AN ALBUM OF URINARY MICROSCOPY
IMAGES IN A CLINICAL CONTEXT |
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PART II |
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G.B. Fogazzi, Milan, Italy
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S. Verdesca, Milan, Italy |
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Slide 35
This is the second case, a man with rapidly progressive renal failure and mild urinary changes.
Slide 36
In December 1996, a 51-year old man was admitted to our unit because of rapid increase of serum creatinine, from 2.1 to 7.7 mg/dL over a 3-week period. The urine output was good but the blood pressure was high in spite of a therapy with clonidine and nifedipine.
The physical examination showed thickened skin and the presence of Raynaud’s phenomenon. At ultrasound, the kidneys were normal.
Slide 37
The search for ANA, ANCA, anti-GBM Abs, and cryoglobulins was negative, and C3 and C4 serum levels were normal. The urine protein excretion was mild. Urine sediment contained 0-2 erythrocytes per high power field, and 1 hyaline or hyaline-granular cast every 3-4 low power fields, which to us means, minor urinary changes.
Slide 38
This is the copy of the urinary sediment report produced in that occasion. Knowing that the patient had a rapidly progressive renal failure, Dr Fogazzi highlighted the fact the urine sediment was not nephritic (bottom line of the report). This fact confirms the added value that urine sediment examination has when it is performed by a nephrologist.
Slide 39
At this point, the patient was submitted to renal biopsy.
Slide 40
The renal sample contained 14 glomeruli, two of which were globally sclerotic (arrow).
Slide 41
The other glomeruli showed a shrinking of the glomerular tuft, which caused an apparent increase of the Bowman’s space (arrows). Between the two glomeruli you can see a small artery, which shows a thickening of the media and a narrowing of the lumen (arrowhead).
Slide 42
In addition, there was interstitial fibrosis, which in some areas was more prominent than in others.
Slide 43
This is another example of a small artery (arrow) with a thickening of the media and a marked narrowing of the lumen.
The lesions shown till now are all consistent with the diagnosis of nephrosclerosis secondary to arterial hypertension.
Slide 44
However, when a subarcuate artery was examined, it was noted that besides a proliferation of the media there also was a proliferation of the intima (arrows).
Slide 45
At a higher magnification this proliferation appears to be quite severe, with a typical “onion skin” appearance, associated with a mucinous aspect (arrow). This lesion,
together with the clinical findings and mild urinary changes led us to the diagnosis of progressive systemic sclerosis (PSS).
Slide 46
Slide 47
Slide 48
In cases of PSS other possible renal lesions, such as fibrinoid necrosis, thrombosis in the arterioles and in the glomeruli can be present.
Slide 49
PSS is a condition characterized by an uncontrolled and irreversible proliferation of connective tissue, which leads to fibrosis of the skin and of visceral organs in association with mucinous thickening of the vascular wall and narrowing of the lumen.
Slide 50
We can classify the PSS into 4 types: pre-scleroderma, scleroderma sine scleroderma, limited scleroderma, and diffuse scleroderma, according to the involvement of skin and of different internal organs. For our patient, we diagnosed a limited type of PSS because of the presence of Raynaud’s phenomenon, a focal and limited skin involvement, and the renal disease.
Slide 51
In the pathogenesis of PSS, the vascular injury is seen as the first step of the disease. The vascular injury leads to an abnormal constriction of blood vessels, which is at first reversible but subsequently causes an overgrowth of endothelial and muscle cells. This leads to a decreased vascularization in tissues and organs and then to fibrosis. In addition, we know that a number of auto-antibodies, such as those shown in the slides, can be found in patients with PSS, even though their pathogenetic role is still unclear.
Slide 52
The diagnosis is usually not difficult in patients with the typical skin lesions and organ involvement, and the laboratory tests and tissue biopsy are confirmatory.
Slide 53
About 10-15% of patients with scleroderma may have a renal crisis. This is defined as a rapidly progressive renal failure associated with a moderate-to-severe hypertension, which is due to the constriction of blood vessels within the kidney. This leads to an impairment of blood flow and to an ischemic activation of the renin-angiotensin system.
In cases with renal crisis, the urine sediment is normal or shows microscopic haematuria and granular casts.
Slide 54
In conclusion, this case shows us that it is possible to have a very severe and rapidly progressive renal disease with only minor urinary abnormalities. This happens typically with ischemic renal diseases such as PSS, haemolytic uraemic syndrome, malignant hypertension, or thrombotic thrombocytopenic purpura.
