84 results on '"Bhimma, R"'
Search Results
2. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome.
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Trautmann, A., Boyer, O., Hodson, E., Bagga, A., Gipson, D.S., Samuel, S., Wetzels, J., Alhasan, K., Banerjee, S., Bhimma, R., Bonilla-Felix, M., Cano, F., Christian, M., Hahn, D., Kang, H.G., Nakanishi, K., Safouh, H., Trachtman, H., Xu, H., Cook, W., Vivarelli, M., Haffner, D., Trautmann, A., Boyer, O., Hodson, E., Bagga, A., Gipson, D.S., Samuel, S., Wetzels, J., Alhasan, K., Banerjee, S., Bhimma, R., Bonilla-Felix, M., Cano, F., Christian, M., Hahn, D., Kang, H.G., Nakanishi, K., Safouh, H., Trachtman, H., Xu, H., Cook, W., Vivarelli, M., and Haffner, D.
- Abstract
Item does not contain fulltext, Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85-90% of patients attain complete remission of proteinuria within 4-6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70-80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given.
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- 2023
3. The role of β-2-microglobulin and cystatin C as urinary biomarkers of focal segmental glomerulosclerosis in the setting of paediatric HIV infection
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Persad, K, Nandlal, L, Bhimma, R, and Naicker, T
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FSGS ,paediatric ,HIV ,Biomarkers ,urinary proteins - Abstract
BACKGROUND. Africa has the highest rate of HIV infection, and HIV-associated nephropathy (HIVAN) is one of the most frequent kidney diseases observed in children. HIVAN in children usually presents as a form of nephrotic syndrome, predominantly focal segmental glomerulosclerosis (FSGS) on histopathology, that often leads to chronic kidney failure. OBJECTIVE. This study determined the urinary concentrations of β-2-microglobulin (β2M) and cystatin C proteins in children with HIVAN and primary FSGS. METHODS. The study group comprised 34 children; 14 with HIVAN and 20 with primary FSGS. The control groups were 20 HIV-positive and 20 HIV-negative children with no kidney disease. Urine samples collected from these 74 children were stored at -80°C. Bio-Plex technology was used to analyse the urinary protein concentration of cystatin C and β2M. RESULTS. A significant increase in urinary β2M levels was observed in the HIVAN group compared with the HIV-negative group (p=0.0240). No other statistically significant differences in urinary β2M concentrations were noted across the study groups. Urinary cystatin C levels were significantly increased in primary FSGS children compared with both HIV-negative (p=0.0041) and HIV-positive controls (p=0.0256). Urinary cystatin C displayed a significant increase in the primary FSGS compared with the HIVAN group (p=0.0150). No significant differences in urinary cystatin C levels were noted in the HIVAN group compared with the HIV-negative and HIV-positive control groups. CONCLUSION. Urinary cystatin C has promising prognostic value to predict primary FSGS from HIVAN.
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- 2023
4. WCN23-0065 CAUSAL AND PUTATIVE PATHOGENIC MUTATIONS WERE IDENTIFIED IN 38.6% OF CHILDREN WITH PRIMARY STEROID-RESISTANT NEPHROTIC SYNDROME IN SOUTH AFRICA
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Bhimma, R., primary
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- 2023
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5. The role of ß-2-microglobulin and cystatin C as urinary biomarkers of focal segmental glomerulosclerosis in the setting of paediatric HIV infection.
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Persad, K., Nandlal, L., Bhimma, R., and Naicker, T.
- Subjects
CYSTATIN C ,FOCAL segmental glomerulosclerosis ,HIV infections ,PEDIATRIC nephrology ,CHRONIC kidney failure - Abstract
Background. Africa has the highest rate of HIV infection, and HIV-associated nephropathy (HIVAN) is one of the most frequent kidney diseases observed in children. HIVAN in children usually presents as a form of nephrotic syndrome, predominantly focal segmental glomerulosclerosis (FSGS) on histopathology, that often leads to chronic kidney failure. Objective. This study determined the urinary concentrations of ß-2-microglobulin (ß2M) and cystatin C proteins in children with HIVAN and primary FSGS. Methods. The study group comprised 34 children; 14 with HIVAN and 20 with primary FSGS. The control groups were 20 HIV-positive and 20 HIV-negative children with no kidney disease. Urine samples collected from these 74 children were stored at -80°C. Bio-Plex technology was used to analyse the urinary protein concentration of cystatin C and ß2M. Results. A significant increase in urinary ß2M levels was observed in the HIVAN group compared with the HIV-negative group (p=0.0240). No other statistically significant differences in urinary ß2M concentrations were noted across the study groups. Urinary cystatin C levels were significantly increased in primary FSGS children compared with both HIV-negative (p=0.0041) and HIV-positive controls (p=0.0256). Urinary cystatin C displayed a significant increase in the primary FSGS compared with the HIVAN group (p=0.0150). No significant differences in urinary cystatin C levels were noted in the HIVAN group compared with the HIV-negative and HIV-positive control groups. Conclusion. Urinary cystatin C has promising prognostic value to predict primary FSGS from HIVAN. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Impact of coronavirus disease-2019 on pediatric nephrology practice and education: an ESPN survey.
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Yazıcıoğlu, Burcu, Bakkaloğlu, Sevcan A., the European Society for Pediatric Nephrology, Abranches, M., Akman, S., Alpay, H., Ariceta, G., Atmış, B., Bael, A., Bakkaloğlu, S. A., Bayrakçı, U. S., Bhimma, R., Bjerre, A., Bonzel, K. E., Çeleğen, K., Delibaş, A., Demircioğlu, B., Dursun, İ., Ertan, P., and Flögelova, H.
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RESEARCH ,REMOTE access networks ,ONLINE education ,HEALTH facilities ,TEACHING methods ,APPLICATION software ,SICK people ,MEDICAL care ,PEDIATRICS ,CLINICS ,MEDICAL personnel ,KIDNEY transplantation ,PATIENTS ,NEPHROLOGY ,SURVEYS ,MEMBERSHIP ,HOSPITAL admission & discharge ,HOSPITAL wards ,DESCRIPTIVE statistics ,PROFESSIONAL associations ,COVID-19 pandemic ,WORLD Wide Web ,OFF-label use (Drugs) ,TELEMEDICINE ,PERSONNEL management - Abstract
Background: Coronavirus disease-2019 (COVID-19) has been challenging for patients and medical staff. Radical changes have been needed to prevent disruptions in patient care and medical education. Methods: A web-based survey was sent to European Society for Pediatric Nephrology (ESPN) members via the ESPN mailing list to evaluate the effects of the COVID-19 pandemic on delivery of pediatric nephrology (PN) care and educational activities. There were ten questions with subheadings. Results: Seventy-six centers from 24 countries completed the survey. The time period was between the beginning of the pandemic and May 30, 2020. The number of patients admitted in PN wards and outpatient clinics were significantly decreased (2.2 and 4.5 times, respectively). Telemedicine tools, electronic prescriptions, online applications for off-label drugs, and remote access to laboratory/imaging results were used in almost half of the centers. Despite staff training and protective measures, 33% of centers reported COVID-19 infected staff, and 29% infected patients. Difficulties in receiving pharmaceuticals were reported in 25% of centers. Sixty percent of centers suspended living-related kidney transplantation, and one-third deceased-donor kidney transplantation. Hands-on education was suspended in 91% of medical schools, and face-to-face teaching was replaced by online systems in 85%. Multidisciplinary training in PN was affected in 54% of the centers. Conclusions: This survey showed a sharp decline in patient admissions and a significant decrease in kidney transplantation. Telemedicine and online teaching became essential tools, requiring integration into the current system. The prolonged and fluctuating course of the pandemic may pose additional challenges necessitating urgent and rational solutions. [ABSTRACT FROM AUTHOR]
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- 2022
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7. POS-450 FIBROBLAST GROWTH FACTOR AS A BIOMARKER OF FOCAL SEGMENTAL GLOMERULOSCLEROSIS IN HIV-POSITIVE AND HIV-NEGATIVE CHILDREN paid for submission 2020-A-WCN21-0093(100981327899)
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Bhimma, R., primary
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- 2021
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8. Basic fibroblast growth factors as a biomarker of focal segmental glomerulosclerosis in HIV-positive and HIV-negative children
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Gumede, N Z, primary, Naicker, T, additional, and Bhimma, R, additional
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- 2020
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9. SUN-077 PRIMARY NEPHROTIC SYNDROME IN THE NEW MILLENNIUM IN KWAZULU-NATAL, SOUTH AFRICA
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Abumregha, O., primary, Naicker, E., additional, Connolly, C., additional, and Bhimma, R., additional
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- 2020
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10. Severe hypertension in children at a central referral hospital in KwaZulu-Natal Province, South Africa
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Murigo-Shumba, D, Bhimma, R, and Naicker, E
- Abstract
BACKGROUND: Hypertension (HPT) is often underdiagnosed in children, although significant morbidity and mortality arises from hypertensive target organ damage and hypertensive crises OBJECTIVES: To determine the prevalence, complications and causes of severe HPT in children
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- 2019
11. Arthritis in association with human immunodeficiency virus infection in Black African children: causal or coincidental?
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Chinniah, K., Mody, G. M., Bhimma, R., and Adhikari, M.
