Case discussion

Extern Theerawat Naksanguan

 Case
Patient profile: หญิงไทยโสดอายุ 46 ปี
Chief complaint: ขา 2 ข้างบวมมากขึ้นมา 1wk
Present illness:
2 เดือนก่อนมารพ.มีอาการบวมขา และลำตัวใบหน้า ไม่มีหอบเหนื่อย ไม่มี
แน่นหน้าอก นอนราบได้ปกติ ไม่มีตวั เหลืองตาเหลือง ไม่มีไข้ ไม่มีเบื่ออาหารน้ำ
หนักลด มาตรวจที่รพ.บุรีรัมย์ได้admit
admit แพทย์บอกว่าเป็ นโรคไต หลังออกจาก
รพ.อาการบวมลดลง มาF/U OPD Med อีก 1 เดือนมีอาการบวมมากขึ้น
และมีภาวะhyperglycemia admit อีกครั้งเพื่อตรวจวินิจฉัยเพิ่มเติม
อาการบวมลดลง
1 wk ก่อนมีนดั F/Uมีอาการบวมมากขึ้นจึงมารพ. ปัสสาวะออกน้อยลง
ประมาณ 2 แก้วน้ำ/วัน
 Case
► Past history :
 underlying DM 20 yr : Mixtard 30-0-20
 HT : amlodipine 1x1, Enarapril 1x1, Propanolol
1x1
 CRF?
 Cataract
 ปฏิเสธประวัติดื่มสุ รา ,การใช้ยาหม้อยาลูกกลอน
► Family history : ปฏิเสธโรคทางกรรมพันธุ์
► Drug allergy : -
 Physical examination

► Vitalsigns : Temp 37, BP 160/110 ,PR 80

RR 20
► GA : a woman , mild pale ,no jaundice,no
dyspnea
► HEENT : Puffy face and ,not pale
conjuctivae , anicteric sclerae, JVP not
engorged ,parotid gland not enlarge , no
malar rash , no oral ulcer ,
► LN. : can’t palpable
► Skin : no petechiae , no ecchymosis
► Chest & Lung : Clear,equal breath sound ,no
adventitious sound
► Abdomen : soft not tender , no
hepatosplenomegaly ,bimanual palpation –ve
► Extremities : Pitting edema 4+ ,no joint swelling
► Neuro : grossly intact
 Investigation
► CBC ;
 Hb 8.47 Hct 25.6 WBC 7360 ; N91, L3.51
 Plt 194000
► Electrolyte BUN/Cr ;
 Na 142.6 ,K 4.41 ,Cl 109.3 ,CO2 27
 BUN/Cr 71/2.0
 Blood glucose 220
► LFTs ;
 TP 5.3 , Glob 3.1 , Alb 2.2 , Chol 581
 Tbil 0.4, Dbil 0.1, AST/ALT 26/61 ,ALP 78
► UA : Sp.gr 1.015 , protein 3+ ,Sugar 2+
WBC 0-1,RBC 0-1 ,
► Urine protein 24 hr ; 9,492 mg
► VDRL = Non react
► ANA = +ve homogenous pattern
► LE cell = negative
 Pertinent findings
► Generalized Edema
► Hyperalbuminuria
► Hypoalbuminemia
► Hypercholesterolemia
► Underlying DM HT
 Problem list
► Nephrotic syndrome DDx Lupus nephritis
 Edema
► Definition ;
 increase volume of interstitial fluid
► Etiology ;
 Localized edema
► Venous / lymphatic obstruction
 Generalized edema
► CHF
► Pericardial disease
 Chronic constrictive pericarditis
 Pericarditis with effusion
► Liver
disease
► Hypoalbuminemic states
 Nephrotic syndrome
 Protein-losing enteropathy
 Malnutrition
 Nephrotic Syndrome
► Characterized by
 Heavy proteinuria (>3.5g/day)
 Hypoalbuminemia (<2.5g/dl)
 Generalized Edema
 Hypercholesterolemia (>250mg/dl)
 Normal renal function
 Secondary Nephrotic syndrome

