+
Glomerulopathies: clinical
syndromes
November 6, 2015
+
Which patient is sicker?

Se-creatinine 561 microm/l

Se-creatinine: 303 microm/l

Previous measurement 576
microm/l

Previous measurement 576
microm/l

Next measurement 542
microm/l

Next measurement 581
microm/l

Daily urine output: 1.4 l

Daily urine output: 150 ml

Se-potassium: 3.5 mmol/l

Se-potassium: 6.3 mmol/l

pH: 7.28

pH: 7.29
+
Which patient is sicker?

Se-creatinine 561 microm/l

Se-creatinine: 303 microm/l

Previous measurement 576
microm/l

Previous measurement 176
microm/l

Next measurement 542
microm/l

Next measurement 581
microm/l

Daily urine output: 1.4 l

Daily urine output: 150 ml

Se-potassium: 3.5 mmol/l

Se-potassium: 6.3 mmol/l

pH: 7.28

pH: 7.29
+
Which patient is sicker?

Se-creatinine 561 microm/l

Se-creatinine: 303 microm/l

Previous measurement 576
microm/l

Previous measurement 176
microm/l

Next measurement 542
microm/l

Next measurement 581
microm/l

Daily urine output: 1.4 l

Daily urine output: 150 ml

Se-potassium: 3.5 mmol/l

Se-potassium: 6.3 mmol/l

pH: 7.28

pH: 7.29
+
Which patient is sicker?

Se-creatinine 561 microm/l

Se-creatinine: 303 microm/l

Previous measurement 576
microm/l

Previous measurement 176
microm/l

Next measurement 542
microm/l

Next measurement 581
microm/l

Daily urine output: 1.4 l

Daily urine output: 150 ml

Se-potassium: 3.5 mmol/l

Se-potassium: 6.3 mmol/l

pH: 7.28

pH: 7.29
+
General aspects for disease
categories

Kidney function

Time course

Urine volume

Urine findings

Histology

Complaints

Symptomes
“Too many secrets”
+
Kidney function

Simplest: eGFR

CKD-EPI (age, gender)

MDRD (age)

Cockroft-Gault (age, gender, body weight)

24 h urine: creatinine clearance

Isotope scintigraphy

Cystatin C

Inulin
+
Time: course of the disease

Acute onset: days to hours

Subacute: week-month

Chronic: years
+
Urine output definition
Oliguria
<500 ml/day
<17-21 ml/h
<0.24-0.3 ml/kg/h
<0.5 ml/kg/h
Anuria
<100 ml/day
Polyuria
>2.5-2 l/day
RIFLE Criteria
+
Urinanalysis findings
Nephrotic
Nephritic*
Protein over 3.5 g/24 h
Protein less than 1.5 g/24 h
Dysmorphic red blood cells =
Acanthocytes
Fatty casts
Red cell casts
White blood cells

* If glomeruli affected diffusely heavy or nephrotic range
proteinuria, hypalbuminaemia, edema, hypertension and renal
insufficiency can also be observed.
+
Proteinuria

Overflow: abnormal serum protein components

Glomerular: abnormal glomerular structure

Selective: minimal-change nephrotic syndrome

Non-selective: glomerulonephritis, diabetic nephropathy

Tubular: interstitial nephritis

Hemodynamic: heart failure
+
Indication for kidney biopsy

Diagnostic in cases with proteinuria greater than 2 g/day,
hematuria, RBC casts

Diagnostic in cases with renal failure and kidney size is
normal and other approaches are non-conclusive

Follow-up in diseases such as SLE, pulmonary-renal
syndromes, paraproteinaemias
+
Approach to kidney patients

Serum chemistry: Na, K, CN, Kreat, Mg, Ca, Phosph, uric acid, albumin

GFR

Urine dipstick

24-hour urine sample

ESR, ANA, ANCA, anti-GBM, C3, cryoglobulins

Hepatitis B, C, AST

Serum and urine protein ELFO

Imaging

Renal biopsy
+
Classification of glomerulopathies

Nephrotic syndrome – massive proteinuria (>3.5 g/day),
hypoalbuminaemia, oedema, lipiduria and hyperlipidaemia.

