Paediatric Dialysis at a Tertiary Hospital in South-West Nigeria: A 4-Year Report.

INTRODUCTION: Dialysis is potentially lifesaving in children with acute kidney injury (AKI) or chronic kidney disease (CKD), but availability is limited in low-income countries and lower-middle-income countries (LMICs). METHODS: In the present study, we perform a 4-year study of patients who received peritoneal dialysis (PD) or haemodialysis (HD) at the Paediatric Nephrology Unit of the University College Hospital Ibadan, Nigeria. Subgroup analysis was performed on patients with sepsis or malaria AKI who underwent HD or PD for predictors of in-hospital mortality. RESULTS: A total of 167 children aged 7 days to 18 years, median 7 (interquartile range 3-12) years, (60.5% males) were studied. In total, 129 (77.2%) had AKI, while 38 had CKD. Regarding AKI, 83 children (64.3%) received HD only, 42 underwent PD only, while 4 underwent both HD and PD. Malaria AKI was treated with HD in 43 (51.8%) or PD in 8 (10.5%), while sepsis AKI was treated with HD in 20 (21.4%) or PD in 33 (78.6%). Mortality in AKI was 16.3% overall, 10.8% in children on HD only, and 26.2% in children on PD only. Patients with sepsis AKI had higher mortality compared to patients with malaria AKI (RR 7.96 [1.70-37.37]). Subgroup analysis showed that age, diagnosis, and dialysis modality were not independent risk factors for mortality. The aetiology of CKD was glomerulonephritis in 26 (68.4%): treatment was HD in 36 and PD in 2 with mortality being 26.3%. CONCLUSIONS: PD for AKI showed relatively good outcomes in a LMIC. However, funding and support for a formal dialysis program for the management of AKI and CKD are needed.

Childhood Nephrotic Syndrome in Africa: Epidemiology, Treatment Trends, and Outcomes.

Nephrotic syndrome is a common childhood glomerular disease that is associated with massive proteinuria and edema. Children with nephrotic syndrome are at risk of chronic kidney disease, disease-related complications, and treatment-related complications. Patients with frequently relapsing disease or steroid toxicity may require newer immunosuppressive medications. However, access to these medications is limited in many African countries owing to prohibitive cost, the need for frequent therapeutic drug monitoring, and a lack of appropriate facilities. This narrative review examines the epidemiology of childhood nephrotic syndrome in Africa, including trends in treatment and patient outcomes. In most of North Africa, as well as among White and Indian populations in South Africa, the epidemiology and treatment of childhood nephrotic syndrome closely resembles that of European and North American populations. Historically, secondary causes of nephrotic syndrome (eg, quartan malaria nephropathy and hepatitis B-associated nephropathy) were predominant among Blacks in Africa. Over time, the proportion of secondary cases has decreased, along with rates of steroid resistance. However, focal segmental glomerulosclerosis increasingly has been reported among patients with steroid resistance. There is a need for consensus guidelines for the management of childhood nephrotic syndrome in Africa. Furthermore, establishing an African nephrotic syndrome registry could facilitate monitoring of disease and treatment trends, and provide opportunities for advocacy and research to improve patient outcomes.

Trends in the epidemiology of childhood nephrotic syndrome in Africa: A systematic review.

