Pulmonary tuberculosis and renal amyloidosis: A rare entity in children

CASE REPORT

An 11-year-old child presented with complaints of intermittent fever for one year together with swollen legs which gradually progressed to anasarca over the previous three months. There was no family history of kidney or inflammatory disease nor previous history of similar episodes. On examination, the child had generalised anasarca with hepato-splenomegaly but no rash, lymphadenopathy, thyroid nor joint swelling. She had no pallor and her blood pressure was normal. Her weight was 23.1 kg (−2.1 SDS), height 120 cm (−3.21 SDS) and body mass index 16.04 kg/m² (0.45 SDS).^1–3

Laboratory tests revealed a serum urea of 1.5 mmol/L, serum creatinine of 17.68 μmol/L, albumin of 20 g/L, cholesterol of 5.92 mmol/L, thyroid-stimulating hormone of 30.76 mIU/L, and thyroxine of 15 nmol/L. Other biochemical findings were normal including C-reactive protein, sedimentation rate, C3, C4, anti-nuclear antibody, and anti-double-stranded-DNA titres. However, urinalysis showed 4+ proteinuria with no leucocytes, erythrocytes nor glycosuria. Nephrotic range proteinuria was confirmed by a 24 h urine test (9.9 mg/24 h). Her tuberculin skin test was positive and there was hilar lymphadenopathy on chest radiography. Chest and abdomen computed tomography scan showed bilateral pleural and pericardial effusions, necrotic mediastinal and abdominal lymphadenopathy, moderate ascites, hepatosplenomegaly and a pulled-up caecum.

The child was started on anti-tubercular therapy (ATT) based on these clinico-radiological findings with prednisolone for nephrotic syndrome two weeks later.

Despite six weeks of oral prednisolone (2 mg/kg/day), remission did not occur; a renal biopsy showed enlarged glomeruli with deposition of a pink amorphous substance in the mesangium and focally in peripheral capillary walls. This material was positive for Congo red stain and showed apple-green birefringence on polarized light. The tubules showed protein resorption granules with medial sclerosis of blood vessels.

On immunohistochemistry, serum amyloid A (SAA) was positive both in glomerular walls of tubules and blood vessels. The findings were suggestive of secondary amyloidosis as shown in Figure 1.

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Figure 1.

(a) H&E staining showing pink amorphous material deposition in the mesangium. (b) Congo red stain showing apple-green birefringence. (c) SAA positivity in the glomeruli.

Steroids were therefore tapered off and stopped. ATT along with enalapril for proteinuria reduction was continued. She attained complete remission of nephrotic syndrome after three months of ATT. We plan to keep her under observation for at least one year.

Informed consent was obtained from her parents for publication.

Discussion

Childhood renal amyloidosis is almost always secondary (AA type) and often associated with chronic inflammatory, infectious and hereditary conditions. While rheumatoid arthritis is the most common cause in rich countries, untreated familial Mediterranean fever and chronic infections constitute a large proportion in low- and middle-income countries. There are limited studies from India. ³ There is often a precipitating factor for amyloid nephropathy with pulmonary infection being predominant. ² Treatment of AA amyloidosis depends on adequate control of the underlying inflammatory disorder, and serum AA concentration can be used to assess response to treatment. ² Remission of nephrotic syndrome can be achieved following timely treatment of tuberculosis but this is rare and many patients progress to end-stage kidney disease despite adequate therapy. ^{4 ,5}

The time taken to develop renal amyloidosis was approximately seven months in our patient as in previous case reports. ³ However, our child attained remission after the intensive phase of ATT and alternate day steroids without using any alternative immuno-suppressive agents, suggesting that these children require patient watchful observation for the treatment of the primary cause before initiating other alternate therapy.

Conclusion

Renal amyloidosis may be associated with pulmonary tuberculosis and successful treatment with anti-tubercular drugs can result in amelioration of renal symptoms; tuberculosis should not be forgotten as a differential for secondary amyloidosis in children especially from low- to middle-income countries.