Natural History of Stones

63
Natural History of Stones

Johann P. Ingimarsson¹ & Amy E. Krambeck²

¹ Maine Medical Center and Tufts School of Medicine, Division of Urology, Portland, ME, USA

² Department of Urology, Indiana University, Indianapolis, IN, USA

Introduction

Technologic advances in the surgical and medical therapy of urinary stone disease over the last three decades have allowed urologists to offer numerous treatment options for symptomatic and asymptomatic upper tract urinary stones. As with any disease, one of the options to be entertained is that of active surveillance/observation for asymptomatic stone disease. Observation is a reasonable approach and an often desired treatment option by the patient to limit costly and potentially painful interventions. However, before choosing observation physician and patients alike must be aware of the potential ramifications of leaving upper tract stones untreated in a variety of different clinical scenarios. In order to assist the urologist in best advising their patient on the risks and benefits of observation, this chapter discusses the natural history of urinary stones, both naturally occurring stones and the residual fragments present after prior treatment.

Natural history of asymptomatic renal stones

The worldwide increase in the incidence and prevalence of stone disease has been attributed, in part, to the incidental detection of asymptomatic calculi secondary to escalating utilization of three‐dimensional radiographic imaging [1, 2]. For example, an Icelandic population study found the annual incidence of stones among the population increased significantly from 108 to 138 per 100 000 over a 5 year period. However, the increase entirely was due to an increase in incidental stones detected at the time of imaging for a concurrent illness, from 7 to 23 per 100 000 with no significant increase in symptomatic stones [2].

Other observational studies have demonstrated a nearly 10% incidence of asymptomatic stones in the general population and thus some insights into the prevalence of asymptomatic renal stones can be obtained from these screening studies. In a series of 5000 patients undergoing screening computed tomography (CT) colonography urinary stones were found in 7.8% of patients, with a mean size of 3 mm and an average of two stones per patient [1]. Similarly, in a series of 2000 CT scans of kidney donors 9.7% harbored asymptomatic stones [3]. Although not the best imaging study for stone evaluation, a prospective renal ultrasound screening trial of 201 patients in Pakistan without a known genitourinary disease found a 3% rate of asymptomatic renal stones [4].

Once the incidental diagnosis of an asymptomatic stone is made, patients will require counseling regarding the implications and clinical relevance. At least ten studies have reported the outcomes of observing asymptomatic renal stones [1, 5–13] (see Table 63.1). These studies vary in population size and demographics, as well as stone location and number. Follow‐up periods for the studies ranged from 1.6 to 10.0 years (median 3.4 years), but collectively they observed the outcome of more than 1800 asymptomatic renal stones, providing significant insight into the natural history of asymptomatic upper tract urinary stones.

Table 63.1 Growth of asymptomatic renal stones treated with observation therapy.

Study	n	Portion of stones that grew (%)	Average growth among growing stones (mm/year)	Spontaneous passage (%)	Symptomatic stone events (%)	Surgical intervention (%)	Follow‐up (years)
Hübner and Popaczy [5]	62	45	–	16	51	40	7.4
Glowacki et al. [6]	107	–	–	15	32	17	2.6
Keely et al. [7]	288	–	–	17	21	10	2.2
Burgher et al. [8]	300	–	–	–	45	26	3.3
Inci et al. [9]	24	33	1.7	13	11	11	4.3
Boyce et al. [1]	395	–	–	–	21	–	10.0
Yuruk et al. [10]	94	–	–	3	19	19	1.6
Koh et al. [11]	50	46	0.7	20	24	7	3.8
Kang et al. [12]	347	–	–	29	54	5	2.6
Dropkin et al. [13]	160	21	–	8	28	17	3.4

Interval growth determined by follow‐up imaging was reported in four studies (see Table 63.1). Hübner and Popaczy looked at 62 patients in 1990, with a mean follow‐up of 7.4 years. Interval stone growth was seen in 28 (45%) patients and eight (13%) developed into staghorn stones [5]. Inci and colleagues followed 27 renal units with 2–12 mm stones every 2 years with a CT scan and found that 30% of stones grew by a mean of 4.4 mm (98% increase in size) at 2 years. Furthermore, 33% had grown by a mean of 7.2 mm (132% increase in size) at last follow‐up (mean 4.3 years) [9]. In contrast, a study by Koh and colleagues found that 46% of stones grew, but only by 2.8 mm over 3.8 years [11]. Dropkin and colleagues reported 21% of stones grew by more than 50% of their initial size in 2 years [13]. Thus, the studies demonstrate varying degrees of stone growth over time, with some demonstrating significant stone size increases. When looking at risk factors for stone growth, two studies found no significant association between initial stone size or location and stone growth [9, 11], whereas the third found stones larger than 15 mm to grow at a slower rate than smaller stones [8]. In summation 21–46% of stones are found to grow on repeat observation. Average growth rates range from 0 to 2 mm per year [9].

