Kidneys and lupus nephritis at SLE 4.6/5 (10)

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Lupus nephritis

Lupus nephritis class II in glomerulum: mesangial cell proliferation (a) and IgG impact by immunofluorescence (b); Kiremitci S, 2014. Open


Lupus nephritis is rheumatic inflammation (no infection) in the kidney tissue filter system (glomeruli) that typically occurs at Systemic lupus erythematosus (SLE). Proteins (egg white) and red blood cells are shown in the urine (hematuria) and the severity is determined from a kidney tissue sample (biopsy). Without treatment, lupus nephritis leads to high blood pressure and life-threatening renal failure. Follow-up should be done by doctors with experience in lupus nephritis and in collaboration with a kidney specialist.

  • Best treatment for lupus nephritis is important for best prognosis at SLE (reference: Reppe Moe SE, 2019).


Data from research indicates that immune system lacks the ability to remove dying cells (apoptosis) efficiently enough. cell Nuclei which contains DNA thus stimulates the immune system which becomes too active. In the event of a defect (loss of tolerance to one's own tissue), the immune system attacks the tissue in the body's own organs. It is formed immune complexes and inflammation. Patients with DNA or C1q -Antibodies are particularly prone to such kidney inflammation (Glomerulonephritis). Reference: Borchers AT, 2012


Among  SLE patients gets 30-50% nephritis

  • Early SLE diagnosis and treatment reduce the risk of nephritis


Lupus nephritis gives no symptoms in early stages of the disease, but is detected by urine test and tissue sample (biopsy).

  • Suspected lupus nephritis in proteinuria (egg white in the urine) more than 200 mg / 24 hours, hematuria (red blood cells in the urine), increasing blood pressure or renal impairment (increasing creatinine and falling GFR in blood samples).
  • Loss of proteins via the urine over time leads to low protein levels in the blood and water accumulation (edema) on the legs and feet occurs


Measure protein / creatinine ratio and quantification of proteins in urine

  • Consider whether edema is present
  • Blood pressure measurement
  • Examine other signs of SLE activity (skin, joints, heart)

Nephrotic syndrome

Total protein secretion. More than 3g / day in urine + edema and low albumin in the blood. Manifest glomerular kidney disease: Protein / Creatinine ratio more than 300

  • Normal proteinuria: up to 150 mg / day
  • Proteinuria between 30-300 mg / day is considered microalbuminuria (normal urine stitch)
  • Pathological proteinuria 300-500 mg / day
  •  Urine sticks measure albuminuria per liter:
    • 1 + equals 300-1000 mg / liter
    • 2 + equals 1000-3000 mg / liter
    • 3+ corresponds to more than 3000 mg / liter
    • By microalbuminuria urine sticks are normal

DNA antibody and C1q antibody dispose of SLE nephritis.

The degree of blood and protein in urine and impaired GFR (renal function) correlates poorly with the severity of nephritis. Biopsy is therefore often necessary.

Kidney biopsy in SLE

Kidney biopsy is important for assessing disease activity, adequate treatment and prognosis and is recommended when there is evidence of renal manifestation (reference: Fanouraiakis A, 2019 (EULAR Recommendations). The biopsy material is placed on formalin for light microscopy and immunofluorescence. In addition, tissue is placed on 2% glutalaldehyde for electron microscopy.

  • Complication Rate 2-5%
  • After biopsy, the patient is monitored for 24 hours (bleeding hazard). Transient blood in the urine (hematuria) occurs in 60-80%. Ultrasound control current
  • Contraindications to prevent kidney biopsy (reference: Bandari J, 2016)
    • Increased bleeding risk
    • Uncontrolled high blood pressure
    • Just a kidney

SLE nephritic classification after WHO (Grande & Balow, Lupus 1998; 611-7). Weening JJ, 2004

Class 1. Normal / Minimal mesangial (lupus) nephritis *. Incidence <1%
Class 2: Mesangial proliferative (lupus) nephritis *. Occurrence 26%
Class 3 Focal proliferative (<50% affected glomeruli). Incidence 18%. Less than 50% of glomeruli are attacked
Class 4 Diffuse proliferative (> 50% affected glomeruli). Incidence 38%. More than 50% of glomeruli attacked
Class 5: Membrane (lupus) nephritis *, Occurrence 16%
Class 6: Chronic nephritis (80% of glomeruli affected) Sclerosis, Occurrence 2%. More than 90% of the glomeruli attack
   * is referred to as lupus-nephritis if SLE is present  

