+

Glomerulopathies: clinical syndromesNovember 6, 2015

+Which patient is sicker?

Se-creatinine 561 microm/l Previous measurement 576

microm/l Next measurement 542

microm/l Daily urine output: 1.4 l Se-potassium: 3.5 mmol/l pH: 7.28

Se-creatinine: 303 microm/l Previous measurement 576

microm/l Next measurement 581

microm/l Daily urine output: 150 ml Se-potassium: 6.3 mmol/l pH: 7.29

+Which patient is sicker?

Se-creatinine 561 microm/l Previous measurement 576

microm/l Next measurement 542

microm/l Daily urine output: 1.4 l Se-potassium: 3.5 mmol/l pH: 7.28

Se-creatinine: 303 microm/l Previous measurement 176

microm/l Next measurement 581

microm/l Daily urine output: 150 ml Se-potassium: 6.3 mmol/l pH: 7.29

+Which patient is sicker?

Se-creatinine 561 microm/l Previous measurement 576

microm/l Next measurement 542

microm/l Daily urine output: 1.4 l Se-potassium: 3.5 mmol/l pH: 7.28

Se-creatinine: 303 microm/l Previous measurement 176

microm/l Next measurement 581

microm/l Daily urine output: 150 ml Se-potassium: 6.3 mmol/l pH: 7.29

+Which patient is sicker?

Se-creatinine 561 microm/l Previous measurement 576

microm/l Next measurement 542

microm/l Daily urine output: 1.4 l Se-potassium: 3.5 mmol/l pH: 7.28

Se-creatinine: 303 microm/l Previous measurement 176

microm/l Next measurement 581

microm/l Daily urine output: 150 ml Se-potassium: 6.3 mmol/l 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 castsWhite 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 ProliferativeClinical 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

MCD FSGS MN

Rapidly progressive GN Anti-GBM GN Immuncomplex D ANCA-pos pauci immun

GN

Acute nephritic syndrome Poststreptococcal GN MPGN

Isolated hematuria IgA

Chronic kidney diease

+Bigger resolution for advanced adverturersAGE Nephrotic Mild nephritic Severe nephritic<15 MCD, FSGS,

MesaProlGPostinfect, IgAN, HSP

Postinfect, MembranoprolGN

15-40 FSGS, MCD, MN, DN

IgAN, thin basal membrane D, LN, MesaProlG

Postinfect, LN, RPGN, IgAN, 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,