Dr. Sachin Verma is a young, diligent and dynamic physician. He did his graduation from IGMC Shimla and MD in Internal Medicine from GSVM Medical College Kanpur. Then he did his Fellowship in Intensive Care Medicine (FICM) from Apollo Hospital Delhi. He has done fellowship in infectious diseases by Infectious Disease Society of America (IDSA). He has also done FCCS course and is certified Advance Cardiac Life support (ACLS) and Basic Life Support (BLS) provider by American Heart Association. He has also done a course in Cardiology by American College of Cardiology and a course in Diabetology by International Diabetes Centre. He specializes in the management of Infections, Multiorgan Dysfunctions and Critically ill patients and has many publications and presentations in various national conferences under his belt. He is currently working in NABH Approved Ivy super-specialty Hospital Mohali as Consultant Intensivists and Physician.

1. NEPHROTIC SYNDROME
IN ADULTS
Dr. Sachin Verma MD, FICM, FCCS, ICFC
Fellowship in Intensive Care Medicine
Infection Control Fellows Course
Consultant Internal Medicine and Critical Care
Web:- http://www.medicinedoctorinchandigarh.com
Mob:- +91-7508677495
References :
1. Harrison’s Principle of Medicine, 16th edn.
2. Oxford Textbook of Nephrology, 3rd edn.
3. The Kidney, 17th edn.

2. NEPHROTIC SYNDROME
Definition : N.S. is a clinical complex
characterized by a no.of renal and extra
renal features, most prominent of which
are proteinuria of > 3.5 gm per 1.73
m2/24hrs (in practice > 3.0 to 3.5
gm/24hrs), hypoalbuminemia, edema,
hyperlipidemia, lipiduria and
hypercoagulabilty.

4. 6 Entities account for >90% of cases of N.S.
in adults.
1. Membranes glomerulopathy
2. Focal & segmental glomerulosclerosis (FSGS)
3. Minimal change diseases.
4. Membranoproliferative glomerulonephritis
(MPGN)
5. Diabetic nephropathy
6. Amyloidosis
Other entities account for <10% of N.S.
- Light chain deposition disease
- Waldenstrom’s macroglobulimia
- Fibrillary immunotactoid glomerulopathy
- IgA nephropathy etc.

5. PROTIENURIA
• The glomerular filter acts as a high capacity
ultrafiltration membrane. It is made up of highly
modified vascular endothelial cells, with only a
thin cytoplasm and large pores allowing almost
direct access of filtrate to the basement
membrane, which has on its outside a unique
pericyte-the glomerular epithelial cell or
podocyte.

6. • Thus the glomerular wall can be pictured
as having two filtration barriers in series;
an inner, charge : dependent membrane;
and a more external, mainly size selective
barrier in the outer basement membrane
and silt diaphragms of the processes.
• Glomerular filter acts via two phenomenon
size selectivity and charge selectivity

7. • Proteinuria (Glomerular) develops when
there is alteration in either charge
selectivity and size selectivity depending
on type of glomerularpathy
• Glomerular haemodynamics
(Intraglomerular hypertension and
hyperfiltration) can alter Glomerular
permeabiality.

8. Selectivity of proteinuria
• Excretion of relatively low M.W. protein
(Albumin or transferrin) is known as selective
proteinuria while if excretion is predominately
high M.W. protein (IgG, IgM or α2
macroglobulin) it is nonselective proteinuria.
• It is also related to relative damage of
Glomerular filter.
• If there is predominantly loss of charge
selectivity → selective proteinuria.
• If there is predominantly loss of size
selectivity → nonselective proteinuria.

9. • A clearance of IgG > 20% of transferrin or
albumin represents nonselective proteinuria
and < 10% is selective proteinuria.
Treatment of Proteinuria
• Proteinuira leaking through damaged
glomeruli are toxic to renal tubules.
• So every attempts should be made to prevent
and reduce proteinuria irrespective of serum
protein level or basic disease.

