Chronic kidney disease in children: Clinical manifestations, evaluation, and diagnosis

INTRODUCTION — 

Chronic kidney disease (CKD) refers to a state of irreversible and progressive reduction in kidney function.

The clinical manifestations, evaluation, and diagnosis of CKD in children will be reviewed here. Other aspects of CKD in children are discussed separately:

●(See "Chronic kidney disease in children: Epidemiology, etiology, and course".)

●(See "Chronic kidney disease in children: Overview of management".)

●(See "Chronic kidney disease in children: Complications".)

●(See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)".)

CLINICAL FEATURES — 

The clinical findings of CKD depend on the underlying disorder (nonglomerular versus glomerular disease) and the severity of kidney impairment. Patients may present with dysmorphic features or physical manifestations representing features of genetic disorders that are associated with kidney anomalies and CKD (eg, hereditary nephritis [Alport syndrome] and cystinosis). (See "Chronic kidney disease in children: Epidemiology, etiology, and course", section on 'Etiology'.)

Nonglomerular disorders — Nonglomerular causes of CKD affect either the tubular components of the nephron and/or the surrounding medullary interstitial space. These disorders are primarily comprised of congenital anomalies of the kidney and urinary tract (CAKUT) and cystic kidney diseases. Approximately 60 percent of childhood cases of CKD are due to congenital anomalies. (See "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)".)

Nonglomerular disorders in children are most often identified by imaging, including routine antenatal ultrasonography that detects structural abnormalities. Early in the course, signs of kidney dysfunction are subtle and may include:

●Polyuria – Polyuria may be an early presenting finding because many CAKUT diagnoses (eg, obstructive uropathy, bilateral renal dysplasia), inherited disorders (eg, nephronophthisis), and tubulointerstitial disorders are associated with reduced urinary concentrating ability. In these conditions, the impairment in concentrating capacity of the kidneys generally precedes a significant reduction in glomerular filtration rate (GFR). During an acute illness (eg, gastroenteritis), such patients are at increased risk for volume depletion and consequent prerenal kidney injury, causing acute-on-chronic kidney injury. (See "Chronic kidney disease in children: Overview of management", section on 'Avoid subsequent kidney injury'.)

●Poor growth – Growth failure is a major complication of children with CKD and correlates with younger age of onset and disease severity [1]. These children may also have urinary salt wasting and/or have poor appetite, which contributes to their poor growth and should be evaluated and addressed. (See "Growth failure in children with chronic kidney disease: Risk factors, evaluation, and diagnosis".)

●Elevated creatinine – Serum creatinine concentration may be elevated for age (table 1) and can be used to estimate GFR and severity of CKD for most children. However, in conditions with reduced muscle mass, such as malnutrition, neuromuscular disease such as spina bifida, or amputation, serum creatinine is lower and thus overestimates GFR. For such children, cystatin C concentrations provide a more accurate estimation of GFR [2]. The reference creatinine values depend on the methodology used by the laboratory (enzymatic or Jaffe) (table 1). (See 'Estimation of glomerular filtration rate' below.)

Glomerular disorders — Children with a glomerular disorder as the cause for CKD often present with more prominent signs and symptoms of kidney disease:

●Signs and symptoms of CKD

•Tea-colored urine – Discolored urine may be the presenting symptom. Glomerular hematuria characteristically presents with brown, rather than red, urine. Microscopy demonstrates dysmorphic red blood cells, and the presence of red blood cell casts are nearly pathognomonic of glomerulonephritis. In other cases, microscopic hematuria may be an incidental finding.

•Proteinuria – Proteinuria is a strongly associated biomarker of CKD and is a possible sign of underlying glomerular disease or tubular dysfunction. Persistent (≥3 months) increased excretion of urinary protein in a first-morning urine sample suggests CKD [3]. (See "Evaluation of proteinuria in children".)

•Edema – Edema may be present due to severe (nephrotic-range) proteinuria or fluid overload (a complication of CKD). (See "Chronic kidney disease in children: Complications", section on 'Sodium and water homeostasis'.)

•Elevated blood pressure – Blood pressure is often elevated for age. (See "Chronic kidney disease in children: Complications", section on 'Hypertension'.)

•Elevated creatinine – Serum creatinine concentration is usually elevated for age and can be used to estimate GFR and severity of CKD in children. (See 'Estimation of glomerular filtration rate' below.)

