Percutaneous Nephrolithotomy in Immunocompromised Patients: Outcomes from a Matched Case

Abstract

Objective:

To compare the outcomes of percutaneous nephrolithotomy (PCNL) in immunocompromised patients with those of PCNL in healthy population.

Patients and Methods:

A matched case–control study was performed from January 2009 through December 2014 using our prospectively collected kidney stone database. Patients with positive serology to human immunodeficiency virus (HIV), hepatitis C (cellular immune dysfunction), and patients on high dose of immunosuppressive drugs for treatment of autoimmune diseases composed the case group. Control group included patients with kidney stones and no other comorbidity. Patients were randomly matched based on Guy's score as a surrogate of case complexity.

Results:

Sixty-two patients were enrolled in this study, 21 cases and 42 controls. There were no significant differences in age, gender, and body mass index between groups. Regarding PCNL technique, there were no differences in patient positioning, number of accesses, and operative time. Complication rate was higher in the case group (38.1% vs 14.3%; p = 0.032); however, major complications, defined by Clavien score ≥3, were not statistically different (4.8% vs 2.4%; p = 0.611). There was a tendency of more postoperative urinary tract infection in the case group (19% vs 4.8%; p = 0.069). Mean decrease in hemoglobin level (3.3 vs 2.4 mg/dL; p = 0.037) and blood transfusion rate (23.8% vs 4.8%; p = 0.036) was significantly higher in the case group. Immunocompromised patients had a 2.8-fold increased risk of complications (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.01, 7.74) and a 5.8-fold increased risk of blood transfusion (OR = 5.8, 95% CI 1.29, 26.55). There were no differences in stone-free rate, nephrostomy tube time, and length of hospital stay.

Conclusion:

Immunocompromised patients are at higher risk for complications such as bleeding after PCNL.

Introduction

Percutaneous nephrolithotomy (PCNL) is the treatment of choice for patients with kidney stones >2.0 cm and staghorn calculi due to its minimally invasive characteristics and high stone-free rate.^1,2 Despite the advantages in terms of stone removal compared with open surgery, extracorporeal shockwave lithotripsy (SWL), and even with retrograde intrarenal surgery, the incidence of complications associated with PCNL is reported as much as 50% and major complication rate is not negligible.^1,3

Several studies have been performed to assess the results, complications, and safety of this procedure on specific populations, such as high-risk patients (American Society of Anesthesiology III and IV), morbidly obese patients, diabetics, and elderly^{4

–12}; nonetheless, there is a paucity of data on literature regarding the outcomes of PCNL in immunocompromised patients. This special population includes patients with human immunodeficiency virus (HIV) or hepatitis C infection and patients on immunosuppressive therapy due to autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome.¹³ These patients may also suffer from large kidney stones since urolithiasis incidence is increasing¹⁴; however, no study has been conducted to evaluate the PCNL feasibility and safeness on this population.

The purpose of this study was to evaluate PCNL success and complication rates in this particular group of patients compared with kidney stone patients with normal immune status. We speculate that immunocompromised patients are at higher risk for complications than regular kidney stone subjects.

Patients and Methods

Study design

After Institutional Review Board approval, a retrospective case–control study was conducted from January 2009 through December 2014, using our prospectively collected kidney stone database. All immunocompromised patients who underwent PCNL for kidney stones >2.0 cm were included. Only first-time elective percutaneous procedures were included. The immunocompromised group comprised patients who were seropositive for HIV (in AIDS stage, taking medications for disease control, but with CD4 > 500 cells/mm³ and undetectable viral load) or hepatitis C (treated with ribavirin and/or interferon), a disease that causes immune cellular dysfunction, and patients with autoimmune diseases on high doses of corticosteroids (>20 mg/day of prednisone or equivalent) or immunosuppressive drugs (systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome).

Patients with no immunological disorders who underwent PCNL in the same frame of time composed the control group. Two controls were randomly selected for each immunocompromised patient (the selector was blinded to the outcome; patients were selected based on stone complexity). Patients were matched 2:1 based on Guy's stone score,¹⁵ which classifies stone disease according to its complexity and works as an independent predictive factor for complications and stone-free rate.

