Chronic Glomerulonephritis

Question 1

What is Chronic glomerulonephritis?

Answer 1

It is a long-standing kidney disorder caused by slow, cumulative damage and scaring usually by inflammation of glomeruli in kidneys.

Question 2

Etiology of Chronic G.N

Answer 2

By infection- B hemolytic streptococcus bacteria
-due to viruses HCV, measles virus

Non-infectious

• alcohol
• due to medicines e.g antibiotics,non-narcotic analgesics,
• paranephrotic syndrome seen in renal cell cancer,cancer of bronchi, lymphogranulomatosis etc
• due to primary renal disease, systemic and miscellaneous conditions

For primary renal diseases-
1.membranoproliferative type- due to expansion and proliferation of mesengial cells due to deposition of complements e.g type 1 granular deposition of C3 or due to irregular processes
2.pure mesengial proliferative GN
3.IgA nephropathy IgA and IgG GN
4. Idiopathic rapidly progressive GN
There is presence of glomerular cresents
3 types - antiglomerular basemement membrane disease, mediated by immune complex, antineutrophil cytoplasmic AB

For systemic diseases
1.vasculitis-wegener granulomatosis/ granulomatosis with polyangitis
2.collagen vascular disease-SLE
3.Cryoglobulinemia - pathological cold sensitive antibodies (proteins) that participate in cold
Cryoglobulinemia often causes vasculitis which will result in damage to kidneys
When Cryoglobulinemia deposits in capillaries, capillary wall, mesengial it leads to membranoproliferative pattern- glomerulonephritis.
4.Polyarteritis nodosa- causes vasculitis-causes GN
5.Henoch Schonlein purpura or IgA vasculitis
6.Good posture syndrome or antiglomerular basement membrane disease
This is an autoimmune disease in which antibodies attack basement membrane leading to GN

Miscellaneous non infectious diseases
-Wilms tumor irradiation
-serum sickness
-DPT vaccine
-Guillain bare syndrome
-Cetuximab(epidermal growth factor receptor inhibitor) this is a targeted cancer drug
Special forms- post eclamptic, genetically determined, irradiactive-GN

Question 3

Pathogenesis of Chronic G.N

Answer 3

-Due to prior untreated infection, ABs to B.hemolytic streptococcus are formed
-On second exposure Ag + AB + complement complex are formed , they begin to circulate in blood towards target organs in this case the kidney,
-the complex sticks to the basal membrane of glomerular capillaries
-local immune reactions are activated accompanied by inflammation
-Glomerular endothelium loses quality of thromboresistance under influence of inflammatory mediators and blood flow
-the result is coagulation inside glomeruli, microthrombus formation which closes capillary space, causes tissue destruction and sclerosis
This causes decrease in GFR,resulting in hyoertrophy and hyper filtration of remaining nephrons leading to initiation of intraglomerulsr hypertension.
-These changes occur in order to increase GFR of the remaining nephrons but instead cause glomerular sclerosis and further nephron loss.

There are also 4 non immune mechanisms which play a role in glomerular lesion;
1.Hemodynamic changes due to AHT known as “renal poison”.
Intraglomerular hypertension and hyper filtration are at the basis of the damaging activity.Blood flow intensification and increase in pressure develop compensatory, stable intraglomerular hypertonia causes lesion of capillary BM which can be penetrated by low macromolecules.these macromolecules accumulate in mesangium causes its proliferation and sclerosis

2.Metabolic disturbances- play a role in etiology as well. Hyperlipidermia promotes glomerulosclerosis development. Lipid influence is realised through peroxide oxidation processes. Oxydated lipoproteids are more active than native ones. Products of lipid peroxidation influence cytotoxic at mesangium and stimulate collagen synthesis causing nephritis progression

3.UTIs - pylonephritis
Inflammation in kidneys caused by infection ascending from urinary tract

4.Medicines e.g NSAIDs and narcotic analgesics
Cause decrease in prostaglandins which regulate renal vessel tone, GFR and electrolyte absorption

