In 2008, China experienced a melamine-contamination event, which has caused widespread concern and criticism [
Although the event has ended, it may still be valuable to provide an overview of the clinical profile and prognosis status of the affected children. There are three reasons. Firstly, the overall clinical and prognosis information may be useful for the treatment of melamine-induced or other similar renal diseases in the future. Young children are still likely to be exposed to melamine-contaminated dairy products, as supported by the fact that (1) the melamine-tainted milk powder reappeared in Chinese markets in 2010 [
PubMed and EMBASE were searched for relevant studies using the following three keywords: “melamine,” “cyanuramide,” and “1,3,5-triazine-2,4,6-triamine.” China National Knowledge Infrastructure and Wanfang database, the two major Chinese electronic databases, were searched for articles published in Chinese. These searches were limited to human studies published between September 2008 and June 2012. The reference lists of retrieved articles were hand-searched for additional studies. Moreover, we searched the PubMed monthly after June 2012 to identify any newly published studies.
Studies were considered to be eligible for the review and meta-analysis if they reported a recovery rate for a specified period after diagnosis or initiation of treatment (i.e., 1 month, 3 months, and 6 months). A customized database was developed for data extraction. The information that was collected from each article included the following: the first author, the number of patients, types of patients, treatment types, follow-up duration, and recovery status; the mean and range of patients’ age and duration of melamine exposure; the gender ratio of patients; types of kidney abnormalities; the clinical manifestation of patients; and the mean and range of diameter of calculi.
Because no standard instrument is available for quality assessment of follow-up studies [
Data syntheses were performed using the Meta-Analyst 3.13 and RevMan 5.1. The pooled recovery rate, male to female ratio, percentage of asymptomatic patients, percentage of patients with calculi <10 mm in diameter, and their 95% confidence intervals were calculated based on random effects model, using the reciprocal of the variance as the weighting factor. Statistical heterogeneity across studies was assessed using the
Our initial search that was conducted on 30 June 2012 yielded a total of 1571 records (1188 in Chinese and 383 in English); after review of the titles/abstracts of 1156 nonduplicate records, we identified 148 potentially relevant records; after reviewing the full text, we identified 26 studies [
Process of study inclusion in meta-analysis.
The 26 studies, involving a total of 2164 patients, were conducted in 11 different provincial administrative areas of China, comprising 10 [
Of the 26 studies, 4 [
The characteristics of studies including in this meta-analysis.
First author | M/F ratio | Diagnostic age (month)* | Duration of exposure (month)* | Diameter of calculi (mm) | Percent of asymptomatic patients (%) |
