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 major source of reduced quality of life and significant premature mortality. Chronic kidney disease (CKD) is a very limiting 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. KDIGO 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 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 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 higher in Native Hawaiians or Pacific Islanders. Rates were 1.3 times higher in Asian Americans. Of note, 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.
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 also 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.
Chronic kidney disease is diagnosed when there is evidence of kidney damage for at least 3 months or in any patient who has a GFR less than 60 mL/min for that same amount of time.
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 true GFR at a GFR greater than 60mL/min.
To quantitate albuminuria, a spot urine protein/creatinine ratio can be done. A value greater than 30 mg of albumin per gram of creatinine is considered abnormal while values greater than 300mg/g is 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, CBC, 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. It can be found on the KDIGO guidelines website.
Coronary Heart Disease is an important 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. The peripheral vascular disease is also commonly seen. It is associated with the following: