Safety and Efficacy of Minimally Invasive Percutaneous Nephrolithotomy in Patients with Autosomal Dominant Polycystic Kidney Disease

Abstract

Purpose:

To review our experience of using minimally invasive percutaneous nephrolithotomy (MPCNL) in patients with autosomal dominant polycystic kidney disease (ADPKD).

Patients and Methods:

We retrospectively reviewed 23 renal units in 23 patients with ADPKD who underwent MPCNL in our center between January 2007 and December 2012. The data on the stone burden, stone locations, patient characteristics, complications according to the modified Clavien system, and stone-free rates (SFR) were analyzed.

Results:

The mean stone area (±standard deviation) was 1382.87±1080.17 mm². There were 10 (43.5%) staghorn stones. Flank pain was noted in 87% of the cases. SFR after initial MPCNL was 69.6% (16/23 renal units). Of the remaining seven renal units, six underwent second-look MPCNL and were rendered stone free, a 95.7% final SFR. Clavien grade I or II complications occurred in nine patients and were managed conservatively. One case needed selective arterial embolization for severe bleeding. There was no deterioration of renal function noted. The mean preoperative creatinine (Cr) and postoperative Cr concentrations were 148.17 μmol/L and 149.24 μmol/L (P=0.48).

Conclusion:

The MPCNL was a safe and effective treatment for upper urinary tract stones in patients with ADPKD, even in patients with staghorn stone. It provided excellent SFR without compromising renal function. This procedure could be considered as a first-line treatment option for patients with ADPKD who have a large stone burden.

Introduction

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, affecting 4 to 6 million people worldwide. It accounts for 7% to 10% of the patients undergoing renal replacement therapy.¹ The incidence of nephrolithiasis among patients with ADPKD is 5 to 10 times more than the general population.² A number factors contribute to stone formation in patients with ADPKD. These include metabolic disorders, the cysts in ADPKD causing compression of the pelvicaliceal system and leading to urinary stasis, structural abnormality, or any combination of these factors.¹

Percutaneous nephrolithotomy (PCNL) is an effective and well-established treatment for patients with upper urinary calculi in anatomically normal kidneys. It has been proven to be highly effective and has a low major complication rate.³

On the other hand, PCNL has not been widely used for the treatment of stone disease in patients with ADPKD. There were concerns that the anatomic abnormalities might make the percutaneous access difficult and dilation through cystic structures might increase complications.

There was a paucity of literature on using PCNL in patients with ADPKD and nephrolithiasis. In a few small series, PCNL has been shown to be highly effective in ADPKD with an overall stone-free rate (SFR) of 88% to 100%.^4
–6

Minimally invasive PCNL (MPCNL) is a modified PCNL technique using a miniaturized scope through a smaller, 18F or less, nephrostomy tract. We have been using this procedure for almost all the upper urinary tract stones that necessitated PCNL in our center for the past 10 years.⁷ We reviewed our experience of using this procedure in patients with ADPKD who had large or complex upper urinary tract stones. The safety and efficacy of this procedure was assessed and reported.

Patients and Methods

Patients

We performed a retrospective review of 23 patients with ADPKD who underwent MPCNL for upper urinary tract stones at our department, the Urology Department of the First Affiliated Hospital of Guanzhou Medical University, between January 2007 and December 2012.

The patients' diagnosis of ADPKD was made with with abdominal ultrasonography using Ravine criteria.⁸

Radiologic evaluation of the stone generally included ultrasonography and noncontrast CT. In patients with creatinine ≤150 μmol/L, intravenous pyelography (IVP) was added when it was indicated.

The stone surface area was calculated by first measuring the length of the stone in a left to right and cephalad to caudad axis on the anterior-posterior radiologic image; the two values were then multiplied to obtain the area. In case of multiple stones, the area of each stone was added together to obtain the total surface area.

Routine complete blood cell count (CBC), urinalysis, serum chemistry, coagulation studies, and urine culture were obtained on all patients before the procedure. Prophylactic antibiotics were routinely administered. In patients with a positive culture, antibiotics were selected according to the bacterial sensitivity result.