10. • All available drugs seems to act through
reversible haemodynamic changes are
accompanied by greater or smaller reduction
in GFR.
- Drugs/Tt acting by increasing afferent
glomerular arteriolar tone – NSAIDs, Protein
restriction and cyclosporin.
- Drugs/Tt acting by reducing efferent
glomerular tone – ACE inhibitors, ARBs and
possibly dipyridamole.

11. • ACE inhibitors : have most favorable results
Linisnopril 5 mg is usually effective in
reducing protienuria by 1/3rd. 10mg will halve
the protienuria but with a 25% reduction in
GFR. A higher dose can further decrease
GFR and carry greater risk of ARF.
• Maximum effect of ACE inhibitors will
achieved after several weeks.
• NSAIDS : reduce protienuria within week or
two but there is risk of inducing
ARF,hyperkalemia, salt and water retention
etc.

12. Protien restriction : reduction in protein intake
0.8g/kg/24 hrs reduces proteinuria. But is also
important to restrict sodium at same time (50-
60 mmol/24hrs), since inhibitory effect on
proteinuria is much greater in sodium depleted
than sodium repleted patients.
• But there is risk of malnutrition.
Nephrectomy : In a few unfortunate individuals,
proteinuria remains torrential despite
aggressive treatment, hypotension oedema
persists, the plasma creatinine increases, and
protein malnutrition becomes increasingly
severe.

13. • In this situation, it may be useful to contemplate
nephrectomy, dialysis, and intensive nutrition.
• Bilateral surgical nephrectomy through a
midline incision is the standard procedures.
• Medical Nephrectomy using administration of
mercurial diuretics or NSAIDs in very high
doses, cyclosporin and angiotensin, or the
injection of polymers, autologous thrombus,
coils, gelfoam, or fat into renal artery can be
employed.

14. HYPOALBUMINEMIA
• It is due to both the proteinuria and due to the increase
renal catabolism (in tubules).
• Infact hepatic albumin synthesis is increased from
145±9mg/kg/day to 213±17mg/kg/day in nephrotic
patients.
• Transcriptiional regulation of human albumin synthesis
is not co-related with plasma oncotic pressure or
albumin concentration, but rather with urinary albumin
execration.
Treatment :
- Reduce proteinuria
- Dietary supplementation is not recommended :
- Little effect on serum albumin level
- Hasten the progression of renal failure.

15. - Albumin infusion - has no advantages :
- Very short life
- Risk of pulmonary edema
EDEMA
• consequence of abnormal accumulation of
interstitial fluid and becomes obvious if in
excess of 10% of B.W.
• Usually present as edema around eyes, ankle
swelling, sacral pad and edematous elbows
and later may leads to ascitis and pleural
effusion.

16. Pathogenesis of Edema :
The classical under filling hypothesis
hypoalbuminemia→decrease intravascular oncotic
pressure
↓
leakage of fluid from blood to interstitium
↓
↓ intravascular volume
↓
activates sympathetic N.S. and RAS and promote
vasopressin secretion & suppressing ANP release.

17. ↓
increase salt and water retension
↓
restore intravascular volume
↓
further leakage of fluid to interstitum.
But this hypothesis does not explain the occurrence edema
in many patients whom plasma volume is expended and are
RAA axis is suppressed like adult nephrotic patients who
have normal to increased plasma volume. High BP argues
against hypovolumia and infact, suggest hypervolumia. In
some study, it is seen that sodium retension preceded the
reduction in serum protein concentration in some patient and
natriuresis developed before protienuria had resolved in
others.
these findings suggest that primary renal salt and water
retention theory.

18. TREATMENT OF EDEMA :
Not more than 1kg/day due to risk of hypovolaemia and pre-
renal azotemia.
1. Salt restriction : Cornerstone of treatment
Usually 1-2 gm/day
sodium restriction potentiate the
antiproteinuric effects of ACE inhibitors.
2. Diuretics : Patients with N.S. often show relative
resistance to diuretic.
- Multifactorial decrease delivery of drug
acting site in the tubular brush border of the kidney.
- Diuretics (Fursemide) are protein bound,
so hypoalbuminemia decreases its availability as well as
increase its inactivation to glucuronide with in kidney.

