Rare Case of C3 Glomerulopathy in a Patient of Type 1 Diabetes Mellitus : Saudi Journal of Kidney Diseases and Transplantation

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Case Report

Rare Case of C3 Glomerulopathy in a Patient of Type 1 Diabetes Mellitus

Godara, Suraj; Saraf, Karan Kumar

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Saudi Journal of Kidney Diseases and Transplantation 33(Suppl 1):p S83-S86, February 2022. | DOI: 10.4103/1319-2442.374385
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Abstract

Introduction

A wide spectrum of primary glomerular diseases may occur in patients with type 1 diabetes mellitus (DM) due to autoimmune mechanisms.[1,2] Here, we report a rare presentation of complement component 3 glomerulopathy (C3G) in a patient with type 1 DM.

Case Report

A 13-year-old boy who is a known case of type-1 DM for the last eight years came with the following chief complaints of frothing in urine for the last 10 months, swelling over his face for the last seven to eight months, and edema over bilateral lower limbs for the last six to seven months.

The patient started developing swelling, which he first noticed around the eyes and then progressed to involve the lower limbs. There is no history of fever, hematuria, sore throat, joint pains, skin rash, burning micturition, loose stools, and jaundice. There is no history of blurring of vision nor tingling and numbness of limbs. He is a vegetarian, has no history of substance abuse and no known drug allergies, and has no history of non-steroidal anti-inflammatory drug abuse. He is not hypertensive and has no history of any chronic illness in the past. Family history is not significant.

Examination

On admission, the patient is awake and alert, he weighed 37 kg, 147 cm in height, the body mass index 16.5 kg/m2, mild conjunctival pallor, peri-orbital edema and bilateral edema of the hands and feet, icterus, lymphadenopathy, clubbing, cyanosis absent. The jugular venous pressure is normal. Vital signs revealed temperature: 98.6°F, blood pressure: 140/90 mm Hg in the right arm in the supine position, heart rate: 86 beats/min, respiratory rate: 20 breaths/min. System: Cardiovascular S1S2 heard, no added sounds. Respiratory system: mild tachypnea, bilateral air entry present, no added sounds. Abdomen not distended, no tenderness, no organomegaly, bowel sounds present. Central nervous system: normal level of consciousness, alert and cooperative. Gait: power, tone, sensation, and reflexes intact and functioning within the normal limits. Dermatological is normal.

The patient’s laboratory profile was as follows: hemoglobin: 9.8 g/dL, total leukocyte count: 7700/mm3, platelet count: 3.4 × 105/mm3, serum albumin: 2.4 g/dL, serum sodium: 127 mEq/L, serum potassium: 5.3 mEq/L. serum calcium: 8.8 mg/dL, serum phosphorus: 5.2 mg/dL, random blood sugar: 284 mg/dL, HbAlc: 12.5 mg%, blood urea: 57.2 mg/dL, serum creatinine: 1.0 mg/dL, HBsAg: negative, anti-HCV: negative, HIV: negative. Chest X-ray is normal. Electrocardiogram is normal. Fundus examination is within the normal limits, and vision is 6/6. Abdominal ultrasound revealed normal-sized kidneys with acute parenchymal changes and mild ascites.

Urine examination color - light yellow, appearance – cloudy, specific gravity – 1.025, pH – 5.5, protein +++, sugar ++++, ketone bodies – nil, urobilinogen – normal, bile pigments – nil, nitrite – nil, centrifuged deposit, pus cells – 4-6/hpf, red cells – 37/hpf, epithelial cells – +/hpf, casts – Granular casts +, Crystals – nil, Organisms – ++, Others – +. Twenty-four-hour urine protein is 6.5 g/day.

As the presence of proteinuria and hematuria was not correlating with the history of type 1 DM and diabetic nephropathy, as fundus was also normal, a renal biopsy was planned in view of concurrent pathology going with type 1 DM.

The biopsy revealed features of mesangiocapillary membranoproliferative injury pattern glomerulonephritis (MPGN). DIF studies – glomerular extraglomerular C3 staining. C3 glomerulopathy (Figure 1, Figure 2).

F1
Figure 1:
Histopathological image showing diffuse variable (mild/moderate) mesangial cell proliferation with matrix expansion, focally prominent intraglomerular neutrophil infiltration in PAS stained sections.
F2
Figure 2:
Histopathological image showing diffuse thickening of capillaries which exhibit membrane texture alterations and several “splits/double contours” discernible in silver methenamine stained sections.

