Original Research

Appearance of ureterorenal stones after gouty arthropathy: a retrospective cohort study for ethnic disparity

AUTHORS

Yu-Cheng Lu 1 MD, Doctor

Chao-Yu Hsu2 DMS, Associate Professor *

CORRESPONDENCE

* Chao-Yu Hsu

AFFILIATIONS

1 Department of Urology, National Taiwan University Hospital, Taipei, Taiwan

2 Department of Family Medicine and Department of Medical Education and Research, Puli Christian Hospital, Puli, Taiwan

PUBLISHED

15 August 2019 Volume 19 Issue 3

HISTORY

RECEIVED: 24 October 2018

REVISED: 6 April 2019

ACCEPTED: 30 May 2019

CITATION

Lu Y, Hsu C.  Appearance of ureterorenal stones after gouty arthropathy: a retrospective cohort study for ethnic disparity. Rural and Remote Health 2019; 19: 5152. https://doi.org/10.22605/RRH5152

AUTHOR CONTRIBUTIONSgo to url

This work is licensed under a Creative Commons Attribution 4.0 International Licence


abstract:

Introduction:  This study aimed to investigate the differences in ureterorenal stone appearance after gouty arthropathy between Taiwanese aboriginal and non-aboriginal patients.
Methods:  Between 2007 and 2015, patients with first diagnoses of ureterorenal stones after diagnosis of gouty arthropathy at Puli Christian Hospital were enrolled in this study. Characteristics, underlying diseases and laboratory data for aboriginal and non-aboriginal patients were recorded. All categorical variables were analysed by χ2 test and continuous variables were compared by t-test.
Results:  A total of 201 patients (66 aboriginal and 135 non-aboriginal) were enrolled in the study. Serum uric acid levels did not differ significantly between aboriginal and non-aboriginal groups. There was a significant difference in the time until ureterorenal stone appearance after gouty arthropathy between aboriginal and non-aboriginal patients (38.0 v 29.3 months, p=0.015). Among males, aboriginal patients exhibited gouty arthropathy at a younger age than non-aboriginal patients (46.0 v 50.2 years, p=0.035). Furthermore, male aboriginal patients exhibited a higher rate of alcoholic hepatitis (26.7% v 12.2%, p=0.046).
Conclusion:  Among males, aboriginal Taiwanese patients exhibited gouty arthropathy at younger ages than did non-aboriginal Taiwanese because of a higher rate of alcoholic hepatitis. The longer time until stone appearance after gouty arthropathy was attributed to alcoholic diuresis. Decreasing alcohol consumption may postpone or halt the development of gouty arthropathy.

Keywords:

arthropathy, ethnicity, gout, stones, Taiwan.

full article:

Introduction

Gout is a common inflammatory arthritis and males have higher prevalence than females1. Gouty arthropathy is a joint disease caused by the formation of uric acid crystals in a joint space. The prevalence of gout has been increasing yearly in Maori and European populations2. In Taiwan, the prevalence of gout increased between 1993–1996 and 2005–2008 (4.7% v 8.2% in men and 2.2% v 2.3% in women)3. The prevalence of gout is 11.7% in Taiwanese aborigines4.

Monoamine oxidase A enzyme activity is associated with risk of gout. Monoamine oxidase plays a major role in renal dopamine metabolic pathways, which influence uric acid level and urate excretion by controlling dopamine-induced glomerular filtration response. The mechanism may explain the higher prevalence of gout in Taiwanese aborigines5.

An Australian study reported an increased rate of urinary stones in aboriginal children, especially those living in remote and arid areas6. In Taiwan, the prevalence of upper urinary calculi is 9.6% (14.5% in men and 4.3% in women)7. Due to a defect in the renal production of ammonia, patients with gout have acidic urine and are prone to urate crystal deposition8. Some risk factors such as alcohol consumption9 may increase gout formation.

There are 16 aboriginal groups in Taiwan. The Atayal and Bunun, as the majority aboriginal groups in the present study, are the third and fourth largest populations of aborigines in Taiwan. The ethnic differences in ureterorenal stone appearance after gouty arthropathy remain unknown. This study investigated the differences in ureterorenal stone appearance after gouty arthropathy between aboriginal and non-aboriginal Taiwanese patients.

