Factors Affecting Kidney Function and Stone Recurrence Rate After ...

Factors Affecting Kidney Function and Stone Recurrence Rate After Percutaneous Nephrolithotomy for Staghorn Calculi: Outcomes of a Long-Term Followup Tolga Akman,* Murat Binbay, Cem Kezer, Emrah Yuruk, Erdem Tekinarslan, Faruk Ozgor, Erhan Sari, Rahmi Aslan, Yalcin Berberoglu and Ahmet Yaser Muslumanoglu From the Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey

Abbreviations and Acronyms BMI ⫽ body mass index CKD ⫽ chronic kidney disease CT ⫽ computerized tomography DM ⫽ diabetes mellitus eGFR ⫽ estimated glomerular filtration rate ESWL ⫽ extracorporeal SWL KUB ⫽ plain x-ray of kidneys, ureters and bladder PCNL ⫽ percutaneous nephrolithotomy SWL ⫽ shock wave lithotripsy UTI ⫽ urinary tract infection Submitted for publication August 14, 2011. * Correspondence: Haseki Teaching and Research Hospital, 34096 Istanbul, Turkey (telephone: ⫹902125294400/1312; FAX: ⫹902125294481; e-mail: [email protected]).

Purpose: There are few studies of the long-term outcome of percutaneous nephrolithotomy for staghorn calculi. We report the long-term outcome of percutaneous nephrolithotomy in patients with staghorn calculi. Material and Methods: A total of 265 study patients (272 renal units) were followed in the long term for greater than 12 months. The estimated glomerular filtration rate was calculated using the 4-variable modification of diet in renal disease equation. Cases were staged for chronic kidney disease by National Kidney Foundation guidelines. The impact of patient and procedure related factors on renal function as well as stone recurrence was analyzed retrospectively. Results: At a mean ⫾ SD followup of 37.3 ⫾ 25.4 months the chronic kidney disease stage classification was maintained in 177 patients (66.8%) while the classification of 34 (12.8%) and 54 (20.4%) had improved and deteriorated, respectively. Multivariate analysis revealed that an immediate postoperative change in the estimated glomerular filtration rate was the only factor predicting a change in renal function in the long term. Stones recurred in 73 of the 234 kidneys (31.2%) that were stone free 3 months after percutaneous nephrolithotomy. Stone size increased in 24 of the 38 kidneys (63.2%) with residual stones after intervention. Recurrent urinary infections during followup and diabetes were associated with stone recurrence and residual stone enlargement. Conclusions: In almost 80% of patients with staghorn stones renal function was improved or maintained after percutaneous nephrolithotomy, as documented during long-term followup. Stones recurred in a third of the patients with staghorn calculi. Key Words: kidney; kidney calculi; nephrostomy, percutaneous; recurrence; kidney function tests

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STAGHORN calculi are defined as large stones that occupy the renal pelvis and include 1 or more calyceal extensions.1 The 10-year mortality rate for untreated patients with staghorn calculi is almost 30%.2 With time these patients are prone to CKD and urosepsis.3 Thus, staghorn stones should

be treated even in asymptomatic patients. PCNL, SWL, open surgery and/or anatropic nephrolithotomy are the treatment alternatives. PCNL is recommended as first line therapy for staghorn stones under the current guidelines.1,4 PCNL has a lower rate

0022-5347/12/1875-1656/0 THE JOURNAL OF UROLOGY® © 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION

Vol. 187, 1656-1661, May 2012 Printed in U.S.A. DOI:10.1016/j.juro.2011.12.061

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FACTORS AFFECTING KIDNEY FUNCTION AND STONE RECURRENCE AFTER NEPHROLITHOTOMY

of morbidity and a higher rate of freedom from stones than open surgery. However, multiple tracts may be required to achieve a complete stone-free rate depending on stone size and complexity. Multiple percutaneous tracts have a higher rate of complications, such as severe bleeding.5,6 Recent studies describe the patient outcome after PCNL for staghorn stones.2,7,8 These studies most often focused on the success rate and complications of the procedure. However, a few groups evaluated long-term PCNL outcomes, focusing especially on the stone recurrence rate and renal function.9 We investigated changes in renal function and stone status (recurrence and regrowth) during long-term followup when PCNL was done for staghorn stones.

