Case presentation on membranous nephropathy

1. CASE PRESENTATION
Dipesh Tamrakar
MSc. Clin. Biochemistry

2. CASE HISTORY
• A 43 years old woman from Banepa presented to emergency department in
one of the renown private hospital in Kathmandu with chief complaints of :
dizziness and easy fatiguability for 1 month
• No history of fever, nausea, vomiting, headache, burning micturition, malena,
• regular periods
• normal bowel and bladder habits

3. GENERAL PHYSICAL EXAMINATION
• GC: conscious, oriented to time, place and person
• Pallor (-), icterus (-), dehydration (-) edema (-)
• BP: 110/70 mmHg,
• Pulse: 68 bpm
• Chest: bilateral equal air entry, no added sounds
• CVS: S1S2M0
• P/A: soft, non tender, no organomegaly, BS(+)
• CNS: grossly intact

4. LAB INVESTIGATIONS ???

5. Test Result Reference Range
RBC 4.7 4.5 to 5.5 million/ul
PCV 32.6 36 – 46 %
Hb (g/dl) 10.0 12.0-16.0
MCV 69.8 82.9 - 98 fL
MCHC 30.7 33-36 %
MCH 21.4 27-33 pg
Total leucocyte count 7090.0 4000-11000/cu mm
Neutrophils 76 40-75
Lymphocytes 18 20-45
Monocytes 5 2-10
Eosinophils 01 0-5
Basophils 00 0-1
Platelets 3.11 1.5 – 4.5 lakhs /cu mm

6. Test Result Reference Range
Glucose 91.0 80 – 140 mg/dl
Urea 23.0 15 - 45 mg/dl
Creatinine 0.5 0.5 – 1.0 mg/dl
Na+ 134.0 135-146 mEq/L
K+ 4.1 3.5-5.2 mEq/L
TSH 2.4 0.46 – 4.68 IU/ml
Iron 12.0 37 – 145 g/dl
TIBC 484.0 265 – 497 g/dl
Ferritin 9.0 10 – 291 ng/ml

7. Test Result Reference range
Color, Transparency,
pH
Pale Yellow, Turbid,
Alkaline
Protein +
Glucose negative
WBC 7 Upto 43.9 / L
RBC 17 Upto 25.8 / L
Epi cell 44 Upto 52.3 / L
Cast 1 Upto 2.5 / L
Bacteria 879.0 Upto 454.1 /hpf

8. Tests Results
Stool for occult blood NEGATIVE
PBS:
RBC:
WBC:
PLATELETS:
PARASITES
Microcytic hypochromic red cells, few pencil
cells
Normal count and morphology, No atypical cells
are seen
Adequate on smear
Parasites: Not seen

9. OTHER INVESTIGATION ???

10. PROVISIONAL DIAGNOSIS
• Generalized weakness
• Iron deficiency Anaemia

11. FOLLOW UP AFTER 9 MONTHS
• Presented with swelling of B/L limbs and facial puffiness
• No urgency, frequency, bilateral flank pain, sore throat, joint pain, fever,
rashes, SOB or cough
• Ortho consultation:
• B/L ankle swelling + pain
• Interscapular ache
• Normal appetite, bowel and bladder habit, menstruation
• Myofascial pain

12. GENERAL PHYSICAL EXAMINATION
• GC: conscious, oriented to time, place and person
• Pallor (-), icterus (-), dehydration (-) edema (-)
• BP: 130/80 mmHg,
• Pulse: 74 bpm
• Chest: bilateral equal air entry, no added sounds
• CVS: S1S2M0
• P/A: soft, non tender, no organomegaly, BS(+)
• CNS: grossly intact

13. LAB INVESTIGATIONS ???

14. Test Result Reference Range
RBC 4.7 4.5 to 5.5 million/microlit
PCV 40.1 36 – 46 %
Hb (g/dl) 13.1 12.0-16.0
MCV 83.3 82.9 - 98 fL
MCHC 32.6 31.8 -34.7 %
MCH 27.2 27-33pg
Total leucocyte count 7190.0 4000-11000/mm3
Neutrophils 77 40-75
Lymphocytes 17 20-45
Monocytes 5 2-10
Eosinophils 01 0-5
Basophils 00 0-1
Platelets 2.25 1.5 – 4.5 lakhs /cu mm

