|Year : 2023 | Volume
| Issue : 2 | Page : 50-54
Evolving epidemiology and chemical analysis of urinary stones: A retrospective analysis
Parul Singla, Anjali Manocha, Seema Bhargava, Mamta Kankra, Anisha Sharma
Department of Biochemistry, Sir Ganga Ram Hospital, New Delhi, India
|Date of Submission||13-Sep-2022|
|Date of Decision||31-Jan-2023|
|Date of Acceptance||01-Feb-2023|
|Date of Web Publication||28-Apr-2023|
Dr. Seema Bhargava
Sir Ganga Ram Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
Background: Renal stones are a painful urological disorder resulting from the combined influence of epidemiological, biochemical and genetic risk factors. A high recurrence risk has been reported for renal stones, and 0.6%–3.2% cases may progress to end stage renal disease. Modern lifestyle, sedentary habits and unhealthy dietary practices are primary promoters of the stone boom in this millennium.
Aims and Objectives: The aim of the present study is to evaluate the percentage of the stone type according to chemical composition and their association with epidemiological factors like sex and age. A retrospective analysis of the chemical composition of the stone samples received was done.
Material and Methods: Stones samples were processed by Stone Analysis Set (BIOLABO S A, France). Qualitative chemical analysis was done for calcium, phosphorus, ammonium ion, oxalate, cystine, magnesium, carbonate and uric acid.
Results: Type of renal stone and its incidence with age and sex have been evaluated. The total number of patients reporting to the hospital with renal stones was 123. Of these, 69.11% were male and 30.89% were female, with a male to female ratio of 2.23:1. The maximum occurrence was in the third and fourth decade of life. On analysis, 72.35% of total stones comprised calcium oxalate and 23.57% of nonoxalate (phosphate, magnesium, carbonate, ammonium ion) stones, whereas uric acid was positive in 4.06%.
Conclusion: The occurrence of renal stones according to epidemiological factors such as age and sex in our study are similar to those reported in studies from developed countries. The data on urinary stones indicate that 98% were located in the upper urinary tract. Oxalate stones represent the main form of urolithiasis, affecting males more than females. The most important cause studied for renal stone formation is metabolic disturbances, but the genetic factors associated with the occurrence and recurrence of stone and mineral homeostasis of ions in kidney of stone formers should be further evaluated.
Keywords: Calcium oxalate, epidemiology, urinary stones, urolithiasis
|How to cite this article:|
Singla P, Manocha A, Bhargava S, Kankra M, Sharma A. Evolving epidemiology and chemical analysis of urinary stones: A retrospective analysis. Curr Med Res Pract 2023;13:50-4
|How to cite this URL:|
Singla P, Manocha A, Bhargava S, Kankra M, Sharma A. Evolving epidemiology and chemical analysis of urinary stones: A retrospective analysis. Curr Med Res Pract [serial online] 2023 [cited 2023 May 30];13:50-4. Available from: http://www.cmrpjournal.org/text.asp?2023/13/2/50/375238
| Introduction|| |
Urolithiasis is the formation of stones in the urinary system and includes both nephrolithiasis, or renal stones and urolithiasis or ureteric stones. Although not life threatening, this condition usually presents with painful haematuria. Urolithiasis is prevalent worldwide, with a 5-year recurrence rate of 50%. Globally, the high incidence has been observed in Scandinavian countries, the Mediterranean region, northern Australia, central Europe and parts of Asia, while the Indian stone belt comprises parts of Maharashtra, Gujarat, Punjab, Haryana, Delhi and Rajasthan.
Stones in the urinary tract are formed by the deposition of calcium, phosphates and oxalates around a nucleus that hardens over time. More than 80% of all stones are calcareous, with calcium oxalate and phosphate as the primary chemical complexes. Approximately 4.5%–23% of stones contain uric acid, while the less frequent stones are those of magnesium ammonium phosphate, ammonia urate, cystine, xanthine, etc.
