End-Stage Renal Disease

Article Author:
Onecia Benjamin
Article Editor:
Sarah Lappin
Updated:
11/15/2019 10:04:05 PM
PubMed Link:
End-Stage Renal Disease

Introduction

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.[1][2]

Etiology

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.

Epidemiology

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.[3][4]

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.

Pathophysiology

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:

  • Nephrotoxins (NSAIDs)
  • Systemic hypertension
  • Proteinuria
  • Dehydration
  • Smoking
  • Hyperlipidemia
  • Uncontrolled diabetes
  • Hyperphosphatemia

History and Physical

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.

Evaluation

Chronic kidney disease is diagnosed when there is evidence of kidney damage for at least three months or in any patient who has a GFR less than 60 mL/min for that same amount of time.[5][6]

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 / Management

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:

  • Treating the underlying cause and managing blood pressure and proteinuria. Blood pressure should be targeted to a systolic blood pressure less than 130 mmHg and diastolic blood pressure less than 80 mmHg in both diabetic and non-diabetic adults whose urine albumin excretion exceeds 30 mg for 24 hours. For diabetic patients with proteinuria, an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) should be started in cases where urine albumin values range between 30 and 300mg in 24 hours and greater than 300 mg in 24 hours. These drugs slow the disease progression, particularly when initiated before the GFR decreases to less than 60 mL/min or before plasma creatinine concentration exceeds 1.2 and 1.5 in women and men, respectively.
  • Other targets in preventive care and monitoring should include tight glycemic control, cardiovascular risk reduction, and general lifestyle recommendations such as smoking cessation and dietary restriction. Glycemic control is critical. A hemoglobin A1C of less than 7% is generally recommended to prevent or delay microvascular complications in this population. Management with sodium-glucose transporter 2 (SGLT-2) inhibitors may reduce the burden of disease in those with Type II diabetes mellitus.
  • Treatment of chronic metabolic acidosis with supplemental renal bicarbonate also may slow the progression of end-stage renal disease.
  • Patients with CKD tend to have dyslipidemia, particularly hypertriglyceridemia. Monitoring fasting lipid panels and initiation of cholesterol-lowering agents such as HMG-CoA reductase inhibitors should be done early in the course of the disease.   
  • Lifestyle modification and dietary restrictions are routinely recommended. Adhering to a low salt diet (less than 2 g/day), a renal diet (avoiding foods that are high in phosphorus), and restricting daily protein to 0.8g per kg body weight per day is essential to managing disease burden.
  • Hypocalcemia should also be monitored. A 25-OH vitamin D level less than 10 ng/mL warrants initiation of ergocalciferol 50,000 IU weekly for 6 to 8 weeks before switching to cholecalciferol 800 to 1000 IU daily.

Staging

KDIGO 2012: CKD classification takes into account the GFR level as well as the severity of albuminuria.

  • Stage 1: Kidney damage with normal GFR (greater than 90ml/min)
  • Stage 2: Mild reduction in GFR (60-89 ml/min)
  • Stage 3a: Moderate reduction in GFR (45-59 ml/min)
  • Stage 3b: Moderate reduction in GFR (30-44 ml/min)
  • Stage 4: Severe reduction in GFR (15-29 ml/min)
  • Stage 5: Renal failure (GFR less than 15 ml/min)

Prognosis

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.

Complications

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:

  • Hypertension
  • Mineral and bone disorders (secondary to hyperparathyroidism, vitamin D deficiency)
  • Hyperuricemia 
  • Metabolic acidosis
  • Hyperphosphatemia
  • Hypoalbuminemia
  • Anemia

Deterrence and Patient Education

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.

Pearls and Other Issues

  • ESRD is a terminal illness defined as having a glomerular filtration rate of less than 15 mL/min.
  • The most common cause of ESRD in the US is diabetic nephropathy, followed by hypertension.
  • Other etiologies can include glomerulonephritis, cystic kidney disease, recurrent kidney infection, chronic obstruction, etc.
  • The disease can present with nausea, vomiting, metabolic, hematologic, electrolyte derangements, seizures, coma, bleeding diathesis, refractory fluid overload, and hypertension unresponsive to pharmacotherapy, uremic pericarditis, etc.
  • Vigilant monitoring of GFR and proteinuria in diabetics and non-diabetics is essential for the management of progression of disease in patients with chronic kidney disease.
  • Early referral to specialists is necessary for timely dialysis or renal transplant planning.

Enhancing Healthcare Team Outcomes

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 team should communicate with the clinical providers to ensure that the patient is receiving optimal care.


References

[1] Scott IA,Scuffham P,Gupta D,Harch TM,Borchi J,Richards B, Going digital: a narrative overview of the effects, quality and utility of mobile apps in chronic disease self-management. Australian health review : a publication of the Australian Hospital Association. 2018 Nov 13     [PubMed PMID: 30419185]
[2] Sgambat K,Cheng YI,Charnaya O,Moudgil A, The prevalence and outcome of children with failure to thrive after pediatric kidney transplantation. Pediatric transplantation. 2018 Nov 11     [PubMed PMID: 30417493]
[3] Harding JL,Pavkov ME,Magliano DJ,Shaw JE,Gregg EW, Global trends in diabetes complications: a review of current evidence. Diabetologia. 2018 Aug 31     [PubMed PMID: 30171279]
[4] Ishigami J,Matsushita K, Clinical epidemiology of infectious disease among patients with chronic kidney disease. Clinical and experimental nephrology. 2018 Sep 3     [PubMed PMID: 30178234]
[5] Kyte D,Bishop J,Brettell E,Calvert M,Cockwell P,Dutton M,Eddington H,Hadley G,Ives NJ,Jackson LJ,Stringer S,Valente M, Use of an electronic patient-reported outcome measure in the management of patients with advanced chronic kidney disease: the RePROM pilot trial protocol. BMJ open. 2018 Oct 28     [PubMed PMID: 30373785]
[6] Weckmann GFC,Stracke S,Haase A,Spallek J,Ludwig F,Angelow A,Emmelkamp JM,Mahner M,Chenot JF, Diagnosis and management of non-dialysis chronic kidney disease in ambulatory care: a systematic review of clinical practice guidelines. BMC nephrology. 2018 Oct 11     [PubMed PMID: 30305035]