► Postinfectious etiologies
► Collagen vascular disease (eg, systemic lupus
erythematosus [SLE], rheumatoid arthritis,
polyarteritis nodosa)
► Henoch-Schönlein purpura
► Hereditary nephritis
► Sickle cell disease
► Diabetes mellitus
 Secondary Nephrotic syndrome
► Amyloidosis
► Malignancy (eg, leukemia, lymphoma, Wilms
tumor, pheochromocytoma)
► Toxins (eg, bee sting, poison ivy and oak, snake
venom)
► Medications (eg, probenecid, fenoprofen,
captopril, lithium, warfarin, penicillamine, mercury,
gold, trimethadione, paramethadione)
► Heroin use
 Post infectious cause
► Group A beta-hemolytic streptococci
► Syphilis
► Malaria
► Tuberculosis
► Viral infections (eg, varicella, hepatitis B,
HIV type 1, infectious mononucleosis)
 Primary nephrotic syndrome
Histologic classification
► Focal segmental glomerulosclerosis*
► Membranous nephropathy
► Minimal change disease
► Membranoproliferative glomerulonephritis*
► Fibrillary-immunotactoid glomerulopathy
► Mesangial proliferative GN(IgM nephropathy)*
► IgA nephropathy

Minimal steroid-responsed*
 Pathophysiology
► concentration of heparan sulfate
mucopolysaccharide in the basement
membrane is lower
► protein cross the barrier are excreted.
► High glomerular permeability
 hyperalbuminuria
 hypoalbuminemia.
 greater transcapillary filtration of water and the
development of edema.
Structural change lead to proteinuria
► endothelial surface damage, causing loss of
the negative charge
► glomerular basement membrane damage
and
► effacement of the foot processes
► Recently,congenital nephrotic syndrome of
the Finnish type has been determined to be
caused by mutations in the gene known as
NPHS1. This gene codes for a cell adhesion
protein called nephrin, which is synthesized
by podocytes.
 Pathophysiology
► Urinary Ig losses lower the patient's resistance to
infections and increase the risk of serious sepsis
and peritonitis.
► The loss of antithrombin III and plasminogen via
urine and the simultaneous increase in clotting
factors, especially factors I, VII, VIII, and X,
increases the risk for arterial thrombosis, venous
thrombosis, and pulmonary embolism, which
occurs in 5% of children with nephrotic syndrome.
► vitaminD–binding protein and complexes
excretion leading to
 (1) malabsorption of calcium and development
of bone disease (eg, osteitis fibrosa cystica)
because of enhanced parathyroid hormone
production
 (2) osteomalacia because of impairment in
mineralization.
Two pathogenic processes are operative,
including
(1) hypoproteinemia stimulating generalized
protein synthesis in the liver, including the
lipoproteins
(2) diminution of lipid catabolism caused by
reduced plasma levels of lipoprotein lipase.
► Inadults, the most common form of
glomerulopathy
 membranous glomerulonephritis,
 FSGS.
 diabetic nephropathy is emerging as a major
cause of nephrotic syndrome.
 Signs and symptoms
► Facialswelling or anasarca
► Edema of dependent parts ; ankles or
legs.
► A hypercoagulable state leading to
thrombotic complications
► lethargy, poor appetite, weakness, and
occasional abdominal pain.
►A quantitative estimation of 24-hour urine
protein excretion is the standard method
(>3.5 g/day)
 Nephrotic levels of proteinuria are
associated with a ratio of urinary protein to
urinary creatinine of greater than 2
► Blood: serum creatinine, urea nitrogen,
serum albumin, and serum lipids.
► Other tests: In adult's, testing cryoglobulins
and performing serum protein
electrophoresis or urine protein
electrophoresis can be useful for detecting
the etiology of nephrotic syndrome.
 Others tests (secondary causes)
► DM ; HbA1c , retinopathy
► SLE ; ANA , anti-dsDNA ,Anti-Sm ,others..
► Post infectious process ; Complement ,
HBV,HCV,HIV,
 Renal biopsy
► Indicated in the following circumstances:
 Congenital nephrotic syndrome
 Children older than 8 years at onset
 Steroid resistance
 Frequent relapses or steroid dependency
 Significant chronic nephritic manifestations
 Renal biopsy
 Adult nephrotic syndrome: Note that a renal
biopsy is not indicated in adults when the
nephrotic syndrome is due to an obvious cause
such as diabetes mellitus, ie, when the patient
has other diabetes-related overt complications.
 Medical Care
 Acute management
 Hospitalization should be considered if a patient
has generalized edema severe enough to cause
respiratory distress
 An effective regimen is to give salt-poor albumin
at 1 g/kg, followed by intravenous furosemide
 A cornerstone of treatment of nephrotic
syndrome in adults is ACE inhibitors and/or
adrenergic receptor binders.
► Medication
 Prednisone (Deltasone, Orasone, Meticorten,
Sterapred)
►60 mg/m2/d PO, titrate to a maximum 80
mg/m2/d until remission; then, 40 mg/m2/d,
titrate to 60 mg/m2 qod for 4 wk
 Immunomodulators
►Cyclophosphamide (Cytoxan)
 40-50 mg/kg IV in 1 divided dose over 3 d
►Cyclosporine (Sandimmune)
 5-15 mg/kg PO qd or divided bid; IV dose is one third
total oral dose via infusion over 6 h
 Medical treatment
► Prednisolone 60 mg/m2/d PO (2mg/kg/day)
divide tid x 4-6 Wks
► Then taper off by once daily day-another
day x 4-6 Wks
► If not response (persistent edema
proteinuria 2+) called “Steroid resistant”
that need Renal biopsy
► In frequent relapser, steroid dependent may
be immunosuppressant is indicated
 General management
► The diet should provide adequate energy (caloric)
intake and adequate protein (1-2 g/kg/d).
► A diet with no added salt is advised if the patient
is edematous.
► Management of hyperlipidemia is controversial and
could be of some importance if the nephrotic state
is prolonged.
► Fluid restriction is not usually required unless the
edema is severe.
 Complications
 1.Infection (major complication)
 susceptibility to
 Streptococcus pneumoniae
 Haemophilus influenzae
 Escherichia coli, other Gram -ve
 Varicella infection
-bacterial sepsis


