Download to read offline
More Related Content
Similar to Lupus Nephritis-Diagnosis and management
![Rheumatic Fever CASE PRESENTATION [Autosaved].pptx](https://cdn.slidesharecdn.com/ss_thumbnails/casepresentationautosaved-251123182512-9d9b0da4-thumbnail.jpg?width=640&height=640&fit=bounds)
Lupus Nephritis-Diagnosis and management
- 1. Overview of LupusNephritis Nnonyelu MD, Chibueze 12/16/2022
- 2. Outline • Introduction • Epidemiology •Pathology • Classification • Clinical presentation • Diagnostics • Treatment • Prognosis • reference
- 3.
- 4. Introduction • Lupus Nephritisis simply the inflammation of the kidney from SLE which is an autoimmune disease. • It is the most dangerous specific manifestation of SLE because of its high morbidity and mortality. • Can manifest as nephritic syndrome and/or nephrotic syndrome , found in up to 50% of individuals with SLE
- 5. Epidemiology • LN typicallyoccurs early in the disease course • Clinically evident kidney disease eventually occurs in up to one-half of patients with SLE, and up to 10 percent of patients with LN will develop ESRD • In a cohort study, 1827 patients with newly diagnosed SLE were followed , 700(38%) developed LN within 4.3 years. • There is higher incidence in black population and Hispanics • Additional the risk of progressive Kidney disease in patient’s with LN are influenced by Male sex, African/Hispanic population, pediatric onset, frequent relaspses and proteinuria >4g/day at diagnosis
- 6.
- 7. Pathology • In Lupus,most cell undergo apoptosis with release of it’s cellular content including components of the nucleus eg DNA, Histones, other proteins (Nuclear antigens). • Immune system recognizes the nuclear antigens as foreign and produces anti- nuclear antibodies against these antigens forming antigen-antibody complexes. • These immune complexes are primarily composed of DNA and anti-dsDNA. However, immune complexes may also have as their components chromatin, C1q, laminin, Sm, La (SS-B), Ro (SS-A), ubiquitin, ribosomes, and glomerular elements including the parts of the glomerular basement membrane (GBM) and mesangium
- 8. Pathology • These immunecomplexes, when deposited in the mesangium and subendothelial space, are in direct communication with the systemic circulation. Subsequent activation of the classical complement pathway, triggered by the DNA/anti-DNA antibody complex formation, generates the potent chemoattractants, C3a and C5a, which elicit an influx of neutrophils and mononuclear cells. This is Type III hypersensitivity reaction. • These changes are manifested histologically by a mesangial, focal, or diffuse proliferative glomerulonephritis and clinically by an active urine sediment (red cells, white cells, and cellular and granular casts), and proteinuria.
- 9. Pathology • In subepithelialspace: a cationic antigen that can cross the GBM and fix in a subepithelial location with subsequent antibody complexing or an autoantibody may be directed against an endogenous epithelial cell antigen. • Although deposits in the subepithelial space can also activate complement, there is no influx of inflammatory cells, since the chemoattractants are separated from the circulation by the GBM. Thus, injury is limited to the glomerular epithelial cells, and the primary clinical manifestation is proteinuria, which is often in the nephrotic range. Histologically, these patients most commonly have membranous nephropathy.
- 10. Classification Table fromMKSAP 19
- 11.
- 12. Clinical Presenetation • Mostkidney abnormality emerge soon as the diagnosis of SLE is made • Most frequently observed abnormality is proteinuria, other features include Microscopic hematuria with or without red cell cast, hypertension, Edema, elevated plasma creatinine • Rarely, there can be silent LN-Studies in which a kidney biopsy is performed in patients without any clinical evidence of kidney disease have found mesangial, focal, or diffuse proliferative glomerulonephritis in some patients.
- 13. Red blood cell(RBC) casts in urine sediment • A tubular cast (blue overlay) is visible in the center of the image. The cast is composed of numerous RBCs, identifiable by their characteristic biconvex shape (examples outlined in yellow), in a matrix of fibrin and plasma proteins. Several epithelial cells surrounding the RBC cast are also visible. Image and caption from Amboss library
- 14. Diagnosis • Urinalysis/Microscopy: Dysmorphicred cells, cellular casts, Proteinuria • BMP: elevated creatinine and reduced GFR • Anti-dsDNS titre • Complement level • Biopsy- Indications: -urine protein excretion >500mg/day -persistent hematuria -a rising creatinine not attributed to any other etiology On immunofluorescence microscopy, the glomerular deposits in LN stain dominantly for IgG with co-deposits of IgA, IgM, C3, and C1q in a “full house” pattern.
