|Year : 2016 | Volume
| Issue : 1 | Page : 44-47
A woman with recurrent hematuria: a diagnostic challenge in Egypt
Mona Abdelrahim1, Ayman Maher Nagib2, Mahmoud Mohamed Khaled2, Ehab Wafa2, Ahmed Farouk Donia2
1 Department of Pathology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
2 Department of Dialysis and Transplantation, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
|Date of Submission||12-Nov-2015|
|Date of Acceptance||25-Nov-2015|
|Date of Web Publication||22-Mar-2016|
MD, Department of Pathology, Urology and Nephrology Center, Mansoura University, Elgomhoria Street, PO Box 35516 Mansoura
Source of Support: None, Conflict of Interest: None
Thin basement membrane disease (TBMD) or benign familial hematuria is common in women. The median age is 37 years among adults. About two-third of the patients with TBMD have at least one other hematuric family member when five relatives are tested.
We hereby present a case of adult TBMD to clarify the clinicopathological characteristics of the disease in 56-year-old woman with long-standing intermittent dark colored urine with proteinuria, normal serum creatinine, and with normal blood pressure. Renal pathology showed normal renal tissue by using the light and immunofluorescence examination. Thinning of the glomerular basement membrane, ranging from 110 to 200 nm, was demonstrated by using electron microscopy.
Although it is part of routine nephropathology worldwide, electron microscopic examination of renal biopsies are rarely used in Egypt. This important diagnostic pillar should be more frequently used among our patients, especially when clinicopathologic diagnosis is unclear.
Keywords: Dark urine; intermittent hematuria; thin basement membrane nephropathy
|How to cite this article:|
Abdelrahim M, Nagib AM, Khaled MM, Wafa E, Donia AF. A woman with recurrent hematuria: a diagnostic challenge in Egypt. J Egypt Soc Nephrol Transplant 2016;16:44-7
|How to cite this URL:|
Abdelrahim M, Nagib AM, Khaled MM, Wafa E, Donia AF. A woman with recurrent hematuria: a diagnostic challenge in Egypt. J Egypt Soc Nephrol Transplant [serial online] 2016 [cited 2017 Jun 26];16:44-7. Available from: http://www.jesnt.eg.net/text.asp?2016/16/1/44/179217
| Introduction|| |
Thin basement membrane disease (TBMD) also known as benign familial hematuria and thin basement membrane nephropathy is, along with IgA nephropathy, the most common cause of asymptomatic hematuria. The only abnormal finding in this disease is a thinning of the basement membrane of the glomeruli in the kidneys. Its importance lies in the fact that it has a benign prognosis . Most patients with TBMD are incidentally discovered to have microscopic hematuria on urinalysis. The blood pressure, kidney function, and the urinary protein excretion are usually normal. Mild proteinuria (<1.5 g/day) and hypertension are seen in a small minority of patients. Frank hematuria and loin pain should prompt a search for another cause, such as kidney stones or loin pain-hematuria syndrome. In addition, there are no systemic manifestations, and thus the presence of hearing impairment or visual impairment should prompt a search for hereditary nephritis such as Alport's syndrome . It is diagnosed as follows. TBMD must be differentiated from the other two common causes of glomerular hematuria: IgA nephropathy and Alport's syndrome. The history and presentation are helpful in this regard. In Alport's syndrome, there is often a family history of kidney failure, which may be associated with hearing impairment. In addition, men tend to be more affected as Alport's syndrome is X-linked in most cases . In IgA nephropathy, episodes of frank hematuria are more common, and a family history is less common. A kidney biopsy is the only way to diagnose TBMD. It reveals thinning of the glomerular basement membrane (GBM) from the normal 300-400 nm to 150-250 nm. However, a biopsy is rarely carried out in cases where the patient has isolated microscopic hematuria, normal kidney function, and no proteinuria. The prognosis is excellent in this setting unless the clinical manifestations progress, as occurs in most men and some women with Alport's syndrome and many patients with IgA nephropathy. Most patients with TBMD need only reassurance. Indeed, this disease was previously referred to as 'benign familial hematuria' because of its usually benign course. Angiotensin-converting enzyme inhibitors have been suggested to reduce the episodes of hematuria, though controlled studies in this regard are lacking. Treating coexisting hypercalciuria and hyperuricosuria will also be helpful in reducing hematuria. The molecular basis for TBMD has yet to be elucidated fully; however, defects in the gene encoding the a4 chain of type IV collagen have been reported in some families . Overall, most people with TBMD have an excellent prognosis. Some reports, however, suggest that a minority might develop hypertension . TBMD may coexist with other kidney diseases, which may in part be explained by the high prevalence of TBMD .
| Case Report|| |
A 56-year-old woman presented with intermittent dark colored urine for 3 months, which was associated with neither upper respiratory tract infection nor skin rash. Previous medical and surgical histories were irrelevant. Clinical examination was unremarkable, apart from mild pretibial pitting edema. Her urine was dark-colored and urine analysis showed hematuria.
