ENDOUROLOGY AND STONE DISEASE Short-term Alteration of Renal Function and Electrolytes after Percutaneous Nephrolithotomy Subhabrata Mukherjee1,4, Rajan Kumar Sinha2,4*, Tarun Jindal3,4, Pramod Kumar Sharma4, Soumendra Nath Mandal4, Dilip Karmakar4 Purpose: To analyse the changes in renal function and serum electrolytes in the early post-operative period of percutaneous nephrolithotomy (PCNL). Materials and Methods: A total of 110 patients with normal renal function, who underwent PCNL in our institute were evaluated prospectively. Haemoglobin percentage, packed cell volume, blood urea nitrogen, serum creatinine and serum electrolytes, namely sodium, potassium, chloride and ionized calcium were measured on the day before surgery and after 72 hours of the procedure. Renal function was assessed by Cockcroft-Gault formula and estimat- ed glomerular filtration rate was calculated by modification of diet in renal disease formula. Results: Serum creatinine increased significantly from a mean value of 0.89 ± 0.199 mg/dL to 0.96 ± 0.252 mg/dL (P = 0.0002) and both creatinine clearance and estimated glomerular filtration rate experienced a significant fall - from a median value (interquartile ranges) of 82.99 (72.37 to 96.88) mL/min to 75.38 (63.89 to 94.05) mL/min in case of creatinine clearance (P = 0.0004) and from a mean value of 95.18 ± 19.87 mL/min/1.73 m2 to 89.30 ± 23.14 mL/min/1.73 m2 in case of estimated glomerular filtration rate (P = 0.003). Furthermore, there were significant drops in both haemoglobin percentage and packed cell volume. There were no significant alterations in serum elec- trolytes - sodium and potassium (mmol/L) [Median (IQR)] changed from a pre-operative figure of 137.5 (134.0 to 140.0) and 3.85 (3.60 to 4.10) to a post-operative value of 138 (135.0 to 140.0) and 3.85 (3.50 to 4.10) respectively. Conclusion: Even though there is no significant variation in serum electrolytes, PCNL causes significant reduction in renal function in the early post-operative period. Keywords: creatinine clearance; estimated glomerular filtration rate; percutaneous nephrolithotomy; serum cre- atinine; serum electrolytes INTRODUCTION Urinary stones have troubled humans since the ear-liest records of civilization(1). Among the various surgical options for management of renal stone, percu- taneous nephrolithotomy (PCNL), a minimally invasive endoscopic treatment, has emerged significantly over the last few decades. It is often the preferred treatment option especially for patients with large or complex re- nal stones, stones that are refractory to shock wave lith- otripsy (SWL), residual stones after failed alternative modalities and so on(2-4). It is an efficient and safe pro- cedure for removal of renal calculi with low incidence of serious complications(5,6). Interestingly, people have different views about the im- pact of PCNL on renal function in the early post-opera- tive period. On the one hand, stone removal can improve renal function by relieving obstruction and eradicating underlying infection(7). On the other hand, dilation and establishment of nephrostomy tract and associated stone removing procedure may negatively impact func- 1Department of Urology, Northwick Park Hospital, London North West University Healthcare NHS Trust, Harrow, UK. 2Department of Urology, Kidney Stone and Urology Clinic, Bhagalpur, India. 3Department of Urology, Tata Medical Centre, Kolkata, India. 4Department of Urology, Calcutta National Medical College and Hospital, Kolkata, India. *Correspondence: Department of Urology, Kidney Stone and Urology Clinic, Bhagalpur, India. Tel: +91-9007205371. E-mail: rajan_rims@yahoo.co.in. Received April 2018 & Accepted May 2019 tional integrity(8-12). To add on, some studies have also demonstrated that kidney function remains unchanged in the initial post-operative period(13-15). Apart from that, usage of large amount of irrigation fluids during PCNL may also alter the serum electrolyte levels. In this study attempts have been made to evaluate the changes in renal function in the form of creatinine clearance (CrCl) by Cockcroft-Gault formula (CGF) and estimated glomerular filtration rate (eGFR) by modification of diet in renal disease (MDRD) formula in the early post-operative period of PCNL along with estimation of changes in serum electrolytes at the same point of time (16,17). Knowledge in this field will help us managing post-operative cases of PCNL in a much better way, especially while making decisions regarding selection of drugs, or offering SWL