Groups were compared for their demographic data, PCNL laterality, operative decubitus (prone vs supine), number of accesses, mean operative time, stone-free rate, overall and major complication rates, postoperative urinary tract infection (UTI), drop in hemoglobin level, need for transfusion, tubeless rate, mean time with nephrostomy tube, length of hospital stay, and stone-free rate. Stone-free rate was evaluated by a noncontrast computed tomography (NCCT) scan routinely performed on the first postoperative day following our institutional protocol. Stone-free status was defined as the complete absence of residual fragments. Complications were stratified according to Clavien's classification and classified as major if ≥3.¹⁶

Surgical procedure

Patients with preoperative positive urine culture received appropriate antibiotic therapy for 1 week according to germ susceptibility before surgery, whereas patients with negative urine culture received prophylactic antibiotic (third-generation cephalosporin) during anesthesia induction.

All procedures were performed under general anesthesia. Patients were positioned in prone or supine position based on surgeon's preference. A 6F ureteral catheter was placed through cystoscopy. After retrograde pyelography, the selected calix was punctured under fluoroscopy guidance. A hydrophilic guidewire was inserted and passed into the ureter. If this guidewire did not reach the ureter, a PTFE guidewire was used to replace it. The tract was dilated with fascial dilators and then a 30F Amplatz sheath was placed. Ultrasonic lithotripter was used for stone fragmentation and suction (Swiss LithoClast^® Master; EMD, Dallas, TX). Irrigation was performed with saline at 25°C and pressure of 30 to 40 cmH₂O. An 18F nephrostomy tube was placed at the end of the procedure in cases of bleeding, residual stones, renal pelvis perforation, or multiple accesses. The ureteral catheter was maintained for 12 hours or a Double-J stent (for 1 to 2 weeks) was left in place at surgeon discretion.

Operative time was considered from the beginning of cystoscopy for ureteral catheter placement until the end of nephrostomy tube placement. An NCCT scan and laboratory examinations were done on the first postoperative day in all cases according to our institutional protocol. Patients with residual stones were submitted to a second-look PCNL, flexible ureteroscopy, or SWL based on residual stone burden and location.

Statistical analyses

Categorical variables were compared using chi-square and Fisher exact tests, whereas continuous variables were compared using Student's t test for independent groups. Odds ratio (OR) was calculated when appropriate. All statistical analyses were performed using SPSS version 20.0 (SPSS, Inc., Chicago, IL). Significance level was set at p < 0.05.

Results

Sixty-two patients were included in this study, 21 immunocompromised patients and 42 healthy controls. Six patients had HIV/AIDS, eight had hepatitis C, two had systemic lupus erythematosus, two had rheumatoid arthritis, and three had Sjögren syndrome. There were no significant differences in regard to age, gender, body mass index (BMI), and laterality between groups. Complex cases (Guy's score 3 and 4) accounted for more than half of cases in both groups (Table 1). There were eight (33.3%) immunocompromised patients and eight (19.0%) healthy subjects with positive preoperative urinary culture (p = 0.129). Only one control patient had ESBL (extended-spectrum beta-lactamase) multiresistant bacteria. All these patients were treated with antibiotics for 1 week before surgery.

Table 1.

Demographic Data

	Cases (n = 21)	Controls (n = 42)	p
Age (years), mean ± SD	49.8 ± 8.7	46.3 ± 8.3	0.131
Gender (male), %	38.10	35.70	0.853
BMI (kg/m²), mean ± SD	26.6 ± 6.4	25.5 ± 3.7	0.489
Side (right), %	57.10	64.10	0.597
Guy's score	14.3% Guy's 1	14.3% Guy's 1	1.000
	33.3% Guy's 2	33.3% Guy's 2
	23.8% Guy's 3	23.8% Guy's 3
	28.6% Guy's 4	28.6% Guy's 4

BMI = body mass index; SD = standard deviation.

