|Year : 2018 | Volume
| Issue : 5 | Page : 1227-1231
|Immune complex-mediated rapidly progressive glomerulonephritis in a patient with family history of systemic lupus erythematosus
Ahmad Alflaiw1, Ghormallah Alghamdi1, Khalid Alsaad2, Noura Aloudah3
1 Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
2 Department of Pathology, King Faisal Specialist Hospital, Riyadh, Saudi Arabia
3 Department of Pathology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
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|Date of Submission||23-Jul-2018|
|Date of Acceptance||23-Jul-2018|
|Date of Web Publication||26-Oct-2018|
| Abstract|| |
We describe here a case of a 53-year-old Saudi female who presented to the emergency room with shortness of breath progressive in nature for the previous one month, associated with a cough and occasional greenish sputum. She turned out to be a case of immunocomplex mediated glomerulonephritis presenting as rapidly progressive glomerulonephritis in a female patient with a history of systemic lupus erythematosus (SLE) in her daughter.
|How to cite this article:|
Alflaiw A, Alghamdi G, Alsaad K, Aloudah N. Immune complex-mediated rapidly progressive glomerulonephritis in a patient with family history of systemic lupus erythematosus. Saudi J Kidney Dis Transpl 2018;29:1227-31
|How to cite this URL:|
Alflaiw A, Alghamdi G, Alsaad K, Aloudah N. Immune complex-mediated rapidly progressive glomerulonephritis in a patient with family history of systemic lupus erythematosus. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2018 Dec 16];29:1227-31. Available from: http://www.sjkdt.org/text.asp?2018/29/5/1227/243949
| Introduction|| |
Rapidly progressive glomerulonephritis (RPGN) is a syndrome characterized by glomerular disease resulting in progressive loss of renal function in days or weeks.
Early diagnosis and treatment of RPGN is of extreme importance because of the morbidity and mortality of the disease when untreated.,
Underlying etiology is a group of disorders characterized by the presence of crescents involving ≥50% of glomeruli, hence the term crescentic glomerulonephritis (GN). These include antineutrophil cytoplasmic antibodies (ANCA) associated GN, anti-glomerular basement membrane (GBM) disease, immunocomplex-mediated GN and other rare disorders. The frequency of crescentic GN being ANCA is 60%, immunocomplex GN is24% and anti-GBM is 15%.
Immunocomplex-mediated GN comprises a group of disorders including immunoglobulin A (IgA) nephropathy, IgA vasculitis, lupus nephritis (LN), infection-related GN (post-streptococcal GN, hepatitis C virus (HCV)-related membranoproliferative GN (MPGN) and fibrillary GN with polyclonal Ig deposits.
However, most of the cases attributed to MPGN are secondary, and there is a decrease in the incidence of the idiopathic form which is seen in both adults and pediatrics.
| Case Report|| |
A 53-year-old Saudi female homemaker, a nonsmoker, presented to our ER with shortness of breath progressive in nature for the previous one month, associated with a cough and occasional greenish sputum. This was interfering with her daily activity such that she was not able to climb stairs.
She had frothy dark urine with polyuria but no dysuria. This change in color was noticed one year earlier.
The systemic inquiry was negative for rash, photosensitivity, arthralgia, joint swelling, mouth or genital ulcers, abortion, seizure, or limb weakness.
She gave a history of intake of herbal medications of unknown nature, one month before presentation.
She was a known hypertensive on enlapril 10 mg for the last three months. There was a family history of LN diagnosed in her daughter.
Her physical examination revealed a blood pressure of 140/85 mm Hg, heart rate of 77 beats per minute with normal sinus rhythm. Cardiac examination revealed normal heart sounds and no friction rub. Chest auscultation revealed basal crackles. There was lower limb edema with no rash or discoloration over the toes.
Urinalysis revealed blood ++, UA protein ++, UA RBC 73, UA glucose 150. Blood urea nitrogen was 22.4 mmol, creatinine 365 μmol/ L, estimated glomerular filtration rate (eGFR) by modification of diet in renal disease (MDRD) of 12 mL/min, hemoglobin 95 g/dL, and albumin of 31 g/L. The protein/creatinine ratio was 9.6.
Chest X-ray showed bilateral interstitial ground glass appearance, airspace opacities in the bases, mostly on the left side. High resolution computed tomography of the chest showed mild-to-moderate destruction of the left lower lobe with cystic changes of bronchiectasis.
Kidney ultrasound revealed normal size kidneys with echogenicity, no obstruction or stones. C3 and C4 were normal, erythrocyte sedimentation rate 51, antinuclear antibody (ANA) negative, anti-dsDNA negative. Hepatitis B virus surface antigen negative, HCV negative, c-ANCA negative, p-ANCA positive with a titer of 86.5, antiGBM negative, lupus anti-coagulant positive (LA1, LA2).
On admission, the patient was diagnosed as a possible case of RPGN and started on pulse methylprednisone 500 mg for three consecutive days. She quickly required hemodialysis (HD) because of fluid overload and progressive rise in creatinine.
