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Nodular glomerulosclerosis with crescents- a double edged sword


1 Department of Pathology, IPGME&R and SSKM Hospital, Kolkata, West Bengal, India
2 Department of Nephrology, IPGME&R and SSKM Hospital, Kolkata, West Bengal, India

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Date of Submission15-Jul-2021
Date of Decision22-Jul-2021
Date of Acceptance23-Jul-2021
Date of Web Publication26-May-2022
 


How to cite this URL:
Sengupta M, Basu K, Roychowdhury A. Nodular glomerulosclerosis with crescents- a double edged sword. Indian J Pathol Microbiol [Epub ahead of print] [cited 2022 Oct 5]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=345893




Diabetic nephropathy (DN) can develop during the disease course of both type 1 and type 2 diabetes mellitus. The distinctive renal biopsy finding is nodular (Kimmelsteil–Wilson) diabetic glomerulosclerosis.[1] But the implication of renal biopsy in diabetes mellitus is debatable and mostly restricted to rule out nondiabetic renal disease (NDRD). Histological findings are categorized in three broad subtypes- I- DN; II- NDRD superimposed on DN and III- isolated NDRD.[2] Worldwide incidence and spectrum of NDRD are quite variable.[3]

A 30-year-old nonsmoker, nonalcoholic male patient was attended with chief complaints of respiratory distress; progressive decline in urine output and swelling of lower limb. He was previously diagnosed as a case of type 2 diabetes 10 years back and was advised with hyperglycemic controlling drugs along with lifestyle modifications.

General physical examination showed pallor with appreciable pedal edema. Systemic examination was unremarkable. Laboratory workup revealed abnormal renal function with baseline creatinine of 13 mg/dL and serum was BUN 80 mg/dL. Urine examination revealed 3 + albumin, dysmorphic RBCs and albumin: creatinine ratio of 3.29 μg/mL. Twenty-four-hour urine proteins were 2.8 g/total volume (2400 mL). His serum albumin was 2.4 g/dL. Ultrasound examination revealed enlarged kidneys (right kidney 13.5 cm and left kidney 12.5 cm) with mildly raised cortical echogenicity and maintained cortico-medullary differentiation. Hemogram showed mild anemia only. Fasting blood sugars was 210 gm/dL. Liver function tests were within normal limits and coagulation workup revealed a prothrombin index of 100%. Lipid profile showed that serum total cholesterol was 334 mg/dL. Serum complement levels were within normal limit. His MPO-ANCA was 180 U/mL and PR3-ANCA was negative. Serum ANA and anti- GBM were negative. Human immunodeficiency virus, hepatitis B surface antigen and anti-hepatitis C virus antibodies were negative. Proliferative diabetic retinopathy was diagnosed on opthalmoscopic examination.

Renal biopsy revealed total 23 glomeruli among which two were globally and one was segmentally sclerosed with adhesion. Rest (20) and the nonsclerosed tuft showed global mesangial matrix expansion along with segmental acellular mesangial nodule (Kimmelsteil-Wilson) formation among eight of them. Mesangial nodules were Periodic acid Schiff (PAS) positive, blue in masson trichrome (MT) stain and black in silver methanamine (SM) stained sections. Congo red-stained section was noncontributory. Circumferential crescents were detected in 12 glomeruli and on morphological assessment 8 were cellular, 3 were fibrocellular and one was fibrous in nature [Figure 1] and [Figure 2]. Glomerular basement membrane was mildly thickened with presence of breakage. Moderate interstitial fibrosis and tubular atrophy (IFTA) along with intratubular colloid casts, granular casts and cellular casts were observed. Arteriolar hyalinosis was detected. Immunoflourescence findings showed segmental nonspecific entrapment of IgM and C3c only [Figure 3]. Depending on light microscpopy and immunoflourescence finding, final diagnosis of pauci-immune crescentic glomerulonephritis in a background of Class III DN was established.
Figure 1: A low-power view of kidney biopsy showing one sclerotic glomerulus and other glomeruli with various stages of crescents. Arrows indicate K.W nodule. (Periodic acid-Schiff stain; 100×)

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Figure 2: A low-power view of kidney biopsy showing glomeruli with various stages of crescents. Mesangial nodules are argyrophillic. (silver methanamine stain, 100×)

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Figure 3: Immunoflourescence photomicrographs show nonspecific peripheral entrapment in IgM and C3c. (FITC, original magnification 100×)

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As initial treatment, Methylprednisolone pulse was administered. Once the categorical diagnosis was established, Cyclophosphamide as per the European Society of Vasculitis (EUVAS) protocol was started. Partial response was noted and patient remained hemodialysis dependent.

