GLOMERULONEPHRITIS assessment and management

1. GLOMERULONEPHRITIS &
NEPHROTIC SYNDROME

2. AGN
 A specific set of kidney diseases in which an immunologic
mechanism triggers inflammation and proliferation of
glomerular tissue that can result to damage of the basement
membrane or capillary endothelium
 Acute nephritic syndrome is the most serious of these
syndromes
 AGN progresses to chronic GN in -30%
 APSGN is the archetype of AGN: incidences have fallen

3.  GN associated with Staph aureus increasing due to increased
antibiotic resistance to staph aureus

4. GN classification
 Immune-complex glomerulonephritis (including infection-related
glomerulonephritis, IgA nephropathy, lupus nephritis)
 Antineutrophil cytoplasmic antibody (ANCA)–associated
glomerulonephritis
 Anti-glomerular basement membrane glomerulonephritis
 C3 glomerulopathy
 Monoclonal immunoglobulin–associated glomerulonephritis –
abnormal immunoglobulins

5.  AGN Manifests with sudden onset of haematuria ,
proteinuria, and RBC casts in urine
 Also usually accompanied by htn , edema, azotemia, renal
salt and water retention
 Can be due to primary or sec renal disease

6. AGN Pathophysiology
 Result from glomerular deposition or in situ formation of
immune complexes : kidneys may be enlarged upto 50% of
cases
 PSGN: Streptococcal protein neuraminidase may alter host
IgG
 IgG/ antiIgG immune complexes form and collect in the
glomeruli
 Other antibody titers to other antigens elevations (evidence
of a recent poststreptococcal infection)=ASOT,
antihyaluronidase, DNAase-B, streptokinase

7. Structural and functional changes
 Cellular proliferation of endothelial, mesangial and epithelial cells
in the glomerular tuft
 Proliferation is in the glomerulus and bowman space
 Proliferation of parietal epithelial cells leads to the formation of
crescents, a feature xstic of rapidly progressive GN
 Leukocytes proliferation within the glomerular capillary
 Thickening of basement memb
 Functional changes: proteinuria, hematuria, low GFR, urine
sedments with RBCs and RBC casts

8. Etiology
1. Infectious
 Strep spp GABH
 Serotype 12: upper airway
infection
 Serotype 49: skin
infection
 Usually dvps 1-3 wks post
infection
 Incidence 5-10% and 25%
in pharyngitis and skin
infection respectively
 Staph
 Other strep
 Mycobacteria
 Salmonella typhosa
 Brucella suis
 T.pllidum

9.  CMC
 EBV
 COXSACKIE
 Hep b
 Rubella
 Mumps
 Hep A
 C. immitis
 P.Malariae
 Schistosoma mansoni
 Toxoplasma gondii
 Wuchereria bancrofti
 Trichinella
 Trypanasomes

10. Aetiology
2. Non infectious
 Primary kidney disease
 Membranoproliferative GN: Due to expansion & proliferation of
mesangial cells as a consequence of complement deposition
 IgA Nephropathy:diffuse mesangial deposition of IgA and IgG
 Idiopathic rapidly progressive GN-xcterised by presence of
glemerular crescents
 Sytemic diseases
 Vasculitis
 Collagen vascular disease e.g. SLE
 Polyarteritis nodosa
 Good pasture syndrome: autoantb against lungs and kidneys

11.  Miscellaneous non infectious AGN causes
 GBS
 Irradiation of wilms tumor
 DPT vaccine
 Covid 19 vaccine

12. Prognosis
 Most epidemic cases follow a course ending in complete recovery
 Sporadic cases of acute nephritis often progress to chronic
 In PSGN long term prognosis is generally good , more than 98% of
individuals are asymptomatic after 5 yrs
 Within a week of onset , most PSGN patients experience
spontaneous resolution of fluid retention, and HTN.Proteinuria
may persist for 6 months and microscopic haematuria upto 1 yr
 Eventually, all urinary abnormalities should disappear,
hypertension should subside, and kidney function should return to
normal
 GN is the most common cause of CKD

13.  The prognosis for nonstreptococcal postinfectious
glomerulonephritis depends on the underlying agent, which
must be identified and addressed
 MRSA associated nephritis usually resolves after treatment

14. Patient education
 Salt restriction during acute phase
 Bp monitoring
 Ongoing long term monitoring
 Consideration of protein restriction and ACE
 Early antibiotic rx for close contacts

15. Presentation
 History:Identification of underlying cause, abrupt onset,
 Usually a boy, 2-14 yrs, sudden puffiness,edema of face with hx of
poststreptococcal infection. Dark urine, scanty, high BP,,,fevers,
weakness,malaise, abdominal pains
 Anorexia
 Itching , easy bruising, nose bleeds,
 Sob , leg edema , dyspnoea
 Haematuria, oliguria,
 Flank pain- stretching of renal capsule