MATERIALS AND METHODS A total of 546 consecutive PCNLs for staghorn stones were performed at our institution between September 2002 and May 2011. A total of 265 patients (272 renal units) who were monitored a minimum of 1 year were included in the study. Excretory urogram and/or CT was done in all cases. Patient demographic data were recorded, such as age, gender, hypertension, diabetes, BMI, stone burden, history of open renal surgery and SWL. Preoperative laboratory tests for all patients included serum creatinine, hemoglobin, platelet count and a coagulation screening test. In all patients sterile urine culture was done or they were treated preoperatively according to antibiotic sensitivity tests. Stones were classified as complete staghorn— occupying the renal pelvis and the whole calyceal system, or 80% or greater of the renal collecting system, or partial staghorn— occupying the renal pelvis, or at least 2 or more calyces.8 Stone size was assessed by calculating surface area according to European Association of Urology guidelines.4 Briefly, PCNL was done under C-arm fluoroscopic guidance using an 18 gauge needle for access with the patient prone, as previously described in detail.10 The access tract was dilated using a high pressure NephroMax™ balloon dilator. The stone burden was fragmented using a Vibrolith® pneumatic or a Swiss Lithoclast® Master ultrasonic lithotripter. Additional tracts were created at each session as needed. Flexible nephroscopy was done at the end of the procedure when we suspected residual stones. A 14Fr nephrostomy tube was placed is the renal pelvis or involved calyx at the termination of the procedure in most cases. Quinolone was administered prophylactically. KUB was done on postoperative day 1 after PCNL. Nephrostomy tubes were removed on the second postoperative day if antegrade nephrostogram revealed ureteral drainage into the bladder. A Double-J® catheter was placed when urine drainage from the tract persisted more than 24 hours after nephrostomy tube removal. Repeat PCNL, ureteroscopy and ESWL were considered auxiliary treatment alternatives, as appropriate. On postoperative day 1 or 2 routine KUB and retrograde nephrostogram were done on all patients to assess for residual stone fragments, urinary leakage and infra-

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renal obstruction. If a radiological study revealed a patent tract and residual stone clearance, the nephrostomy tube was removed. If residual calculi 5 mm or greater were present, SWL or repeat PCNL was considered. All patients were evaluated by excretory urogram and/or helical CT 3 months postoperatively. Success was defined as complete stone clearance. Subsequently a followup schedule with urinalysis, serum creatinine, KUB and urinary ultrasound was used every 6 months in patients who were stone free and every 3 months in those with residual stones. When stones appeared in stone-free patients or the size of residual stones increased, patients were reevaluated by CT to guide the appropriate treatment modality. For each patient eGFR was calculated using the 4-variable modification of diet in renal disease equation.11 CKD was classified by the National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF K/DOQI) classification system.12 CKD stages 1 to 5 were classified as a glomerular filtration rate that was 1—normal, or 2—mildly, 3—moderately or 4 —severely decreased, or 5—a requirement for dialysis or kidney transplantation (greater than 90, 60 to 89, 30 to 59, 15 to 29 and less than 15 ml/minute/1.73 m2, respectively). CKD stages in the preoperative period were compared with measurements at the last followup visit at greater than 12 months. According to changes in CKD stage cases were divided into 2 groups based on renal status at last followup visit, including group 1—improved or maintained and group 2— deteriorated. The effects of patient and procedure related variables on kidney function and stone recurrence or residual stone regrowth after PCNL were evaluated retrospectively. Statistical analysis was done with SPSS® 16 for Windows®. Continuous variables were compared with the Student t or Mann-Whitney U test, as appropriate. Proportions of categorical variables were analyzed for statistical significance using the chi-square or Fisher exact test. Multivariate analysis was done to further investigate any parameter found to be significant on univariate analysis with p ⬍0.05 considered statistically significant.

