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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2020  |  Volume : 31  |  Issue : 3  |  Page : 681-686
Collagenofibrotic glomerulopathy: A case of glomerular deposition disease in the Indian subcontinent and review of the literature

1 Department of Nephrology, Nephrolife the Complete Kidney Care, Swami Narayan Complex, Majura Gate, Surat, Gujarat, India
2 Department of Nephrology, Apollo Hospitals, Chennai, Tamil Nadu, India
3 Department of Pathology, Apollo Hospitals, Chennai, Tamil Nadu, India

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Date of Submission31-May-2019
Date of Acceptance11-Jul-2019
Date of Web Publication10-Jul-2020


Collagenofibrotic glomerulopathy (CG) is a rare renal disease with unknown etiology, defined by deposition of Type III collagen fibers in the subendothelial space and mesangium seen on supported by electron microscopy. There are merely 19 cases reported in the literature from the Indian subcontinent. Herein, we present a case report of CG from the Indian subcontinent and review its literature mainly focusing on histopathological findings.

How to cite this article:
Modi SS, Balasubramaniam S, Sunilkumar K. Collagenofibrotic glomerulopathy: A case of glomerular deposition disease in the Indian subcontinent and review of the literature. Saudi J Kidney Dis Transpl 2020;31:681-6

How to cite this URL:
Modi SS, Balasubramaniam S, Sunilkumar K. Collagenofibrotic glomerulopathy: A case of glomerular deposition disease in the Indian subcontinent and review of the literature. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2023 Jan 31];31:681-6. Available from: https://www.sjkdt.org/text.asp?2020/31/3/681/289454

   Introduction Top

Collagenofibrotic glomerulopathy (CG), first reported in 1979 by Arakawa is rare renal disease described by an accumulation of type III collagen in the glomerular mesangial and subendothelial areas and a marked increase in serum type III procollagen peptide levels.[1] Initially, it was considered as a variant of nail-patella syndrome with no skeletal deformities, as the glomeruli in nail-patella syndrome also showed an accumulation of type III collagen.[2] In the early 1990s, this disease condition was identified as a separate entity and, the World Health Organization included this disease in the classification of glomerular diseases in 1995.[3] Most common clinical presentation of CG is proteinuria, most often in the nephrotic range, hematuria, which is usually microscopic, followed by edema and hypertension. The disease produces a progressive decline in renal function, often leading to end-stage kidney disease. CG has been documented under various names in the literature, such as collagen type III glomerulopathy and primary glomerular fibrosis.[4] Diagnosis is made on a renal biopsy where characteristic electron microscopic findings in conjunction with supporting light microscopic findings and negative immunofluorescence studies are seen. In addition, immunohistochemical assays specific for Type III collagen can be used to support the diagnosis. We report a case of this rare entity from our unit, along with a review of literature mainly focusing on histopathological features.

   Case Report Top

Informed consent was obtained from the patient before publishing the case.

A 51-year-old man presented with pedal edema and anasarca for three months. His past medical history revealed hypertension for eight years and diabetes mellitus (DM) for eight months which was managed by linagliptin (5 mg once a day), prazosin (2.5 mg once a day), domperidone (10 mg twice/day), frusemide (40 mg once a day), atorvastatin (10 mg once a day), bisoprolol (2.5 mg once a day), and ramipril (2.5 mg once a day). DM was well controlled (HbA1c 5.3 g%). He did not have significant past or family history of a connective disease or a renal disease. On examination, the patient had a blood pressure of 170/110 mm Hg and pedal edema. Rest of the systemic examination was unremarkable. Laboratory evaluation showed blood urea of 24 mg/dL, serum creatinine of 1.3 mg/dL and serum electrolytes were normal. Urine routine showed 3+ Proteinuria, occasional RBCs and 2–4 WBCs/HPF. Urine albumin-creatinine ratio was 5196.3 mg/g. He did not have diabetic retinopathy. Renal biopsy was advised in view of nephrotic range proteinuria and absence of diabetic retinopathy. It was done after two months as he deferred it. Laboratory evaluation at the time of biopsy showed serum creatinine of 2.7 mg/dL, blood urea 54 mg/dL with normal serum electrolytes. Urine routine showed 3+ proteinuria, 2-4 RBCs and 4–6 WBCs/HPF. Urine protein creatine ratio was 10.95. The patient underwent a renal biopsy which revealed features suggestive of nodular glomerulosclerosis which was subsequently confirmed as CG by electron microscopy.