Background: Childhood nephrotic syndrome, if left untreated, leads to progressive kidney disease or death. We quantified the prevalence of steroid-sensitive nephrotic syndrome, steroid-resistant nephrotic syndrome, and histological types as the epidemiology of nephrotic syndrome in Africa remains unknown, yet impacts outcomes. Methods: We searched MEDLINE, Embase, African Journals Online, and WHO Global Health Library for articles in any language reporting on childhood nephrotic syndrome in Africa from January 1, 1946 to July 1, 2020. Primary outcomes included steroid response, biopsy defined minimal change disease, and focal segmental glomerulosclerosis (FSGS) by both pooled and individual proportions across regions and overall. Findings: There were 81 papers from 17 countries included. Majority of 8131 children were steroid-sensitive (64% [95% CI: 63-66%]) and the remaining were steroid-resistant (34% [95% CI: 33-35%]). Of children biopsied, pathological findings were 38% [95% CI: 36-40%] minimal change, 24% [95% CI: 22-25%] FSGS, and 38% [95% CI: 36-40%] secondary causes of nephrotic syndrome. Interpretation: Few African countries reported on the prevalence of childhood nephrotic syndrome. Steroid-sensitive disease is more common than steroid-resistant disease although prevalence of steroid-resistant nephrotic syndrome is higher than reported globally. Pathology findings suggest minimal change and secondary causes are common. Scarcity of data in Africa prevents appropriate healthcare resource allocation to diagnose and treat this treatable childhood kidney disease to prevent poor health outcomes. Funding: Funding was provided by the Canadian Institute for Health Research (CIHR) and the National Institute of Health (NIH) for the H3 Africa Kidney Disease Research Network. This research was undertaken, in part, from the Canada Research Chairs program.

Treatment outcomes of Nigerian patients with tuberculosis: A retrospective 25-year review in a regional medical center.

INTRODUCTION: Tuberculosis (TB) remains a global health challenge and leading infectious killer worldwide. The need for continuous evaluation of TB treatment outcomes becomes more imperative in the midst of a global economic meltdown substantially impacting resource-limited-settings. METHODS: This study retrospectively reviewed 25-years of treatment outcomes in 3,384 patients who were managed for TB at a tertiary hospital in Nigeria. Confirmed TB cases were given directly observed therapy of a short-course treatment regimen and monitored for clinical response. RESULTS: Out of 1,146,560 patients screened, there were 24,330 (2.1%) presumptive and 3,384 (13.9%) confirmed TB cases. The patients' mean age was 35.8 years (0.33-101 years). There were 1,902 (56.2%) male, 332(9.8%) pediatric, and 2,878 (85%) pulmonary TB cases. The annual mean measured treatment outcomes were as follows: adherence, 91.4(±5.8) %; successful outcome, 75.3(±8.8) % potentially unsatisfactory outcome, 14.8(±7.2) %; and mortality 10.0(±3.6) %. Female, extra-pulmonary TB (EPTB), newly diagnosed, and relapsed patients compliant with treatment had successful outcomes. Adulthood and HIV infection were mortality risk factors. CONCLUSION: The mean annual successful treatment outcome is 75.3(±8.8) %. Female, pediatric, EPTB, new, and relapsed patients were predisposed to successful treatment outcomes. Lessons learned will guide future program modifications.

Acute kidney injury among paediatric emergency room admissions in a tertiary hospital in South West Nigeria: a cohort study.

BACKGROUND: Epidemiological data on paediatric acute kidney injury (AKI) in sub-Saharan Africa are limited and largely retrospective. We performed a prospective study of AKI among patients admitted through the emergency room. METHODS: Children admitted to the post-neonatal emergency room of the University College Hospital, Ibadan, Nigeria between February 2016 and January 2017 were studied. AKI was defined by Kidney Disease: Improving Global Outcomes serum creatinine criteria. AKI ascertainment relied on serum creatinine measurements carried out in routine care by post-admission Day 1. We compared in-hospital mortality by post-admission Day 7 for patients with and without AKI (no-AKI). RESULTS: Of the 1344 children admitted to the emergency room, 331 were included in the study. AKI occurred in 112 patients (33.8%) with a median age of 3.1 years [interquartile range (IQR) 0.9-9.4] and was Stage 3 in 50.5% of the cases. The no-AKI group had a median age of 1.8 (IQR 0.7-5.8) years. The underlying diagnoses in patients with AKI were sepsis (33.0%), malaria (12.5%) and primary renal disorders (13.4%). Twenty-four of the patients with AKI underwent dialysis: haemodialysis in 20 and peritoneal dialysis in 4. By Day 7 of admission, 7 of 98 (7.1%) patients in the AKI group had died compared with 5 of 175 (2.9%) patients in the no-AKI group [odds ratio 2.6 (95% confidence interval 0.8-8.5)]. Outcome data were not available for 58 (17.5%) patients. CONCLUSIONS: AKI is common among paediatric emergency room admissions in a tertiary care hospital in sub-Saharan Africa. It is associated with high mortality risk that may be worse in settings without dialysis.

