Renal Colic in Pregnancy: Lithiasis or Physiological Hydronephrosis?

Endourology and Stones Renal Colic in Pregnancy: Lithiasis or Physiological Hydronephrosis? Matei Andreoiu and Ross MacMahon OBJECTIVES

METHODS

RESULTS

CONCLUSIONS

To assess the reliability and accuracy of diagnostic investigations in differentiating urinary calculi from physiological hydronephrosis as the cause of renal colic. The appropriateness and efficacy of the treatments used were was also examined. A retrospective review of 300 consecutive patients presenting to 2 local hospitals was carried out. Descriptive and correlational data on clinical presentation, diagnostic imaging, and interventions undertaken were analyzed. A total of 262 patients were included in the final analysis. Most clinical or laboratory features were unhelpful in predicting the presence of a stone. Left-sided colic was more likely to indicate presence of stone (64.9% vs 46.6%, P ⫽ .003). The accuracy of ultrasound findings in predicting presence of stone improved (from 56.2% to 71.9%) when features of obstruction, such as ureteric jet absence and an elevated resistive index (RI), were included in the assessment. Spontaneous resolution occurred in a smaller proportion of patients with stone (63% vs 85%, P ⬍.001). The need for intervention was more prevalent in patients with stones (29.2% vs 5.9%, P ⬍.001). Stent insertion was the most common intervention and was usually completed successfully (95.5%). Ureteroscopy was safe and resulted in stone retrieval 88% of the time. Most clinical signs and symptoms are unhelpful in determining the cause of colic symptoms. Left-sided colic is more likely to represent the presence of a stone. An enhanced ultrasound examination is a reasonably accurate initial study. The standard endoscopic interventions are more likely to be used in colic cases because of actual calculi, and are safe and effective throughout pregnancy. UROLOGY 74: 757–761, 2009. © 2009 Elsevier Inc.

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enal colic is an infrequent but potentially troublesome development during pregnancy that can lead to hospitalization, invasive investigations and treatment, and adverse effects on both mother and fetus. Although a standard management algorithm for documented nephrolithiasis has emerged over the past decade, there remains some uncertainty on how to best differentiate nephrolithiasis from physiological hydronephrosis of pregnancy. Previous studies with smaller numbers of patients have generally looked at the management of colic cases already diagnosed as due to lithiasis. The purpose of our retrospective review was to examine the etiology of renal colic in pregnancy and attempt to determine the reliability of presenting clinical and laboratory features. The relative accuracy of ultrasound and intravenous urography in making the appropriate diag-

From the Department of Urology, Indiana University, Indianapolis, Indiana; and Department of Urology, St Boniface Hospital, Winnipeg, Manitoba, Canada Reprint Requests: Matei Andreoiu, M.D., Department of Urology, Indiana University, 535 N Barnhill Dr, Suite 420 Indianapolis, IN 46202. E-mail: mateiandreoiu@ hotmail.com Submitted: January 12, 2009, accepted (with revisions): March 25, 2009

© 2009 Elsevier Inc. All Rights Reserved

nosis, as well as the use of various interventional procedures was also assessed.

MATERIAL AND METHODS A retrospective chart review study of 300 consecutive patients presenting with renal colic during pregnancy was carried out. The study period was between June 1993 and June 2005. Adequate hospital and follow-up documentation existed for 262 of these patients. Follow-up postdelivery averaged to 2 months and ranged from 2-6 months. A case was classified as a “documented stone” case if a calculus was identified through imaging, intervention, or spontaneous passage. Cases with demonstrable hydronephrosis and no evidence of a stone were classified as having colic attributable to physiological hydronephrosis consistent with pregnancy. Microscopic hematuria was defined as ⬎3 RBCs/HPF (red blood cells/high power field) and pyuria was diagnosed when ⬎5 WBCs/HPF were seen. Resistive index (RI) was defined at the peak diastolic velocity subtracted from the peak systolic velocity and then divided by the latter. When applied clinically, abnormally elevated RI was set at ⱖ0.70 and a significant ⌬RI (inter-renal difference in RI) as ⱖ0.08. Correlational data were obtained using Pearson correlation coefficient calculations and ␹2 calculations were used to com0090-4295/09/$34.00 doi:10.1016/j.urology.2009.03.054

