Table 1.
Summary of key features for each disease.
| Disease | Specific mechanisms of acute damage | Diagnosis | Kidney biopsy | Treatment | Apheresis | Prognostic markers |
|---|---|---|---|---|---|---|
| Anti- GBM disease | Autoantibody against the NC1 domain of the α3-chain of type IV collagen (46, 47) | Clinical signs Anti-GBM antibody CT Kidney/lung biopsy |
Diffuse proliferative GN, crescents, necrosis ± tubular loss IF: Linear deposition of IgG and C3 |
CYC (2 mg/kg/day) + Methylprednisolone (1 g/day for 3 days followed by tapering with oral prednisone) ± TPE |
TPE (Category III, Grade 2B) Volume treated: 1–1.5 TPV Frequency: Daily or every other day Duration: at least 10–20 days, or until resolution of evidence of ongoing glomerular or pulmonary injury |
Glomerular lesions: - crescents necrosis - Tubular damage Dialysis dependent sCr > 600 μmol/L |
| Small Vessel Vasculitis | ANCAs (PR3; MPO) and Neutrophils activation | Clinical signs ANCA antibody Radiological investigations Tissues biopsies/Kidney biopsy |
Necrotizing and extra-capillary crescentic GN Vascular segmental fibrinoid necrosis, sclerosis, thrombosis |
Induction therapy: Methylprednisolone (7 mg/Kg/day for 3 days followed by oral prednisolone 1 mg/Kg/day) + CYC (2 mg/kg/day) or, in alternative, RTX (375 mg/m2 weekly for 4 weeks) Maintenance therapy: AZA (1–2 mg/kg/day) or MMF (up to 1 g twice daily) or MTX (0.3 mg/kg/wk, maximum 25 mg/wk) or RTX |
TPE (Category I, Grade 1A) Volume treated: 1–1.5 TPV Frequency: Daily or every other day Duration: median number is 7, over a median period of 14 days, up to 12 for further improvement of renal function BVAS |
Glomerular lesions: - focal - crescents - mixed - sclerotic |
| SLE: lupus nephritis class IV | Immunocomplexes, complement, leucocytes, TMA | Kidney biopsy | Endocapillary or extracapillary GN, glomerulosclerosis, sub-endothelial immune deposits, tubular atrophy, interstitial fibrosis IF: “full house” pattern |
Induction therapy: CYC (low-dose: 500 mg every 2 weeks for 3 months or high-dose: 0.5–1 g/m2 monthly for 6 months)/MMF (2–3 g/daily) + Corticosteroids. In alternative, RTX (375 mg/m2 weekly for 4 weeks) Maintenance therapy: Low dose Prednisone (<10 mg/day) + AZA (1.5–2 mg/kg/day) or MMF (1–2 g/day in two doses) for at least 12 months after complete remission. CNIs (in patients intolerant to MMF or AZA) |
TPE (Category II, Grade 2C) Volume treated: 1–1.5 TPV Frequency: LN or DAH: daily or every other day; Other severe complications: 1–3 times per week Duration: course of 3–6 TPE |
Glomerular lesions: - crescents - necrosis Heavy proteinuria Racial background |
| IgAN | Massive hematuria; erytro-phagocytosis process, crescents | Kidney biopsy | Mesangial hypercellularity, focal segmental necrotizing GN, crescents, glomerulosclerosis, tubule-interstitial inflammation ± fibrosis | High-dose corticosteroids (Methylprednisolone 1 g/daily for three consecutive days, followed by oral prednisone 0.5 mg/kg/day and subsequent tapering/Oral prednisone 1 mg/kg/day for 2 months followed by tapering) for 6 months + CYC (1–2 mg/kg/day) for 3 months, followed by AZA (1–2 mg/kg/day) for 3 months |
TPE (Category III, Grade 2C) Volume treated: 1–1.5 TPV Frequency: 4–11 over 21 days Duration: until clinical resolution |
High sCr Crescents Duration of hematuria |
| Post-streptococcal GN | Immunocomplexes, complement, leucocytes | Clinical signs Antistreptolysin O and anti–DNase B antibodies |
Diffuse endocapillary GN, monocytes and lymphocytes infiltration | No specific immunosuppressive treatment |
TPE (Category III, Grade 2B) Volume treated: 1–1.5 TPV Frequency: Daily or every other day Duration: 3–6 TPE over 1–2 weeks |
Deficiency of complement regulatory proteins Nephrotic proteinuria Age Diabetic nephropathy |
| TMA | TMA |
