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Predictors of renal recovery in renal failure secondary to bilateral obstructive urolithiasis

Predictors of renal recovery in renal failure secondary to bilateral obstructive urolithiasis Arab Journal of Urology (2016) 14, 269–274 Arab Journal of Urology (Official Journal of the Arab Association of Urology) www.sciencedirect.com STONES/ENDOUROLOGY ORIGINAL ARTICLE Predictors of renal recovery in renal failure secondary to bilateral obstructive urolithiasis a, a Muthukrishna P. Rajadoss , Chandrasingh Jeyachandra Berry , b c c Grace J. Rebekah , Vinu Moses , Shyamkumar N. Keshava , d a a a Kuruthukulangara S. Jacob , Santosh Kumar , Nitin Kekre , Antony Devasia Department of Urology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India Department of Biostatistics, Christian Medical College and Hospital, Vellore, Tamil Nadu, India Department of Radiology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India Department of Psychiatry, Christian Medical College and Hospital, Vellore, Tamil Nadu, India Received 24 June 2016, Received in revised form 24 July 2016, Accepted 10 August 2016 Available online 23 September 2016 KEYWORDS Abstract Objectives: To identify factors predicting renal recovery in patients presenting with renal failure secondary to bilateral obstructing urolithiasis. Calculus anuria; Patients and methods: Data from electronic records of consecutive adult patients Obstructive presenting with bilateral obstructing urolithiasis between January 2007 and April urolithiasis; 2011 were retrieved. Ultrasonography of the abdomen, and kidney, ureter, bladder Renal failure (KUB study) X-ray or abdominal non-contrast computed tomography confirmed the diagnosis. Interventional radiologists placed bilateral nephrostomies. Definitive ABBREVIATIONS intervention was planned after reaching nadir creatinine. Renal recovery was defined AUC, area under the as nadir creatinine of 62 mg/dL. ROC curve; Results: In all, 53 patients were assessed, 50 (94.3%) were male, and 18 (33.9%) CKD, chronic kidney were aged 640 years. Renal recovery was achieved in 20 patients (37.7%). A symp- disease; tom duration of 625 days (P < 0.01), absence of hypertension (P = 0.018), maxi- HR, hazard ratio; mum renal parenchymal thickness of >16.5 mm (P = 0.001), and haemoglobin KUB, kidney, ureter, >9.85 g/dL (P < 0.01) were significant on unadjusted analysis. Symptom duration Corresponding author at: Department of Urology, Christian Medical College and Hospital, Ida Scudder Road, Vellore, Tamil Nadu 632004, India. Fax: +91 (0)416 2232035. E-mail addresses: rajadoss@gmail.com, rajadoss@icloud.com (M.P. Rajadoss). Peer review under responsibility of Arab Association of Urology. Production and hosting by Elsevier http://dx.doi.org/10.1016/j.aju.2016.08.001 2090-598X  2016 Production and hosting by Elsevier B.V. on behalf of Arab Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 270 Rajadoss et al. bladder; of 625 days alone remained significant after adjusted analysis. Symptom duration of PCN, percutaneous 625 days (hazard ratio (HR) 13.83, 95% confidence interval (CI) 4.52–42.26; nephrostomy; P < 0.01), parenchymal thickness of P16.5 mm (HR 5.91, 95% CI 1.94–17.99; ROC, receiver operat- P = 0.002), and absence of hypertension (HR 9.99, CI 95% 1.32–75.37; ing characteristic; P = 0.026) were significantly related to time to nadir creatinine. Symptom duration US, ultrasonography of 625 days (HR 17.44, 95% CI 2.48–122.79; P = 0.004) alone remained significant after adjusted analysis. A symptom duration of 625 days (P = 0.007) was 22-times more likely to indicate renal recovery. Conclusions: Shorter symptom duration (625 days) is predictive of renal recovery in renal failure secondary to bilateral obstructive urolithiasis. 2016 Production and hosting by Elsevier B.V. on behalf of Arab Association of Urology. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). Introduction was retrieved from January 2007 to April 2011. Consecutive adult patients presenting with bilateral obstructing urolithiasis were included in the analysis. Renal failure secondary to bilateral obstructive urolithi- Institutional Review Board clearance was obtained. asis has variable clinical outcomes, which are often The clinical presentation comprised decreased urine dependent on the timing and nature of surgical interven- output associated with flank pain, vomiting, fever, or tion. The prevalence rate for urinary stones ranges from pedal oedema. 1% to 20% and the incidence of hospitalisation for cal- Ultrasonography (US) of the abdomen with kidney, culus disease ranges from 0.03% to 0.1% [1]. The esti- ureter, bladder (KUB study) X-ray or non-contrast mated lifetime risk for urolithiasis is 11% in men and CT scan was used to confirm the diagnosis. The inter- 7% in women with recurrence rates for renal stones ventional radiologists placed bilateral PCNs under US reported as 14%, 35%, 52% at 1, 5 and 10 years, respec- guidance; fluoroscopy was used to confirm the location. tively [2]. The incidence of bilateral calculus disease var- Local anaesthesia and sedation were used to perform the ies between 6% and 20% amongst those presenting with procedure under aseptic conditions. Broad-spectrum urolithiasis [3]. Ureterolithiasis is the most common antibiotics were administered, which was later modified cause of obstructive uropathy, presenting with urosepsis based on the urine culture report. [4]. Obstructing urinary calculus with urosepsis is an Patients who presented with severe metabolic acido- emergency and surgical decompression in the form of sis, persistent hyperkalemia, or fluid overload under- percutaneous nephrostomy (PCN) or ureteric stenting went emergency haemodialysis before PCN placement. has been shown to reduce mortality from 19.2% to A urine sample obtained at initial puncture was sent 8.8% [5]. for culture. Patients were admitted for at least Obstructive uropathy accounts for 10% of commu- 48–72 h, to monitor post-obstructive diuresis, and cor- nity acquired acute kidney injury [6] and urolithiasis is rect fluid and electrolyte imbalance. Serum electrolytes responsible for 10–20% of obstructive uropathy. and renal function tests were monitored on a regular Delay in relieving ureteric obstruction has been shown basis. Maximum renal parenchymal thickness was noted to worsen renal