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Table 1. Prevalence of clinical and laboratory diagnostic features in stone vs nonstone colic cases Sign/Symptom Flank pain Abdominal pain Fever or chills Gross hematuria Microscopic hematuria Pyuria Urinary tract infection Prior history of nephrolithiasis

Documented Stone N ⫽ 144

No Documented Stone N ⫽ 118

Overall (%) N ⫽ 262

P

139 (96.5) 49 (34.0) 15 (10.4) 13 (9.0) 117 (81.3) 43 (29.9) 28 (19.4) 56 (38.9)

115 (97.5) 51 (43.2) 8 (6.8) 11 (9.3) 73 (61.9) 37 (31.4) 24 (20.3) 20 (16.9)

254 (96.9) 100 (38.2) 23 (8.8) 24 (9.2) 190 (72.5) 80 (30.5) 52 (19.8) 76 (29.0)

NS NS NS NS .0001 NS NS .0001

pare categoric variables with significance at P ⬍.05 (SPSS for Windows Version 11.0).

Table 2. Accuracy of standard ultrasonography and intravenous urogram in stone diagnosis during pregnancy

RESULTS There were 262 cases of pregnant women presenting with renal colic, having adequate records of management and follow-up. A total of 144 (55%) of these cases ultimately had a documented stone identified as the likely cause of the symptoms. Most cases occurred in the second (40.1%) and third (56.9%) trimesters. No significant association was found between the trimester of presentation and stone presence, with 62.5%, 53.3%, and 55% of colic cases based on an actual stone in each trimester, respectively. The multiparas presenting with colic were statistically just as likely to have an underlying stone as the cause as were primigravidas (97/165 cases vs 46/97 cases, respectively). Clinical Signs and Laboratory Parameters When assessing the prevalence of clinical signs and symptoms, such as abdominal pain, fever, pyuria, urinary tract infection, and gross hematuria, flank pain was the most common presenting feature, occurring in 96.5% of all cases (Table 1). Microscopic hematuria (81.3% vs 61.9%, P ⬍.05) and a previous history of nephrolithiasis (38.9% vs 16.9%, P ⬍.05) were the only variables found to be significantly more prevalent in the documented stone group. Left-sided colic was significantly more likely to indicate stone presence, with 72 of 111 (64.9%) cases being diagnosed with a stone as compared with only 67 of 146 (46.6%) right-sided colic cases. A total of 5 patients with documented stones initially presented with diffuse abdominal pain but no flank pain. Imaging A total of 229 (87.4%) patients underwent imaging as part of the work-up for their colic. Ultrasound was performed in 223 cases, intravenous pyelogram (IVP) in 29 cases, and 8 patients had both. Only 30.5% of all imaged cases had a stone actually visualized. Ultrasound visualized a stone in 72 of 128 cases with documented stone (56.2%) as compared with IVP, which outlined a stone in 16 of 18 cases (88.9%, P ⬍.05) (Table 2). However, the sensitivity of ultrasound was markedly improved if additional Doppler sonographic features of obstruction, such 758

Stone Location Calyceal/pelvis Proximal ureter/UPJ Distal ureter/UVJ Total

No. No. Stones Stones Visualized Visualized on on Intravenous Ultrasound (%) Urogram (%) 36 (28.1) 10 (7.8) 26 (20.3) 72 (56.3)

2 (11.1) 1 (5.6) 13 (72.2) 16 (88.9)

UPJ ⫽ ureterovesical junction.

