care in these clinics, managed by a nurse manager or facility administrator alongside a medical director. 

The staff complement in these clinics may also include attending physicians, nurse practitioners, physician assistants, social workers, dietitians, biomedical technicians, and administrative staff. The size of a clinic is determined by the number of licensed and operational patient stations, each equipped with a specialized reclining chair or bed and a dialysis machine for administering treatments. A hemodialysis session lasts between 3.5 and 4.5 hours, during which patients receive monitoring from the care team [28]. 

Following treatment, they are re-evaluated by an RN, weighed, and then sent home. Treatments occur three times a week, either on a Monday, Wednesday, Friday, or Tuesday, Thursday, Saturday basis, although some may require more frequent sessions due to fluid management needs, depending on their stage of renal failure. 

Many patients on dialysis prefer the outpatient setting for the social interaction it fosters and the reassurance of professional oversight [41]. However, this option imposes the most stringent dietary and fluid restrictions on patients due to the thrice-weekly treatment regimen and offers less flexibility in scheduling due to the set operating hours and staffing considerations. 

Home Hemodialysis 

Hemodialysis can occur at home, including during sleep hours. Patients and their care partners receive training on how to insert needles and manage their treatments independently.  

Similar to facilities, patients at home can use a recliner for comfort during dialysis. Supplies arrive at the patient’s home either weekly or biweekly, depending on the available storage space. This system of supply delivery, which can reach almost any location, ensures patients can travel with ease while continuing their dialysis regimen uninterrupted. 

Kidney Transplants 

In the U.S., 13% of patients on dialysis, about 100,000 individuals, are on the waitlist for a kidney transplant [43][44]. A kidney transplant involves providing a patient with end-stage renal disease (ESRD), at Stage 5 of renal failure, a kidney from either a living or deceased donor. This procedure has the potential to restore the patient's quality of life to pre-failure conditions.  

The existing, non-functional kidneys remain unless removal is necessary. Kidneys from living donors are often more successful and have a longer functional lifespan than those from deceased donors [45]. 

Candidates for transplantation undergo thorough medical and psychosocial evaluations by the transplant center to minimize the risk of transplant failure and to ensure the recipient is prepared for post-surgery care. Being on the active transplant list requires patients to ensure they are contactable by the transplant center and can promptly reach the center when notified of a potential kidney match.  

Addressing any medical issues and risk factors, such as the need for weight loss or smoking cessation, is crucial before listing for a transplant [46]. Regular lab monitoring, conducted by either the dialysis clinic or the transplant center, is essential to remain on the transplant list. Candidates must not have cancer or other severe conditions that could compromise the transplant's success. Monitoring adherence to post treatment protocols can identify those at a higher risk of post-transplant issues [47]. 

Financial considerations can pose barriers for some candidates. Since 1972, Medicare has provided coverage for ESRD patients with sufficient contributions to the system, offering benefits irrespective of age [48]. Medicare covers about 80% of transplant and associated costs, but offers limited coverage post-transplant, affecting the patient's eligibility for benefits if the new kidney functions well until they reach the standard Medicare eligibility age without ESRD [49].  

Medicare stops covering patients who received kidney transplants 36 months post-transplant if the patient needs ongoing dialysis or another kidney transplant. Yet, the Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act of 2020 eliminated the three-year limit on coverage for immunosuppressive drugs [49]. 

Palliative Care 

A diagnosis of Stage 5 renal failure does not signify a terminal phase unless the patient opts not to pursue further intervention. Those who choose against starting or continuing dialysis or seeking a transplant can receive palliative care to ensure comfort during their final days.  

Pre-arranging treatment preferences, appointing a health care proxy, and establishing power of attorney contribute to a more managed transition. Patients who undergo dialysis may receive palliative care to alleviate common symptoms such as fatigue, itching, diarrhea, and restless leg syndrome, enhancing their quality of life during treatment [50]. 

Home Hemodialysis 

Hemodialysis can also be performed at home, even while the patient sleeps. The patient and care partner are trained to cannulate (insert needles) and facilitate the treatments. In the U.S., patients usually use either a NxStage machine or a Fresenius 2008K at home machine (often referred to as a Baby K because it is slightly smaller than the larger K machines utilized in the outpatient clinics and hospitals).

Both machines have the same function and operate the same way. The patients receive a recliner for their home just like the incenter patients use. There are weekly or biweekly shipments of supplies, depending on how much storage space the patient has available. The supplies can be delivered virtually anywhere, which allows the patients to be able to travel easily without skipping their dialysis treatments. 

Future State of Patients with End Stage Renal Disease 

One in three adults faces a risk of developing kidney disease [52]. There is a compelling need to enhance the number of transplants and to establish home-based therapies as the primary treatment approach for patients with end-stage renal disease (ESRD). The current infrastructure will not suffice to accommodate the increasing number of patients requiring in-clinic dialysis treatments.  

On July 10, 2019, the announcement of the Advancing American Kidney Health initiative by President Trump sets forth three main goals and seven specific objectives [53]. 

• Aim for a 25% reduction in new ESRD cases within a decade. 

• Elevate the adoption of home-based therapies and transplants to 80% by the year 2025.  

• Increase the availability of kidneys for transplantation twofold by 2030. 

Efforts to combat kidney disease are expanding through research. The National Kidney Foundation is supporting this cause with grants and clinical trials aimed at discovering a cure or more effective treatments for chronic kidney disease (CKD). Two decades ago, the Kidney Disease Outcomes Quality Initiative (KDOQI) introduced guidelines to enhance the diagnosis and treatment of kidney disease, benefiting thousands of patients [53]. 

Conclusion  

Given the complex landscape of chronic kidney disease management and the evolving strategies for treatment, including the push for increased transplants and home-based therapies as outlined in the Advancing American Kidney Health initiative, the future state of patients with end-stage renal disease (ESRD) appears poised for significant transformation.  

The initiative's ambitious goals aim to address the critical shortages in available treatment options and the pressing need for a broader implementation of preventative measures and early intervention strategies. The emphasis on home-based therapies and the drive to double the availability of kidneys for transplantation by 2030 reflect a holistic approach to tackling the multifaceted challenges of kidney disease management, promising a future where patients can expect more personalized, accessible, and effective care.  

The ongoing support for research and the development of new treatment modalities further underscore the commitment to improving outcomes for those affected by chronic kidney disease, highlighting the potential for advancements in care that could dramatically alter the ESRD treatment paradigm. 

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