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- 2005
12. The role of kidney injury molecule-1, interleukin-18 and glutathione-S-transferase-π in paediatric HIV-associated nephropathy
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Nandlal, L, Bhimma, R, and Naicker, T
- Abstract
BACKGROUND. HIV-associated nephropathy (HIVAN) in sub-Saharan Africa remains a significant cause of morbidity and mortality in children. Early detection of kidney injury is essential for injury-specific interventions that may avert permanent kidney damage and delay progression of kidney injury. Kidney biopsy is presently the gold standard for diagnosis of related kidney disease; however, it is pervasive with attendant complications, and may not be representative owing to sampling error. Serum creatinine is an insensitive and non-specific marker for the diagnosis of various kidney diseases, particularly in HIV-infected patients, who usually have varying degrees of muscle wasting. Therefore, a non-invasive approach using additional biomarkers for early detection of HIV-related kidney diseases, particularly HIV-associated nephropathy (HIVAN), is urgently needed. OBJECTIVE. To determine the urinary concentrations of kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18) and glutathione-S-transferase-π (GST-π) in children with idiopathic focal segmental glomerulosclerosis (FSGS) and HIVAN. Methods. The study group comprised 34 children: 13 with HIVAN and 21 with idiopathic FSGS. The control groups were 19 HIV-positive and 16 HIV-negative children with no kidney disease. Urine samples collected from these 69 children were stored at -80°C. Urinary concentrations of KIM-1, IL-18 and GST-π were quantified using Bio-Plex assay. RESULTS. A significant increase in urinary KIM-1 levels was observed in the HIVAN group compared with the HIV-positive (p=0.0039) and HIV-negative (p=0.0438) control groups. There was no significant increase in KIM-1 levels on comparison of the idiopathic FSGS group with the control groups (HIV-positive and HIV-negative children) (p=0.0737 and p=0.1757, respectively). No statistically significant differences were noted in urinary IL-18 and GST-π levels across all study groups. CONCLUSION. Urinary KIM-1 levels are significantly elevated in children with HIVAN and may be a useful biomarker to detect kidney disease in HIV-1-infected children.
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- 2018
13. Neonatal HIV-associated nephropathy
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Bhimma, R, primary, Naicker, E, additional, and Mzimela, B W, additional
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- 2018
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14. Severe hypertension in children at a central referral hospital in KwaZulu-Natal Province, South Africa.
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Murigo-Shumba, D., Bhimma, R., and Naicker, E.
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KIDNEY diseases , *NEPHRITIS , *HYPERTENSIVE crisis , *LEFT ventricular hypertrophy , *THERAPEUTICS , *HYPERTENSION , *CHILDREN - Abstract
Background. Hypertension (HPT) is often underdiagnosed in children, although significant morbidity and mortality arises from hypertensive target organ damage and hypertensive crises. Objectives. To determine the prevalence, complications and causes of severe HPT in children =12 years old at a central hospital. Methods. Hospital records of children =12 years old with severe HPT (stage 2 and higher) from 2005 to 2014 were reviewed. Demographics, nutritional status, causes, HIV status, presence of target organ damage and treatment were analysed. Results. Of 821 children admitted to the paediatric nephrology unit, 152 (18.5%) children had severe HPT, with a mean age of 6.3 years; 86 (57%) were boys. A total of 28 (19%) were HIV-positive, and 19 (68%) were treatment naive. Kidney disease accounted for 82% of cases, 46 (30%) having steroid-resistant nephrotic syndrome, 22 (14%) HIV-associated nephropathy, 19 (13%) glomerulonephritis, 21 (14%) congenital urinary tract abnormalities and 17 (11%) other renal causes. Renovascular causes accounted for 12 (8%) cases. Of these 12, 7 (58%) had left ventricular hypertrophy (LVH), compared with 10/125 (8%) who had other forms of kidney disease (p<0.023). Hypertensive crises occurred in 28 (18%) patients, and were significantly more common in children with HPT secondary to renovascular causes than renal causes (p=0.001). Conclusion. Renal diseases were the most common cause of severe HPT in children. Hypertensive crises, retinopathy and LVH are common in renovascular HPT. [ABSTRACT FROM AUTHOR]
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- 2019
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15. The role of kidney injury molecule-1, interleukin-18 and glutathione-S-transferase-Π in paediatric HIVassociated nephropathy.
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Nandlal, L., Bhimma, R., and Naicker, T.
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PEDIATRIC nephrology , *HIV infections , *CHILD mortality , *GLOMERULOSCLEROSIS , *KIDNEY diseases , *CONTROL groups - Abstract
Background. HIV-associated nephropathy (HIVAN) in sub-Saharan Africa remains a significant cause of morbidity and mortality in children. Early detection of kidney injury is essential for injury-specific interventions that may avert permanent kidney damage and delay progression of kidney injury. Kidney biopsy is presently the gold standard for diagnosis of related kidney disease; however, it is pervasive with attendant complications, and may not be representative owing to sampling error. Serum creatinine is an insensitive and non-specific marker for the diagnosis of various kidney diseases, particularly in HIV-infected patients, who usually have varying degrees of muscle wasting. Therefore, a non-invasive approach using additional biomarkers for early detection of HIV-related kidney diseases, particularly HIV-associated nephropathy (HIVAN), is urgently needed. Objective. To determine the urinary concentrations of kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18) and glutathione-Stransferase- p (GST-p) in children with idiopathic focal segmental glomerulosclerosis (FSGS) and HIVAN. Methods. The study group comprised 34 children: 13 with HIVAN and 21 with idiopathic FSGS. The control groups were 19 HIV-positive and 16 HIV-negative children with no kidney disease. Urine samples collected from these 69 children were stored at -80°C. Urinary concentrations of KIM-1, IL-18 and GST-p were quantified using Bio-Plex assay. Results. A significant increase in urinary KIM-1 levels was observed in the HIVAN group compared with the HIV-positive (p=0.0039) and HIV-negative (p=0.0438) control groups. There was no significant increase in KIM-1 levels on comparison of the idiopathic FSGS group with the control groups (HIV-positive and HIV-negative children) (p=0.0737 and p=0.1757, respectively). No statistically significant differences were noted in urinary IL-18 and GST-p levels across all study groups. Conclusion. Urinary KIM-1 levels are significantly elevated in children with HIVAN and may be a useful biomarker to detect kidney disease in HIV-1-infected children. [ABSTRACT FROM AUTHOR]
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- 2018
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16. Correction to: Impact of coronavirus disease-2019 on pediatric nephrology practice and education: an ESPN survey.
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Yazıcıoğlu, Burcu, Bakkaloğlu, Sevcan A., the European Society for Pediatric Nephrology, Abranches, M., Akman, S., Alpay, H., Ariceta, G., Atmış, B., Bael, A., Bakkaloğlu, S. A., Bayrakçı, U. S., Bhimma, R., Bjerre, A., Bonzel, K. E., Çeleğen, K., Delibaş, A., Demircioğlu, B., Dursun, İ., Ertan, P., and Flögelova, H.
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PEDIATRICS ,NEPHROLOGY ,COVID-19 pandemic ,MEDICAL education - Abstract
A correction is presented to the article "Impact of coronavirus disease‑2019 on pediatric nephrology practice and education: an ESPN survey."
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- 2022
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17. Newer Insights into Acute Renal Failure in Children
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Bhimma, R and Bhimma, R
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- 2009
18. Human immunodeficiency virus and urinary tract infections in children
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Asharam, K., primary, Bhimma, R., additional, and Adhikari, M., additional
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- 2003
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19. Improved outcome of systemic lupus erythematosus among children in Durban, South Africa
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Bhimma, R., primary, Coovadia, H. M., additional, and Adhikari, M., additional
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- 1994
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20. The spectrum of chronic kidney disease (stages 2-5) in KwaZulu-Natal, South Africa.
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Bhimma R, Adhikari M, Asharam K, and Connolly C
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- 2008
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21. The impact of the hepatitis B virus vaccine on the incidence of hepatitis B virus-associated membranous nephropathy.
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Bhimma R, Coovadia HM, Adhikari M, and Connolly CA
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- 2003
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22. Hepatitis B Virus-Associated Nephropathy
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Bhimma, R. and Coovadia, H.M.
- Abstract
Abstract A direct causal association between hepatitis B virus (HBV) infection and the development of nephropathy remains controversial. Epidemiological studies have shown that chronic carriage of HBV in some individuals (particularly children) leads to the development of nephrotic syndrome with a strong male predominance, the commonest histological type being membranous nephropathy (MN). Spontaneous clearance of HBV antigens (particularly the HBeAg) leads to abrogation of proteinuria. The isolation of immune complexes in the kidney suggests that the pathogenesis of the disease may have an immune-complex basis. Recent studies showing expression of HBV viral antigens in kidney tissue suggest direct viral-induced pathological alterations and chronic immunologic injury. Biosocial studies have detected no correlation between HBV carriage and proteinuria using both quantitative and qualitative urinary protein analysis. Genetic studies of HLA class I and II genes showed a predisposition to MN but no similar correlation in those with milder degrees of proteinuria. These findings suggest that milder proteinuria is unrelated to HBV carriage or genetic factors but the development of nephropathy, particularly MN, in patients with chronic HBV carriage (HBsAg and/or HBV DNA positive) is based on an interaction of virus and host factors. Although the natural history of the disease tends to remission with preservation of renal function, there is considerable morbidity and a small but significant mortality. Use of naturally occurring cytokines (such as interferon-α2b) and other candidate therapies accelerates clearance of the virus and proteinuria. The most effective tool in reducing the incidence of the disease is the use of HBV vaccines.Copyright © 2004 S. Karger AG, Basel- Published
- 2004
23. Rickets in black children beyond infancy in Natal
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Bhimma, R., John Pettifor, Coovadia, H. M., Moodley, M., and Adhikari, M.
