Renal function markers in single-kidney patients after percutaneous nephrolithotomy: A pilot study
Alireza Ghadian1, Behzad Einollahi1, Mehrdad Ebrahimi1, Mohammad Javanbakht1, Mousa Asadi1, Reza Kazemi2
1 Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
2 Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences; Department of Urology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
|Date of Submission||04-Oct-2021|
|Date of Decision||24-Dec-2021|
|Date of Acceptance||29-Dec-2021|
|Date of Web Publication||18-Feb-2022|
Dr. Reza Kazemi
School of Medicine, Isfahan University of Medical Sciences, Isfahan
Source of Support: None, Conflict of Interest: None
Background: The present study was performed to investigate and compare renal functions of single-kidney patients after 12 h of percutaneous nephrolithotomy (PCNL) surgery through assessing major markers of renal function with focus on serum level of cystatin that performs a consistent accuracy in various conditions. Materials and Methods: This pilot quasi-experimental study was done on 92 patients with single kidney having staghorn calculus who had undergone PCNL and were referred to the Al-Zahra Hospital, Isfahan, Iran, during 2019–2021. Serum levels of cystatin C, creatinine, estimated glomerular filtration rate (eGFR), and neutrophil gelatinase-associated lipocalin (NGAL) urine level were evaluated before and 12 h after surgery. Results: The mean cystatin C decreased significantly 1.58 ± 0.55 versus mg/L 1.46 ± 0.52 after 12 h after surgery (P < 0.001). Furthermore, the mean levels of creatinine (2.04 ± 0.71 vs. 1.89 ± 0.60 mg/dL) and NGAL (39.72 ± 12.87 vs. 24.05 ± 10.89 μg/ml) were decreased significantly after 12 h of procedure (P < 0.05) while the mean eGFR (57.62 ± 27.59 vs. 64.68 ± 31.88 ml/min/1.73 m2) was increased significantly after 12 h (P < 0.001). Conclusion: Due to significant improvement in all markers of renal after PCNL, this procedure can be considered a potentially effective and safe approach for treating large stone in single-kidney patients.
Keywords: Cystatin C, neutrophil gelatinase-associated lipocalin, percutaneous nephrolithotomy, renal function markers, single-kidney patients
|How to cite this article:|
Ghadian A, Einollahi B, Ebrahimi M, Javanbakht M, Asadi M, Kazemi R. Renal function markers in single-kidney patients after percutaneous nephrolithotomy: A pilot study. J Res Med Sci 2022;27:17
|How to cite this URL:|
Ghadian A, Einollahi B, Ebrahimi M, Javanbakht M, Asadi M, Kazemi R. Renal function markers in single-kidney patients after percutaneous nephrolithotomy: A pilot study. J Res Med Sci [serial online] 2022 [cited 2022 May 23];27:17. Available from: https://www.jmsjournal.net/text.asp?2022/27/1/17/337905
| Introduction|| |
Percutaneous nephrolithotomy (PCNL) is a minimally-invasive procedure to remove stones from the kidney by a small incision wound through the skin. It is most suitable to remove stones of more than 2 cm in size, which are present near the pelvic region. This method is mainly used for removal of cystine radiopaque kidney stones with diameter of more than 2 cm.
PCNL is one of the effective monotherapies for removal of kidney stones and is also associated with least mortality and complication rates.,
Studies have indicated that PCNL has efficient long-term results even in patients with high risks, such as the elderly, children, and patients with chronic kidney diseases (CKDs), but very few studies have investigated the effects of PCNL on kidneys within the 1st day after this procedure. Complications of PCNL could be due to the following reasons: inappropriate patient's selection, insufficient equipment, technical problems, vascular injuries, and hemorrhage. Vascular injuries could also lead to postoperative bleeding and might require surgical interactions if persistent for more than 3 weeks.,
Evaluation of estimated glomerular filtration rate (eGFR) is one of the best methods of assessing renal functions. The eGFR assessments could help us to evaluate the exact renal functions. This process could be performed using different agents, such as inulin, iohexol, 125I-iothalamate, and cystatin C.,
Creatinine is the most widely used biomarker of kidney function. However, it is inaccurate at detecting mild renal impairment, and its levels can vary with muscle mass but not with protein intake. Urea levels might change with protein intake. Cystatin C has a low molecular weight (approximately 13.3 kilodaltons), and it is removed from the bloodstream by glomerular filtration in the kidneys. If kidney function and glomerular filtration rate decline, blood levels of cystatin C rise. Cross-sectional studies have suggested that serum levels of cystatin C are a more precise measure of kidney function than serum creatinine levels. There are a limited number of longitudinal studies, but some of them have shown promising results., Although studies are somewhat divergent, most studies have found that cystatin C levels are less dependent on age, gender, ethnicity, diet, and muscle mass compared to creatinine, and that cystatin C is equal or superior to the other available biomarkers in a range of different patient populations including diabetic patients in CKD and after kidney transplant.,
According to the UK's National Institute for Health and Care Excellence guideline for assessment and management of CKD in adults, using serum cystatin C to estimate eGFR is more specific for important disease outcomes than the use of serum creatinine, and may reduce overdiagnosis in patients with a borderline diagnosis, reducing unnecessary appointments, patients' worries, and also the overall burden of CKD on population.,
The neutrophil gelatinase-associated lipocalin (NGAL) is a small glycosylated protein that is filtered in the glomerular membrane and also it is reabsorbed in proximal tubule. The urinary level of NGAL is a biomarker for renal function and renal tubular injury.
