The impact of metabolic syndrome on long-term outcomes of percutaneous nephrolithotomy (PCNL)

Authors


Tolga Akman, Department of Urology, Bezmialem Vakif University, Faculty of Medicine, 34093 Istanbul, Turkey. e-mail: takman36@gmail.com

Abstract

Study Type – Prognosis (cohort)

Level of Evidence 2b

What's known on the subject? and What does the study add?

The presence of metabolic syndrome is associated with development of kidney stones and an increase in the stone-recurrence rate. However, studies reporting long-term results of percutaneous nephrolithotomy (PCNL) in metabolic syndrome are lacking.

The present study showed that metabolic syndrome was associated with worsening renal function at long-term follow-up and the stone-recurrence rate recurrence after PCNL in patients with metabolic syndrome was 3.2-fold higher compared with the control group.

OBJECTIVE

  • • To investigate the impact of metabolic syndrome on long-term kidney function and stone recurrence rates after percutaneous nephrolithotomy (PCNL).

PATIENTS AND METHODS

  • • In all, 73 patients with metabolic syndrome who underwent stone analysis and had a minimum follow-up of 12 months after PCNL were reviewed.
  • • In addition, 73 patients without any metabolic syndrome components who had undergone PCNL and were followed-up for at least 12 months were included in the study as the control group.
  • • These control group patients were selected from 226 patients who were matched with the patients with metabolic syndrome using a 1 : 1 ratio. The matching parameters were age, gender and stone size.

RESULTS

  • • Stone analyses showed that calcium oxalate monohydrate (52.0%) and uric acid (21.9%) were most common among patients with metabolic syndrome, whereas calcium oxalate monohydrate (76.7%) was the most common stone type in the control group.
  • • Stone recurrences occurred with a mean (sd, range) of 36.1 (21.3, 12–109) months follow-up in 26 patients (41.9%) and 12 patients (18.9%) in the metabolic syndrome and control groups, respectively (P= 0.003).
  • • While estimated glomerular filtration rate was decreased from 87.8 to 66.6 mL/min/1.73 m2 in the metabolic syndrome group, it changed from 96.4 to 91.2 mL/min/1.73 m2 in control group at long-term follow-up.

CONCLUSIONS

  • • The most frequent stone type was calcium oxalate monohydrate in patients with or without metabolic syndrome.
  • • In patients with metabolic syndrome who underwent PCNL, the stone recurrence rate was >40%.
  • • Metabolic syndrome is associated with worsening renal function at long-term follow-up.
Abbreviations
DM

diabetes mellitus

eGFR

estimated GFR

BMI

body mass index

HDL

high-density lipoprotein

KUB

plain abdominal radiograph of the kidneys, ureters and bladder

PCNL

percutaneous nephrolithotomy

INTRODUCTION

Metabolic syndrome is a chronic disease with components of obesity, insulin resistance, hypertension, impaired glucose tolerance, hyperinsulinaemia and dyslipidaemia; this disease is also associated with an increased risk for cardiovascular disease, type 2 diabetes mellitus (DM) and urolithiasis [1]. The prevalence of metabolic syndrome is 24% in men and 23.4% in women in the USA [2]. There is also strong evidence that obesity, weight gain, and DM are risk factors for the development of kidney stones and increase the stone recurrence rate [3]. A large series reported that the presence of metabolic syndrome was associated with a ≈two-fold increase in the odds of self-reported kidney stone disease [4].

Percutaneous nephrolithotomy (PCNL) plays an important role in the treatment of kidney stones, and it decreases mortality rates, time lost from work, and the length of hospitalisation. However, in patients with metabolic syndrome, only a few studies have investigated the efficacy and safety of PCNL treatment [5]. Furthermore, studies reporting long-term results of PCNL in metabolic syndrome are lacking. Therefore, in the present study, the impact of metabolic syndrome on long-term kidney function and stone recurrence rates after the PCNL procedure was investigated.