Just to summarize and as general rule:
1) Rapidly progressive renal disease due to a proliferative/necrotizing glomerular disease: rich urinary sediment with many erythrocytes and erythrocytic casts.
2) Rapidly progressive renal disease due to an ischemic disorder: urinary sediment with few and unspecific findings.
DISCUSSION I
Question. The first case. Kidney biopsy, was it really needed to make the diagnosis?
Fogazzi. I believe yes. In fact there wasn’t only a nephritic sediment associated with signs of acute tubular necrosis, but there also was an increase of serum creatinine and no clinical evidence of a systemic disease. The patient only complained about lumbar pain, which was found to be due to back-bone spondyle-arthrosis. We didn’t know what the cause of the renal disease was, and by the biopsy we found a very severe glomerular disease.
Question. But you had a high titre of ANCA.
Fogazzi. Yes, but we had it some days after the patient had been admitted to our ward. On the clinical ground, without renal biopsy, you could have put in the differential diagnosis a number of other glomerular disorders such as acute post-infectious glomerulonephritis, mesangioproliferative glomerulonephritis, etc. each of which would have required a specific and different treatment. For instance once you know the patient has a pauci-immune necrotizing glomerulonephritis you start with cyclophosphamide, while you’re not supposed to use this drug if the patient has an acute post-infectious glomerulonephritis.
Renal biopsy also is a guidance for treatment. What is the opinion of the audience? Would you have performed a renal biopsy in this case? Yes? OK, thanks.
Question. Thank you for your reports. I have 2 questions. The first is for rapidly progressive glomerulonephritis. In your opinion, what is the percentage of isomorphic or dysmorphic red blood cells in the urine? The second question: do you have any opinion in scleroderma, especially in renal crisis, about the percentage of patients who develop malignant hypertension? In your patient antinuclear antibodies were negative, but did you have any ENA results?
Fogazzi. For the first question, the topic of the morphology of the urinary erythrocytes is dealt with in the next case, so we can discuss about it later. For scleroderma, we didn’t actually perform the whole panel of serologic tests. We just looked for the presence of Scl 70, which was negative.
Question. The final diagnosis for the first patient was as limited crescentic glomerulonephritis or micropolyangeitis?
Fogazzi. It was a case of focal segmental necrotizing glomerulonephritis without evidence of vasculitis in the renal biopsy, but with pANCA positivity.
Question. Why did you biopsy the second case, if you had hypertension, thickening of the skin, and the urine sediment you described?
Fogazzi. Again, the clinical situation was somewhat unclear. In fact, the patient had Raynaud, very limited skin thickening and no other physical signs, and a negative serology. To us it was important to know how active or inactive the renal disease was. Of course the negative urine sediment was suggestive for an ischemic disorder, but again it was the renal biopsy that allowed us to identify with certainty the type and severity of the renal disease.
Question. I don’t really see that the urine in these two cases helped much really. For the first case it was clear clinically that the patient had a rapidly progressive glomerulonephritis. You showed us a creatinine of 1.1 which increased to 1.8, and a dipstick which showed microscopic haematuria. So, clearly it was a case of RPGN. The second patient would have even misled you because he had a negative urine and you still did a biopsy and you found a different diagnosis. So, I think that the urine in these 2 cases wasn’t really of great help. Especially for the second case you said he had a benign urine and you did a biopsy and it was a significant renal disease.
Fogazzi. So what is your conclusion?
Question. My conclusion is that the clinical is really more important, and I think the clinical diagnosis would really have reached for both cases without the urine. I don’t think the urine was of major help in these two cases. I would have biopsied the patients without the urine.
Fogazzi. No, I’m strongly in favor of the examination of the urine. Listen, urinalysis by dipstick for the first case showed just albumin + and haemoglobin +++. Without the examination of the urine sediment, you would have missed renal tubular cells, renal epithelial fragments, and erythrocytic casts. All these particles suggested to us the presence of a severe and acute kidney injury. This put pressure on us and led to the renal biopsy, and to the appropriate treatment. If we had done urinalysis with dipstick only, it would have been just one of the many patients with microscopic haematuria and mild albuminuria. At the moment, the patient would probably be on dialysis rather than going around with a serum creatinine of 1.2. I’m sorry but I don’t agree with your view. Now we have to move on.
THE THIRD PART WILL BE PUBLISHED ON APRIL 3RD, 2008