1. An INTERESTING CASE OF PEDIATRIC RPRF
Dr GS Karthik
2nd year PG, NEPHROLOGY
OSMANIA GENERAL HOSPITAL

2. HISTORY 5y male child Informant-mother resident of Hyderabad. C/O-
1) Fever of 10 days duration, high grade, associated with chills.
2) vomitings of 4days ,non-bilious,non-projectile.
3) Blood in urine at the onset of fever for first 2 days, 2-3episodes. Subsided spontaneously.

3. HISTORY CONT…… No H/O of skin rash/ throat pain/cough/cold.
No H/O joint pains.
No H/O cry during micturition
No H/O Pedal edema, no facial puffiness
No H/O decreased appitite.

4. PAST HISTORY
4 Months ago child was admitted with fever in outside hospital found to have anemia.
Hb- 4.7gm%
Wbc-14,400cumm
PLT-4,36,000 lakhs
Renal parameters were normal.
LFT-NOT AVAILABLE.
He was treated with iv antibiotics, 2 units packed cell transfusion and discharged in stable condition , no follow up later on.

5. PERSONAL HISTORY
Product of 3rd degree consanguinous marriage. 2nd in birth order.
FTNVD
Cried immediately at birth.
Vaccinated as per IAP schedule
Attained mile stones normally.

6. COURSE IN HOSPITAL ON GENERAL EXAMINATION TEMP- NORMAL HR -110/MIN
RR -28/MIN
BP -100/70MMHG( 90th percentile)
PALLOR PRESENT
NO ICTERUS, ADENOPATHY, EDEMA ,CYANOSIS OR CLUBBING.

7. ANTROPOMETRY WEIGHT- 15.7KG ; 3rd percentile
HEIGHT CM ; 50th percentile
Mid arm circumference – 14.2cm.

8. SYSTEMIC EXAMINATION ABDOMEN –SOFT,NO TENDERNESS, NO ORGANOMEGALY
RESPIRATORY SYSTEM- NORMAL
CVS –NORMAL
CNS –NORMAL
MUSCULOSKETETAL- NO BONE OR MUSCLE TENDERNESS.

9. INVESTIGATIONS DATE 21/6 22/6 23/6 24/6 25/6 27/6 28/6 HB 3.9(PRBC)
4.9
4.4(PRBC)
4.6(PRBC
6.4(PRBC
8.4
8.9
TLC
9500
7500
6100
4400
5600
5800
PLT
4.5
4.2
4.3
4.4
3.9
UREA
193
264
318
324
218 98 50
CREAT
3.6
5.9
7.3
7.1
5.4
3.3
1.8 Na
128
129
130
133
134 K 5
4.8
6.9(PD)
5.2
3.4
UPCR
0.6
0.7
INVESTIGATIONS

10. LABS CONT…. CUE : specific gravity-1.030 ; albumin 1+
active sediments 2+
pus cells – nil ; sugars –nil.
LFT – normal except for albumin -2.4
Smear for mp- negative
Coagulation profile –normal.
ASO titre- <200
Blood culture- negative
Urine culture-negative

11. IMAGING AND SEROLOGY USG ABDOMEN :GRADE 1 RPC,
RK-9.2X3.8CM, LK-8.4X 4CM
NO HEPATOSPLENOMEGALY, NO OTHER ABNORMALITY.
CT ABDOMEN:RK-9.5 X 4 CM, LK-8.4 X4 CM
(NORMAL -6.4 CM TO 9.1), NORMAL STUDY.
ANA PROFILE- NORMAL
C 3 AND C4 –NORMAL.

12. DIAGNOSIS RPRF AZOTEMIA ANEMIA , NO FLUID OVERLOAD
NO HYPERTENSION, NON-OLIGURIC.
Started on IPD.

13. ANEMIA WORK UP MCV-82.1fl MCH-25.3 pg MCHC – 30.8 g/dl
Corrected Reticulocyte count-1.5%
B12 and folate level- normal
Normocytic normochromic anemia, no schistocytes
Stool for occult blood 2 samples -negative
Direct coombs test- negative
LDH-808
HPLC- no abnormal hemoglobin.
Sickling test- negative

14. BONE MARROW EXAMINATION
Bone marrow aspiration-cellularity-normal
E : M ratio : 1:2
Impression : micronormoblastic erythroid maturation.
Bone marrow biopsy : micronormoblastic erythropoiesis

15. AFTER 60 CYCLES OF IPD RENAL BIOPSY DONE
LM-show 9 glomeruli, these are normal size with normal mesangial cellularity and mesangial matrix,basement membrane not thickened, no evidence of mesangiolysis, endocapillary proliferation or cresents.
Significant tubular injury is present with loss of brush border and focally denuded epithelium.some of tubules show refractile crystals of calcium oxalate.no evidence of tubular atrophy or intestitial fibrosis.some of tubules show RBC casts.mild focal intestitial lymphocytic infiltrate is present.
Blood vessels are unremarkable.

16. IF: Reveal minimal deposits of IgA.
DIAGNOSIS : Acute tubular injury with oxalosis.
mild IgA deposits are present 2+.
So diagnosis of probable primary oxalosis was considered. Genetic work up sent.