TTP: ADAMTS 13 activity, Anti ADAMTS13 autoantibody STEC-HUS: STEC (cultured test) or STX (P.C.R.) aHUS: microangiopathic haemolytic anemia, acute kidney injury, ADAMTS13 and STEC-HUS negativity |
Intraluminal platelet thrombi, partial or complete obstruction of vessel lumina, myointimal proliferation and reduplication of the lamina densa, sever ischemic change |
TTP: ADAMTS 13 auto-antibodies: TPE +/prednisone/prednisolone or RTX Maintenance therapy: PI: Caplacizumab + TPE + immunosuppressive therapy STEC-HUS: i.v 10–15 ml/kg/h of isotonic solution; Eculizumab (900 mg/ weakly for 4 weeks, followed by 1,200 mg every 2 weeks) and/or TPE/PI aHUS: Eculizumab (900 mg/ weakly for 4 weeks, followed by 1,200 mg every 2 weeks) FHAA-mediated aHUS: TPE + immunosuppressive therapy |
TPE (Category III, Grade 2C) Volume treated: 1–1.5 TPV Frequency: Daily Duration: No standardized approach, duration and schedule should be made based upon patient response and condition |
TTP: ADAMTS 13 activity; severe neurological signs; haemolysis STEC-HUS: severe neurological signs; haemolysis aHUS: genetic background |
| MPGN and Mixed Cryoglobulinemia | Immunocomplexes | Cryoglobulins, HCV markers; clinical signs/ symptoms | Mesangial and endocapillary proliferation, extracellular matrix expansion, diffuse leucocytes and monocytes infiltration, double-contouring of the GBM, intraluminal thrombi | TPE + RTX(375 mg7m2/week for 4 weeks)/CYC (2 mg/Kg/day for 2–4 months), + i.v. methylprednisolone (0.5/1 g/Kg/day for three consecutive days followed by oral prednisone), + antiviral therapy |
TPE (Category II, Grade 2B) Volume treated: 1–1.5 TPV Frequency: Every 1–3 days Duration: 3–8 procedures for acute symptoms, weekly or monthly maintenance treatments to prevent recurrent symptoms |
High sCr Nephrotic proteinuria Severe hypertension >50% crescents Marked interstitial fibrosis |
| Membranous nephropathy | Volume depletion Ischemic tubular damage |
Kidney biopsy | Uniform increase in thickness of glomerular capillary walls, double-contouring and “spikes” of the GBM. IF: Diffuse, finely granular deposition of IgG along outer surface of all capillary walls |
Volume correction | – | Severe hypoalbuminemia, age, male sex |
| Scleroderma | Ischemia, microangiopathy | Clinical signs; ANA and anti scl-70 antibody | Malignant hypertensions lesions, TMA in small interlobular and arcuate arteries Glomerular ischemic collapse; fibrinoid necrosis ± tubular atrophy and interstitial fibrosis | ACE-i TPE/ECP |
TPE (Category III, Grade 2C) Volume treated: 1–1.5 TPV Frequency: 1–3 per week Duration: course of 6 TPE over the 2–3 weeks followed by 4 weekly treatments. Long-term TPE protocol (2–3 weekly for 2 weeks, 1 TPE weekly for 3 months, and 1 TPE every other week as a maintenance therapy) was also used. ECP Volume treated: Typically, 1.5 L of whole blood processed Frequency and Duration: Two procedures on consecutive days (one series) every 4–6 wk for 6–12 months |
Anti-DNA polymerase |
GBM, Glomerular Basement Membrane; CT, Computer Tomography; GN, glomerulonephritis; IF, immunofluorescence; CYC, cyclophosphamide; TPE, therapeutic plasma exchange; sCr, serum creatinine; ANCAs, anti-neutrophil cytoplasmic autoantibodies, PR3, proteinase 3; MPO, myeloperosidase; RTX, Rituximab; AZA, azathioprine; MMF, mycophenolate; MTX, methotrexate; BVAS, Birmingham Vasculitis Activity Score; SLE, Systemic Lupus Erythematosus; TMA, Thrombotic Microangiopathy; IgA N, IgA nephropathy; TTP, thrombotic thrombocytopenic purpura; STEC-HUS, Shiga-toxin producing E. coli-associated Hemolytic Uremic Syndrome; STEX, Shiga-toxin; PCR, polymerase chain reaction; aHUS: atypical Hemolytic Uremic Syndrome; PI, Plasma Infusion; i.v., intravenous; FHAA-HUS, Factor H antibody associated Hemolytic Uremic Syndrome; MPGN, Membranoproliferative Glomerulonephritis; ANA, Anti-nuclear antibody; anti scl-70, anti-topoisomerase antibody, ACE-i, ACE inhibitors; ECP, Extracorporeal photopheresis.