Regarding intraoperative data, there was no significant difference on patient's operative decubitus (prone position in 61.9% for both groups), number of accesses (71.4% had only one access in each group), and mean operative time (159 vs 156 minutes; p = 0.874). There was also no significant difference in the stone-free rate evaluated by NCCT performed on the first postoperative day between the groups (52.4% vs 69%; p = 0.195). The prevalence of struvite composition on those patients with a stone analysis was 19% vs 14.3% (p = 0.719).

Overall complication rate was higher in the case group (38.1% vs 14.3%; p = 0.032); however, major complication rate, defined by Clavien score ≥3, was not statistically different between cohorts (4.8% vs 2.4%; p = 0.611). There was a tendency for more postoperative UTI in the case group (19% vs 4.8%; p = 0.069). There was no evidence of preoperative anemia of chronic disease, as demonstrated by similar preoperative hemoglobin (13.5 vs 13.9 mg/dL; p = 0.326). Mean drop in hemoglobin level (3.3 vs 2.4 mg/dL; p = 0.037) and blood transfusion rate (23.8% vs 4.8%; p = 0.036) was significantly higher in the case group.

There were no patients with coagulopathy in the cohort. There were three patients in the immunocompromised group with preoperative low platelet count (one patient with 50,000; one patient with 81,000; and one patient with 140,000 platelets) compared with none in the control group (p = 0.033). Patients with <100,000 platelets received plasmapheresis before surgery. Only one of these patients required postoperative transfusion (Table 2). All patients requiring blood transfusion received these due to symptomatic anemia (hypotension). Considering only patients who received blood transfusion, mean postoperative hemoglobin was 8.8 vs 9.8 mg/dL (cases vs controls; p = 0.832).

Table 2.

Perioperative Data

	Cases (n = 21)	Controls (n = 42)	p
Operative decubitus (prone vs supine)	61.9% vs 38.1%	61.9% vs 38.1%	1.000
Number of accesses, %	One = 71.4	One = 71.4	0.407
	Two = 19.0	Two = 26.2
	Three = 9.5	Three = 4.8
Operative time (minutes)	159.0 ± 51.7	156.6 ± 54.0	0.874
Stone-free rate, %	52.40	69.00	0.195
Overall complications, n (%)	8 (38.1)	6 (14.3)	0.032
Major complications (Clavien ≥3), %	4.80	2.40	0.611
Postoperative UTI, %	19.00	4.80	0.069
Preoperative hemoglobin (mg/dL), mean ± SD	13.5 ± 1.4	13.9 ± 1.3	0.326
Postoperative hemoglobin (mg/dL), mean ± SD	10.1 ± 1.9	11.2 ± 2.7	0.092
Hemoglobin drop (mg/dL), mean ± SD	3.3 ± 1.7	2.4 ± 1.3	0.037
Platelet account, mean ± SD ( × 10³)	227.3 ± 99.0	261.3 ± 67.5	0.191
Transfusion, %	23.80	4.80	0.036
Tubeless PCNL, %	15.00	23.80	0.426
Time with nephrostomy tube (days), mean ± SD	1.8 ± 1.4	2.1 ± 1.6	0.559
Hospital stay (days), mean ± SD	4.3 ± 2.9	3.1 ± 1.8	0.177

PCNL = percutaneous nephrolithotomy; UTI = urinary tract infection.

There was one major complication in each group. One patient presented with bleeding, followed by severe coagulopathy in the case group. This patient had hepatitis C and, despite intensive care support, died on the 5th postoperative day. In the control group, one patient had a hemothorax that required drainage and transfusion. Recovery underwent uneventfully. Table 3 summarizes complications and their management. Immunocompromised patients had a 2.7-fold increased risk of complications (OR = 2.7, 95% confidence interval [CI] 1.06, 6.69; p = 0.015) and a 5.8-fold increased risk of blood transfusion (OR = 5.8, 95% CI 1.29, 26.55; p < 0.001). There were no differences in time with nephrostomy tube (1.8 vs 2.1 days; p = 0.599) and length of hospital stay (4.3 vs 3.1 days; p = 0.177) (Table 2).

