Chronic Kidney Disease (CKD)

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 kidney function, from damaged–at 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.

CKD is associated with an increased risk of cardiovascular disease and end-stage renal disease (ESRD). 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.
The KDOQI and the international guideline group Kidney Disease Improving Global Outcomes (KDIGO) subsequently updated these guidelines.
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
:

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)

By itself, measurement of GFR may not be sufficient for identifying stage 1 and stage 2 CKD, because in those patients 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
:

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.
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 m²) or very high albuminuria (> 300 mg/24 h).

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 m²) 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 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 Presentation for more detail.

Diagnosis

Screening

American College of Physicians guidelines on screening for CKD include the following recommendations:

Do not screen for CKD in asymptomatic adults without risk factors for CKD (grade: weak recommendation, low-quality evidence).

Do not test for proteinuria in adults with or without diabetes who are currently taking an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II-receptor blocker (ARB)(grade: weak recommendation, low-quality evidence).

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

Anti–glomerular 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 kidney 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 kidney 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 kidney biopsy is generally indicated when kidney 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 m²,

irrespective of the cause of the CKD or the presence or absence of other comorbidities

The National Kidney Foundation’s 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.

See Treatment and Medication for more detail.

For a discussion of CKD in children, click here.