nephrotic and nephritic syndrome

1. NEPHROTIC SYNDROME AND
NEPHRITIC SYNDROME
SUBMITTED TO
DR. DIGAMBARNARTAM(HOD,MD)
DR. PAWANGARG(MD)
DR. ARVINDTRIPATHI(MD)
SUBMITTED BY
RATNESH KUMAR SHUKLA
B. A. M. S. Final year

2. • REFERENCE :-
• KUMAR AND CLARKS CLINICAL MEDICINE, 9TH EDITION, CHAPTER 20-KIDNEY AND URINARY
TRACT DISEASE
• HARRISONS PRINCIPLE OF INTERNAL MEDICINE 20TH EDITION
• API TEXTBOOK OF MEDICINE, SECTION 19
• TEXTBOOK OF PATHOLOGY, BY HARSHMOHAN
• ROBINS BASIC PATHOLOGY
• ESSENTIAL OF MEDICAL PHYSIOLOGY 6TH 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:
1. A RENAL CORPUSCLE
(MALPIGHIAN BODY)
2. 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.

6. STRUCTUREOF GLOMERULARWALL
GLOMERULAR CAPILLARY WALL IS FILTERING AREA.
• IT CONSISTS OF THREE BASIC STRUCTURE
1. THE LAYER OF FENESTRATED ENDOTHELIUM
2. GLOMERULAR BASEMENT MEMBRANE
3. VISCERAL EPITHELIAL LAYER(PODOCYTES)

9. GLOMERULARFILTRATIONBARRIER
• URINE FORMATION BEGINS AT THE GLOMERULAR FILTRATION BARRIER.
• THEGLOMERULAR FILTER THROUGH WHICH THE ULTRAFILTRATE HAS TO PASS
CONSISTS OF THREE LAYERS: THE FENESTRATED ENDOTHELIUM, THE
INTERVENINGGLOMERULAR BASEMENT MEMBRANE, AND THE PODOCYTE SLIT
DIAPHRAGM.
• THERE ARE TWO KINDKINDS OF BARRIER FOR FILTRATION .
1. SIZE BARRIER
2. ION BARRIER

10. 1.SIZE BARRIER

12. 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.

13. NEPHROTIC
SYNDROME

14. NEPHROTICSYNDROME
• NEPHROTIC SYNDROME REFERS TO CLINICAL CONDITION THAT INCLUDES FIVE
MAIN CHARACTERS :-
1. MASSIVE PROTEINURIA (MORE THEN 3.5GM/DAY)
2. HYPO ALBUMINAEMIA (LESS THEN 3GM/DL)
3. GENERALIZED EDEMA
4. HYPERLIPIDAEMIA (INCREASE CHOLESTEROL AND TRIGLYCERIDES)
5. LIPIDUREA

15. 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 :-
1. SELECTIVE PROTEINURIA (ONLY ALBUMIN LEAKED OUT)
2. NON-SELECTIVE PROTEINURIA

16. 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.

17. 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:
1. HYPOPROTEINEMIA STIMULATES PROTEIN SYNTHESIS IN THE LIVER,
RESULTING IN THE OVERPRODUCTION OF LIPOPROTEINS.
2. LIPID CATABOLISM IS DECREASED DUE TO LOWER LEVELS
OF LIPOPROTEIN LIPASE, THE MAIN ENZYME INVOLVED IN LIPOPROTEIN
BREAKDOWN.

18. 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.

20. 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”.

22. CAUSESOF NEPHROTICSYNDROME
• NEPHROTIC SYNDROME MAY BE:-
1. PRIMARY
2. SECONDARY
1. Primary causes –
• Minimal change disease
• Membranous glomerulopathy
• Focal segmental glomerulosclerosis
• Membranousproliferative glomerulopathy
2.Secondery causes :-
1. DM,
2. Amyloidosis
3. Drugs (gold, penicillamine)
4. Infection (malaria, syphilis,HIV,… ..)

23. 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.

25. • 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.

26. 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.

27. 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).

28. 2.MEMBRANOUSGLOMERULOPATHY
• 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.

30. CAUSESOF MEMBRANOUSGLOMERULOPATHY
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

31. 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.

32. 3.FOCALSEGMENTALGLOMERULOSCLEROSIS
• 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.
• IMMUNOFLUORESCENCE 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

33. 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.
•

34. B. SECONDARYFSGS
• 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 INCLUDING 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)

36. 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.
Manageme
nt
• 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

37. 4.MEMBRANOPROLIFERATIVEGLOMERULOPATHY
• 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:
1. PROLIFERATION OF MESANGIAL AND ENDOTHELIAL CELLS AND EXPANSION OF THE MESANGIAL
MATRIX
2. THICKENING OF THE PERIPHERAL CAPILLARY WALLS BY SUBENDOTHELIAL IMMUNE DEPOSITS
AND/OR INTRAMEMBRANOUS DENSE DEPOSITS
3. MESANGIAL INTERPOSITION INTO THE CAPILLARY WALL, GIVING RISE TO A DOUBLE-CONTOUR ON
LIGHT MICROSCOPY

38. 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.