- 15. Q1 A 19-year-old womanis evaluated for a 2-week history of fatigue, poor appetite, arthralgia of the hands and knees, and a rash, all of which appeared 1 day after a trip to the beach. She has no other medical problems and takes no medications. On physical examination, vital signs are normal. A malar rash characterized by pink-violet papules and plaques with sparing of the nasolabial folds is noted. The remainder of the examination, including joint examination, is normal. Kidney US shows kidenys of normal size and echogenicity
- 16. Q1 • Which ofthe following is the most appropriate diagnostic test to perform next? A. ESR B. Extractable nuclear antigen panel C. Kidney biopsy D. Skin biopsy
- 17. Treatment • The currentapproach to treating LN is guided by histologic findings with appropriate consideration of presenting clinical parameters and the degree of kidney function impairment • Immunosuppressive therapy is used to treat active focal (class III) or diffuse (class IV) LN or lupus membranous nephropathy (class V LN), whereas it is not usually used to treat minimal mesangial (class I), mesangial proliferative (class II), or advanced sclerosing (class VI) LN. • Rx has 2 components: Induction/initiation phase to slow kidney injury, long-term maintenance therapy and general supporting measure
- 18. Treatment • Induction: Combinationof Glucocorticoids with either MMF or IV or PO Cyclophosphamide • ALMS trial-MMF is not superior to Cyclophosphamide • Duration 3 to 12 months • Pulse dose steroid for the first 3 days IV Methylprednisolone 250-100mg daily (in severe active disease) • Prednisone 0.5-2mg/kg max 60mg/day for 3 to 6 months and then taper to 7.5mg/day • MMF- start 0.5mg BID x 1 week, then 1g BID the next week and then to target of 1.5mg BID • Cyclophosphamide: IV 0.5-1g monthly for 6-7 weeks or 500mg 2 weekly upto 6 doses. Oral 1-1.5mg/kg /day increase by 0.5mg/kg every week till 2mg/kg/day
- 19. Treatment • Maintenance: Aftera complete or partial response has been achieved with initial therapy, patients are switched to a subsequent regimen to decrease the risk of developing ESKD • The importance of continuing immunosuppressive therapy after initial therapy is highlighted by the fact that up to 50 percent of patients with focal or diffuse LN relapse following reduction in or cessation of immunosuppressive therapy • Medication: Azthioprine or MMF; other alternatives Tacrolimus, cyclosporine, low dose glucocorticoid.
- 20.
- 21. Treatment • Other supportivetherapy include: • dietary sodium and protein restriction • blood pressure control • RAAS inhibition • lipid lowering • anticoagulation
- 22. Response to Therapy •Clinical and Histological • Clinical is routinely done while histological is not recommended • No consensus for what determines good clinical response however most nephrologists use -substantial reduction in proteinuria less than 0.33g/day -improvement or stabilization of creatinine <1.2 or 15% decrease from baseline level -improvement in urinary sediments
- 23. Clinic follow up •History and physical examination. • Urine protein –creatinine ratio or 24 hr urine protein • BMP • Urinalysis (with microscopy). • Serum complement levels (C3 and C4) and anti-double-stranded DNA (anti- dsDNA) antibody levels. • Complete blood count (which is monitored every other week in patients receiving higher-dose cyclophosphamide) and liver function tests. • Some experts also monitor erythrocyte sedimentation rate (ESR) as a nonspecific marker of disease activity in those whose anti-dsDNA antibody levels and/or serum complement levels do not return to normal • Blood tacrolimus or cyclosporine trough levels (in patients receiving one of these agents).
- 24. Relapse • This isdefined as patients that have persistent heavy proteinuria (over 3 g daily) despite 6 to 12 months of adequate therapy (ie, are nonresponders) or have an initial response but then develop worsening proteinuria, a new active urinary sediment, or worsening kidney function. • A repeat kidney biopsy is required to confirm that these clinical scenarios are due to persistent lupus membranous nephropathy (LMN) or conversion to a different lupus nephritis (LN) class.
- 25. Relapse • This isapproached as follows • For patients who do not respond to initial treatment with MMF in combination with glucocorticoids, we typically switch to cyclophosphamide therapy, a calcineurin inhibitor (CNI), or rituximab • For patients who initially respond to MMF but then subsequently relapse, modification of immunosuppression depends upon when the relapse occurs: • If the relapse occurs during long-term therapy (when the MMF dose is being tapered) or after MMF has been discontinued, we resume the original dose of MMF (usually with a goal between 1 and 1.5 g twice daily). • If the relapse occurs during the first six months of MMF treatment, we typically continue MMF and add either a CNI or rituximab.
- 26. Prognosis Up to 30%of patients with LN will progress to ESKD within 10 years of diagnosis, depending in large part on the response to the initial course of immunosuppression. Severity of disease at the time of diagnosis is an important predictor of outcomes in LN. Complete response results in better outcome while partial response leads to relapse.
- 27. Q2 • A previouslyhealthy 30-year-old woman comes to the physician because of a 6-month history of a recurring rash on her face, arms, and hands. She has also noticed several painless ulcers in her mouth. She is sexually active with one male partner and they use condoms inconsistently. Her mother has end-stage renal disease. The patient does not smoke or drink alcohol. Her vital signs are within normal limits. Physical examination shows an erythematous rash across the cheeks and extensor surface of the arms and hands. There are three small ulcers on the hard palate. Laboratory studies show: WBC 4000 Platelet count 90000 ESR 80 ANA Pos VDRL pos Urine protein 3+ RBC cast neg RBC neg Urine WBC 10-15
- 28. Q2 cont What isthe appropriate next step? A. Skin biopsy B. Renal biopsy C. Urine culture D. Administration of Hydroxychloroquine E. Administration of Penicillin F. Rapid HIV test
- 30. New Literature New onsetSLE beginning as class V Lupus Nephritis after covide 19 vaccination by Maria et al published in ISN journal 2021 23-year-old woman who presented with nephrotic syndrome 1 week after vaccination with the first dose of AstraZeneca covid vaccine.
- 31. References 1. Uptodate 2. WeeningJJ, D’agati VD, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004; 65(2): p.521-530. doi: 10.1111/j.1523-1755.2004.00443.x 3. Osmosis video-Youtube