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Objective: To determine the clinical spectrum of rickets among black children admitted to King Edward VIII Hospital, Durban. Design: Prospective study of black children with rickets beyond infancy. Setting: Hospital-based population; King Edward VIII Hospital, Durban. Participants: A total of 37 patients, aged 1 - 12 years, were recruited over a 3-year period. None had been on vitamin D or calcium supplementation prior to investigation. Outcome measures: Rickets was diagnosed clinically, radiologically and biochemically (by a raised alkaline phosphatase value of > 350 IU). Gastro-intestinal, hepatic and renal glomerular causes were excluded in all patients using standard clinical and laboratory criteria. Results: Twenty-three patients were diagnosed as having privational rickets. Nine had 25-hydroxyvitamin D (25-0HD) levels of < 10 ng/ml while 14 had levels within the normal range and were suspected of having dietary calcium deficiency. Ten had a phosphopenic variety of rickets; the remaining 4 had healing or healed rickets on the basis of radiological assessment and normal biochemical values. Pain together with difficulty in walking and bowing of the lower limbs were the main reasons for presentation. The main clinical findings were thickened wrists and ankles and rickety rosary (100%), stunting (85%), anterior bowing of lower limbs (70%) and genu valgum (65%). The calcium and vitamin D deficiency group showed a much better clinical, biochemical and radiological response to therapy than the phosphopenic group on follow-up (18 patients). Conclusion: This is the first substantial report on rickets in the older child in Natal, which extends the findings from Transvaal, thereby establishing a recognisable pattern of rickets beyond infancy in South Africa. It draws attention to the common clinical presentations which may alert health professionals to the. presence of this problem. This report demonstrates that the two commonest types are privational rickets (due to calcium and/or vitamin D deficiency) and phosphopenic rickets.S Afr Med J 1995; 85: 668-672
24. Congenital nephrotic syndrome: A diagnostic and management dilemma.
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Moodley, R., Naicker, E., and Bhimma, R.
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NEPHROTIC syndrome in children ,NEPHROTIC syndrome diagnosis ,CONGENITAL disorders ,DILEMMA ,CYTOMEGALOVIRUS diseases ,POLYMERASE chain reaction - Abstract
Congenital nephrotic syndrome (CNS) is characterised by heavy proteinuria, hypoproteinaemia and oedema presenting in the first 3 months of life. We present a 27-day-old female patient admitted to the Inkosi Albert Luthuli Central Hospital with CNS; one of twins and HIV exposed but uninfected. The child had a cytomegalovirus (CMV) polymerase chain reaction (PCR) positive result in the urine, confirmed on two separate occasions. The CMV PCR for qualitative testing of CMV DNA was negative and quantitative testing was not done. CMV retinitis and central nervous system involvement were absent. Despite treatment with gancyclovir, the CNS did not improve. Further management required indomethacin followed by unilateral nephrectomy to decrease administration of albumin infusions to control oedema. Unfortunately, due to loss to follow-up, the patient demised from probable sepsis. We discuss the challenges we faced with respect to the diagnosis and management of CNS in a resource-limited setting where transplantation is not readily available. [ABSTRACT FROM AUTHOR]
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- 2015
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25. Nutcracker.
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Bhimma R and Robbs J
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- 2005
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26. IPNA consensus definitions for clinical trial outcomes in steroid-resistant nephrotic syndrome.
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Hari P, Khandelwal P, Boyer O, Bhimma R, Cano F, Christian M, Duzova A, Iijima K, Kang HG, Qian S, Safouh H, Samuels S, Smoyer WE, Vivarelli M, Bagga A, and Schaefer F
- Abstract
Assessment of the true impact of therapeutic interventions is a challenge in the absence of universal, standardized definitions for clinical trial endpoints in children with kidney diseases. Steroid-resistant nephrotic syndrome (SRNS) is a difficult kidney disease to treat, with unremitting disease progressing to kidney failure. Currently, available therapies result in suboptimal cure rates. Clinical trials with innovative, targeted treatments will likely be conducted for this disease in the foreseeable future. An international consortium of the IPNA Best Practices and Standards Committee and the Pediatric Nephrology Expert Group of the conect4children (c4c) network developed through consensus, standardized, internationally acceptable definitions for trial outcomes for SRNS. The endpoint definitions were formulated for use with urine protein to creatinine ratios and estimated glomerular filtration rates. Definitions of complete remission, partial remission, non-remission of disease, reduction in proteinuria, kidney disease progression, kidney failure, and composite kidney outcome were refined using an iterative process until a consensus was achieved., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)
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- 2024
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27. Case report of a child with nephronophthisis from South Africa.
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Bhimma R, Jembere E, and Hariparshad S
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- Humans, Female, Child, South Africa, Adolescent, Kidney Diseases, Cystic genetics, Kidney Diseases, Cystic diagnosis, Kidney Diseases, Cystic congenital
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Background: Nephronophthisis (NPHP) is an autosomal recessive disorder with a subset of patients presenting with extrarenal manifestations such as retinal degeneration, cerebella ataxia, liver fibrosis, skeletal abnormalities, cardiac malformations, and lung bronchiectasis. However, the involvement of other organ systems has also been documented. Extrarenal manifestations occur in approximately 10-20% of patients. In developed countries, it has been reported as one of the most common causes of monogenic chronic kidney failure (CKF) during the first three decades of life, with more than 25 genes associated with this condition. The current treatment options for managing NPHP include supportive care, management of complications, and kidney replacement therapy when necessary. The index patient is a 10-year-old Caucasian female who presented with recurrent attacks of abdominal pain. Her elder sister, TN, who was 17 years old, was diagnosed with CKF and noted to have persistently elevated liver enzymes (gamma-glutamyl transferase, alanine, and aspartate transaminases). Following genetic testing, her elder sister was shown to have Nephronophthisis Type 3, and a liver biopsy showed early fibrotic changes. Subsequent genetic testing confirmed the index patient as having NPHP Type 3. A kidney biopsy showed focal sclerosed glomeruli with patchy areas of tubular atrophy and related tubulointerstitial changes in keeping with NPHP. We present the first confirmatory case of NPHP from South Africa based on histopathology and genetic testing in a 10-year-old Caucasian female who presented with recurrent attacks of abdominal pain, whose elder sister also presented with CKF and early liver fibrosis, confirmed on biopsy and genetic testing., Conclusion: In low-middle-income countries, genetic testing should be undertaken whenever possible to confirm the diagnosis of NPHP, especially in those with a suggestive biopsy or if there is CKF of unknown aetiology with or without extra-renal manifestations., (© 2024. The Author(s).)
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- 2024
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28. The prevalence of chronic kidney disease in South Africa - limitations of studies comparing prevalence with sub-Saharan Africa, Africa, and globally.
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Hariparshad S, Bhimma R, Nandlal L, Jembere E, Naicker S, and Assounga A
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- Female, Humans, Male, Prevalence, South Africa epidemiology, Renal Insufficiency, Chronic diagnosis, Renal Insufficiency, Chronic epidemiology
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Background: Chronic kidney disease (CKD) is a globally significant non-communicable disorder. CKD prevalence varies between countries and within a country. We compared the prevalence rates of CKD in South Africa with sub-Saharan Africa, Africa, and globally., Methods: We registered a systematic review with the International Prospective Register of Systematic Reviews for prevalence studies reporting CKD stages III-V from 2013 to 2021. The analysis sought to explain any significant differences in prevalence rates. The R statistical package was used for data analysis. Comparisons included measures of effect size due to the large sample sizes analysed. We also compared sex differences in prevalence rates, common aetiologies, and type of study methodologies employed., Results: Eight studies were analysed, with two from each region. The matched prevalence rates of CKD between the various regions and South Africa showed significant differences, except for one comparison between South Africa and an African study [p = 0.09 (95% CI - 0.04-0.01)]. Both sub-Saharan African studies had a higher prevalence than South Africa. One study in Africa had a higher prevalence, while the other had a lower prevalence, whilst one Global study had a higher prevalence, and the other had a lower prevalence compared to South Africa. The statistical differences analysed using the Cramer's V test were substantially less than 0.1. Thus, differences in comparisons were largely due to differences in sample sizes rather than actual differences., Conclusion: Variable prevalence rates between regions included disparities in sample size, definitions of CKD, lack of chronicity testing and heterogeneous laboratory estimations of eGFR. Improved consistency and enhanced methods for diagnosing and comparing CKD prevalence are essential., (© 2023. The Author(s).)
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- 2023
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29. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome.
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Trautmann A, Boyer O, Hodson E, Bagga A, Gipson DS, Samuel S, Wetzels J, Alhasan K, Banerjee S, Bhimma R, Bonilla-Felix M, Cano F, Christian M, Hahn D, Kang HG, Nakanishi K, Safouh H, Trachtman H, Xu H, Cook W, Vivarelli M, and Haffner D
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- Child, Humans, Glucocorticoids therapeutic use, Immunosuppressive Agents adverse effects, Proteinuria drug therapy, Steroids adverse effects, Recurrence, Nephrotic Syndrome diagnosis, Nephrotic Syndrome drug therapy, Nephrotic Syndrome epidemiology, Nephrology
- Abstract
Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85-90% of patients attain complete remission of proteinuria within 4-6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70-80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given., (© 2022. The Author(s).)
