A Clinical Study On Epidemiology Of Chronic Kidney Disease In Children And Its Associated Complications

BackgroundAs a severe public health issue, chronic kidney disease (CKD) is causing heavy social and economic burdens world widely. Epidemic studies have shown that cases of children CKD are increasing in recent years. With an obscure onset, some children CKD patients may finally develop into end stage renal disease (ESRD) while the others are at high risk of having ESRD when they are grown up. The causes of children CKD are different from that in adults. In China, researches on epidemiology of children CKD are usually confined to end stage patients with a limited case library studied. However, with the development of CKD and decreasing kidney functions, a series of chronic complications, like hypertension, anemia, growth failure and metabolic bone disease, will become more and more obvious. And some complications may even occur in the early stage of CKD, affecting patients’outcomes and life qualities. In this study, through clinical analysis of CKD stage 2 to 5 patients from Children’s Hospital of Fudan University in the last 10 years, the etiological factors and onsets of children CKD stage 2 to 5 are summarized, which could give information to the early diagnosis of that disease. Moreover, a cross-sectional study on the occurrence, prevalence and treatment of CKD complications related to patients’growth, anemia, minerals & bones’ metabolism and cardiovascular diseases was conducted in order to provide clinical evidences for diagnosis and treatment of these complications. Meanwhile, these results will be useful in guiding better early diagnosis and management of CKD complications. The level of fibroblast growth factor 23 (FGF23) was also studied. In particular, the change of FGF23 level at different CKD stages and the relationship between FGF23 level and metabolic calcium and phosphorous disorder were investigated. Possibility of using FGF23 level as an indicative factor for early diagnosis of CKD complications was also explored.Methods1. Retrospective etiological analysis:information on 264 cases of children CKD patients from 2004.1 to 2013.12 in Children’s Hospital of Fudan University with CKD stage 2-5 were collected. A retrospective study on the causes, clinical characteristics and onsets was conducted.2. Cross-sectional study of CKD complications:among the 264 cases, demographic data, clinical characteristics, laboratory findings and treatment of patients in the period of 2012.7 to 2013.12 were collected. And their complications of anemia, hypertension, growth failure, metabolic mineral and bone disorder and left ventricular hypertrophy (LVH) were analyzed.3. Study on FGF23 level:intact and C-term FGF23 levels in children CKD patients were analyzed by ELISA. Meanwhile, SCr, Ca, P and PTH were measured. The relationship between FGF23 level at different CKD stages and blood biochemical data was investigated.Results1. In the collected 264 cases,116 cases (43.9%) were caused by Congenital anomalies of the kidney and urinary tract (CAKUT),61 cases (23.1%) by glomerular disease,15 cases (5.7%) by hereditary kidney disease,14 cases (5.3%) by other diseases and 58 cases (22.0%) by unknown causes. In the group with age between 0-5,59.3% (48 cases) patients had primary disease with CAKUT,14.8%(12 cases) with glomerular disease. In the group with age larger than 10,49.2%(30 cases) patients had primary disease with glomerular disease and 32.0%(32 cases) with unknown causes. For diagnosis age,52 cases (19.7%) of patients were diagnosed at stage 2 with a median age of 6.9 (3.7,11.0) years,67 cases (25.4%) at stage 3 with a median age of 8.0 (4.4-10.5) years,52 cases (19.7%) at stage 4 with a median age of 7.31(3.4-10.8) years and 93 cases (35.2%) at stage 5 with a median age of 10.3 (7.6-12.6) years. Since 2011, the number of patients came to our hospital for CKD diagnosis increased a lot with a significant increase in the ratio of known primary diagnosis (χ2=4.653, P=0.031). Cases with unknown causes decreased from 27.1% to 16.2%.42.0%(21/52 cases) patients in Shanghai were diagnosed with an onset at stage 2, percentage of which was higher than that of patients in other areas diagnosed at the same stage. Only 57 cases (21.6%) were diagnosed by physical examination while others were found by occurrence of symptoms.2. In cross-sectional study,123 cases of CKD patients at stage 2-5 were collected. Among them,56 cases (45.5%) were caused by CAKUT,32 cases (26.0%) by glomerular disease,7 cases (5.7%) by hereditary kidney disease,6 cases (4.9%) by other diseases and 22 cases (17.9%) by unknown causes.17 cases (13.8%) were at stage 2,17 cases (13.8%) at stage 3,16 cases (13.0%) at stage 4 and 73 cases (59.3%) at stage 5. The median age was 9.9 (6.3,13.2) years with a median course of disease 1.0 (0.1, 2.3) years. The median follow up time in our department was 0.4 (0,2.0) years with 60 cases (48.8%) larger