nephrotic and nephritic syndrome

nephrotic and nephritic syndrome

1. Nephrotic syndrome and nephritic syndrome Submitted to Dr. Digambar nartam(HOD, MD) Dr. Pawan garg(MD) Dr. Arvind tripathi(MD) SUBMITTED BY RATNESH KUMAR SHUKLA B. A. M. S. Final year

2. Reference :- KUMAR AND CLARKS CLINICAL MEDICINE, 9 TH EDITION, CHAPTER 20-KIDNEY AND URINARY TRACT DISEASE HARRISONS PRINCIPLE OF INTERNAL MEDICINE 20 TH EDITION API TEXTBOOK OF MEDICINE, SECTION 19 TEXTBOOK OF PATHOLOGY, BY HARSHMOHAN ROBINS BASIC PATHOLOGY ESSENTIAL OF MEDICAL PHYSIOLOGY 6 TH EDITION, BY K SEMBULINGAM www.wikipaedia.com www.ncbi.nlm.nih.gov

3. NEPHRON A nephron is the basic unit of structure and function in the kidney. A nephron is used separate to water, ions and small molecules from the  blood , filter out wastes and toxins, and return needed molecules to the blood. Each nephron has two major portions: A Renal corpuscle (Malpighian body) A Renal tubule

4. Glomerulus The glomerulus is a tuft of small blood vessels called capillaries located within Bowman's capsule within the kidney. Glomerular mesangial cells structurally support the tufts. Blood enters the capillaries of the glomerulus by a single arteriole called an afferent arteriole and leaves by an efferent arteriole.

5. Structure of Glomerular wall Glomerular Capillary wall is filtering area. It consists of three basic structure The layer of fenestrated endothelium Glomerular basement Membrane Visceral epithelial layer(podocytes)

6. GLOMERULAR FILTRATION BARRIER Urine formation begins at the  glomerular filtration barrier . The glomerular  filter through which the ultrafiltrate has to pass consists of three layers: the fenestrated endothelium, the intervening glomerular  basement membrane, and the podocyte slit diaphragm . There are two kindkinds of barrier for filtration . Size barrier Ion barrier

7. 1.Size barrier

8. 2. Ion barrier There is another barrier called as negative charges barrier. GBM, endothelium and podocyte are negatively charged. These negetive Charged layers address to the repulsion for negetively charged molecule. Ex. – plasma protein at normal physiological pH charged negetively like albumin.

9. Nephrotic syndrome

10. NEPHROTIC SYNDROME Nephrotic syndrome refers to clinical condition that includes five main characters :- Massive proteinuria (more then 3.5gm/day) Hypo albuminaemia (less then 3gm/dl) Generalized edema Hyperlipidaemia (increase cholesterol and triglycerides) lipidurea

11. 1.proteinurea Proteinuria occurs partly because structural damage to the glomerular barrier (podocytes, membrane, fenestrated endothelium and endothelial charge) allows the passage of more and molecules. Protein leaked out more then 3.5gm/day.(nephrotic range proteinurea) The filtration slit between podocytes and normal podocyte architecture, and Podocyte foot processes are critical to maintaining a barrier to protein loss into the urinary space, as is Functional GBM and healthy capillary endothelium (and its charge).I Proteinurea maybe in two types :- Selective proteinuria (only albumin leaked out) Non-selective proteinuria

12. 2.Hypoalbuminaemia Loss of urinary protein (largely albumin) of the order ≥3.5 g daily in an adult may lead to hypoalbuminaemia. the normal liver can synthesize albumin at a rate of 10–12 g daily. This can be partly explained by increased catabolism of reabsorbed protein, largely albumin, in the proximal tubules, even though the rate of albumin synthesis is increased. Loss of plasma protein in urine can decrease level of oncotic pressure in circulatory compartment and results as anasarca.

13. 3.Hyperlipidaemia This is a consequence of increased synthesis of lipoproteins as a direct consequence of a low plasma albumin. Low-density lipoprotein (LDL) increases, Very-low-density lipoprotein (VLDL) and/or intermediate-density lipoprotein (IDL) fractions increase, with no change (or a decrease) in HDL. Hyperlipidaemia is caused by two factors: Hypoproteinemia stimulates protein synthesis in the liver, resulting in the overproduction of  lipoproteins . Lipid catabolism is decreased due to lower levels of  lipoprotein lipase , the main enzyme involved in lipoprotein breakdown.  

