Acute and chronic glomerulonephritis



Glomerulonephritis heterogenic group of diseases with primary glomerular localization of pathological changes

It is immunologicaly mediated diffuse inflammatory disease which involves both kidneys symmetrically affecting mainly the glomerulus and associated with changes in tubules, interstitial tissue and vessels.


Etiology of Glomerulonephritis


- Beta-hemolytic streptococci of group A ( strains 1, 4, 8, 12, 49). The streptococcal infection is most often in the respiratory tract (pharyngitis, sinusitis, tonsilitis), but infections of other sites (skin and middle car) may also procede nephritis (acute GN)

- infections immunologic factors (infections hepatitis H B3 Ag positive, viruses, rickettsias, mycoplasms)

- noninfectious immunologic factors

Pathogenesis of Glomerulonephritis

The two main prosseses are involved in the pathogenesis of glomerulonephritis.

1. Autoimmune: antibodies (antiglomerular basement membrane) react with an antigen in the glomerular basement membrane and produce glomerulonephritis (5% cases).

2. Immune complex theory.

Streptococcal or other antigenes provoke antibody response, and the subsequent antigenantibody complexes in the circulation are deposited in the glomerular cappillary walls. These complexes activate the complement pathway with the liberation of chemotactic factors causing polymorpho-leucocytic infiltration the release of lysosomal enzymes from neutrophils and the direct effect of the complement system lead to damage of the capillary wall including the glomerular basal lamina.


Clinical features of AGN (nephritic syndrome
Typical clinical picture is presented now rarely.

              A latent period of from 5 days to 4-6 weeks occurs between the streptococcal infectious and the abrupt or acute onset of nephritis

              Sings of intoxication (fatigue decreased appetite)

              Edema (periorbital, leg or sacrlal edema or generalized due to salt and water retention )

              Mild or severe hypertension (headaches, visual disturbances secondary to hypertension, rarely hypertensive encephalopathy may be the presenting complains of AGn)

              Sings of left ventricular failure (ortopnoe, breathlessness, tachicardia)

              Renal impairment manifesting as oliguria or acute renal failure

              Dark urine (cola-colored urine)

              Changes on the retina (spasm of arteries, dilatation of veins, hemorrhages)

              Eclampsia due to cerebral edema and hypertension

           Sometimes the onset of the disease may be insidious with weakness, fatigue and malaise or mild edema as the most prominent symptoms after the history of a sore throat, respiratory disease or other

           In such situation urinalysis should be prescribed

           A history of streptococcal or other infection 1-4 weeks prior to onset of erythrocyturea, proteinurea with development of edema or hypertension are patogonomic of

acute glomerulonephritis

Syndromes in GN

       Urinary syndrome ( proteinuria (less than 3 gm day), RBCs and casts in the urinary sediment)

       Nephritic syndrome (abrupt onset of hematuria, proteinnuria (usually associated with non-nephrogenic range), castiuria, oliguria, hypertension)

       Nephrotic syndrome (proteinurea more than 3,5 gm/day, hypoproteinemia and hypoalbuminemia, severe adema, hyperlipidemia)

       Edema (mostly is locaried on the face (periorbital), is pale, warm, appears in the morning than decreased, in the second part of the day develops on the legs)

       Hypertensive syndrome (hypertension is hyperkinetyc and not severe)


           Hypertensive stage: complains on headache, disturbances of vision, insomnia; objective examination reveals high blood pressure, hypertrophy of left ventricular, signs of heart failure, cerebral and cardiac complications

           Stage of chronic renal failure signs and symptoms according to the stage (I - IV)


Nephrotic syndrome

           - NS clinical and laboratory syndrome wich includes:

           Proteinuriua more than 1 g/m2 24 hours (3,5-4 g/ 24 hours ),

           Hypoproteinemia with hypoalbuminemia

less than 25 g/l, hyper-alfa-2-globulinemia,

           hyperlipiduri, lipiduria,



Complications of NS

            nephrotic crises

            severe pain in abdomen, associated with peritoneal symptoms,


            oliguria and look like thrombosis of mesenterial arteries and need urgent consultation of surgeon),

            skin symptoms migrate erythema

Laboratory findings

                          Urine analysis

                          the urine may be scanty, brown, smoky of franky bloody.