Patient demographics, operative factors (operative time, renal puncture site, and number of nephrostomy tracts) and postoperative outcome (SFR, complications, hemoglobin drop, blood transfusion, stone analysis, nephrostomy drainage duration, and hospital stay) were collected and retrospectively reviewed. SFR was defined as no stones visible on plain radiography of the kidneys, ureters, and bladder (KUB) and ultrasonography, or residual stone <2 mm discovered at postoperative follow-up. The grade of complication was assigned according to the modified Clavien classification for percutaneous procedures.⁹

Surgical technique

The technique of MPCNL has been described in our previous publications.^7,10 Here, a brief description of our techniques. All procedures were performed under general anesthesia. A 4F or 5F ureteral catheter was introduced in retrograde fashion with the patient in the lithotomy position. The bladder was drained with an indwelling Foley catheter. The patient was then placed into the prone position with the upper abdomen supported with a pillow. Percutanous access was obtained using either ultrasonographic or fluoroscopic guidance. We routinely started with ultrasonography; if ultrasonographic guidance was not satisfactory, fluoroscopy was then used. Among our 23 patients, 21 accesses were successfully achieved with fluoroscopy and 2 were performed with ultrasonography.

We performed all renal punctures ourselves. An 18-gauge coaxial needle was used. After the desirable calix was reached, a 0.035" flexible-tip guidewire was introduced. We usually attempted to manipulate the guidewire down to the ureter. If this was not successful, the second choice was to allow the guidewire to coil in a more distant calix. Next, the access tract was dilated from 8F to a maximum 18F using fascial dilators. An 18F matched peel-away sheath was placed as the percutaneous access port. An 8/9.8F semi-rigid ureteroscope was used for pneumatic lithotripsy or holmium laser. The large fragments were extracted with forceps, and small fragments were flushed out with an endoscopic pulsed perfusion pump. When multiple nephrostomy tracts were necessary to clear stones, the same technique was used. At the end of procedure, a 5F double pigtail ureteral stent and a silastic nephrostomy tube were left in place.

Plain KUB radiography, ultrasonography, and CT if indicated were performed 1 to 2 days postoperatively. Levels of hemoglobin, serum creatinine, and serum electrolytes were monitored. A second-look MPCNL was performed in 4 to 6 days after the initial procedure when there were significant residual stone fragments or as a planned staged procedure through the same nephrostomy tract. In patients who were either stone free or with residual stone of <2 mm and with the drainage from nephrostomy tubes being grossly clear, the tubes were first clamped, then removed. The ureteral stents were removed in 4 weeks as an outpatient procedure. The CBC and serum creatinine evaluations were repeated at this time as well. Postoperative follow-up including KUB radiography and/or ultrasonography was generally scheduled in 3months.

Statistical analysis

Continuous normally distributed data were recorded as mean±standard deviation. Median was used for data that were not normally distributed. When appropriate, continuous variables were compared with the Student t test. Statistical significance was set at P<0.05. The data analysis was performed using SPSS 13.0.

Results

From January 2007 to December 2012, 23 ADPKD patients (23 renal units) with upper urinary tract calculi were treated with MPCNL. Of the 23 patients, 14 patients had bilateral urolithiasis. All patients with bilateral urinary stones needed only unilateral MPCNL. The contralateral stones were small and treated with other means. Of the 23 renal units that underwent MPCNL, 43.5% (10 renal units) had staghorn calculi. A complete staghorn (filling the entire collecting system or at least 80% of it) was encountered in two renal units.¹¹ The mean stone area was 1382.87±1080.17 mm² (range 104–3920 mm²). The kidney and stone characteristic are shown in Table 1.

Table 1.

Characteristics of the Kidneys and Stones

Characteristic	Number
Kidney size (cm), mean±SD
Length	14.59±2.82
Width	7.33±1.38
Mean stone size (mm²)±SD, (range)	1382.87±1080.17 (104–3920)
Stone location, no. (%)
Renal pelvis	3 (13.0)
Calyceal	1 (4.4)
Pelvicaliceal (multiple sites)	6 (26.1)
Upper ureter	3 (13.0)
Staghorn	10 (43.5)

SD=standard deviation.

Table 2 shows the preoperative findings for the 23 patients. There were 17 (73.9%) men and 6 (26.3%) women with a mean age of 42.52±11.49 years (range 23–69). Flank pain, 87.0%, was the most common clinical presentation. Other symptoms included hematuria, 34.8%, urinary frequency, 17.4%, loss of appetite, 4.3%, and fever 4.3%. Two (8.6%) patients had positive cultures preoperatively and were treated with culture-specific antibiotics.

Table 2.

