| Abstract|| |
Atypical hemolytic-uremic syndrome (aHUS) can pose a diagnostic challenge due to the multisystem involvement and varied manifestations. Early diagnosis and initiation of Eculizumab have been reported to have favorable renal outcomes. We report a case of 11-month-old male infant who presented at the age of two months with anemia, acute kidney injury, hypertension, and nephromegaly. Renal biopsy confirmed the diagnosis of aHUS and Eculizumab was started. Thrombotic microangiopathy markers showed the resolution. Kidney sizes improved after nine months of Eculizumab therapy. The successful resolution of nephromegaly in an infant with aHUS has not been reported so far in literature. Renal sizes should be monitored in all children with aHUS.
|How to cite this article:|
Kumar G. Nephromegaly in an infant with atypical hemolytic-uremic syndrome resolving successfully with eculizumab. Saudi J Kidney Dis Transpl 2018;29:967-70
|How to cite this URL:|
Kumar G. Nephromegaly in an infant with atypical hemolytic-uremic syndrome resolving successfully with eculizumab. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2022 Aug 14];29:967-70. Available from: https://www.sjkdt.org/text.asp?2018/29/4/967/239636
| Introduction|| |
Atypical hemolytic-uremic syndrome (aHUS) is a rare disease, and we are still in the process of exploring the disease. The disease may have varied presentation, and initial laboratory parameters may not be indicating thrombotic microangiopathy (TMA) posing a diagnostic challenge to clinicians. Clinical presentation may give some clues, and one of the rare clues which is not highlighted usually is nephro-megaly. We present the case of 11-month-old male infant who was diagnosed with aHUS at the age of two months and had significant nephromegaly. The child was started on eculi-zumab and showed gradual improvement in renal sizes along with the improvement in TMA markers.
| Case Report|| |
A 2-month-old previously healthy male infant presented to the emergency department with irritability and fast breathing. He was the product of consanguineous marriage and born at term by cesarean section delivery with birth weight 2.45 kg. The examination revealed averagely nourished infant with moderate pallor and tachypnea and prolonged capillary refill with mottling of the skin. His vital signs were as follows: heart rate was 160/min, blood pressure was 83/63 mm Hg, respiratory rate was 62/min, temperature was 36.5°C. Rest of the systemic examination was unremarkable. He required intubation and ventilation for 48 h. Sepsis markers were negative. There was no change in urine output of the child. Blood transfusion was done in view of initial hemoglobin of 5.9 g/dL. His echo done on admission showed moderate left ventricular hypertrophy, and TMA markers were positive except for platelet count which was normal. Twenty-five percent fall in platelet count was seen subsequently. He required multiple blood transfusions. Amino acid analysis showed normal homocysteine levels in the plasma and normal levels of both homocysteine and methyl malonic acid in the urine ruling out cobalamin C deficiency. Renal ultrasound done showed right kidney 6.9 cm and left kidney 7 cm and bilateral echogenic kidneys (more than 95th centile for age). Subsequently, he developed hypertension requiring two antihypertensives. Complements were done which showed low C3 and C4. Renal biopsy done showed the features of TMA including mesangiolytic changes (“moth-eaten appearance,” stars) and segmental splitting of capillary walls (“double contour,” arrow) as shown in [Figure 1]. Intra-capillary fibrin thrombus was also seen. Genetic testing was sent which did not show any mutation in complement regulatory genes. He was started on eculizumab 300 mg every two weeks and gradually his parameters improved. A renal scan was done after nine months of treatment showed improvement in renal sizes. A plot of the renal sizes as a percentile based on a web-based multivariable pediatric renal nomogram is shown in [Figure 2]. Currently, his complements are normal and hematological and biochemical parameters are stable.
|Figure 1: Renal biopsy done showed features of TMA including mesangiolytic changes (“moth-eaten appearance,” stars) and segmental splitting of capillary walls (“double contour,” arrow).|
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|Figure 2: Renal size percentiles at 2 and 9 months of age showing improvement in renal sizes.|
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[Table 1] shows the laboratories on admission and after nine months on treatment with eculi-zumab.