                          From 0.5 to 30 gr/day of protein excreted

                          The urinary sediment contains RBCs, RBC cast (are the pathognomic of glomerulitis from any etiology)

                          WBC, renal tubular cells, WBC cast and granular (protein droplets) casts are also may be common

                          Urinanalysis Nechyporenko (more than 50 000 RBCs in 1 ml of urine is named as hematuric component)

                          Blood analysis (mild anemia (due to hypervolemia), mild leucocytosis, lympocytosis, increased ESR)



Laboratory findings

                           Biochemical blood analysis

                           (hypoproteinemia and hypoalbuminemia, hyperlipidemia (hypoalbuminemia triggers increased synthesis of all forms of plasma proteins including lipoproteins resulting in hyperlipidemia),

                           elevated level of antistrepolysin-titre (more than 1:3000);

                           serum complements levels (C3, C4 and the total hemolytic activity) are usually diminished during the active phase of the disease (returns to normal at 6-12 weeks);

                           serum urea, creatinine may be elevated due to digurea and creatinine clearance reduced;

                           hypercoagubility may result from

                     increase urinary loss of antitrombin III

                     altered levels and/or activity of protein C

                     hyperfibrunogenemia due to increased hepatic synthesis

                     impared fibrinolysis

                     increased platelet aggregability

Instrumental investigation

                         Renal biopsy usually required for diagnosis in adults

                         Ultrasound examination may show enlarged kidneys

Parculiaritis of clinical and laboratory signs of CGn according to morphologic changes in kidneys

             Mesangioproliferative Gn (Ig A nephropathy) isolated urinary syndrome, nephritic syndrome, hematuria in adults

             Mesangiocapillary Gn nephrotic syndrome, urinary syndrome with hematuric component, hypertension

             Membranosus Gn nephrotic syndrome (80%) in age 40-50

             Focal and segmental Gn - nephrotic syndrome, hypertension in Afro-Americans

             Minimal change disease - nephrotic syndrome in children

             Fibroplastic Gn - nephrotic syndrome (50%), hypertension, chronic renal failure

Differential diagnosis

Urinary syndrome

            Acute pyelonepritis

            Activation of primary chronic glomerulonephritis

            Toxic nephritis

            Goodpastures Syndrome

            Hereditary nephritis (Alports Syndrome)

Nephrotic syndrome


            Diabetic nephropathy

            Colagenic nephtopathy (SLE scleroderma)

Hematuric component

            Malignancy associated nephritis


            Renal stones

An example of diagnosis

           Acute glomerulonephritis, urinary syndrome, hematuric component


           Acute glomerulonephritis, nephrotic syndrome

An example of diagnosis

           Chronical glomerulonephritis, urinary syndrome, hypertensive stage, phase of activation

Duration of acute glomerulonephritis

           Recovering during first 2-4 weeks or 2-3month

           Prolonged duration (duration more than 4 month, full recovering is 2-3 times rare)

           Negative prognostic feature is nephrotic syndrome, associated with severe hypertension

           Development of chronic glomerulonphritis (urinary syndrome, edema or hypertension are present more than 12 month)

Complications of acute glomerulnepherts

           Eclampsia (angiospastic encephalopathy)

           Acute heart (left ventricular) failure

           Acute renal failure

Treatment of acute glomerulonephritis
Acute glomerulonephritis have to be treated only in speciallised nephrologic department

      Regimen: bed-rest during 2-4-6 weeks until desappearing of edema and normalizing of blood pressure

      Diet 7a

      Daily record of fluide intake and output

      Restriction of dietary protein if azotemia and metabolic acidosis are present

      Salt free diet (Sodium intake is restricted only when circulation overload, edema, or severe hypertension is present)

The aim of drug therapy
is recovering of the patient

     Anti microbal drug

     Symptomatic therapy

     Membranenostabilizative therapy

     Pathogenetic therapy

Antimicrobal therapy

           If a bacterial infection is still present when nephritis is discovered, it should be treated with an appropriated antimicrobial drug

           Semisynthetic penicillins in middle therapeutic doses have to be prescripted

Symptomatic therapy

            Loop diuretics such as furosemide or lasix (40-400 mg/day or 1-2 gr/day) help in the management of the expanded extracellular fuid volume (side effects: hypocholremic alkalosis, decreasing K, Na level in blood)

            In patients with decreased of furosemide should be prescribed uregit (50-200-500 mg/day orally) or the combination with the thiazides (hypothiazide 25-100 mgm/day)

            2.4 % solution euphylline 10 ml i/v

            Albumin may help in the management of hypoproteinemia

            Daily weighting to check change in the body fluid status and record of fluid intake and output have to be made in patients which receive diuretics

Hypertensive syndrome

Antihypertensive drug therapy is usually started with single drug, but if there is incomplete response a second drug is added.

