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Approach to Nephritic Syndrome
- 1. An approach toNephritic Syndrome Dr Vilas Naik MD, DM (Nephrology) Fellowship in Nephrology and Kidney Transplant (Toronto, Canada)
- 2. Approach • Definitions • Pathogenesis •List of conditions Approach
- 3. Classification • No perfectclassification for glomerular disease • Three ways to approach it – Clinical syndrome: like nephrotic syndrome has edema, but not HT – Biochemical: NS has hypoalbuminemia and Nephrotic range proteinuria – To complicate it more: Histopathological
- 4. Classification • Eg: 30y/F,edema, BP- 140/80 • urine proteins 4+, blood-4+, 24 hours proteins- 5 gms, sr. albu- 2.1 gm% • urine microscopy shows fatty casts and RBCs • Renal function- normal • Syndromic diagnosis: Nephrotic syndrome
- 5. Classification: case 1 •We got immunological investigations and a kidney biopsy • Immune work up: C3 was low • Kidney biopsy: Membranoprolifeartive GN • Does our syndromic diagnosis change? NO But the diagnosis is MPGN type 1 So the its MPGN presenting as NS Later the patient developed HT and renal dysfunction
- 6. Primary Vs Secondaryglomerular disease • Primary – The cause of which is not obviously know, or has not been found yet • Secondary – Cause-obvious at the time of diagnosis. Eg. systemic features of vasculitis along with renal involvement – Later may turn out to have ANCA positive
- 7. Case 2 • 35/F,married since 10 yrs, no issues • Depression, on and off medications • Taking NSAIDS for low back ache • HOPI: – Edema, Puffiness of face, HT. – Denied any other systemic features – Symptoms dated to increased intake of NSAIDS for back ache
- 8. Case 2 • O/E:edema feet, POF, BP- 160/ 100 • Skin, joints, mucosa normal • SE: nothing specific. • Syndromic diagnosis (clinical)??? Drug induced Acute interstitial Nephritis
- 9. Case 2 • Urine:proteins- 3+, blood- 3 + • microscopy- plenty RBCs, granular casts • albumin -3.6 gm%, creatinine 1.4 mg % Syndromic diagnosis?? Nephritic Syndrome
- 10. Case 2 • Primaryor Secondary?? • No history s/o of secondary glomerular disease – Rash, Photosensitivity, joint pain and swelling, fever, hemoptysis • No signs s/o secondary GN on systemic exam – Skin, joints, MM, systemic examination findings (pulmonary, hepatospleenomeghaly etc)
- 11. Histological patterns presenting asANS Actually they just represent the patterns of glomerular injury
- 12. Diffuse proliferative GN:eg Classical post streptococcal GN
- 13.
- 14. Mesangial proliferative GN IgAnephropathy
- 15. Rapidly progressive GNor Crescentic GN
- 16. Primary causes ofANS • Idiopathic MPGN type 1 • IgA nephropathy (no secondary cause found) • DPGN- idiopathic • Idiopathic Crescentic GN (no systemic signs of vasculitis, all available serology is negative for vasculitis or autoimmune disorders)
- 17. Secondary causes ofANS • SLE – Can present as mesangial proliferaitive GN – DPGN – Focal proliferative GN • Cryoglobulinemia (cryoglobulinemic MPGN) • Bacterial endocarditis – DGPN – MPGN
- 18. Secondary causes ofANS • Henoch-Schönlein purpura (IgA pattern on biopsy) • Hepatitis B and C related GN – Membranous Nephropathy – MPGN type 1 – Associated with cryoglobulinemia – IgA nephropathy pattern
- 19. Secondary causes ofANS • Associated with HIV – HIV associated “lupus like nephritis” – lupus-like" proliferative glomerulonephritis – HIV associated IgAN
- 20. RPGN/Crescentic GN presentingas ANS (secondary GN) • ANCA associated GN – Wegeners granulomatosis associated – Microscopic polyangitis – Churg Strauss syndromes • Good pastures syndrome – Pulmonary renal syndrome – Associated anti- GBM antibodies
- 21. Crescentic GN presentingas ANS • Bacterial endocarditis or shunt nephritis • Cryoglobulinemia • Mixed connective tissue disorder • SLE
- 22. Back to ouryoung 35 yrs lady.. • Her CBC, LFT were normal, ESR- 65 • HIV, Hepatitis B and C were negative • Kidney biopsy was done
- 23. Class IV, global,active lesions
- 24.