Methods

Patients presenting to Puli Christian Hospital between 1 January 2007 and 31 December 2015 with a first diagnosis of ureterorenal stones after diagnosis of gouty arthropathy were enrolled in this study. This is a retrospective cohort study reviewing medical records and using the code of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The study hospital is located in the mountainous area of central Taiwan, which is populated by many aboriginal tribes. According to the Household Registration Service of Nantou Country (2018), the population in the area of Puli, Renai and Xinyi is approximately 112 500. Among this population, approximately 26 000 are aboriginal Taiwanese, mostly Atayal and Bunun people.

The ethnicity, age, sex, location of stone and time until stone appearance after gouty arthropathy were recorded from the electronic medical records. Underlying diseases such as diabetes, hypertension, hyperlipidaemia and hepatitis (alcoholic or non-alcoholic) were included. The authors also analysed serum levels of uric acid, creatinine, blood urea nitrogen (BUN) and estimated glomerular filtration rate (eGFR) when gouty arthropathy was diagnosed. Urine pH was recorded when the ureterorenal stones were diagnosed.

A χ2 test was used to compare differences in ethnicity, sex, location of stone and underlying diseases between aboriginal and non-aboriginal patients. A t-test was used to examine the age, time until stone appearance, serum levels of uric acid, creatinine, BUN, eGFR and urine pH.

Ethics approval

The study was approved by the ethics committee of Puli Christian Hospital (PCH-EC-2015-01).

Results

Between 2007 and 2015, 201 patients (66 aboriginal and 135 non-aboriginal) with a first diagnosis of ureterorenal stones after gouty arthropathy were enrolled in the study. The patients’ characteristics, underlying diseases and laboratory data are shown in Table 1. The aboriginal group demonstrated a higher female-to-male ratio (0.47 v 0.10, p<0.001) and renal stone percentage (65.2% v 48.1%, p=0.034) compared with the non-aboriginal group. The aboriginal patients also exhibited longer times until stone appearance after gouty arthropathy (38.0 v 29.3 months, p=0.015) and had urine that was more alkaline (pH 6.4 v 6.1, p=0.006) when ureterorenal stones were diagnosed. No significant differences were observed between the two groups regarding age, diabetes, hypertension, hyperlipidaemia and alcoholic hepatitis. Laboratory data such as uric acid, creatinine, eGFR and BUN revealed no differences between the two groups.

Among the males, 45 were aboriginal and 123 were non-aboriginal. The patients’ characteristics, underlying diseases and laboratory data are shown in Table 2. The aboriginal patients exhibited gouty arthropathy at a younger age than non-aboriginal patients (46.0 v 50.2 years, p=0.035), and they displayed a higher rate of alcoholic hepatitis (26.7% v 12.2%, p=0.046). The aboriginal group also exhibited longer times until stone appearance after gouty arthropathy (40.1 v 29.8 months, p=0.015) and had urine that was more alkaline (pH 6.4 v 6.0, p=0.017) when the ureterorenal stones were diagnosed.

Among the females, 21 were aboriginal and 12 were non-aboriginal. The patients’ characteristics, underlying diseases and laboratory data are shown in Table 3. Hyperlipidaemia was significantly higher in non-aboriginal patients (9.5% v 50.0%, p=0.029).

Table 1:  Patient characteristics, underlying diseases and laboratory data

Table 2:  Male patient characteristics, underlying diseases and laboratory data

Table 3:  Female patient characteristics, underlying diseases and laboratory data

Discussion

Risk factors for gouty arthropathy and ureterorenal stones are related to lifestyle and social habit10, supporting differences observed between aboriginal and non-aboriginal patients. In this study, the authors identified ethnic differences in ureterorenal stones after gouty arthropathy. It was found that the aboriginal patients exhibited a longer time until stone appearance after gouty arthropathy, and male aboriginal patients developed gouty arthropathy at younger ages than did male non-aboriginal patients.

Age and sex 

A study of gout attacks demonstrated that identifiable triggers are more common in those with early-onset gout11. Males are predisposed to an earlier age of gout onset, which is linked to obesity12. Due to female sex hormones, women are protected against gout in the pre-menopausal period. Therefore, men outnumbered women in all age groups for gout prevalence, more in younger than older age groups, by ratios of 10:1 and 5:1, respectively13. The sex difference is less pronounced with increasing age, but men still outnumber women with gout, even among older adults.