In the patient with asymptomatic renal calculi undergoing observation, subsequent development of renal colic, flank pain, or other symptoms prompting further medical intervention has been recognized and is of significant concern. In 10 studies, the rate of such symptomatic stone events was 11–54% (follow‐up range 1.6–10.0 years) [1, 5–13] with a cumulative event rate of 33% (see Table 63.1). Glowacki et al. estimated the risk of a symptomatic stone episode or need for intervention to be approximately 10% per year, culminating in 49% of patients having a stone event 5 years after their initial diagnosis of an asymptomatic renal calculi [6]. Spontaneous stone passage rates were recorded in eight studies and ranged from 3 to 29% (median 16%, cumulative rate 18%) [5–7, 9–12]. Surgical intervention rates were 5–40% between studies (median 17%, cumulative rate 15%) [1, 5–7, 9–13]. Specifically, the study by Burgher et al. found that 25% underwent surgery at 5 years and 50% at 7 years [8].

The observed differences in reported rates of spontaneous passage versus surgical intervention (e.g. from 3% passage and 19% intervention [10] to 29% passage and 5% intervention [12]), are in part due to differences in patient population such as age, gender, and stone size. Therefore, some work has gone into identifying risk factors of disease progression in asymptomatic renal stones. Studies focusing on risk of symptomatic stone events in patients with incidentally detected renal stones are summarized in Table 63.2.

Table 63.2 Summation of risk factors for clinical progression of asymptomatic stones.

Risk factor	Stone growth	Spontaneous passage	Symptomatic stone event	Surgical intervention
Male gender	–	–	↑	–
Advanced age	–	↓	–	–
Larger stone size	↑	↓	↑	–/↑
Upper pole/interpolar location	–	↑	↑	–

Demographic factors

Kang et al. looked at demographic factors affecting subsequent symptomatic stone events in patients with asymptomatic stones. Age, stone history, stone location (laterality and calyceal location), multiplicity, familial history, and body mass index were not found to be significant risk factors; however, men were more likely to have symptomatic stone events then women (hazard ratio 1.52). Furthermore, younger patients were more likely to spontaneously pass stones than older patients [12].

Size

Stone size appears to be a significant factor for disease progression. Burgher et al. found that 100% of stones over 15 mm at time of detection would grow (71%), cause pain (57%), or necessitate surgery (29%). They also found that stones greater than or equal to 4 mm were 26% more likely to fail observation than smaller stones [8]. Another study found that stones measuring 5 mm or less were significantly more likely to spontaneously pass compared to stones that were larger in size (28 vs. 4%) [11, 12]. However, the authors found no association between stone size and need for intervention [11].

Location

Prior studies have failed to identify any significant association between stone location and stone symptoms, spontaneous passage, or need for intervention. However, a more recent study by Dropkin et al. reported that upper pole and interpolar renal stones were more likely than lower pole stones to become symptomatic (40.6 vs. 24.3%) and more likely to pass spontaneously (14.5 vs. 2.9%) [13].

Observation versus treatment

Raman and Pearle conducted a meta‐analysis seeking optimum management of lower pole calculi. Their study revealed that patients with lower pole stones larger than 2 cm treated with percutaneous nephrolithotomy experienced less morbidity than those treated with other modalities. However, consistent with other previous studies, they also concluded that lower pole stones less than 1 cm may be observed with equivalent morbidity outcomes as shock‐wave lithotripsy (SWL) and ureteroscopy with laser lithotripsy. The authors also noted observation to have the least cost and surgical risk of the available management strategies [14].

It should be noted that while the vast majority of interventions are performed for symptomatic events, not all events were symptomatic. In one study 2% of patients with asymptomatic renal calculi treated with observation developed silent obstruction and hydronephrosis identified on surveillance imaging leading to intervention [13]. Such findings, although rare, support the role for continued imaging observation for patients with asymptomatic renal calculi treated with conservative management. At a minimum, periodic renal ultrasound will provide information on the presence of hydronephrosis with minimal risk and no radiation exposure to the patient.

Although observation is an attractive treatment option for the above‐noted reasons, the American Urological Association (AUA) guidelines on the surgical management of stone disease state that there are certain settings for which observation of asymptomatic renal calculi should not be considered. These settings include: cases of associated infection, vocational reasons in which an acute stone event would be detrimental (such as airline pilots, military), and poor access to contemporary medical care [15]. In such clinical scenarios consideration should be given to active surgical intervention to remove the stone.

Natural history of staghorn calculi

A staghorn calculus is a term used for stones that occupy all or most of the renal collecting system in a branching fashion. These large branching stones are relatively rare, accounting for 1% of all symptomatic first‐time stone events [16]. Staghorns most often involve the renal pelvis and extend into the infundibula and calyces [16]. Branched stones that occupy only a part of the collecting system are called branched stones or partial staghorns. Unlike the non‐staghorn, nonbranched asymptomatic stones discussed earlier in the chapter these branching stones are often associated with infection and have quite an ominous natural course. If left untreated, a staghorn stone has a high likelihood of resulting in a nonfunctioning kidney, severe systemic infections, malignancy, or even patient death [15, 17–19].

