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- PATIENTS AND METHODS
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Renal transplantation is an effective and widely used treatment for end-stage renal disease. Urolithiasis is an uncommon but known complication in renal transplant recipients, with most series reporting a rate of 0.23–6.3%[1,2]. This complication has traditionally been treated with open surgical techniques, with considerable morbidity and mortality. The development of endourological techniques, such as ESWL, ureteroscopy and percutaneous nephrolithotomy (PCNL), might offer a minimally invasive alternative to open surgery [3–5]. The effect of retrograde ureteroscopy is limited for most transplant surgeons performing ureteroneocystostomy at the bladder dome. For medium-sized stones (5–15 mm), ESWL under close surveillance seems to be feasible but sometimes requires several sessions and auxiliary procedures [4,5]. PCNL has the advantage of potentially removing all the stone fragments at one procedure, but it is recommended only when there is a significant stone burden or when ESWL has failed, because of its potential risk and the greater importance of the single kidney . Minimally invasive PCNL (mPCNL) is a modified PCNL using a miniature endoscope via a small assess tract, and is considered to have significantly lower risks than traditional PCNL [6,7]. Here we report our experience with mPCNL for upper urinary tract (UUT) calculi in transplanted kidneys, with the aim of assessing its efficacy and safety.
PATIENTS AND METHODS
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- PATIENTS AND METHODS
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Between August 2002 and June 2006, five men and two women (mean age 40.7 years, range 28–54) were diagnosed with UUT stones in their transplanted kidneys, and transferred to our institution. Of the seven patients, the stone was an incidental finding in three, one presented with a UTI and fever, and three with oliguria and elevated serum urea and creatinine. The patients were diagnosed with urolithiasis at 1 month to 6 years after transplantation. The stone was in the distal ureter in three patients, the proximal ureter in one, the pelvis in two and the pelvis/calyx in one. The stones (largest diameter) were 0.5 × 0.6 to 3.5 × 4.0 cm, and the serum creatinine levels were 1.1–5.2 mg/dL. Urine culture indicated bacteriuria in two patients. Metabolic evaluation showed hyperuricaemia combined with hyperuricuria in one patient, and hyperuricuria and hyperuricaemia in one. The type of transplant was living-related in two patients and cadaveric in five. The allograft kidney was placed in the right iliac fossa in six patients and the left iliac fossa in one. All the allograft ureters were implanted at the ipsilateral bladder wall with an antireflux technique, by transplant surgeons. Immunosuppressive therapy consisted of cyclosporin A (or tacrolimus) and prednisolone and azathioprine (or mycophenolate mofetil). The original nephropathy was mainly glomerulonephritis. (Table 1).
Table 1. The patients’ characteristics and treatment outcomes
|Stone location||Staghorn||Pelvic||Pelvic||Proximal ureter||Distal ureter||Distal ureter||Distal ureter|
|Stone size, cm||3.5 × 4.0||2.3 × 1.7||1.9 × 2.1||1.3 × 0.9||0.8 × 0.8||0.5 × 0.6||0.6 × 0.8|
|Original nephropathy||GN||GN||APKD||Diabetic N||GN||GN||GN|
|Time from transplantation||1 month||3 years||5 years||4 years||6 years||2 years||2.5 years|
|Immunosuppression protocol||Cy, Az, Pr||Cy, MMF, Pr||Tac, MMF, Pr||Cy, Az, Pr||Cy, Az, Pr||Cy, MMF, Pr||Tac, MMF, Pr|
|Urine culture||None||E. coli||None||None||None||Ent. faecalis||None|
|Metabolic evaluation||Normal||Normal||HU||HUA, HU||Normal||HUA||Normal|
|Op. duration, min||100||50||70||20||25||75||30|
|Hb decline, g/dL||0.9||1.2||0.5||0.3||0.2||0.5||0.3|
|Stone analysis||CaOx||Struvite||CaOx, UA||UA||CaOx||UA||CaOx, UA|
|Outcome||NSR, SRF Cr 1.1||NSR, recurrent UTI RF decrease Cr 1.2||NSR, SRF Cr 1.2||NSR, SRF Cr 0.9||NSR, SRF Cr 1.0||NSR, SRF Cr 1.2||NSR, SRF Cr 1.1|
For mPCNL, the patient was placed supine and under epidural anaesthesia, and a single dose of cephalosporin was given during the procedure. First, ultrasonography was used to assess the position of the transplanted kidney and the pelvicalyceal system, and to guide the puncture of an anterior middle calyx by a 18-G 15-cm needle (Cook Urological, IN, USA). Urine was aspirated, and diluted (30–50%) contrast medium was injected into the collecting system. Then a 0.09 mm hydrophilic guidewire (Boston Scientific, Natick, USA) was inserted into the collecting system. After making a 0.5-cm skin incision the percutaneous tract was dilated over the guidewire with a fascial dilator (Cook Urological) from 8 F to 16 F under C-arm fluoroscopic guidance, and a 16 F ‘peel-away’ sheath (Cook Urological) was placed as the percutaneous access port. Subsequently a 8.5/12.5 F nephroscope (Richard Wolf Knittlingen, Germany) or a 8/9.8 F semi-rigid ureteroscope (Richard Wolf) was inserted to inspect the collecting system. Under direct vision the stone was fragmented using a pneumatic lithotripter or holmium:YAG laser. The larger fragments (0.3–0.5 cm) were extracted with forceps and the fragments of <0.3 cm were mainly flushed out with an endoscopic pulsed perfusion pump (MMC Yiyong, Guangzhou, China). Finally, a 4.8 F JJ stent (Boston Scientific) was inserted in the ureter and a 16 F nephrostomy tube left in place. The nephrostomy tube was removed 3–5 days later when the drainage was clear, and the JJ stent was extracted 2–3 weeks later.