RESULTS The study included 265 patients (272 renal units) treated with PCNL. Mean ⫾ SD age was 44.4 ⫾ 15.3 years (range 10 to 81) and mean BMI was 26.8 ⫾ 4.9 kg/m2 (range 15.1 to 44.9). Mean stone size was 1,191 ⫾ 732 mm2 (range 300 to 4,500). A total of 170 kidneys (62.5%) were managed by a single access while multitract PCNL was required for 102 (37.5%). A total of 77 complications were noted in 64 patients (24.2%) according to the Clavien classification. Bleeding necessitating transfusion was the most common complication. Two of the 47 patients who required blood transfusion underwent angioembolization for a pseudoaneurysm and/or an arteriovenous fistula that caused extensive bleeding. The remaining patients were treated conservatively (table 1).

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Table 1. Complications according to Clavien classification in patients with PCNL Grade* 1: Fever Transiently increased serum creatinine 2: Blood transfusion Less than 12-hr urine leakage Infection requiring antibiotics beyond prophylactics Wound infection Urinary tract infection Pneumonia 3a: Double-J stent for greater than 24-hr urine leakage Double-J stent for ureteropelvic ⫹ pelvic injury Urinoma Pneumothorax Retention ⫹ colic due to blood clots 3b: Ureter-bladder stone Calyceal neck stricture Ureteropelvic junction obstruction Arteriovenous fistula Perirenal hematoma needing intervention Perinephritic abscess Periop bleeding requiring stopping operation 4b: Urosepsis

No. Pts 11 9 2 52 45 3 2 0 0 0 7 4 2 0 1 0 6 2 0 0 2 0 1 1

Stone-free status was achieved in 76.5% of kidneys after 1 PCNL. As an auxiliary treatment alternative, 29 patients underwent SWL, 11 received required repeat PCNL and 3 were treated with ureterorenoscopy. We followed 21 renal units with asymptomatic borderline residual stones. A total of 234 renal units (86.0%) were stone free at postoperative month 3. While stone recurred in 73 kidneys (31.2%) at a mean of 36.0 ⫾ 24.0 months (range 12 to 101), 161 remained stone free during long-term followup. Of the 38 kidneys with residual stones the size of the stones increased in 24 (63.2%) and remained unchanged in 9 (23.7%) while the stone passed spontaneously in 5 (13.1%). DM and recurrent UTIs were factors that affected stone recurrence and residual stones growth on stepwise multivariate analysis (OR 2.5, 95% CI 1.1–5.0, p ⫽ 0.02 and OR 2.1, 95% CI 1.03–3.6, p ⫽ 0.04, respectively). As treatment options for stone recurrence or residual stone growth SWL, PNL and flexible ureterorenoscopy were done in 41, 29 and 16 patients, respectively, while nephrectomy due to poor renal function was done in 1.

3

* There were no grade 4a (neighboring organ injury, myocardial infarction, nephrectomy or lung failure) or 5 complications.

Stone analysis done in 82 patients (30.1%) revealed a composition of calcium oxalate in 44, magnesium ammonium phosphate in 13, uric acid in 13, cystine in 3, mixed calcium oxalate and phosphate in 5, mixed uric acid and calcium phosphate in 2, and mixed magnesium ammonium phosphate and calcium oxalate in 2. At a mean followup of 37.3 ⫾ 25.4 months (range 12 to 111) CKD stage improved in 34 patients (12.8%), stabilized in 177 (66.8%) and worsened in 54 (20.4%) (fig. 1). Figure 2 shows the creatinine change in each case. Three patients progressed to end stage renal disease requiring maintenance dialysis during followup. Table 2 shows a comparative analysis of factors related to patients, stones and procedures. On univariate analysis diabetes and an initial alteration in preoperative eGFR to that immediately postoperatively were significant factors for kidney function in the long term. However, multivariate binary logistic regression analysis revealed that an initial change in preoperative eGFR to that immediately postoperatively was the unique important predictive factor indicating renal function (OR 5.3, 95% CI 2.7–10.5, p ⫽ 0.0001). The blood transfusion requirement rate was higher in group 1 but statistical significance was not detected between the groups (31.1% vs 17.8, p ⫽ 0.07).