Acute glomerulonephritis (acute nephritic syndrome) – abrupt
onset of glomerular haematuria (RBC casts or dysmorphic RBC),
non-nephrotic range proteinuria, oedema, hypertension and
transient renal impairment.

Rapidly progressive glomerulonephritis – features of acute
nephritis, focal necrosis with or without crescents and rapidly
progressive renal failure over weeks.

Asymptomatic haematuria, proteinuria or both.

Chronic glomerulonephritis – Persistent proteinuria with or
without haematuria and slowly progressive impairment of renal
function
+
Thesaurus: Pathological terms

Focal: some, but not all, glomeruli show the lesion

Diffuse (global): most of the glomeruli (>75%) contain the lesion

Segmental: only a part of the glomerulus is affected (most focal
lesions are also segmental, e.g. focal segmental glomerulosclerosis)

Proliferative: an increase in cell numbers due to hyperplasia of one
or more of the resident glomerular cells with or without inflammation

Membrane alterations: capillary wall thickening due to deposition of
immune deposits or alterations in basement membrane

Crescent formation: epithelial cell proliferation with mononuclear
cell infiltration in Bowman’s space.
Dr. Járay Jenő, dr. Hidvégi Márta MANET Nagygyűlés, 2002
+
Playground: only two compartments
+
Sites of kidney injury and renal
function
+
Features of glomerulopathies (GN)

primarily an immunologically mediated injury to glomeruli,
(renal interstitial damage is a regular accompaniment)

the kidneys are involved symmetrically

secondary mechanisms of glomerular injury come into play
following an initial immune insult (such as fibrin deposition,
platelet aggregation, neutrophil infiltration)

renal lesions may be part of a generalized disease (e.g.
systemic lupus erythematosus, SLE).
+
Cells involved in GNs
+
Link among syndrome and
treatment
Membranous
Proliferative
Clinical syndrome
Nephrotic-sy
Nephritic-sy
Treatment
Steroid
Immunosuppression
+
Nephrotic syndrome

Heavy proteinuria

Hypalbuminaemia

Hypercholersterolaemia

Edema

Risk of thrombotic events
+
Minimal change nephritis

Mainly childhood or young adults

Nephrotic

Secunder forms: lymphomas, Hodgkin’s disease

EM: foot process fusion

Steroids

ESRD not typical
+
Focal segmental
glomerulosclerosis

Mainly adulthood

Nephrotic

Secunder forms: AIDS, SLE

Remissions and relapses

Steroids

ESRD frequent (30-60%)
+
Membranosus nephropathy

Any age

Isolated proteinuria – nephrosis

Secunder form: malignant diseases, SLE

Prognostic factors determine outcome

Remissions and relapses

Steroid + cytotoxic treatment

ESRD frequent (30-50%)
+
Poor prognostic factors in MN

Age over 50 yrs

Male gender

Hypertension

Reduced GFR

Proteinuria greater than 10 g/day

Interstitial fibrosis in Histology
+
Acute nephritic syndrome

Haematuria (macroscopic or microscopic) – red-cell casts
are typically seen on urine microscopy

Proteinuria

Hypertension

Oedema (periorbital, leg or sacral)

Temporarily oliguria and uraemia.
+
Post-streptococcal GN

Kids

Acute nephritic sy

Streptococcal infection: throat, pyoderma

AST increased

Subepithelial hump deposits

No specific therapy, anti-streptococcal antibiotics

ESRD not likely
+
Membranoproliferative GN

Young adults

Various forms: Nephroso-nephritic, simple proteinuria, acute
nephritis

Secunder forms: Hepatitis B, C, SLE

C3 level low

Steroid+ cytotoxic drugs

ESRD likely 30%
+
Rapidly progressive
glomerulonephritis

50% decline in kidney function in 3 month

Hematuria and casts

Type I: anti GBM disease (type II hypersensitivity)

