Illustrative case histories
Patient 1. The patient was hospitalised with increasing dyspnoea, oedema of the legs, a general sense of malaise and macroscopic haematuria. The patient had a previous medical history of atrial fibrillation, hypertension, ischaemic heart disease and type 2 diabetes. The patient’s clinical status on admission was normal – apart from atrial fibrillation, pitting oedema of the lower extremities and overweight.
Blood tests revealed elevated creatinine, 114 μmol/l, with an estimated glomerular filtration rate (eGFR) of 42 ml/min/1.73 m². Urine dipsticks showed abundant leukocytes (> 500 leukocytes/μl urine), a moderate quantity of erythrocytes (≈ 80 erythrocytes/μl) and slight albuminuria (0.3 g/l). Urine microscopy revealed a moderate quantity of isomorphic (intact) erythrocytes (7 – 25 erythrocytes per field of view enlarged 40 ×) (Fig. 2), a moderate quantity of hyaline casts (findings of hyaline casts in every second field of view with an enlargement of 40 ×) and some squamous epithelial cells (1 – 5 squamous epithelial cells per field of view with an enlargement of 40 ×).
Further examination with chest X-ray and echocardiogram revealed heart failure, and therapy commenced. A CT abdomen showed localised wall thickening in the urinary bladder, and the patient was referred to a urologist with suspected bladder tumour as the cause of the haematuria.
Figure 2 Urine sediment enlarged 40 times shows many intact (isomorphic) erythrocytes. This is a sign of post-glomerular bleeding (from renal tubules, renal pelvis, ureter, bladder or urethra). A preponderance of dysmorphic (irregular, fragmented) erythrocytes points to glomerular haematuria (not shown)
Urine dipsticks react to both intact and damaged erythrocytes and to free haemoglobin and myoglobin, while microscopy may help to determine the source of the erythrocytes in the urine. Isomorphic erythrocytes in the urine mean that the red blood cells are of natural size and shape, in contrast to dysmorphic erythrocyctes, which are deformed after passing through glomerular capillary walls in cases of glomerular disease. They can be detected in the urine as acanthocytes, pencil cells, elliptocytes or fragments.
Isomorphic erythrocytes have a regular, biconcave shape, are the result of post-glomerular bleeding and stem from kidney tubules, renal pelvis, ureter, bladder or urethra. Common causes of isomorphic haematuria are pronounced venous congestion in the urinary tract, urinary infections and cancer. These were all possibilities in the patient in question, and a rational test programme was initiated as a result of the urine microscopy.
Patient 2. The patient was hospitalised after a clinical history of 24 hours of abdominal pain with intermittent episodes of exacerbation, lethargy and nausea. The clinical examination was normal, apart from hypertension (blood pressure 195/140 mm Hg). In the blood sample, the creatinine value was elevated at 183 μmol/l; the other blood test results were within the normal range.
Urine on admission showed the following dipstick levels: leukocytes moderate (≈ 70 – 125 leukocytes/μl), nitrite negative, glucose moderate (14 – 28 mmol/l), albumin moderate (0.3 – 1 g/l), abundant erythrocytes (≈ 200 per μl).
Microscopy showed very large numbers of tubular epithelial cells (large flakes) (Fig. 3), a moderate number of cellular casts of tubular epithelium (4 – 10 in the whole slide), moderate numbers of erythrocytes and leukocytes (7 – 25 per field of view with an enlargement of 40 ×) (Fig. 4). The findings were consistent with acute tubular necrosis.
X-rays of the abdomen and thorax and a CT without contrast of the urinary tract provided no explanation for the patient’s symptoms. The abdominal pain was interpreted as possible constipation, and the patient received intravenous fluid and antihypertensives. The following day, serum creatinine had risen to 551μmol/l and urine production was falling despite infusion of intravenous fluid. The patient was therefore transferred to the Renal Department. A kidney biopsy showed ischaemic kidney damage (acute tubular necrosis). Three months later the patient was still dependent on dialysis.
Figure 3 Urine sediment enlarged 40 times shows abundant tubular epithelial cells. Such a finding is of great diagnostic importance and indicates damage to renal tubules (in this case acute tubular necrosis)
Figure 4 Urine sediment enlarged 40 times shows a cellular cast. These casts are formed by cells (in this case tubular epithelial cells) being deposited in protein casts of tubules. The finding is always a symptom of severe disease and often due, as in this case, to acute tubular necrosis
If the patient’s urine findings had been considered at the time of admission, the renal damage would have been detected before the creatinine value and other blood variables had risen alarmingly. Acute tubular necrosis is acute renal failure where tubular epithelial cells are lost due to ischaemic and/or toxic damage.
Microscopy of urine is helpful for distinguishing acute tubular necrosis from prerenal kidney failure, where there is no structural renal damage. In acute tubular necrosis, the urine typically contains tubular epithelial cells and cell casts of tubular epithelium, as in our patient.
Patient 3. The patient was hospitalised after some weeks of fatigue and chills, in the last few days with dark urine and pruritus. Blood tests showed a highly elevated creatinine level of 2 449 μmol/l, urea 46.2 mmol/l and potassium 6.4 mmol/l. Urine dipsticks showed considerable proteinuria and haematuria (> 20 g/l and ≈ 200 erythrocytes per μl, respectively).
Microscopy showed a nephritic sediment characterised by glomerular haematuria with a moderate quantity of dysmorphic erythrocytes (7 – 25 erythrocytes per field of view with enlargement 40 ×), abundant waxy casts (> 4 in the whole slide). There were also abundant tubular epithelial cells, a moderate presence of granular casts (4 – 10 in the whole slide) and some cellular casts (1 – 3 in the whole slide) (Fig. 5). The patient was transferred the same day to the Renal Department on suspicion of acute glomerulonephritis, which was confirmed by renal biopsy. Appropriate treatment was initiated.
Figure 5 Urine sediment enlarged 40 times shows a waxy cast. These are usually casts of the broad parts of the tubules. They look «waxy», but consist mainly of IgG. They are associated with severe, often terminal renal disease
Waxy casts are always a serious sign and are only present in patients with pathological conditions. A patient with as high a serum creatinine level as in this case would have been promptly transferred to the Renal Department under any circumstances, but in the present case urine microscopy provided important supplementary information about the urgent need for further diagnostics and treatment.