Oxalosis in children

[sangeetha]

14 yrs old adolescent female, a known child with renal stone disease detected at 9 months of age on alkali therapy. She underwent ESWL 3 yrs ago when she developed acute kidney injury secondary to stone obstruction. She recovered from AKI. Her renal functions were stable with the creatinine of 1.2 to 1.5 till november 2013. Now she presented with the creatinine of 3.9. There is no stone obstruction, no evidence of dehydration and sepsis(reversible causes of AKI). Since beginning we have done crystalluria evaluation many times for her which was essentially normal. Parents want to go for RRT in the form of transplant. We have sent genetic analysis for oxalosis. Can we do the genetic study for all the patient with RSD difficult to manage/going for renal failure. What is the current guidelines? If we prove the oxalosis then no point in doing renal transplant alone, We should go for combined liver and kidney transplant

[Badri]

Dear Sangeetha,

Welcome to the Forum. To answer your query I am requesting one of the senior Nephrologists for his opinion. In your summary you have not included all the results from the investigation done so far. I presume urinalysis and full blood screening have been done. You have mentioned creatinine level but what about the GFR. Were renal and liver biopsies done? If you can send all the results it would give a fuller picture of the patient's condition.

There is an excellent paper from The Mayo Clinic Hyperoxaluria Center which summarises the diagnosis, investigation and treatment of this rare condition - It runs to a few pages. If you would like to see it, I can post it to you through the Forum

[uamohammed]

Hello Dr Sangeetha
Thank you for a very informative piece on oxalosis. Frankly I have not heard about this topic before probably my practice is restricted to a small field. I do come across often calcium oxalate crystals in the routine urine examination but not taken that seriously.
Thanks a lot
Expecting more on this subject

UA Mohammed

[gmohan]

Hello Dr Sangeetha,
Welcome. Following is the reference to Primary Hyperoxaluria in the UK guidelines.

Let me know if you need the full document .


UNITED KINGDOM GUIDELINES
FOR
LIVING DONOR KIDNEY TRANSPLANTATION

12.12 Primary Hyperoxaluria
Primary hyperoxaluria is a rare condition that requires careful assessment and specialist
advice to optimise management. Living donor kidney transplantation is a treatment option
in certain circumstances, whereas in others combined liver and kidney transplantation is
preferred.

Primary hyperoxaluria type 1 is generally treated with combined liver and kidney
transplantation (39,40) or early liver transplantation alone (41). However, some groups in
North America have advocated early living donor kidney transplantation, particularly if
there is evidence of pyridoxine responsiveness (42).

Primary hyperoxaluria type 2 has been treated successfully with kidney transplantation
alone. This is ideally pre-emptive, therefore living donor transplantation is a reasonable
treatment option (43)

Recommendation
In appropriately selected cases, living donor kidney transplantation is a
reasonable treatment option in primary hyperoxaluria. Both the donor and
recipient should be counselled regarding the risks of recurrent disease

UK 2011.

G Mohan.

[Badri]

Primary hyperoxaluria includes Type I, II,and III disease. Type I and II are caused by the lack of certain enzymes in the liver that stop oxalate production. This results in excessive production of oxalate that enters the blood stream. As oxalate cannot be degraded any further they must be excreted by the kidneys. Oxalate combines with calcium producing calcium oxalate stones which may be deposited in several organs. The kidney is the most affected.

Pyridoxine we are told can act in some type I patients and reduce the amount of oxalate that is produced. In some they can even reduce the blood levels to normal. It is therefore necessary to try pyridoxine in all patients to see if they will respond. If they respond they will not require a liver transplant. On the other hand if they do not respond and the patient is already in kidney failure, you may have to think twice before you offer them a kidney transplant on its own, as the new kidney will have to deal with continued hyperoxaluria.

Oxalosis is a rare but interesting disease. I am sure Dr Sangeetha will give us a general summary of the whole disease as I understand she has seen more than one case.

Badri.

[sangeetha]

Crystal induced Nephropathy

Case 1
3 months old female infant presented with seizures in the ER. After control of seizure also her BP was pretty high, always more than 99th percentile. On routine evaluation her S.creatinine was found to be sky high for her age(7.6mg/dL), dyselectolytemia. No evidence of sepsis. She was initiated on peritoneal dialysis. Since her kidney size was normal(though hyperechogenic), renal biopsy was done to reveal the underlying renal disease. It was really a challenge for a Pediatric Nephrologist to do the kidney biopsy for that small kid at bedside. Though it gave some gritty feel while doing the biopsy, we never expected this diagnosis. Really surprising, it was oxalosis. We usually don’t expect inherited diseases in a non consanguineous parent. But what for its worth, when the facilities are available we can use that. Both parents are carrier for primary hyperoxaluria type I. Due to financial constraints baby was shifted to government institution and expired on the 7th day of illness.
Renal biopsy of this child:
Radially arranged crystals within the tubules (H&E) & Birefringent oxalate crystals under polarized light The 2 slides are shown at the end of the post.

Case 2
14 yrs old adolescent female, a known child with renal stone disease detected at 9 months of age on alkali therapy. She underwent ESWL 3 yrs ago when she developed acute kidney injury secondary to stone obstruction. She recovered from AKI. Her renal functions were stable with the creatinine of 1.2 to 1.5 till november 2013. Now she presented with the creatinine of 3.9. There is no stone obstruction, no evidence of dehydration and sepsis(reversible causes of AKI). Crystalluria evaluation was essentially normal(done thrice in the past). RSD going for renal failure- she is a suspected case of oxalosis. Genetic studies awaited.