Patient Characteristics

Characteristic	Overall
Mean age (range), years	42.52±11.49 (23–69)
Sex
Male, no. (%)	17 (73.9)
Female, no. (%)	6 (26.1)
BMI, no. (%)
<25 kg/m²	16 (69.6)
25–<30 kg/m²	4 (17.4)
≥30 kg/m²	3 (13.0)
Operated side, left, no. (%)	13 (56.5)
Comorbidities
Hypertension, no. (%)	6 (26.1)
Diabetes mellitus, no. (%)	2 (8.7)
Presentation, no. (%)
Flank pain	20 (87.0)
Hematuria	8 (34.8)
Frequent urination	4 (17.4)
Loss of appetite	1 (4.3)
Fever	1 (4.3)
Asymptomatic	2 (8.7)
Preoperative urine culture, no. (%)
Sterile	21 (91.4)
Escherichia coli	1 (4.3)
Staphylococcus epidermidis	1 (4.3)
Mean serum uric acid level (range), umol/L	399.83±109.81 (232.00–681.00)
Mean serum calcium level (range), mmol/L	2.26±0.14 (2.060–2.491)

BMI=body mass index.

In 20 (87.0%) cases, a single nephrostomy tract was used. In two (8.7%) cases, two tracts were used, and in one (4.3%) case, three tracts were used simultaneously. The number of these tracts obtained through the lower calix, middle calix, and upper calix were 6 (22.2%), 16 (59.3%) and 5 (18.5%), respectively. Operative time was defined as the interval from commencing the ureteral catheter insertion to the placement of the nephrostomy drainage tube. The mean operative time was 95.17 minutes (Table 3).

Table 3.

Operative Characteristics and Treatment Result

Variable
Mean operative time (min)	95.17±14.02
No. of percutaneous tracts per patient (%)
1 tract	20 (87.0)
2 tracts	2 (8.7)
3 tracts	1 (4.3)
No. of point of tracts (%)
Upper polar	5 (18.5)
Midpolar	16 (59.3)
Lower polar	6 (22.2)
Second-look MPCNL requirement, no. (%)	6 (26.1)
Stone free, no. (%)
Primary	16 (69.6)
With second-look MPCNL	22 (95.7)
Residual stones	1 (4.3)
Complications, no. (%)
Fever >38°C (Clavien grade I)	4 (17.4)
Urinary tract infection (Clavien grade II)	3 (13.0)
Blood transfusion (Clavien grade II)	2 (8.7)
Selective renal artery embolization (Clavien grade IIIa)	1 (4.3)
Mean days of hospitalization (range)	10.35±3.54 (5–20)
Median days for nephrostomy removal (range)	7.00 (3–15)

MPCNL=minimally invasive percutaneous nephrolithotomy.

Table 4 shows the effect of MPCNL on hemoglobin and serum creatinine levels. The mean preoperative and postoperative hemoglobin values were 126.26±19.11 g/L and 115.61±18.03 g/L. The change was not statistically significant with P=0.062. The mean (range) decrease in hemoglobin level was 11.35±9.65 g/L (0–33.0). Of the 23 patients, 8 (34.8%) had a preoperative serum creatinine level >133 μmol/L. The mean preoperative creatinine and postoperative creatinine concentrations were 148.17 μmol/L and 149.24 μmol/L; there was no statistically significant difference between these two groups, P=0.480. The mean serum creatinine level at the time of removal of the ureteral stent was 136.22 μmol/L. This was slightly lower than the preoperative value; however, the difference fell short of statistical significance (P=0.568).

Table 4.

Effect of Minimally Invasive Percutaneous Nephrolithotomy on Hemoglobin and Serum Creatinine Levels (Mean±Standard Deviation)

Parameters	Overall
Preoperative Hb, g/L	126.26±19.11
Postoperative Hb, g/L	115.61±18.03
Hb dropped (range), g/L	11.35±9.65 (0–33.0)
P value	0.062
Preoperative Cr >133 μmol/L, no. (%)	8 (34.8)
Preoperative Cr, μmol/L (range)	148.17±110.06 (77.0–568.0)
Postoperative Cr, μmol/L (range)	149.24±86.20 (72.0–475.0)
1 month follow-up Cr, μmol/L (range)	136.22±86.66 (53.0–441.0)
P value	P ₁=0.480/P ₂=0.568

P ₁ value represented the difference between preoperative Cr and postoperative Cr.

P ₂ value represented the difference between preoperative Cr and follow-up Cr.

Hb=hemoglobin; Cr=creatinine.