14. 4. Edema Edema is thought to be caused by two mechanisms. The first being hypoalbuminemia which lowers the  oncotic pressure  within vessels resulting in hypovolemia and subsequent activation of the  renin–angiotensin system  and thus retention of sodium and water. Nephrotic syndrome edema initially appears in parts of the lower body (such as the legs) and in the eyelids. In the advanced stages it also extends to the  pleural cavity  and  peritoneum  (ascites) and can even develop into a generalized anasarca. Edema maybe appear more in most dependent area like, walking-legs, sleeping-back.

15. 5.Lipidurea Lipiduria  or loss of lipids in the urine is indicative of glomerular pathology due to an increase in the filtration of lipoproteins When Lipid passed through nephrons tubules some cells of proximal convulated tubes started pinocytosis and become globulated. These cells become dysfunctional and shut down in urine. In the urine analysis process may be found big fat globules they called as “fat ovale bodies”.

16. Causes of Nephrotic syndrome Nephrotic syndrome may be:- Primary Secondary Primary causes – Minimal change disease Membranous glomerulopathy Focal segmental glomerulosclerosis Membranousproliferative glomerulopathy 2.Secondery causes :- DM, Amyloidosis Drugs (gold, penicillamine) Infection (malaria, syphilis,HIV,… ..)

17. 1.Minimal changes disease the most common cause of nephrotic syndrome in children. It owes its name to the fact that the  nephrons  appear normal when viewed with an  optical microscope  as the lesions are only visible using an  electron microscope . Another symptom is a pronounced proteinuria. The individual foot processes can no longer be made out- it is like they have all just “melted” together into a single thin layer. This important barrier in the filtration process can no longer keep protein from being filtered out of the blood and into the urine.

18. Many drugs have been implicated in MCN, including NSAIDs, lithium, antibiotics (cephalosporins, rifampicin, ampicillin), bisphosphonates and sulfasalazine. Atopy is present in 30% of cases of MCN, and allergic reactions can trigger the nephrotic syndrome. Infections, such as hepatitis C virus (HCV), the human immunodeficiency virus (HIV) and tuberculosis, are rarer causes.

19. Clinical feature MCN is most common in children, particularly boys, and is responsible for the large majority of cases of nephrotic syndrome in childhood. Proteinuria is usually ‘highly selective’, where albumin, but not highermolecular-weight proteins such as immunoglobulins, is lost in the urine. Oedema is usual and in children this may present predominantly around the face.

20. Management Manage symptoms with general measures (above). • The first line therapy to minimal change disease is corticosteroids . High-dose corticosteroid therapy with prednisolone 80mg/day daily • In children, two-thirds relapse after steroid therapy and further courses of corticosteroids are required. One-third of these children regularly relapse on steroid withdrawal, so that a second-line agent shouldbe added after repeat induction with steroids. • Cyclophosphamide 1.5–2.0 mg/kg daily is given for 8–12 weeks with prednisolone 7.5–15 mg/day. This increases the likelihood of long-term remission. Steroid-unresponsive patients may also respond tocyclophosphamide. No more than two courses of cyclophosphamide should be prescribed in children because of the risk of side-effects, which include future infertility (azoospermia and premature ovarian failure).

21. 2.Membranous glomerulopathy Idiopathic membranous glomerulopathy is an autoimmune disease that occurs mainly in adults, and predominantly in men. Microscopic haematuria, hypertension and renal impairment may accompany the nephrotic syndrome. As in other glomerular disease, hypertension and a greater degree of renal impairment are poor prognostic signs. Membranous nephropathy is considered an autoimmune disease, which means that it caused by the body’s own immune system. MN is caused by the build-up of  immune complexes  within the filters (glomeruli) of the kidney itself. antibodies and antigens create immune complexes that get stuck in the kidney filter (glomerulus) and cause disease. These autoantibodies are Anti pla2r ( anti-phospholipase A2 receptor antibody ) and Anti thsd7a( anti-thrombospondin type 1 domain-containing 7A ) Doctors can be diagnosed differ kind of nephrotic syndrome by biopsy of kidney.

