eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Chronic Kidney Disease: Differential Diagnoses & Workup

Author: Sanjeev Gulati, MBBS, MD, DNB(Peds), DM, DNB(Neph), FIPN(Australia), FICN, FRCPC(Canada), Associate Professor, Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences; Senior Consultant in Pediatric Nephrology, Department of Nephrology and Transplant Medicine, Fortis Hospitals, India
Contributor Information and Disclosures

Updated: Aug 12, 2009

Differential Diagnoses

Other Problems to Be Considered

Acute renal failure
Rapidly progressive glomerulonephritis

Workup

Laboratory Studies

• Initial testing must include an examination of the urine and estimation of the glomerular filtration rate (GFR). An important aspect of this initial evaluation is the determination of disease duration. Although the distinction between acute, subacute, and chronic kidney disease (CKD) or failure is arbitrary, the differential diagnosis can frequently be narrowed if the disease duration is known. This assessment is best performed by comparing the current urinalysis or plasma creatinine concentration (PCr) with previous results, if available.
• Urine examination is perhaps the most important test and should be considered a part of the physical examination in all children being screened or evaluated for chronic kidney disease. It can be performed at the bedside or in the clinic using a fresh urine sample.
  • An initial evaluation consists of a multitest detection strip (dipstick) test, followed by urine microscopy. The dipstick is a quick method of screening and detecting proteinuria, hematuria, and pyuria and provides an estimate of the specific gravity (urine-concentrating capacity).
  • Urine microscopy is performed on a centrifuge-spun urine specimen to look for RBCs, WBCs, and casts. Most children with chronic kidney disease have broad hyaline casts. Characteristic findings on microscopic examination of the urine sediment may suggest a diagnosis other than chronic kidney disease. As an example, the presence of muddy-brown granular casts and epithelial cell casts is highly suggestive of acute tubular necrosis, whereas red cell casts would suggest an acute nephritic process.
  • The most appropriate, practical, and precise method for estimation of proteinuria in children is to calculate the protein-to-creatinine ratio in a spot urine specimen. Patients with a positive dipstick test finding (1+ or greater) should undergo quantitative measurement (protein-to-creatinine ratio or albumin-to-creatinine ratio) within 3 months to confirm proteinuria. When postpubertal children with diabetes mellitus of 5 or more years' duration are screened, albumin should be measured in a spot urine sample using either albumin-specific dipstick or albumin-to-creatinine ratio testing.
• Serum chemistry provides a valuable diagnostic tool both in the initial diagnosis and in the subsequent follow-up in these children. BUN and serum creatinine assessments are the most important tests. Estimation of the serum sodium, potassium, calcium, phosphorus, bicarbonate, alkaline phosphatase, parathyroid hormone (PTH), and cholesterol and fractionated lipid levels are important in the treatment and prevention of various chronic kidney disease–related complications.
• Anemia is an important clinical finding in chronic kidney disease, and a CBC count is an important investigation both in the initial evaluation and the subsequent follow-up in these children. Anemia may indicate the chronic nature of the renal failure in the absence of any other obvious causes and may also be a clue to the underlying cardiovascular disease.
• The GFR is equal to the sum of the filtration rates in all of the functioning nephrons; thus, estimation of the GFR gives a rough measure of the number of functioning nephrons. A reduction in GFR implies progression of the underlying disease.
  • The current KDOQI guidelines state that estimates of GFR are the best overall indices of the level of kidney function.⁴ The reference range of GFR in young adults is 120-130 mL/min per 1.73 m². However, the reference range of estimated GFR (eGFR) is much lower in early infancy, even when corrected for body surface area, and subsequently increases in relationship to body size for as long as 2 years. Hence, the eGFR ranges that are used to define the 5 CKD stages apply only to children aged 2 years and older. The eGFR can be estimated from the constant k, PCr (in mg/dL), and body length (L, in cm) according to the Schwartz formula, as follows:
    • GFR = (k X L) / PCr
    • (The value of k is different at different ages.) k = 0.4 (preterm infants), 0.45 (full-term infants), 0.55 (age 2-12 y in children and adolescent girls and 0.7 y in adolescent boys)
  • Therefore, all children with chronic kidney disease should have an eGFR calculated. This should be calculated from the Schwartz (or Counahan-Barratt prediction) equation in children because it is convenient, reasonably precise, and practical. The constants used in the equations differ slightly, likely related to the different assays to measure creatinine.
  • Creatinine clearance estimates are difficult and imprecise because they require 24-hour urine collections, which may be incomplete for various reasons. Remember that estimation of GFR or creatinine clearance from serum creatinine critically depends on calibration of the serum creatinine assay, specific to the expected lower levels found in children without chronic kidney disease.
  • Because of the problems with changes in creatinine production and secretion, other endogenous compounds have been evaluated in an effort to provide a more accurate estimation of GFR. Perhaps the most promising is cystatin C, a low molecular weight protein that is a member of the cystatin superfamily of cysteine protease inhibitors. Cystatin C is produced by all nucleated cells, and its rate of production is relatively constant and is unaltered by inflammatory conditions or changes in diet. The plasma cystatin C concentration may correlate more closely with the GFR than with the PCr.

