Epstein-Barr virus-induced systemic lupus erythematosus

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Primary nephrotic syndrome in the new millennium in KwaZulu-Natal, South Africa

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

Effect of renal Doppler ultrasound on the detection of nutcracker syndrome in children with hematuria

To assess the detection rate of nutcracker syndrome in children with isolated hematuria, renal Doppler ultrasound examinations were routinely performed on 216 consecutive children (176 microscopic hematuria and 40 gross hematuria). Renal Doppler ultrasound was also performed on 32 healthy normal children. The peak velocity (PV) was measured at the hilar portion of the left renal vein (LRV) and at the LRV between the aorta and the superior mesenteric artery. The PV at the aortomesenteric portion (P=0.003) and the PV ratios of the LRV (P=0.003) were significantly higher in children with hematuria than in normal children, while the PV at the hilar portion was not different. If a PV ratio of the LRV of at least 4.1 (the cut-off level set at the mean ±2 SD of the value for the normal children) was defined as abnormal, 72 cases (33.3%) in children with hematuria and no cases in normal children were diagnosed as having nutcracker syndrome. The prevalence of nutcracker syndrome is relatively high in children with isolated hematuria, and the inclusion of renal Doppler ultrasound as a screening examination has a substantial effect on the detection of nutcracker syndrome

Experience with tacrolimus in children with steroid-resistant nephrotic syndrome

Children with steroid-resistant nephrotic syndrome (SRNS) are at risk of developing renal failure. We report here the results of a single-center retrospective observational study of the remission rate in pediatric patients with SNRS receiving tacrolimus. Serial renal biopsies from children on tacrolimus therapy were evaluated for tubulointerstitial fibrosis and transforming growth factor-β immunostaining. Of the 16 children with SRNS, 15 went into complete remission after a median of 120 days of therapy. Nine children were able to stop steroids, while the others were on tapering doses. Forty-seven percent had relapses, most of which were steroid-responsive. Serial renal biopsies were obtained from seven children after a median treatment duration of 24 months; two of these children had increased tubulointerstitial fibrosis and four showed increased transforming growth factor-β tissue staining. Children with worsening histological findings were younger. There was no significant association between tacrolimus exposure and biopsy changes, although the average trough level was higher in those children with worsening histological findings. In conclusion, tacrolimus may be a safe and effective alternative agent for inducing remission in children with SRNS. However, caution needs to be taken when prescribing this agent due to its narrow therapeutic index. Serial renal biopsies are necessary to check for subclinical nephrotoxicity, especially in younger children and those with higher trough levels

Enterohaemorrhagic Escherichia coli and Shigella dysenteriae type 1-induced haemolytic uraemic syndrome

Haemolytic uraemic syndrome (HUS) can be classified according to the aetiology of the different disorders from which it is composed. The most prevalent form is that induced by shigatoxin producing Escherichia coli (STEC) and, in some tropical regions, by Shigella dysenteriae type 1. STEC cause a zoonosis, are widely distributed in nature, enter the food chain in different ways, and show regional differences. Not all STEC are human pathogens. Enterohaemorrhagic E. coli usually cause attachment and effacing lesions in the intestine. This is not essential, but production of a shigatoxin (Stx) is. Because Stx are encoded by a bacteriophage, this property is transferable to naïve strains. Laboratory methods have improved by identifying STEC either via the toxin or its bacteriophage. Shigella dysenteriae type 1 produces shigatoxin, identical to Stx-1, but also has entero-invasive properties that enterohaemorrhagic Escherichia coli (EHEC) do not. Shigella patients risk bacteremia and benefit from early antibiotic treatment, unlike those with EHEC

Hepatitis B and Renal Disease

Glomerulonephritis is an important extrahepatic manifestation of chronic hepatitis B virus (HBV) infection. The uncommon occurrence, variability in renal histopathology, and heterogeneity in clinical course present challenges in clinical studies and have resulted in a relative paucity of data and uncertainty with regard to the optimal management of HBV-related glomerular diseases. The advent of nucleos(t)ide analogue medications that effectively suppress HBV replication has markedly altered the clinical outcomes of kidney transplant recipients with HBV infection, but the emergence of drug resistance is an escalating problem. This article reviews the recent knowledge of the pathogenesis and treatment of HBV-related membranous nephropathy, and discusses the management of hepatitis B in kidney transplant recipients, which is continuously evolving