Table 3.

Perioperative Complications

	Cases (n = 21)		Controls (n = 42)
	Complication	Management	Complication	Management
Clavien 1	0	—	2 Hypotension (4.76%)	Crystalloids
Clavien 2	4 UTI (19.1%)	Antibiotics	2 UTI (4.76%)	Antibiotics
	4 Bleeding (19.1%)^a	Transfusion	1 Bleeding (2.38%)	Transfusion
	1 Adrenal insufficiency (4.75%)	Hydration+corticosteroids
Clavien 3	0	—	1 Hemothorax (2.38%)	Drainage+transfusion
Clavien 4	0	—	0	—
Clavien 5	1 Bleeding+coagulopathy+death (4.75%)	Transfusion	0	—
Overall	8 (38.1%)	—	6 (14.3%)	—

Two patients had UTI and bleeding.

Discussion

In this study, we were able to evaluate and compare the outcomes of PCNL in immunocompromised patients with those in stone patients with normal immune status. Patients with HIV/AIDS, hepatitis C who present persistent infection from a narrow and weak cellular immune response,¹⁷ and patients with autoimmune disorders (systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome) requiring high dose of immunosuppressive drugs for disease control were analyzed together. Our findings suggest that even when prepared for surgery, this specific cohort of patients is at higher risk for complications, such as infections and bleeding.

Moreno-Palacios and colleagues in a retrospective chart review, including 354 PCNL, reported that comorbidities (evaluated by Charlson comorbidity index)¹⁸ are significantly associated with postoperative complications. In this study, patients with Charlson score ≥3 had significantly more overall and major complications, presenting an OR of 6.5 (95% CI 1.5, 27.8) and 23.2 (95% CI 3.5, 15.1), respectively. Moreover, in the same study, there were four deaths (1.1%) due to septic shock (two cases), bleeding of the upper digestive tract (n = 1), and heart failure secondary to pneumonia (n = 1).¹⁹

Resorlu and coworkers and others demonstrated that the risk of bleeding increases with a higher Charlson comorbidity index.^8,20 In a study with 283 patients, those with Charlson comorbidity index ≥2 required transfusion in 23.2% of cases, whereas patients with Charlson index 0 or 1 required transfusion in 7.6% and 11.1% of cases, respectively (p = 0.01). In the same study, higher Charlson comorbidity index was also significantly associated with a lower stone-free rate after PCNL (p = 0.049).⁸ Our immunocompromised patients presented Charlson comorbidity index higher than 3, corroborating that these patients are at higher risk for complications, such as transfusion. A lower threshold of surgeons and anesthesiologists for transfusion might, in part, explain this higher risk. It also may be linked to preoperative conditions, such as hematopoietic disorders and alterations in arterial blood pressure and intracorporeal volume regulation secondary to their baseline condition and medications (i.e., corticosteroids).

With regard to the stone-free rate of our immunocompromised patients, it is comparable with the numbers reported by other authors who analyzed high-risk patients.⁷ We can justify our stone-free rate based on our strict criteria for stone-free status, that is, the complete absence of residual fragments on the NCCT scan performed on the 1st postoperative day. Furthermore, we had a large number of complex cases (>50% of Guy's score 3 and 4).

