approach to the patient with glomerular diseases gülçin kantarcı, md professor of nephrology...
TRANSCRIPT
![Page 1: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/1.jpg)
APPROACH TO THE PATİENT WİTH GLOMERULAR DİSEASES
Gülçin Kantarcı, MD
Professor of
Nephrology Department
![Page 2: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/2.jpg)
OBJECTIVES (knowledge, skills and attitudes)Knowledge:
At the end of this lecture the students
1. Has a good understanding the diagnosis and the differential diagnosis of Glomerular Diseases with their emergent treatment requirements and methods.
2. Has a knowledge about diagnosis methods of Glomerular Diseases. (Laboratuary tests, screening tests, other invasive and non-invasive medical procedures)
Skills:
3. Can name the possible diagnosis and make a differential diagnosis of Glomerular Diseases .
4. Can use the diagnosis methods for Glomerular Diseases economically and properly.(Lab. tests, screening tests, other invasive and non-invasive medical procedures)
5. Can interpret the result of these test correctly.
6. Can choose between emergent and non-emergent situations, and give emergent treatment for diseases.
Attitudes:
7. Presents a worthy thought, attitude and behavior appropriate for a physician in patient communication.
![Page 3: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/3.jpg)
REFERENCE
1. Current Medical Diagnosis and Treatment, Maxine A. Papadakis, Stephen J. McPhee, Eds. Michael W. Rabow, Associate Ed. http://accessmedicine.com
Chapter 22. Glomerular Diseases
2. Bates' Guide to Physical Examination & History Taking 11th edition, Bickleys LS, Szilagyi PG; Lippincott Williams and Wilkins¸
3. Kumar and Clark's Clinical Medicine, 8th edition; Kumar & Clark, Elsevier
4. Andreoli and Carpenter's Cecil Essentials of Medicine 8th edition, Andreoli and Carpenter, Elsevier
PART 11: RENAL AND GENITOURINARY DISEASES 123: Glomerular Disorders and Nephrotic Syndromes
![Page 4: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/4.jpg)
![Page 5: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/5.jpg)
![Page 6: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/6.jpg)
Glomerulus
![Page 7: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/7.jpg)
• Most glomerular diseases are immune-mediated, and described as glomerulonephritis (GN).
![Page 8: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/8.jpg)
GLOMERULAR INFLAMMATION AND INJURY
![Page 9: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/9.jpg)
![Page 10: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/10.jpg)
GLOMERULONEPHRITIS
Primary GN • Minimal Change Disease• FSGS• Membranous GN• Idiopatic MPGN• IgA nephropathy• Proliferatif GN
![Page 11: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/11.jpg)
Sekonder GN
İnfective Fungi (Candida albicans,Coccidioides immitis) Rickettsiae
Connective tissue diseases Henoch-Schönlein purpura Polyarteritis nodosa SLE Wegener’s granulomatosis
Glomerular basement membrane diseases Goodpasture’s syndrome
Hematologic dyscrasias Mixed IgG-IgM cryoglobulinemia Serum sickness Thrombotic thrombocytopenic purpura–hemolyticuremic syndrome
![Page 12: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/12.jpg)
Viral:
Coxsackievirus Cytomegalovirus Epstein-Barr virus Hepatitis B virus Hepatitis C virus Herpes zoster virus Measles Mumps Varicella
![Page 13: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/13.jpg)
GLOMERULAR DISEASES WITHNEPHROTIC SYNDROME
Nephrotic synd: edema, Nephrotic-range proteinuria) greater than 50 mg/kg per day or 40 mg/h/m2 in children and 3.5 g/24 h in adults , hyperlipidemia•Minimal change disease (MCD)•Focal Segmental Glomerulosclerosis (FSGS)•Membranous nephropathy (MN)
![Page 14: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/14.jpg)
MINIMAL CHANGE DISEASE (MCD)
• characterized initially by dramatic increases in glomerular permeability in association with little or no structural abnormalities by light microscopy.
• lipoid nephrosis Munk (1913) • MCD is most common in children, In adults,especially in
elderlies associated with secondary causes• 70% to 90% of cases of nephrotic syndrome in children
younger than age 10 years and 50% of cases in older children.