19. • THIAZIDE  sufficient for mild edema.
• POTASSIUM SPARING DIURETIC  hypokalemic patients.
• LOOP DIURETICS  for moderate to severe nephrotic edema.
Fursemide in used in doses of 40 mg-200 mg/24 hours.
• When efficiency of oral diuretic is impaired a intravenous
administration should be considered. Constant infusion is
preferred to bolus administration because it prevent in post
diuretic sodium reabsorption.
Other drugs may have better bioavailability such as bumetanide
(1-10 mg) or torsemide (10-50 mg), because of their hepatic
rather than renal metabolism.
• Metolazone (5-20 mg) may useful alone or in combination.
1. Albumin infusion
2. Dialysis

20. HYPERLIPIDEMIA
• Due to increase hepatic lipoprotein synthesis that is
triggered by reduced oncotic.
• Defective lipid catabolism has also important role.
• LDL and cholesterol are increased in majority of patients
whereas VLDL and triglyceride tends to rise in patients with
severe disease.
• It increases the relative risk for MI 5.5 fold and coronary
death 2.8 fold. It also increases progression of renal
disease.
TREATMENT
• Remission of NS leads to optimal resolution of hypercholesteremia
and hypertriglyceridemia.
• Dietary therapy provides very little benefits..
- Fish oil has some lipid lowering effect.
- Vegetarian soy protein reach in polyunsaturated fatty acids is
also beneficial.

21. • DRUGS
- HMG COA reductase inhibitors (statins) are most effective
agents in reducing cholesterol synthesis.
- Act by
- Upregualtion of hepatic LDL receptors and thus ↑ed
clearance LDL from plasma.
- ↓ed triglyceride level by activation of lipoprotein lipase.
- Correct endothelial dysfunction.
- Inhibit proliferation of smooth muscles cell with in vascular wall.
- Have antiinflammatory effects & inhibit cell proliferation and
therapy may ↓ progression of renal disease.
- Fibrates  powerful effect on TGs in nephrotics as in other
patient. But reduces LDL cholesterol less effectively.
- Nicotinic acid bile and bile acid binding resins have been used
successfully but there have frequent severe side effect which
leads to poor compliance.
• Other risk factors such as smoking, obesity hypertension &
hyperurecemia must be managed simultaneously.

22. HYPERCOAGULABILITY
Multifactorial in origin
• Increase urinary loss of antithrombin III.
• Altered levels and/or activity of protein C & S.
• Hyperfibronogenemia due to increase hepatic synthesis.
• Impaired fibrinolysis due to decrease plasminogen.
• Increase platelet aggregability – relative immobility
- haemoconcentragtion from
hypovolemia.
- hyperlipidemia
• Alteration in endothelial function
• Corticosteroids increases the concentration of some zymogens
and PT & APTT may be shortened.
• On positive side steroid tends to raise conc. of antithrombin III &
inhibit platelet aggregation but at large doses.

23. HYPERCOAGULABILITY
• Prevalence in adults is 26% (1.8% in children).
• Patients may be develop peripheral arterial or venous thrombosis,
renal vein thrombosis and pulmonary embolism.
• Venous thrombosis is more common then arterial thrombosis.
• Renal vein thrombosis (men >women) is very important and
common (up to 40% adults patients).
- Acute  sudden onset flank or abdominal pain gross
hematuria, left sided varicocele, decrease GFR.
- Chronic  usually asymptomatic.
- Renal thrombosis usually associated with membranous
nephropathy, MPGN and amyloidosis.