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- 2023
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30. Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 Infection in KwaZulu-Natal, South Africa.
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Chinniah K, Bhimma R, Naidoo KL, Archary M, Jeena P, Hoosen E, Singh S, Lawler M, Naby F, and Masekela R
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- United States, Child, Humans, Middle Aged, SARS-CoV-2, South Africa epidemiology, COVID-19 complications, COVID-19 epidemiology
- Abstract
Background: Multisystem inflammatory syndrome in children (MIS-C) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been infrequently described in Africa., Objective: To describe the clinical characteristics, outcomes and associations of severe disease in children hospitalized with MIS-C in KwaZulu-Natal., Methods: Retrospective multicenter study of children (0-13 years) who met the Centers for Disease Control and Prevention criteria for MIS-C. Children with shock were compared with children without shock to determine the characteristics of severe MIS-C., Results: Twenty-nine children with MIS-C were identified, the mean age was 55 (SD ±45) months, 25 (86%) were Black-African, and 8 (28%) had pre-existing comorbidities. The predominant presenting symptoms included fever 29 (100%), gastrointestinal symptoms 25 (83%), skin rash 19 (65%), and shock 17 (59%). Children with shock had significantly increased CRP (P = 0.01), ferritin (P < 0.001), troponin-T (P = 0.02), B-type natriuretic peptide (BNP) (P = 0.01), and lower platelets (P = 0.01). Acute kidney injury (P = 0.01), cardiac involvement (P = 0.02), and altered levels of consciousness (P = 0.03) were more common in children with shock. The median length of hospital stay was 11 (IQR 7-19) days, with a mortality of 20.6%. Children who did not survive had significantly higher ferritin levels 1593 (IQR 1069-1650) ng/mL versus 540 (IQR 181-1156) ng/mL; P = 0.03) and significantly more required mechanical ventilation (OR 18; confidence interval 1.7-191.5; P = 0.005)., Conclusions: Hospitalized children with MIS-C in KwaZulu-Natal had more aggressive disease and higher mortality than children in better-resourced settings. Markedly elevated biomarkers and critical organ involvement were associated with severe disease. Risk factors for poor outcomes include higher ferritin levels and the need for mechanical ventilation., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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31. Causal and putative pathogenic mutations identified in 39% of children with primary steroid-resistant nephrotic syndrome in South Africa.
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Nandlal L, Winkler CA, Bhimma R, Cho S, Nelson GW, Haripershad S, and Naicker T
- Subjects
- Child, DNA Mutational Analysis, Humans, Intracellular Signaling Peptides and Proteins genetics, Membrane Proteins genetics, Membrane Proteins metabolism, Mutation, South Africa, Steroids therapeutic use, TRPC6 Cation Channel genetics, Glomerulosclerosis, Focal Segmental diagnosis, Glomerulosclerosis, Focal Segmental genetics, Nephrotic Syndrome diagnosis, Nephrotic Syndrome drug therapy, Nephrotic Syndrome genetics
- Abstract
There is a paucity of data identifying genetic mutations that account for the high rate of steroid-resistant nephrotic syndrome (SRNS) in a South African paediatric population. The aim was to identify causal mutations in genes implicated in SRNS within a South African paediatric population. We enrolled 118 children with primary nephrotic syndrome (NS), 70 SRNS and 48 steroid-sensitive NS. All children with SRNS underwent kidney biopsy. We first genotyped the NPHS2 gene for the p.V260E variant in all NS cases (n = 118) and controls (n = 219). To further identify additional variants, we performed whole-exome sequencing and interrogated ten genes (NPHS1, NPHS2, WT1, LAMB2, ACTN4, TRPC6, INF2, CD2AP, PLCE1, MYO1E) implicated in SRNS with histopathological features of focal segmental glomerulosclerosis (FSGS) in 56 SRNS cases and 29 controls; we also performed exome sequencing on two patients carrying the NPHS2 p.V260E mutation as positive controls. The overall detection rate of causal and putative pathogenic mutations in children with SRNS was 27/70 (39%): 15 (21%) carried the NPHS2 p.V260E causal mutation in the homozygous state, and 12 (17%) SRNS cases carried a putative pathogenic mutation in the heterozygous state in genes (INF2 (n = 8), CD2AP (n = 3) and TRPC6 (n = 1)) known to have autosomal dominant inheritance mode. NPHS2 p.V260E homozygosity was specifically associated with biopsy-proven FSGS, accounting for 24% of children of Black ethnicity (15 of 63) with steroid-resistant FSGS. No causal or putative pathogenic mutations were identified in NPHS1, WT1, LAMB2, PLCE1, MYO1E and ACTN4. We report four novel variants in INF2, PLCE1, ACTN4 and TRPC6. Conclusion: We report putative missense variants predicted to be pathogenic in INF2, CD2AP and TRPC6 among steroid-resistant-FSGS children. However, the NPHS2 p.V260E mutation is a prevalent cause of steroid-resistant FSGS among Black South African children occurring in 24% of children with SRNS. Screening all Black African children presenting with NS for NPHS2 p.V260E will provide a precision diagnosis of steroid-resistant FSGS and inform clinical management. What is Known: • Limited data is available on the genetic disparity of SNRS in a South African paediatric setting. • The high rate of steroid resistance in Black South African children with FSGS compared to other racial groups is partially explained by the founder variant NPHS2 p.V260E. What is New: • We report putative missense variants predicted to be pathogenic in INF2, CD2AP and TRPC6 among steroid-resistant FSGS children. • NPHS2 p.V260E mutation remains a prevalent cause of steroid-resistant FSGS among Black South African children, demonstrating precision diagnostic utility., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2022
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32. Kidney transplantation in children in KwaZulu-Natal, South Africa.
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Sinada NSA, Naicker E, Tinarwo P, and Bhimma R
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- Adolescent, Child, Child, Preschool, Female, Follow-Up Studies, Graft Rejection epidemiology, Graft Survival, Health Services Accessibility, Humans, Male, Retrospective Studies, South Africa, Tissue Donors supply & distribution, Treatment Outcome, Kidney Failure, Chronic surgery, Kidney Transplantation statistics & numerical data
- Abstract
Background: CKF is an overwhelming illness, especially in children. Kidney transplantation is considered the definitive management of CKF. It has substantial benefits, including increased patient survival, improved skeletal growth, social adjustment, neuropsychological development, and better quality of life compared to chronic dialysis., Methods: This is a retrospective, clinical, observational study in 13 children ≤16 years old who underwent kidney transplantation at IALCH in KwaZulu-Natal, South Africa, from May 2015 to December 2019., Results: Over 4 years and 7 months, 13 kidney transplants were performed; 7 (53.8%) were males, and 6 (46.2%) were females. Eleven (84.6%) were Black African and 2 (15.4%) Indian children. The mean age ± (SD) of transplantation was 10.1 ± 2.8 years (range 5.8-15.8). Eight (61.5%) children were from a rural setting. The mean ± (SD) duration of follow-up was 29.5 ± 15.9 months. All kidney transplants done were from live related donors; 8 (61.5%) were parents of the recipients. None were pre-emptive transplants. Graft loss occurred in 2 (15.4%) children with 100% patient survival. Two (15.4%) children developed acute rejection., Conclusions: The commissioning of transplant services in KwaZulu-Natal, South Africa, has improved access to this modality of treatment, particularly in our Black African patients. The significant limitations we experienced were a shortage of cadaveric donors and resource limitations with no dedicated transplant unit for pediatric patients together with staffing constraints. Enhancing patient and healthcare personal education will hopefully overcome cultural and religious barriers to organ donation., (© 2021 Wiley Periodicals LLC.)
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- 2021
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33. Primary nephrotic syndrome in the new millennium in KwaZulu-Natal, South Africa.
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Abumregha O, Naicker E, Connolly C, and Bhimma R
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- Adolescent, Black People statistics & numerical data, Child, Child, Preschool, Drug Resistance, Female, Glomerulosclerosis, Focal Segmental epidemiology, Glucocorticoids pharmacology, Humans, Infant, Kidney Failure, Chronic epidemiology, Male, Nephrosis, Lipoid epidemiology, Renal Replacement Therapy statistics & numerical data, Retrospective Studies, Sex Distribution, South Africa epidemiology, White People statistics & numerical data, Nephrotic Syndrome epidemiology
- Abstract
Background: The outcome and response of idiopathic nephrotic syndrome (NS) to steroids have been linked to race., Objectives: To determine the age of presentation, sex, race, histopathology, kidney function and disease status at the last hospital visit and correlate these with steroid response in Indian and black African children with idiopathic NS., Methods: This is a retrospective review of 231 children aged 1 - 14 years, who were seen at Inkosi Albert Luthuli Central Hospital, Durban, South Africa (SA) from 2003 to 2018., Results: The mean (standard deviation (SD)) age of presentation was 6.2 (3.4) years, with the majority of children (n=107; 46.3%) presenting at an early age (1 - 3 years) with a mean (SD) follow-up of 3.0 (2.4) years. One-hundred and twenty-one (52.4%) were males and 110 (47.6%) were females, with a male/female ratio of 1.1:1. There were 166 (71.9%) black African and 65 (28.1%) Indian children. The latter presented at a younger age than black African children (p<0.001). Seventy-six (32.9%) children were steroid sensitive (SS) and 155 (67.1%) were steroid resistant (SR). Black African children were more likely to be SR (odds ratio (OR) 2.0; p=0.02; 95% confidence interval (CI) 1.1 - 3.7). A kidney biopsy was performed in 209 (90.5%) children. Minimal change disease (MCD) was observed in 32 (13.9%) children and 162 (70.1%) had focal segmental glomerulosclerosis (FSGS). Black African children were slightly more likely to have FSGS; this, however, did not reach statistical significance (122/166 (73.5%) v. 40/65 (61.5%); OR 1.73; p=0.08; 95% CI 0.94 - 3.18). On comparing disease status at last hospital visit by race, 49/65 (75.4%) Indian and 94/166 (56.6%) black African children were in remission. At last hospital visit, black African children were less likely to be in remission than Indian children (OR 0.47; p=0.02; 95% CI 0.2 - 0.9), while 15/65 (23.1%) Indian and 47/166 (28.3%) black African children had relapsed, with no significant difference between the two groups. One (1.5%) Indian child and 25 (15.1%) black African children had end-stage kidney disease (ESKD) (OR 9.27; p=0.03; 95% CI 1.2 - 70.4) ‒ the majority had FSGS. Sixteen (61.5%) received renal replacement therapy., Conclusions: Our study shows a rising incidence of FSGS, with the majority of patients having SRNS, particularly black African children. This highlights the need for alternative efficacious therapy in the management of this disease. Also, a higher percentage of black African children with both MCD and FSGS were SS on histopathological examination, which was in keeping with reports from other regions in SA. There are still major challenges for the inclusion of all children into a chronic dialysis and transplant programme.