He was treated with predinisolone (1 mg/kg) and calcineurin inhibitor (tacrolimus 0.05 mg/kg). On follow-up of after three months the patient responded to treatment in form of decrease of edema and proteinuria (+1) and fewer RBC’S on urine examination.

The authors obtained all appropriate consent forms from the patient.

Discussion

Renal disease in patients suffering from type 1 DM for over 8–10 years is usually the result of diabetic nephropathy. However, simultaneous presence of nondiabetic renal disease may be seen in up to 28% of patients.[3] The detection of superimposed glomerular disease may have both therapeutic and prognostic importance.[4]

Chihara et al showed that among 164 diabetes patients who had undergone a renal biopsy, 36 had various types of glomerular disease. Diabetic patients with MPGN had a shorter renal survival time (9.0 ± 6.1 years) compared with diabetic patients with other glomerular diseases (13.3 ± 7.1 years) or without any glomerular disease (17.5 ± 6.1 years).[4]

A significantly increased risk of type-1 DM was reported in patients and families with DDD in a US questionnaire-based study of 98 patients (although ascertainment bias cannot be excluded).[5]

McCrory et al described the occurrence of nephrotic syndrome in four diabetic children, together with biopsy findings. In three children, the nephrotic syndrome developed after four, eight, and 12 years duration of diabetes.[6]

The atypical clinical features that have previously been shown to predict renal involvement by NDRD in diabetic patients are sudden onset of proteinuria, proteinuria in the absence of diabetic retinopathy, active urinary sediment, rapidly decreasing renal function, and short duration of diabetes, which are also the indications for doing a renal biopsy in a diabetic patient.[7,8,9,10]

Normally, no immune complexes and obvious complements could be detected by IF and EM in patients with DN. If there is a variety of typical deposition in the glomeruli, such as granular/chunky patterns of immunoglobulin by IF or electron-dense deposits by EM, it usually indicates a superimposed nondiabetic renal disease.[11]

The most common nondiabetic glomerular diseases previously reported in patients with type-2 diabetes are IgA nephropathy,[9,12,13] focal segmental glomerulosclerosis (FSGS)[14,15] and membranous nephropathy.[15,16] Acute tubular necrosis (ATN) was the most common nondiabetic renal pathology super-imposed on DN in type-2 diabetes patients presenting with acute kidney injury.

Studies show that almost half of the patients with type-2 diabetes presenting with atypical features of DN are found to have NDRD upon renal biopsy. Male gender, short duration of diabetes (<8 years), lower glycated hemoglobin, and active urinary sediment were independent predictors of NDRD (±DN), and the absence of diabetic retinopathy is a good indicator of isolated NDRD. ATN is the most common NDRD superimposed on DN, whereas IgA nephropathy is the most prevalent renal pathology in type-2 diabetes patients with isolated NDRD.

The renal histopathology in this particular patient has clearly documented an MPGN (C3G) which responded to cytotoxic treatment. The poor prognosis of super-imposed MPGN in diabetic patients makes a timely diagnosis critical for renal survival. Histological studies confirm that NDRD can occur in isolated form without diabetic nephropathy or superimposed on diabetic nephropathy.

In China, IgA nephropathy was the most frequently biopsy finding seen in all NDRD patients, followed by membranous nephropathy, mesangial proliferative GN, hypertensive nephrosclerosis, renal damage, minimal change disease (MCD), FSGS, and crescentic GN.[17] However, the disease spectrum of NDRD varies in different populations. For example, in the United States, unlike in China which has a high prevalence of IgA nephropathy, two large-scale retrospective studies found that FSGS, ATN, and IgA nephropathy were the most common lesions found in patients with NDRD. Hypertensive nephrosclerosis, MCD, and membranous nephropathies were also common NDRDs of diabetic patients in the United States.[14,18]

Nonrenal manifestations of DDD include ocular drusen, acquired partial lipodystrophy, type-1 DM, and monoclonal gammopathy of undetermined significance.[19]

Conclusion

In patients with clinical and laboratory parameters, which is inconsistent with the natural history of diabetic nephropathy, a complete workup should be done considering all other nondiabetic causes of renal disease, and an early diagnosis of such disease can have therapeutic and prognostic importance.

Conflict of interest:

None declared.

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