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Saudi Journal of Kidney Diseases and Transplantation
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RENAL DATA FROM ASIA - AFRICA  
Year : 2015  |  Volume : 26  |  Issue : 2  |  Page : 398-403
C1q nephropathy in India: A single-center study


1 Department of Pathology, Laboratory Medicine and Transfusion Services and Immunohematology, Institute of Kidney Diseases and Research Centre and Institute of Transplantation Sciences, Civil Hospital Campus, Asarwa, Ahmedabad, India
2 Department of Nephrology and Transplantation Medicine, Institute of Kidney Diseases and Research Centre and Institute of Transplantation Sciences, Civil Hospital Campus, Asarwa, Ahmedabad, India

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Date of Web Publication3-Mar-2015
 

   Abstract 

C1q nephropathy (C1qN) is defined by conspicuous C1q deposits in the glomerular mesangial regions of patients who do not have any evidence of systemic lupus erythematosus (SLE). We present our experience with C1qN over the last three years. In total, 1775 native renal biopsies were reviewed and dominant/co-dominant C1q mesangial deposits in patients with absence of clinical and/or serological evidence of SLE were considered as C1qN. Their clinical profile and renal function status were studied and correlated. C1qN was observed in 11 patients (0.61%), and included eight males and three females; the mean age was 36.6 years. The most common presentation was nephrotic syndrome. Hematuria was noted in eight patients (72%). The mean serum creatinine was 2.78 mg/dL. Hypertension was seen in two patients (18%). Mesangial proliferative glomerulonephritis (MePGN) was the most common histological pattern, followed by focal and segmental glomerulosclerosis and other lesions. The common codeposits along with C1q were IgM, followed by C3 and others. MePGN had better prognosis than others. To conclude, C1qN was noted in 0.61% of all renal biopsies with bimodal age distribution and may present as podocytopathy or non-podocytopathy. The prognosis depends on the morphological pattern and C1q deposits per se are not prognostic indicators.

How to cite this article:
Kanodia K V, Vanikar A V, Patel R D, Suthar K S, Patel H V, Gumber M A, Shah P R, Trivedi H L. C1q nephropathy in India: A single-center study. Saudi J Kidney Dis Transpl 2015;26:398-403

How to cite this URL:
Kanodia K V, Vanikar A V, Patel R D, Suthar K S, Patel H V, Gumber M A, Shah P R, Trivedi H L. C1q nephropathy in India: A single-center study. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2020 Sep 24];26:398-403. Available from: http://www.sjkdt.org/text.asp?2015/26/2/398/152562

   Introduction Top


C1q nephropathy (C1qN) is a recent entrant in the field of renal pathology. It is defined by conspicuous C1q immune deposits in the glomerular mesangial regions of patients with no clinical or serological evidence of systemic lupus erythematosus (SLE). C1qN is different from type-1 membranoproliferative glomerulonephritis (MPGN), which frequently has substantial C1q staining in the glomerular immune deposits. C1qN generally manifests as steroid-resistant asymptomatic proteinuria/nephrotic syndrome (NS). [1],[2],[3],[4] We present our experience with C1qN over the last three years.


   Materials and Methods Top


Overall, 1775 native renal biopsies reported in the period of January 2008 to February 2011 were reviewed for evaluating C1qN. Biopsies with presence of dominant/co-dominant C1q mesangial deposits in patients with absence of clinical and/or serological evidence of SLE were considered as C1qN. Their clinical profile and renal function status were studied and correlated. All the patients were non-reactive to antibodies against human immunodeficiency virus.

All the biopsy samples were subjected to 3-μ-thick paraffin sections for light microscopy (LM) and were stained with hematoxylin and eosin, Periodic acid Schiff, Jone's silver me-thaneamine and Gomori's trichrome stains. The biopsies were evaluated for acute and chronic pathologies as well as injury pattern in glomeruli, tubules, parenchyma and vessels. A biopsy sample was considered adequate if it contained ≥7 glomeruli. For direct immunofluorescence (IF) studies, anti-human IgA, IgG, IgM, C1q, C3, albumin and fibrinogen anti-sera (Glostrup, Denmark) were used on the 3-μ-thick frozen sections. IF findings were graded as trace, +1, +2, +3 and +4, and an intensity ≥+2 was considered as positive.


   Results Top


Clinical presentation

C1qN was observed in 11 patients (0.61%) including eight males and three females with a mean age of 36.63 ± 25.21 years. All study patients were adults except one male child of nine years who had focal and segmental glomerulosclerosis (FSGS). Five patients were 9-18 years old (45.45%), three were between 70 and 78 years (25%) and three others were between 28 and 40 years (25%). Ten patients (83%) presented with NS and one patient (9%) presented with rapidly progressive renal failure. Hematuria was noted in eight patients (72.72%). The mean serum creatinine (SCr) was 2.78 ± 3.03 mg/dL, the mean 24-h urinary protein excretion was 5.83 ± 2.86 g/day and ten patients (83.3%) had nephrotic range proteinuria. Hypo-albuminemia was seen in 10 patients (83.3%), with mean serum albumin of 2.99 ± 0.73 g/dL. Hypertension was seen in two patients (18%) [Table 1].
Table 1: Clinical and laboratory parameters among patients with C1q nephropathy.

