Jastrzębska K*, Gozdowska J, Perkowska-Ptasińska A and Durlik M
Department of Transplantation Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland
Received: 20 June, 2016;Accepted: 18 August, 2016; Published: 22 August, 2016
Katarzyna Jastrzębska, Department of Transplantation Medicine, Nephrology and Internal Diseases, Medical University of Warsaw, 02-006 Warsaw, Nowogrodzka 59, Poland; Tel; +48 22 502 1035; E-mail:
Jastrzębska K, Gozdowska J, Perkowska-Ptasińska A, Durlik M (2016) Rapidly Progressive Glomerulonephritis Associated with Systemic Lupus Erythematosus. Arch Clin Nephrol 2(1): 028-031.
© 2016 Jastrzębska K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Lupus nephritis; Rapidly progressive glomerulonephritis; Crescentic glomerulonephritis
SLE: Systemic Lupus Erythematosus; ANA: Antinuclear Antibodies; dsDNA: Double Stranded/Native DNA; RPGN: Rapidly Progressive Glomerulonephritis; ISN: International Society Of Nephrology; RPS: Renal Pathology Society; DPGN: Diffuse Proliferative Glomerulonephritis; GN: Glomerulonephritis; GFR: Glomerular Filtration Rate; RBC: Red Blood Cells; HTC: Hematocrit; ANCA: Anti-Neutrophil Cytoplasmic Antibodies; AFOG: Acid Fuchsin Orange G; PAS: Periodic Acid–Schiff; Gcs: Glucocorticoid; MMF: Mycophenolate Mofetil; KIDIGO: Kidney Disease: Improving Global Outcomes; CKD: Chronic Kidney Disease; ESDR: End Stage Renal Disease; CYC: Cyclophosphamide; LN: Lupus Nephritis; AZA: Azathioprine; ACE: Angiotensin-Converting Enzyme; AVN: Avascular Necrosis; INF: Interferon; IL: Interleukin: TNF: Tumor Necrosis Factor;
Lupus nephritis is a frequent manifestation of multisystem autoimmune disease - Systemic Lupus Erythematosus and a significant cause of both acute renal injury and the end stage renal disease. Renal involvement is observed in approximately 60% of patients with SLE.
We report a case of crescentic glomerulonephritis in a previously healthy 21-year old man who showed signs of insidious symptoms (lower limbs and facial mild edema) in February 2011 and within a brief period developed such clinical features as fever, nausea, vomiting, headache, loin pain, hematuria, oliguria and hypertension. Rapidly worsening renal function became an important determinant of renal failure therefore hemodialysis therapy was introduced. Conducted immunological tests showed an elevated level of antinuclear antibodies and antibodies to dsDNA as well as low complement (C3, C4) levels. The diagnosis of rapidly progressive glomerulonephritis in the background of diffuse glomerulonephritis with crescent formation was confirmed by the presence of pathological features in a renal biopsy. In addition to hemodialysis, treatment with steroids (methylprednisolone) and immunosuppressive agents (cyclophosphamide) was applied.
The therapy resulted in slow but successful clinical improvement. After two months of treatment there was a recovery of renal function and the patient became dialysis independent. Maintenance therapy has been continued for about 4 years. The serum creatinine level is about 1.2 mg/dL, without proteinuria.
Crescentic glomerulonephritis in the course of SLE correlated with unfavorable prognosis and therefore must be treated promptly to prevent irreversible kidney injury. This case illustrates the potential of long-term high-dose immunotherapy in the treatment of RPGN in the course of SLE.
Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune-related disease of unknown origin with the presence of circulating antibodies against a variety of cellular antigens .
Clinically, SLE may be presented as multi-organ lesions or the involvement of only one system organ accompanied or preceded by additional symptoms in the course of the illness . SLE is more common among women (female-to-male ratio of 9:1) aged 20-40 years. Lupus nephritis is a frequent manifestation of SLE among adult patients. According to current research, approximately sixty per cent of lupus patients will evolve clinically significant kidney damage . The inflammation may involve all components of renal parenchyma, however, glomerular abnormality is a reliable prognostic indicator in lupus nephritis . The clinical expression of lupus nephritis is highly changeable, varying from asymptomatic proteinuria to kidney insufficiency.