The incidence of urolithiasis has increased worldwide. A study evaluating metabolic risk factors for urolithiasis revealed that hyperoxaluria, hyperuricosuria and hypocitraturia are more common in men than in women; moreover, hypercalciuria is more common in patients younger than 60 years14. Metabolic profiles are also observed in different sex and age groups. Men and younger patients have higher lithogenic risks compared with women and older patients. Younger women have lower risk of stone formation, which is attributed to diet and fluid intake.

Alcohol

Alcohol, which is made from fermented grains, plays a vital role in gout. Alcohol decreases kidney uratic acid excretion and increases urate production. Thus, alcohol increases serum uric acid concentration, and it exacerbates and induces gout attacks. Alcohol consumption, especially of beer and hard liquor, increases the incidence of gout15. One study evaluated the effects of quantity and type (beer or wine) of alcohol consumed on the risk of gout attacks. Alcohol consumption, regardless of the type of alcoholic beverage, was associated with an increased risk of gout attacks, even for moderate amounts of alcohol16. In particular, young-onset gout was related to excessive alcohol consumption11. Therefore, individuals with gout should limit alcohol consumption to prevent recurrent gout attacks.

Alcohol acts as a diuretic. The rate of urolithiasis decreases by 10% with an increase of 10 g/day of alcohol consumption17. In the present study, the male aboriginal patients exhibited a longer time until stone formation after gouty arthropathy; this can be attributed to diuresis because of higher prevalence of alcoholic hepatitis. So, decreasing the alcohol consumption will prevent the formation of gouty arthropathy.

Hypertension

Hypertension is associated with a higher incidence of gout15. A recent study strongly supported this association and indicated that the use of diuretics to treat hypertension can induce gout18. Loop diuretics and thiazide were associated with higher risks of gout15. The mechanism of diuretic-induced hyperuricaemia can cause the creation of diuretics; losartan is used to treat hypertensive patients with gout, and possesses mild diuretic properties18.

Diabetes

Diabetes is associated with a higher risk of gout15. Serum uric acid concentration is strongly related to type 2 diabetes, and severe insulin resistance and renal impairment exacerbate gout severity19. Another study, however, revealed that individuals with diabetes are at lower risk of gout, independent of other risk factors. The mechanism was attributed to the uricosuric effect of glycosuria and the impaired inflammatory response20. A Taiwanese study revealed that patients with diabetes treated with pioglitazone exhibited a lower incidence of gout21. By inhibiting the expression of tumour necrosis factor-α and interferon-γ, pioglitazone has anti-inflammatory effects.

An increased prevalence of stone formation has been reported in patients with diabetes. Oral hypoglycaemic agents (such as biguanides) can influence urine properties and induce stone formation22. Diabetes results in lower urine pH through renal impairment and uric acid stone formation23.

Hyperlipidaemia

Hypertriglyceridaemia is associated with a risk of gout24. Hypertriglyceridaemia, especially in men, may promote gout development through its effect on serum uric acid24. According to the vascular aetiology of stone formation, dyslipidaemia theoretically predisposes patients to nephrolithiasis. One study demonstrated that dyslipidaemia is associated with an increased risk of stone disease; the only specific lipid panel associated with lower nephrolithiasis is high-density lipoprotein25. In the present study, the hyperlipidaemia rate was no different between aboriginal and non-aboriginal patients. 

Renal function, serum uric acid and urinary pH

Renal impairment can induce and exacerbate gout attacks19. Nishida demonstrated that urinary creatinine and uric acid excretion in patients with gout were significantly increased when compared with people without gout; increased creatinine synthesis was determined to accelerate uric acid synthesis26. Thus, renal impairment may induce and exacerbate gout attacks. Hyperuricaemia can also cause renal damage, and there is increasing evidence of a correlation between urate-lowering therapy and renal morbidity27. Therefore, early treatment of hyperuricaemia is strongly recommended to prevent chronic kidney disease.

Urinary pH is a primary determinant of ureterorenal stone formation. Alkaline pH favours the crystallisation of calcium- and phosphate-containing stones28. In the present study, aboriginal patients exhibited more-alkaline urine than did non-aboriginal patients, but there were no differences in serum uric acid levels. This can be attributed to early medical treatment after diagnosis.