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- 2020
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34. Nephrotic Syndrome in South African Children: Changing Perspectives in the New Millennium.
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Nandlal L, Naicker T, and Bhimma R
- Abstract
The epidemiological landscape of nephrotic syndrome (NS) in South Africa has changed drastically in the New Millennium. Although the pattern of disease in the 3 main non-Black racial groups (White, Indian, and Mixed race) mirror that seen in Western countries, Black African children show a pattern of disease that is at variance with these 3 racial groups. The incidence of infectious diseases, particularly hepatitis B virus associated nephropathy has sharply declined to being almost extinct in Black children in the New Millennium whereas HIV-related nephropathy surfaced. However, following the widespread use of anti-retroviral therapy, its incidence has also decreased dramatically. Focal segmental glomerulosclerosis (FSGS), which was once uncommon, has, in the New Millennium, emerged as one of the most challenging forms of NS across all racial groups, particularly in Black children. Although the introduction of calcineurin inhibitors, mycophenolate mofetil and monoclonal antibodies (e.g., rituximab) has improved the outcome of children with FSGS, the reponse in Black children is less than optimal, with those having single gene mutations being universally unresponsive to all forms of immunosuppression.
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- 2019
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35. Peritoneal Infections in Children Undergoing Acute Peritoneal Dialysis at a Tertiary/Quaternary Central Hospital in Kwazulu-Natal, South Africa.
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Nepfumbada M, Naicker E, and Bhimma R
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- Acute Kidney Injury mortality, Adolescent, Anti-Bacterial Agents therapeutic use, Child, Child, Preschool, Cohort Studies, Developing Countries, Female, Follow-Up Studies, Hospital Mortality trends, Humans, Infant, Intensive Care Units, Male, Peritoneal Dialysis methods, Peritonitis drug therapy, Peritonitis physiopathology, Poverty, Retrospective Studies, Risk Assessment, Severity of Illness Index, South Africa, Tertiary Care Centers, Treatment Outcome, Acute Kidney Injury diagnosis, Acute Kidney Injury therapy, Peritoneal Dialysis adverse effects, Peritonitis etiology, Peritonitis mortality
- Abstract
Background: In a resource-limited setting, acute peritoneal dialysis (APD) is the modality of choice as a form of renal replacement therapy in children with acute kidney injury (AKI). However, there is a high risk of peritonitis that causes significant morbidity and mortality. Data on PD and peritonitis in developing countries are scarce. The purpose of this retrospective study was to determine the prevalence of APD-related peritonitis at a central referral hospital in KwaZulu-Natal, South Africa., Methods: A retrospective study from January 2010 until December 2014 was done at Inkosi Albert Luthuli Central Hospital (IALCH). All children under the age of 13 years with AKI requiring APD were included in the study., Results: Forty children were included in the study. Age ranged from 0.2 years to 12.25 years; 25 (62.5%) were male and 15 (37.5%) female. Twenty-seven (67.5%) were admitted to the intensive care unit (ICU) and 13 (32.5%) to the pediatric high care ward. Septicemia with multi-organ dysfunction was the was the main cause of AKI requiring APD in 18 (45%) children followed by poststreptococcal glomerulonephritis in 8 (20%). Acute PD was complicated by culture-proven peritonitis in 19 (47.5%) children of whom 16 (84.2%) had a single organism cultured while in 3, (15.7%) there was a mixed culture. The total number of organisms cultured was 24: 8 (33.3%) were gram-positive organisms, 12 (50%) gram-negative organisms, and 4 (16.67%) fungal. The Paediatric Index of Mortality (PIM) 2 Score risk of mortality was 99.4% for patients admitted to ICU. Mortality rate was 65%, and 14 (53%) of the children who demised had peritonitis., Conclusion: This study showed an inordinately high complication rate of peritonitis, mostly secondary to gram-negative organisms, of children undergoing APD in a central referral hospital. The use of surgically placed, tunneled catheters, meticulous attention to aseptic techniques and judicious use of antimicrobials is highly recommended in reducing the incidence of peritonitis in children undergoing APD., (Copyright © 2018 International Society for Peritoneal Dialysis.)
- Published
- 2018
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36. NPHS2 V260E Is a Frequent Cause of Steroid-Resistant Nephrotic Syndrome in Black South African Children.
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Asharam K, Bhimma R, David VA, Coovadia HM, Qulu WP, Naicker T, Gillies CE, Vega-Warner V, Johnson RC, Limou S, Kopp JB, Sampson M, Nelson GW, and Winkler CA
- Abstract
Introduction: In South Africa (SA), steroid-resistant nephrotic syndrome (SRNS) is more frequent in black than in Indian children., Methods: Seeking a genetic basis for this disparity, we enrolled 33 Indian and 31 black children with steroid-sensitive nephrotic syndrome (SSNS) and SRNS from KwaZulu-Natal, SA; SRNS children underwent kidney biopsy. We sequenced NPHS2 and genotyped APOL1 in 15 SSNS and 64 SRNS unrelated patients and 104 controls and replicated results in 18 black patients with steroid-resistant focal segmental glomerulosclerosis (SR-FSGS). Known FSGS genes (n = 21) were sequenced in a subset of patients., Results: Homozygosity for NPHS2 V260E was found in 8 of 30 black children with SRNS (27%); all 260E/E carriers had SR-FSGS. Combining SR-FSGS patients from the 2 groups, 14 of 42 (33%) were homozygous for V260E. One black control was heterozygous for V260E; no Indian patients or controls were carriers. Haplotype analysis indicated that homozygosity for V260E was not explained by cryptic consanguinity. Children with NPHS2 260E/E developed SRNS at earlier age than noncarriers (34 vs. 78 months, P = 0.01), and none achieved partial or complete remission (0% vs. 47%, P = 0.002). APOL1 variants did not associate with NS. Sequencing FSGS genes identified a CD2AP predicted pathogenic variant in the heterozygous state in 1 Indian case with SR-FSGS., Conclusion: NPHS2 260E/E was present in one-third of black FSGS patients, was absent in black controls and Indian patients, and affected patients were unresponsive to therapy. Genotyping V260E in black children from South Africa with NS will identify a substantial group with SR-FSGS, potentially sparing these children biopsy and ineffective steroid treatment.
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- 2018
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37. Prevalence of Primary Hypertension and Risk Factors in Grade XII Learners in KwaZulu-Natal, South Africa.
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Bhimma R, Naicker E, Gounden V, Nandlal L, Connolly C, and Hariparshad S
- Abstract
Hypertension in childhood leads to hypertension in adult life, the strongest risk factor being obesity. This study determined the prevalence of primary hypertension and its risk factors in Grade XII learners in KwaZulu-Natal, South Africa, from March 2016 to June 2017. Weight, height, body mass index (BMI), random finger prick cholesterol and glucose, and spot urine for an albumin : creatinine ratio were measured. An average of three separate blood pressure readings taken was at least 5 minutes apart. Five hundred and sixty-four learners had weight, height, and BMI; 536 had random blood glucose; and 545 had cholesterol and random spot urine albumin : creatinine ratios measured. Prehypertension was detected in 168 (29.7%) and hypertension in 77 (13.7%) of learners. Ninety (15.9%) were overweight and 75 (13,3%) were obese. Hypercholesterolaemia was present in 58 (10.8%) and a high spot random urine albumin : creatinine ratio in 5 (1.0%). None had a high blood glucose level. Both prehypertension and hypertension in all learners showed a significant increase with increasing BMI. Six (1.0%) learners had metabolic syndrome. Female learners in other racial groups (defined as Indian, mixed race, and White learners), overweight, and obese learners showed significantly higher rates of hypercholesterolaemia. We showed overweight and obesity as risk factors for prehypertension and hypertension. This presages the need for an appropriate diet and adequate exercise in a child's school career.
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- 2018
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38. Evaluation of the revised Schwartz creatinine-based glomerular filtration rate estimating equation in Black African children in KwaZulu-Natal, South Africa.