●Signs of underlying systemic disorders – Children with secondary glomerulonephritis may have systemic symptoms and findings associated with the causative disease, such as lupus nephritis or granulomatosis with polyangiitis. Clinical manifestations may include fever, arthralgias/arthritis, rash, and/or pulmonary symptoms. (See "Childhood-onset systemic lupus erythematosus (cSLE): Clinical manifestations and diagnosis", section on 'Clinical manifestations' and "Granulomatosis with polyangiitis and microscopic polyangiitis: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.)

Symptoms associated with disease progression — Clinical findings also increase with the severity of kidney dysfunction (table 2):

●Early CKD (stages G1 and G2) – In early CKD, children are often asymptomatic unless there are signs and/or symptoms that result directly from underlying structural kidney abnormalities or systemic diseases (eg, renal colic from ureteropelvic junction obstruction or nephrotic syndrome due to massive proteinuria). Asymptomatic patients may be identified by elevated serum creatinine for age, abnormalities on urinalysis (proteinuria, hematuria, or concentrating defect), or detection of kidney disease by imaging studies including antenatal ultrasonography.

Nearly one-half of children with stage G2 CKD have elevated blood pressure [4], and many others have masked hypertension demonstrated on ambulatory blood pressure monitoring [5], thereby highlighting the importance of proper blood pressure assessment and recognition of elevated values in this population [6]. Patients may also have anemia and/or vitamin D deficiency [7,8]. (See "Chronic kidney disease in children: Overview of management", section on 'Blood pressure and targeted goals' and "Chronic kidney disease in children: Complications", section on 'Screening and evaluation of anemia' and "Pediatric chronic kidney disease-mineral and bone disorder (CKD-MBD)", section on 'Clinical manifestations'.)

●Moderate CKD (stages G3a and G3b) – In intermediate stages of CKD, children may exhibit growth delay, fatigue, anorexia, anemia, metabolic acidosis, elevated blood pressure, and CKD-mineral and bone disorder. (See "Chronic kidney disease in children: Complications".)

●Severe CKD or kidney failure (stages G4 and G5, respectively) – In severe CKD, the symptoms found in the earlier stages of CKD are more common and may be more severe. The presence of severe electrolyte derangements, anemia, and acidosis may manifest as weakness, fatigue, anorexia, or vomiting. (See "Chronic kidney disease in children: Complications", section on 'Uremia' and "Chronic kidney disease in children: Complications", section on 'Neurodevelopmental impairment'.)

INITIAL EVALUATION

Who should be evaluated — The possibility of CKD should be considered in a child with any risk factors or symptoms, which include kidney diseases, other conditions associated with CKD, family history of kidney disease, and signs and symptoms as outlined in the table (table 3) and above [9]. (See 'Clinical features' above.)

History and physical examination — In addition to the risk factors, signs, and symptoms outlined above, important historical findings include age at onset of symptoms, duration of symptoms, and identification of additional CKD risk factors (eg, family history of CKD in a child who presents with unexplained anemia).

Key elements of the physical examination include evaluation for (table 4):

●Growth parameters (weight and height; head circumference for children <3 years) (see "Measurement of growth in children")

●Blood pressure, comparing with normative standards for the child's sex, age, and height (table 5A-B) (calculator 1)

●Physical signs of hypervolemia (eg, edema, rales)

●Skeletal deformities, which suggest CKD-mineral and bone disorder and/or a syndromic CKD (see "Chronic kidney disease in children: Complications" and "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)")

Laboratory testing — Blood and urine studies are often used to confirm the diagnosis of CKD, assess its severity, determine appropriate staging, and detect associated complications. Abnormalities in these assessments may not be readily apparent during the early stages of CKD but will become increasingly prevalent as the glomerular filtration rate (GFR) decreases. While there is no single pattern of laboratory abnormalities that characterizes pediatric CKD, there are some abnormalities that are commonly present and that are indicative of underlying chronic kidney dysfunction, as discussed in the following sections.

Estimation of glomerular filtration rate — In clinical practice, GFR is estimated indirectly through serum creatinine and/or cystatin C. Appropriate equations include:

●Chronic Kidney Disease in Children (CKiD) U25 equations – For children and young adults 1 to 25 years with CKD, GFR-estimating equations were developed from the CKiD study and are embedded in the CKiD U25 calculator (calculator 2) (another version available here) [2]. The most accurate estimate uses both creatinine and cystatin C, but the same calculator can be used to derive estimated GFR (eGFR) from either one of these markers. To use this calculator, creatinine levels must be based on an enzymatic creatinine assay, which is the method used in most contemporary laboratories. Cystatin C should be derived using an assay that is calculated against International Federation of Clinical Chemistry and Laboratory Medicine standards.