• Minimal change glomerulopathy also causes 10% to 15% of cases of primary nephrotic syndrome in adults.
• %15-20 nephritic features may occur• MCD in children mostly (%80-90) idiopatic
![Page 15: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/15.jpg)
HISTOPATHOLOGY• The principal target of injury is the podocyte,
***podocytopathies• Light microscopy: lack of definitive alteration in glomerular
structure. Lipid droplets in the tubuler cells• Immunofluorescence: also shows no change• Electron mic: fusion of epithelial foot processes
![Page 16: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/16.jpg)
Minimal-change disease (electron microscopy) The glomerular basement membrane is normal; the cytoplasm of the podocytes is vacuolated, with effacement of foot processes and microvilli. Methenamine silver, 2800×.
![Page 17: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/17.jpg)
Laboratory findings of MCD• severe proteinuria. • Microscopic hematuria is seen in fewer than 15% of patients. • Volume contraction may lead to a rise in both the hematocrit and
hemoglobin. • ESR is increased as a consequence of hyperfibrinogenemia as well as
hypoalbuminemia. • The serum albumin <2 g/dL and, in more severe cases, <1 g/dL. • Total cholesterol, LDL, and triglyceride levels are increased.• Pseudohyponatremia has been observed in the setting of marked
hyperlipidemia.• Renal function is usually normal, although a minority of patients have
substantial AKI.• IgG levels may be profoundly decreased—a factor that may result in
susceptibility to infections. • Complement levels are typically normal in patients with minimal change
glomerulopathy
![Page 18: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/18.jpg)
Secondary causes of MCD
• Drugs -NSAID -penicillin -trimetoprim• Toxins -Mercury -lead -bee stings
• Infection -Mononucleosis - HIV - Immunizations• Tumors -Hodgkins lymphoma -other lymhoproliferative dis., -Carcinoma• Obesity
![Page 19: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/19.jpg)
• Emprical steroid theraphy for children <10• In children who have received empirical treatment, a renal
biopsy is indicated when there is failure to respond to a 4- to 6-week course of prednisone.
• oral prednisone be administered as a single daily dose starting at 60 mg/m2 /day
• or 2 mg/kg/day to a maximum 60 mg/day
Specific treatment: corticosteroids
![Page 20: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/20.jpg)
Clinical course of MCD as related to steroid theraphy• STEROID-SENSITIVE NEPHROTIC SYNDROME (SSNS)
- complete remission of proteinuria within 8-12 weeks with infrequent relapses
• FREQUENTLY RELAPSING and STEROID DEPENDENT (FR-SD)
-relapses occur during the taper of steroids -relapses occur at rate of twice every 6 months or six times every 18 months
-relapses occur within 2 weeks of cessation of theraphy• STEROID-RESISTANT NEPHROTIC SYNDROME (SRNS)
-Failure to obtain a remission within 12 weeks
![Page 21: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/21.jpg)
PROGNOSIS • In adults 85-90 % survival rate• The potential efficacy of therapy must be considered in
relation to the natural history of the disease. • Untreated idiopathic MCD was associated with a risk of
mortality due to infection and less commonly thromboembolism
![Page 22: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/22.jpg)
complications• Related to persistent NS (peritonitis, ARF, CKD in
steroid resistant patients)
• Side effect of therapy( stra, cataracts, acne, cushingoid face, hyperglisemia, HT)
![Page 23: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/23.jpg)
FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)
• an important lesion found to underly the nephrotic syndrome in adults and a frequent lesion in children and adolescents
• Pathology: a focal process; not all glomeruli are involved, the glomeruli are segmentally sclerotic, and portions of the involved glomeruli may appear normal by light microscopy.
• Nonsclerotic glomeruli and segments usually have no staining for immunoglobulins or complement.
• The ultrastructural features of FSGS on electron microscopy include focal foot process effacement.
![Page 24: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/24.jpg)
FSGS
![Page 25: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/25.jpg)
histologic variants
Classical
CollapsingTip lesions
NORMAL Glomerulus
![Page 26: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/26.jpg)
Laboratory findings
• Hypoproteinemia is common in patients with FSGS and the serum albumin concentration may fall to below 2 g/dL, especially in patients with the collapsing variant.