|
Treatment types |
|
Follow-up duration (month) | Quality score | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 3 | 6 | 12 | 24 | ||||||||||
Sun [ |
2.13 : 1 | 11.8, 6–36 | 9.5, 0.5–24 | —, — | 0 | IP | ST, CT | 22 | — | 15 | 20 | 22 | — | 8 |
Chen [ |
1.88 : 1 | 24.0, 2–96 | 17.0, 2–69 | —, — | 87.8 | OP | NO | 49 | — | 30 | — | — | — | 8 |
Wen [ |
3.17 : 1 | 23.4, 2–84 | 12.4, — | <10, 100.0% | 38.0 | IP | CT | 50 | 32 | — | — | — | — | 9 |
Wen [ |
2.61 : 1 | 25.5, 16–56 | —, — | —, — | 0 | IP | ST, CT | 195 | — | — | — | — | 194 | 7 |
Zhang [ |
0.67 : 1 | 16.0, 1–16 | 15.7, — | <5, 100.0% | — | OP | CT | 54 | 49 | — | — | — | — | 7 |
Shen [ |
— | —, — | —, — | —, — | 93.6 | OP | DW | 265 | 139 | 178 | 234 | 253 | — | 7 |
Yang [ |
3.00 : 1 | 18.0, 9–33 | 11.1, 5–18 | —, — | 0 | IP | CT | 8 | 6 | — | — | — | — | 10 |
Sun [ |
1.47 : 1 | 13.5, — | 12.5, — | —, 94.9% | 65.8 | IP | CT | 29 | 20 | — | — | — | — | 10 |
OP | CT | 50 | 46 | — | — | — | — | |||||||
Kuang [ |
1.82 : 1 | 19.0, 1–36 | 10.8, 1–19 | 1–72, 89.6% | 73.3 | IP | CT | 96 | — | — | 66 | — | 75/91$ | 7 |
Liu [ |
1.61 : 1 | 19.8, 6–36 | 16.5, 2–36 | 1–9, 100.0% | 91.5 | OP | CT | 47 | — | — | 42 | — | — | 8 |
Chang [ |
1.24 : 1 | —, — | —, — | —, — | — | OP | DW | 43 | 15 | 21 | 36 | — | — | 6 |
Zhang [ |
2.64 : 1 | 14.0, 2–36 | —, — | 5–15, 97.5% | 68.8 | IP | CT | 37 | 30 | — | — | — | — | 8 |
IP | ST | 43 | — | 41 | — | — | — | |||||||
Wang [ |
1.47 : 1 | 11.2, 2–66 | —, — | —, — | 99.4 | OP | CT | 389 | 295 | 306 | — | — | — | 7 |
Sun [ |
0.81 : 1 | 14.0, 2–96 | 11.0, 2–29 | —, 76.9% | 92.3 | IP | CT | 65 | 46 | — | — | — | — | 9 |
Tang [ |
1.68 : 1 | —, 2–120 | —, — | 2–13, — | — | OP | CT | 44 | 30 | — | — | — | — | 7 |
OP | DW | 30 | 14 | — | — | — | — | |||||||
Zhang [ |
— | —, — | —, — | >4, — | — | OP | CT | 41 | 7 | — | — | — | — | 6 |
Zhu [ |
2.15 : 1 | 15.6, 3–36 | —, — | 4–10, 100.0% | — | IP, OP | NO | 75 | — | — | — | 59 | — | 5 |
Zhu [ |
0.77 : 1 | 9.2#, 2–66 | —, — | 3–20, — | 98.2 | OP | CT | 28 | 6 | — | — | — | — | 7 |
He [ |
0.67 : 1 | 18.0, 5–36 | —, 1–18 | <5, 100.0% | 73.3 | OP | CT | 60 | 54 | — | — | — | — | 9 |
Shang [ |
1.70 : 1 | 26.0, 13–48 | —, — | —, 67.9% | — | IP | ST | 27 | — | — | — | 25 | — | 8 |
IP | CT | 54 | — | — | — | 51 | — | |||||||
Zhang [ |
1.78 : 1 | 16.0, 2–36 | 15.0, 2–36 | —, — | — | IP | ST, CT | 98 | — | 61/98 | 78/90 | 86/91 | — | 8 |
Mi [ |
2.00 : 1 | 44.4, 1–72 | —, — | —, 95.0% | — | OP | CT | 15 | 13 | — | — | — | — | 7 |
Long [ |
0.68 : 1 | 37.0, 19–72 | 14.0, 2–32 | 4–11, — | — | IP, OP | CT | 37 | — | 34 | — | — | — | 8 |
Wang [ |
1.54 : 1 | 20.0, 3–36 | —, — | 4–19, — | 80.3 | IP, OP | CT | 127 | 94 | 111 | 113 | — | — | 8 |
Xu [ |
1.55 : 1 | 20.4, 1–60 | —, 1–36 | —, 100.0% | — | OP | DW | 86 | — | 86 | — | — | — | 9 |
M: male; F: female; IP: inpatient; OP: outpatient; ST: surgical treatment; CT: conservative treatment; DW: only drinking more water; NO: no description.
*The data was expressed as mean and range.
#The value was the median; in order to facilitate the calculation, we treated it as mean.