PATIENTS AND METHODS

Preoperatively, all patients were evaluated with IVU and/or CT. The patients' demographic parameters, including age, sex, body mass index (BMI), presence of DM and hypertension, history of ipsilateral kidney surgery as well as the size, number and location of the stones were recorded. Preoperative laboratory tests included serum creatinine, haemoglobin measurements, platelet counts, coagulation screen tests, total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, and urine cultures. All had either sterile urine culture or managed according to the antibiotic sensitivity tests preoperatively.

Of 2121 patients who underwent PCNL, 208 (9.8%) with metabolic syndrome were identified between 2002 and December 2011. There were 73 of these 208 patients who had both stone analysis and a minimum follow-up of 12 months, and these 73 patients comprised the study group with metabolic syndrome.

Metabolic syndrome was defined as the presence of at least three of the following risk factors: central obesity (BMI >30 kg/m2); elevated serum triglyceride levels (≥150 mg/dL), or drug treatment for this abnormality; reduced HDL cholesterol (<40 mg/dL in men, <50 mg/dL in women) or on drug treatment to reduce HDL cholesterol; elevated blood pressure (systolic ≥130 mmHg, or diastolic ≥85 mm Hg) or antihypertensive drug treatment for previously diagnosed hypertension; or elevated fasting glucose (≥100 mg/dL), or drug treatment for elevated glucose [6].

During the same period, 226 patients without any metabolic syndrome components who had undergone PCNL and were followed-up for at least 12 months were identified. From this cohort, we selected 73 patients to serve as the control group in this study. These 73 patients were retrospectively matched at a 1:1 ratio to index metabolic syndrome-control group with respect to age, gender and stone size.

PCNL TECHNIQUE AND FOLLOW UP

Briefly, the procedures were performed under C-arm fluoroscopy using an 18-G needle with the patient prone as previously described in detail [7]. The tract was dilated with a high-pressure balloon dilator (NephromaxTM Microvasive Boston Scientific Corporation, Natick, MA, USA). Fragmentation of the stone burden was accomplished using a pneumatic (Vibrolith®, Elmed, Ankara, Turkey) or ultrasonic lithotripter (Swiss Lithoclast®, EMS Electro Medical System, Nyon, Switzerland). A 14-F nephrostomy tube was placed inside the renal pelvis or into the involved calyx upon termination of the intervention in most cases. The operative duration was calculated as the time from the puncture for an access tract to the final placement of a nephrostomy tube. A plain abdominal radiogram of the kidneys, ureters and bladder (KUB) was taken on the first postoperative day. In cases considered to be stone-free and in those with clinically insignificant residual fragments, the nephrostomy tube was removed on the second postoperative day after an antegrade nephrostogram that showed patency of the entire ureteric drainage system. Repeat PCNL, ureteroscopy and shockwave lithotripsy were considered as accessory treatment alternatives when indicated.

Patients were evaluated by urine analysis, serum creatinine, KUB and spiral CT, or IVU at 3 months postoperatively. For each group, 73 patients who were regularly monitored for a minimum of 12 months were included in the present study. For these patients, a follow-up schedule with urine analysis, serum creatinine, KUB and urinary ultrasonography were performed every 6 months in patients who were stone-free and in those who had residual stones every 3 months. When stones appeared in stone-free patients or when an increase in the size of residual stones was detected, patients were re-evaluated using CT to guide the appropriate treatment method.

The estimated GFR (eGFR) for each patient was retrospectively calculated using a four-variable Modification of Diet in Renal Disease [8].

Normality tests (Kolmogorov–Smirnov test, P > 0.05) were performed to evaluate the distribution of numeric variables. Because there was a normal distribution of numeric variables, statistical analysis was performed using parametric Student's t-tests. However, the Mann–Whitney U-test and Friedman test were used to evaluate numerical variables with a skewed distribution including fluoroscopy screening time, operative duration, duration of nephrostomy, length of hospitalisation and changes in eGFR. Proportions of categorical variables were analysed using the chi-squared or Fisher's exact test because the minimum expended count was <5; comparisons of categorical variables were performed with Fisher's exact test.