• Hypogammaglobulinema and hyperlipidemia are typical; serum complement components are generally in the normal range.
• Serologic testing for HIV infection should be obtained for all patients with FSGS, especially those with the collapsing pattern.
![Page 27: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/27.jpg)
Clinical manifestations
peripheral edema, hypoalbuminemia, and nephrotic range proteinuria. Patients with FSGS also commonly have hypertension, and many have microscopic hematuria.
The level of kidney function may vary.
![Page 28: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/28.jpg)
The relative frequencies of clinical manifestations :
Nephrotic range proteinuria - 60 to 75 % Microscopic hematuria - 30 to 50 %Hypertension - 45 to 65 %Renal insufficiency - 25 to 50 %
![Page 29: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/29.jpg)
PROGNOSIS OF FGS• Untreated primary FSGS often follows a progressive course to end-stage renal disease (ESRD).
• The rate of spontaneous complete remission among patients with nephrotic syndrome is unknown, but is probably less than 10 percent.
• Spontaneous remission is more likely to occur among patients with normal kidney function and non-nephrotic proteinuria.
![Page 30: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/30.jpg)
Response to therapy
• The strongest prognostic indicator is the degrees of reduction in proteinuria
• complete response : <200 to 300 mg/day. • partial response reduction ≥ 50 %• relapse is return of proteinuria to ≥ 3.5 g/day after a complete or partial remission.
• Steroid-dependence relapse while on therapy or requirement for continuation of steroids
• Steroid-resistance little or no reduction in proteinuria after 12 to 16 weeks of prednisone therapy
![Page 31: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/31.jpg)
Therapy of MCD & FSGS
• Prednisone theraphy: not to exceed 60 mg/day
• 50% responding 2-6 wk
• Cyclosporine therapy is the second choice for FSGS
![Page 32: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/32.jpg)
• ACEI may provide a substantial reduction in proteinuria and a long-term renoprotective effect that may be equal to,or greater than, that of immunosuppressive therapy.
• Response rates to immunosuppressive therapy in primary FSGS
45% for complete remission,
10% for partial remission,
45% for no response.
![Page 33: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/33.jpg)
Membranous GN
• Idiopathic membranous glomerulopathy is the most common cause of nephrotic syndrome in adults (25% of adult cases) and can occur as an idiopathic (primary) or secondary disease.
• Secondary membranous glomerulopathy is caused by autoimmune diseases (e.g., lupus erythematosus, autoimmune thyroiditis),infection (e.g., hepatitis B, hepatitis C), drugs (e.g., penicillamine,gold), and malignancies (e.g., colon cancer, lung cancer).
![Page 34: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/34.jpg)
Membranous GN
• In patients over the age of 60, membranous glomerulopathy is associated with a malignancy in 20% to 30% of patients. The peak incidence of membranous glomerulopathy is in the fourth or fifth decade of life.
Pathology• The characteristic histologic abnormality in MGN is diffuse
global capillary wall thickening and the presence of subepithelial immune complex deposits.
![Page 35: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/35.jpg)
The immun deposits of Ig G and complement components develop on the subepithelial surface of the glomerular capillary wall
![Page 36: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/36.jpg)
Light microscopy in membranous nephropathy, uniform increase in the thickness of the glomerular capillary walls throughout the glomerulus without any increase in glomerularcellularity. Spikes of matrix emanating from the outer surface of the basement membrane indicative of advanced MN are revealed by silver–methenamine stain (×400).
spikes
![Page 37: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/37.jpg)
Conditions associated with (secondary) MGN
group common uncommon
Immun dis. SLE, DM RA, Hashimoto’s dis.Ankylosing spondylis.Pr. Biliary cirrhosis
Infectious HBV HCV, malaria, syphilis
Drugs and toxins Gold , NSAIDs Mercury, captopril, formaldehyde
Miscellaous Tumors, renal transplant
Sarcoidosis,Sickle cell dis.
![Page 38: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/38.jpg)
Clinical manifectations• Nephrotic syndrome 80%• Asymtomatic non-nephrotic proteinuria 20%• Proteinuria (5-15 g/day)• Microscobic hematuria may be seen 50% of adults• Renal vein thrombosis 40%• Renal function usually well preserved at the on set of dis.