A kidney biopsy was performed, and light microscopy showed the presence of 24 glomeruli, 10 of which were globally sclerosed. The rest showed mild mesangial expansion with hypercellularity. The GBM showed segmental and focal thickening by PAS and silver staining. There was focal extracapillary proliferation and formation of cellular and fibrocellular crescent in at least five glomeruli. Segmental scarring was seen in eight glomeruli [Figure 1]a and [Figure 1]b.
Using trichrome and Van Gieson stains, the interstitum showed severe interstitial fibrosis and tubular atrophy. There was inflammatory infiltrate mostly of plasma cells and lymphocytes and the tubules showed degenerative-regenerative changes.
In immunostaining, four glomeruli were present, two of which were sclerosed and one showed segmental scarring. There was predominant mesangial and focal capillary staining for IgG (2+), C3 (2+), C1q (2+), kappa (1+) and lambda light chain (1+) b. The rest of antibodies IgA and IgM were negative.
Electron microscopy showed scattered immune mesangial dense deposits [Figure 2]a as well subendothelial deposits [Figure 2]b.
The GBM showed diffuse thickening with segmental wrinkling with epithelial cell injury with diffuse effacement of foot processes.
The patient was started on pulse methylprednisone 500 mg for three days then on 1 mg/ kg/day tapered over six weeks and discontinued. Mycophenolate mofetil (MMF) was started at 500 mg BID. This decision was made as the biopsy showed an advanced disease and the clinical likelihood of recovery was small and thus cyclophosphamide was not considered.
Her condition did not improve and she became dialysis dependent. She was then discharged on three HD sessions per week, MMF 500 mg BID, amlodipine 10 mg daily, hydralazine 25 mg three times daily, candesartan 4 mg daily, sevelamer 1000 mg two times daily, atorvastatin 40 mg daily and furosemide 80 mg two times daily.
After eight weeks, while on HD, her urine output started to increase. Her evaluation at the clinic showed weight 101 Kg, body mass index was 45.49, BP 144/66 mm Hg with peripheral edema but the chest was clear.
Laboratory investigations showed creatinine 458 μmol/L, blood urea nitrogen 18.3 mmol/L, potassium 4.7 meq/L, sodium 137 meq/L, calcium 2.8 mmol/L, and eGFR 9 mL/min (MDRD). Mean GFR for urea and creatinine clearances by 24-h urine collection divided by two was 11.5 mL/min and Hb 10.0 g/dL.
The decision was made to hold HD and increase furosemide to 80 mg three times daily and to increase her MMF to 750 mg two times daily.
Her renal function improved progressively [Figure 3] over the ensuing months and proteinuria improved at the last follow up to 1.7 g/day. She is currently maintained on MMF 750 mg BID and antihypertensive medications.
| Discussion|| |
RPGN carries poor prognosis and outcome if not diagnosed early as an early institution of treatment is crucial., It forms around 2%–10% of all renal biopsies and is normally labeled as crescentic GN. It carries poor outcome when presenting with high serum creatinine and the requirement for HD and in the elderly population.
Immune complex GN is less likely to be the cause of crescentic RPGN compared to ANCA and anti GBM associated GN affecting less than 50% of the glomeruli as in our patient.
Our patient is unlikely to be an ANA negative lupus GN given the IF findings as well as the absence of the required criteria needed for diagnosing SLE.
SLE diagnosis relies on the criteria developed by the American College of Rheumatology (ACR) in 1982 which require four of the 11 criteria. This criterion was revised in 1997.
In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) revised the criteria to include the presence of LN and positivity for ANA or anti-dsDNA or four of the diagnostic criteria including at least one clinical and one immunological. This last criteria attain higher sensitivity (94% vs. 86%) and equal specificity (92%) compared to the old one.
Our patient had a strong family history of LN and had positive lupus anticoagulants. Family studies indicated that first degree relatives of SLE patients had 17–20 fold increased likelihood of developing SLE. This risk extends to second and three degree relatives. Moreover, relatives of SLE patients tend to have increased risk in developing other types of autoimmune diseases.
Patients with negative serology but with a picture of LN-like on renal biopsy, especially with full house immunostaining, may manifest positive serology of lupus in the future. This is more apparent in children than in adults.,
One of the intriguing diagnosis in our patient would be MPGN. However, the normal serum complement levels and the findings on light microscopy preclude such diagnosis. Moreover, MPGN is often secondary to other diseases such autoimmune diseases include systemic lupus, Sjogren’s syndrome, rheumatoid arthritis and mixed connective tissue disease. Idiopathic form of MPGN is becoming rare.
The positivity of p-ANCA in our patient is nonspecific as it is seen in many disorders, especially in lupus patients with a noted association between cANCA and ANA occurrences. In our patient, the titer of p-ANCA had decreased on improvement in renal function and disease remission with treatment.
In conclusion, our case of immune-mediated GN presenting as RPGN with a strong family history of SLE indicated the association of autoimmune disease in relatives. In addition the response to treatment should enhance our approach for early and aggressive institution of therapy which may change the outcome in these patients.
Conflict of interest: None declared.
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Dr. Ahmad Alflaiw
Department of Medicine, King Abdulaziz Medical City, P. O. Box 22490, Riyadh 11426
[Figure 1], [Figure 2], [Figure 3]
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