function and hypertension [7]. There on US. Maximum parenchymal thickness refers to the are published studies on predictors of renal recovery parenchymal thickness on the healthier kidney. The time in the subset of patients with renal insufficiency under- taken to reach nadir creatinine was documented. Nadir going treatment for nephrolithiasis and in the sub- creatinine was defined as the lowest serum creatinine group of patients with bilateral obstructive recorded during the recovery period. Patients were edu- urolithiasis and chronic kidney disease (CKD) [8,9]. cated on the importance of PCN care, close medical There is a need for studies, which look at factors pre- supervision until nadir creatinine and definitive manage- dicting renal recovery as well as investigate the pattern ment of obstructing urolithiasis. of renal recovery. Thus in the present study, we inves- The variables studied included age, gender, duration tigated the factors associated with renal recovery in of presenting symptoms, stone location and number bilateral obstructive urolithiasis and the pattern of and size, infection, maximum renal parenchymal renal recovery. thickness, time to nadir creatinine, and presence of co-morbid factors. Renal recovery was defined as nadir Patients and methods creatinine of 62 mg/dL. Several studies in the past have defined renal recovery as serum creatinine of <2 mg/dL Electronic medical records at the Department of or within 20% of the baseline value, partial renal Urology, Christian Medical College, Vellore, India, Renal recovery in calculus anuria 271 Table 1 Social demographic characteristics and clinical features at presentation. Variable N (%) Median (IQR) Age at presentation, years 48 (18–69) Sex – male 50 (94.3) Duration of symptoms, days 45 (1–730) Haemoglobin, g/dL 9.4 (5.1–15.3) Symptoms at presentation Flank pain 18 (33.9) Vomiting 13 (24.5) Fever 8 (15.1) Fatigue 5 (9.4) Gross haematuria 4 (7.5) Pedal oedema 4 (7.5) Calculuria 2 (3.8) Co-morbid illness Hypertension 14 (26.4) Diabetes mellitus 5 (9.4) Hyperuricaemia 5 (9.4) Stone location Bilateral ureteric 26 (49.1) Ureteric + renal pelvis 17 (32.1) Bilateral renal pelvis 10 (18.8) Stone number and size, mm Pelvis 28 25 (6–68) Staghorn 4 49 (46–56) Upper ureter 42 12 (5–28) Mid ureter 10 8 (6–20) Lower ureter 21 10 (5–19) Creatinine at presentation, mg/dL 5.7 (2.0–24.7) Serum creatinine after PCN, mg/dL 2.5 (1.0–7.5) Renal recovery, creatinine 62 mg/dL 20 (37.7) Poor recovery, creatinine >2 mg/dL 33 (62.3) IQR, interquartile range. recovery as >20% from baseline value, and dialysis model to assess the hazard ratios (HRs) for risk factors dependence as no recovery [10]. for time to nadir creatinine. The statistical software SPSS (version 16.0 for Windows) was used to analyse Statistical analysis the data. The mean and standard deviation (SD) were used to Results describe continuous variables, frequency, and percent- ages to depict categorical data. The variables were In all, 53 patients were evaluated; their social demo- examined for the normality of their distribution using graphics and clinical features at presentation are Kolmogorov–Smirnov and Shapiro–Wilk tests and we described in Table 1. Most of the patients were documented median and interquartile range values. middle-aged men, with bilateral ureteric calculi and 20 The Student’s t-test and chi-squared test were used to (37.7%) patients had renal recovery. Five patients assess statistical significance for continuous and categor- underwent a PCN change for blocked PCNs; two of ical variables, respectively. Receiver operating charac- them had good renal recovery. Three patients were trea- teristic (ROC) curves were used to obtain optimal ted for febrile UTI; one patient had good renal recovery. threshold duration of illness, maximum renal parenchy- Two patients required long-term renal replacement ther- mal thickness, and time to nadir creatinine for predict- apy. There was no mortality noted in the study group. A ing renal recovery. small minority of patients had complications; hence, it Multivariable logistic regression analysis was carried was not possible to do a subgroup analysis. One patient, out using factors significant on bivariate analysis, to who presented with a creatinine of 2 mg/dL, reached a assess the statistical significance of factors associated nadir creatinine of 1 mg/dL. with recovery. We estimated the regression coefficients, calculated the odds ratios and 95% CIs. Survival analy- Factors associated with recovery sis was used to assess the time taken to nadir creatinine. Survival curves were obtained using Kaplan–Meier ROC curves were constructed with the outcome variable estimates for the absence of hypertension, symptom being good renal recovery vs poor renal recovery. They duration, and maximum renal parenchymal thickness. were used to obtain optimal thresholds for the variables, Log-rank statistics was used, with 5% level to evaluate duration of symptoms, haemoglobin at presentation, significance. We also used the Cox proportional hazard and maximum renal parenchymal thickness, which were 272 Rajadoss et al. Table 2 Factors predicting renal recovery on unadjusted analysis. Risk factor Good renal recovery, Bad renal recovery, Unadjusted analysis n (%) N =20 n (%) N =34 OR (95%CI) P Symptoms duration 625 days 15 (78.9) 3 (11.1) 30.0 (5.9–153.1) <0.01 Haemoglobin >9.85 g/dL 15 (78.9) 8 (25.0) 11.25 (2.88–43.94) <0.01 Hypertension not present 1 (5.6) 14 (43.8) 13.22 (1.6–111.7) 0.018 Parenchyma thickness >16.5 mm 14 (77.8) 9 (26.5) 9.72 (2.53–37.40) 0.001 P < 0.05. The following variables were not statistically related to good renal recovery: age, presence of diabetes, stone location, pre-PCN creatinine, and positive urine culture. 