National survey found that managing childhood nephrotic syndrome in Nigeria varied widely and did not comply with the best evidence.

AIM: This study explored any variations in managing childhood nephrotic syndrome between specialist centres in Nigeria and how closely the care reflected the best available evidence. METHODS: In 2016, the heads of Nigerian paediatric nephrology units were asked to complete a study questionnaire that focused on managing nephrotic syndrome. RESULTS: Of the 31 clinicians we approached, 81% returned the completed questionnaire. The majority (64%) had received paediatric nephrology training and 40% had practised for at least 10 years. We found that 60% prescribed an initial daily prednisolone for four weeks before reducing the dose and 32% prescribed it for six weeks. However, more marked variations were observed with the total steroid duration for new-onset nephrotic syndrome, with 16%, 44% and 40% prescribing prednisolone for 8, 12 and at least 16 weeks, respectively. Similarly, 56% prescribed prednisolone for less than eight weeks before diagnosing steroid-resistant nephrotic syndrome (SRNS) and 12% rarely requested a kidney biopsy for SRNS. In addition, 32% of the respondents preferred cyclophosphamide to calcineurin inhibitors for SRNS. CONCLUSION: There were significant variations in the management of childhood nephrotic syndrome in Nigeria and the diagnosis and treatment of SRNS differed substantially from the best available evidence.

Kidney disease in hepatitis B surface antigen-positive children: experience from a centre in south-west Nigeria and a review of the Nigerian literature.

BACKGROUND: Kidney disease is an important extra-hepatic manifestation of hepatitis B virus (HBV) infection. However, there is paucity of recent literature on kidney disease in children and adolescents with HBV infection from several parts of sub-Saharan Africa including Nigeria. OBJECTIVE: To review the pattern of kidney disease in hepatitis B surface antigen (HBsAg)-positive children and adolescents seen at a tertiary hospital in south-west Nigeria. METHODS: A retrospective study was undertaken of HBsAg-seropositive children with kidney disease managed at University College Hospital, Ibadan, from January 2004 to December 2015. Patients were identified from the paediatric nephrology unit admissions and the renal histology registers. RESULTS: 24 children and adolescents were studied, 17 of whom were male (70.8%), and the median age was 10.0 years (range 3-15). Ten (41.7%) had nephrotic syndrome, five (20.8%) had non-nephrotic glomerulonephritis, five (20.8%) were in end-stage renal disease (ESRD), including a patient with posterior urethral valves, and four had acute kidney injury secondary to acute tubular necrosis. Renal histology was available for 10 patients: nine had nephrotic syndrome associated with minimal change disease in six, focal segmental glomerulosclerosis in two and one had membanoproliferative glomerulonephritis. The patient with non-nephrotic glomerulonephritis had diffuse global sclerosis. CONCLUSION: The pattern of kidney disease in HBV-positive children demonstrated a predominance of nephrotic syndrome, followed by non-nephrotic glomerulonephritis, ESRD and acute kidney injury. Better diagnostic facilities and treatment are required. Prevention of HBV infection by universal childhood immunisation is the ultimate goal.

Acquisition, maintenance and adaptation of invasion inhibitory antibodies against Plasmodium falciparum invasion ligands involved in immune evasion.