16. Symptoms specific to underling diseases
 Triad of sinusitis, pulmonary infiltrates, and nephritis, suggesting
granulomatosis with polyangiitis (Wegener granulomatosis)- a rare
disorder where blood vessels become inflammed leading to
damage in major organs
 Nausea and vomiting, abdominal pain, and purpura, observed with
Henoch-Schönlein purpura-inflammation of the small blood vessels
of the skin, joints, bowels and kidneys
 Arthralgias, associated with systemic lupus erythematosus (SLE)
 Hemoptysis, occurring with Goodpasture syndrome or idiopathic
progressive glomerulonephritis
 Skin rashes, observed with SLE

17. PE
 Normal including BP
 Often a combination of edema,
HTN and oliguria
 Periorbital / pedal edema
 Crackles
 Elevated JVP
 Ascites and pleural effusion
 Rash
 pallor
 CVA tenderness
 Hematuria, microscopic or
gross
 Abnormal neurological exam:
HTN, Urea
 Arthritis
 Pharyngitis, impetigo, murmur
 Weight gain

18. Complications
 Kidney failure
 Severe proteinuria: anasarca and htn
 Hypertensive retinopathy
 Hypertensive encephalopathy
 CKD
 Nephrotic syndrome

19. DDX
 Renal syndromes commonly
mimick early stage AGN
 Chronic GN with an acute
exacerbation
 Idiopathic hematuria
 Familial nephritis –Alport
syndrome(hearing
loss/ocular abnormalities)
 AKI
 Goodpasture syndrome
 Lupus nephritis
 Membrenoproliferative GN
 PSGN

20. Workup
 Urinalysis
 Protein
 Blood
 Red blood cells (RBCs)
 White blood cells (WBCs)
 Cellular (ie, RBC,WBC)
casts
 Oval fat bodies
 Presence of RBC casts is
almost pathognomonic of
GN
 Urine sodium
 CBC
 BUN/C/E
 Complement levels

21.  The antistreptolysin O (ASO) titer is increased in 60-80% of
patients.
 The increase begins in 1-3 weeks, peaks in 3-5 weeks, and
returns to normal in 6 months.ASO titer is unrelated to severity,
duration, or prognosis of kidney disease.
 Increasing ASO titers confirm recent infection.
 In patients with skin infection, anti-DNAase B (ADB) titers
are more sensitive than ASO titers for infection with
Streptococcus

22.  Cultures throat and skin
 Blood culture: IVDU, iss, indwelling shunts
 Triglyceride levels
 Hepatitis B and C serologies
 Antineutrophil cytoplasmic antibody (ANCA)

23.  u/s
 Kidney biopsy

24. Treatment
 Treat the underlying infection
 Antimicrobial therapy does not appear to prevent the development
of glomerulonephritis, except if given within the first 36 hours.
Antibiotic treatment of close contacts of the index case may help
prevent development of PSGN.
 Loop diuretics
 Vasodilators in severe hypertension
 Glucocorticoids and cytotoxics are of no value except in severe
cases of PSGN

25. Lifestyle changes
 Sodium and water
restriction
 Limit protein intake
 Calcium supplements
 Healthy diet and exercise
 Physiotherapy

26. NEPHROTIC SYNDROME

27.  A combination of
 Nephrotic range proteinuria
 >3g/day or on a single spot urine collection the presence of 2g/g of
urine creatinine
 Low serum albumin
 Edema

28.  May occur in typical form or
in association with nephritic
syndrome
Classification
 Primary
 Minimal-change
nephropathy
 Focal glomerulosclerosis
 Membranous nephropathy
 Hereditary nephropathies
 secondary
 Diabetes mellitus
 Lupus erythematosus
 Viral infections (eg,
hepatitis B, hepatitis C,
human immunodeficiency
virus [HIV] )
 Amyloidosis and
paraproteinemias
 Preeclampsia
 Allo-antibodies from
enzyme replacement
therapy

29.  From therapeutic perspective
 Steroid sensitive
 Steroid resistant
 Ssteroid dependent
 Frequently relapsing.

30. PATHOPHYSIOLOGY
 <0.1% plasma albumin pass glomerular
filtration barrier in healthy persons
 Urine albumin in health is <50mg/day
 >500mg/day point to glomerular disease
 Glomerular caps endothelium are
fenestrated
 Sits on GBM
 GBM covered by glomerular
epithelium(podocytes)
 In nephrotic syndrome there is damage to
endothelial surface, GBM or the podocytes
Glomerular filtration barrier –filtration slits

31.  Congenital nephrotic syndrome :
 Finnish type-mutated nephrin gene
 Podocin gene mutation

32.  Theories for edema
 Underfill hypothesis –albuminuria-
hypoalbuminaemia
 Overfill hypothesis-filtered intraluminal protein
stimulate renal epithelial sodium reabsorption
 2 facts favour this
 sodium retention is observed even before the
serum albumin level starts falling
 Intravascular volume is normal or even
increased in most patients with nephrotic
syndrome.