22. Causes of membranous glomerulopathy In the primary or idiopathic form (which comprises 75% of the cases), glomerular histology is identical to that seen when membranous glomerulopathy is secondary to another insult. These include: • drugs (e.g. penicillamine, gold, NSAIDs, probenecid, mercury, captopril) • autoimmune disease • infections • cancers • other causes

23. Management • patients should receive ACE inhibition . • The alkylating agents, cyclophosphamide (1.5–2.5 mg/kg per day for 6–12 months with 1 mg/kg per of oral prednisolone on alternate days for the first 2 months) and chlorambucil (0.2 mg/kg per day in months 2, 4 and 6, alternating with oral prednisolone 0.4 mg/kg per day in months 1, 3 and 5), are effective. • Mycophenolate mofetil has demonstrated benefit in smaller studies with short follow-up. • Anti-CD20 antibodies (rituximab, which ablates B lymphocytes) have been shown to improve renal function, reduce proteinuria and increase the serum albumin; no significant adverse affects have been shown in the short term. • Oral corticosteroids are of no benefit alone but may be additive. A pilot study has shown promise with subcutaneous administration of adrenocorticotrophic hormone (tetracosactide) twice weekly, demonstrating an improvement in proteinuria. It is believed that it acts directly on podocytes by binding to melanocortin receptors. It is licensed by the FDA for use in nephrotic syndrome of any cause.

24. 3.Focal segmental glomerulosclerosis Focal segmental glomerulosclerosis (FSGS) describes a sclerotic glomerular lesion that affects some (but not all) glomeruli, and some (but not all) segments of each tuft. hypoalbuminaemia is unusual. I mmunofluorescence description IgM and C3 deposited in focal and segmental manner in the sclerotic segments Electron microscopy description Epithelial cell detachment from glomerular basement membrane Extensive foot process obliteration (even in nonsclerotic glomeruli), mesangial sclerosis with increased matrix and collapsed glomerular loops

25. A. Primary FSGS This disease of unknown aetiology usually presents as massive proteinuria (usually non-selective),haematuria, hypertension and renal impairment. The associated nephrotic syndrome is often resistant to steroid therapy. All age groups are affected. It usually recurs in transplanted kidneys, sometimes days of transplantation, and particularly in patients with aggressive primary renal disease.

26. B. Secondary fsgs Secondary( Secondary, when an underlying cause is identified ) FSGS with similar glomerular changes is seen as a secondary phenomenon when the Number functioning nephrons is reduced for any reason. As nephrons fail, increased flow through the remaining nephrons leads to glomerular hypertrophy and hyperfiltration With the secondary changes of FSGS. This is actually i ncluding numerous causes such as Toxins and drugs such as  heroin  and  pamidronate .   diabetes mellitus Kidney defects from birth Urine backing up into kidneys Obesity Sickle Cell Anemia Viruses (such as HIV)

27. Prednisolone 0.5–2 mg/kg per day is used in most patients and continued for 6 months • Ciclosporin at doses to stopping urinary protein excretion (tacrolimus is an alternative). Relapse after reducing or stopping ciclosporin is very common so that long-term use is required. • Cyclophosphamide, chlorambucil or azathioprine is used for second-line therapy in adults. Management Medications that suppress your immune system Diuretics and low salt diet help to control edema A medication that blocks a hormone system called the renin angiotensin system (ACE inhibitor or ARB) to control blood pressure or lower urine protein Anticoagulants to prevent blood clots Statins to lower the cholesterol level

28. 4.Membranoproliferative glomerulopathy Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of chronic nephritis that occurs primarily in children and young adults. This entity refers to a pattern of glomerular injury based on the following three characteristic histopathologic findings: Proliferation of mesangial and endothelial cells and expansion of the mesangial matrix Thickening of the peripheral capillary walls by subendothelial immune deposits and/or intramembranous dense deposits Mesangial interposition into the capillary wall, giving rise to a double-contour on light microscopy

29. Three variations are founded Type I  – Discrete immune complexes are found in the mesangium and subendothelial space. Immune complexes are combinations of antigens and antibodies which bind to each other and then become lodged in the kidney. This activates the immune system, which causes inflammation and damage to the kidney itself. Type II – This is also called dense deposit disease. When viewed under the microscope, continuous, dense ribbon-like deposits are found along the basement membranes of the glomeruli, tubules, and Bowman’s capsule. Type III – This is also an immune complex disease, similar to Type I. However, the immune complexes are found in the subepithelial space, and there is disruption of the glomerular basement membrane with large open areas.

30. Management In idiopathic MCGN (all age groups) with normal renal function and non-nephrotic-range proteinuria, No specific therapy is required. Good blood pressure control, ideally with an ACE inhibitor, is of benefit. If no benefit is seen, this treatment is discontinued. Regular follow-up, with control of blood pressure, use of agents to reduce proteinuria and correction of lipid abnormalities, is necessary.