Erythrocyte-binding antigens (EBAs) and P. falciparum reticulocyte-binding homologue proteins (PfRhs) are two important protein families that can vary in expression and utilization by P. falciparum to evade inhibitory antibodies. We evaluated antibodies at repeated time-points among individuals living in an endemic region in Nigeria over almost one year against these vaccine candidates. Antibody levels against EBA140, EBA175, EBA181, PfRh2, PfRh4, and MSP2, were measured by ELISA. We also used parasites with disrupted EBA140, EBA175 and EBA181 genes to show that all these were targets of invasion inhibitory antibodies. However, antigenic targets of inhibitory antibodies were not stable and changed substantially over time in most individuals, independent of age. Antibodies levels measured by ELISA also varied within and between individuals over time and the antibodies against EBA181, PfRh2 and MSP2 declined more rapidly in younger individuals (≤15 years) compared with older (>15). The breadth of high antibody responses over time was more influenced by age than by the frequency of infection. High antibody levels were associated with a more stable invasion inhibitory response, which could indicate that during the long process of formation of immunity, many changes not only in levels but also in functional responses are needed. This is an important finding in understanding natural immunity against malaria, which is essential for making an efficacious vaccine.

Haemodialysis for paediatric acute kidney injury in a low resource setting: experience from a tertiary hospital in South West Nigeria.

BACKGROUND: Acute kidney injury (AKI) is an important cause of preventable mortality among children. Management of AKI may require renal replacement therapy (RRT) but access to RRT for children in low resource settings is limited. Our study explored the role of haemodialysis in the management of children with AKI in a low resource setting in terms of aetiology and outcomes. METHODS: A review of patients managed in the Paediatric Nephrology Unit, University College Hospital Ibadan, South-West Nigeria, who underwent haemodialysis for AKI from January 2006 to December 2014. RESULTS: Sixty-eight patients (55.9% males), aged 3-16 (mean ± standard deviation, 9.0 ± 3.4) years were studied. The causes of AKI were sepsis (22.1%), malaria (17.6%) and glomerulonephritis (17.6%), intravascular haemolysis-cause unknown (16.2%), G6PDH deficiency (7.4%), malignancy (8.8%) and haemoglobinopathy (5.9%). The number of sessions of haemodialysis ranged from 1 to 10 (mode = 2 sessions) over a period of 1-55 days. Mortality was 27.9% (n = 19) and was related to the aetiology of AKI (P = 0.000): no deaths among patients with intravascular haemolysis or malaria, six deaths among patients with sepsis (40%), six (50%) among the patients with glomerulonephritis, while all the patients with malignancies died. CONCLUSIONS: The outcome of haemodialysis for AKI in Nigeria is relatively good and is related to the underlying aetiology of AKI. In addition to peritoneal dialysis, intermittent haemodialysis may have a role in the management of paediatric AKI in low resource settings and should be supported.

Trends in the histopathology of childhood nephrotic syndrome in Ibadan Nigeria: preponderance of idiopathic focal segmental glomerulosclerosis.

BACKGROUND: Reports on the histopathology of childhood nephrotic syndrome (NS) had emanated from our Centre since the 1960s and by the late 1980s and early 1990s, a change was observed and reported. Taking into consideration the worldwide changing trend in the histopathology of the NS and our Unit policy change in the indications for renal biopsy, a change was envisaged. We therefore evaluated the current histologic pattern of childhood NS in Ibadan with the view to highlighting any variations from the past and comparing the findings with regional and global trends. METHODOLOGY: We reviewed our database and analyzed the renal biopsy findings in patients who were biopsied before treatment was administered between 1997 and 2001 and those with mostly idiopathic steroid resistant NS (SRNS) and secondary NS, managed between 2006 and 2013. A comparative analysis of the findings from the present study was carried out with two previous reports from our Unit in the 1970s and early 1990s and also with reports from other Centres. RESULTS: A total of 78 patients had successful biopsies done during the study period in children aged between 2 ½ and 16 years. In both pre-treatment biopsy era (1997-2001) and post-treatment biopsy era (2006-2013), focal segmental glomerulosclerosis (FSGS) predominated. 75 % of the patients had idiopathic NS and among the patients that had idiopathic steroid resistant NS, FSGS was the most common followed by MPGN. For secondary NS, MCD was the most common but could be the early stages of either membranous nephropathy (MN) or FSGS. Chronic pyelonephritis and chronic interstitial nephritis occurred in 25 % of the study population but they were more prevalent in secondary nephrotic syndrome. CONCLUSION: FSGS is the most common histopathology in children requiring renal biopsy in Ibadan presently. FSGS is also the most common histopathology in idiopathic SRNS, which is in keeping with reports from most parts of the world. There has been a transition from the preponderance of Quartan Malarial Nephropathy (QMN) in the 1960s to MPGN in the 1980s to FSGS presently. This has great implications with regards to searching for new aetiologic factors, providing more efficacious treatment modalities and ensuring facilities for immunofluorescence, electron microscopic and genetic studies.