![Page 39: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/39.jpg)
Common secondary causes• Membranous lupus nephritis (Class V)• Hepatitis B• Cancer (adults over 50 years incidence of malignancy in
MGN 20%)• Renal allografts
![Page 40: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/40.jpg)
Prognosis of pr. MGN• Spontaneous complete remission of proteinuria occurs in
5 to 30 %• Spontaneous partial remission (≤ 2 g of proteinuria per
day) occurs in 25 to 40 %• ESRD in untreated patients is 14 % at 5 years, 35 % at 10 years, 41 % at 15 years
![Page 41: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/41.jpg)
Laboratory findings in MGN• Proteinuria is usually more than 3 g of protein per 24 hours and
may exceed 10 g/day in 30% of patients. • Microscopic hematuria is present in 30% to 50% of patients• Renal function is typically preserved at presentation.• Hypoalbuminemia is observed if proteinuria is severe. • Complement levels are normal; however, the complex of
terminal complement components known as C5b-9 is found in the urine in some patients.
• Tests for hepatitis B, hepatitis C, syphilis, and immunologic disorders such as lupus, mixed connective tissue disease, and cryoglobulinemia should be obtained to exclude secondary causes.
![Page 42: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/42.jpg)
Theraphy of MGN• Supportive care including ACEI, lipid-lowering therapy • Corticosteroids• Alkylating agents (chlorambucil or cyclophosphamide),with
or without concurrent corticosteroid treatment -Chlorambucil (0.2 mg/kg/day) or cyclophosphamide, alternating
monthly with daily prednisone(0.5 mg/kg/day), in combination with intravenous pulse methylprednisolone(1 g/day) for the first 3 days of each month
• Cyclosporine• The high prevalence of deep vein thrombosis in patients
with membranous glomerulopathy (up to 45%) has led to the use of prophylactic anticoagulation for patients with proteinuria greater than 10 g/day
![Page 43: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/43.jpg)
Management of MGN• Adult patients with good prognostic features, with less than
4 g/day proteinuria and normal renal function, should be managed conservatively.
• Patients at moderate risk (persistent proteinuria between 4 and 6 g/day after 6 months of conservative therapy and normal renal function) or high risk of progression (persistent proteinuria greater than 8 g/day with or without renal insufficiency) should be considered for immunosuppressive therapy
• Individuals who have advanced chronic kidney disease and in whom serum creatinine exceeds 3 to 4 mg/dL are best treated by supportive care awaiting dialysis and renal transplantation
![Page 44: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/44.jpg)
Membranoproliferative GN(Mesangial Capillary Glomerulonephritis)
• MPGN is characterized by diffuse global capillary wall thickening, frequently with a double contoured appearance and either subendothelial deposits (type I MPGN) or deposits within the mesangium and basement membrane (type IIMPGN).
![Page 45: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/45.jpg)
Clinical presentations of MPGN• Nephrotic syndrome (50%)• Combination of asymptomatic hematuria and proteinuria
(25%)• Acute nephritic syndrome (25%)• Hypertension is typically mild • renal dysfunction occurs ( 50%)
![Page 46: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/46.jpg)
Classification of MPGN
![Page 47: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/47.jpg)
Histology of MPGN
light microscopy:• thickening of the glomerular basement membrane
(GBM), due to immune complex deposition and to interposition of the mesangial cell cytoplasm between the GBM and the endothelial cell;
• hypercellularity, lobular appearance of the glomerular tuft
![Page 48: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/48.jpg)
lobular appearance of the glomerular tuft increased glomerular cellularity
thickening of all capillary walls with double contours, cellular proliferation
![Page 49: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/49.jpg)
![Page 50: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/50.jpg)
TYPES OF MPGN
Primary or idiopathic• Type I: mesangiocapillary GN• Type II: dense deposit disease• Type III: an immune complex disease, similar to type 1.