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Renal histopathological patterns [Figure 1]a and b

MePGN was the most common pattern seen in five patients (41.67%), followed by FSGS in three (25%) of whom two had the classical variant and one had the peri-hilar variety. Segmental endocapillary proliferative GN, minimal change disease (MCD) with acute tubulointerstitial nephritis (ATIN) and crescentic (cellular) glomerulonephritis (GN) were seen in one patient (8.33%) each.
Figure 1:

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IF microscopy

There was dominant or co-dominant staining of C1q in all 11 patients (100%) [Figure 1]c. The pattern of staining was fine granular (+2/ +4), predominantly in the mesangial regions of all the glomeruli. In addition to C1q, there was fine granular fluorescence in a similar pattern (+1 to +3) on staining with anti-human IgM in six (54.54%), C3 in six (50 %), IgA in three (25%) and IgG in two patients (16.7%).

Follow-up

Clinical follow-up was available in seven patients (58.3%) for a mean of 6.14 ± 6.64 months (range 1-16). Of these seven patients, three patients had MePGN, two patients had FSGS and one patient each had endocapillary proliferative GN and crescentic GN. Three patients (42.8%) received steroids plus cyclosporin, two patients (28.6%) received steroids plus mycophenolate mofetil (MMF) and two patients (28.6%) received steroids alone. Stable renal function was seen in six of the seven patients (85.7%). One patient (14.2%) with FSGS developed progresssive renal insufficiency.

Proteinuria declined in 85.7% of the patients, including complete remission in two patients (28.6 %) and partial remission in four patients (57.1%); one patient (14.3%) had no remission [Table 2].
Table 2: Follow-up data of patients with C1q nephropathy.

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In patients with MePGN, complete remission was seen in two patients, partial remission was seen in one patient and all had stable renal function. The other two patients were lost to follow-up. Among patients with FSGS, one patient progressed to end-stage renal disease after 15 months and the other patient was in partial remission. Patients with crescentic GN and endocapillary proliferative GN had partial remission and maintained stable renal function after one and three months of follow-up, respectively. We could not correlate the association of hypertension with any findings.


   Discussion Top


C1qN is primarily a histological diagnosis described for the first time by Jennette and Hipp in 1985 in a series of patients who displayed C1q mesangial deposits in the absence of SLE. [1] Sharman et al described nine patients with C1q deposits; these patients were diagnosed to have "seronegative lupus nephritis" initially. [4] None of these patients developed SLE during a mean follow-up of 5.1 years. Subsequently, they were labeled as having C1qN. C1qN has been described to be associated with steroid-resistant NS in older children and young adults. [1],[5],[6] The overall prevalence of C1qN ranges from 0.2% to 2.5%, with a higher incidence of 2.1-6% in children. [1],[2],[3],[4],[6] We observed a prevalence of 0.68% of C1qN in our study, matching with the observation of some Western studies. Interestingly, we found a male preponderance, which could be attributed to the mind-set of our society where women's health is not given equal priority as that of men. Additionally, we observed that, instead of C1qN being a disease of children, it may have a bimodal distribution, affecting more commonly young adolescents/adults or geriatric population.

Our cohort of 11 patients had proteinuria with dominant or co-dominant C1q deposits, which was comparable with other studies. [1],[2] Concomitant IgA deposits were noted in three patients; however, C1q was the predominant deposit in the mesangial regions. Secondly, these patients did not have episodic hematuria to favor IgA nephropathy. Their main clinical presentation was NS and, hence, we classified these patients as C1qN.

Markowitz et al have suggested that C1qN falls in the same spectrum as MCD and FSGS. [3] In a similar study by Iskandar et al, C1qN fell in the spectrum of MCD-FSGS. [7] Fukuma et al described C1qN with MCD (7.3%), mesangial proliferative (20%) and FSGS (7%) in a study of 30 children. They reported disappearance of C1q deposits in repeat kidney biopsies in two of the four treated children with minimal change-like C1qN. [8] However, Davenport et al reported four adult patients with C1qN in association with different glomerulopathies, which included MPGN type III, membranous nephropathy, FSGS and diffuse proliferative GN. [9] We did not encounter MPGN with C1q deposits in our study. Our observation correlates with the findings that C1qN falls in the MCD-FSGS complex, as reported by other authors. [10],[11] However, our study also showed co-existence with non-podocytopathy like other authors, who had observed C1qN presenting as crescentic GN. [1],[12],[13] Jennette et al had noted that 30.6% of the cases of C1qN had full-house IF pattern, without evidence of SLE. [1] We observed co-dominant deposits of IgM (58.3%), followed by C3 (50%) and other immunoglobulins.

