Urine metabolic risk factors and outcomes of patients with kidney transplant nephrolithiasis

Abstract

Background Nephrolithiasis in allograft kidneys is rare but this diagnosis may lead to allograft complications and patient morbidity. Previous studies that have evaluated nephrolithiasis post-transplant focused on surgical stone management with limited data on urine metabolic risk factors and presence of stones after follow-up. Methods We retrospectively evaluated kidney transplant recipients who were diagnosed with transplant nephrolithiasis between 2009–2019. Computed tomography and ultrasound imaging were used to confirm stone presence. Results The incidence of allograft kidney stone formation was 0.86% of 6,548 kidney transplant recipients. Of the 56 cases identified, 17 (30%) had pre-transplant history of nephrolithiasis. Only 4 (7%) patients received a known kidney stone at the time of allograft implantation. Of the 56 cases, 34 had a 24-hour supersaturation study. The urine supersaturation study showed 32 patients (94%) had a urine citrate of less than 450mg excreted in 24 hours (median 124.5 mg/24hr, reference range > 500 mg/24hrs), along with 22 patients (61%) having a urine oxalate excretion of greater or equal to 30 mg in 24 hours (median 34.4 mg/24 hr., reference range < 30 mg/24hrs). Calcium oxalate composition was the most common (91% with greater than 1 supersaturation for calcium oxalate crystals) with normal median urine calcium levels (median urine calcium 103.5mg/24hours, reference range <200 mg/24hrs). After a four-year follow-up, 50% (28) required surgical intervention and 43 (77%) patients continued to have evidence of transplant nephrolithiasis on imaging. Conclusions This is the largest study of transplant nephrolithiasis confirming that hypocitraturia and hyperoxaluria were the most significant urine metabolic risk factors associated with allograft nephrolithiasis and that hyperoxaluria was the most prevalent driver for calcium oxalate stone composition. Our study is first to show low stone free rates at last follow-up and a significant proportion requiring surgical intervention.

Clot stones in transplant kidneys

“…Urinary tract stones in transplant patients may be associated with foreign bodies (suture material at the ureteroneocystostomy site), recurrent infections or due to metabolic changes in the post-transplant kidney 2. A small number of allograft kidney stones are due to pre-existing stones in the donor kidney 3 4. Of the de novo stones formed, about one-third of the recipients are found to be stone formers prior to the transplant 3.…”

“…A small number of allograft kidney stones are due to pre-existing stones in the donor kidney 3 4. Of the de novo stones formed, about one-third of the recipients are found to be stone formers prior to the transplant 3. De novo stones can occur 1 month to many years after kidney transplantation 1–3…”

Kidney Stone Events after Kidney Transplant in the United States

“…Calcineurin inhibitors can lower urine citrate excretion by causing hyperkalemia and impairing ammonium production, leading to excretion of acidic urine or even overt metabolic acidosis. 20,21 Mycophenolate mofetil may also cause hypocitraturia by inducing diarrhea, resulting in bicarbonate loss from the stool and metabolic acidosis. 20,21 The ensuing metabolic acidosis in these patients will further lower urine citrate excretion or urine pH, both significant risk factors for calcium and uric acid stones.…”

“…20,21 Mycophenolate mofetil may also cause hypocitraturia by inducing diarrhea, resulting in bicarbonate loss from the stool and metabolic acidosis. 20,21 The ensuing metabolic acidosis in these patients will further lower urine citrate excretion or urine pH, both significant risk factors for calcium and uric acid stones. 20,22 Although we did not find an association between the use of calcineurin inhibitors or mycophenolate mofetil and kidney stone events, it is possible that longer follow-up time is needed to detect potential effects of maintenance immunosuppression on stone recurrence.…”

Secondary oxalate nephropathy and kidney transplantation

“…Secondary oxalosis is also associated with an increased risk of stone formation in the kidney allograft. In a retrospective study, Bolen et al [23] evaluated kidney transplant recipients diagnosed with transplant nephrolithiasis. The study showed that in patients with nephrolithiasis, 94% of the patients had urine citrate of <450 mg excreted in 24 h, along with 61% of the patients with a urine oxalate execration of !30 mg in 24 h. As expected, CaOx composition was the most common.…”