![Page 51: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/51.jpg)
Secondary (associated with other diseases)
With immun deposits Infections –crioglobulinemia - HBV,HCV, Endocarditis, Malaria, EBV,HIV,mycoplasmaAutoimmun diseases -SLE,RA,Sjörgen’s syndromeDysproteinemia -Light chain deposit dis.,Waldernstrom’s macroglobulinemia, fibrilar
Without immun depositsChronic liver disease -Cirrhosis, α1 antitripsin deficiencyThrombotic microangiopathies - HUS/TTP, Antiphospholipid antibody Syn,Sickle cell anemia
![Page 52: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/52.jpg)
Laboratory findings
• Hematuria is the hallmark of patients presenting with MGPN,• The degree of proteinuria varies widely. • Renal insufficiency occurs in a variable number of cases, but it is
the most ominous feature of the acute nephritic syndrome. • Serologic and clinical evidence of cryoglobulinemia,hepatitis C,
hepatitis B, osteomyelitis, subacute bacterial endocarditis, or infected ventriculoatrial shunt should be sought in type I MGPN.
• C3 is persistently depressed in approximately 75%to 90%of MPGN patients.
• C3 nephritic factor is found in 60% of cases of type II MPGN.
![Page 53: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/53.jpg)
PROGNOSIS bad prognostic signs:at presentation include
• the nephrotic syndrome, • renal insufficiency, • hypertension, • on renal biopsy, crescents
good long-term prognosis: asymptomatic hematuria and proteinuria ,focal glomerular involvement on renal biopsy.
![Page 54: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/54.jpg)
Theraphy of MPGN • The treatment of type I MPGN is based on the underlying
cause of the disease process. MPGN associated with cryoglobulinemia and hepatitis C should be aimed at treating hepatitis C virus infection (interferon/ribavirin),
• The treatment of MPGN associated with lupus or with scleroderma should be based on the principles of care of those rheumatologic conditions.
• Most recommendations for the treatment of idiopathic type I MPGN are limited to studies in children where low-dose prednisone therapy improves renal survival.
![Page 55: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/55.jpg)
New immunsuppresive regiments
• mycophenolate mofetil + corticosteroids
(5 grams/day at baseline to 2 and 2.6 grams/24 hours at 12 and 18 months),
Original ArticleMycophenolate mofetil treatment for therapy-resistantglomerulopathies SAHIN GM, SAHIN S, KANTARCI G.NEPHROLOGY 2007; 12, 285–288
![Page 56: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/56.jpg)
GLOMERULAR DISEASES THAT CAUSENEPHRITIC SYNDROME
IgA nephropathy (IgAN)
• Most common lesion found to cause primary glomerulonephritis throughout most developed countries of the world.
• IgA nephropathy common among Asians and Caucasians, • 2:1 male to female predominance. • The etiology of IgA nephropathy is unknown, but infections
and/or genetic characteristics may predispose to the development of kidney disease.
• IgA nephropathy is often suspected on the basis of the clinical history, but can be confirmed only by kidney biopsy.
![Page 57: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/57.jpg)
Clinical findingsMost patients with IgAN present with• gross hematuria (single or recurrent), usually following an upper respiratory infection (40–50%)
• microscopic hematuria with or without mild proteinuria incidentally detected on a routine examination. (40%)
• Nephritic syndrome (10%)• Malignant hypertension (<5%)
• Rarely, patients may develop AKI with or without oliguria, due either to crescentic IgAN, or to gross hematuria causing tubular occlusion and/or damage by red cells.
![Page 58: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/58.jpg)
Clinical features of IgAN
• Episodes of macroscopic hematuria tend to occur with a close temporal relationship to upper respiratory infection,including tonsillitis or pharyngitis.
• The timing differs from that for PSGN, which has an interval period of 7 to 14 days between the onset of infection and overt hematuria.
![Page 59: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/59.jpg)
Clinical features of IgAN
• Systemic symptoms are frequently found, including nonspecific symptoms such as malaise, fatigue, muscle aches and pains, and fever.
• Microscopic hematuria and proteinuria persist between episodes of macroscopic hematuria.
• Associated hypertension is common
![Page 60: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/60.jpg)
Clinical features of IgAN• Although IgA nephropathy was previously thought to carry
a relatively benign prognosis, it is estimated that renal insufficiency may occur in 20% to 30% of patients within 2 decades of the original presentation.
• Renal failure typically follows a slowly progressive course, a minority of patients with IgA nephropathy manifests a fulminant course resulting in a rapid progression to end-stage renal disease.
