Table 2 Clinical Features of Reported cases of Primary hyperoxaluria diagnosed after kidney transplantation

Riksen et al, 2002 [7]

51/M, Yugoslav.

2000.

PH1

revealed an operation for urolithiasis at the age of 3, developed ESRD at the age of 40. His first kidney transplantation was performed in 1996, and the second in Sep 2000.

On post-op day 64 after the second renal transplant he was readmitted to the hospital for a rise of SCr level.

revealed numerous birefringent crystalline deposits in the proximal and distal tubules, arranged in a rosette-like array, consistent with CaOx crystals.

Not detected.

Biochemical urine analysis revealed elevated excretion rates of oxalate and glycolate, whereas no L-glycerate was present. POC was severely elevated.

treated conservatively with a high fluid intake, avoidance of high oxalate foods, a thiazide diuretic, and a trial of PN.

Eight months after his renal transplantation, the creatinine clearance had stabilised at 21 ml/min and POC had decreased to 29 μmol/l.

Kim et al, 2005 [8]

43/F, Korean.

2004.

PH1

shown renal dysfunction since 1991 without a history or symptoms of renal stones or other signs of systemic oxalosis. HD was initiated in Feb 2000. She received a renal transplant on Sep 12, 2002.

At post-op day 4 to 11, urine volume was abruptly reduced with the rebound of SCr level, eventually it appeared anuria.

Tubular lumens contained numerous rhomboid, polyhedral or cone-shaped crystals attached to the necrotic epithelial cells with calcium deposits.

Not detected.

Liver biopsy was performed at the end of Oct 2004 to measure AGT activity, which was 2.7 mmol/h/mg protein, and AGT immunoreactivity was negative.

Not stated

Her renal function gradually worsened, leading her to receive HD.

Madiwale et al, 2008 [9]

25/M, Indian.

Not stated

PH

with ESRD due to bilateral, multiple nephrolithiasis. He received a renal graft from his mother

SCr rose from 1.1 mg/dL on post-op day 5 and was 2.6 mg/dL by the fourth week.

We reviewed slides of nephrectomy and graft biopsy and noted extensive deposits of birefringent CaOx crystals in the tubules, interstitium, vascular media and even the sclerosed glomeruli of nephrectomy

Not detected.

Skin biopsy showed oxalate crystals in dermal vessels.

Autopsy revealed plentiful oxalate crystals in transplant kidney, myocardium, coronary artery, and in blood vessels of the spleen, pancreas and lungs.

started with PN. Later, he developed oral candidiasis, necrotizing skin lesions on the lower limb, fever, abdominal pain, breathlessness and hemiparesis. He was treated with antibiotics and systemic anti-fungals and immunosuppression was reduced.

He developed hypotension and shock and died 10 weeks post-op.

Celik et al, 2010 [10]

38/M,

Turk

Not stated

PH

with history of recurrent nephrolithiasis developed ESRD because of obstructive uropathy. After 2-year HD treatment, he received a deceased donor transplant.

The patient was re-operated on post-op day 13 because of slowly dropping SCr levels.

ZHIB showed only tubular vacualisation. The 13th post-op day allograft biospy showed intensive oxalate crystals deposition.

In the fundus examination preretinal, intraretinal, and intravascular diffuse oxalate crystals were detected.

In the multislice CT images, diffuse calcifications were observed in left anterior descending, left circumflex, and right coronary arteries.

Not stated

In the 18th month, allograft biospy showed mild interstitial fibrosis and tubular atrophy with only a few crystals. The fundus examination showed the regressive nature of oxalate depositions.

Spasovski et al, 2010 [11]

48/F, Macedonia.

2007

PH1

presented with bilateral flank pain and signs of advanced chronic renal failure (CRF) in the beginning of 2006. In Jan 2007, she underwent a living unrelated paid transplantation.

From post-op 3 weeks to 4 months, she had a gradual increase in SCr levels from 299 to 423 μmol/l.

The second kidney graft biopsy showed ischemic tubular lesions and calcifications (oxalosis).

Heterozygote for 2 variants of the AGTX gene:

-c.33_34InsC

-c.508G > A

Since she was anuric, the monitoring of plasma oxalate was performed during a 2-month trial with increasing doses of PN up to 10 mg/kg/day.

The patient was put again on dialysis in July 2007. Nevertheless, she showed signs of systemic oxalosis.

Malakoutian et al, 2011 [12]

22/F, Iranian.

Not stated.

PH1

had the experience of two nephrolithiasis episodes 3 years earlier and had been under hemodialysis for 2 years later. She underwent kidney transplantation about 3 months before admission to our hospital.

After 2 months of transplantation, she presented with fever, malaise, vomiting, and a high SCr level.

There were large refractile acellular deposits in several of the tubular lumens resembling oxalate crystals making tubular destruction and injury.

Heterozygote for 1 variants of the AGTX gene:

Exon 5: c.584 T > G: PV.

The patient then underwent hemodialysis via a jugular vein catheter despite conservative management.

The patient was discharged on maintenance hemodialysis.

Naderi et al, 2015 [13]

20/M, Iraqi.

2013.

PH1

revealed an operation on the right kidney due to kidney stone at the age of 2.5 and several sessions of extracorporeal shock wave lithotripsy in the following years because of recurrent renal stones. At the age of 14, ESRD was established and he had been on regular HD. He received a renal transplant in Apr 2013.

On the 10th post-op day his SCr level started to rise and reached 1.8 mg/dL.

diffuse tubular deposition of CaOx crystals was seen.

Not detected.