625 days, >9.85 g/dL, and >16.5 mm, respectively. absence of hypertension (HR 9.99; 95% CI 1.32–75.37; For duration of symptoms of 625 days, the area under P = 0.026) were statistically significantly related to time the ROC curve AUC was 0.881 (95% CI 0.774–0.998; to nadir creatinine on univariate analysis. Only duration P < 0.01). For haemoglobin >9.85 g/dL, the AUC of symptoms (HR 17.44; 95% CI 2.48, 122.79; was 0.825 (95% CI 0.701–0.948; P < 0.01). For maxi- P = 0.004) remained significant in the adjusted analysis mum renal parenchymal thickness >16.5 mm, the using the Cox proportional hazard model (Fig. 1). AUC was 0.828 (95% CI 0.714–0.942; P < 0.01). In the good renal recovery group, 17 of 20 (85%) Table 2 shows the factors associated with renal recovery. patients reached nadir creatinine in 22.5 days. There Good recovery, on bivariate analysis, was associated was no further decline in serum creatinine after 42 days with a symptom duration of 625 days, absence of and 53 days in the good and bad recovery groups, hypertension, parenchymal thickness of >16.5 mm, respectively. and haemoglobin of <9.85 g/dL. The following variables were not significantly related to outcome on Discussion bivariate analysis: age, presence of diabetes, stone loca- tion, pre-PCN creatinine, and positive urine culture. The present study examined factors associated with On multivariable analysis, using logistic regression renal recovery and factors linked to the speed of recov- and including all statistically significant variables on ering renal function. It employed a retrospective cohort bivariate analysis in the model, only symptom duration design and used multivariable statistics to adjust for remained significant suggesting its crucial role in renal confounding. recovery (Table 3). Absence of hypertension, maximum Many of the clinical characteristics of the sample are renal parenchymal thickness, and anaemia lost their sta- similar to those reported in the literature. Male predom- tistical significance after multivariate modelling. inance and delayed help seeking in patients presenting Adjusted analysis showed that a symptom duration of with bilateral obstructing urolithiasis have been reported 625 days made renal recovery 22-times more likely. by similar studies [8]. Whilst many variables were related to good renal outcome on bivariate analysis (e.g. dura- Time taken to nadir creatinine tion of symptoms, absence of hypertension, parenchymal thickness, creatinine at presentation, and time to reach Survival curves were obtained using Kaplan–Meier esti- nadir creatinine), only the duration of symptoms mate for duration of symptoms, absence of hyperten- remained statistically significant after adjusting for sion, and parenchymal thickness and compared using confounders. Similarly, multivariable analysis supported Log-rank statistics. Significance was considered at 5% that the duration of the symptoms also seemed to deter- level. Duration of symptoms (HR 13.83, 95% CI 4.52– mine time to reach nadir creatinine, arguing that early 42.26; P < 0.01), maximum renal parenchymal thick- intervention is the key to a good outcome. ness (HR 5.91, 95% CI 1.94–17.99; P = 0.002), and Table 3 Factors predicting renal recovery on adjusted analysis. Risk factor Good renal recovery, Bad renal recovery, Adjusted analysis n (%) N =20 n (%) N =33 OR (95%CI) P Symptoms duration 625 days 15 (78.9) 3 (11.1) 21.49 (2.27–202.76) 0.007 Haemoglobin >9.85 g/dL 15 (78.9) 8 (25.0) 9.25 (0.83–102.86) 0.07 Hypertension not present 1 (5.6) 14 (43.8) 5.154 (0.26–102.84) 0.283 Parenchyma thickness >16.5 mm 14 (77.8) 9 (26.5) 1.288 (0.12–14.37) 0.837 P < 0.05. Renal recovery in calculus anuria 273 Figure 1 Survival curves were obtained using Kaplan–Meier estimate for duration of symptoms compared using Log-rank statistics. Significance was considered at 5% level. The symptom duration refers to the duration of ering these facts, emergency PCNs were placed by inter- patient’s presenting complaints, which could be flank ventional radiologists in our institution for almost all pain, vomiting, fever, fatigue, pedal oedema, calculuria the patients presenting with obstructive urolithiasis. or decreased urine output. This does not strictly repre- Delaying relief of obstruction of iatrogenic ureteric sent the duration of bilateral obstruction. Two patients obstruction beyond 2 weeks has been shown to cause had intermittent flank pain over a period of 2 years with long-term renal damage and hypertension [7]. There no definite point of worsening of symptoms. The long should be no delay in placing PCNs to expedite renal duration of symptoms could represent the chronic nat- recovery. In patients presenting with obstructive uropa- ure of patient’s condition, with multiple insults to the thy and urosepsis, urological source control in the form renal parenchyma. As expected most patients with of immediate low-level invasive treatment (PCN or ure- symptom duration of >60 days had poor renal teric stenting) should be done in the first 6 h [4]. recovery. The criteria to assess renal recovery can be based on Delayed presentations noted in our present study serum creatinine, creatinine clearance, or urine output. could be attributed to various factors including delayed We decided to use serum creatinine to define renal diagnosis, limited access to healthcare, unavailability of recovery in the present study, based on the availability appropriate medical expertise, time taken for trans- of data. Renal recovery could be defined on the rate of portation to referral centre, and financial constraints. decline in serum creatinine. In the present study, we Emergency decompression of the collecting system aimed to study the factors, which predict renal recovery with PCN or ureteric stenting in obstructing urolithiasis and the pattern of renal recovery. In order to have two with sepsis is the standard of care [11]. Placing a PCN in groups for comparison, we decided to use a nadir crea- an obstructed, infected hydronephrotic kidney has many tinine of 2 mg/dL to define renal recovery based on pre- advantages. In addition to monitoring output, it avoids vious studies [10]. Many factors have been implicated to ureteric instrumentation that can worsen urosepsis or affect renal recovery after relief of obstruction. These result in ureteric perforation [12]. It avoids general include the age of the patient, duration and degree of anaesthesia in a sick patient. The disadvantages of obstruction, presence of pyelolymphatic backflow, com- PCN include a longer procedure, patient discomfort, pliance of collecting system, presence of infection, and and morbidity. Whilst clinical outcome with both ure- concomitant use of nephrotoxic agents, like contrast teric catheterisation and PCN for obstructive urolithia- material [16]. Long-term follow-up of patients with sis has been essentially similar [13], PCN placement complete and partial renal recovery after acute renal has been found to be less