INTERNAL MEDICINE DEPARTMENT №2ASSIST. KVASNITSKA O.S.

Introduction to nephrology

Acute and chronic glomerulonephritis

The mechanism of urine formation

Acute glomerulonephritis

Etiology

Infectious Streptococcal Nonstreptococcal postinfectious

glomerulonephritis Bacterial Viral Parasitic

Noninfectious Multisystem systemic diseases Primary glomerular diseases

Glomerulonephritis

Clinical syndromes

urinary (proteinuria ≤1 g/l/24 h, haematuria, leucocyturia),

nephritic (hypertension, gross haematuria, proteinuria 1-3 g/l/24 h, edemas),

nephrotic (proteinuria ≥3,5 g/l/24 h, hypoproteinemia, hypoalbuminemia, hypercholesterolemia, hypercoagulation, edemas),

mixed.

Glomerulonephritis – Diagnostic Tests

CBC (possible anemia, leucocytosis, formula shift to the left, increasing ESR)

Biochemical blood analysis (characterizes the kidney function by the parameters of urea, creatinine, total protein, albumin, serum electrolytes, cholesterol; functional state of the liver (on indicators of ALT, AST, bilirubin)

Examination of the urine (red cells, red-cell casts, nephrotic or sub-nephrotic range proteinuria)

ASO titer (anti streptolysine O)Kidney scan or biopsy

1= Light yellow, normal colour of urine2=Light-brown, urine with presence of low proteinuria and microhaematuria 3=Dark-brown, urine with medium presence of proteinuria and microhaematuria 4=Blood-brown, urine with visible haematuria and high level of proteinuriaSource: The Internet Journal of Tropical Medicine ISSN: 1540-2681 http://yester.ispub.com/journal/the-internet-journal-of-tropical-medicine/volume-6-number-1/urine-colour-as-a-rapid-assessment-indicator-in-evaluating-the-prevalence-of-schistosoma-haematobium-infection-in-two-endemic-areas-of-benue-state-nigeria.html#sthash.vpY8wWcz.dpuf

Glomerulonephritis –Treatment

Dietary protein is restricted when renal insufficiency (elevated BUN) develop.

Sodium is restricted when the patient has hypertension, edema, and heart failure.

Loop diuretic and antihypertensive medications may be prescribed to control hypertension.

Bed rest during acute phase.

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TreatmentTreat the underlying infections when acute GN is associated with

chronic infections. Antimicrobial therapy

Antibiotics (eg, penicillin) are used to control local symptoms and to prevent spread of infection to close contacts.

Antimicrobial therapy does not appear to prevent the development of GN, except if given within the first 36 hours.

Loop diuretic therapy Loop diuretics may be required in patients who are

edematous and hypertensive in order to remove excess fluid and to correct hypertension.

Relieves edema and controls volume, thereby helping to control volume-related elevation in BP

Using ACE-ingibitors, AIIRA (angiotensin II receptor antagonists), statins for treatment high BP and lipid abnormalities

Vasodilator drugs (eg, nitroprusside, nifedipine, hydralazine, diazoxide) may be used if severe hypertension or encephalopathy is present

Rapidly progressive glomerulonephritis (RPGN)

Characterized clinically by A rapid decrease in the GFR of at least 50% over a short

period, from a few days to 3 monthsThe term RPGN was first used to describe a

Group of patients who had an unusually fulminant poststreptococcal glomerulonephritis and a poor clinical outcome

Several years later, The anti-GBM antibody was discovered to produce a

crescentic glomerulonephritis in sheep, and, following this discovery,

The role of anti-GBM antibody in Goodpasture syndrome was elucidated

Anti –GBM: antiglomerular basement membrane

RPGN: Pathology

The main pathologic finding is Extensive glomerular

crescent formation Focal rupture of

glomerular capillary walls that can be seen by light microscopy and electron microscopy