33. Proteinuria consequences
 Infection
 Hyperlipidaemia and atherosclerosis
 Hypocalcemia and bone abnormalities
 Hypercoagulability
 Hypovolaemia
 Htn
 Gut edema
 Ascites and pleural effusion

34. 1. Infection
 A major concern in nephrotic syndrome
 Varicella infection common
 Most common infectious complications
are bacterial sepsis, cellulitis,
pneumonia, peritonitis
 Urinary immunoglobulin losses
 Edema fluid acting as a culture medium
 Protein deficiency
 Decreased bactericidal activity of the
leukocytes
 Immunosuppressive therapy
 Decreased perfusion of the spleen
caused by hypovolemia
 Urinary loss of a complement factor
that opsonizes certain bacteria

35. 2. Hyperlipidaemia
 Hypoproteinaemia leads to reactive hepatic protein synthesis
including of apolipoproteins and lipoproteins
 Reduced serum levels of lipoprotein lipase leads to reduced
lipid catabolism
 Some lipoproteins filtered in kidneys :lipiduria and classic
finding of oval fat bodies and fatty casts in urine

36. 3. Hypocalcaemia
 Loss of vitamin D binding proteins in urine
 Hypovitaminosis D
 Reduced intestinal calcium absorption

37. Hypercoagulability
 Risk forVTEs-renal ven thrombosis
 Urinary loss of anticoagulants
 Loss of Antithrombin III and plasminogen
 Increase in clotting factors I,VII,VIII and X
 Protein C and S Altered levels and activity
 Hyperfibrinogenemia –increased hepatic synthesis
 Impaired fibrinolysis due to decreased plasminogen
 Increased plt aggregability
 Alteration in endothelial function

38. Hypovolaemia

39. Etiology
 Minimal change disease, membraneous nephropathy, focal
glomerulosclerosis
 StimulateT cells , release cytokines, damage podocytes
 Medications – NSAIDs, gold, penicillamine, lithium,
anticancer drugs,
 Has been reported following Covid 19 infection and
vaccination

40. Presentation
 History :
 Swelling of face
 Dependent edema
 Foamy urine
 Fatigue
 Loss of appetite
 Thrombotic event
 Recent start of a drug e.g NSAID

41. PE Ddx
 Edema
 Haematuria
 Htn
 Heart failure
 Cirrhosis
 Dm nephropathy
 HIV associated
nephropathy
 Radiation nephropathy

42. Workup
 Urinalysis
 Urine protein:urine creatine ration >2g/g corresponds to >3gram
protein/day
 Urine sediment examination
 Urinary protein measurement
 Serum albumin
 Serologic studies for infection and immune abnormalities
 Renal ultrasonography
 Kidney biopsy

43. Important definitions
 Response: protein free urine on 3 consequtive days within 7 days
 Relapse: Protein +ve urine on 3 consequtive days within one week
 Frequent relapsing : steroid sensitive NS with 2 or more relapses in
6 months or > 3 in 1 year
 Steroid dependant:responders who relapses while steroid is being
tapered or within 14 days of stopping steroid treatment
 Initial non responders: No response during initial 8 weeks of rx
 Late non responders:Initial steroid responder who fails to respond
to 4 week treatment in relapse

44. Treatment
 Specific treatment depends on the cause
 Diuretics
 Anticoagulation
 Statins
 ARB/ACE for secondary nephrotic syndrome

45. Specific treatment
 Minimal change nephropathy 70-80% of NS: Glucocorticoids e.g
prednisolone
 It is Idiopathic loss of net negative charge in cap BM
 Sec causes:Infections , NSAIDs, Hodgkins lymphoma
 StimulateT cells-cytokines destroy podocytes
 Membraneous nephropathy:Primary:antiPLA2R receptor antibody.
Attacks a protein in podocytes. Sec: HBA/B, syphillis,Gold,
Penicillamine.
 Antibodies deposit in subepithelial region, inflammation, activation
of compliment system, podocyte effacement
 Watchful waiting,Rituximab or cyclophosphamide+/-
glucocorticoids

47. Focal segmental glomerulosclerosis
 Can be primary-idiopathic
 Sec: HIV,SCD, Heroin use
 Sclerosis of parts of the
glomerulous leading to
podocyte effacement
 Longterm
immunosupressants
 In all treat the sec cause

48.  In all treat the sec cause
 In primary cause start on
steroids
 Good response usually
indicates MC disease.Bx
may not be necessary
 Poor response ?FSGS
Longterm
immunosupressants

49. Diet
 Low sodium <2g/day (24hr urine<88mEq/day

50. LONGTERM MONITORING
 Adjustments for diuretics
 Immunizations :Pneumococcal and influenza
 Monitoring corticosteroid toxicity every 3 months
 Supplemental vit D and Calcium may attenuate bone loss