expensive [14]. Availability failure showed age and absence of co-morbid illness as of an interventional radiologist and longer waiting time factors associated with better prognosis [17]. In a large for operating room favour PCN placement [15]. Consid- retrospective review of patients with renal insufficiency 274 Rajadoss et al. [2] Uribarri J, Oh MS, Carroll HJ. The first kidney stone. Ann Intern undergoing treatment for nephrolithiasis, higher preop- Med 1989;15:1006–9. erative creatinine, proteinuria of >300 mg/day, renal [3] Winsbury-White HP. Bilateral urinary calculus. Br J Urol cortical atrophy, stone burden of >1500 mm , and 1935;7:235–43. recurrent UTI were associated with renal deterioration [4] Wagenlehner FM, Lichtenstern C, Rolfes C, Mayer K, Uhle F, [9]. Stone-forming patients have reduced creatinine Weidner W, et al. Diagnosis and management for urosepsis. Int J Urol 2013;20:963–70. clearance when compared with non-stone formers [18]. [5] Borofsky MS, Walter D, Shah O, Goldfarb DS, Mues AC, Age-related decline in creatinine clearance was at a Makarov DV. Surgical decompression is associated with higher rate in stone formers when compared to normal decreased mortality in patients with sepsis and ureteral calculi. J individuals [19]. A case-control study in Olmsted Urol 2013;189:946–51. County showed that hypertension and diabetes in [6] Lian˜ o F, Pascual J. Epidemiology of acute renal failure: a prospective, multicenter, community-based study Madrid Acute patients with kidney stones significantly increase the risk Renal Failure Study Group. Kidney Int 1996;50:811–8. of CKD [20]. In our present study, absence of hyperten- [7] Lucarelli G, Ditonno P, Bettocchi C, Grandaliano G, Gesualdo sion was a significant factor on unadjusted analysis. FP, Selvaggi FP, et al. Delayed relief of ureteral obstruction is A prognostic model for renal recovery has been implicated in the long-term development of renal damage and reported in patients with bilateral obstructive urolithia- arterial hypertension in patients with unilateral ureteral injury. J Urol 2013;189:960–5. sis and CKD (nadir creatinine was >1.5 mg/dL within [8] Mishra S, Sinha L, Ganesamoni R, Ganpule A, Sabnis RB, Desai 5 days of urinary diversion) [8]. The following factors M. Renal deterioration index: preoperative prognostic model for were found significant on adjusted analysis: combined renal functional outcome after treatment of bilateral obstructive renal cortical thickness, presence of proteinuria, positive urolithiasis in patients with chronic kidney disease. J Endourol urine culture, and nadir creatinine. 2013;27:1405–10. [9] Kukreja R, Desai M, Patel SH, Desai MR. Nephrolithiasis Striking inequalities and glaring gaps in health persist associated with renal insufficiency: factors predicting outcome. J in the 21st century both within and between countries. It Endourol 2003;17:875–9. is important to educate health workers at primary and [10] Macedo E, Bouchard J, Mehta RL. Renal recovery following secondary level hospitals on the importance of early acute kidney injury. Curr Opin Crit Care 2008;14:660–5. diagnosis and urgent referral to tertiary care for emer- [11] Preminger GM, Tiselius H-G, Assimos DG, Alken P, Buck AC, Gallucci M, et al. 2007 Guideline for the management of ureteral gency decompression of the collecting system. calculi. Eur Urol 2007;52:1610–31. Limitations of the present study include the small [12] St. Lezin M, Hofmann R, Stoller ML. Pyonephrosis: diagnosis sample size and the retrospective nature of the study. and treatment. Br J Urol 1992;70:360–3. The findings of the present study give direction for [13] Goldsmith ZG, Oredein-McCoy O, Gerber L, Ban˜ ez LL, Sopko future research. Prospective studies are required to vali- MJ, Miller MJ, et al. Emergent ureteric stent vs percutaneous nephrostomy for obstructive urolithiasis with sepsis: patterns of date this predictive scoring. use and outcomes from a 15-year experience. BJU Int 2013;112:122–8. Conclusions [14] Pearle MS, Pierce HL, Miller GL, Summa JA, Mutz JM, Petty BA, et al. Optimal method of urgent decompression of the collecting system for obstruction and infection due to ureteral Renal recovery in bilateral obstructive urolithiasis with calculi. J Urol 1998;160:1260–4. renal failure is facilitated by timely urological interven- [15] Marien T, Miller NL. Treatment of the infected stone. Urol Clin tion. A symptom duration of 625 days made renal North Am 2015;42:459–72. recovery 22-times more likely. [16] Shokeir AA, Provoost AP, Nijman RJ. Recoverability of renal function after relief of chronic partial upper urinary tract obstruction. BJU Int 1999;83:11–7. Conflicts of interest [17] Lian˜ o F, Felipe C, Tenorio M-T, Rivera M, Abraira V, Sa´ ez-de- Urturi J-M, et al. Long-term outcome of acute tubular necrosis: a None. contribution to its natural history. Kidney Int 2007;71:679–86. [18] Worcester EM, Parks JH, Evan AP, Coe FL. Renal function in Appendix A. Supplementary data patients with nephrolithiasis. J Urol 2006;176:600–3. [19] Worcester E, Parks JH, Josephson MA, Thisted RA, Coe FL. Causes and consequences of kidney loss in patients with Supplementary data associated with this article can be nephrolithiasis. Kidney Int 2003;64:2204–13. found, in the online version, at http://dx.doi.org/10. [20] Saucier NA, Sinha MK, Liang KV, Krambeck AE, Weaver AL, 1016/j.aju.2016.08.001. Bergstralh EJ, et al. Risk factors for CKD in persons with kidney stones: a case-control study in Olmsted County, Minnesota. Am J Kidney Dis 2010;55:61–8. References [1] Trinchieri A. Epidemiology of urolithiasis. Arch Ital Urol Androl 1996;68:203–49. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Arab Journal of Urology Taylor & Francis

Predictors of renal recovery in renal failure secondary to bilateral obstructive urolithiasis

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AbstractObjectives To identify factors predicting renal recovery in patients presenting with renal failure secondary to bilateral obstructing urolithiasis.Patients and methods Data from electronic records of consecutive adult patients presenting with bilateral obstructing urolithiasis between January 2007 and April 2011 were retrieved. Ultrasonography of the abdomen, and kidney, ureter, bladder (KUB study) X-ray or abdominal non-contrast computed tomography confirmed the diagnosis....
