on 15-Feb-2021 (Mon)

Coarse, deeply-pigmented granular casts (ie, "muddy brown" or heme-granular casts) are considered characteristic of ATN, the leading cause of acute kidney injury (AKI) in hospitalized patients [56].

In patients with ischemic or toxic injury to the tubular epithelial cells, cell sloughing into the tubular lumen, due either to cell death or to defective cell-to-cell or cell-to-basement membrane adhesion, may lead to the formation of granular and/or epithelial cell casts

Whether crystals form in the urine depends upon a variety of factors, including the degree of concentration of constituent molecules, the urine pH, and the presence of inhibitors of crystallization.

Uric acid crystals as well as amorphous urates are observed in acid urine, a milieu that favors the conversion of the relatively soluble urate salt into the insoluble uric acid (picture 13A-B).

Calcium oxalate crystals, which are not dependent upon the urine pH, may appear in the monohydrate form with a characteristic "dumbbell" appearance or in the dihydrate form as an envelope-like structure. Calcium phosphate crystals only form in a relatively alkaline urine and have a characteristic coffin-like structure (picture 14A-B).

Cystine crystals, with their characteristic hexagonal shape, are diagnostic of cystinuria (picture 15).

Magnesium ammonium phosphate (struvite) and calcium carbonate-apatite are the constituents of struvite stones (picture 16). Normal urine is undersaturated with ammonium phosphate. Struvite stone formation occurs only when ammonia production is increased and the urine pH is elevated, which decreases the solubility of phosphate. Both increased ammonia production and increased urine pH occur only in the setting of a urinary tract infection with a urease-producing organism, such as Proteus or Klebsiella.

The combination of AKI and calcium oxalate crystals, which may suggest ethylene glycol ingestion

The observation of crystals in the urine is useful in patients with known or suspected kidney stones and is a risk factor for recurrent calcium oxalate [57] or cystine [58] stone formation

The presence of a larger number of uric acid crystals occurring in association with AKI, which may suggest tumor lysis syndrome

Lipid droplets, composed primarily of cholesterol esters and, to a lesser degree, cholesterol, are commonly seen on urinalysis in patients with conditions that are associated with the nephrotic syndrome [59,60].

Fat droplets are round and may be confused with red cells. They can be differentiated from red cells under routine light microscopy by their variable size (ranging from larger to much smaller than red cells), their dark outline, and the "Maltese cross" appearance under polarized light

The origin of urinary lipid is not well understood [60]. The initial step is the filtration of lipoprotein-bound cholesterol, particularly HDL-cholesterol. Filtration of lipoproteins is minimal in healthy individuals but is markedly enhanced when glomerular permeability to macromolecules is increased in the nephrotic syndrome. Some of the filtered lipoprotein is taken up by the proximal tubular cells.

Because of the apparent requirement for increased glomerular permeability, lipiduria is almost always diagnostic of some form of glomerular disease (see "Glomerular disease: Evaluation and differential diagnosis in adults"). One exception is autosomal dominant polycystic kidney disease [61,62]

Hematuria with dysmorphic RBCs, RBC casts, and proteinuria — This constellation of findings (eg, dysmorphic red blood cells [RBCs], RBC casts, and proteinuria) is suggestive of a proliferative glomerular disease, which, in the setting of rapidly declining kidney function, constitutes a nephrologic emergency

Heavy proteinuria with oval fat bodies, lipid-laden casts, and absent or minimal hematuria is indicative of nonproliferative glomerular diseases including severe diabetic nephropathy. In addition, this pattern may be seen with membranous nephropathy, focal segmental glomerulosclerosis, minimal change disease, and amyloidosis, each of which has both primary and secondary forms

In a patient with acute kidney injury (AKI), the presence of granular and/or epithelial cell casts with or without free renal tubular epithelial cells is strongly suggestive of acute tubular necrosis (ATN) (picture 18A-B). The number of observed granular or renal tubular casts may also have prognostic significance; in a study of patients with ATN who were diagnosed based upon clinical criteria, a semiquantitative assessment of the burden of granular or renal tubular epithelial cell casts on low-powered fields was associated with an increased risk of death or the subsequent need for renal replacement therapy

The presence and quantity of granular casts or renal tubular epithelial cells in the urine was evaluated as a diagnostic tool in 267 patients with hospitalized AKI [64]. Prior to performing a urinalysis, trained clinicians were asked to make a clinical diagnosis of ATN, prerenal AKI, or other. Since kidney biopsies were not routinely performed, the final diagnosis of ATN versus prerenal disease was determined by whether the renal function improved within 48 hours after fluid resuscitation and/or hemodynamic manipulation. The following observations were made:

● A pre-urinalysis diagnosis (based upon the history, physical examination, and other available data) of ATN had a positive predictive value of 86 percent. In such patients who also had at least one granular cast or tubular epithelial cell in the urinalysis, the positive predictive value increased to 100 percent. Of patients with a pre-urinalysis diagnosis of ATN and no granular casts or tubular epithelial cells, 44 percent had a final diagnosis of ATN. Thus, a diagnosis of ATN is still possible even if the urinalysis has no granular casts or tubular epithelial cells.

● A pre-urinalysis diagnosis of prerenal AKI had a positive predictive value of 77 percent. In such patients, the absence of granular casts or tubular epithelial cells increased the positive predictive value to 91 percent for a final diagnosis of prerenal AKI

Isolated pyuria is usually indicative of bacterial urinary tract infection. The differential diagnosis is broad if a concurrent urine culture is negative and includes a partially or recently treated urinary tract infection, non-bacterial infections (including tuberculosis), prostatitis, interstitial nephritis, and nephrolithiasis [50]

In patients with AKI, a relatively normal urinalysis (few cells with little or no proteinuria and no casts other than hyaline casts) can be associated with ATN but may also indicate one of the following diseases:

● Prerenal AKI due to either an actual or effective decrease in circulating volume

● Urinary tract obstruction

● Hypercalcemia

● Cast nephropathy in multiple myeloma

● Vascular disease that produces glomerular ischemia but not infarction (eg, hypertensive emergency, scleroderma, thrombotic microangiopathies) or that affects extra-glomerular vessels (eg, cholesterol atheroemboli, polyarteritis nodosa)

● Tumor lysis syndrome

● Acute phosphate nephropathy

In patients with chronic kidney disease, a normal urinalysis most commonly indicates states of persistently decreased effective circulating volume, such as in patients with heart failure, urinary tract obstruction, chronic tubulointerstitial diseases, light chain cast nephropathy, and ischemic or hypertensive nephrosclerosis.