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Rampursat Y, Bhimma R, Naicker E, Peer F, and Gounden V
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- Adolescent, Area Under Curve, Child, Child, Preschool, Female, Humans, Limit of Detection, Male, South Africa, Black People, Creatinine urine, Glomerular Filtration Rate, Kidney Function Tests standards
- Abstract
Background The use of serum creatinine equations for estimating glomerular filtration rate is well known in adults and children. We evaluated the revised Schwartz creatinine-based estimated glomerular filtration rate prediction equation in Black African children in KwaZulu-Natal, South Africa. Methods Review of medical records of all Black African patients aged 2-18 years old who have had glomerular filtration rate determined by intravenous Technetium-99 m-diethylene-triamine-pentaacetate, for the period 1 January 2010 to 31 December 2014 at the Inkosi Albert Luthuli Central Hospital, Durban, South Africa was performed. Estimated glomerular filtration rate result obtained using the revised Schwartz equation was compared to Technetium-99 m-diethylene-triamine-pentaacetate plasma clearance measured glomerular filtration rate. Accuracy of the estimated glomerular filtration rate equations within 10% (P
10 ) and 30% (P30 ) of the measured glomerular filtration rate, sensitivity and specificity for predicting glomerular filtration rate < 60 mL/min/1.73 m2 and < 30 mL/min/1.73 m2 was determined. Results Results from 148 African children between 2 and 18 years old were analysed. P10 and P30 values were 16 and 49%, respectively. Sensitivity of 92.9% (95% CI: 80.5-85), specificity of 95.3 (95% CI: 89.3-98.5) and AUC of 0.96 (95% CI 0.92-0.99) were obtained for measured estimated glomerular filtration rate < 60 mL/min/1.73 m2 . Sensitivity of 88.2% (95% CI: 63.6-98.5), specificity of 90.8 (95% CI: 84.5-95.2) and area under the curve of 0.93 (95% CI 0.88-0.96) were obtained for measured estimated glomerular filtration rate < 30 mL/min/1.73 m2 . Conclusions The revised Schwartz equation did not meet the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines of 90% of estimated glomerular filtration rate results within 30% of measured glomerular filtration rate.- Published
- 2018
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39. tarSVM: Improving the accuracy of variant calls derived from microfluidic PCR-based targeted next generation sequencing using a support vector machine.
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Gillies CE, Otto EA, Vega-Warner V, Robertson CC, Sanna-Cherchi S, Gharavi A, Crawford B, Bhimma R, Winkler C, Kang HM, and Sampson MG
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- Data Accuracy, Humans, Polymerase Chain Reaction, Sequence Analysis, DNA methods, Alleles, High-Throughput Nucleotide Sequencing methods, Microfluidics, Software, Support Vector Machine
- Abstract
Background: Targeted sequencing of discrete gene sets is a cost effective strategy to screen subjects for monogenic forms of disease. One method to achieve this pairs microfluidic PCR with next generation sequencing. The PCR step of this pipeline creates challenges in accurate variant calling. This includes that most reads targeting a specific exon are duplicates that have been amplified from the PCR step. To reduce false positive variant calls from these experiments, previous studies have used threshold-based filtering of alternative allele depth ratio and manual inspection of the alignments. However even after manual inspection and filtering, many variants fail to be validated via Sanger sequencing. To improve the accuracy of variant calling from these experiments, we are challenged to design a variant filtering strategy that sufficiently models microfluidic PCR-specific issues., Results: We developed an open source variant filtering pipeline, targeted sequencing support vector machine ("tarSVM"), that uses a Support Vector Machine (SVM) and a new score the normalized allele dosage test to identify high quality variants from microfluidic PCR data. tarSVM maximizes training knowledge by selecting variants that are likely true and likely false variants by incorporating knowledge from the 1000 Genomes and the Exome Aggregation Consortium projects. tarSVM improves on previous approaches by synthesizing variant features from the Genome Analysis Toolkit and allele dosage information. We compared the accuracy of tarSVM versus existing variant quality filtering strategies on two cohorts (n = 474 and n = 1152), and validated our method on a third cohort (n = 75). In the first cohort, our method achieved 84.5 % accuracy of predicting whether or not a variant would be validated with Sanger sequencing versus 78.8 % for the second most accurate method. In the second cohort, our method had an accuracy of 73.3 %, versus 61.5 % for the second best method. Finally, our method had a false discovery rate of 5 % for the validation cohort., Conclusions: tarSVM increases the accuracy of variant calling when using microfluidic PCR based targeted sequencing approaches. This results in higher confidence downstream analyses, and ultimately reduces the costs Sanger validation. Our approach is less labor intensive than existing approaches, and is available as an open source pipeline for read trimming, aligning, variant calling, and variant quality filtering on GitHub at https://github.com/christopher-gillies/TargetSpecificGATKSequencingPipeline .
- Published
- 2016
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40. Mycophenolate mofetil therapy in children with idiopathic membranous nephropathy.
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Bhimma R, Naicker E, and Ramdial PK
- Subjects
- Adrenal Cortex Hormones administration & dosage, Angiotensin-Converting Enzyme Inhibitors administration & dosage, Child, Child, Preschool, Drug Therapy, Combination, Female, Glomerular Filtration Rate, Humans, Male, Mycophenolic Acid therapeutic use, Glomerulonephritis, Membranous drug therapy, Immunosuppressive Agents therapeutic use, Mycophenolic Acid analogs & derivatives
- Abstract
Background: Idiopathic membranous nephropathy (IMN) is a rare form of childhood nephropathy. To date there are no standardized protocols of management for this condition in children. The aim of this study is to report on 4 children with IMN who were treated with mycophenolate mofetil (MMF)., Methods: MMF was given in combination with low dose steroids and angiotensin converting enzyme antagonists in a dose of 1,200 mg/m2 body surface area in two divided doses for a minimum of 6 months., Results: All children had histopathological findings in keeping with Stage III membranous nephropathy. At the last hospital visit, 3 children had achieved a > 50% reduction of proteinuria with preservation of renal function. One patient who failed to respond progressed to Stage III chronic kidney disease. None of the children who were treated with MMF experienced any major side effects of the drug., Conclusions: MMF, administered over a limited period, served as a safe and effective immunosuppressive agent in the treatment of this condition, in conjunction with low dose steroids and angiotensin converting enzyme inhibitors. Large multicenter randomized studies of children with IMN are necessary to assess the efficacy and long term safety of MMF.
- Published
- 2013
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41. Kidney disease in children and adolescents with perinatal HIV-1 infection.
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Bhimma R, Purswani MU, and Kala U
- Subjects
- Adolescent, Anti-HIV Agents adverse effects, Anti-HIV Agents therapeutic use, Child, HIV Infections virology, HIV-1 isolation & purification, Humans, Kidney Diseases etiology, Kidney Diseases pathology, Kidney Diseases therapy, HIV Infections complications, Kidney Diseases epidemiology
- Abstract
Introduction: Involvement of the kidney in children and adolescents with perinatal (HIV-1) infection can occur at any stage during the child's life with diverse diagnoses, ranging from acute kidney injury, childhood urinary tract infections (UTIs), electrolyte imbalances and drug-induced nephrotoxicity, to diseases of the glomerulus. The latter include various immune-mediated chronic kidney diseases (CKD) and HIV-associated nephropathy (HIVAN)., Discussion: The introduction of highly active anti-retroviral therapy (HAART) has dramatically reduced the incidence of HIVAN, once the commonest form of CKD in children of African descent living with HIV, and also altered its prognosis from eventual progression to end-stage kidney disease to one that is compatible with long-term survival. The impact of HAART on the outcome of other forms of kidney diseases seen in this population has not been as impressive. Increasingly important is nephrotoxicity secondary to the prolonged use of anti-retroviral agents, and the occurrence of co-morbid kidney disease unrelated to HIV infection or its treatment. Improved understanding of the molecular pathogenesis and genetics of kidney diseases associated with HIV will result in better screening, prevention and treatment efforts, as HIV specialists and nephrologists coordinate clinical care of these patients. Both haemodialysis (HD) and peritoneal dialysis (PD) are effective as renal replacement therapy in HIV-infected patients with end-stage kidney disease, with PD being preferred in resource-limited settings. Kidney transplantation, once contraindicated in this population, has now become the most effective renal replacement therapy, provided rigorous criteria are met. Given the attendant morbidity and mortality in HIV-infected children and adolescents with kidney disease, routine screening for kidney disease is recommended where resources permit., Conclusions: This review focuses on the pathogenesis and genetics, clinical presentation and management of kidney disease in children and adolescents with perinatal HIV-1 infection.
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- 2013
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42. The spectrum of HIV-related nephropathy in children.