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Abstract

Arab Journal of Urology (2016) 14, 269–274 Arab Journal of Urology (Official Journal of the Arab Association of Urology) www.sciencedirect.com STONES/ENDOUROLOGY ORIGINAL ARTICLE Predictors of renal recovery in renal failure secondary to bilateral obstructive urolithiasis a, a Muthukrishna P. Rajadoss , Chandrasingh Jeyachandra Berry , b c c Grace J. Rebekah , Vinu Moses , Shyamkumar N. Keshava , d a a a Kuruthukulangara S. Jacob , Santosh Kumar , Nitin Kekre , Antony Devasia Department of Urology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India Department of Biostatistics, Christian Medical College and Hospital, Vellore, Tamil Nadu, India Department of Radiology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India Department of Psychiatry, Christian Medical College and Hospital, Vellore, Tamil Nadu, India Received 24 June 2016, Received in revised form 24 July 2016, Accepted 10 August 2016 Available online 23 September 2016 KEYWORDS Abstract Objectives: To identify factors predicting renal recovery in patients presenting with renal failure secondary to bilateral obstructing urolithiasis. Calculus anuria; Patients and methods: Data from electronic records of consecutive adult patients Obstructive presenting with bilateral obstructing urolithiasis between January 2007 and April urolithiasis; 2011 were retrieved. Ultrasonography of the abdomen, and kidney, ureter, bladder Renal failure (KUB study) X-ray or abdominal non-contrast computed tomography confirmed the diagnosis. Interventional radiologists placed bilateral nephrostomies. Definitive ABBREVIATIONS intervention was planned after reaching nadir creatinine. Renal recovery was defined AUC, area under the as nadir creatinine of 62 mg/dL. ROC curve; Results: In all, 53 patients were assessed, 50 (94.3%) were male, and 18 (33.9%) CKD, chronic kidney were aged 640 years. Renal recovery was achieved in 20 patients (37.7%). A symp- disease; tom duration of 625 days (P < 0.01), absence of hypertension (P = 0.018), maxi- HR, hazard ratio; mum renal parenchymal thickness of >16.5 mm (P = 0.001), and haemoglobin KUB, kidney, ureter, >9.85 g/dL (P < 0.01) were significant on unadjusted analysis. Symptom duration Corresponding author at: Department of Urology, Christian Medical College and Hospital, Ida Scudder Road, Vellore, Tamil Nadu 632004, India. Fax: +91 (0)416 2232035. E-mail addresses: rajadoss@gmail.com, rajadoss@icloud.com (M.P. Rajadoss). Peer review under responsibility of Arab Association of Urology. Production and hosting by Elsevier http://dx.doi.org/10.1016/j.aju.2016.08.001 2090-598X  2016 Production and hosting by Elsevier B.V. on behalf of Arab Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 270 Rajadoss et al. bladder; of 625 days alone remained significant after adjusted analysis. Symptom duration of PCN, percutaneous 625 days (hazard ratio (HR) 13.83, 95% confidence interval (CI) 4.52–42.26; nephrostomy; P < 0.01), parenchymal thickness of P16.5 mm (HR 5.91, 95% CI 1.94–17.99; ROC, receiver operat- P = 0.002), and absence of hypertension (HR 9.99, CI 95% 1.32–75.37; ing characteristic; P = 0.026) were significantly related to time to nadir creatinine. Symptom duration US, ultrasonography of 625 days (HR 17.44, 95% CI 2.48–122.79; P = 0.004) alone remained significant after adjusted analysis. A symptom duration of 625 days (P = 0.007) was 22-times more likely to indicate renal recovery. Conclusions: Shorter symptom duration (625 days) is predictive of renal recovery in renal failure secondary to bilateral obstructive urolithiasis. 2016 Production and hosting by Elsevier B.V. on behalf of Arab Association of Urology. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). Introduction was retrieved from January 2007 to April 2011. Consecutive adult patients presenting with bilateral obstructing urolithiasis were included in the analysis. Renal failure secondary to bilateral obstructive urolithi- Institutional Review Board clearance was obtained. asis has variable clinical outcomes, which are often The clinical presentation comprised decreased urine dependent on the timing and nature of surgical interven- output associated with flank pain, vomiting, fever, or tion. The prevalence rate for urinary stones ranges from pedal oedema. 1% to 20% and the incidence of hospitalisation for cal- Ultrasonography (US) of the abdomen with kidney, culus disease ranges from 0.03% to 0.1% [1]. The esti- ureter, bladder (KUB study) X-ray or non-contrast mated lifetime risk for urolithiasis is 11% in men and CT scan was used to confirm the diagnosis. The inter- 7% in women with recurrence rates for renal stones ventional radiologists placed bilateral PCNs under US reported as 14%, 35%, 52% at 1, 5 and 10 years, respec- guidance; fluoroscopy was used to confirm the location. tively [2]. The incidence of bilateral calculus disease var- Local anaesthesia and sedation were used to perform the ies between 6% and 20% amongst those presenting with procedure under aseptic conditions. Broad-spectrum urolithiasis [3]. Ureterolithiasis is the most common antibiotics were administered, which was later modified cause of obstructive uropathy, presenting with urosepsis based on the urine culture report. [4]. Obstructing urinary calculus with urosepsis is an Patients who presented with severe metabolic acido- emergency and surgical decompression in the form of sis, persistent hyperkalemia, or fluid overload under- percutaneous nephrostomy (PCN) or ureteric stenting went emergency haemodialysis before PCN placement. has been shown to reduce mortality from 19.2% to A urine sample obtained at initial puncture was sent 8.8% [5]. for culture. Patients were admitted for at least Obstructive uropathy accounts for 10% of commu- 48–72 h, to monitor post-obstructive diuresis, and cor- nity acquired acute kidney injury [6] and urolithiasis is rect fluid and electrolyte imbalance. Serum electrolytes responsible for 10–20% of obstructive uropathy. and renal function