RPGN: Classification

Immunological classification: based on the + or - of ANCAs

The disorders are also classified based on their clinical presentation

RPGN: Classification

Anti-GBM antibody (Approx. 3% of cases) Goodpasture syndrome (lung and

kidney involvement) Anti-GBM disease (only kidney

involvement) Note: 10-40% of patients may be

ANCA positive

RPGN: Classification Immune complex

Postinfectious (staphylococci/streptococci) Collagen-vascular disease Lupus nephritis Henoch-Schönlein purpura (immunoglobulin A and systemic

vasculitis) Immunoglobulin A nephropathy (no vasculitis) Mixed cryoglobulinemia Primary renal disease Membranoproliferative glomerulonephritis Fibrillary glomerulonephritis Idiopathic

Note: Of all patients with crescentic immune complex glomerulonephritis, 25% are ANCA+; < 5% of patients with noncrescentic immune complex glomerulonephritis are ANCA+

RPGN: Classification

Pauci-immune Wegener granulomatosis (WG) Microscopic polyangiitis (MPA) Renal-limited necrotizing crescentic

glomerulonephritis (NCGN) Churg-Strauss syndrome Note: 80-90% of patients are ANCA+

*Edema (swelling) of the face, eyes, ankles, feet, legs, or abdomen

*Blood in the urine

*Dark or smoke-colored urine

*Decreased urine volume

*Abdominal pain*Cough & Diarrhea

*General ill feeling & Fever

*Joint aches & Muscle aches

*Loss of appetite & Shortness of breath

RPGN: Symptoms

RPGN: Treatment

Depends on the underlying cause Corticosteroids may relieve symptoms in some cases Medications that suppress the immune system may

also be prescribed, depending on the cause Plasmapheresis may relieve the symptoms in some

cases

Persons should be closely watched for signs of progression to kidney failure Dialysis or a kidney transplant may ultimately be

necessary

Chronic glomerulonephritis

Chronic glomerulonephritis represents the end-stage of all glomerulonephritis with unfavorable evolution. This general (glomerular, vascular and interstitial) affection constitutes the so-called "end stage kidney". In most cases, it is associated with systemic hypertension. (Source: http://www.pathologyatlas.ro/chronic-glomerulonephritis.php)

Minimal-ChangeDisease

Nil disease or lipoid nephrosis - normal or very mild abnormalities of the glomeruliChanges can only be seen through electron microscopy.90 percent of cases of nephrotic syndrome in children under the age of 10More than 50 percent of cases in older childrenIn adults: use of nonsteroidal antiinflammatory drugs (NSAIDs)Malignancy: Hodgkin lymphoma

Source: http://dc146.4shared.com/doc/tLt3NKse/preview.htmlSource: http://dc146.4shared.com/doc/tLt3NK

se/preview.html

Membranous NephropathySecond most common cause of primary nephrotic syndrome in adultsAssociated with hepatitis B infectionAutoimmune diseases, thyroid disease, use of certain drugsUnderlying cancer – solid tumorSource: http://dc146.4shared.com/do

c/tLt3NKse/preview.html

Focal segmental glomerulosclerosis

http://www.nature.com/ki/journal/v68/n4/fig_tab/4496260f1.html

The glomeruli are enlarged, markedly  lobulated and ‘rich’ in cells due to proliferation of mesangial cells (more than 2 cells in a plane section) and accumulation of basement membrane-like material.The capillary walls are thick , their lumens – narrow due to the penetration of mesangium in  between the endothelium and basement membrane (so called  ‘mesangial interposition’).With silver stain, this phenomenon is seen as a duplication of basement membrane (‘tram rails’ – metaphor)

Mesangiocapillary glomerulonephritis

Membranoproliferative glomerulonephritis

http://www.unckidneycenter.org/kidneyhealthlibrary/mpgn.html

Clinical Manifestations

Uremia-specific findings EdemasHypertensionJugular venous distension (if severe volume

overload is present) Pulmonary rales (if pulmonary edema is present) Pericardial friction rub in pericarditis Tenderness in the epigastric region or blood in

the stool (possible indicators for uremic gastritis or enteropathy)

Decreased sensation and asterixis (indicators for advanced uremia)

Characteristics of common glomerular diseases at

presentation

Heavy proteinuria Proteinuria & haematuria

Predominant haematuria

Minimal changes Lupus nephritis Acute poststreptococcal glomerulonephritis

Focal sclerosis Membranoproliferativeglomerulonephritis

RPGN (crescentic)

Membranous nephropathy

Henoch-Schonlein purpura

Haemolityc uraemic syndrome

Diabetes mellitus Endocarditis

Amyloidosis of kidney

Acute Nephritic Syndrome

Syndrome characterised in typical cases by:

HaematuriaProteinuria (1-3 g/l/24 hours)oliguriaoedemahypertensionreduced GFRfluid overload

Nephrotic Syndrome

Proteinuria > 3.5g / 24hrs , due to excessive permeability of glomerular capillary wall.