-cellulitis,


-pneumonia


- peritonitis

 Factors precipitate
 -Decreased immunoglobulin levels
 -Edema fluid acting as a culture medium
 -Protein deficiency
 -Decreased bactericidal activity of the
leukocytes
 -Immunosuppressive therapy
 Factors precipitate
 -Decreased perfusion of the spleen caused
by hypovolemia
 -Urinary loss of a complement factor
(properdin factor B) opsonizes certain
bacteria
 Complications
2. Thromboembolism
MN>FSGS >diabetic glomerulopathy
► The factors include
 Thrombocytosis ; plt aggregation
 Antithrombin III, Protein C ,S decrease
 Procoagulant factor(fibrinogen ,factor VII)
increase

-Renal vein thrombosis

-Pulmonary embolism
 Complications
 3. Hypovolemia (hypoalbuminemia<1.5 g/dL)
Symptoms and Signs :

Vomiting

Abdominal pain

Diarrhea

Cold hands and feet

Delayed capillary filling

Oliguria

Tachycardia ,Hypotension
 Complications
 4. Acute renal failure
 Factors

GN

Hypovolemia

Sepsis

Edema of the kidneys  pressure-mediated
reduction in the GFR
 Complications
 Hypertension


-Acute nephritis


-Hyperreninemic state of nephrotic syndrome
induced by hypovolemia and reduced perfusion
of the kidneys
Others
► Tetany (hypocalcemia)
► Adverse effects of treatment Corticosteroids
and other immunosuppressive drugs (eg,
cyclophosphamide, levamisole, cyclosporin)