as an elevated resistance index (RI), inter-renal difference in RI (⌬RI), asymmetric absence of the ureteric jet, or hydronephrosis inconsistent with only physiological changes of pregnancy, were used to further classify the ultrasound findings as “abnormal.” An “abnormal” ultrasound reading was found to accurately predict the presence of a stone in 92 of 128 patients with cases (71.9%). Of 15 cases, 14 cases where an elevated RI was noted had a stone ultimately documented (93.3%). The degree of hydronephrosis observed on imaging did not differentiate between the 2 study groups. Of 128, 50 (39%) patients with stone had moderate-to-severe hydronephrosis on imaging as compared with 32 of 95 (33.7%) patients without stone. Management Among patients who had pain resolution addressed in their charts, 72.7% (178/245) became pain-free. Eightyfive percent of patients without stone had resolution of their pain (91/107) in comparison with only 63% of patients in whom a stone was found (87/138) (P ⬍.001). A total of 68.5% of patients with stones passed them spontaneously (91/133). Five patients with stones who became pain-free were lost to follow-up, and stone passage could not be documented. In cases where stone size was determined, 54.5% (12/22) of stones measuring 0-4 mm were passed as compared with 42.4% (14/33) of stones measuring 5-8 mm; and none of the stones (0/8) measuring ⬎8 mm in diameter were passed. When the association between rate of passage and stone location on initial imaging was examined, it was noted that 42.3% of renal pelvis or calyceal stones were passed as compared with 27.3% (3/11) of ureteropelvic junction and/or proxUROLOGY 74 (4), 2009

Table 3. Rates of intervention in stone vs patients without stone presenting with renal colic during pregnancy First Trimester Stone No Stone Stent attempts Stents tolerated Stent changes Ureteroscopy PCN

1 1 0 1 0

0 0 0 0 0

Second Trimester Stone No Stone 12 11 5 (3 patients) 10 2

3 2 2 1 1

Third Trimester Stone No Stone 24 12 3 14 2

4 2 2 0 1

Total 44 28 10 26 6

PCN ⫽ percutaneous nephrostomy.

imal ureteric stones and 44.1% (15/34) of distal ureteric stones. Overall, 49 patients required intervention (Table 3). A significantly higher proportion of patients with stones required surgical treatment, 29.2% (42/144) vs only 5.9% of patients without stone (7/119) (P ⬍.05). The stent insertion was the most common intervention and was successful in a majority of attempts (42/44) in 32 patients. Nearly all (42/44) stent attempts were successfully completed. The largest number of stent attempts occurred in the third trimester (28/44) as compared with the second (15/44) and first trimesters (1/44). The most common indication was pain (37/44), with 6 requiring it for obstructive urosepsis and 1 for anuric acute renal failure (a stone case). Nearly all ureteroscopies performed occurred in patients with stones (25/26). Laser lithotripsy was carried out in 7 cases, pneumatic lithotripsy in 7 cases, and basket manipulation only in 11 cases. Most patients had no stents left in situ after ureteroscopy. Percutaneous nephrostomy was carried out in 5 stone cases and 1 patients without stone and an equal number was undertaken in both the second and third trimesters. Of those requiring intervention, 17 (34.7%) cases had complications. Twelve of 26 stents (46.2%) placed in the third trimester were poorly tolerated as compared with only 2 of 15 (13.3%) placed during the second trimester. The median stent dwelling time was 27 days. Four patients suffered from recurrent urinary tract infections. Ureteroscopy resulted in perforation in 1 case, which was managed successfully with an indwelling stent. Two patients required management of postobstructive diuresis. Eight patients had stent changes performed. One patient without stone whose stent was inserted in the first trimester required 3 stent changes. Three stents, all in patients without stone, had to be urgently replaced, 2 because of poor tolerance and 1 because of migration of the stent. Of the 6 cases where percutaneous nephrostomy placement occurred, 1 patient had displacement of the tube requiring repositioning and in 1 it had to be removed because of pain and hematuria. Overall, 6.5% (17/262) of patients had premature labor, with 7 premature deliveries. Premature labor occurred in 14.3% (7/49) of those cases where intervention took place and in 4.7% (10/213) of cases where no procedure was undertaken (P ⬍.005). There were 2 occurrences of fetal death, both in patients without stone; 1 UROLOGY 74 (4), 2009

involved a stillbirth at 28 weeks of gestation with no clear cause established and the other took place in the setting of severe urosepsis and shock (unrelated to intervention) necessitating transfer to the intensive care unit. There were 15 women with documented stones who received delayed treatment postpartum, all without complications.