Leads to hypoproteinemia, hypoalbuminemia, decreased colloid oncotic pressure and edema.

Accompanied by sodium and water retention, hyperlipidemia, vulnerability to infection and thrombotic complications.

Nephrotic syndrome biopsy histology in adults at different ages

Indications to perform renal biopsy

Unexplained renal failureAcute nephritic syndromeNephrotic syndrome Isolated nonnephrotic proteinuria Isolated glomerular hematuria Renal masses (primary or secondary)Renal transplant rejectionConnective-tissue diseases (eg, systemic lupus

erythematosus) 

Absolute contraindications to renal biopsy include the following:

Uncorrectable bleeding diathesisUncontrollable severe hypertensionActive renal or perirenal infectionSkin infection at biopsy siteThe following are relative

contraindications to renal biopsy:Uncooperative patientAnatomic abnormalities of the kidney which

may increase riskSmall kidneysSolitary kidney

Treatment of nephrotic syndrome

General measures Dietary sodium restriction Normal protein intake is advisable. A high-protein diet (80–90 g protein daily) increases proteinuria and can

be harmful in the long term Infusion of albumin produces only a transient effect. It

is only given to diuretic-resistant patients and those with oliguria and uraemia in the absence of severe glomerular damage, e.g. in minimal-change nephropathy. Albumin infusion is combined with diuretic therapy and diuresis often continues with diuretic treatment alone.

Treatment of nephrotic syndrome

The target pressure for patients with proteinuria greater than 1 g/d is less than 125/75 mm Hg; for patients with proteinuria less than 1 g/d, the target pressure is less than 130/80 mm Hg. Angiotensin-converting enzyme inhibitors (ACEIs) angiotensin II receptor blockers (ARBs) combination therapy with ACEIs and ARBs.  Diuretics are often required because of decreased

free-water clearance, and high doses may be required to control edema and hypertension when the GFR falls to less than 25 mL/min.   

Beta-blockers, calcium channel blockers, central alpha-2 agonists (eg, clonidine), alpha-1 antagonists, and direct vasodilators (eg, minoxidil, nitrates) may be used to achieve the target pressure.

Renal osteodystrophy can be managed early by replacing vitamin D and by administering phosphate binders.

Seek and treat nonuremic causes of anemia, such as iron deficiency, before instituting therapy with erythropoietin.

Discuss options for renal replacement therapy (eg, hemodialysis, peritoneal dialysis, renal transplantation).

Treat hyperlipidemia (if present) Expose patients to educational programs for early

rehabilitation from dialysis or transplantation.

Treatment of nephrotic syndrome

Treatment of edema Loop diuretics (furosemide, torsemide, bumetanide, ethacrynic acid)

Secreted in the proximal tubulesHave high saluretic effect (decrease sodium reabsorbtion, increase natriuresis)Quick diuretic effectEfficiency is reduced due to decreasing of external cellular fluid

Side effectsHypovolemia, hypokalemia, metabolic alcalosisImpaired glucose toleranceArterial hypotension, irregular heart beatAcute tubulointerstitial nephritisAplastic anemia, nausea, vomiting

ContraindicationsHypokalemia, hyponatremiaHypovolemia with or without hypotension

Interaction:Salycilates – increasing of toxic effectsCardiac hlycosides, corticosteroids, penicillin – the risk of hypokalemia, hypomagnesemia ACE-inhibitors – decreasing of blood pressure with impairment of renal functionNSAIDs – decreasing of hypotension and diuretic effectsIndirect anticoagulants – increasing diuresis and hypokalemiaAppropriate to use with potassium-sparing diuretics

Treatment of edema Potassium-sparing diuretics (amiloride,

triamterene, spironolactone)Acting in the ultimate part of distal tubulesSpironolactone structurrally similar to aldosteroneAmiloride and triamterene are not aldosterone antagonists