Factors such as age, sex, industrialisation, diet, environment and socioeconomic status affect stone formation. In ages >18 years, 6% of women and 12% of men have been inflicted with this condition, with a recurrence rate of 47%–60% and 70%–80%, respectively. Recent studies have shown a rising trend in the incidence of urolithiasis in the paediatric population, and though the exact cause is unclear, dietary, metabolic and anatomic abnormalities have been linked with higher morbidity. Diet plays an important role, and dietary changes reported from many countries, including India, China, Egypt, Russia and the Philippines, are one of the key driving forces for stone formation. Increased intake of animal proteins, calcium, sodium rich foods and starchy foods derived from corn, as well as diminished fluid intake, are known risk factors. Increased oxalate consumption in chocolates also promotes stone formation. Global climate change is another factor that affects the incidence of stone disease, and an association has been documented between raised environmental temperatures and increased rates of kidney stone formation. Rising obesity and high body mass index (BMI) are other factors linked to nephrolithiasis.
Though not serious enough to be fatal, this disease leads to an immense economic burden as it is associated with diminished quality of life and increased anxiety due to an increased risk of developing kidney disease. Hence, this study was undertaken to evaluate the prevalence of stone formation in a north Indian population and to examine its relationship with the age and sex of patients residing in the stone belt region. This study also aimed to qualitatively examine the chemical composition of the stones in view of the evolving socioeconomic lifestyle and changes in the dietary habits of our population. This knowledge will be of great importance in formulating preventive measures to help reduce the incidence and recurrence of urolithiasis in this region.
| Materials and Methods|| |
This retrospective study was done on 123 stone samples obtained by the surgical intervention of patients with urolithiasis in the hospital over a period of 4 years. Demographic and clinical details of the patients were recorded at the time of admission and included age, sex and history of symptoms. Consent was taken from all the patients.
The stones were initially weighed as a minimum of 50 mg sample is required for testing, then examined for physical characteristics such as number, shape, size, colour and consistency. The stones were then washed, dried and pulverised for qualitative chemical analysis as per the protocol of the stone analysis set (BIOLABO SA, France), and a change in colour was noted.
Qualitative chemical analysis
Step 1: 50 mg of the calculus powder was weighed and transferred into a test tube.
Step 2: Carbonate, cystine, phosphate, magnesium, calcium, ammonium, uric acid and oxalate were detected in the sample as per the protocol for each analyte; a specific reagent was added to the stone solution as given in [Table 1].
Demineralised water was used as a negative control for all the analytes except for carbonate and oxalate so as to get a better perception of the change in colour.
The data analysis was done by Microsoft Office Excel 2010 (Washington, United States).
| Results|| |
One hundred twenty-three uroliths received in the lab were tested qualitatively for their chemical composition.
[Table 2] depicts the distribution of urinary stones in relation to sex. A higher percentage of urolithiasis was observed in males, i.e., 69.11% (n = 85) as compared to females 30.89%, (n = 38), with the overall male to female ratio as 2.23:1.
When analysed as per the age of the patients [Table 3] and [Figure 1], maximum preponderance was observed in the middle age group of 30–49 years (43.9%) followed by the age group 50–69 years (28.46%). Only 8.9% of cases were observed in <10 year. The lowest incidence was observed in cases >70 years.
[Table 4] shows the chemical composition of the urinary stones received, and the percentage of the chemical composition of the analysed uroliths is shown in [Figure 2]. 72.35% (n = 89) of the stones contained calcium oxalate, while 11.38% (n = 14) stones consisted of magnesium along with calcium oxalate. 7.32% (n = 9) contained only calcium, while 4.06% (n = 5) stones were composed of uric acid, and 2.44% (n = 3) of the stones tested were composed of calcium phosphate and magnesium ammonium phosphate. None of the stones tested were positive for cystine and carbonate.
| Discussion|| |
The renal stone formation has a multiform aetiology and is associated with significant renal complications. In our study, we observed that urolithiasis predominantly affected males with an observed male to female ratio of 2.23:1, which was in concordance with other global studies., This male preponderance could possibly be due to the supersaturation of urine and precipitation of stones in the urethra due to its longer length. In another recent study, the increased prevalence in males has been associated with BMI. Taylor et al., in their study, enumerated that adiposity played a central role in the association of body size with nephrolithiasis and confirmed an independent association of higher BMI with the development of kidney stones. However, an increased mixed stone formation could be due to a multifactorial aetiology.