Patel and colleagues in another retrospective study evaluating the outcomes from PCNL in patients with American Society of Anesthesiologist (ASA) scores of III and IV reported a significantly lower stone-free rate for high-risk patients compared with low-risk patients (61% high-risk vs 92% low-risk; p = 0.28). High-risk patients also had a longer length of hospital stay (4.0 vs 2.7 days; p = 0.046). In this study, the overall complication rate was also higher in high-risk patients, but did not achieve statistical significance (21.2% vs 18.5%; p = 0.41).⁷

Nouralizadeh and coworkers in a similar study comparing the outcome of PCNL in high-risk patients (ASA III and IV; 359 cases) with PCNL in low-risk patients (ASA I and II; 1922 cases) reported a significantly higher transfusion rate in the high-risk group (15.6% vs 11%; p = 0.014), although the overall complication and stone-free rates were similar in both groups. In this same study, medical conditions, which included cardiovascular events, neurogenic complications, gastrointestinal bleeding, renal insufficiency, and thromboembolic events, were significantly higher in the high-risk group (6.4 vs 3.0%; p = 0.0001).⁵ Again, high-risk patients, as our immunocompromised patients, are at higher risk for complications.

When evaluating specific populations, such as obese or diabetic patients, most studies have demonstrated the efficacy and safety of PCNL.^21

–24 Pearle and colleagues studying patients with BMI >30 kg/m² reported 14% of complications, 8.8% of blood transfusion, average hospital stay of 4.9 days, and overall stone-free rate of 88.3%. The authors concluded that PCNL in obese patients yields a complication rate and stone-free rate that are comparable with that achieved in an unselected patient population.²¹

Tomaszewski and coworkers evaluating the outcomes of 234 PCNL stratified by BMI also reported that stone-free and complication rates, hemorrhage, and length of hospital stay are independent of BMI.²⁴ Duvdevani and colleagues analyzing data from 183 patients with diabetes who underwent PCNL revealed that complications (major 2.2%), need for transfusion (0.5%), and stone-free rate (94.5%) were not significantly different from those observed in nondiabetic patients.²² However, when studying patients with spinal cord injury, the outcomes from PCNL are not always similar to those reported in control patients.^25,26

Symons and coworkers reported the outcome of PCNL in 29 patients with spinal injury in whom 39 PCNL procedures were performed.²⁶ In this population, the morbidity and mortality rates of the procedure were significant, with two (6.9%) postoperative deaths. Major complications associated with three of the procedures included seizures, aspiration pneumonia, and pressure ulcer. Nine (31%) patients had minor complications, including fever, transitory hypotension, and nephrostomy site leakage. Nine (31%) patients required intensive unit care after surgery and the average hospital stay for the group was 13.3 days. The stone-free rate was only 62% on the initial procedure.

In our cohort of immunocompromised patients, 19% of patients had postoperative UTI, 23% required transfusion, and one patient died due to severe coagulopathy. Although, major complications occurred in only one patient, minor complications were seen in seven (33%) immunocompromised patients. This rate is similar to those described for spinal cord injury patients. The present study shows the vulnerability of this particular population and makes clear that careful patient selection, adequate preparation, and surgical planning are essential to reduce complications and optimize outcomes.

To the best our knowledge, this is the first study to describe the outcomes of PCNL in patients with any degree of immunological disorder. Our findings may impact on PCNL indication for immunocompromised patients as a key point of preoperative counseling for PCNL is a balanced cost–benefit analysis regarding high stone-free and acceptable complication rates. In low-risk patients, it has been proved to be a right concept. However, for high-risk immunocompromised patients, it is not so clear and more studies are needed to achieve a definitive conclusion. Maybe, a conservative approach in selected severe cases might be a reasonable option.

Our study has limitations that are inherent to its retrospective design. However, a standardized method of data collection and a matched case–control population were performed to minimize such limitations. The relative small number of patients with each disease prevented us from performing a subgroup analysis. Prospective evaluation of this population may require multicenter cooperation as PCNL in immunocompromised patients is a rare procedure.

Conclusion

Immunocompromised patients are at higher risk for postoperative complications after PCNL, such as bleeding and infections. A detailed preoperative evaluation and a careful selection of patients who are candidates for surgical stone removal are mandatory.

Footnotes

Acknowledgments

Partial data of this work were presented in the 33rd World Congress of Endourology and published as abstract in the 33rd World Congress of Endourology & SWL Program Book, Journal of Endourology, 2015.

Author Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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Percutaneous Nephrolithotomy in Immunocompromised Patients: Outcomes from a Matched Case–Control Study