![Page 61: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/61.jpg)
IgA nephropathy may be the glomerular expression of a systemic disease Henoch-Schönlein purpura
![Page 62: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/62.jpg)
poor prognoctic features
• Sustained hypertension, • Persistent proteinuria greater than 1 g/day,• Impaired renal function,• Nephrotic syndrome
![Page 63: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/63.jpg)
Laboratory Findings of IgAN• microscopic hematuria and dysmorphic erythrocytes• Proteinuria majority of subjects have less than 1 g/day of
protein.• There are no specific serologic or laboratory tests
diagnostic of IgA nephropathy or Henoch-Schönlein purpura.
• Although serum IgA levels are elevated in up to 50% of patients, the presence of elevated IgA in the circulation is not specific for IgA nephropathy.
• Complement levels such as C3 and C4 are typically normal
![Page 64: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/64.jpg)
PATHOLOGYimmunofluorescence microscopy• globular deposits of IgA (often accompanied by C3 and
IgG) in the mesangium and, to a lesser degree, along the glomerular capillary wall.
large, globular mesangial IgA deposits
![Page 65: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/65.jpg)
Treatment of IgAN
![Page 66: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/66.jpg)
![Page 67: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/67.jpg)
• ACE-I or ARB treatment (1B) in IgAN, use blood pressure treatment goals of 130/80mmHg in patients with proteinuria <1 g/day, and
125/75mmHg when initial proteinuria is >1 g/day• Corticosteroids(2C)in IgAN patients with persistent
proteinuria>1 g/day, despite 3–6 months of optimized supportive care (including ACE-I or ARBs and blood pressure control), and GFR >50 ml/min per 1.73m2, receive a 6-month course of corticosteroid therapy.
• Fish oil in treatment(2D)of IgAN with persistent proteinuria >1 g/d, despite 3–6months of optimized supportive care (including ACE-I or ARBs and blood pressure control).
![Page 68: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/68.jpg)
Immunosuppressive agents (cyclophosphamide, azathioprine, MMF, cyclosporine)
• We suggest not treating with corticosteroids combined with cyclophosphamide or azathioprine in IgAN patients (unless there is crescentic IgAN with rapidly deteriorating kidney function (2D)
• We suggest not using immunosuppressive therapy in patients with GFR <30 ml/min per 1.73m2 unless there
is crescentic IgAN with rapidly deteriorating kidney function
![Page 69: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/69.jpg)
Glomerular Diseases Associated with Infection • GN may occur as a concequence of infections. • Post strep. GN: Patients presenting with features of
acute GN recent infection of pharynx or skin with group A b-hemolytic strep.
• Diagnosis is suggested by history and urinalysis and confirmed by low complement. Prognosis is excellent. Treatment is supportive
![Page 70: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/70.jpg)
Acute poststreptococcal glomerulonephritis (PSGN)• affects primarily children, with peak incidence between the ages of 2
and 6 years. • It may occur as part of an epidemic or sporadic disease, and only
rarely do PSGN and rheumatic fever occur concomitantly.• A latent period is present (7–21 days) from the onset of pharyngitis to
that of nephritis. • The hematuria is microscopic in more than two thirds of cases.• Hypertension occurs in more than 75% of patients• The clinical manifestations of acute PSGN typically resolve in 1 to 2
weeks as the edema and hypertension disappear after diuresis.• Both the hematuria and proteinuria may persist for several months,
but are usually resolved within a year.
![Page 71: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/71.jpg)
Laboratory findings• presence of dysmorphic red blood cells or red
blood cell casts. • Proteinuria is nearly always present, typically
in the subnephrotic range. • Nephrotic-range proteinuria may occur in as many as 20%
of patients and is more frequent in adults than in children.• Throat or skin cultures may reveal group A streptococci• elevated ASO titer above 200 units may be found in 90%
of patients;• CH50 and C3 are reduced
![Page 72: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/72.jpg)
Diffuse proliferative GN
![Page 73: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/73.jpg)
Treatment of acute PSGN• Supportive • Supportive therapy may require the use of loop diuretics
such as furosemide to ameliorate volume expansion and hypertension
![Page 74: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/74.jpg)
![Page 75: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/75.jpg)
RAPIDLY PROGRESSIVE GLOMERULONEPHRITISAND CRESCENTIC GLOMERULONEPHRITIS
• Immune Complex–Mediated Crescentic GN (e.g., MPGN, PSGN, or IgA nephropathy)
• Anti–Glomerular Basement Membrane GN• 10% to 20% of crescentic GN• This disease is characterized by circulating antibodies to the GBM and
deposition of IgG or rarely IgA along the GBM. Anti-GBM disease occurs as a renal-limited disease (anti-GBM glomerulonephritis) and as a pulmonary-renal vasculitic syndrome (Goodpasture syndrome).
