NEPHRITIC/NEPHROTIC SYNDROME

7/28/2019 NEPHRITIC/NEPHROTIC SYNDROME.

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NEPHRITIC/NEPHROTICSYNDROMESBY

DR. SAMUEL.N UWAEZUOKE,MB;BS. FWACP (Paed), Dip Th.

SENIOR LECTURER/CONSULTANTPAEDIATRICIAN


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OUTLINE

GENERAL CONSIDERATIONS

DEFINITION

AETIOLOGY

CLINICAL FEATURES

LABORATORY EVALUATION

TREATMENT

DIFFERENTIAL DIAGNOSIS

PROGNOSIS


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NEPHRITIC SYNDROME

-SYNONYMS INCLUDE

ACUTE GLOMERULONEPHRITIS

ACUTE NEPHRITIS

ACUTE NEPHRITIC SYNDROME


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EACH KIDNEY HAS ABOUT ONE MILLIONNEPHRONS- THE FUNCTIONAL UNIT

THE NEPHRON RECEIVES BLOOD THROUGHTHE AFFERENT ARTERIOLE

THE AFFERENT ARTERIOLE FORMS THECAPILLARY TUFTS OR GLOMERULUS-

REUNITE TO FORM THE EFFERENT ARTERIOLE


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THE MAJOR ELEMENTS OF RENALFUNCTION INCLUDE GLOMERULAR

ULTRAFILTRATION, TUBULAR REABSORPTIONAND TUBULAR SECRETION

GLOMERULAR CAPILLARY HYDROSTATICPRESSURE GENERATES AN ALMOST

PROTEIN-FREE FILTRATE OF PLASMA INTOTHE BOWMANS CAPSULE


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GLOMERULAR FILTRATION RATE(GFR) ISMAINLY DETERMINED BY THE RELATIVE

DEGREE OF CONSTRICTION OF AFFERENTAND EFFERENT ARTERIOLE

ANGIOTENSIN II CAUSES A PREFRENTIALCONSTRICTION OF EFFERENT ARTERIOLE

RAISING THE GLOMERULAR CAPILLARYPRESSURE AND INCREASE IN GFR.


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DEFINTION

-A RENAL PATHOLOGY CHARACTERIZED BYABRUPT ONSET OF

HAEMATURIA(VARIABLE DEGREES)OEDEMA

HYPERTENSION

OLIGURIA

-FOLLOWING INFECTION WITH A VARIETY OFORGANISMS ESPECIALLY BETA-HAEMOLYTICSTREPTOCOCCI


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Aetiology of acute nephriticsyndrome

POST INFECTIOUS

Streptococci, staphylococci ,treponemapallidum, salmonella typhi, leptospirosis.

Plasmodium malariae, toxoplasma.

Hepatitis B and C , cytomegalovirus,parvovirus, Ebstein Barr virus

Infections of shunts, prostheses, bacterialendocarditis


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Aetiology of acute nephriticsyndrome

SYSTEMIC VASCULITIS

Henoch Schonlein purpura, Systemic lupus

erythematosusMicroscopic polyarteritis, Wegeners

granulomatosis

OTHERS

Membranoproliferative glomerulonephritis Ig A nephropathy

Acute interstitial nephritis


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PATHOGENESIS

-POST STREPTOCOCCAL ACUTEGLOMERULONEPHRITIS ( PSGN )

AS THE PROTOTYPE OF AGN REMAINS THE COMMONEST CAUSE IN

DEVELOPING COUNTRIES

OFTEN FOLLOWS PHARYNGITIS, IMPETIGO

OR RARELY A MIDDLE EAR INFECTIONCAUSED BY GROUP A BETA-HEMOLYTICSTREPTOCOCCI


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PATHOGENESIS The nephritogenic strains of streptococci are

capable of producing AGN

These include several protein M-types such as4,12,25 and 49

Host factors, genetically determined, areimportant in the formation of antibodies tostreptococcal antigens

Glomerular injury in PSGN results fromdeposition of immune complexes in theglomerular capillaries


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PATHOGENESIS Nephritogenic antigens derived from

streptococci may bind directly to sub-

epithelial glomerular sites Antibodies formed against these antigens

combine(immune complexes) and result in aninflammatory response

Activation of complement, infiltration of

neutrophils, proliferation of glomerular cellsand expansion of mesangial matrixfollow(glomerular injury).


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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 to4 weeks

Peak age incidence : 5 to 12 years. Rarebelow the age of 3 years

A male preponderance is reported


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CLINICAL FEATURES

Gross hematuria and mild facial edemaare the most common presenting features

Urine usually cola coloured or reddishbrown

Oliguria ( less than 0.5ml-1ml/kg/hour )orsometimes anuria

Hypertension(from volume overload) maylead to headache


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CLINICAL FEATURES

Atypical presentations (complications ofAGN) include

- Acute pulmonary edema

- Hypertensive encephalopathy(even atcomparatively lower BP levels)

- Acute renal failure

- Nephrotic syndrome( so-called nephriticnephrotic syndrome)


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LABORATORY INVESTIGATIONS

Urinalysis- mild proteinuria

Urine microscopy- dysmorphic red cells,

red cell casts, and neutrophils. Hyalineand granular casts may also be seen.