RESULTS

In all, 36 men and 37 women in the metabolic syndrome group and 40 men and 33 women in the control group were included in the study (P= 0.51). The mean (sd) age was 50.8 (9.1) years in the metabolic syndrome group and 49.1 (9.7) years in the control group (P= 0.27). In the metabolic syndrome and control groups, the mean (sd) stone size was 782 (537) and 760 (580) mm2, respectively (P= 0.8). In 19 patients (26.0%) in the metabolic syndrome group and 21 patients (28.8%) in the control group, partial or complete staghorn stones were detected (P= 0.8).

Operative parameters are summarised in Table 1. The mean duration of nephroscopy, fluoroscopy screening time and operative duration did not differ between the groups. Multiple accesses were required in 23.3% of patients with metabolic syndrome and in 19.2% of the control group (P= 0.5). The most common complication was bleeding requiring blood transfusion, and the rate of this complication was higher in the metabolic syndrome group but was not statistically significant (P= 0.2). A JJ stent was inserted in two patients (2.7%) in the metabolic syndrome group and in three patients (4.1%) in the control group due to pelvi-calyceal system perforation or prolonged urine leakage from the nephrostomy tube tract.

Table 1. Comparison of operative variables of both groups
VariablesMetabolic syndrome groupControl group P
Mean (sd):   
 Operative duration, min68.7 (20.4)71.3 (26.1)0.6
 Fluoroscopy screening time, min7.8 (4.0)8.3 (3.9)0.4
 Duration of nephrostomy tube, days2.6 (0.9)2.9 (1.7)0.8
 Length of hospitalisation, days2.7 (0.9)3.1 (2.2)0.9

The stone analysis showed that calcium oxalate monohydrate (52.0%), uric acid (21.9%) and mixed calcium oxalate monohydrate and uric acid stones (16.4%) were most common among patients with metabolic syndrome, while calcium oxalate monohydrate (76.7%) was the most common stone type in the control group (Table 2) and uric acid stones were detected in only 4.1% of the control group.

Table 2. Comparison of stone type in the metabolic syndrome and control groups
Stone typeMetabolic syndrome group, n (%)Control group, n (%) P
Calcium oxalate monohydrate38 (51.1)56 (76.7)<0.001
Uric acid16 (21.9)3 (4.1)
Mixed calcium oxalate monohydrate and uric acid12 (16.4)3 (4.1)
Mixed calcium oxalate monohydrate and dehydrate6 (8.2)5 (6.8)
Cystine1 (1.4)4 (5.5)
Mixed magnesium ammonium phosphate and calcium oxalate stones.02 (2.7)

At 3 months after PCNL, the stone-free rates were 84.9% (62 patients) and 90.4% (66) in the metabolic syndrome and control groups, respectively (P= 0.3). Stone-recurrence rates occurred during a mean (sd, range) of 36.1 (21.3, 12–109) months of follow-up and were 41.9% (26 patients) and 18.9% (12) in patients in the metabolic syndrome and the control groups, respectively (P= 0.003). In the metabolic syndrome group, of the 11 patients with residual stones 3 months postoperatively, the stone passed spontaneously in one patient, the stone size did not change in six patients, and the residual stones increased in size in four patients. However, in the control group, spontaneous stone passage occurred in two patients, the residual stones increased in size in two patients, and the dimensions of the stones remained the same in three patients. When the stones were evaluated based on subgroups, the recurrence rates of calcium oxalate stones in patients with or without metabolic syndrome were 43.3% (13/30) and 19.2% (10/52), respectively (P= 0.03). In patients with metabolic syndrome, the recurrence rates for uric acid and pure calcium oxalate monohydrate stones were six of 14 and six of 12, respectively. (Table 3)