Of the 2164 patients, 2044 (94.5%) had urinary calculi, 103 (4.8%) had hydronephrosis, and 17 (0.7%) had urinary obstructions. Of the 26 studies, 13 [
Of the 26 studies, 15 reported a recovery rate at one month after diagnosis or initiation of treatment, 10 reported a recovery rate at 3 months, 7 at 6 months, 5 at 12 months, 1 at 18 months, and 1 at 24 months. The pooled recovery rates at 1, 3, 6, and 12 months were 67.1% (95% CI 57.1%–75.8%), 76.3% (95% CI 67.0%–83.6%), 85.4% (95% CI 78.6%–90.3%), and 92.3% (95% CI 83.6%–96.6%), respectively; the corresponding values of
Subgroup analyses regarding the pooled recovery rates (%) at 1, 3, and 6 months.
Subgroup | Rate (95% CI) | ||
---|---|---|---|
1 month | 3 months | 6 months | |
Treatment types | |||
Nonspecific treatment | 46.2 (35.5–57.3)* | 72.5 (48.7–88.1) | 87.6 (83.4–90.8) |
Specific treatment | 71.9 (61.7–80.3) | 81.5 (71.0–88.8) | 85.2 (74.7–91.9) |
Patient types | |||
Inpatient | 70.5 (63.5–76.6) | 77.6 (51.9–91.8) | 82.1 (64.3–92.1) |
Outpatient | 64.5 (49.2–77.3) | 71.2 (62.0–80.8) | 87.8 (83.9–90.8) |
Diagnostic age | |||
≥18 months | 77.8 (66.1–86.3) | 88.2 (68.1–96.3) | 83.5 (65.5–93.1) |
<18 months | 74.7 (60.8–84.9) | 76.5 (62.0–86.6) | 87.4 (79.8–92.4) |
Duration of exposure | |||
≥12 months | 81.2 (62.8–91.8) | 71.7 (52.8–85.2) | 79.9 (48.2–94.4) |
<12 months | 71.2 (59.8–80.4) | 68.2 (46.6–84.0) | 87.5 (80.7–92.1) |
*
The funnel plots regarding the recovery rates at 1 month and at 3 months were slightly asymmetric (Figure
Funnel plots for the recovery rate at 1 month (a) and at 3 months (b).
In this review and meta-analysis, we found that about 95% of the patients had urinary calculi and about 95% of the patients did not require surgical intervention. We also found that about 85% of the patients recovered in the first 6 months, whereas in the subsequent 6 months, only about half of the remaining 15% of patients recovered. We identified very few studies that reported a recovery rate for more than 12 months.
The summary of clinical characteristics showed that the majority of patients had urinary calculi, which corroborates the view that the melamine-related kidney abnormalities are primarily induced by physical obstruction of the calculi [
To the best of our knowledge, this is the first meta-analysis to summarize the clinical profile and recovery status of the affected children. We synthesized 26 small-scale studies from one-third of the provincial administrative areas in China and provided some relatively robust estimates, such as pooled male to female ratio and pooled recovery rate. In addition to the main pooled analyses, we conducted various subgroup and sensitivity analyses to test the robustness of the pooled recovery rate and to explore potential sources of heterogeneity. Despite these strengths, our review has limitations. First, due to the lack of detailed information in the original reports, we were unable to conduct subgroup analyses by gender, diameter of calculus, consumption of milk powder, and disease severity; these subgroup findings may be of broad interest and clinical significance. Second, we selected studies primarily based on the availability of information on recovery status because we aimed to provide a complete clinical profile, especially the prognosis status, of the affected children. The strict selection criteria may have led to exclusion of studies that provided only the clinical characteristics of patients but with no information on recovery status.
This review and meta-analysis provides an overview of clinical profile and the recovery status of Chinese children affected by melamine-resulted urinary diseases. We found that the majority of patients had small urinary calculi, were asymptomatic or mildly symptomatic, and could recover from kidney abnormalities without surgical intervention. We also found that about 8% of the patients still had kidney abnormalities one year after diagnosis or treatment initiation. The lack of up-to-date data on recovery status of the affected children indicates the need for further investigation.
The authors declare that they have no conflict of interests.
The study was supported by a grant from the National Nature Science Foundation of China (Grant no. 81072372).