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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT  
Year : 2021  |  Volume : 32  |  Issue : 1  |  Page : 223-226
A Rare Cause of Nephrotic Syndrome in Adults – Collagenofibrotic Glomerulopathy


1 Department of Nephrology, K S Hegde Medical Academy, Mangalore, Karnataka, India
2 Department of Pathology, K S Hegde Medical Academy, Mangalore, Karnataka, India

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Date of Web Publication16-Jun-2021
 

   Abstract 


Adult-onset nephrotic syndrome (NS) is commonly caused by minimal change disease, focal segmental glomerulosclerosis, andmembranous nephropathy. Rare causes of NS include amyloidosis, immunoglobulin deposition disease, fibronectin glomerulopathy, and Collagenofibrotic glomerulopathy (CG). CG is caused by deposition of Type 3 collagen in the mesangium and subendothelial area. It usually presents as asymptomatic proteinuria, NS, hypertension, and renal failure. Histologically, it can present as Congo red-negative nodular glomerulosclerosis and requires electron microscopy for confirmation of diagnosis. Electron microscopy shows characteristic fibers which are curved, frayed and have a transverse band with periodicity of 43–65 nm. There is no specific treatment, and it can recur after kidney transplantation.

How to cite this article:
Shenoy P, Divya J. A Rare Cause of Nephrotic Syndrome in Adults – Collagenofibrotic Glomerulopathy. Saudi J Kidney Dis Transpl 2021;32:223-6

How to cite this URL:
Shenoy P, Divya J. A Rare Cause of Nephrotic Syndrome in Adults – Collagenofibrotic Glomerulopathy. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2021 Jul 31];32:223-6. Available from: https://www.sjkdt.org/text.asp?2021/32/1/223/318528



   Introduction Top


Nephrotic syndrome (NS) is characterized by nephrotic range proteinuria (>3.5 g/day), hypoalbuminemia, edema, hypercholesterolemia. Common causes of NS in adults are minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. NS could be due to primary or idiopathic and secondary to drugs, malignancy, autoimmune disease, infectious disease. Glomerular deposition diseases such as amyloidosis, immunoglobulin deposition disease, fibronectin glomerulopathy, and collageno-fibrotic glomerulopathy (CG) are rare causes of NS in adults. Here, we report a case of CG presenting as NS. CG is a rare disease characterized by deposition of type III collagen fibers in the subendothelium and mesangial area of glomerulus.[1],[2]


   Case Report Top


Informed consent was obtained from the patient for the publication of this case report.

A 31-year-old female presented with swelling of feet and facial puffiness of two months duration. There was no history of similar complaints in the past or recent drug intake or history of any allergy or significant family history. On evaluation, she was found to have edema with normal blood pressure, proteinuria without microscopic hematuria, hypoalbuminemia (serum albumin 2.1 g/dL), and hypercholesterolemia with normal renal function. The 24-h urinary protein estimation was found to be 3.7 g/day. She was diagnosed as adult-onset NS and underwent further evaluation including renal biopsy. Her serology was negative for viral markers (HIV, HCV, and HBsAg), antinuclear antibodies were negative, and complement levels were normal. She underwent percutaneous renal biopsy without any complications.

Renal biopsy showed 34 glomeruli with four obsolescent glomeruli. There was glomerulomegaly with diffuse and global accumulation of pale eosinophilic, acellular, weak periodic acid–Schiff (PAS)-positive and silver-negative material in the sub-endothelial location and mesangium forming a nodule. There was no endothelial proliferation, tuft necrosis, or crescent formation. The Congo red stain did not show apple green birefringence. There was also mild diffuse acute tubular injury and arteriolar hyalinosis. Immunofluorescence study revealed focal and segmental trapping of C3 without any extraglomerular deposits. Rest of the panel including IgG, IgM, C1q, Kappa, and Lambda are negative. Overall features were suggestive of non-amyloid deposition disease and electronic microscopy was suggested for further evaluation. Electron microscopic study revealed focal effacement of foot processes of visceral epithelial cells (30%–35%) and glomerular sub-endothelial expansion and accumulation of banded fibrillary material, showing periodicity of about 40–60 nm in the sub-endothelial and mesangial area. The morphological features, immunofluorescence findings, and electron microscopic study were consistent with a diagnosis of CG.


   Discussion Top


CG was first described by Arakawa in 1979.[3] It can present in various age groups (2–66 years) without any gender predominance.[4] Initially, it was considered as a variant of nail–patella syndrome without any skeletal manifestation; however, later, it was classified as a distinct glomerular disease.[5],[6] Common clinical presentations include various degrees of proteinuria, NS, and hypertension with or without renal failure.[7] CG is reported more frequently from Asian countries, especially in Japanese population, possibly indicating ethnic or geographical factors associated with disease.[4] Few cases reported from Europe were in children. Various proposed mechanisms for deposition of type III collagen in CG include production by mesangial cells or abnormal systemic metabolism of collagen III.[8]

Our patient was a 32-year-old female who presented with swelling of the lower limbs and facial puffiness of 2 months duration. Edema with or without NS is a common presentation. Up to 60% of patients can have nephrotic range proteinuria, and hypertension is seen in 66% of patients. Our patient had nephrotic range proteinuria without hypertension. Renal function is usually preserved in most cases at presentation, as seen in our patients. Urine examination may show microscopic hematuria which was absent in our case.

