Glomerular diseases Lecture-4- Hazem.K.Al-Khafaji FICMS Department of internal medicine College of medicine Al-Qadissyia University

Acute Nephritic Syndromes Clinical types, associations & causes Post streptococcal Glomerulonephritis Subacute Bacterial Endocarditis Lupus Nephritis( diagnostic criteria of SLE) Anti-glomerular Basement Membrane Disease(Goodpasture΄s syndrome) IgA Nephropathy(henoch-SchÖnlein purpura) ANCA Small Vessel Vasculitis Membranoproliferative Glomerulonephritis Mesangioproliferative Glomerulonephritis

Sub acute Bacterial Endocarditis Endocarditis-associated glomerulonephritis is typically a complication of subacute bacterial endocarditis. Particularly in patients who: Remain untreated for an extended period of time Have negative blood cultures Have right-sided endocarditis (IVDU)

Subacute Bacterial Endocarditis associated glomerulonephritis Pathogenesis Endocarditis is infection of endothelium of the heart & blood vessels. The bacteremia accompanying endocarditis persists over long periods of time and represents a prolonged antigenic challenge to the immune system. Various antibodies and immune complexes appear in the blood—more so with longer duration of illness,antibodies like IgG & IgM form circulating immune complexes and activate complement system.These are of major importance because they cause microvascular damage. Renal deposition of circulating immune complexes , frequently result in glomerulonephritis & if deposited in the skin cause vasculitic skin lesion.

Subacute Bacterial Endocarditis associated glomerulonephritis Grossly, the kidneys in subacute bacterial endocarditis have subcapsular hemorrhages with a "flea-bitten" appearance. Microscopy on renal biopsy reveals a focal proliferation around foci of necrosis associated with abundant mesangial, subendothelial, and subepithelial immune deposits of IgG, IgM, and C3(immune complex).

Patients present with: Gross hematuria Microscopic hematuria Pyuria Mild proteinuria RPGN with rapid loss of renal function(less common) Primary treatment is eradication of the infection with 4–6 weeks of antibiotics, and if accomplished early, the prognosis for renal recovery is good.

Lupus nephritis Systemic lupus erythematosus (SLE) is THE Most common connective tissue disease.Bout 90% of patients are women.The peak age of at onset 20-30years a disease of incompletely understood cause that may produce variable combinations of fever, rash, hair loss, arthritis, pleuritis, pericarditis, nephritis, anemia, leukopenia, thrombocytopenia, and central nervous system (CNS) disease. The clinical course is characterized by periods of remissions and acute or chronic relapses. Characteristic immune abnormalities, especially antibodies to a number of nuclear and other cellular antigens, develop in patients with SLE. The diagnosis is facilitated by determining whether the patient has 4 of the 11 clinical and/or laboratory criteria developed for the classification (Revised American Rheumatism Association criteria for SLE).

Butterfly rash of SLE Typically bridge the nose & SPARES THE NASOLABIAL FOLDS

Renal disorder(criteria) Persistent proteinuria > 0 Renal disorder(criteria) Persistent proteinuria > 0.5g ̸ day or cellular casts(red cells, granular or tubular.

Renal involvement due to anti -DNA Ab bind Or precipitated in the glomeruli & induce inflammatory reaction.GN may greatly influence the course and therapy of SLE . The incidence of clinically detectable renal disease about 50%. Histologic evidence of renal involvement by immune deposits is found in the vast majority of biopsy specimens, even in the absence of clinical renal disease.

The World Health Organization (WHO) classification of lupus nephritis has been widely used for both clinical and research activities . It has the advantages of using LM, IF, and EM to classify each biopsy; of separating the milder mesangial disease from true proliferative lupus nephritis. The WHO classes correlate well with the clinical picture and subsequent course of patients with SLE.

In general, all patients with class IV lesions (diffused proliferative GN) had the worst prognosis & require vigorous therapy for their lupus nephritis. Vigorous lupus nephritis therapy has included corticosteroids, plasmapheresis, azathioprine, or cyclophosphamide, as well as other more recent immunosuppressive medications such as cyclosporine, gamma globulin, and mycophenolate mofetil. Plasmapheresis, reported to be successful mode of treatment

ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE(anti-GMB disease) Goodpasture’s disease This nephritis is one of rapidly progressive (crescentic) Gn. Within days-weeks result in uraemia. rPGN=Rapidly progressive uraemia

Pathogenesis Due to deposition of IgG antibodies along the glomerular basement membrane. These antibodies deposited also in small vessels resulting in vasculitis & sometime hemorrhage( mostly pulmonary).

Clinical features The patient may presented with kidney limited disorder; features of nephritis as hypertension,oedema,oliguria,haematuria & rapid decline in renal function. Or ,may presented with massive haemoptysis due to pulmonary haemorrhage ,which is may be life threatening. Or the patient may presented with both (renal+pulmonary)

Treatment Cyclophosphamide,mycophenolate mofetil(celcept) or corticosteriods. In case of severe nephritis & extrarenal manifestations (pulmonary haemorrhage),plasma exchange indicated.

IgA nephropathy was originally thought to be an uncommon and benign form of glomerulopathy (Berger's disease). It is now recognized as the most frequent form of idiopathic glomerulonephritis worldwide (comprising 15 to 40% of primary glomerulonephritides in parts of Europe and Asia) and clearly can progress to ESRD. The predominant antibody is composed of polymeric IgA1 .The antigen-whether infectious dietary or other-to which it is directed is unknown in the majority of cases.