Serum electrolyte, urea and creatinine-elevated urea/creatinine, hyperkalemia,metabolic acidosis( in patients with ARF ).

Hematology- anemia due tohemodilution


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LABORATORY INVESTIGATIONS

Imaging study(Chest X-ray)- may showcardiomegaly and pulmonary congestion

Serology ( ASO titre and C3 levels)-elevated ASO titre within 3 to 5 weeksafter streptococcal infection, anddecreased serum C3 levels

Renal biopsy- not required in typical casesbut indicated under special conditions


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Indications for renal biopsy inAGN

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, lowC3 levels past 6-8 weeks and microscopichematuria/proteinuria beyond 6-12 months


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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 cardiacfailure are present


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TREATMENT

Drug treatment:

- Eradication of streptococcal infections

using penicillin or alternativelyerythromycin.

- Intravenous furosemide(1mg/kg) foredema and circulatory congestion

- For hypertension, the use of vasodilators(hydralazine, nifedipine, ACEI) may beeffective


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Acute interstitial nephritis

Shunt nephritis

Nephritis in SBE

Glomerulonephritis associated withhepatitis B or C

Ig A nephropathy


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Prognosis

Most cases resolve within the first week

Gross hematuria rapidly clears but

microscopic hematuria may be detectedfor 6 to 12 months

The long-term prognosis of PSGN inchildren is excellent

Even those with severe diseasecompletely recover


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NEPHROTIC SYNDROME


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NEPHROTIC SYNDROME

Not a distinct renal disease

A clinical and biochemical state that maydevelop during the course of severaldifferent renal diseases of known andunknown aetiology


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CAUSES/ CLASSIFICATION

CONGENITAL :

- FINNISH TYPE (AUTOSOMAL RECESSIVE)

- MICROCYSTIC KIDNEY DISEASE(CONGENITAL NEPHROSIS)

- INTRAUTERINE INFECTIONS SUCH ASSYPHILIS, CMV, TOXOPLASMA

ACQUIRED :IDIOPATHIC OR PRIMARY ANDSECONDARY


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CAUSES/CLASSIFICATION PRIMARY / IDIOPATHIC: Minimal change

nephropathy (MCN), Mesangial proliferative

GN, Focal segmental glomerulosclerosis (FSG),Membranoproliferative GN (MPGN), andMembranous nephropathy

SECONDARY: Systemic lupuserythematosus(SLE), Henoch-Schonleinpurpura (HSP), amyloidosis, hepatitis B, HIV, P.malariae, SCD, Bee stings, Gold salts/ heavymetals such as mercury etc.


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Minimal change nephroticsyndrome( MCNS)

Occurs in about 85% of children withidiopathic nephrotic syndrome

Often steroid responsive

Onset usually between the age of 2-6years

More common in boys

Hypertension, hematuria and raised urealevels are rare


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PATHOGENESIS OF NEPHROTICSYNDROME

Increasedglomerular

permeability

Gross proteinuria

Hypoalbuminaemia

hyperlipidaemia

Reduced oncoticpressure

Diminished effectiveplasma volume

Oedema- due tosalt/water retention


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Clinical features of MCNS Insidious onset with periorbital swelling and

facial puffiness

Swelling gradually increases to involve theextremities 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)


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LABORATORY EVALUATION Urinalysis : dipstick test(3+/4+), spot urine test or

protein/creatinine concentrations (ratios


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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 mayresult in a longer remission and fewer relapses


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TREATMENT PATTERN OF RESPONSE TO STEROID THERAPY:

Remission: Protein-free urine(urine proteinnegative or trace) for 3 consecutive days

Relapse: Proteinuria(urine protein 3+ or more)for 3 consecutive days

Frequent relapser: 2 or more relapses within 6months of initial episode or more than 3relapses within any 12 month period

Steroid dependent: 2 consecutive relapsesduring alt. day pred. or within 2 weeks ofstopping therapy


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TREATMENT

ALTERNATIVE OR ADJUNCT DRUGS USED INFREQUENT RELAPSES AND STEROID

DEPENDENCE INCLUDE; LEVAMISOLE

CYCLOPHOSPHAMIDE

CYCLOSPORINE A


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TREATMENT Use of ACEI : Enalapril, Lisinopril ( anti-

proteinuric effect)

Management of edema: diuretics,intravenous albumin or pooled plasmatransfusion

Dietary management: high biologicalvalue protein, salt restriction, supplementsof vitamins and micronutrients

Management of complications


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Complications of Nephroticsyndrome

Infections : peritonitis, cellulitis

Hypovolemia

Thromboembolism

Hyperlipidemia


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Angioneurotic edema

Protein-losing enteropathy

Chronic liver disease

Malnutrition with edema

Congestive heart failure


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Prognosis

The final outcome of steroid sensitivenephrotic syndrome is excellent

Most patients stop getting relapsesbetween the ages of 14 to 20 years

Fully recover without any residualdysfunction

Some may continue to have relapses intoadulthood

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NEPHRITIC/NEPHROTIC SYNDROME