Renal function in patients with urinary stones of varying compositions

Kaohsiung Journal of Medical Sciences (2011) 27, 264e267

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ORIGINAL ARTICLE

Renal function in patients with urinary stones of varying compositions Yii-Her Chou a,b, Ching-Chia Li a, Hsing Hsu b, Wei-Chiao Chang c,d, Chia-Chu Liu a, Wei-Ming Li b, Hung-Lung Ke b, Mei-Hui Lee b, Mu-En Liu c, Shu-Ching Pan b, Hsun-Shuan Wang a,b,* a

Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan b Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan c Graduate Institute of Medical Genetics, Kaohsiung Medical University, Kaohsiung, Taiwan d Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Received 14 October 2010; accepted 22 November 2010 Available online 20 April 2011

KEYWORDS Chronic kidney disease; Renal function; Stone component; Urolithiasis

Abstract Kidney stones are a potential risk factor for chronic kidney disease. The impact of different urinary stone components on renal function is unknown. In this study, we retrospectively reviewed 1,918 medical records of patients with urolithiasis. The renal function was evaluated as estimated glomerular filtration rate. All the stones were analyzed by Fourier transform infrared spectroscopy. The patients were divided into five groups according to the stone components. Statistical analysis was performed with analysis of variance. All the patients with stones had Stage 2e3 chronic kidney disease. The patients with uric acid and struvite stones had significantly lower estimated glomerular filtration rate compared with those having other stone components (p < 0.01). Furthermore, the patients with calciumcontaining stones (calcium oxalate and calcium phosphate) had significantly better renal function than those with non-calcium-containing stones (struvite and uric acid, p < 0.01). Patients with urolithiasis had decreased renal function, and the impact of renal function varied depending on the stone components. We conclude that stone analysis is important in predicting the change in renal function in patients with urolithiasis. Moreover, the patients with noncalcium-containing stones, such as struvite and uric acid stones, should be carefully evaluated and treated to preserve their renal function. Copyright ª 2011, Elsevier Taiwan LLC. All rights reserved.

* Corresponding author. Department of Urology, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 807, Taiwan. E-mail address: [email protected] (H.-S. Wang). 1607-551X/$36 Copyright ª 2011, Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.kjms.2010.11.008

Renal function in patients with urolithiasis

Introduction Kidney stones are a common disease in the general population, its prevalence being 5e10%, with a male predominance and an estimated recurrence rate of 50%. Furthermore, the prevalence of kidney stones has been increasing in the recent decades [1e3]. Previous studies have considered kidney stones as a potential risk factor for chronic kidney disease (CKD), associated with significant morbidity, mortality, and heath care cost [4e6]. To date, the mechanism accounting for this association is not completely understood. There are several components of urinary stones, such as calcium oxalate, calcium phosphate, uric acid, and struvite [7]. The relationships between stone components and the change of renal function are unclear. The purpose of this study was, therefore, to analyze the impact of urinary stones on renal function, according to the different stone components. We observed an association between renal stone components and estimated glomerular filtration rate (eGFR) of the stone formers.

Materials and methods We reviewed the medical records of patients with upper urinary tract stones, hospitalized from February 2004 to March 2009 in the Department of Urology, Kaohsiung Medical University Hospital. All patients had radiological evidence of urinary stones; most of the stones had passed spontaneously, whereas some of them were collected by surgical procedures. The exclusion criteria were as follows: preexisting chronic renal failure, chronic ureteral obstruction in both kidneys or in a solitary kidney, congenital renal anomalies, and autosomal dominant polycystic kidney disease. Clinical data, such as gender, age, and stone components, were collected. Renal function was evaluated with eGFR using the modification of diet in renal disease formula [8,9]. The stone components were analyzed by Fourier transform infrared spectroscopy [10]. All patients were classified into five groups according to the stone components, namely, calcium phosphate, calcium oxalate, calcium oxalate mixed with calcium phosphate, struvite, and uric acid stones. Statistical analysis was performed with Student t test, analysis of variance, and Tukey’s post hoc test. A p value less than 0.05 was defined as statistically significant.