The CKiD U25 equations were based on a cohort of children in the CKiD study and validated in an external cohort of children with CKD [10,11]. They are only recommended for use in children and young adults with childhood-onset CKD [12]. These equations are most accurate for estimating GFR with severe kidney function impairment and tend to underestimate kidney function as it nears the normal range (eg, when GFR is >75 mL/min/1.73 m²) [10,11,13,14].

Cystatin C is increasingly used to estimate GFR in clinical practice. In addition to its use for children with CKD, it is appropriate to use in children with prominent non-GFR determinants of serum creatinine (ie, children with decreased muscle mass, eg, neuromuscular disorders, malnutrition, limb amputations) or variations in dietary creatinine intake (ie, people on a vegetarian diet or taking creatinine supplements) [15,16]. In these circumstances, the most accurate GFR estimate is derived from an equation based on cystatin C alone or both cystatin C and creatinine. (See "Assessment of kidney function", section on 'Limitations of creatinine-based eGFR' and "Assessment of kidney function", section on 'eGFR from cystatin C'.)

●Schwartz equation

•If creatinine is measured using the Jaffe assay, then GFR must be estimated using the Schwartz equation (calculator 3) rather than the CKiD U25 equations [17]. The equation includes the child's height, serum creatinine (mg/dL), and a constant "k" that varies with the child's age.

•If creatinine is measured by the enzymatic method, a slightly different equation is used (calculator 3), in which the constant "k" does not vary by age [18,19].

●Other methods – The following methods used to measure GFR are based on determining the clearance of a filtration marker and are not practical for routine clinical use (see "Assessment of kidney function"):

•Inulin, a physiologically inert substance that is freely filtered at the glomerulus, has been the gold standard marker. However, it is not commercially available and requires continuous intravenous infusion, multiple blood samples, and, at times, bladder catheterization.

•Creatinine clearance is determined by serum creatinine and a timed urine collection for creatinine clearance; however, the collection is often inconvenient for families and inaccurate due to challenges collecting all required samples during school or the presence of nocturnal enuresis or voiding dysfunction.

•Other methods include single-injection techniques for plasma disappearance of iohexol, inulin, and other exogenous filtration markers (⁵¹Cr-Labeled EDTA and ^99mTc-DTPA) and are mostly used on a research basis.

Other diagnostic laboratory tests — Other tests obtained in the evaluation of a child with CKD include:

●Urinalysis – A urinalysis is a useful screening test for abnormalities of the kidney and urinary tract and as an aid in identifying the underlying cause of CKD. The urinary dipstick tests for protein, pH, concentration (specific gravity), glucose, red blood cells, and white blood cells. The different patterns of urinary findings associated with acute kidney injury and CKD are discussed separately. (See "Urinalysis in the diagnosis of kidney disease".)

●Urinary protein – Persistent proteinuria is an important biomarker for CKD and indicates underlying glomerular and/or tubulointerstitial disease. The severity of kidney disease is generally associated with the amount and duration of proteinuria [20-24]. Moreover, ongoing urinary protein excretion for children with CKD may contribute to disease progression.

Initial evaluation of proteinuria is as follows (see "Evaluation of proteinuria in children"):

•If low levels of protein are detected in a random urine sample (1+ detected by urinary dipstick evaluation), we perform several additional measurements to determine if the proteinuria is persistent.

•If the repeated dipstick measurements confirm persistent proteinuria, we determine the urine protein/creatinine ratio in a first-morning sample of urine (calculator 4). This test helps to exclude orthostatic proteinuria, a benign condition in which proteinuria is absent when urine is obtained immediately following the recumbent state. (See "Evaluation of proteinuria in children", section on 'Spot urine sample'.)

•If proteinuria is high grade (2+ protein or greater by dipstick evaluation) and persistent, we evaluate promptly for signs of kidney dysfunction.

Measurement of urinary protein (protein/creatinine ratio) rather than albuminuria is generally preferred for children with CKD because the majority of children with CKD have nonglomerular conditions and a relatively higher preponderance of tubular proteinuria, which may be missed if only albuminuria is assessed [20-23].

DIAGNOSIS AND STAGING — 

CKD is defined as the presence of structural or functional kidney damage that persists over a minimum period of three months. Functional damage is characterized by sustained reduction of estimated glomerular filtration rate (eGFR), persistent elevation of urinary protein excretion, or both. Based on this definition, clinical practice guidelines from Kidney Disease: Improving Global Outcomes (KDIGO) in 2012 included criteria for the diagnosis and staging of pediatric CKD [25].