Complications were listed on Table 3. Overall, 10 complications were recorded. There were nine Clavien grade I or II complications, which were managed conservatively. One patient needed selective arterial embolization for severe bleeding. The mean hospital stay was 10.35±3.54 days.

Radiography of the KUB was used postoperatively to assess the SFR in 21 patients. KUB radiography combined with ultrasonography was performed in 6 patients. For 2 patients with a complex stone that was radiolucent, CT was performed to assess SFR.

Of our 23 patients (69.6%) patients, 16 were stone free after the primary MPCNL. Six (26.1%) patients needed a second-look MPCNL during the same hospitalization to remove residual stone fragments. The SFR at discharge was 95.7% (Table 3). Stone analyses were available in 17 of 23 (73.9%) cases. The most common stone composition was calcium oxalate (52.9%, 9/17). Uric acid and magnesium ammonium phosphate were detected in six and two cases, respectively.

Follow-up KUB radiography and/or ultrasonography available for 14 patients showed no recurrent calculi at 3 months. We lost nine ecdemic patients during the follow-up period because of the long distance between the hospital and their residence.

Discussion

Patients with ADPKD are more prone to the development of nephrolithiasis than the general population.^1,2,12 Anatomic abnormalities and metabolic disturbances might be the contributing factors. Compression of the pelvicaliceal system by the cysts in the polycystic kidney could lead to urinary stasis and heightened risk of urinary tract infections; this also increases the probability of stone formation.² Metabolic disturbances of ADPKD include low urinary pH, hypocitraturia, hyperuricemia, and hyperuricosuria.¹³ Nishiura and associates¹ found hyperoxaluria was significantly higher in patients with ADPKD and nephrolithiasis. In our patients, the most common stone type was indeed calcium oxalate. It accounted for 52.9% of the stones.

ADPKD is often clinically silent for many years. Nephrolithiasis is rare during childhood. It commonly develops after age of 20.¹⁴ In our study, all patients were more than 20 years old (23–69). The most common symptoms were flank pain (87.0%) and hematuria (34.8%). Flank pain might result from renal colic, urinary tract infection, bleeding into the cysts, and the pressure caused by the cysts. Hematuria was intermittent and usually resolved spontaneously.

The principles for nephrolithiasis therapy in patients with ADPKD are the same as in patients with normal kidneys. The optimal treatment has not been settled. Before the 1980s, open surgery was the only treatment option to remove stones in anatomically abnormal kidneys.¹⁵ With the introduction of extracorporeal shockwave lithotripsy (SWL) in the 1980s, it quickly became the treatment of choice for the majority of urinary tract stones in patients with ADPKD. Delakas and colleagues¹⁶ reported on using SWL in the treatment of 13 patients with ADPKD and nephrolithiasis. Eleven (85%) patients were stone free at 3 months. There were no serious complications. Most stones, however, were smaller than 2 cm, and a ureteral stent

SWL is generally not recommended as monotherapy for large upper urinary tract stones. In our current series, 10 (43.5%) patients had staghorn stones with a mean stone area of 1382.87±1080.17 mm². These patients certainly could not be adequately managed with SWL monotherapy. Flexible ureteroscopy with a holmium laser might be an option for mangement of upper tract stones. It also has its limitation, however, in bulky stones, such as staghorn stones. In a recent series by Yili and coworkers,¹⁷ they treated 15 renal stones in 13 patients with ADPKD using flexible ureteroscopy and holmium laser. Most of the stones were located in the renal pelvis and/or calices; the largest stone was 1.7 cm in diameter. Their overall SFRs after one and two procedures were 84.5% and 92.3%, respectively. There were no serious complications.

PCNL has the potential to remove large or complex stone in normal kidneys with a single procedure. There has been reluctance to apply it in patients with ADPKD, however, especially in view of the distorted anatomy caused by the large number and sizes of renal cysts.

There were several small series using conventional PCNL to treat kidney stones in patients with ADPKD. The SFR was in the range of 88% to 100% (Table 5).^4
–6 Al-Kandari and colleagues⁵ had 19 patients who underwent PCNL using fluoroscopic guidance, and their SFR was 89.4%. Three patients needed second-look PCNL. Umbreit and associates⁴ reviewed nine patients with ADPKD and renal calculi. All their patients also underwent PCNL with fluoroscopic guidance. In 9 of 11 (82%) kidneys, nephrostography performed 24 hours after the final procedure showed no residual stone fragments. The authors reported no significant complications. Two patients needed percutaneous basket extraction to achieve stone-free status. Srivastava and coworkers⁶ used a 28F nephroscope to perform PCNL in patients with ADPKD. They reported an overall success rate (either completely stone free or with residual fragments <4 mm) of 88%.