Renal Doppler Indices in Children with Nephrotic Syndrome: Findings from a Tertiary Hospital in Nigeria.

The resistive and pulsatility indices are known tools for assessing renal function in kidney diseases, especially in proteinuric conditions like Paediatric Nephrotic syndrome (NS) which is a glomerular disease. However, there is a limited knowledge in the use of Doppler Resistive and pulsatility indices in the management of this disease condition. This was a case control study involving 53 cases and 57 controls. The Doppler parameters, resistive index (RI) and pulsatility index (PI) of the renal interlobar arteries were determined for the upper, middle, and lower poles bilaterally for both controls and cases. The mean RI on the right and left were 0.59 ± 0.06 and 0.58 ± 0.06 respectively for the NS cases whereas for the controls it was 0.61 ± 0.05 and 0.60 ± 0.04 on the right and left respectively. The mean PI on the right and left measured 0.96 ± 0.16 and 0.94 ± 0.15 respectively for the NS cases while that for the control cases measured 0.98 ± 0.13.and 0.95 ± 0.12 on the right and left respectively. Although, the interlobar arteries mean RIs were generally less than that for the controls, but only the left middle pole showed statistically significant mean difference (p= 0.004). There was also statistically significant mean difference (p= 0.048) between the cases and controls in the left middle pole PI. However, no correlation was found when the renal RI and PI are compared with the serum albumin and creatinine. Although there was no statistical significance between the mean RI and PI of the NS cases and controls, except in the left middle pole RI, it is recommended that Doppler ultrasound should still be part of management of Nephrotic syndrome patients especially those who have developed end stage renal disease in order to monitor their renal function.

Paediatric end-stage renal disease in a tertiary hospital in South West Nigeria.

BACKGROUND: Children and adolescents with end-stage renal disease (ESRD) in sub-Saharan Africa may have the worst outcomes globally. Barriers to management include late presentation, poor socioeconomic conditions, absence of medical insurance, limited diagnostic facilities and non-availability of chronic renal replacement therapy (RRT). Our study was to determine the incidence, aetiology, management and outcomes of paediatric ESRD in a tertiary hospital in Nigeria. METHODS: A retrospective case review of paediatric ESRD at the University College Hospital Ibadan, Nigeria, over 8 years, from January 2005 to December 2012. RESULTS: 53 patients (56.6% male), median age 11 (inter quartile range 8.5-12) years were studied. Mean annual incidence of ESRD in Ibadan for children aged 14 years and below was 4 per million age related population (PMARP) while for those aged 5-14 years it was 6.0 PMARP. Glomerulonephritis was the cause in 41 (77.4%) patients amongst whom, 29 had chronic glomerulonephritis and 12 had nephrotic syndrome. Congenital anomalies of the kidneys and urinary tract (CAKUT) accounted for 11 (21.2%) cases, posterior urethral valves being the most common. Acute haemodialysis, acute peritoneal dialysis or a combination of these were performed in 33 (62.3%), 6 (11.3%) and 4 (7.5%) patients respectively. Median survival was 47 days and in-hospital mortality was 59%. CONCLUSIONS: Incidence of paediatric ESRD in Ibadan is higher than previous reports from sub-Saharan Africa. Glomerulonephritis, and then CAKUT are the most common causes. Mortality is high, primarily due to lack of resources. Preventive nephrology and chronic RRT programmes are urgently needed.