24. TREATMENT OF EVIDENT THROMBOSIS
• Patients should be mobilized.
• Sepsis should be avoided or treated promptly.
• Dehydration from incidental cause (e.g. diarrhoea)
should be treated.
• Diuretics used with care & hemoconcentration
minimize.
• Heparin act mainly through activation of antithrombin III
whose concentration may be diminished in nephrotics.
Thus higher doses of heparin are required.warfarin has
similar problem as it also bound to albumin.
• Full anticoagulation should be done starting with
heparin followed by warfarin with a target INR
maintained at 2-3.

25. TREATMENT OFEVIDENT THROMBOSIS
• It should be given minimum period of 3 months and
with some extra benefits from 6 months. Stopping
warfarin at any time in continuing presence of NS may
lead to rethrombosis so, warfarin until edema remits or
at least the serum albumin is greater than 25 mg/dl.
• Renal vein and venacaval angiogrpahy are probably
indicated only when embolization occur on full
anticoagulation and insertion of a caval filter is
contemplated.
• Prophylactic anticoagluation in nephrotic patients
There is no consensus about it but if in very high risk
sub group aspirin or dipyridamole can be used.

26. OTHER COMPLICATIONS OF NS
INCREASED SUSCEPTIBILITY TO INFECTION
• Due to low levels of IgG
- Increase urinary loss
- Increase catabolism
• Due unpredictable changes in pharmacokinetics of
therapeutic agents.
• Decreased factor B level which is crucial for alternate
pathway of complements system.
• Loss of transferrin which is essential for lymphocyte
function and act as carrier for number of metals
including zinc (reduces production of zinc dependent
thymic hormone thymuline).
• Peritonitis and cellulitis are common complications.

27. PROPHYLAXIS AND TREATMENT
• Prophylactic pencillin should be given in patients who
already experienced pneumococcal infection atleast
during edematous stage.
• The most important feature of treatment for established
sepsis in a nephrotic patient is that it should be begin
quickly. This in-turn rests with anticipation, suspicion
and rapid diagnosis. TLC may be misleading in those
taking steroids.
• Parenteral antibiotics should always be used, even
when the infection appears to be localized, because
septicemia is always present.
• A broad spectrum cephalosporin with an
aminoglycoside may used as initial blind treatment.
• Any severe infection should prompt discontinuation of
cytotoxic therapy.

28. FUNCTIONAL CONSEQUENCE OF URINARY LOSS OF
PLASMA PROTEIN
• Thyroid binding globulins and thyroxin – may lead to
hypothyroidism.
- But most of patient remain clinically euthyroid.
- Free T4 and free TSH are better marker
- Corticosteroid therapy may decreased TSH level in some
patients and inhibit conversion of T4 to T3.
• Vit D binding protein – oesteomalasia, but rare
- Total calcium is also low due to low albumin level.
- Concomitant corticosteroid therapy may induced oesteoporosis.
- Replacement of either calcium or vit D is not recommended
except in prolonged cases of nephrosis or when steroid is
given.
• Transferrin and erythropoietin and – microcytic hypochromic
anemia.
• ARF – is rare in nephrotic syndrome. In whom it occur patient
are elderly of minimal changes disease / FGSS.

29. MINIMAL CHANGE DISEASE
• Also called as lipoid nephrosis or foot process disease.
• It comprises 20% nephrotic cases in adults. While 80%
of nephrotic cases in children.
• Microscopic hematuria present in 20-30%.
Hypertension and renal failure are very rare.
• In children urine contains albumin principally while in
adults proteinuria is typically non selective.
• Light microscopy - no changes.
• Immuno-fluorescence - typically negative for
immunoglobulin and C3.
• Electron microscopy – diffuse effaciment of the foot
processes of visceral epithelial cell.

30. MAJOR CAUSES OF MCD
• Idiopathic (majority)
• In association with systemic disease or drugs.
- Drug induced interstitial nephritis induced by
NSAIDs, rifampin, interferon alpha.
- Hodgkin’s disease and other lymphoproliferative
malignancy.
- HIV infection.
TREATMENT
• MCD is highly steroid responsive and carries an
excellent prognosis.
• Approximately 90% children and 50% of adults enter
remission following 8 week of high dose oral
glucocorticoid.

