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| Year : 2015 | Volume
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| Issue : 1 | Page : 149-151 |
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| Irreversible renal failure in two infants |
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Kiran P Sathe1, Uma S Ali2, Alpana Ohri1
1 Bai Jerbai Wadia Hospital for Children, Parel, Mumbai, India
2 Division of Pediatric Nephrology, Bai Jerbai Wadia Hospital for Children, Parel, Mumbai, India
Click here for correspondence address and email
| Date of Web Publication | 8-Jan-2015 |
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How to cite this article:
Sathe KP, Ali US, Ohri A. Irreversible renal failure in two infants. Saudi J Kidney Dis Transpl 2015;26:149-51 |
To the Editor,
Renal failure resulting from primary hyperoxaluria in infancy is uncommon. The rarity of the disease, unfamiliarity with the diagnostic clues and the difficulty in establishing the diagnosis in the presence of renal failure leads to the condition going unrecognized and underreported. Non-feasibility of existing therapeutic options leads to a poor outcome.
We had two cases of infants with primary hyperoxaluria with anuric renal failure.
The first case was a 4-month-old girl, the second child of Muslim parents with thirddegree consanguinity, presenting with severe oliguric renal failure and convulsions following a brief episode of acute gastroenteritis.
The previous sibling had died at three months of age due to convulsions. Physical examination revealed severe anemia, acidotic breathing, dehydration and failure to thrive. Despite fluid resuscitation and a furosemide challenge, there was no improvement in the urine output. Peritoneal dialysis was undertaken and packed red blood cell transfusion was given. Initial investigations revealed hemoglobin 5.4 g/dL, total leukocyte count 12.4 × 10 9 /L, platelet count 3.5 × 10 9 /L, reticulocyte count 0.5%, blood urea nitrogen (BUN) 39.27 mmol/ L, serum creatinine 618.8 μ mol/L, serum Na/ K/Cl 135/5.2/105 mEq/L respectively, anion gap of 25 and venous blood gases showing pH 7.15 and HCO 3 -6.5 meq/L. Urinalysis revealed proteinuria 2+, RBC 60-80/hpf, WBC 10-12/hpf, urine albumin/creatinine ratio 7.2 and fractional excretion of sodium (FeNa) 67.8. Ultrasonography suggested bilateral diffuse nephrocalcinosis involving both the cortex and the medulla, with normal kidney sizes (right kidney 5.1 cm × 1.5 cm, left kidney 4.7 cm × 1.8 cm) [Figure 1]. Automated peritoneal dialysis with a cycler was continued. Renal biopsy revealed widespread deposition of birefringent oxalate crystals in the renal tubules with focal interstitial fibrosis [Figure 2]. Because of poor prognosis and financial constraints, dialysis was discontinued. | Figure 1: USG kidneys suggesting bilateral cortico-medullary hyperechogenecity suggestive of nephrocalcinosis.
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 | Figure 2: (a) Renal biopsy 20×, H&E stain showing oxalate crystals (arrow) in the renal tubules and (b) Renal biopsy 20× Polarized microscopy showing extensive birefringent oxalate crystals (arrow) in renal tubules.
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The second case was that of a 5-month-old girl who presented with vomiting and anuric renal failure to another center. She had high BUN and serum creatinine. She underwent peritoneal dialysis for 72 h. As she failed to improve, she was referred to our hospital as a suspected case of Bartter's syndrome based on ultrasound findings of nephrocalcinosis. On evaluation, she was the first child born to Maharashtrian parents of third-degree consanguinity. She was a well grown child with no history of polyuria or polydipsia. Review of her ultrasound showed normal-sized kidneys that were bright due to both cortical and medullary nephrocalcinosis. Peritoneal dialysis was reinstituted. Serum oxalate levels were 5068 ng/mL. Because of the persistence of renal failure and poor therapeutic options, the parents decided to withhold dialysis.
The diagnosis of primary hyperoxaluria was suspected in both cases based on characteristic ultrasound findings showing diffusely bright kidneys due to both cortical and medullary nephrocalcinosis. The presence of oxalosis was confirmed by the presence of extensive deposition of birefringent oxalate crystals on renal biopsy in the first child and the finding of extremely high serum oxalate levels in the second.