Patterns of clinical presentation of IgA nephropathy Common    Asymptomatic haematuria +/- proteinuria    Hypertension    Chronic renal failure    Henoch-SchÖnlein purpura Uncommon    Malignant hypertension    Acute nephritic syndrome    Acute Kidney injury    Nephrotic syndrome

Henoch – SchÖnlein purpura Henoch-Schönlein purpura (HSP) is characterized by a small-vessel vasculitis with arthralgias, skin purpura, and abdominal symptoms along with a proliferative acute glomerulonephritis that has similar histopathologic features to IgA nephropathy. HSP is predominantly a disease of childhood, although cases do occur in adults. Despite the finding of circulating IgA-containing immune complexes, no infectious agent or allergen has been defined as causative.

What are the symptoms of Henoch-Schönlein purpura? Typical HSP skin rash The main symptom of HSP is a painless rash (purpura) that usually appears on the legs, buttocks, and arms (though it can occur elsewhere). The rash starts off as red dots, then turns purple over a period of three to six days and looks like bruises. The rash does not change color when it is pressed on. The symptoms of HSP are often preceded by cold and flu symptoms, such as fever, headache, nausea, loss of appetite, or diarrhea. The other main symptoms of HSP are: Abdominal pain: Approximately two-thirds of children with HSP have abdominal pain, which may be accompanied by vomiting. Occasionally, blood may appear in a child’s vomit or stool. Rarely, patients develop an abnormal bowel folding called intussusception. Joint pain: Children with HSP often have swelling and tenderness in the knees, ankles, elbows, and wrists. The swelling usually lasts 1-3 days. Sometimes whole limbs will swell. The inflammation does not cause crippling arthritis. Boys with HSP may also have painful swelling in the scrotum. HSP can also affect the kidneys, and patients may have features of glomerulonephritissmall amounts of blood in the urine. Between 20 and 50 percent of children with HSP have GN. The majority of these kidney problems resolve (get better) over 6 months. Symptoms usually last between 2 - 12 weeks, typically about a month. Recurrences are not frequent but do occur.

Palpable purpura . Here they are occurring in a very dense pattern with coalescing lesions.

Arm rash . It is more common to have a purpuric outbreak on the lower extremities. However, an outbreak can occur on the abdomen, chest, or as in the case with this woman, on the upper extremities

Swelling around the hand and wrist Swelling around the hand and wrist . Although arthralgias are more common in HSP, arthritis can occur as well as periarticular swelling, such as the tenosynovitis shown here.

Treatment Like IgA nephropathy, HSP has no proven therapy. Episodes of rash, arthralgias, and abdominal symptoms usually resolve spontaneously. Some patients with severe abdominal findings have been treated with short courses of high doses of corticosteroids. Patients with severe glomerular involvement may benefit by modalities used to treat patients with severe IgA nephropathy. Although most patients with HSP recover fully, patients with a more severe nephritic or nephrotic presentation(usually adults) and more severe glomerular damage on renal biopsy have an unfavorable long-term prognosis.

ANCA Small Vessel Vasculitis Antineutrophil cytoplasmic antibodies(ANCA) of IgG type directed againist cytoplasmic constitute of granulocyte,resultin in necrosis of small blood vessels & focal segmental(necrotising) glomerulonephritis.there is extracapillary proliferation in the absence of significant glomerular immune deposits(Pausi-immune GN). 10-40% of patients with rapidly progressive GN may be ANCA positive.RPGN result in duplication of serum creatinine during 3 months.

Occurs in older adults(50-60years) Clinical features Occurs in older adults(50-60years) Associated with small-vessel systemic vasculitis in majority of patients (microscopic polyangiitis, Wegener’s granulomatosis, Churg-Strauss syndrome) Presents as rapidly progressive nephritis (dysmorphic erythrocytes, red blood cell casts, proteinuria) Prodrome with fever or flu-like symptoms Skin: purpura and petechiae Wegener’s granulomatosis: granulomatous inflammation of the respiratory tract with pulmonary renal syndrome (hemoptysis, dyspnea); antibodies are commonly of PR3-ANCA (cANCA) specificity In renal limited forms.

Treatment may use one or more of these medication combinations to induce remission: Corticosteroids: Prednisilone , prednisone , Medrol , cortisone or dexamethasone. Biologic Therapy: Rituximab is a biologic protein chimeric monoclonal antibody drug that attacks the B- cells, which are the precursors to cells that make antibodies. This type of treatment is considered a form of passive immunotherapy. Responses to ritxumab reported in patients with relapsing or refractory disease. Immunosuppressive Drugs: These drugs inhibit or prevent activity of the immune system. Some drugs include cyclophosphamide, cyclosporine, azathioprine, and mycophenolate mofetil. Plasmapheresis: An important use of plasmapheresis is in the therapy that removes the ANCA from the blood, where the rapid removal of disease-causing auto-antibodies from the circulation is required in addition to other medical therapy to help prevent further damage.  

Choose the most appropriate answer: WHICH OF THE FOLLOWING IS FEATURE OF ANCA vasculitis & NEPHRITIS: A-Disease of childhood. B- Immune complex mediated. C- Crescent formation is not reported. D- Absence of significant glomerular immune deposits. E- Renal function tests normal in most cases.

Write short notes about Plasmapheresis & therapeutic plasma exchange Write short notes about Plasmapheresis & therapeutic plasma exchange? & mention its indications in glomerulonephritis?

Thank you Next lecturs : Nephrotic syndrome