Jennette and Hipp described the presence of amorphous electron-dense deposits in the mesangial region in all their study cases. Extensive or segmental podocyte foot process effacement and cytoskeleton condensation occurred in patients with NS/nephrotic range proteinuria. In the group with proliferative GN, the podocyte lesion was seen along with capillary wall immune deposits. [1],[2] We did not perform electron microscopic examination in our study.

Our study showed better prognosis in patients with MePGN. Among patients with FSGS, one out of two is in partial remission. This is comparable with other studies. [10],[12],[13] In our study, the crescents were well developed and cellular in nature; this morphological appearance prognosticated good chance of recovery. This patient is so far in partial remission. This suggests that C1q deposits should not be considered as harbingers of guarded prognosis like IgM deposits in IgM nephropathy; rather, morphology should be given greater emphasis for the management and prognosis. [13]

The limitations of this study are small sample size, short and limited patient follow-up and non-availability of EM findings. A national registry of C1qN may guide us in the future to study C1qN in Indians. Also, genetic studies should be undertaken. Thirdly, the role of C1q deposits in the absence of SLE need to be studied with reference to the complement pathway.


   Conclusion Top


In conclusion, we noted C1qN in 0.61% of all renal biopsies. It had bimodal age distribution and presented as podocytopathy or non-podocytopathy. The prognosis depends on the morphological pattern, and C1q deposits per se are not prognostic indicators.


   Acknowledgments Top


The authors thank Ms. Jyotsna Suthar for providing the literature search and Ms. Yogita Tirgar for typing and preparing the manuscript.

Conflict of interest: None declared.

 
   References Top

1.
Vizjak A, Ferluga D, Roži M, et al. Charles Jennette. Pathology, Clinical Presentations, and Outcomes of C1q Nephropathy. J Am Soc Nephrol 2008;19:2237-44.  Back to cited text no. 1
    
2.
Jennette JC, Hipp CG. C1q nephropathy: A distinct pathologic entity usually causing nephritic syndrome. Am J Kidney Dis 1985;6: 103-10.  Back to cited text no. 2
    
3.
Markowitz GS, Schwimmer JA, Stokes MB, et al. C1q nephropathy: A variant of focal segmental glomerulosclerosis. Kidney Int 2003; 64:1232-40.  Back to cited text no. 3
    
4.
Sharman A, Furness P, Feehally J. Distinguishing C1q nephropathy from lupus nephritis. Nephrol Dial Transplant 2004;19:1420-6.  Back to cited text no. 4
    
5.
Lau KK, Gaber LW, Delos MN. C1q nephropathy: Features at presentation and outcome. Pediatr Nephrol 2005;20:744-9.  Back to cited text no. 5
    
6.
Nishida M, Kawakatsu H, Okumura Y. C1q nephropathy with asymptomatic urine abnormalities. Pediatr Nephrol 2005;20:1669-70.  Back to cited text no. 6
    
7.
Iskandar SS, Browning MC, Lorentz WB. C1q nephropathy: A pediatric clinicopathologic study. Am J Kidney Dis 1991;18:459-65.  Back to cited text no. 7
    
8.
Fukuma Y, Hisano S, Segawa Y, et al. Clinicopathologic correlation of C1q nephropathy in children. Am J Kidney Dis 2006;47:412-8.  Back to cited text no. 8
    
9.
Davenport A, Maciver AG, Mackenzie JC. C1q nephropathy: Do C1q deposits have any prognostic significance in the nephritic syndrome? Nephrol Dial Transplant 1992;7:391-6.  Back to cited text no. 9
    
10.
Thomas DB, Franceschini N, Hogan SL, et al. Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int 2006;69:920-6.  Back to cited text no. 10
    
11.
Srivastava T, Chabda V, Taboada EM, Alon US. C1q nephropathy presenting as rapidly progressive crescentic glomerulonephritis. Pediatr Nephrol 2000;14:976-9.  Back to cited text no. 11
    
12.
Imai H, Tadashi Y, Satoh K, Miura AB, Sugawara T, Nakamoto Y. Pan-nephritis (glomerulonephritis, arteriolitis and tubulointerstitial nephritis) associated with predominant mesangial C1q deposition and hypocomplementemia: A variant type of C1q nephropathy? Am J Kidney Dis 1996;27:583-7.  Back to cited text no. 12
    
13.
Singhai AM, Vanikar AV, Goplani KR, et al. Immunoglobulin M nephropathy in adults and adolescents in India: A single-center study of natural history. Indian J Pathol Microbiol 2011;54:3-6.  Back to cited text no. 13
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Correspondence Address:
Dr. K V Kanodia
Department of Pathology, Laboratory Medicine, Transfusion Services and Immunohematology, Institute of Kidney Diseases and Research Centre and Institute of Transplantation Sciences, Civil Hospital Campus, Asarwa, Ahmedabad
India
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DOI: 10.4103/1319-2442.152562

PMID: 25758901

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