31. Congenital Nephrotic syndrome Congenital nephrotic syndrome (Finnish type) is an autosomal recessively inherited disorder due to mutations in the gene coding for a transmembrane protein, nephrin; . Nephrin is a critical element of the filtration slit, and its loss of function results inmassive proteinuria shortly after birth. The disorder can be diagnosed in utero, as increased α- fetoprotein in amniotic fluid is a common feature. Histologically, some glomeruli are small and infantile, whereasothers are enlarged and more mature, and have diffuse mesangial hypercellularity. Because of the massive proteinuria, some tubules develop microcysts and are dilated. On electron microscopy, complete effacement of the foot processes of visceral epithelial cells is observed. This condition is characterized by relentless progression to ESKD.

32. Treatment Early and aggressive treatment is needed to control this disorder. Treatment may involve: Antibiotics to control infections Blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) to reduce the amount of protein leaking into the urine Diuretics ("water pills") to remove excess fluid NSAIDs, such as indomethacin, to reduce the amount of protein leaking into the urine Fluids may be limited to help control swelling. The provider may recommend removing the kidneys to stop protein loss. This may be followed by  dialysis  or a  kidney transplant .

33. Secondery causes of NS :- HIV associated nephrotic syndrome In HIV-associated nephropathy (HIVAN), glomeruli are characteristically ‘collapsed’ on light microscopy podocytes are enlarged, hyperplastic and coarsely vacuolated, containing protein absorption droplets and overlying capillaries with varying degrees of wrinkling and collapse of the walls. Direct podocyte HIV-1 infection is associated with loss of podocyte-specific markers such Wilms’ tumour factor and synaptopodin in HIVAN. HIVAN presents with nephrotic-range proteinuria, edema and CKD, which can be rapid in progression. Antiretroviral therapy (ART) may reverse the reanal lesions seen, and restores renal function if treatment is commenced early

34. Management Treatment with  highly active antiretroviral therapy  and  angiotensin converting enzyme inhibitors  or  angiotensin receptor blockers has been shown to be beneficial and should be given to all patients unless otherwise contraindicated. General renoprotective measures and the treatment of the complications of nephrotic syndrome and kidney failure are adjunctive. Corticosteroid  treatment can be useful in patients who do not respond to initial treatment. There is some evidence that  ciclosporin  might be helpful in selective cases, however further study of both steroids and ciclosporin is needed before these types of drugs can be considered standard treatment.

35. Amyloidosis Amyloidosis is a systemic acquired or inherited disorder of protein folding, in which normally soluble proteins or fragments are deposited extracellularly as abnormal insoluble fibrils,causing progressive organ dysfunction and death. The abnormal protein may be derived from light chains or immunoglobulin (AL amyloid), or Serum amyloid A protein (AA amyloid). The renal consequences are similar, even if systemic features Differ.

36. Management Treatments that reduce production of the amyloidogenic protein can improve organ function and survival in immunoglobulin-light-chain-related (AL) amyloidosis and hereditary transthyretin-associated (ATTR) Amyloidosis . In AA amyloidosis, production of serum amyloid A can sometimes be decreased by treatment of the underlying inflammatory condition but cannot be completely suppressed. Renoprotective measures should be started. The success of dialysis and kidney transplantation depends on the extent of amyloid deposition in extrarenal sites, especially the heart.

37. Diabetic nephropathy Diabetic renal disease is the leading cause of ESKD in the Western world, arising largely as acomplication of type 2 diabetes mellitus. Diabetic kidney disease occurs in about 20–30% of both type 1 and type 2 diabetics the natural history is similar from the onset of proteinuria, and the histological lesion is the same. Pathology there is constriction of the  efferent arterioles  and dilation of  afferent arterioles , with resulting glomerular capillary hypertension and hyperfiltration . Glomerular hyperfiltration (the GFR increases to >150 mL/min/m2 ) and initial enlargement of kidney volume occur as local vasoactive factors increase flow. The GBM thickens and the mesangium expands.Progressive depletion of podocytes from the filtration barrier (through apoptosis or detachment) results in podocyturia early in the disease. Proteinuria evolves as filtration pressures rise and the filter is compromised. Later, glomerulosclerosis develops with nodules (Kimmelstiel–Wilson lesion - matrix invades the glomerular capillaries and produces deposits called Kimmelstiel-Wilson nodules ) and hyaline deposits in the glomerular arterioles .

38. Management Lifestyle changes (cessation of smoking, attention to salt intake, weight loss and increased exercise) are necessary in preventing progression of any diabetic complication. Aim for good (intensive) glycaemic control. If achieved for even a limited period, this reduces the incidence of ESKD and other microvascular complications in the long term (the so-called ‘legacy effect’. Control dyslipidaemia. • Control blood pressure to <120/80 mmHg with ACE inhibitors or AII-RA; these should be used once microalbuminuria develops, even if blood pressure control is good. Combined use of ACE inhibitors and AII-RA (dual blockade) does not provide additional benefit but is associated with an increased risk of AKI and hyperkalaemia; it is no longer recommended in recent trials.

