Nephrotic syndrome


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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.

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Nephrotic syndrome

  1. 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:- Mob:- +91-7508677495References :1. Harrison’s Principle of Medicine, 16th edn.2. Oxford Textbook of Nephrology, 3rd edn.3. The Kidney, 17th edn.
  2. 2. NEPHROTIC SYNDROMEDefinition : N.S. is a clinical complexcharacterized by a no.of renal and extrarenal features, most prominent of whichare proteinuria of > 3.5 gm per 1.73m2/24hrs (in practice > 3.0 to 3.5gm/24hrs), hypoalbuminemia, edema,hyperlipidemia, lipiduria andhypercoagulabilty.
  3. 3. 6 Entities account for >90% of cases of N.S. in adults.1. Membranes glomerulopathy2. Focal & segmental glomerulosclerosis (FSGS)3. Minimal change diseases.4. Membranoproliferative glomerulonephritis (MPGN)5. Diabetic nephropathy6. AmyloidosisOther entities account for <10% of N.S.- Light chain deposition disease- Waldenstrom’s macroglobulimia- Fibrillary immunotactoid glomerulopathy- IgA nephropathy etc.
  4. 4. 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.
  5. 5. • 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
  6. 6. • 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.
  7. 7. 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.
  8. 8. • 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.
  9. 9. • 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.
  10. 10. • 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.
  11. 11. 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.
  12. 12. • 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.
  13. 13. 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.
  14. 14. - 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.
  15. 15. 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.
  16. 16. ↓increase salt and water retension ↓restore intravascular volume ↓further leakage of fluid to interstitum.But this hypothesis does not explain the occurrence edemain many patients whom plasma volume is expended and areRAA axis is suppressed like adult nephrotic patients whohave normal to increased plasma volume. High BP arguesagainst hypovolumia and infact, suggest hypervolumia. Insome study, it is seen that sodium retension preceded thereduction in serum protein concentration in some patient andnatriuresis developed before protienuria had resolved inothers.these findings suggest that primary renal salt and waterretention theory.
  17. 17. 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.
  18. 18. • 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 infusion2. Dialysis
  19. 19. 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.
  20. 20. • 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.
  21. 21. HYPERCOAGULABILITYMultifactorial 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.
  22. 22. 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.
  23. 23. 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.
  24. 24. 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.
  25. 25. OTHER COMPLICATIONS OF NSINCREASED 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.
  26. 26. 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.
  27. 27. FUNCTIONAL CONSEQUENCE OF URINARY LOSS OFPLASMA 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.
  28. 28. 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.
  29. 29. 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.
  30. 30. 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
  31. 31. 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 malignancyTreatment 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.
  32. 32. - 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.
  33. 33. 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).
  34. 34. 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.
  35. 35. • 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.
  36. 36. 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, Sjogrens syndrome, Hashimotos 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, Crohns disease, Guillain-Barre syndrome, Fanconis syndrome alpha-1 antitrypsin deficiency
  37. 37. 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.
  38. 38. • 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.
  39. 39. ETIOLOGY OF FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS• Idiopathic (majority)• In association with systemic diseases or drugs HIV infection Diabetes mellitus Fabrys 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
  40. 40. 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)sclerosisBiopsy not 48 31 (64.6) 0 (0) 17 (35.4) done Total 502 281 (55.8) 52 (10.3) 170 (33.9)
  41. 41. 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
  42. 42. 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).
  43. 43. • 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.
  44. 44. • 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 approach1. Adults with idiopathic MPGN, proteinuria (>3 g/day), or impaired renal functions should undergo a trial of therapy with dipyridamole or aspirin.
  45. 45. 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.
  46. 46. 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.
  47. 47. • 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.
  48. 48. 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.
  49. 49. • 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.