15. Test Result Reference Range
Glucose 74.0 80 – 140 mg/dl
Urea 17.0 15 - 45 mg/dl
Creatinine 0.5 15 - 45 mg/dl
Na+ 135.0 135-146 mEq/L
K+ 3.4 3.5-5.2 mEq/L
Albumin 2.5 3.5 – 5.0 g/dl
HbA1c 6.2 Non Diabetic <6.4%
Urinary creatinine 45.3 800 – 2800 mg/day
Urinary protein 105.6 <12.0 mg/dl

16. Test Result Reference Range
Uric acid 3.6 2.5 - 6.2 mg/dl
Triglyceride 125 <150.0 mg/dl
Cholesterol 227 <240 mg/dl
HDL cholesterol 63.0 >45 mg/dl
LDL cholesterol 139.0 <130.0 mg/dl
SGOT 21.0 14 – 46 U/L
SGPT 18.0 9 – 52 U/L
CRP 1.0 <5.0 mg/L
Anti-CCP 39.4 <45.0 U/ml
RF <14.97 <30.0 IU/ml

17. Test Result Reference range
Color, Transparency,
pH
Pale Yellow, Clear,
Acidic
Protein ++
Glucose Negative
WBC 20 Upto 43.9 / L
RBC 2 Upto 25.8 / L
Epi cell 35 Upto 52.3 / L
Cast 0 Upto 2.5 / L
Bacteria 12 Upto 454.1 /hpf

18. Test Result Reference range
24 hrs urinary protein 1827.0 42 – 225 mg/day
Urine vol: 1400 ml
Urine protein: 130.5 mg/dl
PT 13.1 11.1 – 14.4 sec
INR 1.02
Phospholipase A2 receptor antibody (PLA2R) : Negative

19. Test Result Reference Range
ANA 6.78 <40 AU/ml: Negative
>40 AU/ml: Positive
Anti-HIV 1+2 0.09 Reactive: 1.0
Negative: <0.9
Borderline: 0.9 and <1.0
Anti-HCV 0.03 Reactive: 1.0
Negative: <0.9
Borderline: 0.9 and <1.0
HBsAg 0.08 Reactive: 1.0
Negative: <0.9
Borderline: 0.9 and <1.0

20. ABDOMINAL AND PELVIC USG REPORT
• Normal impression for Liver, Gall bladder, CBD, Pancrease, Spleen,
Bladder and Uterus
• Right kidney: 11.1 cm size with normal impression
• Left Kidney: located in the pelvis in left paravertebral region measuring
5.7 x 9.2 cm in size with no other abnormalities
• Final Impression: Pelvic left Kidney

21. RENAL BIOPSY

22. PROVISIONAL DIAGNOSIS
• Membranous nephropathy
• Persistent proteinuria

23. IRON DEFICIENCY ANEMIA
• “A condition in which the number of RBCs or their oxygen
carrying capacity is insufficient to meet the physiological needs,
which vary by age, sex, altitude, smoking and pregnancy status”
• Iron deficiency anemia is a type of anemia in which the supply of iron
to bone marrow is inadequate and total body iron is deficient to
support optimal erythropoiesis in the developing red cell mass
• IDA is characterized by a defective development of red cells resulting in
the production of small pale erythrocytes.

24. • Iron is a component of various heme proteins, including cytochromes,
myoglobin, catalase and peroxidase.
• Microcytic hypochromic red cells
• MCV<80fl
• MCH<25pg
• Body iron stores depleted
• Level of circulating iron is reduced
• In Nepal, 35% of non-pregnant women of age group 15 – 49 yrs
suffers from anemia in the year 2011 (Nepal National Anemia Profile)

25. DAILY IRON REQUIREMENTS
• Infants up to 4 months : 0.5 mg
• Infants 5-12 months and children : 1 mg
• Menstruating women : 3 mg
• Pregnancy : 3-4 mg
• Adult men and postmenopausal women : 1 mg
• The loss is about 1 mg / day.
• To balance the daily iron loss of 1 mg , about 10% of the daily iron
intake is absorbed.

26. CLINICAL FEATURES
• Fatigue, restless legs, palpitations, breathlessness.
• Koilonychia/plantynychia: finger nail become thin, flattened, brittle & finally spoon
shaped.
• Angular stomatitis, glossitis: papillae of tongue making the surface smooth.
• Atrophic gastritis – Inflammation of the lining of the stomach
• Achlorhydria – lack of hydrochloric acid secretion in the stomach
• Dysphagia – difficulty in swallowing because of esophageal web, known as
Plummer-Vinson syndrome
• Most common characteristics symptoms is PICA i.e. an abnormal and intense
desire to eat strange substances such as clay, paint, cardboard, coal, etc.