39. Systemic lupus erythematosus : T his  autoimmune disease  can affect a number of organs, among them the kidney, due to the deposit of  immunocomplexes  that are typical to this disease. The disease can also cause  lupus nephritis . Sarcoidosis : This disease does not usually affect the kidney but, on occasions, the accumulation of inflammatory  granulomas (collection of  immune cells ) in the glomeruli can lead to nephrotic syndrome. Syphilis : kidney damage can occur during the secondary stage of this disease (between 2 and 8 weeks from onset). Hepatitis B : certain  antigens  present during hepatitis can accumulate in the kidneys and damage them. Sjögren's syndrome : this autoimmune disease causes the deposit of immunocomplexes in the glomeruli, causing them to become inflamed, this is the same mechanism as occurs in systemic lupus erythematosus. Other related nephropathy

40. Vasculitis : inflammation of the blood vessels at a glomerular level impedes the normal blood flow and damages the kidney. Cancer : the invasion of the glomeruli by cancerous cells disturbs their normal functioning. Drugs  ( e.g. gold salts,  penicillin ,  captopril gold salts can cause a more or less important loss of proteins in urine as a consequence of metal accumulation. Penicillin is nephrotoxic in patients with kidney failure and captopril can aggravate proteinuria.

41. Sign and symptoms A few other characteristics seen in nephrotic syndrome are: Puffiness around the  eyes , characteristically in the morning. Pitting edema  over the  legs . Fluid in the  pleural cavity  causing  pleural effusion . More commonly associated with excess fluid is pulmonary edema. Fluid in the  peritoneal cavity  causing  ascites . Generalized edema throughout the body known as  anasarca .

42. Complications

43. 1. Infections Patients with NS are at increased risk for infections. ) . Sepsis remains one of the main causes of death in children with NS. 2. Thromboembolism NS is a well-known risk factor for arterial or venous thromboembolism (TE), and patients with severe proteinuria . Due to loss of antithrombin protein with heavy proteinurea. . Hormonal, Urinary loss of hormone-binding proteins contributes to various hormonal abnormalities in patients with NS.

44. 3. Cardiovascular complications An increased risk of cardiovascular disease exists in patients with NS because of hyperlipidemia, increased thrombogenesis, and endothelial dysfunction 21) . Hypercholesterolemia is strongly associated with severity of hypoalbuminemia. There is little or no risk of cardiovascular disease in children with MCNS who are responsive to CS because hyperlipidemia is intermittent and of short duration. Elevated VLDL and LDL should place patients at increased risk for developing atherosclerosis. Endothelial damage from hyperlipidemia may favor influx of lipoprotein into the mesangium, leading to proliferation and sclerosis .

45. 4. Hypovolemic crisis Risk factors for hypovolemic crisis include severely depressed albumin levels, high dose diuretics, and vomiting. The clinical manifestations are tachycardia, cold extremities, poor capillary refill, and moderate to severe abdominal pain, and laboratory tests may show elevated hematocrit and uric acid levels. 5. Anemia Mild anemia is observed on occasion in patients with NS. Anemia is usually microcytic and hypochromic, typical of iron deficiency, but is resistant to therapy with iron because of large loss of serum transferrin in the urine of some nephrotic patients ) . reported some data on the metabolism and regulation of erythropoietin (EPO) and transferrin, which are essential for erythropoiesis in nephrotic children

46. Ayurvedic management of nephrotic syndrome A. Vardhamana pippali:- Fine powder of pippali (Piper longum Linn.) was given in increasing and tapering dosepattern. In this pattern 1 g powder of Piper longum was given twice with honey on the first day. Every day the dose was increased by 1 g eventually to reach to 5 g twice daily. The dose of 5 g was kept for 5 days and then tapered down 1 g every day to finally reach 1 g again. This took 13 days. On the 14th day we performed mild virecana (purgation) with eranda sneha (oil of the seeds of Ricinus communis Linn.). The dose of eranda sneha was 30-40 ml according to the patients’ kostha (frequency and sensitivity of bowels).

