Nephrotic syndrome & GN

Ebadur RahmanEbadur RahmanFRCP (Edin),FASN, Specialty Certificate in FRCP (Edin),FASN, Specialty Certificate in

Nephrology(UK)Nephrology(UK)MRCP(UK),DIM(UK),DNeph(UK),MmedSciNephrologMRCP(UK),DIM(UK),DNeph(UK),MmedSciNephrolog

y(UK).y(UK).Consultant & clinical tutorConsultant & clinical tutorDepartment of NephrologyDepartment of NephrologyRiyadh Armed Forces HospitalRiyadh Armed Forces Hospital

Nephrotic syndrome This is characterized by proteinuria

(Typically > 3.5g/24h), hypoalbuminemia ( less than 30g/dL ) and

edema. Hyperlipidaemia.

“nephrotic range” –nephrotic proteinuria

Presentation New-onset oedema

Initially periorbital or peripheral Later genitals, ascites, anasarca

Frothy urine Generalised symptoms – lethargy,

fatigue, reduced appetite

Figure 1. Nephrotic edema.

Heavy proteinuria (albuminuria)

Further possible presentations... Oedema BP Leukonychia Breathlessness:

Pleural effusion, fluid overload, AKI,PE,MI. DVT Eruptive xanthomata/ xanthalosmata

Hemoconcentration Immobility, especially in patients with

anasarca thrombocytosis, increased platelet

activation, decreased levels of

antithrombin, free protein S, and plasminogen (due to urinary losses),

NEPHROTIC SYNDROMENEPHROTIC SYNDROME

- Secondary - Primary glomerular Primary glomerular diseasedisease

Primary glomerular diseasePrimary glomerular disease

PRIMARY NEPHROTIC SYNDROMEPRIMARY NEPHROTIC SYNDROME

Minimal Change Disease- commonest in children

Focal Segmental Glomerulosclerosis Membranous Nephropathy- commonest

in adult Membranoproliferative

Glomerulonephritis(MPGN) Iga nephropathy RARE to cause

nephrotic syndrome but commonest GN

For exam Minimal change gn Membranous gn Amiloidosis SLE DM

Urine dipstick  The urine sediment (or direct counting

of RBC per mL of uncentrifuged urine) is the gold standard for the detection of microscopic hematuria.

Dipsticks for heme detect 1 to 2 RBCs per high power field

false positive tests due to the following: Semen is present in the urine after

ejaculation and may cause a positive heme reaction on the dipstick [

urine pH greater than 9 or contamination with oxidizing agents used to clean the perineum

The presence of myoglobinuria

False negative tests have been reported in patients

ingesting large amounts of vitamin C

Isolated glomerular hematuria Renal biopsy is not usually performed there is no specific therapy for these conditions renal prognosis is excellent management of these patients is not usually

affected by the biopsy When renal biopsy is performed in such

patients, the most common findings-are a normal biopsy IgA nephropathy, Thin basement membrane disease (benign familial

hematuria), mild nonspecific glomerular abnormalities, Alport syndrome

 All patients should have a urine culture to exclude infection prior to evaluation of hematuria.

Hyperlipidemia

total cholesterol and low-density lipoprotein (LDL)

Lipoprotein (a) [Lp(a)]

high-density lipoprotein (HDL) cholesterol .

Renal biopsy Nephrotic syndrome Nephritic syndrome Unexplained renal impairement Vasculitis where kidneys are commonly involved Renal allograft dysfunction

Percutaneous renal biopsy is generally contraindicated in the following settings:

Uncorrectable bleeding diathesis Small kidneys which are generally indicative

of chronic irreversible disease Severe hypertension, which cannot be

controlled with antihypertensive medications Multiple, bilateral cysts or a renal tumor Hydronephrosis Active renal or perirenal infection An uncooperative patient