tests were monitored on a regular Delay in relieving ureteric obstruction has been shown basis. Maximum renal parenchymal thickness was noted to worsen renal function and hypertension [7]. There on US. Maximum parenchymal thickness refers to the are published studies on predictors of renal recovery parenchymal thickness on the healthier kidney. The time in the subset of patients with renal insufficiency under- taken to reach nadir creatinine was documented. Nadir going treatment for nephrolithiasis and in the sub- creatinine was defined as the lowest serum creatinine group of patients with bilateral obstructive recorded during the recovery period. Patients were edu- urolithiasis and chronic kidney disease (CKD) [8,9]. cated on the importance of PCN care, close medical There is a need for studies, which look at factors pre- supervision until nadir creatinine and definitive manage- dicting renal recovery as well as investigate the pattern ment of obstructing urolithiasis. of renal recovery. Thus in the present study, we inves- The variables studied included age, gender, duration tigated the factors associated with renal recovery in of presenting symptoms, stone location and number bilateral obstructive urolithiasis and the pattern of and size, infection, maximum renal parenchymal renal recovery. thickness, time to nadir creatinine, and presence of co-morbid factors. Renal recovery was defined as nadir Patients and methods creatinine of 62 mg/dL. Several studies in the past have defined renal recovery as serum creatinine of <2 mg/dL Electronic medical records at the Department of or within 20% of the baseline value, partial renal Urology, Christian Medical College, Vellore, India, Renal recovery in calculus anuria 271 Table 1 Social demographic characteristics and clinical features at presentation. Variable N (%) Median (IQR) Age at presentation, years 48 (18–69) Sex – male 50 (94.3) Duration of symptoms, days 45 (1–730) Haemoglobin, g/dL 9.4 (5.1–15.3) Symptoms at presentation Flank pain 18 (33.9) Vomiting 13 (24.5) Fever 8 (15.1) Fatigue 5 (9.4) Gross haematuria 4 (7.5) Pedal oedema 4 (7.5) Calculuria 2 (3.8) Co-morbid illness Hypertension 14 (26.4) Diabetes mellitus 5 (9.4) Hyperuricaemia 5 (9.4) Stone location Bilateral ureteric 26 (49.1) Ureteric + renal pelvis 17 (32.1) Bilateral renal pelvis 10 (18.8) Stone number and size, mm Pelvis 28 25 (6–68) Staghorn 4 49 (46–56) Upper ureter 42 12 (5–28) Mid ureter 10 8 (6–20) Lower ureter 21 10 (5–19) Creatinine at presentation, mg/dL 5.7 (2.0–24.7) Serum creatinine after PCN, mg/dL 2.5 (1.0–7.5) Renal recovery, creatinine 62 mg/dL 20 (37.7) Poor recovery, creatinine >2 mg/dL 33 (62.3) IQR, interquartile range. recovery as >20% from baseline value, and dialysis model to assess the hazard ratios (HRs) for risk factors dependence as no recovery [10]. for time to nadir creatinine. The statistical software SPSS (version 16.0 for Windows) was used to analyse Statistical analysis the data. The mean and standard deviation (SD) were used to Results describe continuous variables, frequency, and percent- ages to depict categorical data. The variables were In all, 53 patients were evaluated; their social demo- examined for the normality of their distribution using graphics and clinical features at presentation are Kolmogorov–Smirnov and Shapiro–Wilk tests and we described in Table 1. Most of the patients were documented median and interquartile range values. middle-aged men, with bilateral ureteric calculi and 20 The Student’s t-test and chi-squared test were used to (37.7%) patients had renal recovery. Five patients assess statistical significance for continuous and categor- underwent a PCN change for blocked PCNs; two of ical variables, respectively. Receiver operating charac- them had good renal recovery. Three patients were trea- teristic (ROC) curves were used to obtain optimal ted for febrile UTI; one patient had good renal recovery. threshold duration of illness, maximum renal parenchy- Two patients required long-term renal replacement ther- mal thickness, and time to nadir creatinine for predict- apy. There was no mortality noted in the study group. A ing renal recovery. small minority of patients had complications; hence, it Multivariable logistic regression analysis was carried was not possible to do a subgroup analysis. One patient, out using factors significant on bivariate analysis, to who presented with a creatinine of 2 mg/dL, reached a assess the statistical significance of factors associated nadir creatinine of 1 mg/dL. with recovery. We estimated the regression coefficients, calculated the odds ratios and 95% CIs. Survival analy- Factors associated with recovery sis was used to assess the time taken to nadir creatinine. Survival curves were obtained using Kaplan–Meier ROC curves were constructed with the outcome variable estimates for the absence of hypertension, symptom being good renal recovery vs poor renal recovery. They duration, and maximum renal parenchymal thickness. were used to obtain optimal thresholds for the variables, Log-rank statistics was used, with 5% level to evaluate duration of symptoms, haemoglobin at presentation, significance. We also used the Cox proportional hazard and maximum renal parenchymal thickness, which were 272 Rajadoss et al. Table 2 Factors predicting renal recovery on unadjusted analysis. Risk factor Good renal recovery, Bad renal recovery, Unadjusted analysis n (%) N =20 n (%) N =34 OR (95%CI) P Symptoms duration 625 days 15 (78.9) 3 (11.1) 30.0 (5.9–153.1) <0.01 Haemoglobin >9.85 g/dL 15 (78.9) 8 (25.0) 11.25 (2.88–43.94) <0.01 Hypertension not present 1 (5.6) 14 (43.8) 13.22 (1.6–111.7) 0.018 Parenchyma thickness >16.5 mm 14 (77.8) 9 (26.5) 9.72 (2.53–37.40) 0.001 P < 0.05. The following variables were not statistically related to good renal recovery: age, presence of diabetes, stone location, pre-PCN creatinine, and positive urine culture. 