Shoaib Mithani ( The Kidney Center Postgraduate Training Institute, Karachi. )
Zafar Zaidi ( The Kidney Center Postgraduate Training Institute, Karachi. )
September 2005, Volume 55, Issue 9
Original Article
Abstract
Objective: To identify the difference in urinary citrate excretion between Stone Formers (SF) and Healthy Volunteers (HV) as a metabolic risk factor, that predisposes to urinary stone formation and to compare levels of urinary citrate in (HV) with reference values.
Methods: The 24 hours urinary citrate was evaluated in 40 patients treated for renal citrate and declared stone free, and 40 age matched healthy adults taken as controls. Both the groups had a similar living environment, extrinsic factors, diet and similar genetic descent.
Results: There was no significant difference in urinary citrate excretion level among stone formers (mean 262 SD 197) and normal volunteer subjects (mean 269 SD 140). Using the previously defined normal values (200) of urinary citrate in the local population, 55% of stone patients in our study group were hypocitric. While using the same value, 45% of our normal volunteers were also hypocitric. If 320 was taken as normal limit, 70 % of the patient's population and 72 % of controls were hypocitric. The prevalence of hypocitraturia was similar in the age matched adult groups.
Conclusion: Certain intrinsic factors in our local subjects may account for the high prevalence of urolithiasis than in western population. Although the urinary citrate excretion of stone patients is similar to normal volunteers, uniformly low urinary citrate excretion may be a feature as a nation and not a predisposing factor for the lithogenesis. This supports the view that there may be more often prominent influences in stone formers possibly of genetic origin (JPMA 55:371;2005).
Introduction
Several studies indicate that urinary stone disease has a high prevalence in our country. But unfortunately the epidemiology of urolithiasis remains poorly investigated in the region. Prevalence rates are mostly based on hospital admissions. The etiology of stone formation in a given population is reflected in the composition of calculi, metabolic studies, and dietary habits.1 There are various extrinsic and intrinsic factors for renal stones in the different population groups in different provinces of Pakistani population. More than half the people live in rural areas and the climate is moderate to hot.3 Poor nutritional status and inadequate health facilities are common in the region. However, there are few published studies objectively comparing the risk factors for urinary stone disease and its recurrence in local population. The most common type of urinary stone in our local population is calcium oxalate (60-65%), confirming that the composition of urinary stones in Sind, lower Punjab and Balochistan is inconsistent with international findings. Metabolic studies from the region show that the major risk factors are low urinary volume (20-30%), hyperuricosuria (20-60%), hyperoxaluria (50-60%), hypomagnesuria (20-30%) and hypocitraturia (30-40%).1 These results suggest that dietary and environmental factors are more important in this region, as oxalate-rich and calcium-poor diets prevail with low intake of proteins. Furthermore, chronic diarrhea and malabsorption in the tropics could be a major causative factor for hyperoxaluria.4
It is now frequently recognized that hypocitraturia is a frequent biochemical disturbance among patients with nephrolithiasis. There is no consensus on the normal range for urinary citrate. Arbitrary but different values are used in western and local studies to define the lower normal limits. The purpose of this study was to identify urinary citrate levels in stone formers and normal individuals and to compare the prevalence with other published data.
Subject and Methods
Subject and Methods |
Each participant was given verbal and written instructions about the collection of urine sample. Subjects were also instructed to collect the sample while on their usual diet and to avoid any medical therapy that may alter the urinary citrate levels. The 24 hours urinary excretion of citrate was measured in both the groups. All samples were collected in a special jar containing fixed quantity of citrate preservative, Thymol. All samples were checked in the same laboratory. Citrate level was estimated by enzymatic citrate lyase analysis (Bergmeyer method). Improper collection of urine was excluded.
All data was analyzed by SPSS version 10.0 data files. Description statistics regarding age distribution of the subjects was calculated. Difference in the mean and median of urinary citrate of both groups was tested with student-t at the level of significance of p value <0.05.
Results
As the urinary excretion of citrate did not differ significantly with gender, they were included as one group among patients, and a t-test used to assess the significance of any differences when comparing with the citrate levels of control subjects (HV) (Table 1);Mean urinary citrate excretion among the patients was 262 ± 198 mg (median value 174 mg) compared to 269 ± 140.5 mg (median value 232 mg) in control subjects. This shows no significant differences of excretion of urinary citrate between patients and control population in the study Figure.
Table 1. Mean Urinary Volume and Mean Urinary Citrate. | |||
Total | Urinary Volume | Urinary Citrate | |
(n) | mls/24hrs | mls/24hrs | |
Cases | 40 | 2214 ± 934 | 262 ± 197 |
Control | 40 | 1568 ± 1044 | 269 ± 140 |
[(0)] |
Figure. Citrate Values of Stone formers and Health Volunteers. |
Table 2. Stone formers and normal volunteers with urinary citrate levels below reference levels. | |||
Reference levels for 24 hrs Urinary Citrate | Hypocitraturic Stone Formers n= (%) | Hypocitraturic Controls (HV) n=(%) | |
Nabeel5 | 200 mg | 22 (55%) | 18 (45%) |
Rizvi1 | 300 mg | 27 (67%) | 28 (70%) |
Talati6 | 320 mg | 28 (70%) | 29 (72.5) |
Discussion
Urine could supersaturate with the crystals of salts (calcium, oxalate and phosphate) and in the absence/low concentration of urinary inhibitors. These inhibitors include small ions such as magnesium and citrate as well as polyanions of high molecular weight such as glyconaminglycans.9
In the present study, gender distribution was comparable with previous international data.7 Gender has some affects on urinary constituents; normal women have higher urinary citrate and lower urinary calcium than normal men.10 Because of the gender difference we compared the mean of the excreted urinary citrate between men and women in the patients. Mean urinary citrate in male stone forming patients was 259 mg (median value 170 mg) and among females 265.8 mg (median value 255 mg). There was no age difference between the genders in the two groups.
Dehydration and low urinary volume are widely accepted risk factors for urinary stone disease. There was a higher level of high urinary output in the study patients 2214 ml ± 934 compared to controls, 1568 ± 1044 (Table 1), probably because the patients group was told to drink more water during their post operative hospital stay or after lithotripsy sessions.
Hypocitraturia may be an ominous sign for stone formation and an obvious finding in our study when compared to other studies. The frequencies of the 24 hours urinary citrate excretion between the cases and the control groups (262 ± 197 and 269 ± 140 respectively) were statistically insignificant. Control group (HV) had no significant difference in mean urinary citrate excretion than patients group (SF). There was also only a minor difference in the excretion of any urinary citrate between men (259 mg) and women (265.8 mg) in patients groups.
There appears to be no consistency in deciding cutoff values for hypocitraturia. Different authors have used different levels.1,5,6 Looking at the urinary citrate excretion values at the different cut off of 200 mg, 300 mg and 320 mg, there was equal distribution of patients and normal subjects. Consistency of the results at different cut off levels, also supports the finding that there is no significant difference in the mean urinary citrate excretion. However as there is no consistency in lower acceptable levels, true frequency of hypocitraturia in subject and control population is difficult to determine.
Overall there was not a major difference between the two groups in urinary citrate as risk factors that predispose to stone formation.
Conclusion
References
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8. Khamesra HL, Barjatiya MK, Srehlata A. Urinary stone risk factors in north-west India population. In Rodgers AL, Hibbert BE, Hess B, Khan SR, Preminger GM, eds. Urolithiasis 2000. Cape Town: University of Cape Town 2000;343-5.
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