COMMENT Of the women presenting with colic, the majority sought attention during the second or third trimesters. Only 8 women were treated during the first 8 weeks of pregnancy. Although there were a greater number of both colic and patients with stone in the third trimester, the trimester of presentation did not significantly alter the proportion of colic cases because of an actual stone. Others have speculated that progressive dilatation of the ureter during pregnancy would allow a greater number of previously asymptomatic renal calculi to migrate downward and cause pain when lodged at the pelvic brim. Our data do not support this notion. Although previous studies have commented on the epidemiologic aspects of the clinical presentation of renal colic in pregnancy, limited data are available on the utility of using clinical signs and symptoms or laboratory parameters to distinguish between colic secondary to a stone vs physiological hydronephrosis or other causes. Our study found a poor predictive value for nearly all such variables studied. Microscopic hematuria was present in only 81.2% of documented patients with stones, which is similar to the rates reported in other studies.1,2 However its specificity was poor. This is consistent with the knowledge that microscopic hematuria can be due to normal changes associated with pregnancy, including vascular dilatation and rupture of renal veins or pyramids, as well as its nearly universal presence in cases of pyelonephritis. Although previous studies have shown a somewhat lower prevalence of previous nephrolithiasis in patients with stones,1,2 in our study those patients with documented stones were more than twice as likely to have had a previous history of nephrolithiasis (38.9%) than their no-stone counterparts (17.4%). Physiological hydronephrosis is more pronounced on the right side because of a dextro-rotating enlarged uterus and a dilated uterine vein compressing the right collecting system.3,4 In contrast, the left ureter is protected by 759

the sigmoid colon. Our study confirms that the incidence of stones is approximately equal on either side.3-6 Accordingly, as confirmed by our study, a majority of patients presented with right-sided colic. As physiological compression tends to be much less common on the left side, one would expect left-sided colic to be more predictive of a stone. In our study, this was confirmed with 64.9% of left-sided colic cases having a stone documented as compared with only 46.6% of patients with right-sided colic (P ⬍.01). The current consensus is that ultrasonography should be the first-line imaging modality given its availability, noninvasiveness, and limited cost. However, its sensitivity has been reported to range anywhere from 38%95%.1,2,6 In our study, ultrasonography visualized a stone in 56.2% of cases as compared with an 88.9% rate with IVP. If the ultrasound interpretation was further modified using features of upper tract obstruction, such as hydroureter extending below the pelvic brim, the asymmetric absence of a ureteric jet, or an elevated resistive index, the accuracy of ultrasound to predict the presence of a stone improved significantly to 71.9%. Shokeir and Abdulmaaboud found that RI measurements had 77% sensitivity and 83% specificity in diagnosing unilateral obstruction by a stone.7,8 Although the number of cases in our study where RI was measured could not be reliably determined, it is striking that the existence of obstructive stones was ultimately confirmed in 14 of 15 studies where RI was specifically noted to be abnormally elevated (93.3%). In the absence of partial or intermittent obstruction, the presence of a unilaterally absent ureteric jet is also helpful in raising suspicion of active stone-related obstruction, with a sensitivity of 100% and a specificity of 91%.9,10 The calculi visualized by ultrasound tended to be mostly located in the renal pelvis, ureteropelvic junction, or distal ureter (86.1%) which was as expected because the middle third is difficult to visualize due to bowel gas and bony structures. Despite its greater accuracy, IVP is used as a second-line study because of the potential risks of contrast allergy and potential teratogenic effects of ionizing radiation. The rate of stone detection using a limited IVP (16/18) was nearly the same as that reported by Stothers and Lee (16/17).1 The MRI was not used largely because of lack of availability for the investigation of renal colic, except in 2 cases where active obstruction was evident, initial ultrasonography was inconclusive, and IVP was medically contra-indicated as a result of renal insufficiency. However, this modality is being increasingly used in the setting of renal colic during pregnancy. It does not expose the patient to any ionizing radiation, and unless the patient is extremely obese or claustrophobic, it provides good anatomic detail in a noninvasive way. The major drawback is the relative difficulty in picking up small stones and its relatively greater expense. 760