• Pauci-Immune Crescentic Glomerulonephritis
![Page 76: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/76.jpg)
Renal and Systemic Vasculitis
![Page 77: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/77.jpg)
Segmental glomerular necrosis and crescent formation in a patient with ANCA–associated small vessel vasculitis. The fibrinoid material is red. The uninvolved segments appear normal.
Pauci-Immune Crescentic Glomerulonephritis• The characteristic feature of
pauci-immune crescentic glomerulonephritis is a focal necrotizing and crescentic glomerulonephritis in association with a circulating ANCA.
• Pauci-immune crescentic glomerulonephritis is usually a component of a systemic small vessel vasculitis,
![Page 78: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/78.jpg)
ANCA-associated syndromes
• Microscopic polyangiitis• Wegener granulomatosis • Churg-Strauss syndrome
![Page 79: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/79.jpg)
• The presence of arteritis in a biopsy specimen with pauci-immune crescentic glomerulonephritis indicates that the glomerulonephritis is a component of a more widespread vasculitis, such as microscopic polyangiitis,
• Wegener granulomatosis,or the Churg-Strauss syndrome. • The pathogenesis of pauci-immune crescentic
glomerulonephritis is currently not fully understood.• Many patients have a circulating ANCA, it has not been
conclusively proved that ANCA are involved in the pathogenesis of pauci-immune small vessel vasculitis or glomerulonephritis.
![Page 80: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/80.jpg)
Laboratory Findings
• Approximately 80% to 90% of patients with pauci-immune necrotizing and crescentic glomerulonephritis will have a circulating ANCA.
• By indirect fluorescence microscopy on alcohol fixed neutrophils, ANCA yields two patterns of staining:
• perinuclear (P-ANCA) • cytoplasmic (C-ANCA)
![Page 81: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/81.jpg)
• 60-70 % patients with pauci-immune necrotizing
crescentic glomerulonephritis without clinical evidence of
Systemic vasculitis will have MPO-ANCA or P-ANCA, • approximately 30% will have PR3-ANCA or C-ANCA.
• Urinalysis findings include hematuria with dysmorphic red blood cells, with or without red blood cell casts, and proteinuria.
• Serum creatinine usually is elevated at the time of diagnosis and rising
• Serum complement component levels are typically within
normal limits.
![Page 82: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/82.jpg)
Fibrillary immunotactoid glomerulopathy• characterized by patterned deposits seen by electron
microscopy. • Most renal pathologists distinguish fibrillary
glomerulonephritis from immunotactoid glomerulopathy based on the presence of fibrils of approximately 20-nm diameter in the former and larger 30- to 40-nm diameter microtubular structures
• The etiology and pathogenesis of fibrillary glomerulonephritis and immunotactoid glomerulopathy are not known, but both conditions have been associated with lymphoproliferative diseases.
![Page 83: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/83.jpg)
Clinical features
• less than 1% of native renal biopsies.• Patients typically present with a mixture of the nephrotic and
nephritic syndrome features. • Proteinuria is typically in the nephrotic range.• Renal insufficiency, hematuria, and hypertension are
common at the time of presentation.• 40% to 50% of patients develop end-stage renal disease
within 6 years of presentation
![Page 84: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/84.jpg)
Secondary Glomerular Diseases
- SLE- Antiphospholipid antibody syndrome- Polyarteritis nodosa- Churg-Strauss syndrome- Glomerular involvement in other vasculitides (temporal arteritis,takayasu disease)
- Sjögren syndrome, sarcoidosis, amyloidosis, monoclonal immunoglobulin deposition disease
![Page 85: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/85.jpg)
Lupus nephritis• Renal involvement is common in idiopathic systemic lupus
erythematosus (SLE). • An abnormal urinalysis with or without an elevated
plasma creatinine is present in a large proportion of patients at the time of diagnosis, and may eventually develop in more than 75 % of cases.