Question 4

Classification of chronic G.N

Answer 4

1.By clinical forms
-Latent
-Hematuric
-Nephrotic
-Hypertonic
-Mixed
1.Latent-characterised only by urine changes i.e moderate proteinuria, isolated or in combination with microhematuria. It can only be confirmed after biopsy due to hidden symptoms for many years, terminal renal insufficiency occurs in 15 years.Usually it mesangioproliferative type.
2.Hematuric- rarely occurs.Manifests as isolated hematuria. It can be manifestation of mesangioproliferativd nephritis with accumulation of IgA. It is manifested as hematuria episodes at the phone of respiratory diseases accompanied by fever. Disuric disorders and dull pain in lumbar region may occur. In other patient the disease flows latently, macrohematuria can be combined with proteinuria. Signs of renal insufficiency don’t occur in about 10years.
3.Nephrotic -massive edema, massive proteinuria (>3.5g daily), hypoproteinemia,dysproteinemia(decrease albumin and increase alpha 2 globulin level), hyperlipidermia (increase cholesterol,triglycerides,LDL, apoprotein B,non esterified fat acids. Arterial pressure is normal or decrease.There is nephrotic crisis- high BP,abdominal pains with muscle defence,hypovolemia with hypotonia, symptoms of intravessel blood coagulation, maybe renal veins thrombosis development.
4.Hypertonic-course at first is latent then progresses slowly. Patients complaints connected with increase in BP. Course is prolonged 20years the end is always chronic renal insufficiency.When it develops, arterial BP rises sharply, proteinuria increases and macro hematuria occurs.
5.Mixed- presence of nephrotic syndrome + arterial hypertension
Morphological basis is proliferative changes - mesangioproliferative, membranoproliferative. It is characterised by steady progressing , nephrotic syndrome is expressed greatly .Terminal renal insufficiency develops in 3-4years

2.By stages- exacerbation and remission
Exacerbation- causes by different factors influencing on immune system. Manifestations are nephrotic syndrome and increase daily loss of protein with urine. In disease progression signs of chronic renal insufficiency appear, immunologic reactiveness decreases greatly. GFR decreases at first, specific gravity decreases to 1018 and less it’s daily flactuation , its daily fluctuations decrease that is determined by Zimnitsky test.Patient complains of polydypsia and polyuria, renal ability to dilute urine is lost, urine density becomes similar to density of non protein filtrate of plasma (1007-1008), creatinine level in blood increases. Without assistant therapy (chronic hemodialysis or renal transplantation) the disease ends with uremic coma developing .

3.By stage of renal failure(CKD)
Stage 1- GFR 290ml/min
Stage 2-GFR 89-60ml/min
Stage 3- GFR 59-30ml/min
Stage4-GFR 29-15ml/min
Stage 5-GFR less than 15ml/min(kidney failure)

4.By morphology - non proliferative and proliferative
1.Nonproliferative- minimal changes in glomerulus, focal segmental glomerular membrane sclerosis or hyalinosis, membranous nephropathy.
2.Proliferative-mesangiocapillary (membrane proliferative)
Type 1- subedithelial deposits, Type 2- dense deposits disease.(mesangioproliferative, endocapillary (acute,post infectious), extra capillary(subacute)
3.Sclerosis(1 fibroplastic)
-focal segmental(in systemic disease)
-fibroplastic

5. By etiology
6. By forms- primary and secondary

Question 5

Clinical picture of Chronic G.N

Answer 5

Patient complains of
Edema
Uraemia symptoms-weakness and fatigue,loss of energy, appetite and weight, prurits(itchiness), vomiting in the morning, tremor 
Leg cramp due to hypocalemia 
Fatigue
Oliguria
Dark urine
Pale skin due to anemia
Headache
Polyuria, polydypsia, nocturia

Physical examination-jugular distension, pulmonary rales, pericardial friction rub

Question 6

Lab-instrumental diagnosis of Chronic G.N

Answer 6

CBC- anemia, inflammatory markers
Zimnisky test- decrease SG
Immunologic-elevated serum IgA
US of abdominal cavity-if vasculitis is suspected
Biochemical - increase or normal creatinine,increase electrolytes, hypoalbuminemia
ECG- hypertension and heart failure
Kidney biopsy shows deposition of IgA
Routine urine analysis-macro hematuria,mild proteinuria

Question 7

Treatment of Chronic G.N

Answer 7

Diet for high blood pressure, hyperlipidermia and edema treatment.
Antibacterial therapy at the early stages of post streptococcal infection
Glucocorticoids for pathogenetic treatment e.g prednisolone 1-2mg/kg for 2-6months
Pulse therapy in severe C.G with methylprednisalone
Anticoagulants and antiaggregant therapy - heparin 15-20000 units. In 2-3months heparin must be changed to anticoagulant of indirect action
ACEi for hypertension
In severe edema diuretics for example furosemide

In high activity 4 component therapy is used- glucocorticosteroids + cytostatics(cyclophosphan)+anticoagulant +antiagregant(dypiridamol)
For hyperlipidermia-statins,fibrates

• kidney transplant
• dialysis

Question 8

Difference between acute and chronic glomerulonephritis

Answer 8

Acute- develops in 10-14days after infection

        - S.G normal or increased
        - hypertrophy of LV not present 
        - no concentration function impairment 
        - pointing finger sign
         - 70-80% recovery

Chronic-lasts more than 3 months

           - decrease S.G
           - hypertrophy in L.V
           - no recovery