OBJECTIVE To evaluate the role of vitamin A on renal scarring in recurrent urinary tract infections (UTIs).
DESIGN Twenty three children with UTIs and renal scarring (mean (SD) age 7.3 (3.9) years) and 91 children without renal scarring (6.4 (3.4) years) were studied. All the children had serum vitamin A and β-carotene measurements and nutritional evaluation. Renal scarring was assessed by technetium-99m dimercaptosuccinic acid (99mTc DMSA) scanning. Nutritional status of all the patients was within normal limits and not different between the groups.
RESULTS Mean (SD) serum vitamin A and β-carotene concentrations were not significantly different between the patients with and without renal scarring (vitamin A 53.2 (22.6)/46.8 (17.0) μg/dl and β-carotene 232.3 (201.3)/272.4 (86.0) μg/dl respectively). However, when the patients with renal scarring and with greater than 10% difference among the DMSA uptakes of their kidneys (11 cases) were evaluated, a significant negative correlation was determined between the serum vitamin A concentrations and the magnitude of the difference in uptakes of each kidney. The same relation was not true for serum β-carotene concentrations.
CONCLUSION This study demonstrated a relation between serum vitamin A concentrations and magnitude of hypoactivity in99mTc DMSA scanning in kidneys with advanced scarring.
- vitamin A
- renal scarring
- technetium-99m DMSA
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The role of vitamin A in recurrent urinary tract infections (UTIs) and urolithiasis has been assessed previously.1 Vitamin A was proposed as effective in the regeneration of epithelial tissue in the urinary tract2 ; β-carotene has been reported to have antioxidant properties.3 Technetium 99-m dimercaptosuccinic acid (99mTc DMSA) scintigraphy is the gold standard for demonstration of scarring in renal cortical tissue.4
We hypothesised that the regenerative effect of vitamin A on epithelial tissue could also be considered to play a part on renal parenchymal epithelium, as in the case of epithelium lining the lower urinary tract. The aim of this study was to evaluate the relation between vitamin A metabolism and scarred and unscarred renal parenchymal tissues and also to evaluate whether vitamin A and β-carotene had an effect on prevention of renal scarring.
Subjects and methods
Children with renal scarring due to recurrent UTIs were enrolled in this study. A control group was composed of children with recurrent UTIs but without renal scarring.
Each patient was evaluated twice by 99mTc DMSA scans performed at least six months apart. Persisting hypodense areas on two consecutive DMSA scans were considered as renal scarring.4Patients with normal or non-persisting DMSA findings were considered as free of scarring. Uptake of each kidney was determined as per cent of total uptake of both kidneys which was considered to be 100%. When the difference between uptakes of kidneys exceeds 10% on scanning, renal function was considered to be diminished on the lower uptake side.4 All the scans were read blindly by two specialists.
Nutritional status of patients was evaluated by body mass index and the results were compared with published standards.
Vitamin A and β-carotene concentrations were measured by the Neeld and Pearson method in venous blood samples obtained during acute UTI episodes.5 The intrabatch coefficients of variation for vitamin A and β-carotene were 6.5% and 7.8 % respectively in preliminary standardisation.
Patients were grouped according to whether they had renal scarring (study group) or not (control group). The groups were compared for serum vitamin A and serum β-carotene concentrations and nutritional status. In addition, the extent of kidney scarring was compared with serum concentrations of vitamin A and β-carotene, when the difference between 99mTc DMSA uptakes of kidneys was greater than 10%.
Results were analysed by unpaired t test and correlation analysis.
There were 23 children with renal scars (mean (SD) age 7.3 (3.9) years and 91 unscarred children (mean age 6.4 (4.4) years). The mean age difference between the groups was statistically insignificant. All the patients were well nourished and there was no difference in nutritional status of the two groups. Weight and height of the subjects were between 25th and 75th centile and their weight for height indices were higher than 90%. The mean (SD, range) serum vitamin A and β-carotene concentrations in patients with renal scars were 53.2 (22.6, 13.5–102.4) μg/dl and 232.3 (201.3, 130.0–1154.0) μg/dl respectively. These values were 46.8 (17.0, 14.4–104.0) μg/dl and 272.4 (86.0, 103.0–496.0) μg/dl in the group without renal scarring. No significant difference was present between the groups (p>0.05) (table 1).
Patients with renal scarring and with greater than 10% difference between negative uptakes of kidneys (11/23) had a mean (SD, range) serum vitamin A concentration of 56.27 (23.63, 25.0–105.0) μg/dl and β-carotene concentration of 269.72 (94.0 (102.0–486.0) μg/dl. These values did not differ from those of the patients without renal scarring (p>0.05) (table 1). However, there was a significant negative correlation between serum vitamin A and magnitude of the difference in uptakes of each kidney in patients with renal scarring and greater than 10% difference between negative uptakes of kidneys (r = −0.607, p<0.05) (fig 1). The serum β-carotene concentrations were not related to the per cent of negative uptakes (r = 0.384, p>0.05). Isolated hypovitaminosis A was 8.6% (2/23) and 8.7% (8/91) in patients with or without renal scarring respectively. The difference was insignificant (p>0.05). β-carotene deficiency was not present in any of the subjects.
The relation between vitamin A metabolism and respiratory, gastrointestinal, and urinary infections has been recognised previously.1 2 Deficiency of vitamin A is responsible for epithelial changes in the body. Hyperkeratosis and squamous metaplasia have been stated to predispose to infections.6 In addition, vitamin A and its metabolites have been reported to be necessary for T and B cell functions and its deficiency could lead to alterations in immune status.3
In this study, evaluation of the proximal tubular epithelial changes determined by 99mTc DMSA scintigraphy did not demonstrate any difference in patients with or without renal scarring with respect to their serum vitamin A and β-carotene concentrations. Carotenoids have been proposed to have antioxidant activities.3However, since none of our cases was deficient in β-carotene, it could be hypothesised that β-carotene was not sufficient by itself to prevent renal scarring in UTIs. On the other hand, patients with renal scarring were also shown to have serum vitamin A concentrations which were no lower than those of the patients without scarring. However, the degree of hypoactivity in scarred kidneys of patients with greater than 10% difference between negative uptakes of their kidneys was significantly inversely related to serum vitamin A concentrations. This finding emphasises the importance of the serum vitamin A concentration in advanced renal scarring due to recurrent UTIs. In this study, serum vitamin A and β-carotene were measured by the time irreversible renal injury (scarring) had occurred. Since renal scarring is defined as the persistence of hypoactivity in DMSA scintigraphy for 4–6 months, prospective studies could not be performed within a short time by this method.4 If serum vitamin A is determined at the time of the initial DMSA scan, nutritional factors and other intervening infections could alter its level during the next 4–6 months.
In this study, serum vitamin A was found to be related to the level of hypoactivity in patients with advanced renal scarring. This relation could result from the interaction between vitamin A and systemic immune response or epithelial tissue lining renal parenchyma and/or urinary tract.3 6
Isolated hypovitaminosis A ratio was not different among the patients with or without renal scarring. Isolated β-carotene deficiency was not present in any of the patients. Since β-carotene deficiency was not present, low vitamin A concentrations could be explained as secondary to infections.6 Furthermore, besides the effect of vitamin A deficiency on UTIs and renal scarring, recurrent UTIs could be the cause of low vitamin A.7
We conclude that our study demonstrated a relation between serum vitamin A concentrations and magnitude of hypoactivity in99mTc DMSA scan in patients with advanced renal scarring. However, no relation was determined between β-carotene and renal scarring.