Compelling observational data exist from before the current era of endourology. A study from 1976 looked at 60 staghorn patients treated with observation alone. The overall mortality rate in these staghorn calculi patients treated with observation was 28%, of which nine (15%) patients died of renal failure, four (7%) developed renal pelvis carcinoma, and 16 (27%) life‐threatening pyonephrosis [17]. Another study from the same era found that nine of 30 (30%) patients treated conservatively for a staghorn calculus died of renal failure or urosepsis [18]. In a pathology‐focused study, examination of kidneys removed due to staghorn stones found that 49% demonstrated significant renal parenchyma pathology. The findings included pyonephrosis (20%), xanthogranulomatous pyelonephritis (8%), severe or end‐stage pyelonephritis (13%), end‐stage hydronephrosis (7%), and perinephric abscesses (5%) [19]. A more recent study from the early 1990s of patients with conservatively treated staghorn stones found that 36% developed chronic renal failure and 11% died from uremia [20]. Furthermore, in a study from 1995, the early era of endourology, found none of 77 patients treated for staghorn stone and rendered stone‐free died of renal disease at a mean follow‐up of 7.7 years, compared to one of 35 (3%) with residual stone fragments after treatment and two of three (67%) of those treated conservatively [21].

In light of this unequivocal evidence against observation of staghorn calculi, published guidelines have since strongly advised for the complete surgical removal of staghorn stones in all patients fit to undergo surgery [15, 22].

A caveat in discussing the natural history of staghorn stones is that the most extensive data come from an era where the majority (59–68%) of staghorn stones were infection‐stone compositions such as struvite. More contemporary series indicate that metabolic stones now account for 56% of staghorn stones, with calcium phosphate accounting for the majority [19, 23–25]. The natural history of metabolic stones may potentially be different from that of infection stones, and thus the natural history in the current era could differ from decades ago.

A 2015 study looked prospectively at 22 minimally symptomatic or asymptomatic staghorn stone patients who were treated conservatively, either because they were unfit or unwilling to undergo surgery. Among the 17 patients who had a unilateral staghorn stone, recurrent urinary tract infections occurred in seven (41%) patients, one (6%) required dialysis, and none died of renal disease or renal‐related conditions at a median follow‐up of 6 years. Such observed outcomes are notably better than in prior series. However, among five patients with bilateral staghorn stones, 80% had recurrent urinary tract infections, 20% required dialysis, and 40% died of renal disease [26]. The contemporary results can be compared to a recent series reporting long‐term outcomes of percutaneous nephrolithotomy for staghorn stones in patients with reduced renal function at presentation. The authors found that 20% of patients had a decline in renal function postoperatively, but only three of 262 (1.8%) of patients developed end‐stage renal failure at 3 years of follow‐up [27]. Despite the more recent promising results of observation for staghorn calculi, active treatment is still recommended by the AUA and Endourology Society if the patient is healthy enough for surgical intervention [15]. The guideline recommendations are based on the fact that minimally invasive treatment of staghorn calculi with percutaneous nephrolithotomy is highly successful with minimal morbidity in most scenarios.

Natural history of asymptomatic ureteral stones

While the renal pelvis and calices are capacious and can frequently accommodate stones without causing significant obstruction, the ureter is smaller in diameter and a stone in this location would be more likely to result in symptoms and/or obstruction. In fact, only 1.1–5.3% of all treated ureteral stones are silent [28, 29]. As previously mentioned, silent ureteral stones have been subsequently found in 2% of patient undergoing surveillance imaging who were on observation for asymptomatic renal stones. The population incidence of silent ureteral stones among subjects without a history of known stone disease is low. Among 5047 patient undergoing screening CT colonography only six (0.1%) were found to have an incidental silent ureteral stone [1]. Given their rare presentation, very limited data exist regarding spontaneous passage rates among asymptomatic ureteral stones with one study reporting one of 40 (2.5%) patients passing their stone before a scheduled surgery date [28]. Wimpissinger and colleagues [30] prospectively looked at 14 asymptomatic ureteral stones. They found 11 (76%) kidneys to be associated with hydronephrosis on imaging and on MAG3 scintigraphy and of the 11 kidneys with hydronephrosis, five (36%) were unobstructed, seven (50%) were obstructed, and two (14%) had no excretory function. There was a positive correlation between stone size and likelihood of obstruction, with larger stones more likely to result in complete obstruction or no excretory function [30]. Based on this limited data, most physicians should consider only a short trial of passage, 6 weeks or less per AUA and Endourology Society guidelines [15], with scheduled follow‐up imaging to assess for definitive stone passage if observation is chosen for the asymptomatic ureteral calculi.