Chronic kidney disease (CKD)or chronic renal failure (CRF), as it was historically

termedis a term that encompasses all degrees of decreased renal function, from
damagedat risk through mild, moderate, and severe chronic kidney failure. CKD is a
worldwide public health problem. In the United States, there is a rising incidence and
prevalence of kidney failure, with poor outcomes and high cost (see Epidemiology).
CKD is more prevalent in the elderly population. However, while younger patients
with CKD typically experience progressive loss of kidney function, 30% of patients
over 65 years of age with CKD have stable disease. [1]
CKD is associated with an increased risk of cardiovascular disease and chronic renal
failure. Kidney disease is the ninth leading cause of death in the United States.
The Kidney Disease Outcomes Quality Initiative (KDOQI) of the National Kidney
Foundation (NKF) established a definition and classification of CKD in 2002. [3] The
KDOQI and the international guideline group Kidney Disease Improving Global
Outcomes (KDIGO) have subsequently updated these guidelines. [4, 5] These
guidelines have allowed better communication among physicians and have
facilitated intervention at the different stages of the disease.

The guidelines define CKD as either kidney damage or a decreased glomerular

filtration rate (GFR) of less than 60 mL/min/1.73 m2 for at least 3 months. Whatever
the underlying etiology, once the loss of nephrons and reduction of functional renal
mass reaches a certain point, the remaining nephrons begin a process of irreversible
sclerosis that leads to a progressive decline in the GFR.
Hyperparathyroidism is one of the pathologic manifestations of CKD. See the image
below.

Calciphylaxis due to secondary hyperparathyroidism.

Staging
The different stages of CKD form a continuum. The stages of CKD are classified as
follows [5] :
Stage 1: Kidney damage with normal or increased GFR (>90 mL/min/1.73 m 2)
Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m 2)
 Stage 3a: Moderate reduction in GFR (45-59 mL/min/1.73 m 2)
Stage 3b: Moderate reduction in GFR (30-44 mL/min/1.73 m 2)
Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m 2)
Stage 5: Kidney failure (GFR <15 mL/min/1.73 m 2 or dialysis) In stage 1 and stage 2
CKD, reduced GFR alone does not clinch the diagnosis, because the GFR may in fact
be normal or borderline normal. In such cases, the presence of one or more of the
following markers of kidney damage can establish the diagnosis [5] :
Albuminuria (albumin excretion >30 mg/24 hr or albumin:creatinine ratio >30
mg/g [>3 mg/mmol])
Urine sediment abnormalities
Electrolyte and other abnormalities due to tubular disorders
Histologic abnormalities
Structural abnormalities detected by imaging
History of kidney transplantation in such cases
Hypertension is a frequent sign of CKD but should not by itself be considered a
marker of it, because elevated blood pressure is also common among people
without CKD.
In an update of its CKD classification system, the NKF advised that GFR and
albuminuria levels be used together, rather than separately, to improve prognostic
accuracy in the assessment of CKD. [4, 5] More specifically, the guidelines
recommended the inclusion of estimated GFR and albuminuria levels when
evaluating risks for overall mortality, cardiovascular disease, end-stage kidney
failure, acute kidney injury, and the progression of CKD. Referral to a kidney
specialist was recommended for patients with a very low GFR (<15 mL/min/1.73 m)
or very high albuminuria (>300 mg/24 h). [4, 5]

Patients with stages 1-3 CKD are frequently asymptomatic. Clinical manifestations
resulting from low kidney function typically appear in stages 4-5 (see Presentation).

Signs and symptoms

Patients with CKD stages 1-3 are generally asymptomatic. Typically, it is not until
stages 4-5 (GFR <30 mL/min/1.73 m) that endocrine/metabolic derangements or
disturbances in water or electrolyte balance become clinically manifest.

Signs of metabolic acidosis in stage 5 CKD include the following:

Protein-energy malnutrition
Loss of lean body mass
Muscle weakness

Signs of alterations in the way the kidneys are handling salt and water in stage 5
include the following:
Peripheral edema
Pulmonary edema
Hypertension

Anemia in CKD is associated with the following:

Fatigue
 Reduced exercise capacity
Impaired cognitive and immune function
Reduced quality of life
Development of cardiovascular disease
New onset of heart failure or the development of more severe heart failure
Increased cardiovascular mortality

Other manifestations of uremia in end-stage renal disease (ESRD), many of which are
more likely in patients who are being inadequately dialyzed, include the following:
Pericarditis: Can be complicated by cardiac tamponade, possibly resulting in death
if unrecognized
Encephalopathy: Can progress to coma and death
Peripheral neuropathy, usually asymptomatic
Restless leg syndrome
Gastrointestinal symptoms: Anorexia, nausea, vomiting, diarrhea
Skin manifestations: Dry skin, pruritus, ecchymosis
Fatigue, increased somnolence, failure to thrive
Malnutrition
Erectile dysfunction, decreased libido, amenorrhea
Platelet dysfunction with tendency to bleed

Screen adult patients with CKD for depressive symptoms; self-report scales at
initiation of dialysis therapy reveal that 45% of these patients have such symptoms,
albeit with a somatic emphasis.