When the stone was in the distal ureter and the nephroscope or the ureteroscope could not reach it, or the ureter was kinked, a 12.5 F flexible ureteroscope (Olympus, Tokyo, Japan) was inserted, the stone fragmented with the holmium:YAG laser, or extracted with a basket (Cook Urological).
If the patient had a febrile UTI or purulent pelvic urine was aspirated, a nephrostomy tube was placed initially and the mPCNL done 1 week later. During surgery, if bleeding obscured the endoscopic vision or the duration of nephroscopy was >90 min, manipulation was stopped and a second-stage mPCNL done 5–7 days later.
The operative duration was calculated from making the puncture to placing the nephrostomy tube. The haemoglobin level was estimated before and 48 h after surgery. During the follow-up, every 2–3 months the serum urea, creatinine, and uric acid levels were measured, with urine culture and ultrasonography.
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- PATIENTS AND METHODS
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Urolithiasis is an uncommon but known complication of renal transplantation. With advances in immunosuppression and improvement in technique, renal transplants have become more common and the duration of graft survival has increased. Therefore, this complication has also become more noticeable, with most series reporting a rate of 0.23–6.3%[1,2].
The risk factors for urinary stone disease in renal transplant recipients include the use of steroids, cyclosporin A, and when combined with other chronic diseases causing immunosuppression, which increases the rate of infection in the body and in the urinary system [3,8]. Glucocorticoids at high levels can produce hyperuricaemia and cyclosporin A produces hyperuricuria in about 50–60% of patients receiving this medication for immunosuppression; all this can increase the risk of forming uric acid stones in renal transplant recipients [4,8]. In the present series stone analysis showed that the stones of four patients contained uric acid, which concurs with this view. However, in the series of Klingler et al., only 0.2% (two of 1027) of all patients had documented uric acid stones, which suggests no lithogenic effect of these drugs. In addition, ureteric stricture and poor urinary drainage due to changes in anatomical positioning, such as the superior pole placed in a caudad position, can be conducive to stone formation in the grafted kidney.
Even with these risk factors, urolithiasis is less common in renal transplant recipients than in the general population . We assume that the risk factors alone are not enough to cause urinary stone disease in transplant recipients. Recent studies established immunological and biochemical mechanisms that diminish the risk of stone in renal transplant recipients. Rhee et al. found that urinary interleukin-6 was significantly elevated in the general stone population, unrelated to bladder pathology, and inferred that the effect of immunosuppression, e.g. cyclosporin (interleukin-2 inhibitor) might be to decrease the incidence of stone through the role of cytokines. Also, Dumoulin et al. reported no increase in urinary calcium oxalate supersaturation in long-term kidney transplant recipients, which is universally accepted as one mechanism of stone formation. The stones in transplanted kidneys can also be present in the graft itself. In the present series, the patient with a staghorn stone diagnosed 1 month after transplantation was obviously a case of a donor calculus. We think that ultrasonography should be used to assess the graft before transplantation, to easily detect stones in the allograft, and then to remove them during transplantation. Recently Rashid et al. reported the ex vivo ureteroscopic complete clearance of renal calculi in 10 kidneys without compromising ureteric integrity or renal allograft function.
Because the grafted kidney is denervated, urinary stone disease does not present in renal transplant recipients as in the general population, as classic renal colic is absent. Sometimes confirming the diagnosis of calculi in transplanted kidney with plain abdominal film and ultrasonography is not usually helpful, due to interference from the bony pelvis and overlying bowel. If the differential diagnosis is difficult, CT with no i.v. contrast material should be used.
