Donor Calculi Induced Acute Renal Failure

Abstract

Nephrolithiasis is an infrequent complication following renal transplantation and acquisition of a stone with the donor kidney is rare. Indeed only a few cases of donor stones causing renal failure have been reported. Since the grafted kidney is denervated, stone disease may not present with the classic renal colic but rather with acute renal failure secondary to the obstruction. Identification of the precise cause is critical in order to avoid inappropriate therapy. We present our experience of two renal transplant patients who developed obstructive uropathy by stones originating from the donor kidneys.

Each atom of that stone, each mineral flake of that night filled mountain, in itself forms a world.

—Albert Camus (The myth of Sisyphus)

• Donor calculi
• Acute renal failure
• Nephrolithiasis

Introduction

Lithiasis in renal graft occurs infrequently and acquiring a stone with the donor kidney is a rare entity. Indeed, only a few cases of stone disease directly transmitted with the implanted kidney have been reported.[[1]], [[2]], [[3]] The infrequency and rather unusual presentation can make the diagnosis and treatment in the renal transplant recipient more challenging. We report two renal transplant patients who developed renal failure by stones originating from the donor kidneys. We review the clinical presentation, diagnosis, and management of renal stones acquired with donor kidneys. Index words: Lithiasis, Renal transplantation.

Case No. 1

A 44-year-old Caucasian male with end stage kidney disease secondary to IgA Nephropathy underwent a cadaveric renal transplant. His past medical history included hypertension, COPD, and gout but nephrolithiasis was specifically denied. Surgery and the post-operative course were uneventful. The patient's immunosuppressive regimen initially included antithymocyte globulin (ATGAM), mycophenolate mofetil, and prednisone. Cyclosporine (Neoral) was begun on Day 4 when the creatinine had fallen by 50%. Protocol ultrasound performed on postoperative Day 1 showed a V shaped echogenic density in the mid-portion of the transplanted kidney consistent with an intra-parenchymal stone without any evidence of hydronephrosis (Fig. 1). A subsequent CT scan confirmed that diagnosis. The patient was discharged on the fifth post-operative day with a serum creatinine of 1.2 mg/dL.

Figure 1. Ultrasound performed 24 h post-renal transplantation. Arrow denotes stone in the renal parenchyma.

Five weeks post-transplant the patient complained of vague abdominal discomfort especially around the transplant site and laboratory studies showed a serum creatinine of 2.9 mg/dL. Ultrasound now revealed hydronephrosis of the transplanted kidney, a proximal ureteral calculus and the intra-parenchymal stone was no longer detected (Fig. 2). Attempted stent placement was met with technical difficulties and a percutaneous nephrostomy was performed. This resulted in a decline of the serum creatinine to 1.2 mg/dL and a decision was made to observe the patient with the nephrostomy in place. The patient developed pyelonephritis 10 weeks post-transplant, which required IV antibiotics. About 12 weeks post-transplant, urine output decreased and the abdomen became distended. The serum creatinine rose to 4 mg/dL and an ultrasound showed a large lymphocele involving the post-lateral aspect of the kidney. Computed Tomography guided percutaneous drainage was performed but a post-procedure ultrasound showed persistence of the hydronephrosis and fluid collection around the transplanted kidney.

Figure 2. Ultrasound performed five weeks post transplantation for acute deterioration in renal function. Arrow denotes hydronephrotic calyceal system. Stone annotated in proximal ureter.

A retrograde ureterogram revealed a filling defect in the distal ureter, but a ureteral stent could still not be placed. Subsequently, the patient underwent an open exploration and multiple perinephric hematomas were noted. A stone was extracted with a basket placed via ureteronephroscopy and an ureteroneocystostomy was performed. Post-operatively, the patient did well and the serum creatinine fell to 1.8 mg/dL. The 5 × 5 mm stone proved to be composed of calcium oxalate and calcium phosphate. Approximately 12 weeks later, a 24-h urine study (volume 2460 mL) showed the patient to excrete 123 mg of calcium, 303 mmol of sodium, and 1495 mg of creatinine. The serum calcium at that time was 9.4 mg/dL (8.5–10.2 mg/dL), phosphate 3.4 mg/dL (2.5–4.5 mg/dL), PTH 73 pg/mL (10–65 pg/mL), and uric acid of 6.2 mg/dL (2.6–8.3 mg/dL).