See Clinical Presentation for more detail.

Diagnosis
Laboratory studies

Laboratory studies used in the diagnosis of CKD can include the following:
Complete blood count (CBC)
Basic metabolic panel
Urinalysis
Serum albumin levels: Patients may have hypoalbuminemia due to malnutrition,
urinary protein loss, or chronic inflammation
Lipid profile: Patients with CKD have an increased risk of cardiovascular disease

Evidence of renal bone disease can be derived from the following tests:
Serum calcium and phosphate
25-hydroxyvitamin D
Alkaline phosphatase
Intact parathyroid hormone (PTH) levels

In certain cases, the following tests may also be ordered as part of the evaluation of
patients with CKD:
Serum and urine protein electrophoresis and free light chains: Screen for a
 monoclonal protein possibly representing multiple myeloma
Antinuclear antibodies (ANA), double-stranded DNA antibody levels: Screen for
systemic lupus erythematosus
Serum complement levels: Results may be depressed with some
glomerulonephritides
Cytoplasmic and perinuclear pattern antineutrophil cytoplasmic antibody (C-ANCA
and P-ANCA) levels: Positive findings are helpful in the diagnosis of
granulomatosis with polyangiitis (Wegener granulomatosis); P-ANCA is also
helpful in the diagnosis of microscopic polyangiitis
Antiglomerular basement membrane (anti-GBM) antibodies: Presence is highly
suggestive of underlying Goodpasture syndrome
Hepatitis B and C, human immunodeficiency virus (HIV), Venereal Disease
Research Laboratory (VDRL) serology: Conditions associated with some
glomerulonephritides

Imaging studies

Imaging studies that can be used in the diagnosis of CKD include the following:
Renal ultrasonography: Useful to screen for hydronephrosis, which may not be
observed in early obstruction or dehydrated patients; or for involvement of
the retroperitoneum with fibrosis, tumor, or diffuse adenopathy; small,
echogenic kidneys are observed in advanced renal failure
Retrograde pyelography: Useful in cases with high suspicion for obstruction
despite negative renal ultrasonograms, as well as for diagnosing renal stones
Computed tomography (CT) scanning: Useful to better define renal masses and
cysts usually noted on ultrasonograms; also the most sensitive test for
identifying renal stones
Magnetic resonance imaging (MRI): Useful in patients who require a CT scan but
who cannot receive intravenous contrast; reliable in the diagnosis of renal
vein thrombosis
Renal radionuclide scanning: Useful to screen for renal artery stenosis when
performed with captopril administration; also quantitates the renal
contribution to the GFR

Biopsy

Percutaneous renal biopsy is generally indicated when renal impairment and/or

proteinuria approaching the nephrotic range are present and the diagnosis is unclear
after appropriate workup.

See Workup for more detail.

Management
Early diagnosis and treatment of the underlying cause and/or institution of
secondary preventive measures is imperative in patients with CKD. These may slow,
or possibly halt, progression of the disease.The medical care of patients with CKD
should focus on the following:
 Delaying or halting the progression of CKD: Treatment of the underlying condition,
if possible, is indicated
Diagnosing and treating the pathologic manifestations of CKD
Timely planning for long-term renal replacement therapy

The pathologic manifestations of CKD should be treated as follows:

Anemia: When the hemoglobin level is below 10 g/dL, treat with erythropoiesis-
stimulating agents (ESAs), which include epoetin alfa and darbepoetin alfa
after iron saturation and ferritin levels are at acceptable levels
Hyperphosphatemia: Treat with dietary phosphate binders and dietary phosphate
restriction
Hypocalcemia: Treat with calcium supplements with or without calcitriol
Hyperparathyroidism: Treat with calcitriol or vitamin D analogues or calcimimetics
Volume overload: Treat with loop diuretics or ultrafiltration
Metabolic acidosis: Treat with oral alkali supplementation
Uremic manifestations: Treat with long-term renal replacement therapy
(hemodialysis, peritoneal dialysis, or renal transplantation)

Indications for renal replacement therapy include the following:

Severe metabolic acidosis
Hyperkalemia
Pericarditis
Encephalopathy
Intractable volume overload
Failure to thrive and malnutrition
Peripheral neuropathy
Intractable gastrointestinal symptoms
In asymptomatic patients, a GFR of 5-9 mL/min/1.73 m, [2] irrespective of the
cause of the CKD or the presence or absence of other comorbidities