DISCUSSION Various groups have evaluated the short-term outcome of PCNL for staghorn stones. Most of them focused on stone-free and complication rates. As a

Long term CKD stage

1

2

3

4

5

Preop CKD stage 1 (n= 105)

79

22

4

0

0

2 (n= 98)

20

62

14

2

0

3 (n= 51)

2

10

30

9

0

4 (n= 10)

0

0

2

5

3

5 (n= 1)

0

0

0

0

1

: Improved : Stable : Worsened

Figure 1. CKD stage preoperatively and during long-term followup.


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and 12.8%. Changes in eGFR in the early postoperative period were the most important factor associated with renal function in the long term. When the immediate postoperative eGFR improved or was maintained compared with the preoperative value, eGFR remained the same in the long term in approximately 87% of the cases (table 2).

Table 2. Factors affecting kidney function during long-term followup after PCNL

Figure 2. Creatinine change in each patient

consequence of these studies, PCNL is recommended as a primary treatment alternative for removing staghorn calculi.1 However, post-PCNL alterations in renal function and recurrent stone disease are the factors that matter in the long term. During the natural course of staghorn stones various complications have been reported, such as worsening renal function and end-stage kidney failure at a rate of 77%.13 Only a few groups have investigated the longterm outcome in patients after PCNL, especially for stone recurrence and renal function.9,14 Teichman et al analyzed 177 staghorn calculi to determine risk factors for renal dysfunction and renal specific causes of death.14 They treated patients using PCNL (65), ESWL (21) and PCNL-ESWL as a combination therapy, and reported deteriorating renal function in 28% during a mean followup of 7.7 years. In a recent retrospective study El-Nahas et al presented the long-term outcome of 122 patients with staghorn calculi managed by PCNL.9 They evaluated renal function in 70 patients who underwent preoperative and postoperative radio isotope scanning, and noted that in 91.5% PCNL did not adversely affect renal function.9 In our series at a mean followup of 37.3 ⫾ 25.4 months renal function worsened in 20.4% of patients, remained the same in 66.8% and improved

Mean ⫾ SD creatinine (mg/dl): Baseline Early postop Last followup Mean ⫾ SD age Mean ⫾ SD BMI (kg/m2) Mean ⫾ SD stone size (mm2) Mean ⫾ SD operative time (mins) % Gender (No.): M F % Open surgery history (No.): Yes No % SWL history (No.): Yes No % DM (No.):* Yes No % Hypertension (No.): Yes No % Preop CKD stage (No.): 1 2 3 4 5 % Blood transfusion due to bleeding (No.): Yes No % Supracostal (No.) % Subcostal (No.) % Access (No.): 1 Multiple % Early postop eGFR change (No.):† Stable or improved Decreased % 3-Mo status (No.): Stone free Residual calculi % Recurrent UTI (No.): Yes No * OR 2.44 (95% CI 1.1–5.5). † OR 5.6 (95% CI 2.9–11.0).

Group 1

Group 2

Univariate p Value

1.08 ⫾ 0.51 1.10 ⫾ 0.52 1.04 ⫾ 0.42 43.6 ⫾ 15.6 26.4 ⫾ 4.6 12.0 ⫾ 7.6 80.2 ⫾ 35.2

1.11 ⫾ 0.67 1.31 ⫾ 1.02 1.41 ⫾ 0.64 46.4 ⫾ 13.5 27.8 ⫾ 5.4 11.1 ⫾ 5.6 75.7 ⫾ 34.3

0.20 0.24 ⬍0.0001 0.23 0.06 0.73 0.20

62.6 (132) 37.4 (79)

53.7 (29) 46.3 (25)

27.0 (57) 73.0 (154)

29.6 (16) 70.4 (38)

23.2 (49) 76.4 (162)

24.1 (13) 75.9 (41)

9.5 (20) 90.5 (191)

20.4 (11) 79.6 (43)

31.8 (65) 68.2 (146)

40.7 (22) 59.3 (32)

37.4 (79) 38.9 (82) 19.9 (42) 3.3 (7) 0.5 (1)