Discussion
Oxaluria in children Primary hyperoxaluria may occur at almost any age from birth to the sixth decade of life with a median age at onset of 5.5 years. The clinical presentation may vary from infantile nephrocalcinosis and failure to thrive as a result of renal impairment to recurrent or only occasional stone formation in adulthood. Roughly 10% of patients receive a diagnosis of primary hyperoxaluria only when the disease recurs after kidney transplantation. Oxaluria, the defect is in glyoxylate metabolism which can be primary or secondary. Primary hyperoxaluria(PH) is an autosomal recessive inherited disease caused by enzyme alanine: glyoxylate aminotransferase (AGT)(Type I PH) and glyoxylate reductase/ hydroxypyruvate reductase (GRHPR) (Type II). Among all PH patients, type 1 accounts for 77%, type 2 for 9% and non-type 1 non-type 2 for 14%. PH1 is one of the most challenging issues for both adult and pediatric nephrologists worldwide. Type I is caused by the functional defect of the liver-specific peroxisomal, pyridoxal phosphate-dependent enzyme AGT leading to oxalate overproduction. Along with progressive decline of glomerular filtration rate (GFR) due to renal parenchymal involvement, continued overproduction of oxalate by the liver along with reduced oxalate excretion by the kidneys leads to oxalate deposition in many organs(‘oxalosis’) and bone is the major compartment of the insoluble oxalate pool. PH1 has five presentations: (1) an infantile form with early nephrocalcinosis and kidney failure; (2) recurrent urolithiasis and progressive renal failure leading
to a diagnosis of PH1 in childhood or adolescence (3) late-onset form with occasional stone passage in adulthood (4) diagnosis suggested and confirmed only by post-transplantation recurrence and (5) pre-symptomatic subjects with a family history of PH1. The major sites of crystal deposition are the kidneys, blood vessel walls. Oxalosis can also affect the joints, retina, skin, bone marrow, heart and central nervous system leading to severe illness and death.

Evaluation
The combination of both clinical and sonographic signs is a strong argument for PH1, i.e., the association of renal calculi, nephrocalcinosis and renal impairment. Family history may bring additional information. Infrared spectroscopy, 24 hours oxalate levels(in patient with normal GFR) may help to make the diagnosis.AGT levels measurement in liver biopsy and genetic study prove the diagnosis. Prenatal diagnosis can be performed from chorionic villi or amniocentesis

Management
A multidisciplinary approach is needed to achieve the best possible management of primary hyperoxaluria. Encourage fluid intake of more than 2 to 3 liters per square meter of body-surface area per day is essential for stone prevention. Oral alkali therapy to alkalinize urine. Pyridoxine supplementation is helpful in primary hyperoxaluria type 1 (but not in other forms of primary hyperoxaluria). A starting dose of 5 mg, gradually increase upto 20 mg/kg for a trial period of at least 3 months.Responsiveness is defined as a decrease in the level of urinary oxalate by more than 30% from the point of treatment initiation. Extracorporeal shock-wave lithotripsy (ESWL) is not recommended in patients with primary hyperoxaluria who have a heavy stone burden. Because calcium oxalate stones do not easily fragment and the risk of parenchymal damage.
Dialysis
Conventional hemodialysis and peritoneal dialysis do not eliminate sufficient levels of oxalate.
Short daily sessions of high-flux dialysis, nocturnal dialysis, or combinations of hemodialysis
and nocturnal peritoneal dialysis are needed.

Transplantation

Since the liver is the sole organ responsible for glyoxylate detoxification, the excessive production of oxalate will continue as long as the native liver is present in patients with primary hyperoxaluria type 1. Thus, preemptive liver transplantation is ideal to avoid the complications of systemic oxalosis. Kidney transplantation without liver transplantation confers a very high risk of recurrence. Combined liver and kidney transplantation is the treatment of choice for these patients.

[sangeetha]

Its really interesting. I have got nice response and guidelines from the seniors. I have also utilized this opportunity to read bout this topic. Thanks a lot.

[admin]

Dear Sangeetha,

It is a good summary of Oxalosis. I have two questions regarding the child you are investigating now. You had indicated that she had a kidney injury in the past and she was recovering from it. I presume that oxalate crystals were identified in her urine at some stage. I also presume that she did not have a kidney or liver biopsy. You indicated that her crystalluria evaluation was normal now. What was the serum level and what is her present GFR. If serum level of oxalate was raised, has she been tried on pyridoxine?

If I am not mistaken, these investigations should give you the answer to whether a kidney transplant alone is enough or the child will require a liver transplant as well.

Badri

[sangeetha]

Our second child's 24 hours oxalate level was normal. Urinary oxalate excretion may be normal with reduced eGFR. Her eGFR is 24ml/min/1.73m2. We don't have the facility for S.Oxalate measurement. Renal biopsy was deferred in this child in view of small kidneys. We don't have the facility for doing AGT levels also

[sangeetha]

11 yrs old adolescent girl child has been referred in view of gross hematuria on & off for 1 yr, evaluated, had nephritic range proteinuria. Her renal function was stable. Suspected diagnosis was IgA Nephropathy. Surprisingly her renal biopsy light microscopy and immunoflourescent study were normal. Electron microscopy revealed Alport syndrome. How frequently we encounter Alport in females?