47. B . After the completion of purgation following treatment was given for the next 2 weeks: 1. Gokshuradi Guggulu[] – 1 g, 3 times in a day after food with warm water. 2. Varunadi kvatha[] – 40 ml 2 times in a day after food. 3. Haritakyadi kvatha – 40 ml 2 times in a day after food. 4. Rasayana Churna (powder of fruit of Gokshura - Tribulus terrestris Linn. + fruit of Amalaki - Embelica officinalis Gaertn. + stem of Guduchi - Tinospora coridifolia Miers. in equal quantities) – 3 g, 3 times a day with water.

48. Discussion about treatment There is evidence in the literature that nephrotic syndrome may be a consequence of a primary glomerular defect, circulating factors, or an immunological abnormality. Primary glomerular defects mostly due to the proteins which creates the mutations in genes encoding podocyte and GBM proteins. In circulating factors,Protein A immune-adsorption is responsible for the primary nephrotic syndrome. Immunological abnormalities, mostly auto-immune process also creates the primary nephrotic syndrome.

49. All these factors can be concluded under the broad heading of ama according to ayurveda. Immunological abnormalities can be correlated with balabhransha (one of the feature of ama) according to ayurveda. Oja (extreme qualities of all the dhatus) is responsible for appropriate bala. Rasayana therapy increases the quality of all the dhatus. So rasayana therapy increases the proper bala (immunity according to modern medicine) in the body. According to Ayurvedic principles of management of the disease, tissue damage can be prevented and repaired by rasayana drugs because they have the capability to improve qualities of tissues and hence increase resistance of the tissues.

50. Vardhamana pippali rasayana is one of the rasayana therapies which not only increase quality of the tissues but also decrease the ama factors by its ama pachana properties. Recent researches indicate that Pippali (fruits of Piper longum) has antiinflammatory action[we can also use gudadraka) . Extract of Piper longum fruits have been shown to posses various activities like Bio-availibity enhancer, immunemodulatory effect, antiasthamatic and hepatoprotective activity. Varunadi kvatha h aving the kapha-vata shaman and meda-mutradoshahar properties. Though all the three doshas as well as all the dushyas are involved in the disease, kapha and vata are more aggravated in th is disease. Goksuradi guggulu and rasayana churna (combined Ayurvedic preparation) is rasayana for mutravaha srotas and it has also properties for mitigation of kapha and vata . Haritakyadi kvatha is indicated in mutrakricchra and prameha roga.

51. Some other useful drugs :- Kansa haritaki Punarnavaadi kwatha GoKshuradi kashaya Chitraka ghrita Gandeeradyarishtha Phalatrikadyarishtha Agnitundi vati ETC. Single drug therapy :- Punarnava varuna Guduchi Ashwagandha Haridra Badriphala manzishtha

52. NEPHRITIC SYNDROME

53. Nephritic syndrome Glomerular diseases presenting with a nephritic syndrome are often characterized by inflammation in the glomeruli. The nephritic patient usually presents with hematuria, red cell casts in the urine, azotemia, oliguria, and mild to moderate hyperten sion. Proteinuria and edema are common, but these are not as severe as those encountered in the nephrotic syndrome, discussed later.

54. Hematuria Blood in the urine which often, but not necessarily, leads to red discoloration. There are two types of hematuria: microhematuria, which indicates unseen blood, macrohematuria, in which the blood is visible to the eye. Shape of RBC is star shaped also called as dismorphic RBC.

55. RBC cast in urine :- When RBC leak heavy then it produces a kind of resistance to flow in tubules. Then RBC stuck with each other and compresed itself. Filtrate fluid also start to accumulate and kicked out these group of RBC. It come out in urine in cylindrical shape.,this cylindrical shaped structure called as RBC cast. They form in the  distal convoluted tubule  and  collecting ducts  of  nephrons , then dislodge and pass into the urine, where they can be detected by  microscopy .

56. Oliguria Inflamed glomeruli are not make easily leakage of all of these so glomerular filtration rate become less. If GFR become less then formation of urine is not enough. urine formation is less then 400ml/day, this condition called as oliguria. Azotemia Increase level of urea and creatinine in blood stream called as azotemia. When GFR become less then formation of urine is also is not enough. In this condition waste products like urea and creatinine goes up into the blood. And patients start developing azotemia.