Renal biopsy showed two linear cores of renal cortical tissue showing up to 36 glomeruli, of which one showing ischemic obsolescence. The viable glomeruli were enlarged and showed lobular accentuation displaying expanded mesangial matrix, which is obscuring the capillary lumens and fibrin caps, thickening, and focal reduplication of the capillary walls [Figure 1]a. The expanded nodular mesangial matrix was weakly positive for Periodic acid–Schiff (PAS) stain [Figure 1]b and negative for Congo-red and Periodic Schiff–Methenamine silver stain [Figure 1]c. The trichrome stain was positive with mesangial nodular deposits. The interstitium showed patchy areas of chronic inflammation, multifocal tubular atrophy, and interstitial fibrosis. Blood vessels appeared unremarkable [Figure 1]d. Immunofluorescence showed linear smooth artifactual immunofluorescence of IgG with kappa and weak lambda deposits along glomerular basement membrane (GBM) with no tubular basement membrane or mesangial deposits suggestive of diabetic changes. Staining for IgA, IgM, C3, and C1q were negative in intact glomeruli. In summary, the renal biopsy revealed diffuse glomerular nodular glomerulopathy with organized deposits and diabetic glomerular changes. Electron microscopy was done in view of unexplained glomerular deposits which were weakly PAS positive. The electron microscopy showed the markedly enlarged glomerulus with distributed foot process flattening. Almost the entire loop distended with banded collagen fibers. The basement membrane thickness was 710 nm [Figure 2]. These findings reinforced the diagnosis of CG with background of diabetic nephropathy.
Figure 1: (a) The glomerular enlargement with the mesangial expansion with the formation of nodules. The nodules were (b) weakly positive with Periodic Acid–Schiff stain (c) negative Periodic Schiff – Methenamine silver stain (d) mesangial nodular deposits with Masson trichrome stain (blue) (×400).

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Figure 2: The electron microscopic study of renal biopsy specimen fixed using glutaraldehyde shows (a) thickened basement membrane with foot process flattening (×20.00 kx magnification) (b) accumulation of curvilinear banded collagen fibers confirming the diagnosis of collagenous glomerulopathy (×50.00 kx magnification).

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   Discussion Top

CG, a rare glomerular deposition disease, often encountered in the Asian population, especially from Japan, is also reported from other parts of the globe.[5] Ethnic/genetic factors play a crucial role in etiopathogenesis. It is inherited as autosomal recessive though sporadic cases have been reported. It occurs across a wide age range without any gender bias.[6]

Normal GBM contains collagen Type IV, V, and VI; type III collagen is usually seen in the interstitium and blood vessels throughout the body but it is not detectable in glomeruli.[7] Whenever there is a dysregulated formation of type III collagen, it gets deposited in the GBM, subendothelium or mesangium and propagates fibrosis. Pathogenesis leading to dysregulation remains unclear, with some evidence implicating interleukin-4, which selectively stimulates type III collagen synthesis and the suppression of collagen type I and V. Alternatively elevated blood levels of PIIINP (N terminal propeptide of type III procollagen) accumulation of similar collagen fibers in other organs including, liver, spleen, myocardium and thyroid gland indicates systemic nature of disease.[8] Another point, human complement factor H deficiency, hemolysis, and hemolytic uremic syndrome are also associated with the cause of CG.[9] Hence the source of collagen type III may be mesangial cells or as a part of systemic disorder with secondary mesangial deposits.[6]

Only 19 cases of CG have reported from India to much of our knowledge. With the literature review, the clinical profile of published cases of CG from India compiled in [Table 1].[6],[10],[11],[12],[13],[14]
Table 1: Clinical profile of published cases of collagenofibrotic glomerulopathy from India.

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Histologically, it is considered as a spectrum of organized glomerular deposition disease, characterized by enlarged lobular glomeruli with membranoproliferative glomerulonephritis pattern.[8],[9] Lobules are eosinophilic mesangial deposits, which are weakly PAS positive; silver and Congo-red stain negative and, negative for immunoglobulins and complements on the immunofluorescence. Electron microscopy findings of collagen fibers seen as curved frayed structures with a periodicity of 45–60 nm in the mesangial and subendothelial regions are diagnostic.[15] Eosinophilic nodular deposits can be seen in many other diseases such as nodular diabetic nephropathy, membranoproliferative glomerulonephritis, amyloidosis, monoclonal immunoglobulin deposition disease, fibronectin glomerulopathy, immunotactoid glomerulonephritis, and fibrillary glomerulonephritis. A clinical history of longstanding diabetes, distribution of nodular lesions (uniform or variable), staining characteristics, immunofluorescence findings of immunoglobulins/complements/kappa-lambda light chain; and ultrastructure study helps in differentiating almost all the differential diagnoses.[16] The details of staining characteristics of various diseases presenting with nodular glomerulosclerosis on light microscopy is complied in [Table 2].
Table 2: Utilization of histochemical stains in the differential diagnosis of nodular glomerulosclerosis.[16],[17]

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Although the confirmation of a diagnosis of CG must be obtained by electron microscopy or specific immunohistochemistry (not done in our patient), clues to its diagnosis can be obtained by light microscopy.