Limitations

This retrospective study identified the ethnic differences in ureterorenal stones after gouty arthropathy. However, the present study had several limitations. First, gouty arthropathy was diagnosed by individual physicians, thus it was not possible to determine whether diagnoses were confirmed subjectively through clinical impression or objectively by joint aspiration or imaging. However, the National Health Insurance in Taiwan ensures that all insurance claims are scrutinised by medical reimbursement specialists. Therefore, the diagnoses of gouty arthropathy in this study were highly reliable. Similarly, the diagnoses of ureterorenal stones were also reliable, regardless of the specialist’s diagnostic method (X-ray imaging or ultrasound). Second, patients with ureterorenal stones can exhibit no clinical symptoms. The authors may have underestimated the incidence of stones after gouty arthropathy. Third, some patients’ characteristics, such as lifestyle and dietary information, were not available in this study. These factors could influence the incidences of gouty arthropathy and ureterorenal stones. Despite several limitations, this study accurately reflects the situation in this area of Taiwan.

Conclusion

Among males, aboriginal Taiwanese patients in this study exhibited gouty arthropathy at younger ages than did non-aboriginal Taiwanese because of a higher rate of alcoholic hepatitis. The longer time until stone appearance after gouty arthropathy was attributed to alcoholic diuresis. Decreasing alcohol consumption may postpone or halt the development of gouty arthropathy.

references:

1 Doherty M. New insight into the epidemiology of gout. Rheumatology (Oxford) 2009; 48(Suppl2): ii2-ii8. https://doi.org/10.1093/rheumatology/kep086 PMid:19447779
2 Klemp P, Stansfield SA, Castle B, Roberston MC. Gout is on the increase in New Zealand. Annals of the Rheumatic Diseases 1997; 56(1): 22-26. https://doi.org/10.1136/ard.56.1.22 PMid:9059136
3 Chuang SY, Lee SC, Hsieh YT, Pan WH. Trends in hyperuricemia and gout prevalence: nutrition and health survey in Taiwan from 1993-1996 to 2005-2008. Asia Pacific Journal of Clinical Nutrition 2011; 20(2): 301-308.
4 Chou CT, Lai JS. The epidemiology of hyperuricaemia and gout in Taiwan aborigines. British Journal of Rheumatology 1998; 37(3): 258-262. https://doi.org/10.1093/rheumatology/37.3.258
5 Tu HP, Ko AM, Wang SJ, Lee CH, Lea RA, Chiang SL, et al. Monoamine oxidase A gene polymorphisms and enzyme activity associated with risk of gout in Taiwan aborigines. Human Genetics 2010; 127(2): 223-229. https://doi.org/10.1007/s00439-009-0765-z PMid:19915868
6 Carson PJ, Brewster DR. Unique pattern of urinary tract calculi in Australian aboriginal children. Journal of Paediatrics and Child Health 2003; 39(5): 325-328. https://doi.org/10.1046/j.1440-1754.2003.00147.x
7 Lee YH, Huang WC, Tsai JY, Lu CM, Chen WC, Lee MH, et al. Epidemiological studies on the prevalence of upper urinary calculi in Taiwan. Urology International 2002; 68(3): 172-177. https://doi.org/10.1159/000048445 PMid:11919463
8 Kramer HJ, Choi HK, Atkinson K, Stampfer M, Curhan GC. The association between gout and nephrolithiasis in men: the health professional's follow-up study. Kidney International 2003; 64(3): 1022-1026. https://doi.org/10.1046/j.1523-1755.2003.t01-2-00171.x PMid:12911552
9 Wang M, Jiang X, Wu W, Zhang D. A meta-analysis of alcohol consumption and risk of gout. Clinical Rheumatology 2013; 32(11): 1641-1648. https://doi.org/10.1007/s10067-013-2319-y PMid:23881436
10 Singh KB, Sailo S. Understanding epidemiology and etiologic factors of urolithiasis: an overview. SciVis 2013; 13(4): 169-174.
11 Abhishek A, Valdes AM, Jenkins W, Zhang W, Doherty M. Triggers of acute attacks of gout, does age of gout onset matter? A primary care based cross-sectional study. PLoS One 2017; 12(10): e0186096. https://doi.org/10.1371/journal.pone.0186096 PMid:29023487
12 Ma LD, Sun RX, Xin Y, Wang Y, Li CG, Liu T, et al. Clinical characteristics in gout patients with different body mass index. [In Chinese]. Chinese Journal of Internal Medicine 2017; 56(5): 353-357.
13 Singh JA. Racial and gender disparities in patients with gout. Current Rheumatology Reports 2013; 15(2): 307. https://doi.org/10.1007/s11926-012-0307-x PMid:23315156
14 Lancina Martín JA, Rodríguez-Rivera García J, Novás Castro S, Rodríguez Gómez I, Fernández Rosado E, Alvarez Castelo L, et al. Metabolic risk factors in calcium urolithiasis according to gender and age of the patients. [In Spanish]. Actas Urológicas Españolas 2002; 26(2): 111-120. https://doi.org/10.1016/S0210-4806(02)72742-3
15 Singh JA, Reddy SG, Kundukulam J. Risk factors for gout and prevention: a systematic review of the literature. Current Opinion in Rheumatology 2011; 23(2): 192-202. https://doi.org/10.1097/BOR.0b013e3283438e13 PMid:21285714
16 Neogi T, Chen C, Niu J, Chaisson C, Hunter DJ, Zhang Y. Alcohol quantity and type on risk of recurrent gout attacks: an internet-based case-crossover study. American Journal of Medicine 2014; 127(4): 311-318. https://doi.org/10.1016/j.amjmed.2013.12.019 PMid:24440541
17 Wang X, Xu X, Wu J, Zhu Y, Lin Y, Zheng X, et al. Systematic review and meta-analysis of the effect of alcohol intake on the risk of urolithiasis including dose-response relationship. Urology International 2015; 94(2): 194-204. https://doi.org/10.1159/000365358 PMid:25033956
18 Gibson TJ. Hypertension, its treatment, hyperuricaemia and gout. Current Opinion in Rheumatology 2013; 25(2): 217-222. https://doi.org/10.1097/BOR.0b013e32835cedd4 PMid:23370375
19 Suppiah R, Dissanayake A, Dalbeth N. High prevalence of gout in patients with Type 2 diabetes: male sex, renal impairment, and diuretic use are major risk factors. New Zealand Medical Journal 2008; 121(1283): 43-50.
20 Rodríguez G, Soriano LC, Choi HK. Impact of diabetes against the future risk of developing gout. Annals of Rheumatic Disease 2010; 69(12): 2090-2094. https://doi.org/10.1136/ard.2010.130013 PMid:20570836
21 Niu SW, Chang KT, Lin HY, Kuo IC, Chang YH, Chen YH, et al. Decreased incidence of gout in diabetic patients using pioglitazone. Rheumatology (Oxford) 2018; 57(1): 92-99. https://doi.org/10.1093/rheumatology/kex363 PMid:29040733
22 Yarovoi SK, Golovanov SA, Khaziakhmetova MR, Dzhalilov OV. Nephrolithiasis coexisting with type 2 diabetes: current concept of the features of stone formation and the effects of hypoglycemic therapy on lithogenesis. [In Russian]. Urologiia 2017; 3: 92-97. https://doi.org/10.18565/urol.2017.3.92-97
23 Daudon M, Traxer O, Conort P, Lacour B, Jungers P. Type 2 diabetes increases the risk for uric acid stones. Journal of the American Society of Nephrology 2006; 17(7): 2026-2033. https://doi.org/10.1681/ASN.2006030262 PMid:16775030
24 Chen JH, Pan WH, Hsu CC, Yeh WT, Chuang SY, Chen PY, et al. Impact of obesity and hypertriglyceridemia on gout development with or without hyperuricemia: a prospective study. Arthritis Care Research (Hoboken) 2013; 65(1): 133-140. https://doi.org/10.1002/acr.21824 PMid:22933424
25 Masterson JH, Woo JR, Chang DC, Chi T, L'Esperance JO, Stoller ML, et al. Dyslipidemia is associated with an increased risk of nephrolithiasis. Urolithiasis 2015; 43(1): 49-53. https://doi.org/10.1007/s00240-014-0719-3 PMid:25193087
26 Nishida Y. Relation between creatinine and uric acid excretion. Annals of Rheumatic Disease 1992; 51(1): 101-102. https://doi.org/10.1136/ard.51.1.101 PMid:1540011
27 Viazzi F, Bonino B, Ratto E, Desideri G, Pontremoli R. Hyperuricemia and renal risk. [In Italian]. Giornale Italiano di Nefrologia 2015; 32( Suppl 62): pii: gin/32.S62.6.
28 Wagner CA, Mohebbi N. Urinary pH and stone formation. Journal of Nephrology 2010; 23(Suppl 16): S165-S169.