57. Hypertension hypertension is result of both of these:- Fluid retention Renin secretion from ischemic kidney

58. Symptoms

59. CAUSES Post-streptococcal glomerulonephritis : - Post-streptococcal glomerulonephritis (PSGN) occurs in childhood. An acute nephritis follows 1–3wee ks after a streptococcal infection. The latent interval between infection and the development of symptoms and signs ofrenal involvement reflects the time taken for immune complex formation and deposition and glomerular injury to occur. Renal biopsy shows diffuse, florid, acute inflammation in the glomerulus (without necrosis but occasionally cellular crescents), with neutrophils and deposition of IgG and complement . U Ultrastructural findings are those of electron-dense deposits, characteristically in the sub-epithelial aspects of the capillary walls. Endothelial cells often are swollen. Similar biopsy findings may be seen in non-streptococcal post-infectious Glomerulonephritis .

60. Management The acute phase should be treated with good blood pressure control, diuretics and salt restriction For oedema, and dialysis as necessary. If recovery is slow, corticosteroids may be helpful. The prognosis is usually good in children. A small number of adults develop hypertension and/or CKD later in life. Therefore, in older patients, an annual blood pressure check and measurement of serum creatinine are Required. In non-streptococcal post-infectious glomerulonephritis, prognosis is equally good if the underlying infection is era dicated. In the case of live bacteria remain inside the body antibiotic sHould Be administered for complete eradication.

61. IgA nephropathy(Berger disease) IgA nephropathy has replaced post-streptococcal glomerulonephritis as the most common form of GN worldwide. IgA nephropathy (), also known as Berger's disease, is a kidney disease that occurs when an antibody called immunoglobulin A (IgA) builds up in your kidneys. This results in local inflammation that, over time, can hamper your kidneys' ability to filter waste from your blood. IgA  nephropathy usually progresses slowly over years, but the course of the disease varies from person to person. Some people leak blood in their urine . Signs and symptoms of IgA nephropathy include: Cola- or tea-colored urine (caused by red blood cells in the urine) Repeated episodes of cola- or tea-colored urine, and sometimes visible blood in your urine, usually during or after an upper respiratory or other infection and sometimes after strenuous exercise Foamy urine from protein leaking into your urine (proteinuria) Pain in the one or both sides of your back below your ribs Swelling (edema) in your hands and feet High blood pressure

62. Management • All patients, with or without hypertension and proteinuria, should receive an ACE inhibitor , to reduce proteinuria and preserve renal function. • Patients with proteinuria of over 1–3 g/day, mild glomerular changes only and preserved renal function should be treated with steroids. Steroids reduce proteinuria and stabilize renal function. • In patients with progressive disease (falling to eGFR <60 mL/min), fish oils or prednisolone with cyclophosphamide for 3 months, followed by maintenance with prednisolone and azathioprine, may be tried

63. Alport syndrome Alport syndrome is a rare hereditary nephritis with haematuria, proteinuria (<1–2 g/day), progressive kidney disease and high-frequency nerve deafness. Approximately 15% of cases may have ocular abnormalities. Alport  syndrome  is caused by  mutations  in three possible  genes :  COL4A3 ,  COL4A4 ,  or COL4A5 . These genes each provide instructions for making one component of a  protein  called type IV collagen, which plays an important role in the glomeruli GBM of the kidneys.  Proteinuria in Alport syndrome is often mild and is the result of glomerular sclerosis, rather than primary loss of slit pores. Type IV collagen is also an important component of the  organ  of Corti, the inner ear structure that transforms sound waves into nerve impulses for the brain Alport  syndrome  is characterized by  kidney disease ,  hearing loss , and eye abnormalities (   type IV collagen plays a role in the eye, where it helps maintain the shape of the lens and the  cells  of the retina. ) Symptoms typically begin in childhood, and the first sign of the condition is usually the presence of blood in the urine ( hematuria ).

64. Management The disease is progressive and accounts for some 5% of cases of ESKD in childhood or adolescence. Patients with mild CKD can be treated with ACE inhibitors to attenuate proteinuria. Exciting experimental evidence suggests that mesenchymal stem cells can transdifferentiate into podocytes and repair basement abnormalities and slow the rate of progression.

65. Anti-GBM glomerulonephritis Goodpasture syndrome (GPS), also known as anti-glomerular basement membrane disease, is a  rare   autoimmune disease  in which antibodies attack the  basement membrane  in lungs and kidneys, leading to bleeding from the lungs and  kidney failure . It is thought to attack the alpha-3 subunit of  type IV collagen , which has therefore been referred to as Goodpasture's antigen. At this point, a triggering stimulus has not been identified for the development of anti-glomerular basement membrane antibodies. However, there are certain human leukocyte antigen (HLA) subtypes that have been paying attention for increased genetic susceptibility to Goodpasture syndrome, most notably HLA-DR15. Goodpasture syndrome is due to circulating auto-antibodies directed at the glomerular basement membrane. The resulting crescentic glomerulonephritis is the result of the antigen-antibody complexes that form at the basement membrane. [ The inflammatory response in that area results in the typical glomerulonephritis clinical picture . The anti glomerular basement membrane (GBM)  antibodies  primarily attack the kidneys and lungs, although, generalized symptoms like malaise, weight loss, fatigue, fever, and chills are also common, as are joint aches and pains.