Table 3. Stone-recurrence rates in both groups according to stone types
Stone typesMetabolic syndrome groupControl group P
Stone-free rates at 3 months after PCNL, nRecurrence rates, n/N (%) or n/NStone-free rates at 3 months after PCNL, nRecurrence rates, n/N (%)
Calcium oxalate monohydrate3013/30 (43.3)5210/52 (19.2)0.019
Uric acid146/14300.51
Mixed calcium oxalate monohydrate and uric acid126/1231/31.0
Mixed calcium oxalate monohydrate and dehydrate5030NA
Cystine11/131/31.0
Mixed magnesium ammonium phosphate and calcium oxalate stones.0020NA

The mean (sd) eGFR values of the metabolic syndrome group during the preoperative period, at discharge and at long-term follow-up (>12 months) were 87.8 (29.3) mL/min/1.73 m2, 81.3 (29.4) mL/min/1.73 m2 and 66.6 (35.6) mL/min/1.73 m2, respectively (Fig. 1). In the control group, the preoperative, early postoperative and long-term follow-up mean (sd) eGFR values were 96.4 (24.2) mL/min/1.73 m2, 96.3 (29.3) mL/min/1.73 m2 and 91.2 (22.1) mL/min/1.73 m2, respectively.

Figure 1.

Comparative evaluation of the effects of metabolic syndrome on kidney function after PCNL.

DISCUSSION

When compared with other treatment alternatives, PCNL has higher stone-free rates and is a cost-effective procedure. Therefore, PCNL is recommended as the first treatment option for complex renal stones and for stones of >2 cm [9,10]. Although recent series reported increasingly lower incidences, major complications related to PCNL, e.g. serious bleeding, adjacent organ injury, urosepsis, and hydrothorax, may always occur because of the inherent nature of the procedure [11]. In a recent multicentre study, major bleeding (7.8%), renal pelvis perforation (3.4%), and hydrothorax (1.8%) were reported in patients undergoing PCNL [12]. In recent publications, factors related to PCNL complications have been reported to be prolonged operative durations, stone size, complexity, multi-tract procedures and the presence of DM, which is one of components of the metabolic syndrome [13–16].

To the best of our knowledge, only a few studies to date have investigated the effects of metabolic syndrome on PCNL outcomes and morbidity. Tefekli et al.[5] reported a 9.5% incidence rate for patients with metabolic syndrome undergoing PCNL; they also reported an overall success rate of 96.3% for PCNL and a complication rate of 11.4%. They detected that the risk of major complications was 2.5-times higher in patients with hypertension, 2.7-times higher in patients with DM, and 2.45-times higher in patients with metabolic syndrome [5]. In their study, the need for auxiliary treatments after PCNL was more common in patients with DM and the metabolic syndrome, but not in those with a BMI of >30 kg/m2 and serum lipid abnormalities. In our present study, the requirement for blood transfusion was higher in patients with metabolic syndrome, but this difference was not statistically significant. Components of metabolic syndrome, e.g. DM and hypertension, induce the development of microangiopathies that are relatively prone to bleeding; eventually, all vascular structures are affected.

The present study has shown that primarily pure calcium oxalate monohydrate and uric acid stones are found in patients with metabolic syndrome. The incidence of uric acid stones was 4.1% in the control group and 21.9% in the patients with metabolic syndrome. In the literature, higher prevalence rates were reported for uric acid stones in diabetes. Daudon et al.[17] retrospectively analysed stone components of 2464 calculi and found that the proportion of uric acid stones was 35.7% in patients with type 2 DM and 11.3% in patients without DM. Their stepwise regression analysis showed that diabetes was independently the strongest risk factor for uric acid stones [17]. In another study, Pak et al.[18] showed that uric acid stones occurred more frequently in patients with type 2 DM than in those without DM (33.9% vs 6.2%). Insulin stimulates renal tubular Na+/H+ exchanger 3 (NHE3) activity and ammoniagenesis in renal proximal tubular segments. The development of insulin resistance might decrease urinary excretion of ammonium and renal ammoniagenesis with ensuing lower urinary pH. Persistently lower urinary pH can induce the formation of uric acid and mixed urate-calcium oxalate stones [19]. In the present study, in 16.4% of patients with metabolic syndrome, mixed uric acid and calcium oxalate stones were detected. This incidence, although not statistically significant, is higher than that of the control group. Lack of difference may be related to the few cases. Calcium oxalate stones may also develop by heterogeneous nucleation of calcium oxalate by uric acid.