18. CASE 1

19. CASE 1

20. ELDER BROTHER LEADS THE STORY FURTHER
Elder brother 6yrs age, He presented with transient maculopapular skin rash ,cold and cough anasarca, reduced urine output,cola coloured urine
He also has h/o anemia
h/o anemia- worked up- iron indices(serum iron, ferritin, transferrin saturation, TIBC), b12, folate levels were normal.
Increased osmotic fragility index.
Smear-normocytic normochromic, no microsphrocytes.
G-6-PD deficiency ruled out.
Sickling test, Hb electrophoresis showed no abnormal hemoglobin.
LDH – normal.
Past h/o blood transfusion

21. On evaluation-
CBP-HB-4.5gm%, TLC-4800cumm,PLT-301lakhs
blood urea-46
Serum creatinine
UPCR-2.6
24 hours urine protein-2500mg
CUE-Blood -1+, protein-2+
LFT-WNL, ASO titre-<200
USG abdomen-Rk-8x4cm, LK-8X 4.5cm, gr 1 rpc
No hepatosplenomegaly.

22. Is it still oxalosis ? Favoring points Anemia in both siblings
Renal failure in both
Consanguinous marriage.
Expecting oxalate crystals went ahead with renal biopsy in elder sibling.

23. Renal biopsy
LM-15 glomeruli and 2 arteries.glomeruli are enlarged and cellular , show widening of mesangial matrix with moderate increase in mesangial cellularity with focal endocapillary proliferation in 2 glomeruli.segmental sclerosis seen in 7 tufts. Cresents are seen in 5 glomeruli 3 appear to be cellular and 2 fibrocellular.
Tubules show tubular injury with dilated lumina showing flattening and denudation of lining epithelium with few tubules containing red cell casts. No tubular atrophy.
Intestium has patchy and mild infiltrate of lymphocytes.
Vessles are unremarkable.
IF-16 Glomeruli with significant mesangial deposits of IgA, C3c, Insignificant IgM

24. DIAGNOSIS
Consistent with IgA Nephropathy with focal cresents (5/15) and no IFTA.
OXFORD score-M1 E 1 S1 T0- C2

25. CASE 2

26. CASE 2

27. CASE 2

28. What helped in solving the dilemma ?
Genetic testing ?

31. PRESENT STATUS 1st child-Discharge serum creatinine was-0.9
Was discharged on oral probiotics and pyridoxine .
On follow up serum creatinine is 0.7
Hemoglobin is 10.8.
2nd child(IgA with cresents)-given 3 dose of methyprednisolone and started on oral endoxan.
At discharge serum cratinine-1.8
Discharge hb-9.6gm%

32. DIAGNOSIS REVISED
FAMILIAL Ig A NEPHROPATHY probably secondary oxalosis.
Genes for oxalosis enzymes normal , enzyme activity testing in liver??

33. Is it OXALOSIS?

34. Favoring oxalosis… Oxalosis is an important cause of CKD in children
Anemia is commonly associated
Autosomal recessive
Consanguinity

35. Oxalosis
Definition of hyperoxaluria is urinary oxalate excretion that exceeds
Adults 40 mg/day
Children
Urine oxalate awaited

36. This child all are normal
This child no history

38. This child no systemic oxalate even bone marrow normal
Clinical findings of calcium oxalate (CaOx) deposits in PH1. (A) X-ray (plain film of the abdomen), demonstrating multiple kidney stones (some with a staghorn appearance) patient with PH1 and renal failure. Initial oxalate osteopathy, with cystic lesions in both femoral necks and pelvic bones, can also be observed. (B) Ultrasonogram (right kidney), demonstrating a “white” kidney, attributable to diffuse nephrocalcinosis, in a 3-mo-old patient with renal failure. (C) Eyeground examination image (6-yr-old patient), demonstrating numerous pitch-black foci (consisting of multiple layers of hyperplastic and hypertrophic retinal pigment epithelium) and multiple CaOx crystals in the inner retina.
This child no systemic oxalate even bone marrow normal

39. Is it familial IgA?

40. Points in favor… Entity is known….
Both siblings have IgA in biopsy- one florid other minimal

41.  Familial forms of IgAN are frequently underrecognized because the associated urinary abnormalities in affected family members are often mild or intermittent

45. Points against FAMILIAL IgA NEPHROPATHY
 Autosomal dominant manner
long arm of chromosome 6 (6q22-23).
But
parents normal
Index child- minimal IgA
IgA presenting as RPRF so early in life unusual
Does not explain anemia

46. Way forward.. Definitive test to rule out oxalosis
Enzyme estimation in liver as Genes may be normal but enzyme activity in liver low
Planned
Genetic testing for IgA
Close follow up

47. Avoidance of oxalate rich food

48. MANAGEMENT Liberal fluid intake(<0.4millimol/l urinary oxalate).
Neutral phosphate(30-40mg/kg),potassium citrate(0.15mg/kg),magnesium oxide(500mg)
Pyridoxine
High flux, increased frequency of dialysis
Combined liver and kidney transplant.