NEPHRITIC/ NEPHROTIC SYNDROMES

BY DR. SAMUEL.N UWAEZUOKE, MB;BS. FWACP (Paed), Dip Th. SENIOR LECTURER/CONSULTANT PAEDIATRICIAN

OUTLINE
GENERAL

CONSIDERATIONS DEFINITION AETIOLOGY CLINICAL FEATURES LABORATORY EVALUATION TREATMENT DIFFERENTIAL DIAGNOSIS PROGNOSIS

NEPHRITIC SYNDROME
-SYNONYMS INCLUDE
ACUTE ACUTE ACUTE

GLOMERULONEPHRITIS

NEPHRITIS
NEPHRITIC SYNDROME

GENERAL CONSIDERATIONS
EACH

KIDNEY HAS ABOUT ONE MILLION NEPHRONS- THE FUNCTIONAL UNIT THE NEPHRON RECEIVES BLOOD THROUGH THE AFFERENT ARTERIOLE THE AFFERENT ARTERIOLE FORMS THE CAPILLARY TUFTS OR GLOMERULUSREUNITE TO FORM THE EFFERENT ARTERIOLE

GENERAL CONSIDERATIONS
THE

MAJOR ELEMENTS OF RENAL FUNCTION INCLUDE GLOMERULAR ULTRAFILTRATION, TUBULAR REABSORPTION AND TUBULAR SECRETION GLOMERULAR CAPILLARY HYDROSTATIC PRESSURE GENERATES AN ALMOST PROTEIN-FREE FILTRATE OF PLASMA INTO THE BOWMANS CAPSULE

GENERAL CONSIDERATIONS
GLOMERULAR

FILTRATION RATE(GFR) IS MAINLY DETERMINED BY THE RELATIVE DEGREE OF CONSTRICTION OF AFFERENT AND EFFERENT ARTERIOLE ANGIOTENSIN II CAUSES A PREFRENTIAL CONSTRICTION OF EFFERENT ARTERIOLE RAISING THE GLOMERULAR CAPILLARY PRESSURE AND INCREASE IN GFR.

DEFINTION
-A RENAL PATHOLOGY CHARACTERIZED BY ABRUPT ONSET OF HAEMATURIA(VARIABLE DEGREES) OEDEMA HYPERTENSION OLIGURIA -FOLLOWING INFECTION WITH A VARIETY OF ORGANISMS ESPECIALLY BETA-HAEMOLYTIC STREPTOCOCCI

Aetiology of acute nephritic syndrome

POST INFECTIOUS Streptococci, staphylococci ,treponema pallidum, salmonella typhi, leptospirosis. Plasmodium malariae, toxoplasma. Hepatitis B and C , cytomegalovirus, parvovirus, Ebstein Barr virus Infections of shunts, prostheses, bacterial endocarditis

Aetiology of acute nephritic syndrome

SYSTEMIC VASCULITIS Henoch Schonlein purpura, Systemic lupus erythematosus Microscopic polyarteritis, Wegeners granulomatosis OTHERS Membranoproliferative glomerulonephritis Ig A nephropathy Acute interstitial nephritis

PATHOGENESIS
-POST STREPTOCOCCAL ACUTE GLOMERULONEPHRITIS ( PSGN ) AS THE PROTOTYPE OF AGN REMAINS THE COMMONEST CAUSE IN DEVELOPING COUNTRIES OFTEN FOLLOWS PHARYNGITIS, IMPETIGO OR RARELY A MIDDLE EAR INFECTION CAUSED BY GROUP A BETA-HEMOLYTIC STREPTOCOCCI

PATHOGENESIS

The nephritogenic strains of streptococci are capable of producing AGN These include several protein M-types such as 4,12,25 and 49 Host factors, genetically determined, are important in the formation of antibodies to streptococcal antigens Glomerular injury in PSGN results from deposition of immune complexes in the glomerular capillaries

PATHOGENESIS

Nephritogenic antigens derived from streptococci may bind directly to subepithelial glomerular sites Antibodies formed against these antigens combine(immune complexes) and result in an inflammatory response Activation of complement, infiltration of neutrophils, proliferation of glomerular cells and expansion of mesangial matrix follow(glomerular injury).

CLINICAL FEATURES
History

of sore throat or pyoderma (impetigenous lesions) is noted in most cases Latent period in the history of sore throat is 7 to 14 days while that of pyoderma is 2 to 4 weeks Peak age incidence : 5 to 12 years. Rare below the age of 3 years A male preponderance is reported

CLINICAL FEATURES
Gross

hematuria and mild facial edema are the most common presenting features Urine usually cola coloured or reddish brown Oliguria ( less than 0.5ml-1ml/kg/hour )or sometimes anuria Hypertension(from volume overload) may lead to headache

CLINICAL FEATURES
Atypical -

presentations (complications of AGN) include Acute pulmonary edema Hypertensive encephalopathy(even at comparatively lower BP levels) Acute renal failure Nephrotic syndrome( so-called nephritic nephrotic syndrome)

LABORATORY INVESTIGATIONS
Urinalysis-

mild proteinuria Urine microscopy- dysmorphic red cells, red cell casts, and neutrophils. Hyaline and granular casts may also be seen. Serum electrolyte, urea and creatinineelevated urea/creatinine, hyperkalemia, metabolic acidosis( in patients with ARF ). Hematology- anemia due to hemodilution

LABORATORY INVESTIGATIONS
Imaging

study(Chest X-ray)- may show cardiomegaly and pulmonary congestion Serology ( ASO titre and C3 levels)elevated ASO titre within 3 to 5 weeks after streptococcal infection, and decreased serum C3 levels Renal biopsy- not required in typical cases but indicated under special conditions