- 25. Case 2 • Soour lady has secondary glomerulonephritis – Lupus nephritis • Where are the systemic features • Where are the 4 major and minor criterias..
- 26. Case 2 • C3and C4 were low, ANA was positive, dsDNA was positive • Although she did not fulfill the criteria of SLE she is SLE (lupus nephritis) • Guidelines and criteria
- 27. Case 3 • 30/male, PMHx none • High fever 6 to 7 days • Improved over 1 week • Presented with edema, HT, decrease urine output after 7 days • Urine showed 4 + proteins and blood, creatinine was 2.4, Sr albu- 3.1
- 28. Case 3 • Viralmarkers negative • C3 low, rest immune work up negative • • Kidney biopsy- MPGN type 1, immune complex GN • NO obvious systemic features
- 29. MPGN type 1 •Initial classification was based on IF and EM picture as type I, II and III. • Presently its classified on the base of pathogenesis: – Type 1- or immune complex based disease – Type 2- secondary to complement mediated damage, alternate pathway activation – Rarely by non immune mechanism: endothelial injury
- 30. MPGN type 1(the most common) • Primary • Secondary: – Lupus Nephritis – Hepatitis B and C related – Dysproteinemias • Secondary: – Cryoglobulinemic – Chronic infections like endocarditis, shunt or chr abscess, chr parasitic infections – Autoimmune disorders: – SLE, Sjogrens, RA etc
- 31. Evaluation and management •Depending on the clinical, biochemical and histological findings, evaluate for the potential etiology • Normal RFT, subnephrotic proteinuria and normal BP (mild disease): ACEI & ARBs to maximum tolerated dose • Nephrotic range proteinuria, normal or slight rise in creat (upto 1.5)- steroids at 1mg /kg / day
- 32. Treatment • rising creatininewith or without Nephrotic range proteinuria: – Steroids + cyclophosphamide – Rituximab if progressive worsening of renal function • RPGN like picture, with or without crescents: treat like RPGN
- 33. Case 4 • 16/ male • Painless hematuria on and off since 6 m • Associated with URI, fever or exertion • USG – WNL • Referred to nephrologist • Urine Proteins- 2 +, blood 4 +, albumin and creatinine is normal • BP normal
- 34. Case 4 • Immunework up (C3, C 4, Ds DNA), Viral markers normal • Other obvious causes of hematuria ruled out • Kidney Biospy: Ig A nephropathy
- 35. Ig A nephropathy •Pathogenesis: – Increased concentration of poorly O glycosylated IgA1 – Increased propensity of this IgA1 to get deposited in the mesangium – Decreased clearance of IgA from serum and mesangium – Genetic predisposition and infections
- 36. Clinical associations • Cirrhosisof liver • HIV • Celiac disease • Minimal change disease • Wegeners granulomatosis
- 37. Oxford classification • Mesangialhypercellularity (M1 or M0) • Segmental glomerulosclerosis (S1 or S0) • Endocapillary hypercellularity (E1 or E0) • Tubular atrophy/interstitial fibrosis (T0, 1, 2)
- 38. Treatment of IgANephropathy • Non immune therapy • Indications for immunotherapy • Immunosupressive theraphy – Steroids – Steroids + cyclophosphamide, f/b Azathioprine – Cyclosporine and MMF
- 39. IgA nephropathy • Othertherapies – Tonisllectomy – IV immunoglobulins – Treat like RPGN in crescentic disease
- 40.
Editor's Notes
- #3 I will be talking about the approach, the way we look at the problem. You know the definations since your UG days, the list of the conditions can be found in any standard textbook. The pathogenesis will again will be found in any pathology, medicine or nephrology text book. Here we are going to discuss the approach when you get a edematous patient who is suspected to have a kidney disease or rather more specifically, a glomerular disease. And the probably the approach towards the treatment, and the evidence behind treating such patients.