One of the following drugs as a single drug treatment can be used:

             ACE inhibitors(or angiotensine II reseptors blockers)

             (loop) diuretics

             calcium channel blockers (non dihydropiridine agents)

If single drug treatment is unsuccessful then the combination therapy may be given as two-drugs or three drugs therapy

Two drug therapy:

             calcium channel blocker + diuretic

             ACE inhibitor + diuretic

Triple drug therapy is used very rare

             calcium channel blocker + diuretic + ACE inhibitor

Such drugs as adelfan or trirezide (which contained fixed doses of several hypotensive drugs) are not good in therapy of hypertensive syndrome

Hematuric component

           Dicinon (etamsilate) 2 ml 12.5% solution twice a day (7-10 days) i/m, then 0.25-0.5 three times a day orally

           Kvarcetin 1.0 in a half of glass of water three times a day.

           Ascorbinic acide 500 mg a day.

           Ascorutine 1 tabl. three times a day

           Rutine and other.

Membranostabilizative therapy

           Have to be prescribed in patients with AGn, urinary syndrome, hematuric component, after prescription of symptomatic therapy.

           Unitiol (5 ml 5% solution i/m during 1 month)

           Dimephosphon (100 mkg/kg/day 1 month)

           Aminochinolytic drugs (delagil 0.25 two times a day orally 1 month, then 0.25 a day during 5-12 month)

             (side effects: leucopenia, degeneration of retina, allergy, dyspepsia)

           ά-tocoferol ( 50 mgm/day 5-12 month)

Pathogenetic therapy
to be used in patients with:

          Gn, nephrotic syndrome after 3-4 weeks from the beginning of the disease, when symptomatic and membranostabilisative therapy is unsuccessful

Pathogenetic therapy includes:



           Anticoagulants and antiagregative drugs


      Prednisolone 1 mg/kg/day for 4-6 weeks followed by decreasing of dosage on 2.5 mg each 5-7 days

      In patients with high activity of patogenetic process pulse-therapy with metylprednisolone (metipred, soly-pred, solu-medrol) (1000 mg/d three days) can be used and then therapy in previous doses

       (Side effects: obesity, hirsutism, disturbances of menstrual function, achne, Cushing syndrome, ulcers of alimentary tract, hyperglycemia, hemorrhagic, pancreatitis, psychiatric disturbances.

      After abrupt discontinuoing of the drug usage can be worsening of the duration of the main disease)

Cytotoxic drugs.

            Cytotoxic drugs should be given in refractory cases or if glucocorticosteroids are contraindicated.

            Cyclophosphamide (1.5-2 mg/kg/day), imuran (2-3 mg/kg/day), leukeran, chlorbutin (0.2 mg/kg/day), cyclosporn A (sandimun) or others are given for 4-6 weeks at the nephrologic department and then 4-6 months at home under the control of blood analysis each 7 days.

            Pulse-therapy of cytotoxic drugs (1000-1200 mg of cyclophosphane i/v once a month 5-6 times) at specialized nephologic department can be used

             (Side effects: cytopenia, dyspepsia, hemorrhagic cystitis, toxic hepatitis, sexual dysfunction, infertility)

Anticoagulants and antiagregants

          Direct anticoagulants (fraxiparine 0.3-0.6 ml/day subcutaneous 10-14 days, heparin 5000-10000 subcutaneous 4 times a day 1-1.5 month (under the control of time of blood coagulation or time of bluding) then gradual decreasing of the dose during 1 week)

Side effects: hemorrhages, allergy.

          Non direct anticoagulants (pheniline 0,045 0,06/d 1 2 month)

          Antiagregative therapy (curantyl 200 400 mg/d, trental 600 mg/d 2 6 month)


           In patients with high activity of pathologic process 4-component therapy have to be used (glucocorticosteroids, cytotoxic drugs, anticoagulants and antiagregants simultaneously)

Treatment of eclampsia

           i/m: 25% solution of magnesium sulfates 10 ml 2-4 times a day;

           1 ml of 25% solution of aminazine;

           10 ml of 2,4% solution of euphyllin;

           80-120 mg of furosemide;

           30 ml of 40% glucose solution.

Instrumental methods of treatment.

Indications: side effects or nonefficasy of pathogenetic therapy

Contraindications: level of the Hb less than 80 gm/l, hypotension, leucocytopenia, thrombocytopenia, allergy on protein preparations, hemorrhagic complications, ulcer disease.


            Plasmapheresis (may be safer and more effective when high titers of anti GBL antibodies are present in the case of fulminant immune complex disease)