Imaging Studies

Imaging studies help in confirming the diagnosis of chronic kidney disease and may also provide clues to its etiology. The following studies are helpful:

• Ultrasonography: This is a commonly used radiographic technique in patients who present with kidney disease because of safety, ease of use, and the information provided. Because obstruction is a readily reversible disorder, all patients who present with acute or chronic failure of unknown etiology should undergo ultrasonography, the modality of choice to assess possible obstructive disease. Although less sensitive than CT scanning in initially revealing a renal mass, ultrasonography can be useful in differentiating a simple benign cyst from a more complex cyst or a solid tumor. It is also commonly used to screen for and to diagnose types of polycystic kidney disease.
• Radionuclide studies: Early detection of renal scarring is possible with radioisotope scanning with 99m-technetium dimercaptosuccinic acid (DMSA). This is more sensitive than intravenous pyelography (IVP) in detecting renal scars and is considered the criterion standard for diagnosing reflux nephropathy, if present.
• Voiding cystourethrography: Voiding cystourethrography, which can be performed with a radionuclide tracer study, is used to detect vesicoureteral reflux.
• Retrograde or anterograde pyelography: Antegrade or retrograde pyelography may be used to better diagnose and relieve urinary tract obstruction. Their use for the diagnosis of obstruction has largely been supplanted by ultrasonography and CT scanning. However, antegrade or retrograde pyelography may be indicated when the history is highly suggestive (unexplained acute renal failure with a bland urine sediment in a patient with known pelvic malignancy) despite ultrasonography and CT scanning findings negative for hydronephrosis (because of possible ureteral encasement). Consultation with a pediatric urologist is suggested if antegrade or retrograde pyelography is considered.
• Skeletal survey: This is useful in evaluating for secondary hyperparathyroidism, a component of osteodystrophy, as well as for bone-age estimation prior to starting or in continuation of growth hormone therapy.

Procedures

• Kidney biopsy: A renal biopsy is commonly performed in patients with suspected glomerulonephritis or vasculitis and in those with otherwise unexplained chronic kidney disease or acute kidney failure. If a child has small shrunken kidneys, a kidney biopsy is often unnecessary to establish a diagnosis of chronic kidney disease.

Histologic Findings

• In advanced stages of chronic kidney disease, irrespective of the underlying etiology, the findings often consist of segmental and globally sclerosed glomeruli and tubulointerstitial atrophy, often with tubulointerstitial mononuclear infiltrates.

Staging

The following is the KDOQI recommended classification of chronic renal disease by stage:^10,4

• Stage I disease is defined by a normal GFR (>90 mL/min per 1.73 m²) and persistent albuminuria.
• Stage II disease is characterized by a GFR of 60-89 mL/min per 1.73 m² and persistent albuminuria.
• Stage III disease is characterized by a GFR of 30-59 mL/min per 1.73 m².
• Stage IV disease is characterized by a GFR of 15-29 mL/min per 1.73 m².
• Stage V disease is characterized by a GFR of less than 15 mL/min per 1.73 m² or end-stage renal disease (ESRD).

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