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Ramsuran D, Bhimma R, Ramdial PK, Naicker E, Adhikari M, Deonarain J, Sing Y, and Naicker T
- Subjects
- AIDS-Associated Nephropathy complications, AIDS-Associated Nephropathy pathology, Adolescent, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Antiretroviral Therapy, Highly Active, Blotting, Western, Child, Child, Preschool, Enzyme-Linked Immunosorbent Assay, Female, Glomerulosclerosis, Focal Segmental etiology, Glomerulosclerosis, Focal Segmental pathology, Growth Disorders etiology, HIV Infections epidemiology, HIV Seropositivity, Humans, Infant, Kidney pathology, Kidney Failure, Chronic etiology, Kidney Failure, Chronic pathology, Kidney Function Tests, Male, Nephrotic Syndrome etiology, Proteinuria drug therapy, Proteinuria etiology, South Africa epidemiology, Viral Load, AIDS-Associated Nephropathy physiopathology
- Abstract
Background: Despite the burden of human immunodeficiency virus (HIV) disease in Southern Africa, there have been few reports of HIV-related nephropathy in children. This study outlines the spectrum of HIV-1-related kidney diseases of children in KwaZulu-Natal, South Africa., Methods: A review of the clinical presentation, laboratory and histopathological findings of children diagnosed with HIV-related nephropathy., Results: Forty-nine out of 71 children (1-16 years old) with HIV-1 related nephropathy underwent kidney biopsy. The most common histopathological finding was focal segmental glomerulosclerosis (FSGS), which was present in 32 (65.3%) children; 13 (26.5%) having collapsing glomerulopathy and 19 (38.8%) classic FSGS. The majority of patients showed haematological (86.4%) and electrolyte abnormalities (69.4%). Renal impairment was present in 41% of patients on initial presentation. However, end-stage kidney disease was present in only 4% of these patients. All patients were treated with highly active anti-retroviral therapy (HAART), the majority (79.6%) showed decreased proteinuria with 38.8% having complete remission., Conclusions: This study, one of the largest series of children reported from Africa, demonstrates that nephrotic syndrome due to HIV-associated nephropathy (HIVAN) is the commonest presentation of HIV-related nephropathy in childhood. Highly active anti-retroviral therapy in combination with angiotensin-converting enzyme antagonists is highly effective in decreasing proteinuria and preserving renal function.
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- 2012
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43. Pediatric renal cryptococcosis: novel manifestations in the acquired immunodeficiency syndrome era.
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Ramdial PK, Sing Y, Deonarain J, Bhimma R, Chotey N, and Sewram V
- Subjects
- AIDS-Related Opportunistic Infections complications, Acquired Immunodeficiency Syndrome complications, Acquired Immunodeficiency Syndrome drug therapy, Antiretroviral Therapy, Highly Active, Child, Cryptococcosis complications, Cryptococcosis microbiology, Cryptococcus neoformans, Female, Humans, Kidney Diseases complications, Male, Proteinuria complications, Proteinuria microbiology, AIDS-Related Opportunistic Infections microbiology, Acquired Immunodeficiency Syndrome microbiology, Cryptococcosis diagnosis, Kidney Diseases microbiology
- Abstract
Pediatric cryptococcosis has been documented in various organs, but pediatric renal cryptococcosis (RC) remains undocumented to date. The authors report RC in 2 children with AIDS, 7 and 9 years of age, with proteinuria. Both patients, on antiretroviral therapy (ARV) for 28 (patient 1) and 54 (patient 2) weeks each, had secured viral immunosuppression, but immune restoration was realized by patient 1 only. Cryptococcal immune reconstitution inflammatory syndrome (IRIS) was diagnosed on the renal biopsy from patient 1 based on the clinicopathological profile and the presence of segmental glomerular and an interstitial lymphoplasmacytic and granulomatous reaction to Cryptococcus neoformans, with a predominance of capsule-deficient fungal forms. The renal biopsy from patient 2 demonstrated typical HIV-associated nephropathy with focal intratubular and interstitial C neoformans yeasts. Pediatric AIDS-associated renal disease must be expanded to include RC and cryptococcal IRIS, and the kidney must be included as a potential sentinel site of IRIS.
- Published
- 2011
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44. Retrospective characterization of the S open reading frame of HBV isolated from children with membranous nephropathy treated with interferon-alpha2b.
- Author
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Gous N, Bhimma R, Kew M, and Kramvis A
- Subjects
- Africa South of the Sahara ethnology, Child, DNA, Viral analysis, DNA, Viral genetics, Genetic Markers, Glomerulonephritis, Membranous ethnology, Glomerulonephritis, Membranous etiology, Hepatitis B Surface Antigens analysis, Hepatitis B virus drug effects, Hepatitis B, Chronic complications, Hepatitis B, Chronic drug therapy, Humans, Interferon alpha-2, Mutation, Open Reading Frames, Phylogeny, Protein Precursors analysis, Recombinant Proteins, Retrospective Studies, Sequence Analysis, DNA, Treatment Failure, Antiviral Agents therapeutic use, Glomerulonephritis, Membranous drug therapy, Hepatitis B Surface Antigens genetics, Hepatitis B virus genetics, Hepatitis B, Chronic virology, Interferon-alpha therapeutic use, Protein Precursors genetics
- Abstract
Background: A causal relationship exists between HBV infection and membranous nephropathy. The association is especially close in Black children in sub-Saharan Africa. Interferon-alpha2b is commonly used to treat this condition, but is effective in only 30-40% of patients. The reason for the poor response is unknown. The objective of this study was to determine if mutations in the surface gene of HBV isolated from Black children with HBV-associated membranous nephropathy before, during and after interferon treatment, have any effect on treatment response and vice versa., Methods: HBV DNA was extracted from a responder, a reverter and a non-responder before and after initiation of 16 weeks of interferon-alpha2b treatment. The preS1/preS2/S region was amplified, cloned and sequenced., Results: The preS2 region was the most variable in the reverter and the non-responder, and the S region was the most variable in the non-responder. Phylogenetic analysis showed that the viral population dynamics between the responder and the reverter/non-responder strains differed as a result of mutations in the surface gene., Conclusions: The presence of mutations in the S region of HBV could be used as predictive markers to differentiate interferon-alpha2b responders from non-responders provided that detailed analysis of further genomes confirms our findings.
- Published
- 2010
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45. Steroid-resistant nephrotic syndrome: the influence of race on cyclophosphamide sensitivity.
- Author
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Bhimma R, Adhikari M, and Asharam K
- Subjects
- Adolescent, Black People, Child, Child, Preschool, Female, Humans, India, Infant, Male, Retrospective Studies, South Africa, White People, Cyclophosphamide pharmacology, Drug Resistance, Nephrotic Syndrome drug therapy, Nephrotic Syndrome ethnology, Steroids therapeutic use
- Abstract
Steroid-resistant (SR) forms of nephrotic syndrome (NS) have a poorer outcome in blacks compared to other racial groups. In this study, 223 children with SRNS, aged 1-16 years old, were analysed retrospectively for the period 1976-2004. Treatment schedules included oral cyclophosphamide (2-3 mg/kg) with prednisone 0.5-1 mg/kg (maximum 60 mg) only (n=90); prednisone on alternate days with methylprednisolone (30 mg/kg, maximum 1 g) and oral cyclophosphamide (n=117); oral prednisone on alternate days, three doses of intravenous methylprednisolone on alternate days and monthly doses of intravenous cyclophosphamide (500-750 mg m(-2) dose(-1)x7 doses monthly) (n=10); or cyclosporine 5 mg kg(-1) day(-1) adjusted to a trough level of 150-200 mg/ml (n=6). We compared the clinical and biochemical characteristics and outcome using different forms of therapies. A total of 183 (82.1%) underwent biopsy; 84 (45.9%) were Indian and 99 (54.1%) were black. Sixty-six (36.1%) had minimal change NS, 66 (36.1%) had focal segmental glomerulosclerosis (FSGS), 15 (8.2%) had a proliferative form of NS, and 36 (19.7%) had other forms of NS. Of the 84 Indian children biopsied, 58 (69.0%) were in complete remission, including 29 of 40 (72.5%) treated with oral cyclophosphamide and prednisone only. Of the 99 black children who were biopsied, 20 (20.2%) achieved complete remission; none of those treated with oral cyclophosphamide and prednisone only achieved complete remission. Of the 40 Indian children who were not biopsied who received only oral prednisone and cyclophosphamide, 32 (80%) achieved complete remission. This study shows Indian children with SRNS respond better to treatment than black children (69.0 vs. 20.2%). Since 80% of Indian children with SRNS responded to a trial of oral cyclophosphamide and prednisone, we propose the use of oral cyclophosphamide therapy in non-black children before embarking on renal biopsy.
- Published
- 2006
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46. Management of steroid-resistant focal segmental glomerulosclerosis in children using tacrolimus.
- Author
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Bhimma R, Adhikari M, Asharam K, and Connolly C
- Subjects
- Adolescent, Child, Female, Humans, Immunosuppressive Agents adverse effects, Male, Steroids therapeutic use, Tacrolimus adverse effects, Treatment Outcome, Glomerulosclerosis, Focal Segmental drug therapy, Immunosuppressive Agents therapeutic use, Tacrolimus therapeutic use
- Abstract
Background: The use of tacrolimus in steroid-resistant (SR) focal segmental glomerulosclerosis (FSGS) has been reported in single and small series case reports., Aim: To determine the efficacy of tacrolimus in the management of SR FSGS in children., Study Design: This was a prospective study of 20 children with SR FSGS treated with tacrolimus (0.2-0.4 mg/kg/day in two divided doses over 12 h adjusted to a trough level between 7 and 15 ng/ml) for 12 months in combination with low-dose steroids. Other therapies included angiotensin-converting enzyme inhibitors, folic acid, multivitamins and lipid-lowering agents., Results: The mean age at study entry was 11.1 years (range 5.6-16.8). The mean duration of nephrotic syndrome before initiation of tacrolimus therapy was 4.7 years (range 2.1-7.6). At the end of the treatment period, 8 (40%) children were in complete remission, 9 (45%) were in partial remission, and 3 (15%) failed to respond. The average follow-up period following cessation of tacrolimus treatment was 27.5 months (range 13.7-43.7). At last hospital follow-up, 5 (25%) children were in complete remission, 10 (50%) in partial remission, and 2 (10%) in relapse. Three children died from dialysis-related complications following cessation of tacrolimus treatment. Adverse events included sepsis (2), nausea (2), diarrhea (2), anemia (4) and worsening of hypertension (4)., Conclusion: Tacrolimus is a safe and effective treatment for SR FSGS. However, like cyclosporine, some children tend to relapse following cessation of treatment., (Copyright 2006 S. Karger AG, Basel.)