Nephrocalcinosis seen commonly in infancy is medullary in location due to conditions such as distal renal tubular acidosis, Bartter's syndrome or vitamin D toxicity that do not give rise to severe renal failure at this age. The finding of bilateral diffuse cortical nephrocalcinosis or cortical and medullary nephro-calcinosis in an infant with renal failure is almost diagnostic of primary hyperoxaluria type 1, although this ultrasound pattern is not invariable and purely medullary nephrocalcinosis can be seen. The finding of high urinary oxalate levels is a useful supportive test prior to the onset of renal failure. However, once renal failure sets in, the urinary oxalate levels fall. Serum oxalate levels are more reliable under these circumstances. [1]
Primary hyperoxaluria type 1 results from an autosomal recessive inherited enzyme defect of glyoxylate metabolism leading to oxalate overproduction, hyperoxaluria, nephrocalcinosis, nephrolithiasis and renal failure. [2]
Although recurrent nephrolithiasis is the most common presentation, the most severe form of primary hyperoxaluria type 1 can present in infancy in the form of failure to thrive, poor feeding, anemia, convulsions or nephrocalcinosis and progress rapidly to end-stage renal disease on account of the high oxalate burden faced by a kidney with a physiologically low glomerular filtration rate. [3] This is further complicated by systemic oxalate deposition once renal failure sets in and is associated with a high mortality. Cortical nephrocalcinosis in infants with renal failure is a strong pointer to oxalosis. In certain cases, kidney, liver or bone marrow biopsy can help in identifying the birefringent oxalate crystals under polarized microscopy. [4],[5] Diagnostic tests include estimating urinary organic acid levels using gas chromatography and mass spectrometry and, definitively, by measuring the enzyme alanine glyoxylate aminotransferase (AGT ) levels on liver biopsy. Mutation analysis is not feasible in all cases, but can be useful in assessing pyridoxine responsiveness and in antenatal diagnosis. Secondary causes are rare in infancy.
Early diagnosis is the key to successful treatment. Therapeutic measures useful before the kidneys fail comprise of oral pyridoxine (3-3.5mg/kg/day) that acts as a coenzyme for the deficient enzyme and helps to lower the oxalate burden. High fluid intake, the use of citrate, neutral phosphate and thiazides to prevent crystallization are other important measures. Early liver transplantation replaces the deficient enzyme and can be curative. Once renal failure sets in, no treatment is beneficial. [6] Hemodialysis is ineffective in reducing the systemic oxalate load and systemic oxalosis rapidly sets in. Isolated renal transplantation is contraindicated as there is an unacceptably high risk of recurrence in the renal allograft. Combined simultaneous or sequential liver-kidney transplantation is the treatment of choice and needs to be instituted as early as possible. Although this has shown encouraging results, it is not feasible at a very young age. [6]
 Acknowledgment | |  |
The authors would like to thank Dr. Jaya Deshpande, Consultant Histopathologist, Bai Jerbai Wadia Hospital for Children, Mumbai.
Conflict of Interest: None
| References | | |
| 1. | Orazi C, Picca S, Schingo PM, Fassari FM, Canepa G. Oxalosis in primary hyperoxaluria in infancy: Report of a case in a 3-month-old baby. Follow-up for 3 years and review of literature. Skeletal Radiol 2009;38:387-91.  |
| 2. | Hoppe B, Beck B, Milliner DS. The Primary Hyperoxalurias. Kidney Int 2009;75:1264-71. |
| 3. | Morris MC, Chambers TL, Evans PW, Malleson PN, Pincott JR, Rose GA. Oxalosis in Infancy. ArchDis Child 1982;57:224-8. |
| 4. | Pralhad N, Vijayakumar M, Nammalwar BR. Unusual Cause of Acute Renal Failure in Infancy. Indian Pediatr 2004;41:607-10. |
| 5. | Broyer M, Jouvet P, Niaudet P, Daudon M, Revillon Y. Management of Oxalosis. Kidney Int 1996;53:S93-8. |
| 6. | Cochat P, Gaulier JM, Koch Nogueira PC, et al. Combined liverKidney Transplantation in primary Hyperoxaluria type 1.Eur J Pediatr 1999;158Suppl 2:S75-80. |
Correspondence Address:
Dr. Uma S Ali
Division of Pediatric Nephrology, BaiJerbaiWadia Hospital for Children, Parel, Mumbai
India
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DOI: 10.4103/1319-2442.148767 PMID: 25579739 
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