|Table 1: Laboratory parameters on admission and after 9 months on treatment with Eculizumab.|
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| Discussion|| |
Nephromegaly can be seen in children due to multiple etiologies such as:
- obstruction which can be with (a) hydro-nephrosis such as ureteropelvic junction obstruction or vesicoureteric reflux, (b) without hydronephrosis such as myoglobi-nuria or hemoglobinuria
- cystic disease such as polycystic kidney disease
- Metabolic such as glycogen storage disease type 1 and hereditary tyrosinemia
- Inflammatory causes such as acute tubulointerstitialnephritis, pyelonephritis, and acute tubular necrosis
- Hematological causes such as sickle cell anemia and renal vein thrombosis
- Oncologic causes such as Wilms tumor and acute lymphoblastic leukemia
- Miscellaneous causes such as Beckwith-Wiedemann syndrome.
Most of the times, aHUS is overlooked as the cause of nephromegaly. Our index case emphasizes the need to keep this important differential diagnosis in mind when dealing with rare and complex disease such as aHUS.
There has been no reported case of nephro-megaly in infant with aHUS.
Anuria or oliguria may lead to enlarged kidneys in hemolytic-uremic syndrome (HUS). However, our index case was never oligo-anuric. One of the possibilities of renomegaly could be venous congestion of the renal capillary glomeruli secondary to microthrombi which resolves once the TMA process resolves.
Kenney et al studied patients with HUS and found to have normal or enlarged kidneys as compared to the healthy controls.
Losito et al described a 14-year-old boy who presented with hypertension, proteinuria, and nephromegaly, and subsequently developed progressive pulmonary hypertension. Renal histology showed TMA and pulmonary hypertension was controlled by endothelin receptor antagonist, i.e. bosentan. Nephromegaly persisted in the child, although renal function deteriorated at the onset of pulmonary hypertension and later improved after the bosentan treatment.
Fraga-Rodriguez et al reported 21-month-old girl with two rare and life-threatening conditions, aHUS, and hemophagocytic lympho-histiocytosis (HLH), triggered by a cyto-megalovirus (CMV) infection and abdominal ultrasound revealed nephromegaly, with increased renal cortical echogenicity and normal arterial and venous flow in both kidneys. The child showed clinical improvement with Eculizumab therapy; however, the resolution of nephromegaly is not elaborated in follow-up.
Literature is scarce on nephromegaly in aHUS. The need to look into radiological findings of kidneys and plot the renal sizes as percentiles are important in all children with this rare disease. It is also emphasized that a close follow-up regarding the persistence or resolution of nephromegaly should be done.
Conflict of interest: None declared.
| References|| |
Chen JJ, Zhi J, Mao W, Steinhardt GF. MrNomogram: A web-based multivariable pediatric renal nomogram. J Pediatr Urol 2006;2:436-8.
Kenney PJ, Brinsko RE, Patel DV, Spitzer RE, Farrar FM. Sonography of the kidneys in hemolytic uremic syndrome. Invest Radiol 1986;21:547-50.
Losito A, Pittavini L, Covarelli C. Thrombotic microangiopathic nephropathy, pulmonary hypertension and nephromegaly: Case report of a patient treated with endothelin receptor antagonist. Clin Nephrol 2012;77:164-70.
Fraga-Rodriguez GM, Brió-Sanagustin S, Turón-Viñas E, Dixon BP, Carreras-González E. Eculizumab in a child with atypical haemo-lytic uraemic syndrome and haemophagocytic lymphohistiocytosis triggered by cytomegalo-virus infection. BMJ Case Rep 2017;2017. pii: bcr-2016-219065.
Dr. Gurinder Kumar
Division of Pediatric Nephrology, Sheikh Khalifa Medical City, Abu Dhabi
United Arab Emirates
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]