A highly accurate imaging option increasingly in use is low-dose computed tomography. Recent evidence highlights a sensitivity and specificity of ⬎98% for the diagnosis of urolithiasis in the setting of colic during pregnancy,11,12 while exposing the patient and fetus to only a third of the radiation dose associated with standard CT. This suggests low-dose computed tomography as an equivalently safe and more accurate alternative to excretory urography if diagnosis after enhanced transvaginal and/or color Doppler ultrasonography remains inconclusive in the setting of a high index of suspicion for urolithiasis. Potential advantages include shorter examination time, avoidance of contrast complications, and an improved ability to detect non–lithiasis-related abnormalities. According to previous studies, a majority of stones will pass spontaneously.1,4,13 Our own study had a somewhat lower rate of 63% that is similar to what was obtained in the studies by Maikranz et al (66%)14 and Parulkar et al (64%).2 The standard approach of hydration, rest, and analgesic control will be successful in most patients. Some controversy exists between those advocating ureteroscopy as a safe and effective method of visualizing and removing a stone during pregnancy and those who feel that it exposes the mother and fetus to an undue risk of complications and fluoroscopic radiation. Ureteroscopic intervention occurred in 26 of our patients, with nearly all procedures appropriately performed in cases with documented stones. Ureteroscopy was shown to be a safe intervention in this setting, with only 1 complication involving ureteric perforation. A published review of the relevant literature reveals that the success rate of ureteroscopy has been reported to range between 69% and 81%.15 In our study, the surgeon was unable to retrieve the stone in only 3 patients with stones, giving our institution a success rate of 88%. Fourteen of the procedures carried out in this study were in the third trimester when the dilated, tortuous ureter should supposedly be difficult to navigate. This was not found to be the case. The advent of new and smaller ureteroscopes should make it even easier to retrieve stones causing colic. Despite some worry about harmful effects of ultrasonic energy on the fetal tissue, no clear evidence exists to support this concern. The holmium laser, in particular, likely has the largest margin for safety.16,17 Despite some concerns existing regarding the need for general anesthesia, nearly all cases with the exception of 2 were carried out either through IV sedation or mostly through the use of spinal anesthesia. In fact, several authors have reported very good success, using sedation or spinal anesthesia.17,18 There were 44 patients requiring the placement of a stent, with unsuccessful attempts in two third-trimester cases. The most common indication was refractory pain. Despite the notion that stent placement would be more difficult in the third trimester because of extreme tortuosity of the ureter,19 nearly all stent attempts undertaken in the last trimester, with the exception of 2, were sucUROLOGY 74 (4), 2009

cessful. In contrast to other studies suggesting that early stent placement leads to increased intolerance over time,20 46.2% of patients with initial stent placement in the third trimester tolerated the stents poorly as compared with only 13.3% of those who had a stent placed during the second trimester. Ultrasonography was carried out every 6-8 weeks to monitor for excessive encrustation. Nearly all stent insertion attempts were carried out with the aid of fluoroscopy and requisite precautions. Ultrasound has increasingly been used to guide stent placement during pregnancy21,22 but was not yet being used in this setting by the institutions in our study. Percutaneous nephrostomy is infrequently used in the setting of nephrolithiasis in pregnancy but may be indicated for the decompression of an obstructed urinary tract in the setting of sepsis and/or for failure of stent insertion. Only 6 patients required this intervention. One case had migration of the nephrostomy tube necessitating readjustment and another case required tube removal because of severe pain and hematuria. There are recognized weaknesses to our study. The well-known limitations on conclusions drawn from a retrospective review certainly apply. Given the absence of a recognized gold-standard diagnostic imaging modality and the possibility of stone passage unknown to the patient in some cases, there is no definite way to verify that all “non-stone” patients, in fact, lacked stones. However, only 11 patients without stone were noted to have uncertain resolution of pain symptoms. Our interpretations can also draw some strength from a good postpartum median follow-up time of 2 months and substantial recorded follow-up on 248 of the 262 patients until resolution of symptoms. The data may not allow for any definitive conclusions but provide strong support for the observed findings.