31. Treatment
• Adults – 1-1.5 mg/kg body weight (pridinisone) per day
for 4 weeks, followed by 1 mg/kg/day on alternate day
for 4 weeks.
• Upto 90% of adults enter remission if therapy extended
for 20-24 weeks.
• Steroid dependent – relapse occur whenever dose is
reduced or within two weeks of discontinuation of
steroid.
• Steroid responder – absence of protein in urine for
three consecutive days.
• In frequent relapse - <3 relapse in a year.
• Frequent relapse - > 3 relapse in a year.
• Steroid resistance – no response to treatment after 6
month of therapy

32. Treatment of relapse and steroid dependent MCD
• Cyclophosphamide – induction of remission with
pridinisone followed by institution of cylcophosphamide
(2 mg/kg) for 8-12 weeks.
Side effects – hemorrhagic cystitis, infection, gonadal
dysfunction, bone marrow supprresion and potential
mutagenic events.
• Chlorembucil - 0.1 to 2.0 mg/kg/day
Side effect – higher incidence of malignancy
Treatment of storied resistant MCD
• Causes
- Poor compliance due to toxic side effect
- Alternate day therapy may not provide sufficient
amounts of corticosteroid to induce clinical remains.

33. - Oral steroid therapy may not be well absorbed in
edematous patients.
• Pulse methylprednisolone
- May induce remission in some corticosteroid resistant
children
• Cyclosporine-
- 5mg/kg/day, patient may respond but long term
remission is rare.
• Levamisole –
- 2.5mg/kg/day on alternate day.
- It is an antihelmenthic drug (Immunomodulating role)
- Transient cytopenia may occurs in 2/3rd patients.

34. MEMBRANUS GLOMERULOPATHY
• Leading cause of idiopathic nephrotic syndrome in
adults (30 to 40%) with male to female ratio of 2 :1.
• Prtoeinuria is usually non selective, microscopic
hematuria is present in upto 50% of cases,
hypertension in only 10-30% of patients.
• Light microscopy – diffuse thickening of GBM
without evidence of inflammation or cellular
proliferation.
• Immunofluorescence – granular deposition of IgG,
C3 and compliments (C5b-9).

35. Stage I—subepithelial deposits
• A few small, flat, electron-dense deposits are seen on the
epithelial surface of the GBM.
Stage II—'spike' formation
• 'Spikes' protruding from epithelial surface of GBM become clearly
visible.
• The spikes extend between the electron-dense deposits, and are
present in virtually every capillary loop.
Stage III—incorporation of deposits
• Electron-dense deposits become surrounded by and incorporated
into the GBM. This results in an irregular thickening of the GBM.
Stage IV—disappearing deposits
• The deposits incorporated within the GBM lose their electron
density. Areas of the GBM will have a vacuolated or lucent
appearance.
Stage V—reparation stage
• During this 'healing' phase, the deposits have become completely
rarified, and the GBM appearance is returning to normal.

36. • Nephrotic syndrome remits spontaneously and
completely in up to 40% of patients.
• Features that predict a poor prognosis include male
gender, older age, hypertension, severe proteinuria
and hyperlipidemia, and impaired renal function.
• Controlled trials of glucocorticoids have failed to
show consistent improvement.
• Cyclophosphamide, chlorambucil, and cyclosporine
have shown to reduce proteinuria and/or slow the
decline in GFR in patients with progressive disease
in small or uncontrolled study.
• Mycopthenolate mofetil and rituximab are under trial.
• Transplantation is a successful treatment option for
patients who reach ESRD.