- #4 There is no perfect classification for glomerular disease. The reason being there are three ways to approach- clinical syndrome, eg the NS patient has edema but no HT, as against Nephritic syndrome. Biochemical- as already discussed the nephrotic patient has hypoalbuminemia, and nephrotic range proteinuria, as against there will be no nephrotic range proteinuria in nephritic syndrome The last but the most important and diagnostic thing will be histopathological- it might finally chage the diagnosis
- #5 To give you an example of each situation, say a 30 year old female comes to you with edema, hypoalbuminemia and nephrotic range proteinuira, and normal BP- syndromic diagnosis would be Nephrotic syndrome.
- #6 So MPGN usually presents as Acute nephritic syndrome and in less than 10 % cases as Nephrotic syndrome, so with MPGN as histopatholoigcal diagnosis, does our syndromic diagnosis change? No, it’s the nephrotic presentation of a disease which usually presents as a nephritic syndrome. Later the patient developed HT and renal dysfunction, and will fall in the syndromic diagnosis of nephritic syndrome The whole exercise of this case was to tell you that the classification of glomerular disease is not perfect.
- #9 Classical history of NSAIDS intake, mild HT, no obvious history suggestive of secondary GN. Still no biochemistory or urine examination available. So too early to comment. But still common scenario to find a drug induced disease here.
- #10 Why did you change the syndromic diagnosis? You have a significant proteinuria which is unlikely in AIN. Still could be a condition NS + AIN that can be associated with NSAIDS, phenylbutazone has been implicated, but for now we will keep the syndromic diagnosis simple for teaching
- #11 Remember- most secondary causes of glomerular disease are vasculitis- and vasculitis have other clinical features which involve visibly the skin, joints, mucos membrane, and other organ systems
- #12 This pattern of glomerular injury will present as proteinuria- usually subnephrotic, hematuria, HT, decreased GFR. And inflammation in the glomerular tissue along with proliferative changes. The urine examination with show active urinary sediment like red cell and RBC casts
- #13 marked cellular proliferation and neutrophilic infiltration (arrows) within the glomerular tuft in postinfectious glomerulonephritis. Few open capillary lumens can be seen.
- #14 thickening of all capillary walls with double contours (long arrows) and focal areas of cellular proliferation (short arrow). The double-contour or tram-track appearance represents interposition of mesangial cell elements with new glomerular basement membrane synthesis.
- #15 mesangial glomerulonephritis showing segmental areas of increased mesangial matrix and cellularity (arrows). This finding alone can be seen in many diseases, including IgA nephropathy and lupus nephritis. Immunofluorescence microscopy demonstrating large, globular mesangial IgA deposits that are diagnostic of IgA nephropathy
- #16 The hypercellular circumferential crescent (arrows) is compressing the glomerular tuft in the center of the glomerulus and closing the capillary lumens.
- #22 The pattern of injury in bacterial endocarditis or shunt nephritis, meaning when have a infected VP or VA shunt could be crescentic GN, and here the treatment of the primary conditions is the treatment of GN. The list of conditions is still longer- including some drugs NOW THAT MIGHT HAVE BEEN TOXIC TO YOU GUYS….
- #24 membranoproliferative pattern in lupus nephritis, characterized by areas of cellular proliferation (long arrows) and by thickening of the glomerular capillary wall (due to immune deposits) that may be prominent enough to form a "wire-loop" (short arrows). Although proliferative changes can be focal (affecting less than 50 percent of glomeruli), disease of this severity is usually diffuse.
- #25 Massive lumpy deposits of IgG, IgM, C3 and C1q- a full house patter suggestive of lupus nephritis
- #27 Although the criterias guide you to reach a diagnosis, the patient may not present to you with a book picture, neither all the criteria may be present at the time of first presentation- this patient may develop rash, joint symptoms, hematological criteria later on.
- #31 If you note, the chronic infections cause persistent antigenemia and formation of immune complexes, which trap in the glomerular filter and give rise to inflamation and proliferation