than 6 months. The overall prevalence of anemia in this group was 80.5%with 11.8% for stage 2,58.8% for stage 3,87.5% for stage 4 and 100% for stage 5. For stage 2,100% patients had Hb greater than 110 g/L, stage 330.0%, stage 435.7% and stage 534.2%. The overall usage rates of iron supplementation and EPO were 91.9% and 79.8%, respectively. For stage 5 patients, the usage rates were 98.6%(72/73 cases) and 95.9%(70/73 cases). For those who had a follow up time larger than 6 moths, the Hb Level was significantly better than those who had follow up time less than 6 months (χ2=15.338, P<0.05). The prevalence of hypertension was 61.8% with 29.4% for stage 2,41.2%for stage 3,43.8% for stage 4 and 78.1% for stage 5.51.3% SBP and 55.3% DBP of the overall patients has not reached the 95th percentile for the same sex, age and height, respectively. And for stage 5,49.1% SBP and 52.6% DBP has not reached the 95th percentile for the same sex, age and height, respectively.65.8%(50/76) patients have used CCB while 64.5% (49/76) patients have used ACEI or ARB. Other 27.6%(21/76) patients have used β-blocker with 6.6%(5/76) used no drugs.50.0% (38/76) patients have used more than 1 drug.37.4% patients had growth failure with 11.8% for stage 2. And the number in stage 3-5 was 35.3%-43.8%. The prevalence of CKD mineral and bone disease (CKD-MBD) was 93.5%. It already has a high prevalence in early stage CKD patients while all patients in stage 5 had this disease. In 116 cases with echocardiography,55 cases were diagnosed with LVH while 22 cases diagnosed with severe LVH. The diagnosed LVH patients had a shorter course of disease and were younger, compared with those patients who had no LVH. Logistic regression analysis indicated that hypertension, secondary hyperparathyroidism, Hb 60-90 g/L and age<10 were the independent risk factors of LVH.3. The study of FGF23 level shows that with the decrease of eGFR, FGF23 level tended to increase. FGF23 level in the group of eGFR<15 ml/min·1.73m2 increased significantly, compared to groups with eGFR≥45 ml/min·1.73m2 and 15 ml/min· 1.73m2≤eGFR<45 ml/min·1.73m2 while FGF23 Level in those two groups had no significant differences. Calcium level also tended to decrease but without statistical significance. Phosphorous level had a tendency to increase with a significant difference between group with eGFR≥45 ml/min·1.73m2 and group with eGFR<15 ml/min· 1.73m2. Pearson correlation analysis indicated there was a linear positive correlation between lniFGF23 (natural logarithm of iFGF23) and lncFGF23 (natural logarithm of cFGF23) (P<0.001). LniFGF23 had a positive correlation with CKD course of disease, serum phosphorous and serum calcium (calibrated) while had a negative correlation with eGFR. LncFGF23 had a positive correlation with serum phosphorous, serum calcium (calibrated) and lniPTH (natural logarithm of intact parathyroid hormone) while had a negative correlation with eGFR (r=-0.431, P< 0.001). Multiple regression analysis indicated calibrated calcium, phosphorous, eGFR and lniPTH were the influential factor of lniFGF23 while calibrated calcium, eGFR and lniPTH were the influential factor of lncFGF23. The iPTH, iFGF23 and cFGF23 level in high phosphorous group were significantly larger than those in normal phosphorous group. Patients in group with secondary hyperparathyroidism had relatively low calcium but high phosphorous. However, iFGF23 and cFGF23 levels had no significant difference in these two groups.Conclusion1. The major cause of children CKD in our hospital for the last ten years was CAKUT with 43.9% patients diagnosed. The second one is glomerular disease with 23.1% patients diagnosed. The onset age of CAKUT was relatively small. The early intervention thus would benefit for the prognosis. Using urinary imaging examination would be helpful to early diagnosis of CKD in young age patients.2. For children CKD patients in stage 2-5, lots of chronic complications including anemia, hypertension, growth, nutrition, electrolytes disorder and metabolic calcium and phosphorous disorder are affecting their life qualities and outcomes. Anemia and CKD-MBD are the most common ones among all these complications. Their occurrence rates increase with the decrease of GFR level. Metabolic calcium& phosphorous disorder has been found in the very early stage children CKD patients. After treatment, clinical characteristics improved but anemia and hypertension rates were still not satisfied in this group. Age, anemia and hypertension are risky factors of LVH. Therefore, more attention needs to be paid on the diagnosis, treatment and management of CKD related complications.3. FGF23 level had a significant increase with the decrease of kindy function. Since FGF23 is invovled in mineral metabolism, its level is related to that of phosphorous, clacium and PTH. With a most intimate relationship with phsophorous, it may become an early indicator for phosphorous increase in CKD patients.