PCNL for large stones in patients with CKD, particularly in single-kidney patients, poses an important challenge and potential threat or progression of CKD. As we are aware, there is no previous study evaluating the effect of PCNL in single-kidney patients suffering from large stones. Therefore, the current pilot study has been conducted to evaluate the efficacy and safety of PCNL in these patients through evaluating the improvement in major markers of renal function including serum levels of cystatin C, creatinine, eGFR, and NGAL urine level.
| Materials and Methods|| |
Study design and participants
This pilot quasi-experimental study was done on 92 patients with single kidney having staghorn calculus who had undergone PCNL and were referred to the Al-Zahra Hospital, Isfahan City, Isfahan Province, Iran, during 2019–2021. The protocol of the current study was approved (IR.BMSU.BAQ.REC.1399.008) by the Baqiyatallah University of Medical Sciences, Tehran, Iran. Furthermore, informed consent was obtained from all the subjects for participation in the study. Inclusion criteria included the patients with solitary kidney aged more than 10 years with kidney stone (diameter of more than 2 cm and staghorn calculus based on multidetector computed tomography [MDCT] scan findings) who were willing to cooperate in the study. Furthermore, the patients with two kidneys and normal kidney function, renal failure (eGFR below 15 ml/min/1.73 m2), heavy bleeding (over than 1000 cc), or low blood pressure (under 90/50 mmHg) during surgery and patients who had recently undergone extracorporeal shock wave lithotripsy were excluded from the study.
Surgical procedure and main study outcomes evaluation
All patients underwent the same general anesthesia with thiopental sodium (5–7 mg/kg), atracurium besilate (0.4–0.5 mg/kg), fentanyl (50–100 μg/kg), and propofol. A 5–6-Fr ureteral catheter was placed in ureter for patients and then secured to a Foley catheter. Position of patients was placed prone and a pad was used for under pressure protection. An 18-gauge Chiba needle and a guidewire were used to access calyx under fluoroscopic guidance. Amplatz dilators up to 28 Fr were used for tract dilation. After screening with nephroscopy, stones were fragmented with pneumatic LithoClast (SWISS LithoClast) and then removed of kidney. After ensuring the absence of stones in pyelocaliceal subguide of fluoroscopy, 4.8-Fr ureteral stent and 16-Fr nephrostomy tube were placed in renal pelvis.
The blood sample (3 cc) was taken from patients 6 h before surgery and 12 h after surgery, and blood samples (at a temperature range of 2°C–4°C) were sent to laboratory to evaluate the serum level of cystatin C and then serum level of cystatin was evaluated with enzyme-linked immunosorbent assay (ELISA) (Human Cystatin C Quantikine ELISA Kit DSCTC0: R&D Systems, USA) kit based on manufacturer's instructions.
Serum level of creatinine was evaluated with 3 cc of blood samples before and 12 h after surgery. The urine sample (4 cc) were collected from patients 2 h before and 12 h after procedure and sent to laboratory for measurement of NGAL urinary levels with using ELISA assay by kit produced via R&D Systems Company (USA). Furthermore, eGFR of patients was calculated using cystatin level before and 12 h after surgery; the formula for measurement of eGFR was 100/cystatin c-14 formula.,
Complications and other variables
Complications following PCNL included bleeding during surgery, thoracic complication (pneumothorax, hemothorax, and nephropleural fistula), injury and obstruction to renal pelvic and renal collecting ducts, colon perforation, spleen and liver injury, postoperative fever, sepsis, and neurologic complication (facial nerve injury, blurry vision, hemiplegia, paraplegia, neurovascular disease, and comma). These complications were evaluated during and after surgery, so MDCT scan was performed for suspected patients to organ injury.