66. Management • plasma exchange to remove circulating anti-GBM antibodies • steroids to suppress inflammation from antibody already deposited in the tissue • cyclophosphamide to suppress further antibody synthesis.

67. Rapidly progressive glomerulonephritis Rapidly progressive glomerulonephritis (RPGN) is a syndrome with glomerular haematuria (red blood cell casts or dysmorphic red blood cells), rapidly developing acute kidney failure over weeks to monthsand focal glomerular necrosis with or without glomerular crescent development on renal biopsy. The ‘crescent’ is an collection of macrophages and epithelial cells in Bowman's space . RPGN can develop with immune deposits or without immune deposits. It can be classified based on the pattern of immune complex deposition in glomeruli (seen on immunofluorescence): that is, linear, granular and negative immunofluorescent patterns.

68. Management Administer cyclophosphamide either intravenously or orally. Another protocol, which Azathioprine is administered at 2 mg/kg orally in a single daily dose. This is continued for 6-12 months. Methotrexate has been substituted for cyclophosphamide in the initial treatment of granulomatosis F or mild disease and has been used for treatment after initial induction therapy with cyclophosphamide in more severe disease.   Plasmapheresis may be a beneficial addition to therapy for patients who present with severe renal failure (serum creatinine >6 mg/dL) or those who progress despite treatment. Rituximab may improve renal outcomes in antineutrophil cytoplasmic antibody–associated vasculitis .

69. Glomerulonephritis with infective endocarditis GN occurs rarely in patients with infective endocarditis (usually intravenous drug users), or in patients with infected ventriculoperitoneal shunts (shunt nephritis). Histology appearances resemble postinfectious GN but lesions are usually focal and segmental. Crescentic GN with AKI has been described, particularly with Staphylococcus aureus infection. Appropriate antibiotic therapy or surgical eradication of infection in severe cases usually results in a return of normal renal function. GN also occurs associated with visceral abscesses (mainly pulmonary) and is Differantiated from post-infectious GN. Complement levels are normal and immune deposits are absent on biopsy. Management Antibiotic therapy and surgical drainage of the abscess result in complete recovery of renal function in approximately 50% of patients.

70. Thin glomerular basement membrane disease This condition is inherited as an autosomal dominant and typically presents with persistent microscopic glomerular haematuria (red blood cell casts or dysmorphic red blood cells). The diagnosis is made on renal biopsy, which shows thinning of the glomerular capillary basement membrane on electron microscopy. The condition was under-diagnosed and is much more common than previously believed. The prognosis for renal function is usually very good but some patients develop renal insufficiency over decades. The cause of renal impairment in this condition is not known but may be due to secondary FSGS or concomitant IgA nephropathy. Misdiagnosis occurs with Alport syndrome, which shares similar histological features. No treatment is of known benefit.

71. Diagnosis In examining a person with potential nephritic syndrome, a doctor might carry out the following tests: 1 Take patient history:  A doctor will ask the affected person about the time at which their symptoms began and attempt to determine the point at which the kidneys began to excrete protein into the urine. Check appearance and colour of urine:  Urine that is dark in colour may be very concentrated and contain blood. Blood pressure:  Hypertension can be a sign of disrupted kidney function. Edema assessment:  Edema, or fluid gathering in the tissues, can be a sign that there is not enough protein in the blood and may suggest proteinuria. Urine dipstick test:  A simple form of urinalysis that is used as a quick test for blood and protein in the urine. They will use a dipstick test, in which a test-strip of paper is immersed in a urine sample, to check for blood and protein in the urine Urinalysis:  A urine sample will be sent to a laboratory to do a precise check for protein levels and red blood cells. Blood tests:  To check levels of electrolytes, creatinine, blood urea nitrogen, immunoglobulins, antibodies, and other substances. Kidney biopsy:  This relatively straightforward procedure may be performed as an outpatient procedure or after hospital admission, depending on the patient’s particular circumstances. It uses only local anesthetic and is done using ultrasound and specialized biopsy needles to remove a small sample of tissue. 7 Kidney biopsies are a very reliable way of distinguishing chronic glomerulonephritis from other, similar, disorders. 2