The incidence of kidney stones in our study showed a variable pattern when compared with age. A high occurrence of urinary tract stones was observed in the age group 30–40 years, t which was in agreement with the results of a study in Iraq by Kadhum and Kandel, where they observed a similar occurrence in the 30–50 years age group. However, in an earlier study by Baker et al., the peak age observed for calcium oxalate renal stone was mainly in the group of 50–60 years. The probable cause of an earlier presentation of the stone disease, as observed in our study, could predominantly be due to the changes in dietary habits, which include increased intake of non-vegetarian diet, higher consumption of sweet corn rich products, chocolates, fruits, vegetables rich in oxalates as well as increased intake of alcohol and soft drinks, all coupled with an increasingly sedentary lifestyle. Hence suitable dietary changes can be advised depending on the type of stone to prevent kidney stone formation. The patient may be asked to avoid oxalate in the diet in case of a high incidence of calcium oxalate stones. Similarly, dietary sodium, potassium, animal protein, calcium citrate, etc., may be modified in diet to reduce the risk of increased stone formation.
The chemical composition of the majority of stones (72.35%) in our study was composed of calcium salts with oxalate, followed by mixed stones of calcium, magnesium, phosphate (23.58%) and urate stones (4.07%). These results were in agreement with a study by Singh et al., who also observed a higher occurrence of calcium salt in stone, specifically of oxalate, from the north eastern region of India, followed by phosphate and urate stones. Studies from other parts of the world, specifically Japan, Australia, Africa and Saudi Arabia, also observed similar results., The most probable cause for this high occurrence of calcium oxalate stones could be the increased consumption of a diet rich in oxalate, like spinach, tea, chocolate, nuts, beetroot, colas, etc., leading to increased substrate delivery in the intestine. The presence of an oxalate anion exchange transporter Slc26a6 in the apical portion of the small intestine increases oxalate absorption, leading to its increased level in plasma. This further increases oxalate excretion in urine, promoting binding with calcium to form an insoluble calcium oxalate stone formation. Another study postulated that disturbed calcium homeostasis led to calcium-phosphate precipitation in the tubular interstitium of kidney tubules beneath the uroepithelial cells of renal papilla known as Randall's Plaque which erodes the uroepithelial layer, thus exposing them to supersaturated stone forming salts in urine. Oxalate deposits on the epithelium cover this plaque and result in calcium oxalate stone formation. Hence, though limiting only oxalate rich foods helps reduce stone formation, research has shown that a better strategy would be to eat and drink calcium and oxalate rich foods together as oxalate and calcium would bind in the stomach and intestines. Fluids, too, affect stone formation, and changes in intake can help prevent their incidence. Drinking adequate amounts of fluids keeps the urine dilute. Citrus in drinks like lemonade and orange juice prevents the binding of calcium with other urinary constituents, thus reducing the incidence of stone formation. Higher consumption of Vitamin C supplements also increases the risk of stone formation as Vitamin C is converted to oxalate in the body.
The recurrent stone formation has also been linked to a genetic aetiology with a complex and polygenic mode of inheritance. An autosomal recessive inheritance for cystinuria and primary hyperoxaluria has been reported. Curhan et al. suggested that a 60% increased risk of stone formation in the relatives of patients with idiopathic urolithiasis was due to genetic inheritance. Goldfarb et al. also examined genetic and non-genetic factors associated with stones and reported similar results. One of the main risk factors for idiopathic urolithiasis is the familial occurrence of hypercalciuria. In a study by Thorleifsson et al., in a large cohort of hypercalciuric stone formers from Iceland and the Netherlands, identified Claudin 14 as a possible major gene of nephrolithiasis. In yet another study, disturbed calcium homeostasis was another hypothesis put forth by Vezzoli et al., who observed an association between stone formation and calcium sensing receptors (CaSR), which could play a crucial role in the regulation of renal divalent mineral transport process. Aida et al., in another study, cloned CaSR from human kidney and researched its role in regulating calcium ion concentration in blood. They observed that CaSR reduced calcium reabsorption in distal tubules, increased phosphate reabsorption in proximal tubules and stimulated water and proton excretion in collecting ducts. These studies suggested CaSR could be a candidate gene associated with an increased predisposition to calcium nephrolithiasis. Hence, though the genetic association is well established for a vast majority of kidney stones, its association with recurrent stone formers needs to be further evaluated.
| Conclusion|| |
The incidence of renal stone disease is increasing slowly but steadily and has become a hidden economic burden. The pathophysiological mechanisms are multifactorial and complex. Unhealthy dietary habits, a sedentary lifestyle and obesity add to the multisystem pathology. A detailed history with careful evaluation for metabolic disturbances, along with information on regional diversities and inheritance patterns, can play a major role in preventing and reducing the occurrence of renal stones.
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Conflicts of interest
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]