More than 500,000 people in the United States live with end-stage renal disease (ESRD). The development of chronic kidney disease (CKD) and its progression to this terminal disease remains a significant source of reduced quality of life and significant premature mortality. Chronic kidney disease (CKD) is a debilitating disease, and standards of medical care involve aggressive monitoring for signs of disease progression as well as early referral to specialists for dialysis or possible renal transplant. Kidney Disease Improving Global Outcomes (KDIGO) foundation guidelines define CKD using markers of kidney damage, specifically markers that determine proteinuria and glomerular filtration rate. By definition, the presence of both of these factors (glomerular filtration rate [GFR] less than 60mL/min and albumin greater than 30mg per gram of creatinine) along with abnormalities of kidney structure or function for greater than three months signifies chronic kidney disease. End-stage renal disease, moreover, is defined as a GFR less than 15mL/min.
End-stage renal disease can be caused by many chronic diseases. In the United States, diabetes mellitus is the leading cause. Other causes include hypertension, glomerulonephritis, polycystic kidney disease, prolonged obstruction of the urinary tract, vesicoureteral reflux, recurrent pyelonephritis, and certain medications such as non-steroidal anti-inflammatory drugs (NSAIDs), calcineurin inhibitors, and antiretrovirals.
According to the United States Renal Data System, in 2015, there were 124,411 new ESRD diagnoses, reflecting an increasing burden of kidney failure. The prevalence of the disease has been rising at a stable number of about 20,000 cases per year.
The degree of kidney failure varies widely by race in the US. In 2015, the rate of ESRD was three times higher in African Americans as compared to Caucasians (393.5 versus 139.9 per million population). In that same year, the ESRD prevalence was about ten times higher in American Indians or Alaska Natives and twice as high in Native Hawaiians or Pacific Islanders. Prevalence rates were 1.3 times higher in Asian Americans, as well. Of note, incidence rates in the African American population have been decreasing each year since 2006, leading to an overall decrease of 21%. This reduction has been even more pronounced in American Indians/Alaska Natives.
The decline of kidney function is gradual and initially may present asymptomatically. The natural history of renal failure depends on the etiology of the disease but ultimately involves early homeostatic mechanisms involving hyperfiltration of the nephrons. As nephrons become damaged, the kidney increases the rate of filtration in the residual normal ones. As a result, the patient with mild renal impairment can show normal creatinine values, and the disease can go undetected for some time. This adaptive mechanism will run its course and will eventually cause damage to the glomeruli of the remaining nephrons. It is at this point that antihypertensives such as ACEs or ARBs may be beneficial in slowing the progress of the disease and preserve renal function.
Factors that may worsen renal injury include:
End-stage renal disease can present with a constellation of signs and symptoms. Some include volume overload refractory to diuretics, hypertension poorly responsive to medication, anemia, mineral and bone disorders, and metabolic derangements including hyperkalemia, hyponatremia, metabolic acidosis, hypo/hypercalcemia, and hyperphosphatemia. Uremic toxicity can present as anorexia, nausea, vomiting, bleeding diatheses, pericarditis, uremic neuropathy or encephalopathy, seizure, coma, and death. Uremic toxicity is an indication for urgent dialysis.
In general, the symptoms of ESRD appear in stages 4 and 5 when the GFR is less than 30 ml/min. Some patients with nephrotic syndrome and cystic renal disease may present earlier.
Depression is ubiquitous in patients with ESRD and should be screened for on presentation.
To calculate GFR, three equations are commonly used (the MDRD, CKD-EPI, and Cockcroft-Gault formula). However, the best estimate of GFR is the CKD-EPI equation, which adjusts for age, race, and gender. It is important to note, however, that the formula tends to underestimate the actual GFR at a GFR greater than 60mL/min.
To quantitate albuminuria, a spot urine protein/creatinine ratio can be done. A value higher than 30 mg of albumin per gram of creatinine is considered abnormal, while values greater than 300mg/g are considered severely impaired renal function. Additionally, a 24-hour urine protein can also be performed. A value greater than 3.5 g is concerning for nephrotic range proteinuria.
Further evaluation of kidney disease can include a renal ultrasound, complete blood count (CBC), basic metabolic panel (BMP), urinalysis, and/or kidney biopsy. An ultrasound can provide data estimating size, obstructions, stones, cystic renal disease, mass lesions, echogenicity, and cortical thinning. Blood work will determine if there is secondary anemia and will detect evidence of electrolyte derangement. In cases of severe anemia secondary to CKD, erythropoiesis-stimulating agents should be started at a hemoglobin level below 10g/dL.
Finally, a renal biopsy may be necessary if the etiology remains unclear.
Treatment of end-stage renal disease involves correcting parameters at the level of the patient presentation. Interventions aimed at slowing the rate of kidney disease should be initiated and can include:
KDIGO 2012: CKD classification takes into account the GFR level as well as the severity of albuminuria.
End-stage renal disease is a progressive disorder, and timely renal replacement therapy is necessary to prevent death. The disorder is associated with numerous hospitalizations, increased healthcare costs, and numerous metabolic changes. The mortality rates for patients with end-stage renal disease are significantly higher than those without the disease. Even with timely dialysis, the death rates vary from 20-50% over 24 months. The most common cause of death is hyperkalemia, followed by adverse cardiac events.
In children, puberty is delayed in both genders, and low levels of vitamin D are common, which is an independent risk factor for death.
Coronary Heart Disease is a significant complication of chronic kidney disease and is the most common cause of death in this population. Patients on dialysis have a 10 to 30 times higher cardiovascular mortality risk than in the general population. Peripheral vascular disease is also commonly seen.
Common complications of progressive renal failure include the following:
The U.S. Preventive Services Task Force (USPSTF) recommends against screening asymptomatic individuals for CKD. However, for those individuals who are at higher risk for the disease, such as those with diabetes or hypertension, USPSTF recommends ongoing screening for CKD with proteinuria testing. It is important to note, however, that a patient who is already on ACEI or ARB therapy screening for proteinuria is not necessary.
Once a patient has been diagnosed with ESRD, a significant number of them will require dialysis, and the lucky few may be eligible for a renal transplant. End-stage renal failure significantly increases morbidity and mortality; in addition, it also leads to enormous costs to the healthcare system. Thus, the disorder is best managed by an interprofessional team that is dedicated to adequate disease control and improving outcomes for these patients.
There is no cure for end-stage renal disease, and all the available treatments are short term. Thus, the key to improving long-term outcome is in preventing the progression of the disease.
A dedicated interprofessional team should be comprised of a nurse educator, a specialized pharmacist, a nutritionist, a social worker, and a team of clinical providers, including a primary care provider as well as a trained nephrologist.
The specialized nurse educator plays a vital role in educating the patient about lifestyle modifications necessary to prevent the progression of CKD. In patients with advanced CKD, the dedicated nurse's role become crucial in protecting an arm for future fistula placement. During hospitalizations, the clinical nurse should place limb restrictions on that arm to ensure venipunctures and blood pressure readings are not taken on that arm.
The pharmacist should identify those patients who carry a diagnosis of CKD and provide specialized instructions to these patients, particularly in regard to avoiding nephrotoxic agents and medications. The pharmacist plays a crucial role in communicating and guiding the clinical providers about the patient's medications to limit those that can adversely affect the kidneys.
A trained nutritionist should also be involved in the care of these patients to provide guidance on an appropriate diet plan specific to their needs.
A social worker should be involved in the care to ensure that the patient has a support system and the financial resources to continue with therapy.
To improve outcomes, each member of the interprofessional team should communicate with the clinical providers to ensure that the patient is receiving optimal care.
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