or repeat PCNL. MATERIALS AND METHODS Study Population This prospective observational study was carried out at Urology Journal/Vol 16 No. 6/ November-December2019/ pp. 530-535. [DOI: 10.22037/uj.v0i0.4558] Vol 16 No 06 November-December2019 531 Calcutta National Medical College and Hospital, Kolk- ata over a period of one and half year. Ethical clearance was obtained from the institutional ethical committee when our first author requested for it as a part of his dissertation at the beginning of the study. Inclusion and exclusion criteria Patients with renal stone who were planned for PCNL (size >2 cm for non-lower pole stones, size > 1 cm for lower pole stones and stones of any size that were SWL resistant or within a calyceal diverticulum) and gave consent for the study were included. Whereas, patients with age < 18 years; radiolucent stones; preoperative impaired renal function (serum creatinine > 1.4 mg/dL or eGFR by MDRD equation < 60 mL/min/1.73 m2); poorly functioning contralateral kidney on intravenous urography (IVU); solitary kidney; history of previous renal surgery; history of SWL within 6 months; history of anticoagulant intake or uncontrolled coagulopathy; history of intraoperative or postoperative blood trans- fusion; patients who required repeat PCNL in same admission with nephrostomy tube in situ; and patients who did not give consent for the study were excluded. A total of 110 patients were ultimately selected follow- ing these criteria. Procedures All patients underwent thorough clinical evaluation be- fore the procedure. Urinary infection, if present, was treated with the antibiotics as per culture and sensitivity report. All patients received injection ceftriaxone (1g) and in- fusion levofloxacin (500mg/100mL) intravenously just before the procedure(18). Standard prone PCNL were performed by the same surgical team using 0.9% nor- mal saline as irrigation solution. All patients received 0.9% normal saline intra-operatively followed by 0.9% normal saline and 5% dextrose solution in 2:1 ratio in first 24 h after operation. Serial tract dilatation was done with Amplatz fascial dilators up to 26 Fr. Nephroscopy was performed with 24 Fr rigid nephroscope (Richard Wolf) and stone fragmentation was carried out using Swiss pneumatic lithoclast. At the end of the procedure, stone clearance was checked on combined fluoroscopy and nephroscopy. Antegrade double - J stent (DJ stent) was inserted in all the cases. 24 Fr nephrostomy tube was placed in case of perforation of pelvicalyceal sys- tem, suspected residual fragments, incomplete stone clearance or bleeding from the tract. Intraoperative data like number of access, type of access, total procedure time (from cystoscopy to postoperative retrograde DJ stenting ± nephrostomy tube insertion), scope time (du- ration of nephroscopy) and amount of irrigation fluid (only during nephroscopy) were recorded in all the cas- es. Nephrotoxic drugs like aminoglycosides and nonsteroi- dal anti-inflammatory drugs were avoided during this period(19,20). X-ray of kidney, ureter and bladder (X-ray KUB) was performed after 48 hours and nephrostomy was removed before 72 hours unless there was no evi- dence of big residual fragments. PCNL procedure suc- cess was defined as no residual stone visible on X-ray KUB. Complications were also recorded. Evaluations Haemoglobin percentage (Hb), packed cell volume (PCV), blood urea nitrogen (BUN), serum creatinine (SeCr) and serum electrolytes, namely sodium (Na+), potassium (K+), chloride (Cl-) and ionized calcium (iCa++) were measured on the day before surgery and repeated after 72 hours. CrCl (by CGF) and eGFR (by MDRD formula) were calculated both pre and post pro- cedure. Statistical Analysis Data were summarized by routine descriptive statistics namely mean and standard deviation (SD) for normal- ly distributed numerical variables and count and per- centage for categorical variables. Median values with interquartile ranges (IQR) have been presented for nu- merical variables with skewed distribution. Pre and post procedure values of numerical parameters have been Table 1. Demographic data of the study population along with op- erative details Parameters Data No. of patients 110 Age (years) [Mean ± SD] 40.27 ± 11.525 Sex [No. (Percentage)] Male 70 (63.64%) Female 40 (36.36%) Body weight (kg) [Mean ± SD] 57.09 ± 10.656 Laterality of stones [No. (Percentage)] Left 53 (48.18%) Right 57 (51.82%) No. of access [No. (Percentage)] One 103 (93.64%) Two 7 (6.36%) Type of access [No. (Percentage)] Infracostal 