The course and progression of the DN is mainly anticipated by the duration of the disease. But the clinical predictors of concurrent or isolated nondiabetic kidney diseases are the following: (1) Nephrotic range proteinuria with maintained renal function and vice versa, (2) no other microvascular complication, (3) rapid decline of renal function, (4) active urinary sediments and (5) low serum compliments.[3] Renal biopsy is essential for early detection and timely intervention to ensure the renal survival.

A wide spectrum of primary glomerulonephritis of both proliferative and nonproliferative nature was reported as NDRD by previous literatures.[4] Crescentic form of glomerular injury of any etiology is a rare occurrence and sparse literature was available from our population.[5] The largest series published earlier included 23 cases.[6]

The causal relationship between diabetes nephropathy and crescentic pattern of injury is not well established. Some author postulated that diabetic induced glomerular damage makes it more susceptible to immune-mediated injury.[2] We have reported these cases of ANCA positive pauci-immune crescentic glomerulonephritis without any systemic manifestation. Absence of extrarenal manifestation may lead to delay in intervention thus healing of crescents and scar formation. Rapid progression to end-stage renal disease was described by other author also.[7] The expression of nephrin and claudin 1 was analyzed in true as well as pseudo crescents in diabetic kidney and stated that both parietal and visceral epithelial cells contribute in framework.[8]

[Table 1] shows a comparative analysis with other literatures.[1],[6]
Table 1: Comparative analysis with other literatures

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In conclusion, NDKD should be kept in mind while evaluating patients with unexplained renal dysfunction and history of diabetes mellitus.

Declaration of patient consent

Obtained.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Otani N, Akimoto T, Yumura W, Matsubara D, Iwazu Y, Numata A, et al. Is there a link between diabetic glomerular injury and crescent formation? A case report and literature review. Diagn Pathol 2012;7:46.  Back to cited text no. 1
    
2.
Prakash J. Non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (type 2 DM). J Assoc Physicians India 2013;61:194-9.  Back to cited text no. 2
    
3.
Kritmetapak K, Anutrakulchai S, Pongchaiyakul C, Puapairoj A. Clinical and pathological characteristics of non-diabetic renal disease in type 2 diabetes patients. Clin Kidney J. 2018;11:342-7.  Back to cited text no. 3
    
4.
Fiorentino M, Bolignano D, Tesar V, Pisano A, Biesen WV, Tripepi G, et al. Renal biopsy in patients with diabetes: A pooled meta-analysis of 48 studies. Nephrol Dial Transplant 2017;32:97-110.  Back to cited text no. 4
    
5.
Kanodia KV, Vanikar AV, Goplani KR, Trivedi HL. Diabetic nephropathy with crescentic GN. Saudi J Kidney Dis Transpl 2009;20:672-3.  Back to cited text no. 5
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6.
Nasr SH, D'Agati VD, Said SM, Stokes MB, Appel GB, Valeri AM, et al. Pauci-immune crescentic glomerulonephritis superimposed on diabetic glomerulosclerosis [published correction appears in Clin J Am Soc Nephrol 2009;4:516]. Clin J Am Soc Nephrol 2008;3:1282-8.  Back to cited text no. 6
    
7.
Ko YS, Yun H, Lee EY, Jang K, Yi JH, Han SW. Rapid progression of diabetic glomerulosclerosis with crescents to end-stage renal disease in newly diagnosed type 2 diabetes. Korean J Med 2016;90:46-9.  Back to cited text no. 7
    
8.
Gaut JP, Hoshi M, Jain S, Liapis H. Claudin 1 and nephrin label cellular crescents in diabetic glomerulosclerosis. Hum Pathol 2014;45:628-35.  Back to cited text no. 8
    

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Correspondence Address:
Moumita Sengupta,
244 AJC Bose Road, Kolkata - 700 020, West Bengal
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_727_21



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