48.1 (26) 29.6 (16) 16.7 (9) 5.6 (3) 0

0.23

0.7

0.9

0.02

0.21

0.51

0.07 14.7 (31) 85.3 (180) 18.0 (38) 82.0 (173)

25.9 (14) 74.1 (40) 13.0 (7) 87.0 (47)

61.6 (130) 38.4 (81)

64.8 (35) 35.2 (19)

0.38 0.66

⬍0.0001 86.7 (183) 13.3 (28)

53.7 (29) 46.3 (25)

84.8 (179) 15.2 (32)

90.7 (49) 9.3 (5)

19.4 (41) 80.6 (170)

18.5 (10) 81.5 (44)

0.26

0.96

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Canes et al retrospectively evaluated the effect of PCNL on the kidney function of 81 patients with a solitary kidney.15 At 1-year followup the CKD classification was stable, improved or worse in 55.9%, 37.3% and 6.8% of patients, respectively. On multivariate analysis female gender and an initial increase in eGFR postoperatively predicted improved renal function throughout the first year of followup evaluation.15 In our study DM was associated with an increased risk of impaired renal function on univariate analysis but it did not affect kidney function on multivariate regression analysis. Krambeck et al retrospectively reviewed the longterm outcome of patients treated with PCNL or SWL.16 At 19 years of followup the stone recurrence rate was approximately 37% for the group with PCNL and 53.5% for the group with ESWL. Carr et al evaluated the stone-free state of 62 consecutive patients treated with PCNL at month 3 postoperatively using KUB and CT.17 The post-PCNL recurrence rate at 1 and 2 years was 4.2% and 22.6%, respectively. El-Nahas et al analyzed the long-term outcome of 126 patients with staghorn stones treated with PCNL and noted recurrent stones in 25% who were stone-free.9 Of patients with residual stones 65% experienced a rate of regrowth that necessitated repeat intervention.9 In our series stones recurred in 31.2% of patients who were stone-free after PCNL. Of those with residual stones postoperatively 63.2% showed an increase in stone size that required intervention. In our study stone recurrence did not correlate with patient age, BMI, stone size or hypertension. However, during long-term followup DM increased the stone recurrence rate 2.5-fold. Of patients with DM 54.8% experienced stone recurrence or growth of residual stones. In nonDM cases the corresponding rate was 32.4% (table 3). Insulin resistance may be the underlying cause since it is linked to decreased renal ammoniagenesis and decreased urinary ammonium excretion relative to net acid excretion.18 This results in more acidic urine pH, which favors uric acid and mixed urate-calcium oxalate stone formation. Clinical studies confirm the correlation between DM and urolithiasis. Taylor et al evaluated the relationship between DM and the prevalence of kidney stones.19 They found a higher prevalence of previous kidney stones and a higher incidence of stone episodes in participants with vs without DM. Meydan et al compared the prevalence of kidney stone disease in 286 patients with DM and 111 age matched controls.20 The prevalence of urinary stone disease and the recurrence rate were higher in patients with DM than in controls. A significant correlation exists between UTIs and urolithiasis. Stones are the consequence of

Table 3. Long-term outcome of factors affecting stone recurrence or residual regrowth after PCNL in patients with staghorn calculi Recurrence or Regrowth

Mean ⫾ SD age Mean ⫾ SD BMI (kg/m2) Mean ⫾ SD stone size (mm2) % Gender (No.): M F % Open surgery history (No.): Yes No % SWL history (No.): Yes No % DM (No.):* Yes No % Hypertension (No.): Yes No % Bilat PCNL (No.): Yes No % Access (No.): 1 Multiple % Recurrent UTI during followup (No.): Yes No

No

Yes

43.4 ⫾ 15.5 26.7 ⫾ 5.0 1,225 ⫾ 750

46.3 ⫾ 14.8 26.9 ⫾ 4.7 1,132 ⫾ 698

61.6 (106) 38.4 (66)

59.1 (55) 40.9 (38)

24.6 (43) 75.4 (132)

34.0 (33) 66.0 (64)

25.1 (44) 74.9 (131)

