Approach Considerations
Laboratory studies and procedures that may be used in the diagnosis and follow-up of chronic glomerulonephritis include the following:
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Urinalysis
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Urinary protein excretion measurement
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Complete blood cell count (CBC)
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Serum chemistry
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Renal ultrasonography
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Kidney biopsy
Urinalysis
The presence of dysmorphic red blood cells (RBCs), albumin, or RBC casts suggests glomerulonephritis as the cause of kidney failure. Waxy or broad casts are observed in all forms of chronic kidney disease (CKD), including chronic glomerulonephritis. Low urine specific gravity indicates loss of tubular concentrating ability, an early finding in persons with CKD. See Urinalysis.
Urinary protein excretion
Urinary protein excretion can be estimated by calculating the protein-to-creatinine ratio on a spot morning urine sample. The ratio of urinary protein concentration (in mg/dL) to urinary creatinine (in mg/dL) reflects 24-hour protein excretion in grams. For instance, if the spot urine protein value is 300 mg/dL and the creatinine value is 150 mg/dL, the protein-to-creatinine ratio is 2. Thus, in this example, the 24-hour urine protein excretion is 2 g.
The estimated creatinine clearance rate is used to assess and monitor the glomerular filtration rate (GFR). The following 3 formulas are available for calculation of the GFR:
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Cockcroft-Gault formula
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Modification of Diet in Renal Disease (MDRD) Study formula
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Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation
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Race-adjusted GFR estimation using creatinine and cystatin clearance [29] .
The Cockcroft-Gault formula is simple to use but overestimates the GFR by 10-15% because creatinine is both filtered and secreted. The MDRD formula is much more complex and has been found to underestimate GFR by 6.2% in patients with CKD and by 29% in healthy persons. [28] The CKD-EPI is based on the same four variables as the MDRD Study formula but uses a 2-slope “spline” to model the relationship between estimated GFR and serum creatinine, and a different relationship for age, sex, and race. The National Kidney Foundation (NKF) recommends using the CKD-EPI Creatinine Equation to estimate GFR; a CKD-EPI calculator is available on the NKF Web site.
Equations to calculate eGFR have been undergoing revisions to avoid biases introduced when race was included in CKD EPI equation, due to errors in estimating creatinine production and excretion in African Americans. Consequently, clearance of another chemical, cystatin C, is being considered for estimation of GFR. Since laboratories across the United States might not have the capability to measure cystatin C clearance, many clinicians may still be using the CKD EPI equation. In that situation, when estimated GFR is around 30 mL/min by CKD EPI equation, underestimation of the estimated GFR could lead to errors—such as inappropriately stopping metformin or sodium-glucose cotransporter–2 (SGLT2) inhibitors, which are agents that may help prevent CKD progression—that might preferentially impact African Americans. [30]
The estimated creatinine clearance rate is also used to monitor response to therapy and to initiate an early transition to renal replacement therapy (eg, dialysis access placement and transplantation evaluation). The degree of proteinuria, especially albuminuria, helps predict the renal prognosis in patients with chronic glomerulonephritis. Patients with proteinuria exceeding 1 g/day have an increased risk of progression to end-stage renal failure.
Complete blood count
Anemia is a significant finding in patients with some decline in the GFR. Physicians must be aware that anemia can occur even in patients with serum creatinine levels lower than 2 mg/dL. Even severe anemia can occur at low serum creatinine levels. Anemia is the result of marked impairment of erythropoietin production, as well as alterations in iron absorption that accompany CKD from ferroportin and fibroblast growth factor 23 (FGF23), among other factors.
Serum chemistry
Serum creatinine and blood urea nitrogen levels are elevated. Impaired excretion of potassium, free water, and acid results in hyperkalemia, hyponatremia, and low serum bicarbonate levels, respectively. Impaired vitamin D-3 production results in hypocalcemia, hyperphosphatemia, and high levels of parathyroid hormone. Low serum albumin levels may be present if uremia interferes with nutrition or if the patient is nephrotic.
Levels of fibroblast growth factor 21 (FGF21) have been found to be significantly elevated in patients with CKD12 and the high levels of FGF21 may explain the excess overall and cardiovascular mortality in patients with CKD. These adverse effects of elevated FGF21 are not clearly understood but research is under way to elucidate its biologic effects.
Renal ultrasonography
Obtain a renal ultrasonogram to assess for the presence of both kidneys, determine kidney size, and exclude structural lesions that may be responsible for azotemia. Small kidneys often indicate an irreversible process.
Kidney biopsy
If the kidney is small, kidney biopsy is usually unnecessary; no specific pattern of disease can be discerned at this point. A kidney biopsy may be considered in the minority of patients who exhibit an acute exacerbation of their chronic disease. This may be particularly pertinent to patients with preserved kidney size and in those with lupus nephritis.
In early stages, the glomeruli may still show some histologic evidence of the primary disease. In advanced stages, the glomeruli are hyalinized and obsolescent. The tubules are disrupted and atrophic, and marked interstitial fibrosis and arterial and arteriolar sclerosis occur.
A study by Murray et al of 75 patients with suspected familial kidney disease who underwent genetic sequencing after kidney biopsy found that accurate genetic diagnosis can result in changes in clinical diagnosis, understanding of pathological mechanism, and treatment. These authors recommended considering next-generation sequencing as a complement to kidney biopsy in the evaluation of patients with kidney disease. [27]
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Renal corpuscle.
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Photomicrograph of a kidney biopsy from a patient with crescentic glomerulonephritis showing prominent fibrocellular crescent formation and moderate mesangial proliferation in a glomerulus. Hematoxylin and eosin stain. Image courtesy of Wikipedia.
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Membranoproliferative glomerulonephritis (MPGN) type I. Glomerulus with lobular accentuation from increased mesangial cellularity. A segmental increase occurs in the mesangial matrix, and the peripheral capillary walls are thickened (hematoxylin and eosin stained section; original magnification × 250). Courtesy of John A. Minielly, MD.
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