Pediatric Nephrology

https://doi.org/10.1007/s00467-020-04784-0

CLINICAL QUIZ

A rare complication of pauci-immune crescentic glomerulonephritis

in a child: Questions
Sidharth Kumar Sethi 1 & Abhyuday Rana 2 & Shyam Bihari Bansal 2 & Alka Rana 3 & Dinesh Kumar Yadav 2 &
Kritika Soni 2 & Marie-Agnès Dragon-Durey 4 & Rupesh Raina 5 & Vijay Kher 2

Received: 22 August 2020 / Accepted: 15 September 2020

# IPNA 2020

Keywords Child . Pauci-immune crescentic glomerulonephritis . Anemia . Hypertension . Thrombocytopenia . Thrombotic

microangiopathy . aHUS

Case summary negative. ANCA by immunofluorescence and anti-GBM anti-

bodies were negative. She was transfused with a unit of packed
A 6-year-old female born of non-consanguineous marriage with RBCs at the local center due to severe anemia (Hb-5.1 g/dL).
no previous comorbidities was referred to our center with rapidly On admission, her physical examination was unremarkable
progressive kidney failure. She reported having a minor upper except for hypertension (BP 144/86 mmHg), anasarca, and
respiratory tract infection 1 month ago followed by progressive pallor. Laboratory evaluation at our center showed anemia
anasarca. There was no history of rash, abdominal pain, overt (Hb 6.2 mg/dL) and elevated levels of sCr (5.2 mg/dL), urea
hematuria, dyspnea, cough, palpitations, joint swelling/pain, or (372 mg/dL), and LDH (854 U/L), and normal complement
neurological deficits. Prior to the referral, her evaluation done levels were noted (C3 89 mg/dL, C4 26 mg/dL). Kidney ul-
externally showed serum creatinine (sCr) of 3 mg/dL with a urine trasound revealed normal-sized kidneys with enhanced
protein to creatinine ratio of 1.2 g/g. Urinalysis showed micro- echogenicity, consistent with parenchymal pathology. Chest
scopic hematuria. Serological evaluation was unremarkable with X-ray showed no abnormalities.
normal C3 and C4 levels (130 mg/dL and 30 mg/dL) and neg- Considering rapidly progressive glomerulonephritis, she
ative ASO, anti-DNase, ANA, anti-GBM, anti-dsDNA, anti- was administered a dose of intravenous cyclophosphamide
Smith, anti-RNP, anti-Ro, anti-La, anti-MPO, and anti-PR3 an- (500 mg/m2), and pulse methylprednisolone therapy (30
tibodies. Serological evaluation for HIV, hepatitis B, and C was mg/kg intravenous daily for 3 days) was started in addition
to diuretic and antihypertensive medications.
The answers to these questions can be found at https://doi.org/10.1007/ A kidney biopsy was then obtained, and fifteen glomeruli
s00467-020-04786-y. were sampled for light microscopy. Cellular and fibrocellular
crescents were seen in 8 and 5 glomeruli, respectively. Two
Both Sidharth Sethi and Abhyuday Rana shall be first authors.
other glomeruli had fibrous crescents (Fig. 1a, b, and c).
* Sidharth Kumar Sethi
Tubulointerstitial compartment showed 15–20% tubular atro-
sidsdoc@gmail.com phy and interstitial fibrosis (Fig. 1d). Vascular compartment
did not show any pathology or features suggestive of vasculi-
1 tis. Immunofluorescence revealed granular C3 (2+) staining in
Pediatric Nephrology, Kidney Institute, Medanta the Medicity,
Haryana 122001 Gurgaon, India mesangium and focally around capillary loops in only 2 glo-
2 meruli. Staining with IgG, IgA, C1q, κ, and λ C4d was neg-
Kidney Institute, Medanta the Medicity,
Haryana 122001 Gurgaon, India ative. On electron microscopy, no immune-complex-like
3 electron-dense deposits were seen. The biopsy findings were
Department of Pathology , Medanta the Medicity,
Haryana 122001 Gurgaon, India compatible with pauci-immune crescentic glomerulonephritis
4 (PICGN). She was continued on oral steroids and subsequent-
Université de Paris, Hôpital Européen Georges Pompidou, APHP,
INSERM UMRS1138, Paris, France ly underwent therapeutic plasma exchange (TPE) with albu-
5 min replacement. This was followed by a noticeable improve-
Pediatric Nephrology, Akron Children’s Hospital, Cleveland, OH,
USA ment in her clinical condition and laboratory parameters.
 Pediatr Nephrol

Fig. 1 a Silver HE stain × 40

magnification highlighting a
fibrocellular crescent. b Silver HE
stain × 40 magnification
highlighting a fibrous crescent. c
Silver HE stain × 40
magnification highlighting a
small cellular crescent. d Silver
HE stain × 40 magnification
highlighting tubular atrophy with
interstitial fibrosis. Also seen are
2 glomeruli, one showing fibrous
crescent

After three sessions of TPE, the patient’s condition abrupt- Questions

ly deteriorated with a marked rise in sCr and progressive re-
duction in urine output. She developed hypertensive emergen- 1 How can you explain thrombotic microangiopathy in this
cy and an episode of non-convulsive status epilepticus. She child with a known biopsy proven pauci-immune crescen-
was started on multiple anticonvulsant and antihypertensive tic glomerulonephritis?
medications. MRI of the brain revealed findings consistent 2 What investigations should now be done to evaluate this
with posterior reversible encephalopathy syndrome and bilat- child further?
eral focal posterior parietal lobe infarcts. Laboratory work-up 3 What should be done next in the management of this
showed worsening anemia (Hb 5.4 mg/dL), thrombocytope- patient?
nia (platelet count 98,000/mm3), decreased haptoglobin (12
mg/dL), reticulocytosis (4%), and markedly increased LDH Compliance with ethical standards
levels (2140 U/L). A peripheral smear showed numerous
schistocytes (> 8%). ADAMTS13 enzyme activity level was Competing interests The authors declare that they have no competing
interests.
normal (> 67%). A functional assay of ADAMTS13 inhibito-
ry antibodies yielded a normal result (≤ 0.4 inhibitor units).
Her C3 level decreased to 40 mg/dl with a normal C4 of 18
Publisher’s note Springer Nature remains neutral with regard to jurisdic-
mg/dl. Due to concerns of fluid overload and persistent severe tional claims in published maps and institutional affiliations.
hyperkalemia (7.2 mEq/L), hemodialysis was performed. She
also received multiple blood transfusions. The patient’s clini-
cal condition was now consistent with aHUS (atypical hemo-
lytic uremic syndrome).