Demographic, clinical, and surgical informations such as age, gender (male, female), body mass index (BMI, kg/m2), glomerular filtration rate (eGFR), side of involved single kidney (right, left), cause of having single kidney (atrophy as renal stone or trauma, hypoplasia as pyelonephritis, congenital agenesis, atresia, and nephrectomy), size of renal stone, place of kidney stone (upper, middle, lower), number of access, and duration of surgery and hospitalization were recorded in baseline.
All statistical analyses were performed by using SPSS version 24 (SPSS Inc., Chicago, Ill., USA). Continuous and categorical data were reported as mean ± standard deviation and frequency percentage. Normality of continuous variables was evaluated by Kolmogorov–Smirnov test and Q-Q plot. Change from baseline for continuous variables was evaluated using paired samples t-test.
| Results|| |
The current study was performed on 92 single-kidney patients (63 males and 29 females) with a mean age of 44.29 ± 12.55 years. The mean of kidney stone size was 2.78 ± 0.65 cm, and most of stones were placed in lower region of kidney. [Table 1] presets the complete demographic and clinical features of included patients in the current study.
The mean cystatin C decreased significantly 1.58 ± 0.55 vs. 1.46 ± 0.52 mg/L after 12 h after surgery (P < 0.001). Furthermore, the mean levels of creatinine (2.04 ± 0.71 vs. 1.89 ± 0.60 mg/dL) and NGAL (39.72 ± 12.87 vs. 24.05 ± 10.89 μg/ml) were decreased significantly after 12 h of procedure (P < 0.05) while the mean eGFR (57.62 ± 27.59 vs. 64.68 ± 31.88 ml/min/1.73 m2) was increased significantly after 12 h (P < 0.001) [Table 2].
|Table 2: Changes in renal function markers before and 12 h after percutaneous nephrolithotomy|
Click here to view
Three patients (3.2%) had fever after procedure that these patients were afebrile within 4 days and then discharged from hospital. Furthermore, two cases (2.1%) had gross hematuria (following acute kidney injury [AKI] and raising of creatinine) after procedure that these patients underwent complete bed rest, hydration therapy, and received pack cells and then these patients were recovered after 5 days of procedure.
| Discussion|| |
In the present study, 92 patients undergoing PCNL were examined and our results showed that mean serum levels of cystatin and creatinine were decreased significantly within 12 h after surgery. Furthermore, the means of NGAL urine level were significantly decreased after 12 h of procedure and the means of eGFR were significantly increased after 12 h.
Previous studies have also evaluated the effects of PCNL on kidney functions. Sairam et al. evaluated data of 5644 patients from 96 centers and followed them for 1 year. They showed that impaired renal functions could negatively influence results of PCNL, but no evidence was observed on the negative effects of PCNL on kidney functions. They also explained that serum creatinine and kidney function indicators did not increase immediately after PCNL. Our results were in line with the findings of this study. Akman et al. (2011) evaluated outcomes of PCNL in 47 patients with solitary kidney. They showed that PCNL is a safe and beneficial technique, especially in patients with single kidney accompanied by no immediate complication and negative effects on kidney functions. However, a 10.6% complication rate was observed within a mean follow-up time of 18.7 ± 11.8 (6–60) months. Hosseini et al. conducted a study on 412 single-kidney patients in 2015. They found that PCNL had no significant adverse effects on kidney functions and was considered a safe method for removal of kidney stone in patients with single kidney. They also suggested that more attention should be given in order to prevent even minor complications.
Our findings emphasize that PCNL is safe and had minimal adverse effects on patients with single kidney. Most of the previous studies have evaluated kidney function within long follow-up times, but here, kidney function was investigated 12 h after PCNL. Basiri et al. studied the safety and efficacy of PCNL for management of large renal stones in 60 patients with single-functioning kidneys and double-functioning kidneys, respectively. They used quantitative single-photon emission computed tomography (CT) measurement of technetium-99m dimercaptosuccinic acid scan uptake and showed that renal function was preserved or even was often improved after percutaneous stone removal, and the procedure had no detrimental effects on renal function in both groups. They also showed no statistically significant difference between these groups in terms of morbidity and stone clearance. In the current study, the serum levels of cystatin and creatinine were investigated and both factors were found to significantly decrease after PCNL showing effectiveness of this method.
