Factors associated with carotid intima media thickness in South African children with chronic kidney disease
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BACKGROUND: Increased carotid intima media thickness (cIMT) is one of the early changes seen in chronic kidney disease (CKD) associated cardiovascular disease. This study aimed to determine cIMT measurements and its association with cardiovascular risk factors, including fibroblast growth factor-23 (FGF-23) and fetuin-A, in South African children with CKD. MATERIALS AND METHODS: 72 children (5 - 18 years) with CKD; 20 with CKD I, 23 with CKD II - IV, 29 with CKD V (on dialysis) were recruited. Each patient had a clinical examination and blood samples assessed for creatinine, urea, albumin, calcium, phosphorus, parathyroid hormone, alkaline phosphatase, total cholesterol, hemoglobin, C-reactive protein, vitamin D, fetuin-A, and FGF-23. cIMT was measured with high-resolution ultrasound. RESULTS: The mean age was 10.8 (3.5) years, and there were 49 males and 23 females (2 : 1). The overall median (range) cIMT was 0.505 mm (0.380 - 0.675) and was highest in patients with dialysis-dependent CKD (p = 0.003). Mean arterial pressure (MAP), hemoglobin, and PTH showed a significant correlation with cIMT (p < 0.001, p = 0.034, and p = 0.002, respectively). After adjusting for confounders in a multivariable analysis, disease duration, MAP, hemoglobin, and estimated glomerular filtration rate (eGFR) were independently associated with cIMT, p = 0.039, 0.001, 0.006, and 0.001, respectively. No significant relationship between cIMT and plasma levels of fetuin-A and FGF-23 was found. CONCLUSION: This study reports high cIMT measurements and their independent association with disease duration, MAP, hemoglobin, and eGFR. However, no similar association was found with fetuin-A and FGF-23.

Cardiovascular risk factors and mortality in children with chronic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) begins early in children with chronic kidney disease (CKD), and its progression is determined by the presence of single or multiple cardiovascular risk factors (CVRFs). OBJECTIVE: To determine the prevalence of CVRFs in children with CKD and their association with mortality in children on chronic dialysis. METHODS: This comparative cross-sectional study recruited children aged 5 - 18 years with all stages of CKD. All patients had a short history taken along with a physical examination, and their blood samples were assessed for serum creatinine, urea, albumin, calcium, phosphorus, parathyroid hormone, alkaline phosphatase, total cholesterol (TC), haemoglobin and C-reactive protein. Urine samples were also assessed for proteinuria. RESULTS: One hundred and six children who met the study criteria were recruited, 34 with CKD I, 36 with CKD II - IV and 36 with CKD V (dialysis). The overall median age was 11 years (range 8 - 14), and the male/female ratio was 2.1:1. The most common CVRF was anaemia (39.6%). The rate of anaemia was higher in the dialysis group than in the CKD II - IV and CKD I groups (77.8%, 33.3% and 5.9%, respectively). Other CVRFs detected were hypertension, proteinuria, hypercholesterolaemia and dysregulated mineral bone metabolism. Seven deaths were recorded in the dialysis group during the study period. Severe hypertension and intracranial bleeding were the most common causes of death. Modifiable risk factors such as increased TC and decreased albumin levels were more common than other CVRFs in the dialysis patients who died. CONCLUSIONS: CVRFs may be present in early CKD, even before the decline in GFR. Routine screening for CVRFs, along with timely intervention, may prevent the progression of CVD and mortality later in life.

Cardiac Changes and Their Association with Fetuin-A and Fibroblast Growth Factor-23 in Children with Chronic Kidney Disease.

AIMS: In children with chronic kidney disease (CKD), fetuin-A and fibroblast growth factor-23 (FGF-23) have been implicated in the mechanism and progression of several cardiac changes. This study aimed to determine the types and rates of cardiac changes in children with CKD and their association with fetuin-A, FGF-23, and other cardiovascular risk factors (CVRFs). METHODS: This comparative cross-sectional study recruited 88 children (5-18 years): 27 CKD I with a glomerular filtration rate (GFR) >90 mL/min/1.73 m2 and 61 with a GFR of <90 mL/min/1.73 m2 (29 CKD II-IV, 32 CKD V-dialysis). Each patient had a short demographic and clinical history taken along with a physical examination. Blood was taken and sent for routine tests and for fetuin-A and FGF-23 assay. All patients had an echocardiogram to evaluate cardiac structure and function. RESULTS: The distribution of left atrial diameter (LAD) and left ventricular (LV) mass differed significantly (p < 0.05) across the different CKD groups. Abnormal LAD was seen in 10% of patients; LV hypertrophy (LVH) in 27%; LV systolic dysfunction in 6% and diastolic dysfunction in 1 patient. Fetuin-A was the only independent predictor for abnormal LAD; mean arterial pressure was independently associated with concentric LVH, and age and hypoalbuminemia with eccentric LVH. Overall, the dialysis group had the highest rate of cardiac changes and associated risk factors. CONCLUSION: Though not common, the importance of left atrial changes in children with CKD is highlighted along with the need to address modifiable CVRFs such as hypertension and hypoalbuminemia.