CONCLUSIONS Although a potentially challenging scenario in pregnancy, an effective approach to the diagnosis and management of renal colic can be implemented. Presenting laboratory values and physical symptoms or signs are generally unhelpful in determining whether a stone is causing the problem. However, left-sided colic is more likely to represent the presence of a stone, with a larger proportion of right-sided hydronephrosis and colic caused by uterine compression. The most appropriate initial investigation is a Doppler ultrasound, with the ability to display associated features of obstruction such as an elevated resistive index and the absence of ureteric jets. In the event of an inconclusive examination, a limited IVP is indicated. Spontaneous resolution of pain will occur in

UROLOGY 74 (4), 2009

most cases overall but in a significantly greater proportion of cases in which stones are not involved. Ureteroscopy and/or ureteric stent placement are safe and effective interventions during all stages of pregnancy. The need for nephrostomy tube urinary diversion is infrequent. References 1. Stothers L, Lee LM. Renal colic in pregnancy. J Urol. 1992;148: 1383-1387. 2. Parulkar BG, Hopkins TB, Wollin MR, et al. Renal colic during pregnancy: a case for conservative treatment. J Urol. 1998;159:365368. 3. Biyani C, Joyce A. Urolithiasis in pregnancy. BJU Int. 2002;89: 811-823. 4. Lewis DF, Robichaux AG, Jaekle RK, et al. Urolithiasis in pregnancy. J Reprod Med. 2003;48:28-32. 5. Swanson SK, Heilman RL, Eversman WG. Urinary tract stones in pregnancy. Surg Clin North Am. 1995;75:123-142. 6. Butler EL, Cox SM, Eberts EG, et al. Symptomatic nephrolithiasis complicating pregnancy. Obstet Gynecol. 2000;96:753-756. 7. Shokeir A, Abdulmaaboud M. Resistive index in renal colic: a prospective study. Br J Urol. 1999;83:378-382. 8. Shokeir A, Mahran M, Abdulmaaboud M. Renal colic in pregnant women: role of renal resistive index. Urology. 2000;55:344-347. 9. Boridy IC, Maklad N, Sandler CM. Suspected urolithiasis in pregnant women: imaging algorithm and literature review. Am J Roentgenol. 1996;167:869-875. 10. Deyoe LA, Cronan JJ, Breslaw BH, et al. New techniques of ultrasound and color Doppler in the prospective evaluation of acute renal obstruction. Do they replace the intravenous urogram? Abdom Imaging. 1995;20:58-63. 11. White WM, Zite NB, Gash J, et al. Low-dose computed tomography for the evaluation of flank pain in the pregnant population. J Endourol. 2007;21:1255-1260. 12. Hamm M, Knopfle E, Wartenberg S, et al. Low dose unenhanced helical computerized tomography for the evaluation of acute flank pain. J Urol. 2002;167:1687-1691. 13. Loughlin KR, Kerr LA. The current management of urolithiasis during pregnancy. Urol Clin North Am. 2002;29:701-704. 14. Maikranz P, Lindheimer M, Coe F. Nephrolithiasis in pregnancy. Baillieres Clin Obstet Gynaecol. 1994;8:375-386. 15. Keating MA, Heney NM, Young HH, et al. Ureteroscopy: the initial experience. J Urol. 1986;135:689-693. 16. Watterson JD, Girvan AR, Beiko DT, et al. Ureteroscopy and holmium:YAG laser lithotripsy: an emerging definitive management strategy for symptomatic ureteral calculi in pregnancy. Urology. 2002;60:383-387. 17. Ulvik NM, Bakke A, Hoisaeter PA. Ureteroscopy in pregnancy. J Urol. 1995;154:1660-1663. 18. Shokeir AA, Mutabagani H. Rigid ureteroscopy in pregnant women. Br J Urol. 1998;81:678-681. 19. Drago JR, Rohner TJ Jr, Chez RA. Management of urinary calculi in pregnancy. Urology. 1982;20:578-581. 20. Denstedt JD, Razvi H. Management of urinary calculi during pregnancy. J Urol. 1992;148:1072-1074. 21. Wolf MC, Hollander JB, Salisz JA, et al. A new technique for ureteral stent placement during pregnancy using endoluminal ultrasound. Surg Gynecol Obstet. 1992;175:575-576. 22. Jarrard DJ, Gerber GS, Lyon ES. Management of acute ureteral obstruction in pregnancy utilizing ultrasound-guided placement of ureteral stents. Urology. 1993;42:263-267.

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