Table 5.

Review of the Literature on Standard Percutaneous Nephrolithotomy Treatment of Kidney Stones in Patients with Autosomal Dominant Polycystic Kidney Disease

Authors	Number of renal units	Stone size	Access single/multiple	Stone-free rate	Complications
Al-Kandari et al⁵	19	>3 cm	18/1	89.4% (17/19)	2 fever 1 hematuria
Umbreit et al⁴	11 (9 patients)	1.6–3.6 cm	6/5	100% (2 kidneys needed flexible nephroscopy)	None
Srivastava et al⁶	25 (22 patients)	2.4±0.8 cm	20/5	88%	4 fever 3 blood transfusion

In our patients, the SFR after primary MPCNL was 69.6%. Six patients needed second-look PCNL through the established nephrostomy tract to remove residual calculi. The final SFR at the time of discharge was 95.7%. This result was on par with those in the literature. Multitract PCNL was often needed for large or complex stones and for altered anatomy. We used multiple minitracts in our patients with ADPKD and staghorn stone. We found this approach safe, efficient, and with acceptable morbidity.

Conventional PCNL is usually performed through a 24 to 34F renal access tract. Recently, several authors had advocated the use of MPCNL, a modified procedure using a smaller percutaneous nephrostomy tract.^7,18,19 The use of a smaller access tract might decrease the risk of bleeding and reduce the transfusion rate.^20,21

In our series, the transfusion rate was 8.7%. This was in line with rates in the literature in which conventional PCNL was used.^4
–6 Therefore, we found no evidence to support that MPCNL would reduce the transfusion rate.

Renal function in patients with ADPKD usually remains stable for long time. It generally starts to deteriorate in the fourth decade of life. Thus, it is imperative to preserve renal function during the treatment of nephrolithiasis in these patients. In our current study, there were no significant changes in the serum creatinine levels before and after MPCNL (P=0.480). In addition, at 1-month follow-up, the mean serum creatinine level was slightly lower than the preoperative values. The difference again fell short of statistical significance (P=0.568), however. We therefore concluded that MPCNL did not affect renal function.

The key steps of PCNL include renal puncture, nephrostomy tract dilation, and lithotripsy. Optimal renal puncture can affect the outcomes of the procedure. The options for puncture guidance included fluoroscopy, ultrasonography, CT, and MRI. The most commonly used modalities are fluoroscopy and ultrasonography. Ultrasonogrphic guidance has the advantage of avoiding radiation exposure to the patient and the surgical staff. Because the adjacent viscera can often be seen on the ultrasonography images, there could be reduced risk of their injury. Finally, with color Doppler, there is also the potential to avoid injury to renal vasculatures.²²

In our experience, however, ultrasonography guidance was inferior to fluoroscopy in patients with ADPKD. Only 2 of our 23 patients had successful renal puncture under ultrasonograaphy guidance. Unfortunately, in one of these two patients, severe postoperative bleeding with pseudoaneurysm formation that necessitated selective arterial embolization developed. This patient had only a single nephrostomy tract. The presence of multiple cysts and the distorted anatomy of the caliceal system were the causes of making puncture with ultrasonography guidance difficult. On the other hand, with contrast material injected in retrograde fashion through the ureteral catheter placed at the beginning of the procedure, the pyelocaliceal system could be much better visualized, thus making the puncture easier and more accurate.

Our hospital stay is significantly longer than those reported in Western literature. This is because of the extremely low cost of a hospital stay in China (average 10 dollars per day and set by the government) and the unique culture in our society. It is not socially acceptable to discharge patients to home before they are fully recovered. It is even less tolerated for patients to go home with drains or tubes in place.

Conclusion

Our experience showed that MPCNL was a safe and effective treatment modality for upper urinary tract stones in patients with ADPKD. It provided excellent SFR without compromising renal function. As matter of fact, we did not see much difference in treating patients with ADPKD than those in the general population. We found fluoroscopy-guided puncture is easier and more accurate than ultrasonography guidance. It probably should be used first. We had more staghorn stones than to be expected. This, however, might be because of being the tertiary referral center for stone disease in our region.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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