There is no specific treatment approach available for CG. Various supportive measures are incorporated as the part of treatment such as control of hypertension, Renin-Angiotensin- Aldosterone System blockade to reduce proteinuria and retard progression and, diuretics to relieve edema. Furthermore, renal replacement therapy may be required in patients with end-stage renal disease. There have been case report of patients with CG having received a transplant, to date, none have shown recurrence of the disease.[6],[7],[8],[12],[13],[16]

The incidence of CG has increased as per recent literature. However, the underlying etiology of CG is not clear. It is possible that decreased access to treatment of chronic infections, environmental factors, and disease may play a role or that different genetic factors may be involved.[13]

To conclude, CG is a significant and rare cause of nodular glomerulosclerosis. This brief report highlights the possibility of the cooccurrence of CG with systemic and metabolic diseases such as DM. In future, reporting and pooling of similar cases will assuredly contribute to a better understanding of the pathogenesis and biological behavior of this disease.

   Acknowledgment Top

The authors express their heartfelt gratitude to Mrs. Feral Daruwala for manuscript writing assistant.

Conflict of interest: None declared.

   References Top

Arakawa M. Idiopathic mesangio-degenerative glomerulopathy. Jpn J Nephrol 1979;21:914-5.  Back to cited text no. 1
Arakawa M. Collagenofibrotic glomerulopathy. In: Collagenofibrotic Glomerulopathy: A New Type of Primary Glomerulopathy. London, UK: Smith Gordon; 1991. p. 3-8.  Back to cited text no. 2
Churg J, Bernstein J, Glassok RJ. Collagenofibrotic glomerulopathy, Renal Disease: Classification and Atlas of Glomerular Diseases. 2nd ed. New York: Igaku Shoin; 1995. p. 406-43.  Back to cited text no. 3
Gubler MC, Dommergues JP, Foulard M, et al. Collagen type III glomerulopathy: A new type of hereditary nephropathy. Pediatr Nephrol 1993;7:354-60.  Back to cited text no. 4
Cohen AH. Collagen type III glomerulopathies. Adv Chronic Kidney Dis 2012;19: 101-6.  Back to cited text no. 5
Patro KC, Jha R, Sahay M, Swarnalatha G. Collagenofibrotic glomerulopathy - Case report with review of literature. Indian J Nephrol 2011;21:52-5.  Back to cited text no. 6
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Anitha A, Vankalakunti M, Siddini V, Babu K, Bonu R, Ballal S. Type III collagen disorders: A case report and review of literature. Indian J Pathol Microbiol 2016;59:75-7.  Back to cited text no. 7
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Alchi B, Nishi S, Narita I, Gejyo F. Collagenofibrotic glomerulopathy: Clinicopathologic overview of a rare glomerular disease. Am J Kidney Dis 2007;49:499-506.  Back to cited text no. 8
Herrera GA, Turbat-Herrera EA. Renal diseases with organized deposits: An algor-ithmic approach to classification and clinic-pathologic diagnosis. Arch Pathol Lab Med 2010;134: 512-31.  Back to cited text no. 9
Khubchandani SR, Chitale AR, Gowrishankar S. Banded collagen in the kidney with special reference to collagenofibrotic glomerulopathy. Ultrastruct Pathol 2010;34:68-72.  Back to cited text no. 10
Soni SS, Gowrishankar S, Nagarik AP, et al. Collagenofibrotic glomerulopathy in association with Hodgkin’s lymphoma. Saudi J Kidney Dis Transpl 2011;22:126-9.  Back to cited text no. 11
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Duggal R, Nada R, Rayat CS, Rane SU, Sakhuja V, Joshi K. Collagenofibrotic glome-rulopathy-a review. Clin Kidney J 2012;5:7- 12.  Back to cited text no. 12
Kurien AA, Larsen CP, Cossey LN. Collagenofibrotic glomerulopathy. Clin Kidney J 2015;8:543-7.  Back to cited text no. 13
Nimmagadda S, Mukku K, Devaraju SR, Uppin MS. Unusual cause of glomerular deposition disease: Collagenofibrotic glomerulopathy. Indian J Nephrol 2017;27:62-5.  Back to cited text no. 14
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Fogo A. Atlas of renal pathology type III collagen glomerulopathy (Collagenofibrotic glomerulopathy) 2001;38:15-6.  Back to cited text no. 15
Alsaad KO, Edrees B, Rahim KA, Alanazi A, Ahmad M, Aloudah N. Collagenofibrotic (Collagen Type III) glomerulopathy in association with diabetic nephropathy. Saudi J Kidney Dis Transpl 2017;28:898-905.  Back to cited text no. 16
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Alsaad KO, Herzenberg AM. Distinguishing diabetic nephropathy from other causes of glomerulosclerosis: An update. J Clin Pathol 2007;60:18-26.  Back to cited text no. 17

Correspondence Address:
Suny S Modi
Department of Nephrology, Nephrolife the Complete Kidney Care, Swami Narayan Complex, Majura Gate, Surat - 395001, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.289454

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  [Table 1], [Table 2]


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