265 Table 1

Clinical characteristics of patients with urolithiasis

Characteristics Gender Male Female Male:female ratio

1,384 (72) 534 (38) 2.59:1

Age (yr), mean (standard deviation)

54.0  13.8

Stone components Calcium-containing stones Calcium phosphate Calcium oxalate Calcium oxalateecalcium phosphate Non-calcium-containing stones Struvite Uric acid

1,736 (90.5) 204 (10.6) 579 (30.2) 953 (49.7) 182 (9.5) 21 (1.1) 161 (8.4)

renal function in relation to stone components, patients with calcium oxalate mixed with calcium phosphate stones showed the highest eGFR: 73.4  22.6 mL/min/1.73 m2; in contrast, patients with uric acid stones had the lowest eGFR: 54.1  17.1 mL/min/1.73 m2. The eGFR values were 67.0  23.7 mL/min/1.73 m2, 70.3  21.5 mL/min/1.73 m2, and 54.9  18.6 mL/min/1.73 m2 in patients with calcium phosphate, calcium oxalate, and struvite stones, respectively. Patients with calcium-containing stones (calcium phosphate and calcium oxalate) had significantly better renal function compared with those with non-calciumcontaining stones (struvite and uric acid, p < 0.01) (Table 2). The renal function was significantly different among the five groups of patients with varying stone compositions (p < 0.01, analysis-of-variance test). Tukey’s post hoc test revealed that the eGFR of struvite stone formers was significantly different from those of calcium oxalate, calcium phosphate, and mixed calcium oxalate/calcium phosphate stone formers. The eGFR of uric acid stone

Table 2 The estimated glomerular filtration rate in relation to stone components Stone components

Results This study included 1,918 patients with upper urinary tract stones. The patients’ average age was 54.0  13.8 years, and the male:female ratio was 2.59:1. With regard to the prevalence of stone composition, there were 1,736 (90.5%) calcium-containing stones, including 953 (49.7%) calcium oxalate mixed with calcium phosphate stones; 579 (30.2%) calcium oxalate stones; 204 (10.6%) calcium phosphate stones; and 182 (9.5%) non-calcium-containing stones, of which 21 (1.1%) were struvite stones and 161 (8.4%) were uric acid stones (Table 1). The most common chemical component of stones was calcium oxalate mixed with calcium phosphate, followed by calcium oxalate, calcium phosphate, uric acid, and struvite. When analyzing the

n (%)

Calcium phosphate Calcium oxalate Calcium oxalate/calcium phosphate Struvite Uric acid Calcium-containing stones Non-calcium-containing stones

MDRD eGFR (mL/min/1.73 m2) 67.0  23.7 70.3  21.5 73.4  22.6 54.9  18.6a 54.1  17.1a 71.7  22.5b 54.6  17.6b

a A p value <0.05 as determined by analysis of variance and Tukey’s post hoc test. b A p value <0.05 as determined by Student t test. Data are presented as mean  standard deviation. eGFR Z estimated glomerular filtration rate; MDRD Z modification of diet in renal disease.

266 formers also varied significantly from those of calcium oxalate, calcium phosphate, and mixed calcium oxalate/ calcium phosphate stone formers. The difference between struvite and uric acid stone formers was not statistically significant.

Discussion The impact of CKD on public health is well documented. CKD patients have an increased risk of morbidity and mortality compared with the general population. Hence, the identification of possible risk factors associated with the development of renal disease has become an important focus area for researchers [11,12]. Because the incidence of CKD has been increasing worldwide over the last decades, the frequency of renal stone disease has also increased [1]. Although much is known about the treatment of stone disease, the clinical consequences of stone disease remain relatively unidentified. In particular, little is known about the effect of stone disease on renal function except for renal obstruction [13]. Some studies have shown an association between kidney stone disease and chronic kidney function impairment. However, some stone formers may develop chronic kidney function impairment and some may not. The possible causes and risk factors for renal function damage in patients with urinary stones include anatomical abnormality (e.g., obstructive nephropathy); infection and inflammation with parenchymal scar formation; underlying metabolic disorders (e.g., chronic urate nephropathy); environmental factors; repeated interventions; dietary factors; and molecular or genetic factors [14e16]. Hypertension and diabetes, the well-established risk factors, were significantly associated with chronic kidney functional impairment in general population as well as in stone formers [17,18]. According to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines for CKD, all the stone groups analyzed in this study fall into CKD Stage 2e3. The eGFR was significantly lower in uric acid and struvite stone patients than in patients with other stone types (p < 0.01). In terms of the underlying causes of renal function impairment, recent studies have indicated that the formation of stones is associated with the deposition of particles in the basement membranes of the thin loops of Henle and in the deep medullary interstitium [19]. Such a deposition may cause interstitial inflammation and facilitate the development of fibrosis, which results in tubular cell injury and damage of renal function. Furthermore, stone passage itself causes transient obstruction, and obstruction is a well-established risk factor for renal damage. Stone treatments, such as extracorporeal shock-wave lithotripsy and percutaneous nephrolithotripsy, have been shown to cause renal injury in experimental animal and human studies and may result in the loss of renal function. However, most clinical studies have suggested that the initial decline in eGFR, secondary to treatment-induced kidney injury, improved over time [20,21]. Currently, there is no evidence suggesting an association among the number of stones, the procedures used for treatment, and the risk of functional impairment in CKD. Obesity, one of the risk factors for urolithiasis, is another risk factor for