Nomenclature of renal biopsy

  • Hyper-cellularity (from cells in glomeruli such as endothelium, epithelium and mesangial cells)
  • Wire-loop is eosinophil thickening of glomerulus basement membrane
  • Chronic lesions: Poorest prognosis. Interpreted by number of glomeruli found: 10% glomeruli indicate 35% chance that no lesions are detected. 20% Glomeruli: 12% chance of overcoming affection. Many have both proximal and distal tubular dysfunction. The degree of interstitial nephritis best correlates with renal impairment
  • Segmental changes mean that only a portion of glomerulus is affected and that not all glomeruli have changes
  • Crescent formation is synonymous with extracapillary proliferation. The cells come from parietal part of Bowmans capsule. Necrosis is neutrophilic infiltrates with karyorrhexis, fibrin exudates and discontinuities in the basement membrane IgG, IgM, C1q and C3 precipitation
  • Hematoxylin bodies are formed of degenerate material from the nucleus, seen in only 25%, but diagnostic for SLE
  • Electron microscopy: electron dense structures (EDS) in mesangium, subendothelial, subepitelial
  • Podocytopathy (reference: Singh L, 2015) is a group of kidney diseases that attack cells with long thin outlets (podocytes) and which participates in the filtration of urine in kidney glomerulum.

Treatment of moderately-serious active lupus nephritis

The purpose of the treatment is to reduce the risk of end-stage renal failure and to reduce the mortality of the disease.

The treatment will always be individual, based on the severity of the disease, the patient's age and general condition, as well as the patient's wishes. Induction treatment is started to stop the inflammation. After 3-6 months, the disease is often in a calm phase (remission), and one can switch to milder maintenance treatment (reference: Fanouraiakis A, 2019)

There are several treatment regimens.

  • Methylprednisolone iv (Solu-Medrol) 750 mg / day for 3 days (lower dose in some cases, individual adjustment)
  • Cyclophosphamide (Sendoxane) Iv 500mg (or 7,5mg / kg) every in 3 months (EURO-Lupus protocol)
    • After 3 months: Transition to azathioprine (Imurel) 2 - 2,5 mg / kg / day or mycophenolate (CellCept, Myfortic) 1 -2 g / day
  • Alternatives to cyclophosphamide:
    • Mycophenolate (CellCept, Myfortic) 1 - 3 g / day (caution in low renal function)
    • Tacrolimus (Prograf) is an alternative if mycophenolate cannot be used. In severe cases, tacrolimus can be combined with Mycophenolate (caution in low renal function)
  • Prednisone
    • Week 1-4 Prednisolone 20 mg / day
    • Week 5-6 Prednisolone 15 mg / day
    • Week 7-8 Prednisolone 10 mg / day
    • Week 9-10 Prednisolone 7,5 mg / day
    • Week 11-6 Months Prednisolone 5 mg / day
    • After one year: Consider terminating Prednisolon

In nephrotic syndrome and low albumin in serum there is an increased risk of thromboembolism. Consider antithrombotic treatment

Control of proteinuria that is important prognostic factor, as well as reduce hematuria and stabilize GFR

  • Anti-proten uric treatment with ACE inhibitors (eg enalapril / Renitec) or AT-II inhibitors (eg losartan / Cozaar)
    • After initiation of treatment, proteinuria is expected to reach stable and low or absent levels after 18 months
    • After 3-4 months, measurable efficacy is expected
    • Lack of efficacy after 6-12 months is considered to be partially ineffective
    • If no effect after 24 months lacks a complete response
  • Hypertension (high blood pressure) is common in kidney disease and increases kidney damage, is associated with encephalopathy and increased cardiovascular complications. Routine treatment with ACE inhibitors or angiotensin receptor blockers is recommended
    • Blood pressure should not exceed 120 / 80 Hg
  • Regular monitoring over time is indicated in all cases
  • Renal manifestation rarely begins without other SLE manifestations also present
  • Plaquenil tablets have shown effects on disease activity, organ damage and survival (reference: Ruiz-Irastorza G, 2010)
  • In anemia caused by chronic renal failure, treatment with EPO (Aranesp) can be useful

After induction of lupus nephritis, at least three years of successive immunosuppressive therapy is recommended

Treatment options for lack of treatment effect (treatment resistant cases)

  • If Sendoxan (cyclophosphamide intravenously) is not effective, switch to mycophenolate (CellCept tablets) 2-3 g / day
  • If mycophenolate (CellCept) does not work, switch to Sendoxan is considered
  • If neither Sendoxan nor CellCept is working, rituximab (MabThera) may be considered
  • Tacrolimus has comparable efficacy to mycophenolate as induction therapy (Mug CC, 2020)
  • An alternative in treatment-resistant cases is to combine CellCept (1-2g / d) with Tacrolimus (4mg / kg / d in adults) (references: Liu Z, 2015 (induction treatment); Zhang H, 2017 (maintenance treatment)
  • Prednisolone is continued and stepped down over time. Initially, intravenous methylprednisolone (SoluMedrol) 500mg iv may be considered (eg three days in a row)


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