40. 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.

41. CONGENITAL NEPHROTICSYNDROME
• 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.

42. • 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.

43. SECONDERY CAUSES OF NS :-
HIVASSOCIATEDNEPHROTICSYNDROME
• 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

44. MANAGEMENT
• TREATMENT WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY AND ANGIOTENSIN
CONVERTING ENZYME INHIBITORS OR ANGIOTENSIN RECEPTOR BLOCKERSHAS 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.

45. 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.

46. 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.

47. 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 .

49. 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.

50. • SYSTEMICLUPUSERYTHEMATOSUS:
THIS 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).
• HEPATITISB:
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,
Other related nephropathy

51. • 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.GOLDSALTS,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.

52. 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.

55. COMPLICATIONS
•

56. • 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.

57. • 3. CARDIOVASCULARCOMPLICATIONS
• AN INCREASED RISK OF CARDIOVASCULAR DISEASE EXISTS IN PATIENTS WITH NS
BECAUSE OF HYPERLIPIDEMIA, INCREASED THROMBOGENESIS, AND
ENDOTHELIAL DYSFUNCTION21). 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 VLDLAND 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.

58. • 4. HYPOVOLEMICCRISIS
• 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

59. 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).

60. 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.

61. 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.

62. • 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.

63. • 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 HAVING 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 THIS 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.

65. SOME OTHER USEFUL
DRUGS :-
1. KANSA HARITAKI
2. PUNARNAVAADI KWATHA
3. GOKSHURADI KASHAYA
4. CHITRAKA GHRITA
5. GANDEERADYARISHTHA
6. PHALATRIKADYARISHTHA
7. AGNITUNDI VATI ETC.
Single drug therapy :-
1. Punarnava
2. varuna
3. Guduchi
4. Ashwagandha
5. Haridra
6. Badriphala
7. manzishtha

67. NEPHRITIC SYNDROME
•

68. NEPHRITIC SYNDROME
• GLOMERULAR DISEASES PRESENTING WITH A NEPHRITIC SYNDROME ARE OFTEN
CHARACTERIZED BY INFLAMMATION IN THE GLOMERULI.
• THE NEPHRITIC PATIENT USUALLY PRESENTS WITH
1. HEMATURIA,
2. RED CELL CASTS IN THE URINE,
3. AZOTEMIA,
4. OLIGURIA,
5. AND MILD TO MODERATE HYPERTENSION.
• PROTEINURIA AND EDEMA ARE COMMON, BUT THESE ARE NOT AS SEVERE AS
THOSE ENCOUNTERED IN THE NEPHROTIC SYNDROME, DISCUSSED LATER.

70. HEMATURIA
• BLOOD IN THE URINE WHICH OFTEN, BUT NOT
NECESSARILY, LEADS TO RED
DISCOLORATION.
• THERE ARE TWO TYPES OF HEMATURIA:
1. MICROHEMATURIA, WHICH INDICATES
UNSEEN BLOOD,
2. MACROHEMATURIA, IN WHICH THE
BLOOD IS VISIBLE TO THE EYE.
• SHAPE OF RBC IS STAR SHAPED ALSO
CALLED AS DISMORPHIC RBC.

71. RBCCASTIN 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.

73. • 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.

74. HYPERTENSION
HYPERTENSION IS RESULT OF BOTH OF THESE:-
1. FLUID RETENTION
2. RENIN SECRETION FROM ISCHEMIC KIDNEY

75. • SYMPTOMS

76. CAUSES
POST-STREPTOCOCCALGLOMERULONEPHRITIS:-
• 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
.

78. • 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 ERADICATED.
• IN THE CASE OF LIVE BACTERIA REMAIN INSIDE THE BODY ANTIBIOTIC SHOULD BE
ADMINISTERED FOR COMPLETE ERADICATION.

79. IGA NEPHROPATHY(BERGERDISEASE)
• 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:
1. COLA- OR TEA-COLORED URINE (CAUSED BY RED BLOOD CELLS IN THE URINE)
2. 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
3. FOAMY URINE FROM PROTEIN LEAKING INTO YOUR URINE (PROTEINURIA)
4. PAIN IN THE ONE OR BOTH SIDES OF YOUR BACK BELOW YOUR RIBS
5. SWELLING (EDEMA) IN YOUR HANDS AND FEET
6. HIGH BLOOD PRESSURE

81. 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

82. ALPORT SYNDROME
• ALPORTSYNDROME 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, ORCOL4A5 . 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).

84. 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.

85. ANTI-GBMGLOMERULONEPHRITIS
• 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 ANTIGLOMERULAR 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.

87. 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.

88. 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.

91. • 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 FOR 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.

92. GLOMERULONEPHRITISWITHINFECTIVE 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.

93. THIN GLOMERULARBASEMENT 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.

94. 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