The prevaling classification (revised by the International Society of Nephrology – ISN and the Renal Pathology Society – RPS in 2003) based on pathology proved in renal biopsy, has divided the varied forms of renal injury in SLE nephritis into six histological categories . Diffuse proliferative glomerulonephritis (DPGN) (ISN/RPS class IV) tend to exhibit the worst prognosis . Rapidly progressive glomerulonephritis (RPGN) is a clinical term defined by severe loss of renal function induced by expansion of inflammatory process in glomerulus. A common effect of RPGN is the rapid reduction in the glomerular filtration rate of at least 50% over 3 months and clinical evidence of glomerular injury in the form of active urinary sediment including red blood cell casts. In patients with RPGN, renal biopsy typically demonstrate widespread glomerular crescent formation. Standard nephrological diagnosis is performed using a fluorescence technique which allows to divide glomerular disorders into three possible patterns: granular positivity consistent with immune complex-mediated GN, linear positivity caused by anti-glomerular basement membrane disease, or no significant positivity, corresponding to ”pauci-immune” crescentic GN.
A previously healthy 21-year old man was admitted to a provincial hospital with complaints of fever, nausea, vomiting, headache, loin pain, hematuria, oliguria and hypertension. Laboratory tests showed: hemoglobin 9.7 g/dL (hematocrit 29%), platelet count 75 G/L, white blood cell count 4 G/L, C-reactive protein 24.5 mg/dL, blood urea nitrogen levels of 143 mg/dL and serum creatinine concentration of 6 mg/dL, estimated GFR 12 mL/min. In urinalysis, protein of 1210 mg/dL, red blood cell (RBC) 50-70/ high power field, urinary cast. The patient was diagnosed with nephrotic syndrome characterized by high range proteinuria (protein 3630 mg/day), hypoalbuminemia, (serum albumin of 1.7 g/dL), hyperlipidemia (cholesterol 276 mg/dL, triglycerides 366 mg/dL) and edema. Ultrasound scans showed enlarged kidneys (12 cm length) and increased renal parenchyma echogenicity. Within a brief period, renal function had severely deteriorated therefore treatment was initially changed to hemodialysis therapy. Glomerulonephritis was suspected and patient was referred to the Department of Transplantation Medicine and Nephrology.
On hospital admission urinalysis showed an active urine sediment: 1200.9 mg/dL protein, hematuria, leukocyturia and urinary cast. Levels of complement components C3 and C4 were reduced (C3 42 mg/dL, C4 3.7 mg/dL). Laboratory test showed decreased hematocrit (HCT 28%) and hemoglobin (Hb 9.4 g/dL). Immunological tests for the detection of antinuclear antibodies and antibodies to double-stranded DNA, were positive and showed an elevated titer of both serum antibodies: ANA 1:10 000; anti-dsDNA 1: 1000. The patient’s serum tested negative for anti-neutrophil cytoplasmic antibodies (cANCA, pANCA) and anti–glomerular basement membrane antibodies.
Differential diagnosis to exclude other illnesses such as a renal vein thrombosis, infective endocarditis, hepatitis B, hepatitis C, monoclonal gammopathy, rheumatoid arthritis, antiphospholipid syndrome and cryoglobulinemia was conducted.
The patient underwent an ultrasound monitored biopsy, twenty-nine glomeruli were evaluated. An examination of renal tissue by light microscopy revealed the presence of crescents in more than 82% of glomeruli - seventeen glomeruli, with epithelial crescents, seven with fibroepithelial crescents and the appearance of segmental capillary sclerosis. (Figures 1-6) Immunofluorescence studies showed a moderately diffuse deposition of IgG, C3, C1q along the glomerular capillary and in the mesangium. Proliferating cells accompanied by fibrin deposition and inflammatory cell infiltration were found in renal parenchyma. Therefore, the patient was diagnosed with diffuse glomerulonephritis with epithelial and fibroepithelial crescent formation involved more than 50 % of glomeruli in the biopsy. Immunofluorescence tests and clinical history indicate SLE as a primary cause of acute kidney injury. The presence of Lupus nephritis was certified and classified as an IV G a/c class according to INS/RPS classification.