Type II: immuncomplex disease (type III hypersensitivity) eg:
SLE, Schonlein-Henoch purpura, SLE

Type III: ANCA positive vasculitis, pauci-immune GN
+
Anti-GBM glomerulonephritis

Above 50 yrs

If lungs are involved Goodpasture’s sy

Rapidly progressive GN

C3 normal

ANCA positivity

Plasmapheresis

ESRD frequent
+
ANCA-positive vasculitides

Wegener’s granulomatosis,

microscopic polyangiitis

Churg–Strauss syndrome
+
ANCA positive (pauci-immun) GN

Focal ( ≥50% normal glomeruli that are not affected by the
disease process)

Crescentic ( ≥50% of glomeruli with cellular crescents)

Mixed (a heterogeneous glomerular phenotype wherein no
glomerular feature predominates)

Sclerotic (≥50% of glomeruli with global sclerosis).
+
IgA nephropathy

Adult, male

Mesangial IgA deposits

Asymptomatic hematuria, but 10% nephrotic

Secondary forms: hepatic cirrhosis, gluten sensitive
enteropathy, dermatitis herpetiformis

No optimal therapy: steroid, fish oil, ACEi

ESRD possible in 20-30%
+
Lupus nephritis

Class I – Minimal mesangial lupus nephritis (LN), with immune deposits but
normal on light microscopy. Asymptomatic.

Class II – Mesangial proliferative LN with mesangial hypercellularity and
matrix expansion. Clinically, mild renal disease.

Class III – Focal LN (involving <50% of glomeruli) with subdivisions for active
or chronic lesions. Subepithelial deposits seen. Clinically have haematuria and
proteinuria; 10–20% of all LN.

Class IV – Diffuse LN (involving >50% of glomeruli) classified by the presence
of segmental and global lesions as well as active and chronic lesions.
Subendothelial deposits are present. Clinically, there is progression to the
nephrotic syndrome, hypertension and renal insufficiency. Most common and
most severe form of LN.

Class V – Membranous LN affects 10–20% of patients. Can occur in
combination with III or IV. Good prognosis.

Class VI – Advanced sclerosing LN (≥90% globally sclerosed glomeruli
without residual activity). This represents the advanced stages of the above, as
well as healing. Immunosuppressive therapy is unlikely to help as it is
‘inactive’. Progressive CKD.
+
Therapeutical approaches

Volume control: Appropriate circulating volume, no overload
either

RR control: hypertension, hypotension should be avoided

Proteinuria: ACEi, ARB: maximal tolerable dose

Hyperlipidaemia: statins

Dietary: sufficient energy, protein restriction
+
Practical map


Nephrotic syndrome

Acute nephritic syndrome

MCD

Poststreptococcal GN

FSGS

MPGN

MN
Rapidly progressive GN

Anti-GBM GN

Immuncomplex D

ANCA-pos pauci immun GN

Isolated hematuria


IgA
Chronic kidney diease
+
Bigger resolution for advanced
adverturers
AGE
Nephrotic
Mild nephritic
Severe nephritic
<15
MCD, FSGS,
MesaProlG
Postinfect, IgAN,
HSP
Postinfect,
MembranoprolGN
15-40
FSGS, MCD,
MN, DN
IgAN, thin basal
Postinfect, LN, RPGN,
membrane D, LN, IgAN,
MesaProlG
MembranoprolGN
>40
FSGS, MN,
DN, MCD,
IgAN
IgAN

RPGN, vasculitis, IgAN
MCD: minimal change, FSGS: focal segmental glomerulosclerosis,
MesaProl: mesangioproliferative GN, MN: Membranosus
nephropathy, DN: Diabetic nephropathy, IgAN: IgA nephropathy,
Postinfect: postinfectious nephropathy, HSP: Henoch-Schonlein
purpura,