Diagnostic criteria — The KDIGO diagnosis of pediatric CKD is based on fulfilling either of the following clinical criteria for >3 months, with implications for health [25]:

●GFR <60 mL/min per 1.73 m² (or, for children <2 years, use age-specific GFR standards (see 'Age <2 years' below))

and/or

●Markers of kidney damage – Including functional kidney abnormalities (proteinuria or abnormal urine sediment), electrolyte abnormalities due to tubular disorders, or pathologic abnormalities detected by histology or inferred by imaging. This category also includes patients with functioning kidney transplants.

The KDIGO diagnosis criteria and staging classification are the standard used in clinical practice, research, and public health in the care of children with CKD and will be used throughout this topic.

Staging — Normal levels of GFR vary with age, sex, and body size. GFR increases with maturation from infancy and generally approaches adult values by two years of age (table 6) [26,27]. As a result, standards used to categorize CKD differ by age:

Age <2 years — For infants and toddlers with CKD, age-specific standards for GFR can be used to categorize the degree of kidney function impairment (table 6). Values more than one standard deviation (SD) below the age-specific mean should raise concern and prompt continued monitoring of kidney function [25]:

●Moderate reduction – GFR value between 1 and 2 SD below the mean for age

●Severe reduction – GFR value ≥2 SD below the mean for age

For this age group, use of the GFR values of older individuals outlined below would underestimate their kidney function and would incorrectly place them in a more advanced stage of disease [25]. As an example, a six-month-old infant with normal kidney function would be incorrectly classified as having GFR category G2 disease because the mean GFR for this age is normally below 89 mL/min per 1.73 m².

Age ≥2 years — The KDIGO CKD staging for children older than two years of age stratifies the risk for progression of CKD and its complications based on GFR and is used to guide management (table 2):

●G1 – GFR ≥90 mL/min per 1.73 m² (normal)

●G2 – GFR ≥60 to 89 mL/min per 1.73 m²

●G3a – GFR ≥45 to 59 mL/min per 1.73 m²

●G3b – GFR ≥30 to 44 mL/min per 1.73m²

●G4 – GFR ≥15 to 29 mL/min per 1.73 m²

●G5 – GFR <15 mL/min per 1.73 m² (kidney failure)

Stage G5 defines kidney failure, a state of permanent loss of kidney function that generally requires long-term dialysis or kidney transplant to sustain life.

FURTHER EVALUATION — 

Children with suspected CKD should be referred to a pediatric nephrologist to guide additional evaluation and long-term management. The next steps in the evaluation include:

Imaging — Imaging may be useful in identifying the underlying cause of CKD and assessing renal parenchymal structure.

Ultrasound — All children with suspected or confirmed CKD should have ultrasonography of the kidneys. Ultrasonography is useful to assess the kidney dimensions and structure. It may be diagnostic for some underlying causes of CKD, such as cystic kidney disease or hypoplasia. Antenatal ultrasonography may identify neonates at risk for CKD, especially if there are abnormalities of both kidneys.

The ultrasound examination should compare the measured length of each kidney with normative age-appropriate values (figure 1) [28-30]. Kidneys that are smaller than normal indicate a decrease in kidney mass, which may be due to congenital anomalies of the kidney and urinary tract (CAKUT; eg, renal hypoplasia), poor growth, or loss of renal parenchyma due to an underlying disorder or injury.

Children with a congenital solitary kidney (unilateral renal agenesis) are at risk for CKD. Risk factors for a decreased glomerular filtration rate (GFR) with a solitary kidney include additional anomalies of the kidney and urinary tract and a kidney length not consistent with expected compensatory hypertrophy (defined as a kidney length that is at least 10 percent less than predicted for a solitary kidney) [31]. Children with a solitary kidney without CKD typically have a kidney length greater than the 95^th percentile due to compensatory kidney hypertrophy [32]. (See "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Unilateral renal agenesis'.)

Other modalities

●Voiding cystourethrogram (VCUG) – Patients with hydronephrosis and recurrent febrile urinary tract infections should be evaluated with a VCUG. Additionally, the VCUG can diagnose lower urinary tract obstruction (eg, due to posterior urethral valves) and provide further anatomic information regarding the structure and function of the bladder and urethra.