Renal biopsy under light microscopy shows mesangiocapillary or membranoproliferative pattern; however, in our case, there was glomerulomegaly with mesangial nodule and subendothelial deposits [Figure 1]. Mesangial expansion is due to deposition of amorphous, weakly PAS-positive material which is Congo red negative. Thickened capillary loops are due to the subendothelial deposits rather than basement membrane abnormality as depicted in PAS and methenamine silver stains. Diabetic glomeruloscleros is and monoclonal immunoglobulin deposition disease can closely mimic CG in H&E stain, but can be differentiated by PAS stain. Immunofluorescence stain is usually negative or may show focal trapping of IgM or C3 in the mesangium, which are nonspecific changes. Immunohistochemistry for collagen type 3 may show subendothelial or mesangial deposits.
Figure 1: Light microscopic picture of renal biopsy (a) glomerulus showing mesangial expansion with pale, eosinophilc deposits with thickening of the basement membrane. (b) Trichrome stain showing the blue color of the deposits indi cation the substance to be collagen.

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Immunofluorescence-negative and Congo red-negative glomerular deposition diseases such as diabetic glomerulosclerosis, fibronectin glomerulopathy, and CG require electron microscopic studies for confirmation. Electron microscopy shows characteristic fibers which are curved, frayed and have a transverse band with periodicity of 43–65 nm. These fibers are absent in the lamina densa of basement membrane which is typical of nail–patella syndrome. There may be associated diffuse foot process effacement. Our case also had characteristic curved fibers with periodicity and diffuses foot process effacement [Figure 2].
Figure 2: Electron microscopic picture showing the deposition of fibrillary material with periodicity of 40–60 nm which are curvilinear and have disorganized morphology, suggestive of deposition of type III collagen fiber.

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There is no specific therapy for CG. General measures of glomerular disease such as control of blood pressure, use of angiotensin (ACE) inhibitor or angiotensin receptor blocker, and diuretics are often used. There is no evidence for effectiveness of immunosuppressive therapy such as steroids. CG can slowly progress to end-stage renal disease and may require renal replacement therapy. There are case reports of kidney transplant in CG without any recurrence.[7]In our case, we had treated with ACE inhibitor and diuretics, and the patient had partial remission at 12-months follow-up.

To conclude, CG is a rare cause of NS in adults, and this case highlights the importance of electron microscopy in accurate diagnosis of glomerular pathology.

Conflict of interest: None declared.



 
   References Top

1.
Ikeda K, Yokoyama H, Tomosugi N, Kida H, Ooshima A, Kobayashi K. Primary glomerular fibrosis: A new nephropathy caused by diffuse intra-glomerular increase in atypical type III collagen fibers. Clin Nephrol 1990;33:55-9.  Back to cited text no. 1
    
2.
Imbasciati E, Gherardi G, Morozumi K, et al. Collagen type III glomerulopathy: A new idiopathic glomerular disease. Am J Nephrol 1991;11:422-9.  Back to cited text no. 2
    
3.
Arakawa M. Idiopathic mesangio-degenerative glomerulopathy (Japanese). Jpn J Nephrol 1979;21:914-5.  Back to cited text no. 3
    
4.
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. 4
[PUBMED]  [Full text]  
5.
Vernier RL, Hoyer JR, Michael AF. The nail-patella syndrome-pathogenesis of the kidney lesion. Birth Defects Orig Artic Ser 1974;10:57-9.  Back to cited text no. 5
    
6.
Dombros N, Katz A. Nail patella-like renal lesions in the absence of skeletal abnormalities. Am J Kidney Dis 1982;1:237-40.  Back to cited text no. 6
    
7.
Alchi B, Nishi S, Narita I, Gejyo F. Collageno-fibrotic glomerulopathy: Clinicopathologic overview of a rare glomerular disease. Am J Kidney Dis 2007;49:499-506.  Back to cited text no. 7
    
8.
Iskandar SS, Herrera GA. Glomerular diseases with organized deposits. In: Jennette JC, Silva FG, Olsan JL, D’Agati VD, editors. Hiptenstall’s Pathology of Kidney. 7th ed. Philadelphia: Wolters Kluwer; 2015. p. 1029-31.  Back to cited text no. 8
    

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Correspondence Address:
Pradeep Shenoy
Department of Nephrology, K S Hegde Medical Academy, Mangalore, Karnataka
India
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DOI: 10.4103/1319-2442.318528

PMID: 34145135

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