 Abstract | | |
We describe a 42-year-old male patient who presented with high grade fever associated with acute renal failure requiring hemodialysis. Renal biopsy revealed that he had focal proliferative glomerulonephritis on light microscopy, dominant mesangial deposition of C1q by immunofluorescent staining, and electron dense deposits on electron microscopy, with no evidence of systemic lupus erythematosus, compatible with the diagnosis of C1q nephropathy. Intensive treatment with a combination of methyl prednisolone pulse therapy and oral prednisolone was successful in achieving complete remission and disappearance of proteinuria in our patient.
How to cite this article:
Malleshappa P, Ranganath R, Chaudhari AP, Ayiangar A, Lohitaksha S. C1q nephropathy presenting as acute renal failure. Saudi J Kidney Dis Transpl 2011;22:324-6 |
How to cite this URL:
Malleshappa P, Ranganath R, Chaudhari AP, Ayiangar A, Lohitaksha S. C1q nephropathy presenting as acute renal failure. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2013 May 22];22:324-6. Available from: http://www.sjkdt.org/text.asp?2011/22/2/324/77620 |
| Introduction | |  |
C1q nephropathy is an immune complex glomerulonephritis defined by the presence of mesangial immunoglobulins and complement deposits, most notably C1q, and the absence of clinical and laboratory evidence of systemic lupus erythematosus. [1] C1q nephropathy often manifests as steroid-resistant asymptomatic proteinuria or nephrotic syndrome. It can also present with asymptomatic hematuria. Patients presenting primarily with acute renal failure requiring dialysis have not been reported in C1q nephropathy thus far.
| Case Report | | |
A 42-year-old male patient presented to us with high-grade fever with chills, nausea and vomiting for the preceding five days, and decreased urine output for the last two days. He denied any history of dysuria, hematuria, skin rash, joint pains and pain abdomen. He was a known hypertensive which was under good control with medications and was also suffering from alcoholic liver disease. On examination, he was febrile, icteric and breathless at rest with a respiratory rate of 32 beats/min. His blood pressure was 170/110 mmHg. He had bilateral pitting edema of the legs and sinus tachycardia. Auscultation of the lungs revealed pulmonary congestion.
Laboratory data confirmed advanced renal failure. His laboratory tests revealed serum creatinine of 9 mg/dL, blood urea nitrogen of 75 mg/dL, hemoglobin of 13.3 g/dL, white blood cell count of 5,830/mm 3 , platelet count of 99,000/mm 3 , serum sodium of 133 mEq/L, potassium of 4.2 mEq/L, chloride of 102 mEq/ L and bicarbonate of 12 mEq/L. Urine analysis revealed specific gravity of 1.020, albumin 2+, RBC 40-50/hpf, pus cells 80-100/hpf and spot urine for protein-creatinine (PCR) ratio was 1.6. The patient was negative for malarial parasite, dengue and Leptospira. The serum was negative for HIV 1 and 2, hepatitis B surface antigen and hepatitis C virus antibodies. Complement 3 and 4 levels were within normal limits. Vasculitis work-up was negative for ANA, ds DNA, p and c-ANCA, anti-GBM antibody and ASO titer. Ultrasonography of the abdomen revealed chronic liver disease, bilateral bulky kidneys with normal echotexture and cortical reflectivity and minimal ascites. The blood and urine cultures were negative.
In view of oliguria, fluid overload, azotemia and metabolic acidosis, he was initiated on hemodialysis (HD). Kidney biopsy was planned in view of the acute onset of unexplained renal failure. He underwent kidney biopsy after four sessions of HD. On light microscopy, there were eight enlarged glomeruli showing thin basement membranes and patent capillary lumina; three glomeruli showed proliferation of mesangial cells (3-5 per region) with neutrophilic infiltration and sparse endothelial proliferation. The tubules revealed foci of necrosis and atrophy. The interstitium was stippled with lymphocytes, eosinophils and plasma cells. The blood vessels showed luminal narrowing due to myointimal thickening, suggestive of focal proliferative glomerulonephritis. Immunofluorescence study revealed prominent deposits of C1q along with C3 in the mesangium and along the capillary loops [Figure 1]. Electron microscopy showed numerous mesangial, subendothelial and rare intra-membranous electron dense deposits, confirming the diagnosis of C1q nephropathy [Figure 2]. | Figure 1: Immunoflurescence with prominent deposits of C1q along with C3 in the mesangium and along the capillary loops.