- Published
- 2006
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47. HLA associations with HBV carriage and proteinuria.
- Author
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Bhimma R, Coovadia M, Hammond MG, Kramvis A, Adhikari M, and Kew MC
- Subjects
- Adolescent, Child, Child, Preschool, Female, Genotype, Glomerulonephritis, Membranous etiology, Glomerulonephritis, Membranous genetics, HLA-DQ Antigens analysis, HLA-DQ beta-Chains, Hepatitis B genetics, Humans, Male, Probability, Proteinuria genetics, Carrier State, HLA-DQ Antigens physiology, Hepatitis B etiology, Proteinuria etiology
- Abstract
Human leucocyte antigen (HLA) associations have been reported in children with hepatitis B virus (HBV) associated membranous nephropathy (MN). In a previous study, we found an association with HLA DQB1*0603 in black children with HBVMN. To determine whether HLA DQB1*0603 predisposes to HBV carriage and development of abnormal proteinuria, we studied 70 family members of 14 children with HBVMN positive for HLA DQB1*0603. HBV was determined using third generation ELISA, slot-blot hybridisation, and nested polymerase chain reaction. HLA class I antigens were determined using a two-staged lymphocytotoxic test whereas class II antigen typing was done using sequence-specific primers. Abnormal proteinuria was defined by a protein/creatinine ratio > or =0.2. Associations of HLA DQB1*0603 with HBV carriage and abnormal proteinuria were determined using the mean probability ratio (LOD scores). Forty-seven (67%) family members were positive for HBV infection. Nineteen (27%) had abnormal range proteinuria. LOD scores in the study subjects with DQB1*0603 who were HBV negative versus those with DQB1*0603 who were HBV positive was not significant (anti-log sum =2.0559 and average 0.23). When a similar calculation was made for abnormal proteinuria, there were no significant findings (anti-log sum =3.8587 and average 0.43). This lack of association of HLA DQB1*0603 with either HBV carriage or abnormal proteinuria in family members suggests that additional factors may play a role in predisposing children to chronic HBV carriage and the development of MN. We therefore conclude that the main effect of HLA DQB1*0603 that distinguishes family members from HBVMN is the degree of proteinuria, which is a reflection of the severity of glomerular basement membrane damage in the latter.
- Published
- 2002
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48. Hepatitis B and C virus co-infection in black children with membranous nephropathy.
- Author
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Sithebe NP, Kramvis A, Kew MC, Bhimma R, Coovadia HM, and Naidoo P
- Subjects
- Adolescent, Black People, Blotting, Southern, Child, Child, Preschool, Enzyme-Linked Immunosorbent Assay, Female, Glomerulonephritis, Membranous epidemiology, Hepatitis B epidemiology, Hepatitis C epidemiology, Humans, Male, RNA, Viral biosynthesis, RNA, Viral genetics, Reverse Transcriptase Polymerase Chain Reaction, South Africa epidemiology, Glomerulonephritis, Membranous complications, Hepatitis B complications, Hepatitis C complications
- Abstract
Membranous glomerulonephritis is a recognized complication of hepatitis B virus infection, especially in children, and an occasional complication of hepatitis C virus infection. Co-infection with the two viruses has not previously been described in membranous glomerulonephritis. We report five black African children with membranous glomerulonephritis who were co-infected with hepatitis B and C viruses. Proof of hepatitis B virus infection was obtained using serological and molecular detection methods. Hepatitis C virus infection was demonstrated using reverse transcription to convert viral RNA to cDNA followed by amplification of the cDNA using a double round of the polymerase chain reaction with confirmation by Southern hybridization and nucleotide sequencing. The clinical, biochemical, immunological, and pathological characteristics of the co-infected children, as well as the natural history of the disease, did not differ from those in 24 children with hepatitis B virus-associated membranous glomerulonephritis. Of the 24 family and household contacts of the five co-infected children, 7 were infected with hepatitis B virus, 1 with hepatitis C virus, and none with both viruses. It is not known whether infection with the two viruses was acquired simultaneously or sequentially. Thus, black children with membranous glomerulonephritis are occasionally co-infected with hepatitis B and C viruses. The resulting disease appears to be no more severe than that in children infected with hepatitis B virus alone.
- Published
- 2002
- Full Text
- View/download PDF
49. Treatment of hepatitis B virus-associated nephropathy in black children.
- Author
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Bhimma R, Coovadia HM, Kramvis A, Adhikari M, and Kew MC
- Subjects
- Adolescent, Alanine Transaminase metabolism, Antiviral Agents adverse effects, Child, Child, Preschool, Cohort Studies, DNA, Viral analysis, Female, Hepatitis B immunology, Hepatitis B Surface Antigens analysis, Hepatitis B e Antigens analysis, Hepatitis B virus genetics, Humans, Infant, Infant, Newborn, Interferon alpha-2, Interferon-alpha adverse effects, Kidney pathology, Kidney physiopathology, Kidney Diseases ethnology, Kidney Diseases physiopathology, Liver enzymology, Liver pathology, Male, Prospective Studies, Recombinant Proteins, Treatment Outcome, gamma-Glutamyltransferase metabolism, Antiviral Agents therapeutic use, Black People, Hepatitis B complications, Interferon-alpha therapeutic use, Kidney Diseases drug therapy, Kidney Diseases virology
- Abstract
The efficacy of interferon (IFN) in the treatment of hepatitis B virus (HBV)-associated nephropathy in black children has not been established. Twenty-four black children with biopsy-proven HBV-associated nephropathy were recruited into the study during the period April 1997 to June 1999. Five defaulted treatment and were excluded from the primary analysis. IFNalpha 2b was administered for 16 weeks. Response to treatment was defined as loss of HBeAg, decrease in proteinuria, and prevention of deterioration in renal and liver function. A control group of 20 patients was followed up for the same period. Ten (52.6%) of the treated children responded with clearance of HBeAg by 40 weeks. None cleared HBsAg. All responders showed remission of proteinuria, 90% maintained normal renal function and 1 (10%) showed improvement of renal function. HBV DNA levels decreased in this group. Nine patients did not clear HBeAg; none showed remission of proteinuria, and two showed deterioration of renal function. Liver enzymes rose during treatment but subsequently declined irrespective of response to therapy. No serious side effects were encountered. Only 5% of controls showed spontaneous clearance of HBeAg, and none had remission of proteinuria. Black children with HBV-associated nephropathy show accelerated clearance of HBeAg with remission of proteinuria following treatment with IFNalpha 2b. IFNalpha 2b was well tolerated.
- Published
- 2002
- Full Text
- View/download PDF
50. HLA class I and II in black children with hepatitis B virus-associated membranous nephropathy.
- Author
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Bhimma R, Hammond MG, Coovadia HM, Adhikari M, and Connolly CA
- Subjects
- Adolescent, Alleles, Child, Child, Preschool, Gene Frequency, Genetic Predisposition to Disease, Glomerulonephritis, Membranous complications, Glomerulonephritis, Membranous genetics, HLA-DQ Antigens analysis, HLA-DQ Antigens genetics, HLA-DQ beta-Chains, HLA-DR Antigens analysis, HLA-DR Antigens genetics, HLA-DRB1 Chains, Histocompatibility Antigens Class I genetics, Histocompatibility Antigens Class II genetics, Humans, Nephrotic Syndrome complications, Phenotype, Reference Values, Black People, Glomerulonephritis, Membranous virology, Hepatitis B complications, Histocompatibility Antigens Class I analysis, Histocompatibility Antigens Class II analysis
- Abstract
Background: The pathogenetic mechanisms by which individuals with chronic hepatitis B virus (HBV) infection develop membranous nephropathy (MN) are probably dependent on interactions between viral, host and environmental factors; some evidence suggests a genetic predisposition. HBVMN constitutes a major etiological group in black children with nephrotic syndrome. We therefore explored the HLA associations in black children with HBVMN., Method: Thirty black children, age range 2 to 16 years, with biopsy-proven HBVMN, were the subjects of the study. HBV status was determined using third generation ELISA. HLA A, B and C antigens were determined using a two-stage lymphocytotoxic test. HLA DRB1* and DQB1* typing was done using sequence-specific primers. HLA class 1 and II antigen frequencies of the study subjects were compared to controls that were randomly chosen healthy blood donors from the same population., Results: HLA DQB1*0603 was increased in patients with HBVMN compared to controls (chi2 = 13.65, RR = 4.3). DRB1*07 and DQB1*02 were increased in frequency in the study subjects but failed to reach statistical significance. There was no significant difference in the frequencies of class 1 antigens in the study group compared to controls., Conclusion: To our knowledge, this is the first report of HLA associations in black patients with HBVMN in whom Class 1 and 11 antigens were determined using molecular methodology. There was a high frequency of DQB1*0603 in subjects compared to controls, suggesting a possible genetic predisposition to the development of HBVMN.
- Published
- 2002
- Full Text
- View/download PDF
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