38. CONDITIONS ASSODATED WITH MEMBRANOUS
GLOMERALOPATHY
• Idiopathic (majority)
• In association with systemic diseases or drugs
Infection
Hepatiitis B and C, syphilis, malaria, leprosy, hydatid disease,
filariasis, enterococcal endocarditis.
Systemic auto immune diseases
SLE, Rheumatoid arthritis, Sjogren's syndrome, Hashimoto's disease,
grave’s disease, primary biliary cirrhosis, ankylosing spondylitis,
myasthenia gravis.
Neoplasia
Ca breast, lung, colon, stomach, and esophagus; melanoma, renal
cell carcinoma; neuroblastoma; carotid body tumor.
Drugs
Gold, penicillamine, captopril, NSAIDs, probenecid, trimethadione,
mercury
Miscellaneous
Sarcoidosis, diabetes mellitus, sickle cell disease, Crohn's disease,
Guillain-Barre syndrome, Fanconi's syndrome alpha-1 antitrypsin
deficiency

39. FOCAL AND SEGMENTAL
GLOMERULOSCLEROSIS
• The pathognomonic morphologic lesion in FSGS is
sclerosis with hyalinosis involving portions
(segmental) of fewer than 50% (focal) of glomeruli
on a tissue section.
• Primary FSGS comprises about one third of cases of
NS in adults.
• Secondary FSGS can complicate a number of
systemic diseases and sustained glomerular capillary
hypertension following nephron loss from any cause.
• In addition to nephrotic proteinuria it presents with
hypertension, mild renal insufficiency, and an
abnormal urine sediment that contains red blood
cells and leukocytes. Proteinuria is nonselective in
most cases.

40. • Light microscopy - Entrapment of amorphous
hyaline material.
• Electron microscopy - evidence of damage to
visceral epithelial cell.
• The etiology of primary FSGS is unclear, but
appears to be, at least in part, immunologic.
• There is evidence that a circulating
nonimmunoglobulin permeability factor, possibly
a lymphokine triggers FSGS in at least a
subgroup of patients.
• Secondary FSGS is a potential long-term
consequence of nephron loss from any cause.
• It appears that >50%, of nephrons must be lost
for development of secondary FSGS.

41. ETIOLOGY OF FOCAL AND SEGMENTAL
GLOMERULOSCLEROSIS
• Idiopathic (majority)
• In association with systemic diseases or drugs
HIV infection
Diabetes mellitus
Fabry's disease
Sialidosis
Charcot-Marie-Tooth disease
• As consequence of sustained glomerular capillary hypertension
Congenital oligonephropathies
Unilateral renal agenesis
Oligomeganephronia
Acquired nephron loss
Surgical resection
Reflux nephropathy
Glomerulonephritis or tubulointerstitial nephritis
Other adaptive responses
Sickle cell nephropathy
Obesity with sleep apnea syndrome
Familial dysautonomia
Miscellaneous
Heroin use

42. Response to corticosteroids in adult patients with
idiopathic nephrotic syndrome (1961–1986)
Patients Complete Partial Failures
(n) remissions (%) remissions (%) (%)
Minimal 301 226 (75.8) 21 (7) 55 (18.2)
changes
Focal 153 24 (15.6) 31 (20.2) 98 (64.2)
sclerosis
Biopsy not 48 31 (64.6) 0 (0) 17 (35.4)
done
Total 502 281 (55.8) 52 (10.3) 170
(33.9)

43. RECOMMENDATION
• First, nephrotic FSGS in adults must always be
allowed to benefit from a course of corticosteroid
treatment, followed by other drugs (Azathioprine,
Cyclosporine, Tacroliumus, Mycophenolate, Mofetil)
when ineffective.
• Second, high-dose prednisone is clearly more effective
than dosages less than 1 mg/kg/day.
• Third, response of FSGS to corticosteroids is much
slower in adults than in children and that steroid
resistance cannot be pronounced before a minimum of
4 months of full-dose corticosteroid treatment

44. MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS
• Is characterized by thickening of the GBM and
proliferative changes on light micros­copy.
• Two major types : Type I MPGN and type II
MPGN.
Type I MPGN
• The hallmark is presence of subendothelial and
mesangial deposits on electron microscopy that
contents C3 and IgG and IgM rarely IgA.
• It is associated with a variety of chronic infection
(bacterial endocarditis, HIV, hepatitis B and C),
systemic immune complex diseases (SLE,
cryoglobulinemia), and malignancies (leukemias,
lyphomas).

