Perspectives: Neonatal acute kidney injury (AKI) in low and middle income countries (LMIC).

Neonatal AKI (NAKI) remains a challenge in low- and middle-income countries (LMICs). In this perspective, we address issues of diagnosis and risk factors particular to less well-resourced regions. The conservative management pre-kidney replacement therapy (pre-KRT) is prioritized and challenges of KRT are described with improvised dialysis techniques also included. Special emphasis is placed on ethical and palliation principles.

Factors associated with graft survival in South African adolescent renal transplant patients at CMJAH over a 20-year period (GRAFT-SAT Study).

BACKGROUND: In the developed world, studies on transition of adolescent renal transplant patients have noted high rates of rejection, non-adherence and graft loss. There is a paucity of data in developing countries and none from South Africa. METHODS: We evaluated patient and graft outcomes during adolescence (10-19 years), of patients who received a renal transplant over a 20-year period (1990-2010), at a tertiary hospital in Johannesburg. Cox proportional hazards models and Kaplan-Meier curves were used to analyse graft and patient survival. RESULTS: A total of 213 kidney transplants were done in 162 patients during the study period, 165 transplants occurred during the adolescent period. Factors associated with graft failure on multivariate analysis included non-white race, transplant during the adolescent period ([aHR] 3.94; 95% [CI], 2.25-6.91), non-compliance with follow-up (aHR 3.89; 95% CI, 1.76-8.60) and receipt of a DD graft (aHR 2.10; 95% CI, 1.27-3.48). Patient survival rates at 1-, 3-, 5- and 10-years were 98.8%, 97.6%, 95.1% and 93.9% respectively. CONCLUSION: High rates of graft rejection and loss occurred in South African renal transplant recipients in the adolescent period, especially in those retained in paediatric care. Establishment of transition clinics may improve the graft outcomes of this vulnerable group and warrant further research.

Contemporary outcomes of the pediatric kidney transplant program in Johannesburg, South Africa, between 2004 and 2017: Better or not-And which way forward?

BACKGROUND: Outcomes for the pediatric kidney transplant program in Johannesburg (1984-2003) were found to be suboptimal. In this study, we compared (a) early (era 1:1984-2003) to contemporary (era 2:2004-2017) outcomes and (b) compared contemporary outcomes between the public and private sector hospitals in our program. METHODS: We conducted a retrospective record review of all pediatric (<18 years) KA transplants performed in our kidney transplant program at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) and Wits Donald Gordon Medical Centre (WDGMC) from 2004 to 2017. We collected the following data per site: number of recipients, transplants performed, mean follow-up time, and grafts lost; per recipient: age at time of transplant, sex, self-reported population group; transplant history; donor type; etiology of ESKD; recipient and graft survival. Outcomes for era 1 were based on data published on our kidney transplant program, based at CMJAH. RESULTS: At CMJAH (public sector), there was no improvement in recipient and graft survival over time. In the contemporary analysis, 1-, 5-, and 10-year recipient survival, as % (95% CI) was 93 (84-97); 76 (64-84); 59 (44-70) for CMJAH, and 98 (90-99); 95 (86-99); 82 (54-94) for WDGMC (private sector). Similarly, 1-, 5- and 10-year graft survival was 75 (63-84); 55 (42-66); 36 (24-49) for CMJAH, and 96 (87-99); 84 (73-91); 64 (48-76) at WDGMC. CONCLUSION: Contemporary outcomes for the pediatric kidney transplant program at WDGMC are comparable to outcomes achieved in middle- and high-income settings. However, outcomes at CMJAH are suboptimal, reflecting numerous health system, infrastructural and human resource challenges.

The podocin V260E mutation predicts steroid resistant nephrotic syndrome in black South African children with focal segmental glomerulosclerosis.

In black African children with focal segmental glomerulosclerosis (FSGS) there are high rates of steroid resistance. The aim was to determine genetic associations with apolipoprotein L1 (APOL1) renal risk variants and podocin (NPHS2) variants in 30 unrelated black South African children with FSGS. Three APOL1 variants were genotyped and the exons of the NPHS2 gene sequenced in the cases and controls. APOL1 risk alleles show a modest association with steroid sensitive nephrotic syndrome (SSNS) and steroid resistant nephrotic syndrome (SRNS). The NPHS2 V260E variant was present in SRNS cases (V/V = 5; V/E = 4; E/E = 11), and was absent in SSNS cases. Haplotype analysis suggests a single mutation origin for V260E and it was associated with a decline in kidney function over a 60-month period (p = 0.026). The V260E variant is a good predictor of autosomal recessive SRNS in black South African children and could provide useful information in a clinical setting.

Factors associated with carotid intima media thickness in South African children with chronic kidney disease
.

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.

The Financial Cost Incurred by Families of Children on Long-Term Dialysis.

BACKGROUND: Costs of dialysis reported in countries where dialysis is government-funded are often those incurred by the state, and only a few take into account the financial burden to the family of the index patient. This study investigated the financial cost implication to families of pediatric patients on maintenance dialysis and how aid provided by the government alleviates their financial burden. METHODS: This descriptive cross-sectional study recruited 24 children on peritoneal dialysis (PD) and hemodialysis (HD), and a structured questionnaire was administered to the parents/caregivers of these patients to obtain information on their family size, total family income, cost of transportation, employment status of attending caregiver, and number of work days missed due to hospital visits. RESULTS: Complete data were available for 19 patients (7 on PD and 12 on HD). The mean age was 14 ± 6 years, and there were 11 males and 8 females. The average monthly income of the families recruited was 2,946 ZAR (261 USD). This amount included the contribution of a monthly state-provided social grant of 1,300 ZAR (115 USD) in 16/19 subjects. The average monthly expenditure of the HD and PD groups made up 27.1% and 4.9% of their average income. CONCLUSION: Transport cost for our patients on dialysis significantly impacts on the overall family income, especially for patients on HD, and, without government aid, the families of our patients would have far less money available for their daily needs.

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.