![Page 86: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/86.jpg)
EPIDEMIOLOGY • The prevalence of clinically evident renal disease in
patients with SLE ranges from 40 to 75 percent.• Most renal abnormalities emerge soon after diagnosis
(commonly within the first 6 to 36 months)
![Page 87: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/87.jpg)
PATHOGENESIS• The pattern of glomerular injury seen in systemic lupus
erythematosus (and in other immune complex-mediated glomerular diseases) is primarily related to the site of formation of the immune deposits, which are primarily due to anti-DNA.
![Page 88: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/88.jpg)
![Page 89: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/89.jpg)
Treatment of LN• Class I LN (minimal-mesangial LN)treated as dictated by the
extrarenal clinical manifestations of lupus. (2D)• Class II LN (mesangial-proliferative LN) and proteinuria <1 g/d
as dictated by the extrarenal clinical manifestations of
lupus. (2D)• Class II LN with proteinuria >3 g/d be treated with
corticosteroids or CNIs as described for MCD (2D)• Class III LN (focal LN) and class IV LN (diffuse LN)—initial
therapy initial therapy with corticosteroids (1A), combined with either cyclophosphamide (1B) or MMF (1B).
• If patients have worsening LN (rising SCr, worsening proteinuria) during the first 3 months of treatment, a change be made to an alternative recommended initial therapy, or a repeat kidney biopsy be performed to guide further treatment. (2D)
![Page 90: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/90.jpg)
Class III LN (focal LN) and class IV LN (diffuse LN)—maintenance therapy
• after initial therapy is complete, patients with class III and IV LN receive maintenance therapy with azathioprine (1.5–2.5 mg/kg/d) or MMF (1–2 g/d in divided doses), and low-dose oralcorticosteroids (1B)
• CNIs with low-dose corticosteroids be used for maintenance therapy in patients who are intolerant of MMF and azathioprine. (2C)
• After complete remission is achieved, maintenance therapy be continued for at least 1 year before consideration is given to tapering the immunosuppression. (2D)
![Page 91: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/91.jpg)
class V LN• We recommend that patients with class V LN, normal
kidney function, and non–nephrotic-range proteinuria be treated with antiproteinuric and antihypertensive medications, and only receive corticosteroids and immunosuppressives as dictated by the extrarenal manifestations of systemic lupus. (2D)
• We suggest that patients with pure class V LN and persistent nephrotic proteinuria be treated with corticosteroids plus an additional immunosuppressive agent: cyclophosphamide (2C), or CNI (2C), or MMF(2D), or azathioprine (2D).
![Page 92: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/92.jpg)
C1 q Nephropathy• C1q nephropathy refers to a disorder in which mesangial
proliferation is associated with mesangial deposits on electron microscopy and prominent C1q deposits on immunofluorescence microscopy.
• C1q nephropathy has been thought to be a subgroup of primary focal segmental glomerular sclerosis
![Page 93: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/93.jpg)
• reports describe different symptoms, histopathologies, therapeutic responses and prognoses, suggesting that C1q nephropathy may be a combination of several disease groups rather than a single disease entity.
• C1q nephropathy may be associated with either MCD, FSG, or proliferative glomerulonephritis. Criteria: predominant C1q deposits on immunofluorescence microscopy and no clinical evidence of systemic lupus erythematosus.
![Page 94: APPROACH TO THE PATIENT WITH GLOMERULAR DISEASES Gülçin Kantarcı, MD Professor of Nephrology Department](https://reader030.vdocument.in/reader030/viewer/2022032800/56649d305503460f94a097c7/html5/thumbnails/94.jpg)
SUGGESTED READING
Goldman's Cecile Medicine 24th edition Elsevier Goldman L, Schafer AI
Case files Internal Medicine 5th edition
Mc Graw Hill LANGE Toy Patlan
The Cleveland Clinic Intensive Review of Internal Medicine 5th edition
Lippincott Williams and Wilkins
Stoller JK, Michota FA, Mandell BF