Treatment protocols for calculi in the transplanted kidney are those used for single kidneys in general. Because of the potential risk of infection, and poor wound healing, open surgery is not recommended. The effect of retrograde ureteroscopic management is limited for most transplant surgeons using ureteroneocystostomy at the bladder dome, which causes difficulty in locating and cannulating the ureteric orifice. In addition, retrograde irrigation under ureteroscopy in an obstructed system can be devastating in an immunocompromised patient if infection occurs proximal to the obstruction. Between January 1995 and August 2002, nine patients with ureteric calculi in their transplanted kidneys had retrograde ureteroscopy in our institution; the procedure was successful only in three and one of them required a nephrostomy tube to control infection . From that time we did not use it as the initial therapy, because of the potential risk of infection.
Many authors reported success with ESWL for medium-sized calculi (5–15 mm) in transplanted kidneys, with the patient prone [4,5]. Although less invasive, ESWL has several limitations. Locating such stones can be difficult due to the position of the kidney over the bony pelvis. The clearance of stone fragments can be limited, especially with lower calyceal stones. Residual fragments carry the risk of UTI and can serve as a nidus for new stones. Once ESWL is used, steinstrasse can be troublesome due to retrograde inaccessibility of the ureter, and thus PCNL might be the next step in the treatment. Finally, ESWL seems to require several sessions and auxiliary procedures. Challacombe et al. reported that of 13 patients treated by ESWL, eight required several sessions; eight required a ureteric stent insertion before a second procedure, and four required a nephrostomy tube to relieve obstruction. In our institution we prefer to manage only simple and small stones in the middle or lower calyx with ESWL.
PCNL for urolithiasis in transplanted kidney was first described in 1982 by Fisher et al., and it has the advantage of potentially removing all stone fragments in one procedure. Although some favourable long-term results have been reported, PCNL is recommended for transplanted kidneys only when there is a significant stone burden or if ESWL has failed, because of its potential risks and the greater importance of the single kidney . We prefer mPCNL instead of traditional PCNL for stone retrieval in transplanted kidneys, because the smaller tract (16 F) can significantly decrease the risk of bleeding and tearing of the renal cortex. The data from mPCNL for managing stones in children also support its use. Desai et al. reported that the degree of dilatation and the size of the sheath introduced are the most critical considerations in reducing blood loss during PCNL. Jackman et al. used an 11 F access sheath in pre-school children to decrease the operative risk; they argued that a smaller tract leads to less tissue displacement and less nephron injury. In the present series, the mean haemoglobin decrease was only 0.55 g/dL and no patient had a significant deterioration in renal function on follow-up creatinine assessments or radioisotope scans. Some reports express concern that the small tract of mPCNL might result in a longer operation and high pressure in the collecting system, which can cause pyelovenous or pyelosinus backflow, or even sepsis. We think that the operative duration is not a problem in experienced hands; in the present series it was 53 (20–100) min, and even for the patient with the staghorn stone (3.5 × 4.0 cm), the duration was only 100 min. We assessed the pelvic pressure during mPCNL and found that within 14, 16, 18 and 16/16 F percutaneous tracts, the mean renal pelvic pressure was 24.85, 16.23, 11.68 and 5.8 mmHg, respectively, which remained lower than the level to back-flow (30 mmHg) (unpublished data). The most important factor causing urosepsis during PCNL is infected pelvic urine or calculi, and not pelvic pressure.
There are several important technical aspects of the procedure. To avoid visceral injury and minimize radiation exposure, ultrasonographic guidance is recommended for percutaneous access, to aid the anterior middle calyceal puncture, which traverses the minimum of cortical tissue, avoids injury to any major intrarenal vessels, and establishes the shortest straight tract between the skin and the calyx; via the shortest tract the nephroscope can be easily extended to the distal ureter. Some have noted that percutaneous dilatation was difficult because of marked perirenal reactive tissue. In our experience, pushing the fascial dilators with rotation easily solves this problem, and it can also decrease the risk of tearing renal tissue, and of bleeding.
In conclusion, mPCNL is safe and effective for managing calculi in transplanted kidneys. Ultrasonographically guided anterior middle calyceal puncture and dilating the tract with rotating the fascial dilators make mPCNL an easy procedure. In the present series, mPCNL resulted in primary complete stone removal in all cases without compromising graft function. This procedure should be considered as the initial approach for most cases of UUT stones in transplanted kidneys, except for simple and small stones in the middle or lower calyx.