625 days, >9.85 g/dL, and >16.5 mm, respectively. absence of hypertension (HR 9.99; 95% CI 1.32–75.37; For duration of symptoms of 625 days, the area under P = 0.026) were statistically significantly related to time the ROC curve AUC was 0.881 (95% CI 0.774–0.998; to nadir creatinine on univariate analysis. Only duration P < 0.01). For haemoglobin >9.85 g/dL, the AUC of symptoms (HR 17.44; 95% CI 2.48, 122.79; was 0.825 (95% CI 0.701–0.948; P < 0.01). For maxi- P = 0.004) remained significant in the adjusted analysis mum renal parenchymal thickness >16.5 mm, the using the Cox proportional hazard model (Fig. 1). AUC was 0.828 (95% CI 0.714–0.942; P < 0.01). In the good renal recovery group, 17 of 20 (85%) Table 2 shows the factors associated with renal recovery. patients reached nadir creatinine in 22.5 days. There Good recovery, on bivariate analysis, was associated was no further decline in serum creatinine after 42 days with a symptom duration of 625 days, absence of and 53 days in the good and bad recovery groups, hypertension, parenchymal thickness of >16.5 mm, respectively. and haemoglobin of <9.85 g/dL. The following variables were not significantly related to outcome on Discussion bivariate analysis: age, presence of diabetes, stone loca- tion, pre-PCN creatinine, and positive urine culture. The present study examined factors associated with On multivariable analysis, using logistic regression renal recovery and factors linked to the speed of recov- and including all statistically significant variables on ering renal function. It employed a retrospective cohort bivariate analysis in the model, only symptom duration design and used multivariable statistics to adjust for remained significant suggesting its crucial role in renal confounding. recovery (Table 3). Absence of hypertension, maximum Many of the clinical characteristics of the sample are renal parenchymal thickness, and anaemia lost their sta- similar to those reported in the literature. Male predom- tistical significance after multivariate modelling. inance and delayed help seeking in patients presenting Adjusted analysis showed that a symptom duration of with bilateral obstructing urolithiasis have been reported 625 days made renal recovery 22-times more likely. by similar studies [8]. Whilst many variables were related to good renal outcome on bivariate analysis (e.g. dura- Time taken to nadir creatinine tion of symptoms, absence of hypertension, parenchymal thickness, creatinine at presentation, and time to reach Survival curves were obtained using Kaplan–Meier esti- nadir creatinine), only the duration of symptoms mate for duration of symptoms, absence of hyperten- remained statistically significant after adjusting for sion, and parenchymal thickness and compared using confounders. Similarly, multivariable analysis supported Log-rank statistics. Significance was considered at 5% that the duration of the symptoms also seemed to deter- level. Duration of symptoms (HR 13.83, 95% CI 4.52– mine time to reach nadir creatinine, arguing that early 42.26; P < 0.01), maximum renal parenchymal thick- intervention is the key to a good outcome. ness (HR 5.91, 95% CI 1.94–17.99; P = 0.002), and Table 3 Factors predicting renal recovery on adjusted analysis. Risk factor Good renal recovery, Bad renal recovery, Adjusted analysis n (%) N =20 n (%) N =33 OR (95%CI) P Symptoms duration 625 days 15 (78.9) 3 (11.1) 21.49 (2.27–202.76) 0.007 Haemoglobin >9.85 g/dL 15 (78.9) 8 (25.0) 9.25 (0.83–102.86) 0.07 Hypertension not present 1 (5.6) 14 (43.8) 5.154 (0.26–102.84) 0.283 Parenchyma thickness >16.5 mm 14 (77.8) 9 (26.5) 1.288 (0.12–14.37) 0.837 P < 0.05. Renal recovery in calculus anuria 273 Figure 1 Survival curves were obtained using Kaplan–Meier estimate for duration of symptoms compared using Log-rank statistics. Significance was considered at 5% level. The symptom duration refers to the duration of ering these facts, emergency PCNs were placed by inter- patient’s presenting complaints, which could be flank ventional radiologists in our institution for almost all pain, vomiting, fever, fatigue, pedal oedema, calculuria the patients presenting with obstructive urolithiasis. or decreased urine output. This does not strictly repre- Delaying relief of obstruction of iatrogenic ureteric sent the duration of bilateral obstruction. Two patients obstruction beyond 2 weeks has been shown to cause had intermittent flank pain over a period of 2 years with long-term renal damage and hypertension [7]. There no definite point of worsening of symptoms. The long should be no delay in placing PCNs to expedite renal duration of symptoms could represent the chronic nat- recovery. In patients presenting with obstructive uropa- ure of patient’s condition, with multiple insults to the thy and urosepsis, urological source control in the form renal parenchyma. As expected most patients with of immediate low-level invasive treatment (PCN or ure- symptom duration of >60 days had poor renal teric stenting) should be done in the first 6 h [4]. recovery. The criteria to assess renal recovery can be based on Delayed presentations noted in our present study serum creatinine, creatinine clearance, or urine output. could be attributed to various factors including delayed We decided to use serum creatinine to define renal diagnosis, limited access to healthcare, unavailability of recovery in the present study, based on the availability appropriate medical expertise, time taken for trans- of data. Renal recovery could be defined on the rate of portation to referral centre, and financial constraints. decline in serum creatinine. In the present study, we Emergency decompression of the collecting system aimed to study the factors, which predict renal recovery with PCN or ureteric stenting in obstructing urolithiasis and the pattern of renal recovery. In order to have two with sepsis is the standard of care [11]. Placing a PCN in groups for comparison, we decided to use a nadir crea- an obstructed, infected hydronephrotic kidney has many tinine of 2 mg/dL to define renal recovery based on pre- advantages. In addition to monitoring output, it avoids vious studies [10]. Many factors have been implicated to ureteric instrumentation that can worsen urosepsis or affect renal recovery after relief of obstruction. These result in ureteric perforation [12]. It avoids general include the age of the patient, duration and degree of anaesthesia in a sick patient. The disadvantages of obstruction, presence of pyelolymphatic backflow, com- PCN include a longer procedure, patient discomfort, pliance of collecting system, presence of infection, and and morbidity. Whilst clinical outcome with both ure- concomitant use of nephrotoxic agents, like contrast teric catheterisation and PCN for obstructive urolithia- material [16]. Long-term follow-up of patients with sis has been essentially similar [13], PCN placement complete and partial renal recovery after acute renal has been found to be less expensive [14]. Availability failure showed age and absence of co-morbid illness as of an interventional radiologist and longer waiting time factors associated with better prognosis [17]. In a large for operating room favour PCN placement [15]. Consid- retrospective review of patients with renal insufficiency 274 Rajadoss et al. [2] Uribarri J, Oh MS, Carroll HJ. The first kidney stone. Ann Intern undergoing treatment for nephrolithiasis, higher preop- Med 1989;15:1006–9. erative creatinine, proteinuria of >300 mg/day, renal [3] Winsbury-White HP. Bilateral urinary calculus. Br J Urol cortical atrophy, stone burden of >1500 mm , and 1935;7:235–43. recurrent UTI were associated with renal deterioration [4] Wagenlehner FM, Lichtenstern C, Rolfes C, Mayer K, Uhle F, [9]. 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In our present study, absence of hyperten- [7] Lucarelli G, Ditonno P, Bettocchi C, Grandaliano G, Gesualdo sion was a significant factor on unadjusted analysis. FP, Selvaggi FP, et al. Delayed relief of ureteral obstruction is A prognostic model for renal recovery has been implicated in the long-term development of renal damage and reported in patients with bilateral obstructive urolithia- arterial hypertension in patients with unilateral ureteral injury. J Urol 2013;189:960–5. sis and CKD (nadir creatinine was >1.5 mg/dL within [8] Mishra S, Sinha L, Ganesamoni R, Ganpule A, Sabnis RB, Desai 5 days of urinary diversion) [8]. The following factors M. Renal deterioration index: preoperative prognostic model for were found significant on adjusted analysis: combined renal functional outcome after treatment of bilateral obstructive renal cortical thickness, presence of proteinuria, positive urolithiasis in patients with chronic kidney disease. J Endourol urine culture, and nadir creatinine. 2013;27:1405–10. [9] Kukreja R, Desai M, Patel SH, Desai MR. Nephrolithiasis Striking inequalities and glaring gaps in health persist associated with renal insufficiency: factors predicting outcome. J in the 21st century both within and between countries. It Endourol 2003;17:875–9. is important to educate health workers at primary and [10] Macedo E, Bouchard J, Mehta RL. Renal recovery following secondary level hospitals on the importance of early acute kidney injury. Curr Opin Crit Care 2008;14:660–5. diagnosis and urgent referral to tertiary care for emer- [11] Preminger GM, Tiselius H-G, Assimos DG, Alken P, Buck AC, Gallucci M, et al. 2007 Guideline for the management of ureteral gency decompression of the collecting system. calculi. Eur Urol 2007;52:1610–31. Limitations of the present study include the small [12] St. Lezin M, Hofmann R, Stoller ML. Pyonephrosis: diagnosis sample size and the retrospective nature of the study. and treatment. Br J Urol 1992;70:360–3. The findings of the present study give direction for [13] Goldsmith ZG, Oredein-McCoy O, Gerber L, Ban˜ ez LL, Sopko future research. Prospective studies are required to vali- MJ, Miller MJ, et al. Emergent ureteric stent vs percutaneous nephrostomy for obstructive urolithiasis with sepsis: patterns of date this predictive scoring. use and outcomes from a 15-year experience. BJU Int 2013;112:122–8. Conclusions [14] Pearle MS, Pierce HL, Miller GL, Summa JA, Mutz JM, Petty BA, et al. Optimal method of urgent decompression of the collecting system for obstruction and infection due to ureteral Renal recovery in bilateral obstructive urolithiasis with calculi. J Urol 1998;160:1260–4. renal failure is facilitated by timely urological interven- [15] Marien T, Miller NL. Treatment of the infected stone. Urol Clin tion. A symptom duration of 625 days made renal North Am 2015;42:459–72. recovery 22-times more likely. [16] Shokeir AA, Provoost AP, Nijman RJ. Recoverability of renal function after relief of chronic partial upper urinary tract obstruction. BJU Int 1999;83:11–7. Conflicts of interest [17] Lian˜ o F, Felipe C, Tenorio M-T, Rivera M, Abraira V, Sa´ ez-de- Urturi J-M, et al. Long-term outcome of acute tubular necrosis: a None. contribution to its natural history. Kidney Int 2007;71:679–86. [18] Worcester EM, Parks JH, Evan AP, Coe FL. Renal function in Appendix A. Supplementary data patients with nephrolithiasis. J Urol 2006;176:600–3. [19] Worcester E, Parks JH, Josephson MA, Thisted RA, Coe FL. Causes and consequences of kidney loss in patients with Supplementary data associated with this article can be nephrolithiasis. Kidney Int 2003;64:2204–13. found, in the online version, at http://dx.doi.org/10. [20] Saucier NA, Sinha MK, Liang KV, Krambeck AE, Weaver AL, 1016/j.aju.2016.08.001. Bergstralh EJ, et al. Risk factors for CKD in persons with kidney stones: a case-control study in Olmsted County, Minnesota. Am J Kidney Dis 2010;55:61–8. References [1] Trinchieri A. Epidemiology of urolithiasis. Arch Ital Urol Androl 1996;68:203–49.

Journal

Arab Journal of UrologyTaylor & Francis

Published: Dec 1, 2016

Keywords: AUC; area under the ROC curve; CKD; chronic kidney disease; HR; hazard ratio; KUB; kidney, ureter, bladder; PCN; percutaneous nephrostomy; ROC; receiver operating characteristic; US; ultrasonography; Calculus anuria; Obstructive urolithiasis; Renal failure

References