Case No. 2

A 56-year-old white male with end stage renal disease secondary to chemotherapeutic agents used about 25 years ago, underwent a cadaveric renal transplant. His past medical history was negative for any kidney stone disease. The patient received antithymocyte globulin, mycophenolate mofetil, prednisone, and cyclosporine for immunosuppression. The sonogram done on the first postoperative day revealed several parenchymal non-obstructive renal calculi (Fig. 3). The patient's postoperative course was unremarkable and he was discharged on the fifth postoperative day with a serum creatinine of 1.7 mg/dL. Subsequently in the transplant clinic the serum creatinines were consistently found to be between 1.4–1.5 mg/dL range. On routine testing four weeks after transplantation, patients creatinine was noted to be 2.4 mg/dL which when repeated on the same day had risen to 2.8 mg/dL. The patient was asymptomatic, the physical examination unremarkable and an emergent ultrasound showed hydronephrosis and hydroureter in the transplanted kidney (Fig. 4). The urinalysis revealed 2+ hematuria, the cyclosporine level was 309 ng/mL, which was unchanged from preceding values. A decision to watch the patient expectantly proved efficacious. The patient passed the kidney stones spontaneously experiencing only mild discomfort in the urethra. Subsequently the creatinine dropped to 2 mg/dL next day and returned to a baseline of 1.5 mg/dL three days later. The repeat ultrasound showed the hydronephrosis to have resolved. Although a few intraparenchymal stones could still be visualized, the number was less than seen on the initial postoperative ultrasound (Fig. 5). A 24-h urine collection (volume 1900 mL) obtained six weeks later showed the patient to excrete 194 mg of calcium, 169 mmol of sodium, 447 mg of uric acid, 1300 mg of creatinine, and 172 mg of citric acid. The serum calcium, uric acid, and intact parathyroid hormone levels were all within normal levels.

Figure 3. Ultrasound performed 24 h post transplant showing multiple parenchymal stones.

Figure 4. Ultrasound performed for acute deterioration in renal function showing hydronephrosis.

Figure 5. Ultrasound performed after passage of stones showing resolution of hydronephrosis and fewer stones.

Discussion

The incidence of donor kidney lithiasis is around 0.37%,[[4]] a rate not unexpectedly similar to the rate of asymptomatic stone detection in the general population.

The clinical presentation of transplant kidney stones may be non-specific, as was the case in our patients. Since the grafted kidney is denervated, the patient may not present with the classic “renal colic.” The initial manifestation may be a rising creatinine and azotemia, making it difficult to differentiate from acute rejection, acute tubular necrosis, or calcineurin toxicity. Sudden anuria or oliguria with or without hematuria may also be the initial presentation. Occasionally patients may have graft tenderness mimicking a rejection. Indeed our first patient presented with poorly localized abdominal pain while the second patient experienced no discomfort until the stone traversed the urethra. Patients may inadvertently be started on steroids and since some improvement in nonspecific symptoms may occur, the diagnosis may be delayed further resulting in damage to the allograft.

The diagnostic evaluation of renal impairment in a transplanted patient with suspected stone disease should include an ultrasound and/or renal flow scan initially.[[5]] These tests besides identifying stone disease as the cause of renal impairment may help exclude the presence of any vascular complications or urinary leakage. It must be kept in mind though that hydronephrosis may be minimal in early graft-obstruction, and that the studies may not distinguish acute rejection or ATN from ureteral obstruction in all cases.[[6]] A CT scan with or without contrast (depending on the renal function) may be obtained for the exact location of the stone especially when a surgical intervention is being contemplated.

The therapeutic approach to renal transplant recipients with calculi varies, and must take into account factors like size, position, number of stones, and presence of associated abnormalities such as ureteral strictures or unusual urinary tract reconstruction. While a small stone may pass spontaneously, active intervention may be required in other situations. Extracorporeal shock wave lithotripsy (ESWL) may be a safe and effective treatment of renal calculi especially smaller calculi when radiological localization is possible and if there is no distal obstruction.[[3]], [[7]] The potential technical difficulties in administering ESWL originate from the anterior positioning of the kidney in the pelvis and from the presence of bone behind the kidney that can render shock waves ineffective. The invasive approach such as a ureteral stent to facilitate stone passage and percutaneous nephrolithotomy should be reserved for larger stones (i.e., >3 cm), stones present in distal ureter and patients with nephrostomy tube placement. Percutaneous nephrolithotomy procedures though facilitated by the superficial placement of the kidney may still be difficult to perform due to the fibrous tissue that surrounds the transplanted kidney.[[8]] Urethroscopy with basket extractors may be used for ureteral stones with good results, however excessive manipulation may cause scarring and stenosis. Open surgical exploration should be reserved for those patients failing one of these less invasive procedures. The difficulties that can be encountered with stone management and extraction in transplant patients were exemplified in the first patient who eventually required an aggressive approach to rectify his pathology.

In view of a very low incidence of renal stones in the donor kidneys, routine donor kidney ultrasonography or nephrotomography may not be cost effective though a careful inspection and palpation may be helpful.[[9]] Because of the shortage of donors, presence of stones in the donor kidney is not an absolute contraindication for transplantation. At many centers including our center, protocol ultrasounds are performed in the immediate postoperative period and these sonograms may detect incidental renal stones.

In conclusion, acquiring renal stones with donor kidneys in transplant recipients is rare and clinical presentation may be atypical. With proper medical and surgical management, post-transplant lithiasis usually can be treated with minimal graft dysfunction.

Acknowledgment

Dr. Bhupendra Mepani (Department of Radiology, Erie County Medical Center, Buffalo, NY) for assistance in reviewing imaging studies.