Idiopathic nephrotic syndrome in South African children.

BACKGROUND: Different histo-pathological types and treatment response patterns of Idiopathic nephrotic syndrome (INS) have been associated with differences in ethnicity and geographical location. OBJECTIVE: To provide an update on the steroid response and renal histo-pathological pattern in children treated for INS. METHOD: Medical records of children with INS treated at the Charlotte Maxeke Johannesburg Academic Hospital were reviewed. RESULTS: Mean age was 5.3 years ± 2.8. The majority (68.1%) of the 163 children were of the black racial group. The highest rate of INS was seen in the 2-6 year age group (71.2%). The black racial group had the highest rate (42/111; 37.8%) of focal segmental glomerulosclerosis (FSGS), and the white race had the highest rate (9/14; 64.3%) of minimal change disease (MCD). Ninety four (57.7%) patients were steroid sensitive (SSNS) while 69 patients (42.3%) were steroid resistant (SRNS). Minimal change disease was the most common histo-pathological type seen in SSNS (60%), while FSGS was the most common observed in patients who had SRNS (65.2%). CONCLUSION: There appears to be a higher rate of FSGS in all the racial groups, and also a higher rate of MCD in the black race group, when compared to previous reports.

Paediatric cancer survivors demonstrate a high rate of subclinical renal dysfunction.

BACKGROUND: Clinical manifestations of renal dysfunction in childhood cancer survivors include hypertension, proteinuria, tubulopathy (and its biochemical consequences) and renal insufficiency. This study aimed to determine the factors associated with renal dysfunction in paediatric cancer survivors at a single centre in Johannesburg. PROCEDURE: A descriptive cross-sectional study was performed on 130 cancer survivors between 2 and 18 years of age. Physical examination and screening urine dipstick were performed on all patients. Blood results of samples routinely drawn were analysed. RESULTS: After a median follow-up period of 2 years, the various manifestations of renal dysfunction included decreased estimated glomerular filtration rate (eGFR), hypomagnesaemia, hypophosphataemia, proteinuria, haematuria and hypertension. In total, 34 survivors (26.15%) had at least one manifestation of renal dysfunction after completing treatment. The most prevalent manifestation of renal dysfunction was decreased eGFR (17.7%) followed by hypomagnesaemia (6.2%) and hypophosphataemia (4.6%). Patients with pre-existing renal dysfunction were three times more likely to have renal dysfunction post-treatment (P = 0.020). Ifosfamide (P = 0.010) and nephrectomy (P = 0.003) had independent significant impact on reduction in eGFR. High cumulative ifosfamide doses were identified as a possible cause for hypophosphataemia (P = 0.021). CONCLUSION: While not clinically evident in the early follow-up period, the high rate of renal dysfunction is concerning. We suggest that patients with pre-existing renal dysfunction should be assessed by a nephrologist prior to initiation of cancer therapy, and nephro-protective measures should be employed stringently in all children with cancer. Patients with decreased eGFR should be followed up closely in a multidisciplinary late effects clinic.

Persistent microalbuminuria in human immunodeficiency virus infected children in kano, Nigeria.

Microalbuminuria has been reported to be a precursor of HIV related renal disease, which if detected early and coupled with appropriate intervention may slow or retard the progress of the disease. One hundred and seventy-eight HIV infected children aged 15 years and below were recruited from the Paediatric Infectious Disease Clinic of Aminu Kano Teaching Hospital (AKTH), Kano, to determine the prevalence of persistent microalbuminuria using the albumin creatinine ratio (ACR). Early morning urine samples and spot urine samples were analyzed using a dipstick specific for microalbumin. Those who tested positive had their samples reanalyzed in the laboratory using immunometric assay and Jaffe reaction method for albumin and creatinine, respectively. Patients that had ACR of 30-300 mg/g were said to have microalbuminuria and had their urine samples retested after 6 to 8 weeks. Twelve children (6.7%) had persistent microalbuminuria and had a mean age of 7.5 ± 3.3 years, with a male to female ratio of 1 : 1. There was no significant relationship between the finding of microalbuminuria and age, sex, duration of infection, and the use of highly active antiretroviral therapy. Periodic screening for microalbuminuria using albumin specific dipstick should be considered for children with HIV infection.