Laboratory investigations were as follows: serum creatinine 0.6 mg/dl (0.2-1.0 mg/dl), sodium 139 mEq/l (135-145 mEq/l), potassium 4.2 mEq/l (3.5-5.0 mEq/l), uric acid 5.2 mg/dl (2.7-5.7 mg/dl), phosphorus 3.4 mg/dl (2.9-5.4 mg/dl), total protein 6.9 g/dl (6.6-8.7 g/dl), albumin 4.2 g/dl (3.4-4.8 g/dl), cholesterol 245 mg/dl(<200 mg/dl), alanine aminotransferase 19 U/l (0-41 U/l), and aspartate aminotransferase 22 U/l (0-40 U/l). Hemoglobin, white blood cell and platelet counts were within the normal ranges. Antinuclear antibodies, anti-double-stranded DNA (anti-dsDNA), and anti-Jo 1 antibodies were negative. Hepatitis C virus antibodies (HCV Ab), hepatitis B surface antigen (HBsAg), and HIV IgM and IgG were negative. Renal ultrasonography revealed normal echogenicity with normal size, shape, and corticomedullary differentiation of both kidneys.
Light microscopic examination revealed 10 glomeruli, of which one was globally sclerosed and the remaining were unremarkable for mesangium cellularity or basement membrane thickening. The tubules were unremarkable except for rare foci of minimal tubular atrophy. The interstitium showed minimal focal interstitium fibrosis as evident in the Masson trichrome stain. The blood vessels were unremarkable; small arteries were just slightly thickened [Figure 1],[Figure 2],[Figure 3] and [Figure 4]. Immunofluorescence microscopy revealed no staining for either IgG, IgA, IgM, C1q, C3, or fibrinogen.
|Figure 1: Light microscopy of thin basement membrane showing no abnormalities (H and E stain ×400 ).|
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|Figure 2: Light microscopy of thin basement membrane showing minor abnormalities (PAS stain ×400 ).|
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|Figure 3: Light microscopy of thin basement membrane showing minor abnormalities in the form of segmental mesangial thickening (PAS stain ×40 0).|
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|Figure 4: Light microscopy of thin basement membrane showing minor abnormalities in the form of minimal focal interstitial fi brosis (Masson trichrome stain ×20 0).|
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Electron microscopy revealed diffuse thinning of the GBM without any other alterations or deposits. The basement membrane thickness ranged from 110 to 160 μm to a maximum thickness of 200 μm. No evidence of deposits or foot process abnormalities was found.
| Discussion|| |
The light microscopic appearance of the renal biopsy in thin basement membrane nephropathy (TBMN) is nearly normal with only mild mesangial cell proliferation and slight mesangial matrix expansion. Premature glomerulosclerosis and tubule interstitial fibrosis may occur. Small mesangial deposits of IgM, C3, and C1q are seen sometimes but are nonspecific.
The GBM width is thinner in children than in adults, and in females compared with males. TBMN is diagnosed when the GBM width on electron micrographs is less than the normal range. The criteria for TBMN in children vary from less than 200 to 250 nm depending on age, and in adults from less than 200 nm to less than 250 nm .
In TBMN, the GBM is thinned in the majority of the capillary loops, and at least 50% of the GBM in individual capillaries. There are only isolated regions of lamellation or thickening, and there is no progressive thickening or splitting over time.
There are differences between TBMN and the thining of GBM observed in normal children  and in IgA , minimal change of lupus glomerulonephritis . Whereas the GBM thinning in children is diffuse; the thinning in most of these glomerular diseases is focal.
The clinical pathologic diagnosis of TBMD is problematic because of the wide range of normal thickness of the GBM in the general population, the lack of uniformity of diagnostic criteria, and the fact that thinning may occur in other glomerular conditions as a pre-existing or acquired process .
Thus, a diagnosis of TBMD requires the systematic exclusion of other glomerular abnormalities that point to another disease process. Thinning of the GBM, whether focal or diffuse, is particularly common in IgA nephropathy, suggesting an associated dysregulation of GBM synthesis or maintenance .
Segmental thinning of GBM is also common in forms of endocapillary proliferative glomerulonephritis due to postinfections glomerulonephritis or lupus nephritis, as well as in the thrombotic microangiopathies and necrotizing glomerulonephritis. Segmental thinning of the GBM is commonly observed as a nonspecific localized finding in a host of immune complex-mediated glomerular diseases, especially in foci of resorbed deposits with remodeled glomerular capillary walls.
Thinning of the basement membrane may be the only detectable abnormality in some kinds with hereditary nephritis/Alport's syndrome, especially early in the disease. Full clinical history, including mode of inheritance and a family history of renal failure and deafness, and the use of antibodies to the a subunits of collagen IV, are helpful. In TBMD, the GBMs retain normal immunoreactivity for the a 3, 4, and 5 chains of collagen IV, which is lost in hereditary nephritis.
| Conclusion|| |
TBMD, also known as benign familial hematuria, is common in women. It is one of the most common cause of asymptomatic hematuria. Kidney biopsy is the only way to diagnose TBMD. It reveals thinning of the GBM from the normal 300-400 nm to 150-250 nm. It has a benign course, and thus the treatment of patients with TBMD need only reassurance.
Although it is part of routine nephropathology worldwide, electron microscopic examination of renal biopsies is rarely used in Egypt. This important diagnostic pillar should be used more frequently among our patients, especially when clinicopathologic diagnosis is unclear [Figure 5],[Figure 6] and [Figure 7].
|Figure 5: Electron micrograph of thin basement membrane showing diffuse thinning of glomerular basement membrane (GBM) (×30 00).|
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|Figure 6: Electron micrograph of thin basement membrane showing diffuse thinning of glomerular basement membrane (GBM), thickness range from 110 to 200 μm (~3 800).|
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|Figure 7: Electron micrograph of thin basement membrane showing diffuse thinning of glomerular basement membrane (GBM) without other alteration (×5000).|
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]