19.6 (19) 80.4 (78)

8.1 (14) 91.9 (158)

18.3 (17) 81.7 (76)

32.0 (55) 68.0 (117)

34.4 (32) 65.6 (61)

1.7 (3) 98.3 (172)

4.1 (4) 95.9 (93)

60.6 (106) 39.4 (69)

66.0 (64) 34.0 (33)

Univariate p Value 0.12 0.83 0.31 0.70

0.09

0.30

0.01

0.68

0.23

0.38

0.02 15.1 (26) 84.9 (146)

26.9 (25) 73.1 (68)

* OR 2.5 (95% CI 1.2–5.4). † OR 2.1 (95% CI 1.1–3.8).

UTIs in approximately 10% to 15% of patients with stone disease.21 In our study recurrent UTIs increased the risk of stone regrowth and recurrence more than twofold. Urolithiasis and recurrent UTIs may induce each other, leading to a vicious cycle. This study has limitations due to its retrospective design. There may have been some bias in treatment strategies, and changes in differential renal function between preoperative and postoperative kidney function were evaluated using eGFR rather than renal scintigraphy. The other limitation is the lack of metabolic evaluation and stone analysis in most patients. Recent studies highlighted the impact of aggressive medical treatment together with metabolic evaluation on post-PCNL stone recurrence and residual stone regrowth.22

CONCLUSIONS In almost 80% of patients with staghorn stones renal function was improved or maintained. The most important predictive factor for renal function in the long term was the change in eGFR in the early


postoperative period. Stones recurred in approximately a third of patients with staghorn calculi. More than 60% of patients with residual stones after

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PCNL required further treatment. DM and recurrent UTIs after PCNL placed patients at higher risk for stone recurrence.

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6. El-Nahas AR, Shokeir AA, El-Assmy AM et al: Post-percutaneous nephrolithotomy extensive hemorrhage: a study of risk factors. J Urol 2007; 177: 576.

12. Levey AS, Coresh J, Balk E et al: National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. National Kidney Foundation. Ann Intern Med 2003; 139: 137.

7. Desai M, De Lisa A, Turna B et al: The clinical research office of the endourological society percutaneous nephrolithotomy global study: staghorn versus nonstaghorn stones. J Endourol 2011; 25: 1263.

13. Vargas AD, Bragin SD and Mendez R: Staghorn calculi: its clinical presentation, complications and management. J Urol 1982; 127: 860.

8. Soucy F, Ko R, Duvdevani M et al: Percutaneous nephrolithotomy for staghorn calculi: a single

14. Teichman JM, Long RD and Hulbert JC: Longterm renal fate and prognosis after staghorn calculus management. J Urol 1995; 153: 1403.

15. Canes D, Hegarty NJ, Kamoi K et al: Functional outcomes following percutaneous surgery in the solitary kidney. J Urol 2009; 181: 154. 16. Krambeck AE, LeRoy AJ, Patterson DE et al: Long-term outcomes of percutaneous nephrolithotomy compared to shock wave lithotripsy and conservative management. J Urol 2008; 179: 2233. 17. Carr LK, D’A Honey J, Jewett MA et al: New stone formation: a comparison of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy. J Urol 1996; 155: 1565. 18. Abate N, Chandalia M, Cabo-Chan AV Jr et al: The metabolic syndrome and uric acid nephrolithiasis: novel features of renal manifestation of insulin resistance. Kidney Int 2004; 65: 386. 19. Taylor EN, Stampfer MJ, Curhan GC: Diabetes mellitus and the risk of nephrolithiasis. Kidney Int 2005; 68: 1230. 20. Meydan N, Barutca S, Caliskan S et al: Urinary stone disease in diabetes mellitus. Scand J Urol Nephrol 2003; 37: 64. 21. Thomas B and Tolley D: Concurrent urinary tract infection and stone disease: pathogenesis, diagnosis and management. Nat Clin Pract Urol 2008; 5: 668. 22. Zilberman DE and Preminger GM: Long-term results of percutaneous nephrolithotomy: does prophylactic medical stone management make a difference? J Endourol. 2009; 23: 1773.