●Renal scans – Renal scans are used to assess differential kidney function. The indications, choice of isotope, and addition of adjunctive medication (eg, furosemide) are based on the clinical setting and the underlying goal of the study:

•A static renal scan with ^99mTc-DMSA (dimercaptosuccinic acid) can detect focal kidney abnormalities such as scars. In low-resource settings, this scan may be performed with ^99mTc-GHA (glucoheptonate). (See "Evaluation of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Static renal scan'.)

•A dynamic renal scan (also known as diuretic renography) can assess for potential urinary tract obstruction as well as split kidney function. It is typically performed with either ^99mTc-MAG3 (mercaptoacetyltriglycine) or ^99mTc-DTPA (diethylenetriamine pentaacetate). (See "Evaluation of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Dynamic renal scan'.)

●Other imaging – Computed tomography (CT) or magnetic resonance imaging or angiography (MRI/MRA) are used in specific clinical settings when better visualization of the kidney and urinary tract or its vasculature is required. Imaging studies such as angiography and magnetic resonance urography are used to clarify or delineate abnormalities found on standard imaging studies.

Imaging studies with contrast agents require special considerations:

•Ionic and nonionic contrast agents may be nephrotoxic and cause acute kidney injury. To reduce the risk of contrast-associated acute kidney injury in children with CKD, guidelines recommend administration of isotonic saline before and after infusion of iodinated contrast for CT scan [33]. (See "Prevention of contrast-induced acute kidney injury associated with computed tomography", section on 'Prevention among high-risk patients'.)

•Gadolinium-based contrast agents for MRI and MRA have been associated with nephrogenic fibrosing dermopathy and, sometimes, fatal nephrogenic systemic fibrosis in both children and adults with CKD [34,35]. However, the newer group II and group III MRI contrast agents appear to be much safer in patients with kidney disease due to improved stability of the macrocyclic nonionic structure. The potential harms of delaying or withholding group II or III agents in patients with CKD must be carefully weighed against the very small potential risk of nephrogenic systemic fibrosis in this population. Guidelines recommend that kidney function does not need to be assessed with the use of a group II agent, although it is still recommended with group III agents due to more limited research data [36]. (See "Patient evaluation before gadolinium contrast administration for magnetic resonance imaging", section on 'Gadolinium group and risk for nephrogenic systemic fibrosis'.)

Kidney biopsy — Kidney biopsy is often performed in patients with glomerular causes for CKD. However, kidney biopsy in patients near kidney failure (G5 stage, previously referred to as end-stage kidney disease) may not identify the etiology of CKD, because of the presence of diffuse global sclerosis of the glomeruli and severe tubulointerstitial fibrosis.

Tissue samples obtained via kidney biopsy are typically evaluated by light microscopy, immunofluorescence staining, and electron microscopy. These studies may be useful in providing a diagnosis for the cause of CKD and guiding therapeutic choices. Even if the biopsy does not provide a specific diagnosis, it often serves to exclude other disease entities in the differential diagnosis. The biopsy results also provide information about disease severity, including whether any abnormalities may be reversible, and the degree of interstitial fibrosis and parenchymal scarring, which is generally not reversible.

Assessment for complications of chronic kidney disease — Complications due to kidney impairment become more prevalent with decreasing GFR in children as CKD advances from stage G3 to stage G5 (table 2).

The following evaluations to detect complications are warranted at diagnosis of CKD and periodically thereafter. (See "Chronic kidney disease in children: Complications".)

●Growth impairment – Monitor weight, height, and growth velocity. (See "Growth failure in children with chronic kidney disease: Prevention and management".)

●Hypertension – Measure blood pressure at every visit, with periodic ambulatory blood pressure monitoring. Ambulatory blood pressure monitoring reveals masked hypertension in approximately 40 percent of children with CKD [5]. (See "Chronic kidney disease in children: Overview of management", section on 'Blood pressure and targeted goals' and "Chronic kidney disease in children: Complications", section on 'Hypertension'.)

●Fluid and electrolyte abnormalities – Common abnormalities associated with CKD are metabolic acidosis, hyperkalemia, or hypokalemia. (See "Chronic kidney disease in children: Complications", section on 'Fluid and electrolyte abnormalities'.)

●Anemia – Perform a complete blood count with red blood cell indices to detect anemia and evidence of systemic diseases. The anemia associated with CKD is typically normocytic and normochromic. If the red blood cell indices do not show these characteristics, further evaluation to determine the cause(s) of anemia is warranted. (See "Chronic kidney disease in children: Complications", section on 'Screening and evaluation of anemia' and "Approach to the child with anemia".)