100 (90.91%) Supracostal 8 (7.27%) Combined 2 (1.82%) Total procedure time (min) [Mean ± SD] 80.05 ± 20.782 Scope time (min) [Median (IQR)] 45 (30 to 55) Irrigation fluids (L) [Mean ± SD] 13.44 ± 6.147 Stone clearance [No. (Percentage)] Complete 78 (70.91%) Incomplete 32 (29.09%) Effect of percutaneous nephrolithotomy on renal function and electrolytes-Mukherjee et al. Figure 1. Scatter diagram and regression line showing significant positive correlation of preoperative serum creatinine with change in eGFR by MDRD formula measured 72 hours after PCNL (r= 0.31 , P = 0.001) compared by paired t test or Wilcoxon’s matched pairs signed rank test as appropriate. Change in eGFR was compared between subgroups by student’s unpaired t test. Association between change in eGFR and numer- ical variables were explored by calculating Pearson's correlation coefficient r or Spearman's rank correlation coefficient rho as appropriate. Scatter plots were con- structed wherever relevant. Analysis has been two tailed and P < .05 has been con- sidered as statistically significant. MedCalc version 11.6 (Maria Kerke, Belgium; MedCalc software, 2011) was used for statistical analysis. RESULTS Demographic data of the study population along with operative details are presented in Table 1. The comparative preoperative and 72 hours postopera- tive data are illustrated in Table 2. There were no sta- tistically significant alterations in the values of serum electrolytes and BUN. However, SeCr was increased significantly from a mean value of 0.89 ± 0.199 mg/dL to 0.96 ± 0.252 mg/dL (P = .0002). Along with it, both CrCl and eGFR experienced a significant fall - from a median value (IQR) of 82.99 (72.37 to 96.88) mL/min to 75.38 (63.89 to 94.05) mL/min in case of CrCl (P = .0004) and from a mean value of 95.18 ± 19.87 mL/ min/1.73 m2 to 89.30 ± 23.14 mL/min/1.73 m2 in case of eGFR (P = .003). Furthermore, there were significant fall in both Hb and PCV. Preoperative mean values of Hb and PCV were 13.78 ± 2.01 gm/dL and 40.59 ± 5.85 percent respec- tively, and these declined to 11.68 ± 1.74 gm/dL and 34.6 ± 5.21 percent respectively in the postoperative period (P < .0001 in both the cases). The relationship between the change in eGFR and different preoperative variables were analysed in de- tail and are summarised in Table 3. Sex, post-opera- tive residual stone, age, body weight, total procedure time, scope time and amount of irrigation fluid did not have any significant association with eGFR change. Although the fall in eGFR was more in two-accesses group (a mean drop of 13.94 ± 16.35 mL/min/1.73 m2) compared to one-access group (a mean drop of 5.33 ± 20.94 mL/min/1.73 m2), it did not achieve statistical significance (P = .29). Preoperative SeCr had a significant positive correlation (r = 0.31, P = .001) (Figure 1) and preoperative CrCl and eGFR had a significant negative correlation (r = -0.21, P = .025 and r = -0.35, P = .0002 respectively) with the change in eGFR. Similarly, the relationship between the change in Hb and different preoperative variables were analysed. Interestingly, men had significant drop in Hb (a mean decline of 2.46 ± 1.93 gm/dL) as compared to women (a mean decline of 1.48 ± 1.39 gm/dL). However, fall in Hb was comparable between one access and two ac- cesses - both had an average decline of around 2 gm/ dL. Only preoperative Hb had a significant negative Table 2. Comparative preoperative and 72 hour postoperative data Dataa Preoperative 72 Hours Postoperative P-value Na+ (mmol/L) [Median (IQR)] 137.5 (134.0 to 140.0) 138 (135.0 to 140.0) .1870 K+ (mmol/L) [Median (IQR)] 3.85 (3.60 to 4.10) 3.85 (3.50 to 4.10) .9407 Cl- (mmol/L) [Mean ± SD] 100.94 ± 3.449 101.88 ± 3.534 .0704 iCa++ (mmol/L) [Median (IQR)] 1.12 (1.00 to 1.23) 1.15 (0.99 to 1.21) .6391 BUN (mg/dL) [Mean ± SD] 9.34 ± 3.223 9.81 ± 3.887 .2749 Serum creatinine (mg/dL) [Mean ± SD] 0.89 ± 0.199 0.96 ± 0.252 .0002 Creatinine clearance (mL/min) [Median (IQR)] 82.99 (72.37 to 96.88) 75.38 (63.89 to 94.05) .0004 MDRD eGFR (mL/min/1.73 m2) [Mean ± SD] 95.18 ± 19.868 89.30 ± 23.143 .0036 Hb (gm/dL) [Mean ± SD] 13.78 ± 2.006 11.68 ± 1.742 < .0001 PCV (%) [Mean ± SD] 40.59 ± 5.847 34.6 ± 5.215 < .0001 A. Categorical Variables [No. (Percentage)]a Change in eGFR(mL/min/1.73 m2) [Mean ± SD] P-value Sex Male [70 (63.64%)] -4.67 ± 18.328 .4219 Female [40 (36.36%)] -7.99 ± 24.481 No. of access One [103 (93.64%)] -5.33 ± 20.944 .2895 Two [7 (6.36%)] -13.94 ± 16.349 Post-operative residual stone No (Complete clearance) [78 (70.91%)] -7.5397 ± 18.872 .1898 Yes (Incomplete clearance) [32 (29.09%)] -1.8172 ± 24.538 B. Numerical Variablesb r or rho Value P-value Age -0.1543 .1076 Body weight -0.02319 .8100 Total procedure time -0.005153 .9574 Scope time 0.0416 .6661 Amount of irrigation fluid -0.06213 .5190 Preoperative serum creatinine 0.3056 .0012 Preoperative creatinine clearance -0.2131 .0254 Preoperative MDRD eGFR -0.3506 .0002 a Change in eGFR was compared between subgroups by student’s unpaired t test. b Association between change in eGFR and numerical variables were explored by calculating Pearson's correlation coefficient r or Spear- man's rank correlation coefficient rho as appropriate. Effect of percutaneous nephrolithotomy on renal function and electrolytes-Mukherjee et al. Table 3. Association between change in eGFR and different variables Endourology and Stone Diseases 532 Vol 16 No 06 November-December2019 533 correlation with change in Hb (r = -0.59, P = < .0001). Rest of the parameters did not have any significant cor- relation with Hb change. DISCUSSION PCNL is one of the most commonly performed surgical intervention for management of renal stone disease with minimum morbidity(2-6). Most of the clinical studies have almost uniformly established that PCNL does not have any significant effect on long term renal function and even, at times, it may ameliorate renal performance (21-23). However, the literature is inadequate and even contradictory regarding the consequence of PCNL on early renal function (Table 4). According to Webb and Fitzpatrick, who worked in a canine model, CrCl were similar at baseline, 48 hours, or 6 weeks after the procedure(13). Saxby measured uri- nary CrCl and urinary prostaglandin F2α immediate- ly before and at 24 hours and 2 weeks after PCNL.(14) There was no difference in CrCl values. Although uri- nary prostaglandin level was increased at 24 hours, it returned to preoperative levels at 2 weeks. Additionally, in the study by Hegarty and Desai, CrCl was unchanged in single tract PCNL in the early post-operative period (15). In contrast, there are some literatures suggesting a de- cline in renal function in the early period after PCNL. Handa and colleagues demonstrated a statistically sig- nificant fall in GFR in their consecutive animal studies at 1h, 1.5 h and 4.5 h after operation which returned to baseline at 72 hours(8,10). This group also performed a retrospective analysis of 196 patients undergoing sin- gle-stage unilateral PCNL and detected an overall sig- nificant increase in SeCr concentration (0.14 ± 0.02 mg/ dL; P < .001) 24 hours after the procedure(8). Nouralizadeh and co-workers prospectively evaluated 94 patients who underwent unilateral PCNL and CrCl was estimated by CGF preoperatively and at 6, 24, 48 and 72 hours after operation(11). The mean ± SD of preoperative CrCl was 87.5 ± 32.2 mL/min, which de- creased to 85.5 ± 29.4 mL/min 6 hours after operation. Continuous decrease in CrCl was observed up to 48 hours after operation (75.9 ± 25.0 mL/min), and then, a slight increase in CrCl level was noted at 72 h after op- eration (81.9 ± 26.4 mL/min) although it was quite low compared to the pre-operative value. The drops in CrCl at 24 and 48 hours after PCNL were statistically signif- icant relative to their preoperative values (P < .05). Ta- bibi and associates retrospectively assessed 486 cases that underwent PCNL and CrCl was measured by CGF preoperatively and at 6, 24, 48 and 72 hours after oper- ation and on the day of discharge(12). Their findings in the initial post-operative days were almost similar to the study by Nouralizadeh and colleagues. CrCl returned to baseline level at the time of discharge from hospital. Interestingly, a study by Bayrak and co-workers has Table 4. Previous studies showing the effect of PCNL on renal function in the early post-operative period Study Parameter Measured Time Point(s) After Preoperative Measurement Change (Compared to Preoperative Value) A. Animal Model 1. Webb and Fitzpatrick (1985) (13) CrCl 48 h Nil 6 wk Nil 2. Handa et al (2006) (8) GFR by inulin clearance 1.5 h Drop* 4.5 h Drop* 3. Handa et al (2009) (9) GFR by inulin clearance Single tract 1.5 h Drop* 4.5 h Drop* Multiple tract 1.5 h Drop* 4.5 h Drop* 4. Handa et al (2010) (10) GFR by inulin clearance 1 h Drop* 72 h Nil B. Human Model 1. Saxby (1997) (14) Urinary CrCl 24 h Nil Urinary prostaglandin F2α 2 wk Nil 24 h Rise 2 wk Nil 2. Handa et al (2006) (8) SeCr 24 h Rise* 3. Hegarty and Desai (2006) (15) CrCl (CGF) Single tract Post op Nil