Chronic Kidney Disease

Updated: Jul 24, 2016

Author: Pradeep Arora, MD; Chief Editor: Vecihi Batuman, MD, FASN more...

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

The National Kidney Foundations Kidney Disease Outcomes Quality Initiative (KDOQI)
issued a Clinical Practice Guideline for Nutrition in Chronic Renal Failure, as well as a
revision of recommendations for Nutrition in Children with Chronic Kidney Disease.