●CKD-mineral and bone disorder – Monitor serum calcium, phosphorus, 25-hydroxyvitamin D3, alkaline phosphatase, and parathyroid hormone to evaluate for abnormalities in bone and mineral metabolism. (See "Pediatric chronic kidney disease-mineral and bone disorder (CKD-MBD)".)

●Dyslipidemia – Measure total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. (See "Chronic kidney disease in children: Complications", section on 'Dyslipidemia'.)

Additional evaluation for other complications of CKD is warranted for children with suggestive symptoms or signs, including:

●Endocrine abnormalities (see "Chronic kidney disease in children: Complications", section on 'Endocrine dysfunction')

●Uremia (decreased clearance of substances excreted by the kidneys) (see "Chronic kidney disease in children: Complications", section on 'Uremia')

●Neurodevelopmental and neurocognitive delay (see "Chronic kidney disease in children: Complications", section on 'Neurodevelopmental impairment')

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic kidney disease in children".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Chronic kidney disease (The Basics)" and "Patient education: Medicines for chronic kidney disease (The Basics)" and "Patient education: Bone problems caused by kidney disease (The Basics)")

●Beyond the Basics topic (see "Patient education: Chronic kidney disease (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Clinical manifestations – The clinical presentation of chronic kidney disease (CKD) in children varies with the underlying disorder:

•Nonglomerular disorders – Usually identified by imaging studies that reveal structural abnormalities. Affected children are often asymptomatic or have clinical findings that include polyuria (reduced renal concentrating ability), elevated serum creatinine, and poor growth. (See 'Nonglomerular disorders' above.)

•Glomerular disorders – Typically present with more prominent signs and symptoms, including gross hematuria, proteinuria, edema, hypertension, and elevated serum creatinine. Those with secondary glomerulonephritis may also present with findings consistent with the underlying systemic disease such as fever, arthralgias/arthritis, rash, and/or pulmonary symptoms. (See 'Glomerular disorders' above.)

Clinical findings also increase with the severity of kidney function impairment. (See 'Symptoms associated with disease progression' above.)

●Initial evaluation

•History and physical examination – The possibility of CKD should be considered in a child with risk factors for CKD (eg, family history or congenital anomalies of the kidney and urinary tract [CAKUT]) or symptoms suggesting CKD (eg, hypertension or poor growth) (table 3). The examination should include measurement of growth parameters, blood pressure, and cardiovascular examination and evaluation for edema and for bony deformities (table 4). (See 'Who should be evaluated' above and 'History and physical examination' above.)

•Laboratory tests – Laboratory testing determines the severity of kidney impairment and detects the presence of associated complications.

-Tests for the diagnosis and staging of CKD include serum creatinine and cystatin C (if available), which are used to estimate glomerular filtration rate (GFR) (calculator 2). (See 'Estimation of glomerular filtration rate' above.)

-Other initial tests include urinalysis, quantification of urinary protein by a urine protein-to-creatinine ratio, serum electrolytes, and complete blood count. (See 'Laboratory testing' above.)

●Diagnosis and staging

•CKD is defined as functional and/or structural kidney damage that persists for at least three months:

-Functional kidney impairment is based on decreased GFR.

-Structural kidney damage is based on markers such as proteinuria or abnormalities in urine sediment or electrolytes, or pathologic abnormalities detected by histology or inferred by imaging. (See 'Diagnostic criteria' above.)

•For children ≥2 years, stages of CKD are defined by estimated GFR (table 2). For those <2 years, the degree of kidney function impairment is defined by comparing the estimated GFR with age-specific standards. (See 'Staging' above.)

●Further evaluation – Children with confirmed CKD should be referred to a pediatric nephrologist to guide additional testing and evaluation and long-term monitoring and care. This includes imaging to help identify the underlying cause of CKD and assess kidney size and parenchymal structure. Typically, ultrasonography is the preferred initial modality. Periodic 24-hour ambulatory blood pressure monitoring should be performed due to the high prevalence of masked hypertension. Kidney biopsy is often performed in patients with glomerular causes for CKD. (See 'Further evaluation' above.)

●Complications – Loss of kidney function is associated with complications including hypertension, fluid and electrolyte abnormalities, bone disease (CKD-mineral and bone disorder), anemia, and dyslipidemia. (See 'Assessment for complications of chronic kidney disease' above and "Chronic kidney disease in children: Complications".)