Nephrotic syndrome & GN Ebadur Rahman FRCP (Edin),FASN, Specialty Certificate in Nephrology(UK) MRCP(UK),DIM(UK),DNeph(UK),MmedSciNephrology(UK). Consultant & clinical tutor Department of Nephrology Riyadh 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,antithrombin  free protein S,  and plasminogen (due to urinary losses),

NEPHROTIC SYNDROME - Secondary - Primary glomerular disease 

Primary glomerular disease

PRIMARY 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 adults Proteinuria – nephrotic range Hematuria – 29 percent Hypertension – 43 percent Acute 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 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 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 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

Treatment 1. General treatment 1. Relief edema 2. Rx Htn 2. Symptomatic treatment Treating dyslipidemias, anticoagulate treatment, 3. Immunosupressive treatment