45. • It has protracted course and about 50% of
patients reach ESRD by 10 years.
Type II MPGN
• Type II MPGN is an autoimmune disease in
which patients have an IgG autoantibody,
termed C3 nephritic factor, that binds to C3
convertase, the enzyme that metabolizes C3,
and renders it resistant to inactivation and
deposits on GBM.
• Type II MPGN is associated with partial
lipodystrophy.
• Poor prognosis than type I MPGN.

46. • In general, 1/3 pt. Spontaneous remission, 1/3
progressive disease and 1/3 have waxing and
waning course.
• No proven therapy for patients with progressive
disease beyond eradicating underlying cause.
• Corticosteroid dipyridamole, aspirin, and
warfarin with or without cyclophosphamide
have been tried.
Treatment approach
1. Adults with idiopathic MPGN, proteinuria (>3
g/day), or impaired renal functions should
undergo a trial of therapy with dipyridamole or
aspirin.

47. 2. Patients with rapidly progressive renal failure or a
recent deterioration in renal function especially those
with crescents on histopathology should be treated with
pulse methylprednisolone therapy followed by oral
prednisone and cyclophosphamide.
3. Patients with microscopic haematuria, proteinuria (<3
g), and normal renal function should be followed up
every 3 months. They can be treated with ACE
inhibitors.
4. Patients with chronic renal failure should be managed
conservatively.
5. Patients with HCV-associated MPGN should be treated
with IFN-α and immunosuppressive agents should be
avoided.

48. DIABETIC NEPHROPATHY
• Nephropathy complicates 30% of cases of
type I DM and approximately 20% of
cases type IIDM.
• Risk factors for the development of
diabetic nephropathy include
hyperglycemia, systemic hypertension,
glomerular hypertension and'
hyperfilteration, proteinuria, and possibly
cigarette smoking, hyperlipidemia and
gene polymorphisms affecting the activity
of renin angiotensin aldosteron axis.

49. • Diabetic nephropathy is usually diagnosed on
clinical grounds without a renal biopsy. Supportive
clues are the presence of normal sized or enlarged
kidneys, evidence, proliferative diabetic
retinopathy, and a bland urinary sediments.
Retinopathy is found in 90% and 60% of patients
with type I and type II diabetes mellitus
respectively, who develop nephropathy.
• The earliest morphologic abnormalities
nephropathy are thickening of the GBM and
expansion mesangium due to accumulation of
extracellular matrix.
• Prominent nodular matrix expansion (classical
Kimmelsteil-Wilson lesion) are often found.

50. TREATMENT
• Aim is to control blood sugar, systemic blood pressure and
glomerular capillary blood pressure.
• ACE in inhibitor and ARBs are drugs of choice for both
systemic blood pressure & intraglomerular hypertension.
RENAL AMYLOIDOSIS
• Glomeruli are involved in 75 to 90% of patients.
• Hypertension is present in 20-25%. Renal size is usually
normal or slightly enlarged.
• A minority of patients present with renal failure.
• Rectal biopsy and abdominal fat pad biopsy reveal
amyloid deposits in about 75% of patients and may
obviate the need for renal biopsy.

51. • Renal biopsy earliest pathologic changes are
mesangial expansion by amorphous hyaline material
and thickening of GBM. Further deposition results in
large nodular esinophilic masses.
• When stained with congo red these deposit show
apple – green birefringence under polarized light.
• Electron microscopy reveals non branching
extracellular amyloid fibrils.
TREATMENT
• No treatment has shown consistently improvement.
However some success has been reported with
combination of melphalan and pridinsone.
• Renal replacement therpay is offered to patients with
ESRD.
• Most patients die from extra renal complications,
particularly cardiovascular diseases.