The diagnosis was confirmed by low AGT enzyme activity on liver biopsy.

treated with vigorous serum therapy and daily HD along with previous medications. However, the patient underwent graft nephrectomy on the 98th post-op day.

The patient is now under treatment with PN, potassium citrate and regular HD, looking forward to a chance of LKT in the future.

Rios et al, 2017 [14]

33/F, Colombian.

2011.

PH1

presented ESRD associated with coral calculi in 2002, requiring bilateral nephrectomy and to start HD. She was first transplanted in 2004, and second transplanted in 2010.

One year after second transplantation, she presented a SCr elevation.

documented acute rejection of cellular Banff 1A and extensive deposits of oxalate in the interstitial tubule.

Heterozygote for 2 variants of the AGTX gene:

-c.731 T > C (p. lle244Thr): PV.

-c.307G > A (p. Gly103Arg): VUS, probably pathogenic.

treated with steroid boluses and conversion to Tac.

At her last follow-up at 6 years, her SCr was 4.8 mg/ dl; she is in pre-dialysis stage and being evaluated for LKT.

Rios et al, 2017 [14]

53/Not stated, Colombian.

2010.

PH2

with a history of recurrent untreated nephrolithiasis who progressed to ESRD, which required to initiate HD in May 2008. A cadaveric donor kidney transplant was performed on July 9, 2010.

In Nov 2010, the patient presented renal function impairment.

showed Banff 2A acute cell rejection and extensive tubular damage, with presence of CaOx crystals and micro-calcifications.

Heterozygote for 2 variants of the GRHPR gene:

-c.478G > A (p. Gly160Arg)

-c.626C > T (p. Ser209Phe)

handled with pulses of Methylpred, ATG and conversion to Tac. Management with diet low in oxalate, PN, potassium citrate and HCT.

The renal function became progressively deteriorated until a terminal stage, with reentry to HD in May 2015.

Liu et al, 2018 [15]

33/M, Chinese.

2014.

PH2

diagnosed with nephrolithiasis in Mar 2004. In Nov 2014, the patient developed dizziness and nausea with SCr 2500 mol/l. The patient was diagnosed with ESRD and underwent maintenance HD. He received an allogeneic renal transplant in Dec 2014.

On post-op day 15, serum creatine levels gradually increased to 291 μmol/l.

revealed borderline lesions of the renal graft and tubulitis accompanied by a small amount of crystal deposition within the renal tubules

Heterozygote for 1 variant of the GRHPR gene:

The renal graft was removed in Feb 2015. Renal pathology revealed interstitial injury due to crystal deposition within the renal tubules, with renal pelvis stones.

The patient received post-transplant HD and the date of the last follow-up visit was October 2015.

Current report case 1

27/M, Chinese.

2018.

PH2

With symptomatic kidney stones for more than 10 years and elevated SCr level for more than 3 years, accompanied with hypertension, the patient was diagnosed with ESRD, obstructive nephropathy and kidney stones. After right nephrectomy as well as left mini-PCNL, he underwent renal transplantation on Apr 28, 2018.

Due to the delayed recovery of renal function on post-op day 46.

revealed acute TCMR (Banff 1A) and extensive tubular damage, with the presence the emerging deposition of CaOx crystals in the allograft.

Heterozygote for 3 variants of the GRHPR gene

Exon4: c.295C > T (p. Arg99*): nonsense PV.

Exon6: c.512G > A (p. Arg171His): missense VUS.

Exon2: c.211G > A (p. Ala71Thr): missense VUS.

The patient was treated with PN and temporary intensive HD besides the basic immunosuppression.

The patient currently reentered to the maintenance HD in the clinic and looked forward to a chance of LKT in the future.

Current report case 2

26/M, Chinese.

2016.

PH1.

With an 8-year history of the elevated SCr, which included a 7-year history of maintenance HD. On Aug 12, he was transplanted with a deceased kidney donor.

The allograft function did not obviously recovery on post-op day 38.

Deposition of diffuse CaOx crystal as well as acute TCMR (Banff 2A) were detected.

Heterozygote for 2 variants of the AGXT gene

Exon1: c.33dupC (p. Lys12fs): frameshift PV.

Exon2: c.215A > T (p. Asn72Ile): missense VUS.

Heterozygote for 1 variants of the MUT gene

Exon11: c.1897G > C (p. Val633Leu): missense VUS.

Treated with PN and temporary intensive HD. Due to the anemia, bone marrow biopsy was conducted on Oct 21, which showed intertrabecular spaces occupied by abundant CaOx crystals. He was treated with CRBC transfusion and rhEPO to correct the anemia.

He returned to the maintenance HD and received the optimal immunosuppression. Up till now, the patient was investigated for the overall decline in health.

Current report case 3

34/M, Chinese

2016.

PH.

With the elevated SCr level for more than 12 months as well as hypertension. He received a kidney allograft on Jan 6, 2016.

The course was unfavorable with delayed recovery of renal function on post-op day 75.

documented acute TCMR (Banff 2A) and extensive deposits of CaOx crystals in the interstitial tubule.

Not detected.

In view of the fact that no oxalate crystals deposited in the ZHIB, as well as the history of kidney stones in the recipient, recurrence of CaOx nephropathy following kidney transplantation was confirmed, which led to the diagnosis of PH.

Treatment by HD besides the drug immunosuppression. PJP was confirmed on May 25 by FOB biopsy. The patient was initially treated with Micafungin and γ-globulin. And immunosuppression was replaced with the pulse intravenous Methylpred.

Even though the clinicians enhanced the anti-infection therapy with administration of TMP/SMX and VOR as well as MEM was used in the final stage, he died on Jun 28, 2016.