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 | Figure 2: E.M. showing numerous mesangial, subendothelial and rare intra-membranous electron dense deposits of C1q nephropathy.
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The patient was initiated on intravenous methylprednisolone 1 g/day for three days, following which his serum creatinine dropped significantly from 6.2 to 3.9 mg/dL. He was taken off HD, and he was put on oral prednisolone 1 mg/kg/day (60 mg/day). His renal functions were monitored on a daily basis. The serum creatinine gradually decreased from 3.9 to 1.9 mg/dL within a span of 10 days. He was continued on oral prednisolone in a dose of 60 mg/day for one month and gradually tapered to the current levels of 30 mg/day. The renal functions returned to normal (creatinine 1.1 mg/dL) with no significant proteinuria (spot urine PCR-0.2).
| Discussion | | |
Jennette and Hipp proposed to define the clinical entity of C1q nephropathy by the following criteria: (a) the presence of predominant or co-dominant deposition of C1q in the mesangium on immunofluorescence, (b) corresponding mesangial or para-mesangial electrondense deposits under electron microscopy, and (c) lack of clinical and pathological evidence of systemic lupus erythematosus (SLE). [1] Generally, C1q deposition is caused by the activation of C1 by immunoglobulin G (IgG) and IgM; therefore, C1q nephropathy is considered as an immune complex glomerulonephritis. However, in C1q nephropathy, it remains unclear whether the deposition of C1q in the glomeruli is in response to the deposition of immunoglobulin or immune complex, or whether deposition is non-specific trapping that accompanies increased glomerular protein trafficking associated with proteinuria. Since both the pathogenesis of C1q deposition in the glomeruli as well as its significance are still uncertain, it has not yet been established as an independent disease.
A variety of histological findings have been reported on light microscopy. They include minor glomerular abnormalities, mesangial proliferative glomerulonephritis with or without segmental sclerosis, and focal segmental glomerulosclerosis (FSGS). [2] There are few case reports wherein the patients had presented with rapidly progressive glomerulonephritis. [3]
Clinical outcomes of C1q nephropathy are diverse. Patients with the nephrotic syndrome and C1q nephropathy often show a poor response to corticosteroid treatment. Methylprednisolone pulse therapy has been shown to be effective in steroid resistant cases. Aggressive treatment with a combination of cyclosporine, prednisolone and methylprednisolone pulse therapy could be a treatment of choice for C1q nephropathy with FSGS. Sequential therapy with cyclophosphamide, azathioprine, mycophenolate mofetil and tacrolimus used separately or in combination with steroids has shown good clinical response in different studies. [4]
Our patient presented with acute renal failure requiring HD. Such a presentation has not yet been reported in patients with C1q nephropathy. The fact that the response to steroids is immediate and complete prompts us to believe that this is an immune mediated problem causing a proliferative disease.
| Acknowledgment | | |
The authors would like to acknowledge Dr. Shaila Khubchandani, Histopathologist, Jaslok Hospital, Mumbai, India, for her contribution in preparing this case report.
| References | | |
| 1. | Jennette JC, Hipp CG. C1q nephropathy: A distinct pathologic entity usually causing nephrotic syndrome. Am J Kidney Dis 1985;6:103-10. 
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| 2. | Alenka V, Dusan F. Pathology, clinical presentations, and outcomes of C1q nephropathy. J Am Soc Nephrol 2008;19(11):2237-44.
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| 3. | Srivastava T, Chadha V. C1q nephropathy presenting as rapidly progressive crescentic glomerulonephritis. Clin Exp Nephrol 2009;13(4): 263-74.
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| 4. | Satoshi H, Yuko F. Clinicopathologic correlation and outcome of C1q nephropathy. Clin J Am Soc Nephrol 2008;3:1637-43.
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Correspondence Address:
Pavan Malleshappa
Senior Registrar, Department of Nephrology, A-791, Lilavati Hospital and Research Centre, Bandra Reclamation, Bandra-West, Mumbai400050, Maharashtra State
India
PMID: 21422635
[Figure 1], [Figure 2] |