Multiple tract Post op Drop* 4. Handa et al (2009) (9) CrCl (CGF) Single tract 24 h Drop* 48 h Drop* Multiple tract 24 h Drop* 48 h Drop* 5. Nouralizadeh et al (2011) (11) CrCl (by CGF) 6 h Drop 24 h Drop* 48 h Drop* 72 h Drop 6. Bayrak et al (2012) (7) CrCl (by CGF) 72 - 96 h Rise* 7. Tabibi et al (2014) (12) CrCl (by CGF) 6 h Drop 24 h Drop* 48 h Drop* 72 h Drop Discharge Nil * = statistically significant change Effect of percutaneous nephrolithotomy on renal function and electrolytes-Mukherjee et al. demonstrated an improvement in renal function in the early post-operative period(7). They prospectively eval- uated 80 patients who underwent unilateral PCNL and measured CrCl by CGF preoperatively and between 72 to 96 hours after operation. The result was a statistically significant increase (104.30 ± 37.30 ml/min preopera- tive and 112.38 ± 40.1 ml/min postoperative) in CrCl. In our study, we prospectively evaluated 110 patients with normal SeCr and found a statistically significant reduction in both CrCl and eGFR at 72 hours after uni- lateral PCNL. The results are in accordance with the outcome of other previous studies that reported a fall in CrCl in the early post-operative period(8,11,12). Alike other studies sex, age, body weight, total proce- dure time, scope time and amount of irrigation fluid did not have any significant association with eGFR change (7,11,12). In this study, we observed that even though the fall in eGFR was more in two-accesses group compared to single-access group, it was not statistically significant (P = .29). Handa and colleagues also compared single tract and multiple tracts PCNL in animal and human model and found significant decrease in renal function in both the groups, at 1.5 hours and 4.5 hours in animal study and at 24 and 48 hours in human study, without any significant difference between them(9). Similarly, Nouralizadeh and co-workers and Bayrak and co-work- ers did not find any significant difference in fall of renal function between the patients with multiple accesses (usually two) and single access(7,11). On the contrary, in the study by Hegarty and Desai comparing 40 patients with single tract versus multiple tract PCNL (2 to 6 tracts), a significant decrease in CrCl was observed in only multiple tract group, whereas there was no change in single tract cohort(15). Limited study population and more than two accesses might be the cause of this single divergent result. Although in the study by Saxby, a fall in serum potas- sium, sodium and calcium were noted 24 hours after PCNL, majority of other studies including ours did not find any change in electrolytes in the early post-opera- tive period(7,14,,24,25). In the study by Sichani and groups serum sodium slightly decreased from preoperative val- ue of 140.3 ± 2.8 mEq/l to 140.1 ± 3.6, 139.1 ± 3.4 (p < 0.01) and 139.3 ± 2.7 (p < 0.05) at 6, 24 and 48 h after the operation, respectively(26). It was probably due to the use of hyponatremic solution in postoperative period. One of the limitations of this study is measurement of serum creatinine and electrolytes only 72 hours after operation. It would have been interesting to get some longer term data to determine long term effects. Also, the implementation of these wide exclusion criteria may compromise the generalizability of results. In addition, the degree of statistically significant drop in renal func- tion may arguably not be clinically significant in this group of normal creatinine level patients. Finally, if the patients were compared with a controlled group that was given anaesthesia and did not perform kidney sur- gery other factors could have been excluded which may affect the results. CONCLUSIONS The results of this study show that significant impair- ment of renal function persists even at 72 hours after PCNL. No alteration in serum electrolytes has been observed during this period. Also, no significant differ- ence has been noticed in drop in renal function between the patients with multiple accesses (usually two) and single access. One should keep these factors in mind when planning for PCNL and try to avoid factors which may further impair renal function in the early post-op- erative period like nephrotoxic drugs, contrast agents, ESWL or redo-PCNL. CONFLICT ON INTEREST No competing financial interest exist. REFERENCES 1. Stoller ML. Urinary Stone Disease. In: Tanagho EA, editor. Smith's general urology, 17th ed. New York: The McGraw-Hill Companies; 2008. p. 246-77. 2. 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