Y.-H. Chou et al. renal damage. Gillen et al. [4] reported that obese patients with stone disease had a higher frequency of decreased renal function than those without the disease. With regard to the effect of stone components on renal function, few studies have compared the effects of different stone components on renal function. The presence of struvite stones in some patients may cause the development of renal failure because of recurrent urinary infection [22,23]. This study indicated the presence of a lower eGFR in patients with non-calcium stone components than in those with calcium stone components. This finding suggests that the stone component is another risk factor for the progression of functional impairment in CKD. Traditional risk factors for stone formers included hypertension, diabetes, obstruction, and recurrent urinary tract infection. Two of the most common components of non-calcium stones were uric acid and struvite. Uric acid stone formers are commonly associated with diabetes and gout, diseases that are known to result in renal function impairment [22,24,25]. Struvite stones are associated with chronic recurrent urinary tract infection because they grow rapidly to occupy the entire renal collecting system, resulting in the loss of renal function [22]. Hypertension, diabetes, aging, chronic urinary tract infection, and nephrotoxic drug medication are all important risk factors for CKD. Besides these, we found that urolithiasis, especially in non-calcium urinary stone disease, is also a risk factor for CKD. In our study, because the sample size was large, we assumed that the percentage of patients with hypertension and diabetes was similar among different stone component groups. We analyzed the renal function of patients with urolithiasis on the basis of different stone components rather than different associated diseases, such as urinary tract infection, diabetes, hypertension, or aging. The patients with different stone components may have various comorbidity rates. In fact, the patients with struvite stones may develop chronic urinary tract infection, whereas patients with uric acid stones have a higher probability to develop diabetes, which may result in chronic renal disease. Aging is also an important risk factor for CKD. In this study, we found that patients with non-calcium stones had a worse renal function as compared with those with calcium-containing stones; this is a very important finding that should be noted by both physicians and patients, including young subjects, to maintain renal function. Our study does have some limitations. In our retrospective analysis, we did not consider the methods used for treatment, the association of stone disease duration with renal function, and the patients’ body mass index. Further work in different patients is needed to validate our finding and to determine the possible mechanisms underlying impaired kidney function. Our results indicate that nephrolithiasis can be regarded not only as a stone disease, but also as a kidney functionimpairing disease. Traditional risk factors for CKD include obstruction, diabetes, hypertension, and urinary tract infection. Our study showed that stone components were associated with an impaired renal function. In fact, renal function in non-calcium-containing stone patients deteriorated significantly as compared with those with calciumcontaining stones. Hence, stone analysis is important in

Renal function in patients with urolithiasis predicting the change of renal function in patients with urolithiasis. Patients with non-calcium stones, such as struvite and uric acid stones, should be carefully evaluated and treated to preserve the renal function.

Acknowledgments This work was partly supported by Excellence for Cancer Research Center grant, Department of Health, Executive Yuan, Taiwan, ROC (No. DOH99-TD-C-111-002), to Kaohsiung Medical University (W.C. Chang), and National Science Council, Taiwan, ROC (No. 99-2314-B-037-019-MY3) to Y.H. Chou.

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