Table 4

The clinical findings at presentation in adultsProteinuria – nephrotic rangeHematuria – 29 percentHypertension – 43 percentAcute renal failure – 18 percent

In children- diagnosis of MCD is usually made based upon the clinical. Almost all children with MCD respond to a short course of glucocorticoids. it is considered steroid-resistant (SR-NS) when no remission is achieved after about two months of full-dose steroid therapy. Pediatricians usually restrict renal biopsy to individuals with SR-NS

PRIMARY NEPHROTIC SYNDROMEPRIMARY NEPHROTIC SYNDROME

Minimal Change Disease Focal Segmental

Glomerulosclerosis Membranous Nephropathy Membranoproliferative

Glomerulonephritis(MPGN)

Figure 6. Light microscopic appearances in focal segmental glomerulosclerosis. Segmental scars with capsular adhesions in otherwise normal glomeruli.

Table 5

PRIMARY NEPHROTIC SYNDROMEPRIMARY NEPHROTIC SYNDROME

Minimal Change Disease Focal Segmental Glomerulosclerosis Membranous Nephropathy Iga nephropathy Membranoproliferative

Glomerulonephritis(MPGN)

Membranous nephropathy (MN) - one-third of biopsy diagnoses in adult nondiabetics diffuse thickening of the glomerular basement

membrane (GBM) on light microscopy, "spikes" on silver stain, diffuse granular IgG and complement deposition on immunofluorescence, and subepithelial dense deposits on electron microscopy

Antibodies to the M-type phospholipase A2 receptor (PLA2R ) are found in a high proportion of patients with primary (idiopathic) MN.

Most patients with MN present with the nephrotic syndrome with normal or near normal serum creatinine.

10% associated with malignancy

Table 6

Figure 7a. Early MN: a glomerulus from a patient with severe nephrotic syndrome and early MN, exhibiting normal architecture and peripheral capillary basement membranes of normal thickness (Silver–methenamine ×400).

Figure 7b morphologically advanced MN

Figure 7c. Morphologically more advanced MN (same patient as in (b))

IgA nephropathy most common cause of primary

glomerulonephritis. in Asians and Caucasians. There is a 2:1 male to female predominance IgA nephropathy is characterized by prominent,

globular deposits of IgA in the mesangium on immunofluorescence microscopy.

Electron microscopy shows dense deposits primarily in the mesangium

Most patients with IgA nephropathy present with either visible hematuria (single or recurrent), usually following an upper respiratory infection, or invisible hematuria with or without mild proteinuria incidentally detected on a routine examination

40 to 50 percent present with one or recurrent episodes of visible hematuria, usually following an upper respiratory infection

Another 30 to 40 percent have microscopic hematuria and usually mild proteinuria, and are incidentally detected on a routine examination

Less than 10 percent present with either nephrotic syndrome or rapidly progressive glomerulonephritis

A kidney biopsy only protein excretion above 0.5 to 1 g/day,

elevated serum creatinine concentration, or hypertension.

PRIMARY NEPHROTIC SYNDROMEPRIMARY NEPHROTIC SYNDROME

Membranoproliferative Glomerulonephritis(MPGN)

Figure 8. Pathology of membranoproliferative glomerulonephritis type I.

(a) Light microscopy shows a hypercellular glomerulus with accentuated lobular architecture and a small cellular crescent (methenamine silver).

Table 7

Diagnosis

fasting blood sugar and glycosylated hemoglobin antinuclear antibody test serum complement, In selected patients, cryoglobulins, hepatitis B

and C serology, anti-neutrophil cytoplasmic antibodies (ANCAS), anti GBM antibodies, renal biopsy to define the pattern of glomerular

involvement.

Complications

Infection Coagulation disorders Protein malnutrition and dyslipidemia Acute renal failure

Treatment1. General treatment

1. Relief edema2. Rx Htn

2. Symptomatic treatment Treating dyslipidemias, anticoagulate treatment,

3. Immunosupressive treatment