Indications for renal biopsy in AGN

Associated systemic features like fever, rash, joint pain, heart disease. Normal ASO titre and C3 levels Mixed picture of AGN and Nephrotic syndrome Delayed cases of resolution -oliguria, hypertension and/or azotemia beyond 2 weeks, gross hematuria past 3-4 weeks, low C3 levels past 6-8 weeks and microscopic hematuria/proteinuria beyond 6-12 months

TREATMENT

GENERAL MEASURES Fluid balance : strict input/output if oliguria is present, daily weight measurement. Diet : restriction of sodium intake in all children with edema or hypertension, restriction of foods high in potassium until oliguria resolves Bed rest: if hypertension, edema or cardiac failure are present

TREATMENT
Drug

treatment: Eradication of streptococcal infections using penicillin or alternatively erythromycin. Intravenous furosemide(1mg/kg) for edema and circulatory congestion For hypertension, the use of vasodilators (hydralazine, nifedipine, ACEI) may be effective

DIFFERENTIAL DIAGNOSIS
Acute

interstitial nephritis Shunt nephritis Nephritis in SBE Glomerulonephritis associated with hepatitis B or C Ig A nephropathy

Prognosis
Most

cases resolve within the first week Gross hematuria rapidly clears but microscopic hematuria may be detected for 6 to 12 months The long-term prognosis of PSGN in children is excellent Even those with severe disease completely recover

NEPHROTIC SYNDROME

NEPHROTIC SYNDROME
Not A

a distinct renal disease

clinical and biochemical state that may develop during the course of several different renal diseases of known and unknown aetiology

CAUSES/ CLASSIFICATION
CONGENITAL

: - FINNISH TYPE (AUTOSOMAL RECESSIVE) - MICROCYSTIC KIDNEY DISEASE (CONGENITAL NEPHROSIS) - INTRAUTERINE INFECTIONS SUCH AS SYPHILIS, CMV, TOXOPLASMA ACQUIRED :IDIOPATHIC OR PRIMARY AND SECONDARY

CAUSES/CLASSIFICATION

PRIMARY / IDIOPATHIC: Minimal change nephropathy (MCN), Mesangial proliferative GN, Focal segmental glomerulosclerosis (FSG), Membranoproliferative GN (MPGN), and Membranous nephropathy SECONDARY: Systemic lupus erythematosus(SLE), Henoch-Schonlein purpura (HSP), amyloidosis, hepatitis B, HIV, P. malariae, SCD, Bee stings, Gold salts/ heavy metals such as mercury etc.

Minimal change nephrotic syndrome( MCNS)

Occurs

in about 85% of children with idiopathic nephrotic syndrome Often steroid responsive Onset usually between the age of 2-6 years More common in boys Hypertension, hematuria and raised urea levels are rare

PATHOGENESIS OF NEPHROTIC SYNDROME

Increased glomerular permeability

Oedema- due to salt/water retention

Gross proteinuria

Reduced oncotic pressure Diminished effective plasma volume

Hypoalbuminaemia hyperlipidaemia

Clinical features of MCNS

Insidious onset with periorbital swelling and facial puffiness Swelling gradually increases to involve the extremities and abdomen and if untreated may become massive resulting in anasarca May occasionally be associated with gross hematuria and oliguria ( mixed picture of nephrotic syndrome and acute nephritis)

LABORATORY EVALUATION

Urinalysis : dipstick test(3+/4+), spot urine test or protein/creatinine concentrations (ratios <0.5 in children <2 years and <0.2 in older children are normal. A ratio >2 suggests nephrotic range proteinuria),24-hr urine protein estimation Urine microscopy and culture: microscopic hematuria, exclude UTI Blood chemistry: serum urea, creatinine and electrolytes, cholesterol Serology : Hbsag, C3 levels, HIV Imaging : CXR, Abdominal US

TREATMENT

Initial episode: Control of massive edema and infection before starting steroid therapy Oral prednisolone 2mg/kg in 2 to 3 divided doses for 6weeks and single morning dose alternate days for the next 6 weeks Prolonging the treatment for 6 months may result in a longer remission and fewer relapses

TREATMENT

PATTERN OF RESPONSE TO STEROID THERAPY: Remission: Protein-free urine(urine protein negative or trace) for 3 consecutive days Relapse: Proteinuria(urine protein 3+ or more) for 3 consecutive days Frequent relapser: 2 or more relapses within 6 months of initial episode or more than 3 relapses within any 12 month period Steroid dependent: 2 consecutive relapses during alt. day pred. or within 2 weeks of stopping therapy

TREATMENT
ALTERNATIVE

OR ADJUNCT DRUGS USED IN FREQUENT RELAPSES AND STEROID DEPENDENCE INCLUDE; LEVAMISOLE CYCLOPHOSPHAMIDE CYCLOSPORINE A

TREATMENT
Use

of ACEI : Enalapril, Lisinopril ( antiproteinuric effect) Management of edema: diuretics, intravenous albumin or pooled plasma transfusion Dietary management: high biological value protein, salt restriction, supplements of vitamins and micronutrients Management of complications

Complications of Nephrotic syndrome

Infections

: peritonitis, cellulitis Hypovolemia Thromboembolism Hyperlipidemia

DIFFERENTIAL DIAGNOSIS
Angioneurotic

edema Protein-losing enteropathy Chronic liver disease Malnutrition with edema Congestive heart failure

Prognosis
The

final outcome of steroid sensitive nephrotic syndrome is excellent Most patients stop getting relapses between the ages of 14 to 20 years Fully recover without any residual dysfunction Some may continue to have relapses into adulthood