There have been also some other studies that indicated the effectiveness of PCNL in patients with kidney problems, and they have reported no significant complications., Based on the results of our study, improvements in renal functions were also detected whether PCNL might become transiently worse kidney functions within hours after the procedure. Furthermore, significant direct correlations were found between serum cystatin and creatinine levels with age, BMI, and length of hospital stay. Therefore, this procedure is suggested to be performed on older patients with higher BMI with more care, as mentioned in the study by Bozzini et al.
Spahillari et al. compared serum level of cystatin C and creatinine for detection of AKI and showed that serum level of cystatin C was less sensitive than creatinine to detect AKI and also cystatin C and creatinine were among markers to detect mortality and dialysis outcomes. However, the results of another study indicated that serum level of cystatin C was better than creatinine to estimate kidney function.
In a study by Mohammadi and Ghamari, who evaluated urinary NGAL for patients with double kidneys underwent PCNL. The authors conducted that urinary NGAL and serum creatinine were increased after the procedure compared to before. GFR was also decreased after the procedure compared to before. These changes were observed based on AKI in patients. In our study, patients with single kidney underwent PCNL, so eGFR was increased and urinary NGAL and creatinine were decreased after procedure. The current study is a novel study about the effect of PCNL in single kidney so previously and also cystatin C and NGAL were measured for first time in patients with single kidney under PCNL. The main limitation of our study is the lack of a control group to compare the effectiveness of PCNL with normal subjects.
| Conclusion|| |
Significant improvement was observed in all markers of renal function, particularly in serum level of cystatin after PCNL, in our study patients. An observed significant improvement in cystatin C is a promising biomarker for better estimate of kidney function in this population in the current study that provides primary evidence on considering PCNL as a potentially effective and safe approach for treating large stone in single-kidney patients. Randomized clinical trials for comparing the effectiveness of PCNL with competitors' other standard approaches are suggested.
The protocol of the current study was approved (IR.BMSU.BAQ.REC.1399.008) by the Baqiyatallah University of Medical Sciences, Tehran, Iran.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sairam K, Scoffone CM, Alken P, Turna B, Sodha HS, Rioja J, et al.
Percutaneous nephrolithotomy and chronic kidney disease: Results from the CROES PCNL global study. J Urol 2012;188:1195-200.
Skolarikos A, Alivizatos G, de la Rosette JJ. Percutaneous nephrolithotomy and its legacy. Eur Urol 2005;47:22-8.
Ganpule AP, Vijayakumar M, Malpani A, Desai MR. Percutaneous nephrolithotomy (PCNL) a critical review. Int J Surg 2016;36:660-4.
Yang T, Liu S, Hu J, Wang L, Jiang H. The evaluation of risk factors for postoperative infectious complications after percutaneous nephrolithotomy. Biomed Res Int 2017;2017:4832051.
Alsmadi J, Fan J, Zhu W, Wen Z, Zeng G. The influence of super-mini percutaneous nephrolithotomy on renal pelvic pressure in vivo
. J Endourol 2018;32:819-23.
Xiao Y, Li Q, Huang C, Wang P, Zhang J, Fu W. Perioperative and long-term results of retroperitoneal laparoscopic pyelolithotomy versus percutaneous nephrolithotomy for staghorn calculi: A single-center randomized controlled trial. World J Urol 2019;37:1441-7.
Wollin DA, Preminger GM. Percutaneous nephrolithotomy: Complications and how to deal with them. Urolithiasis 2018;46:87-97.
Kumar S, Keshavamurthy R, Karthikeyan VS, Mallya A. Complications after prone PCNL in pediatric, adult and geriatric patients – A single center experience over 7 years. Int Braz J Urol 2017;43:704-12.
Ng DK, Schwartz GJ, Warady BA, Furth SL, Muñoz A. Relationships of measured iohexol GFR and estimated GFR with CKD-related biomarkers in children and adolescents. Am J Kidney Dis 2017;70:397-405.
Ebert N, Shlipak MG. Cystatin C is ready for clinical use. Curr Opin Nephrol Hypertens 2020;29:591-8.
Pasala S, Carmody JB. How to use… serum creatinine, cystatin C and GFR. Arch Dis Child Educ Pract Ed 2017;102:37-43.