Epidemiology of chronic kidney disease in children

In the past 30 years there have been major improvements in the care of children with chronic kidney disease (CKD). However, most of the available epidemiological data stem from end-stage renal disease (ESRD) registries and information on the earlier stages of pediatric CKD is still limited. The median reported incidence of renal replacement therapy (RRT) in children aged 0–19 years across the world in 2008 was 9 per million of the age-related population (4–18 years). The prevalence of RRT in 2008 ranged from 18 to 100 per million of the age-related population. Congenital disorders, including congenital anomalies of the kidney and urinary tract (CAKUT) and hereditary nephropathies, are responsible for about two thirds of all cases of CKD in developed countries, while acquired causes predominate in developing countries. Children with congenital disorders experience a slower progression of CKD than those with glomerulonephritis, resulting in a lower proportion of CAKUT in the ESRD population compared with less advanced stages of CKD. Most children with ESRD start on dialysis and then receive a transplant. While the survival rate of children with ERSD has improved, it remains about 30 times lower than that of healthy peers. Children now mainly die of cardiovascular causes and infection rather than from renal failure

Following specific podocyte injury captopril protects against progressive long term renal damage

Background: Angiotensin converting enzyme inhibitors (ACEi) reduce proteinuria and preserve kidney function in proteinuric renal diseases. Their nephroprotective effect exceeds that attributable to lowering of blood pressure alone. This study examines the potential of ACEi to protect from progression of injury after a highly specific injury to podocytes in a mouse model. Methods: We created transgenic (Podo-DTR) mice in which graded specific podocyte injury could be induced by a single injection of diphtheria toxin. Transgenic and wild-type mice were given the ACEi captopril in drinking water, or water alone, commencing 24h after toxin injection. Kidneys were examined histologically at 8 weeks and injury assessed by observers blinded to experimental group. Results: After toxin injection, Podo-DTR mice developed acute proteinuria, and at higher doses transient renal impairment, which subsided within 3 weeks to be followed by a slow glomerular scarring process. Captopril treatment in Podo-DTR line 57 after toxin injection at 5ng/g body weight reduced proteinuria and ameliorated glomerular scarring, matrix accumulation and glomerulosclerosis almost to baseline (toxin: 17%; toxin + ACEi 10%, p<0.04; control 7% glomerular scarring). Podocyte counts were reduced after toxin treatment and showed no recovery irrespective of captopril treatment (7.1 and 7.3 podocytes per glomerular cross section in water and captopril-treated animals compared with 8.2 of wild-type controls, p<0.05). Conclusions: Observations in Podo-DTR mice support the hypothesis that continuing podocyte dysfunction is a key abnormality in proteinuric disease. Our model is ideal for studying strategies to protect the kidney from progressive injury following podocyte depletion. Demonstrable protective effects from captopril occur, despite indiscernible preservation or restoration of podocyte counts, at least after this degree of relatively mild injury

Vitamin D Deficiency and Its Health Consequences in Africa

Africa is heterogeneous in latitude, geography, climate, food availability, religious and cultural practices, and skin pigmentation. It is expected, therefore, that prevalence of vitamin D deficiency varies widely, in line with influences on skin exposure to UVB sunshine. Furthermore, low calcium intakes and heavy burden of infectious disease common in many countries may increase vitamin D utilization and turnover. Studies of plasma 25OHD concentration indicate a spectrum from clinical deficiency to values at the high end of the physiological range; however, data are limited. Representative studies of status in different countries, using comparable analytical techniques, and of relationships between vitamin D status and risk of infectious and chronic diseases relevant to the African context are needed. Public health measures to secure vitamin D adequacy cannot encompass the whole continent and need to be developed locally