28. LABORATORY INVESTIGATIONS OF IDA
• Routine RBC parameters:
• Hb, RBC count, hematocrit & Red cell indices
• Microscopic examination
• Peripheral blood film
• Grading of marrow iron stores (Gold standard)
• Serum assays
• Serum ferritin
• Serum iron
• Serum transferrin, TIBC
• Transferrin saturation

29. KIDNEY
• A retroperitoneal organ
• Normal size: 11-15 cm in adults
• Right kidney usually shorter than
the left (upper limit of variation in
length between right & left 1.5 cm)

30. ECTOPIC KIDNEYS
• An ectopic kidney is a birth defect in which a
kidney is located in an abnormal position. In
most cases, people with an ectopic kidney
have no complaints.
• In other cases, the ectopic kidney may create
urinary problems, such as urine blockage,
infection or urinary stones.
• Researchers estimate that ectopic kidney
occurs once in every 1,000 births
• An ectopic kidney may remain in the pelvis,
close to the bladder.

31. MEMBRANOUS NEPHROPATHY
• Membranous Nephropathy (MN) is a kidney disease that can occur by itself (primary) or
in conjunction with several other diseases (secondary)
• Glomerular disease
• The diagnosis of MN is made on kidney biopsy (immunofluorescence, and electron
Microscopy)
• The most common cause of Nephrotic syndrome in 60 - 70%
• Normal or mildly elevated blood pressure at presentation
• Urine: Benign urinary sediment and non selective proteinuria
• MN is caused by the build- up of immune complexes within the kidney itself.
• Usually occurs in adults older than forty

32. SYMPTOMS
• Edema or swelling typically starts in the feet and legs that can move into the
hips and abdomen as well
• High blood pressure
• High cholesterol
• Tendency to form blood clots
• Cause protein in the urine alone – NEPHROTIC SYNDROME
• (The commonest presentation of IMN is nephrotic syndrome with
preserved kidney function)

36. CHARACTERISTICS OF IDIOPATHIC MN
PATHOGENESIS
• Anti PLAR2 Ab (70 – 80%)
• Th2 Humoral Immunity (Anti thrombospondin type 1 domain
containing 7A – THSD7A 2.5 – 5%)
• IgG4 subclass
• C5b9 (MAC)

37. GENERAL SUPPORTIVE THERAPY
• Angiotensin inhibition
• Lipid lowering
• Anticoagulation (if serum albumin <2.5 g/dl and additional risks for
thrombosis
• Diuretics to control edema, salt restriction
• Maintenance of adequate nutrition

39. • Autoimmune: SLE, RA,Autoimmune thyroid disease
• Infections: HCV, HBV, malaria
• Malignancies
• Drugs/toxins: NSAIDS, mercury compounds, COX2 inhibitors
• Miscellaneious: DM, sickle cell disease, sarcoidosis, polycystic kidney disease

42. • The conventional definition of nephrotic syndrome in the published
literature is proteinuria 43.5 g per 24 hours (in children, 440
mg/m2/hr or PCR 42000 mg/g [4200 mg/ mmol] or 4300 mg/dl or 3þ
on urine dipstick) plus hypoalbuminemia and edema.

43. SUMMARY
• The first case of anemia may be due to inadequate supply of iron which was
cured after folic acid and iron supplements.
• The second case diagnosed as membranous nephropathy as far don’t seem to
be linked with first case of anemia
• The case was diagnosed by renal biopsy but cause is not confirmed yet.
• The condition of left pelvic kidney seems to have least importance in causing
this ailment but this could be of greater importance in drug dose
management and monitoring if severity persists.

44. • Since the PLA2R antibody was negative, the management went for
supportive therapy.
• The management was done by Antihypertensive (Losartan 50 mg and
lipid lowering drug (Atorvastatin 20 mg)
• If the case worsen with proteinuria >3.5 g/day and positive for PLA2R
antibody, the treatment would be by use of steroids.
• Still research is ongoing on for better non-invasive marker of
membranous nephropathy

45. THANK
YOU