Ebert N, Delanaye P, Shlipak M, Jakob O, Martus P, Bartel J, et al.
Cystatin C standardization decreases assay variation and improves assessment of glomerular filtration rate. Clin Chim Acta 2016;456:115-21.
Keddis MT, Amer H, Voskoboev N, Kremers WK, Rule AD, Lieske JC. Creatinine-based and cystatin C-based GFR estimating equations and their non-GFR determinants in kidney transplant recipients. Clin J Am Soc Nephrol 2016;11:1640-9.
McFerran DJ, Stockdale D, Holme R, Large CH, Baguley DM. Why is there no cure for tinnitus? Front Neurosci 2019;13:802.
Hosseini J, Fallah-Karkan M, Rahavian A, Soleimanzadeh F, Salimi H, Ghadimi K, et al.
Feasibility, complication and long-term follow-up of the newly nelaton based urethral dilation method, retrospective study. Am J Clin Exp Urol 2019;7:378-83.
Lasserson DS, Shine B, O'Callaghan CA, James T. Requirement for cystatin C testing in chronic kidney disease: A retrospective population-based study. Br J Gen Pract 2017;67:e732-5.
Major RW, Shepherd D, Brunskill NJ. Reclassification of chronic kidney disease stage, eligibility for cystatin-C and its associated costs in a UK primary care cohort. Nephron 2018;139:39-46.
Ning M, Mao X, Niu Y, Tang B, Shen H. Usefulness and limitations of neutrophil gelatinase-associated lipocalin in the assessment of kidney diseases. J Lab Precis Med 2018;3:1.
Mohammadi-Sichani M, Radmanesh F, Taheri S, Ghadimi K, Khodadadi S, Salehi H, Hatampour M, Kazemi R. Evaluation of glomerular filtration rate decline in patients with renal colic. Am J Clin Exp Urol 2022;10:31-6.
Herget-Rosenthal S, Bökenkamp A, Hofmann W. How to estimate GFR-serum creatinine, serum cystatin C or equations? Clin Biochem 2007;40:153-61.
Reddy SV, Shaik AB. Outcome and complications of percutaneous nephrolithotomy as primary versus secondary procedure for renal calculi. Int Braz J Urol 2016;42:262-9.
Akman T, Binbay M, Tekinarslan E, Ozkuvanci U, Kezer C, Erbin A, et al.
Outcomes of percutaneous nephrolithotomy in patients with solitary kidneys: A single-center experience. Urology 2011;78:272-6.
Hosseini MM, Yousefi A, Hassanpour A, Jahanbini S, Zaki-Abbasi M. Percutaneous nephrolithotomy in solitary kidneys: Experience with 412 cases from Southern Iran. Urolithiasis 2015;43:233-6.
Basiri A, Shabaninia S, Mir A, Soltani MH. The safety and efficacy of percutaneous nephrolithotomy for management of large renal stones in single- versus double-functioning kidney patients. J Endourol 2012;26:235-8.
Resorlu B, Kara C, Oguz U, Bayindir M, Unsal A. Percutaneous nephrolithotomy for complex caliceal and staghorn stones in patients with solitary kidney. Urol Res 2011;39:171-6.
Gupta NP, Mishra S, Seth A, Anand A. Percutaneous nephrolithotomy in abnormal kidneys: Single-center experience. Urology 2009;73:710-4.
Bozzini G, Verze P, Arcaniolo D, Dal Piaz O, Buffi NM, Guazzoni G, et al.
A prospective randomized comparison among SWL, PCNL and RIRS for lower calyceal stones less than 2 cm: A multicenter experience: A better understanding on the treatment options for lower pole stones. World J Urol 2017;35:1967-75.
Spahillari A, Parikh CR, Sint K, Koyner JL, Patel UD, Edelstein CL, et al.
Serum cystatin C- versus creatinine-based definitions of acute kidney injury following cardiac surgery: A prospective cohort study. Am J Kidney Dis 2012;60:922-9.
Kirelik D, Fisher M, DiMaria M, Soranno DE, Gist KM. Comparison of creatinine and cystatin C for estimation of glomerular filtration rate in pediatric patients after Fontan operation. Congenit Heart Dis 2019;14:760-4.
MohamadiSichani M, Ghamari ZT. Investigation of urinary neutrophil gelatinase associated lipocalin (NGAL) for early diagnosis of acute kidney injury after percutaneous nephrolithotomy. Afr J Urol 2017;23:214-8.
[Table 1], [Table 2]