Various studies have reported stone recurrences in the first, second, third, and fifth years after PCNL of 0–17%, 22.6–27%, and 31.4–36.8%, respectively [20]. UTIs, renal failure, anatomical abnormalities, positive family history, nutritional factors, nutritional deficiencies, lifestyle factors, stone episodes, smoking, and stone complexity constitute risk factors for stone recurrence [21]. On the other hand, the association between the components of metabolic syndrome and urinary system stone recurrence has been investigated in various studies [19,21]. In one of the studies in which the correlation between urinary stone disease and DM was investigated, the prevalence of urinary tract disease and stone recurrence rates in diabetics was higher than those of the control group [22]. Obesity is one of two important components of metabolic syndrome. Lee et al.[19] investigated the effect of obesity on stone recurrence. At a median follow-up of 54.0 months, their study showed that obesity was associated with serum and urine metabolic alterations as well as increased recurrent stone formation [19]. Dietary indiscretion and coexisting type 2 DM are thought to be responsible for the increased risk of stone recurrence in obese patients [21]. The present study is the first to analyse the effects of metabolic syndrome on the long-term outcomes of PCNL. In the present study, stone recurrences after PCNL occurred in 41.9% of patients in the metabolic syndrome group and in 18.9% of the control subjects. Metabolic syndrome significantly increased stone recurrence rates when compared with age-, gender-, and stone size-matched controls. In patients with metabolic syndrome, ≈43% (13 of 30) of calcium oxalate monohydrate and six of 14 uric acid stones recurred. However, in patients without metabolic syndrome, one fifth of the calcium oxalate monohydrate stones recurred, while no evidence of recurrence was detected in three stone-free cases with uric acid stones before PCNL at long-term follow up. Higher dietary protein intake in patients with metabolic syndrome might be one of the triggering factors for the formation of uric acid stones. Therefore, appropriate metabolic evaluation, selective medical therapy and dietary recommendations to decrease animal protein intake have been shown to diminish the risk of recurrent stone formation in these patients [20].

In the present series, eGFR slightly decreased in the control group during long-term follow-up. In patients with metabolic syndrome, eGRF worsened be ≈25% at long-term compared with the preoperative period (87.8 vs 66.6 mL/min/1.73 m2). In patients with chronic kidney disease recent studies have investigated the long-term outcomes of PCNL and have shown that one of the metabolic syndrome components, DM, is a predictive factor for worsening kidney function [23,24]. The yearly rate of decrease in GFR has been reported to be 1 mL/min in patients without DM [25]. On the other hand, yearly rates of decrease in GFR in patients with type 1 or type 2 DM with untreated diabetic nephropathy are ≈12 mL/min/year and 6 mL/min/year, respectively [26]

The present retrospective study design has some limitations. First, metabolic evaluations were not performed. Second, although uric acid stone-recurrence rates were higher in patients with metabolic syndrome, a statistically significant difference was not detected relative to the control group. This finding might be related to the few cases with uric acid stones. Therefore, these results should be confirmed in multicentre studies on a larger scale.

In conclusion, perioperative and postoperative early period outcome including stone-free rates were comparable between the metabolic syndrome and control groups. Calcium oxalate monohydrate was the most frequently foundd stone type in patients with or without metabolic syndrome. Uric acid stones were found in 20% of patients with metabolic syndrome. During the long-term follow-up, in patients undergoing PCNL, stone-recurrence rates were >40%. After PCNL stone-recurrence risk in patients with metabolic syndrome was 3.2-fold higher than the control group. Metabolic syndrome is associated with worsening renal function at long-term follow-up. Therefore, aggressive monitoring of patients with metabolic syndrome and treatment of their DM and hypertension may prevent renal deterioration.

CONFLICT OF INTEREST

None declared.

Ancillary