Side effectsVomiting, diarrheaIncreasing of asotemiaMenstrual disorders, amenorrheaAllergic dermatitisHyperkalemia

ContraindicationsAnuriaAcute renal failureChronic renal failure III-V st.Hyperkalemia

Interaction:With other diuretics – potentiates their effect; It is recommended to reduce dose up to 50 %

Treatment of edema Thiazide diuretics (benzothiadiazine, chlorothiazide, hydrochlorothiazide)

Acting in the distal tubulesDo not change concentration kidney abilityIncreasing potassium, magnesium, chloride, phosphate excretion with urineDelay the calcium in the bodyNo depend on the acid-base balance of the organism

Side effectsGout exacerbationOrthostatic hypotension, tachycardiaPhotosensitivityNecrotizing vasculitisHypokalaemia, hyperglycemiaCholestatic jaundice

ContraindicationsGout Hypersensitivity to sulfonamidesLiver insufficiencyGFR less than 30 ml/minDiabetes mellitus

Interaction:Not combined with potassium-sparing diureticsGanglioplegic – increasedohypotension

The most commonly used diuretics in nephrology

Medication Route of administration

Initial single dose

Maximal dose Top of effect

Duration of effect

Lasix(furosemide)

i/v 0,5-1,0 mg/kg

2-4 mg/kg up to 200mg (in case of ARF 10-20 mg/kg/24 hrs)

3-5 min 5-6 hours

Lasix(furosemide)

Per os 0,5-1,0 mg/kg

2-5 mg/kg 30-60 min

7-8 hours

Hypothiazide (Hydrochloro-thiazide)

Per os 2,5 mg/kg 1 hour 8-12 hours

Verospiron (spironolacton)

Per os 3-5 mg/kg/24 hours in 2-3 doses

10 mg/kg/24 hours 2-5 days

Triamterene Per os 150-250 mg/24 hours

300 mg/24 hours 15-20 min

12-18 hours

TreatmentMinimal change glomerulonephritis (MCGN)

Acute glomerulonephritis:Prednisolone 1mg/kg/24 hours 4-6 weeks with next reduces of

dose and addition of chlorbutin 0,2 mg/kg/24 hours or azathioprine 2 mg/kg/24 hours during of all period of prednisolone receiving

In the ineffectiveness of this treatment – cyclosporine A 3-5 mg/kg/24 hours in combination with mild doses of corticosteroids 6-12 weeks

Chronic glomerulonephritis:Prednisolone 1mg/kg/24 hours 6-8 weeks to the disappearance

or stabilization at the minimum level of proteinuria, further - to 0.5 mg/kg for 4 weeks followed by 5 mg cancellation of in a month. Cytostatics appointed along prednisolone cancellation.

Prognosis: 1% progress to ESRF.

Treatment

Focal segmental glomerulosclerosis Prednisolone 1mg/kg/24 hours 4-16 weeks. If the full or partial remission achieved, cyclophosphamide added 2 mg/kg or chlorbutin 0.15 mg/kg.

In the ineffectiveness of this treatment – prednisolone 0,5 mg/kg every other day and cyclosporine A 2-3 mg/kg during 12 monthes

Prognosis: 30–50% progress to ESRF.

Treatment

Membranous nephropathyPrednisolone 1mg/kg/24 hours and chlorbutin

0.15 mg/kg or cyclophosphamide 2-3 mg/kg 6-8 weeks

In case of relapce or in the ineffectivenes - cyclosporine A 2-3 mg/kg/24 hours 12 monthes in combination with prednisolone 0,5 mg/kg every other day

Prognosis: Untreated, 15% complete remission, 9% ESRF at 2–5yrs and 41% at 15yrs

Treatment

Mesangiocapillary glomerulonephritisTreatment: None is of proven benefitPrognosis: 50% develop ESRF

Mesangial proliferative GNAntibiotics, diuretics, and antihypertensives as necessary. Dialysis is rarely required. Prognosis: Good.

Treatment

In the absence of morphological verification of diagnosis

Prednisolone 1mg/kg/24 hours 6-8 weeks with subsequent dose reduction and addition of chlorbutin 0.2 mg / kg / day or azathioprine 2 mg / kg / day

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