Peter D. Thomson

The hemolytic uremic syndrome.

HUS is one of the most common causes of acute renal failure in childhood. D+ HUS is the most common form and usually follows an episode of hemorrhagic colitis due to VTEC or S. dysenteriae type 1. The SLT elaborated by these organisms is responsible for the endothelial damage that is the initial insult in the pathogenesis of the acute renal failure. Excellent supportive care is necessary to reduce the mortality and morbidity due to HUS.

Cell‐Free DNA in Urine

Abstract: Intrigued by the rapid clearance of free fetal DNA from the maternal circulation, we have investigated whether this fetal genetic material could be cleared via the kidney. For this purpose, we examined for the presence of Y chromosome‐specific DNA sequences in urine samples obtained from 8 women pregnant with male fetuses. No male‐specific sequences could be detected, despite the use of a very sensitive nested PCR assay nor a highly reproducible real‐time PCR assay. We did, however, detect maternal DNA sequences. To determine if this cell‐free DNA was derived from the kidney or another source, we next examined urine from female kidney transplant patients who had received male kidneys. Y chromosome‐specific sequences were indeed detectable by both nested and real‐time PCR in these samples, thereby confirming a recent report describing urinary DNA microchimerism. Quantitative analysis of serially obtained samples furthermore suggests that transplant‐derived sequences are elevated during periods of graft rejection. These results imply that the measurement of graft‐derived urinary DNA may serve as a new marker for kidney graft tolerance.

Paediatric renal transplantation non-compliance

The aim of this study was to quantify and where possible objectively confirm the magnitude of non-compliance (NC) in our paediatric renal transplant recipients. A total of 94 paediatric transplants were performed between 1984 and 1989; 17 were excluded due to graft loss (2), death (3), oxalosis (2) and transfer to the adult unit (10). NC was assessed as missed clinic visits plus medication shortages or actual admission of NC. NC was found in 22% (17/77) of transplanted patients. NC showed no correlation with parental marital status, sex, distance lived from the hospital, pre-emptive transplant status or total lymphoid irradiation. Most NC was peripubertal with a smaller NC in the late teenager group. Social class correlated positively with NC; 82.3% of NC was from social classes III and IV, who formed 52.4% of the patients. NC in social class II (3/26) was significantly different from social class IV (12/24) (P=0.01); 91% of black patients with NC were from social class IV. Race, corrected for social class, failed to reach significance (P>0.05). Confirmation of compliance was sought from retrospective cyclosporin A (CsA) trough levels (twice daily dosage). Concomitant phenytoin therapy and CsA given as a daily dosage were excluded as significant confounding variables. The CsA dosage was not significantly different between the compliant (C) and patients with NC. Patients with NC were 8 times more likely to have a CsA level<10 ng/ml (P=0.0026) than C patients. Patients with NC have needed more grafts (P=0.037), have a shorter graft survival, have lost more grafts (P=0.0003), and more have died (P=0.0197), than C patients.

Platelet, erythrocyte, and fibrinogen kinetics in the hemolytic-uremic syndrome of infancy.

Thrombocytopenia, anemia, and uremia compose the “triad” of the hemolytic-uremic syndrome of infancy. To elucidate further the mechanism of the hematologic findings, radiochromium-labeled compatible allogeneic platelets, erythrocytes, and 125I fibrinogen were infused into ten infants with this syndrome. In all four patients into whom labeled platelets were infused, platelet life-span was shortened. External counting and scintiscan failed to demonstrate accumulation of radioactivity in the kidneys, suggesting that platelet deposition in this organ may not account for the persistent thrombocytopenia. In the three patients in whom erythrocyte survival was studied, the life-span of transfused cells was shortened, and external counting and scintiscan revealed a pattern compatible with sequestration in the reticuloendothelial system. Evidence for associated intravascular hemolysis was demonstrated. The clearance from the plasma of 125I fibrinogen was not rapid, and no excessive accumulation of 125I fibrinogen could be demonstrated in the kidneys. These findings suggest that when the diagnostic triad of the hemolytic-uremic syndrome of infancy is seen, the renal lesion is already established and continuing intravascular coagulation is not a feature.

Hypertension as the major problem of idiopathic arterial calcification of infancy

We describe two infants with severe hypertension associated with idiopathic arterial calcification of infancy. In both children, blood pressure control was refractory to aggressive antihypertensive therapy. There was radiologic and laboratory evidence of renovascular disease requiring the use of specific renin antagonists and later nephrectomy, resulting in moderate improvement of hypertension. Although on occasion there is a familial incidence, in the vast majority of cases the diagnosis hinges on a high index of suspicion.

Renal problems in black South African children.

Abstract. Black South African children have an increased prevalence of acute post-streptococcal glomerulonephritis, focal glomerulosclerosis, hepatitis B-associated membranous nephropathy, congenital syphilis, congenital nephrotic syndrome with Alport-like basement membrane changes and Takayasu’s arteritis, but a paucity of reflux nephropathy, polycystic kidney disease and non-shigella-induced haemolytic uraemic syndrome. However, in recent years, the haemolytic uraemic syndrome has become more prevalent in black children; this is usually due to Shigella dysenteriae type 1, and could indicate a different emphasis in the pathogenic mechanism. Focal glomerulosclerosis is the commonest reason for renal failure requiring transplantation in black children with rapidly progressive glomerulonephritis (usually streptococcal induced) being second. Transplantation has been somewhat problematic with a scarcity of kidneys at times, many mismatches and poor compliance in the lower socio-economic groups. The association of tuberculosis with focal glomerulosclerosis and Takayasu’s arteritis in black South African children is intriguing. The progression of focal glomerulosclerosis is accelerated in those patients with evidence of previous tuberculosis, and in Takayasu’s arteritis the association is almost absolute as experienced locally, with the data suggesting an autoimmune reaction.

Management of severe hypertension in childhood Takayasu's arteritis

Six children presented with severe hypertension caused by Takayasus arteritis (TA), of whom four had bilateral renal artery narrowing and two coarctation syndrome. Two presented with hypertensive encephalopathy and four with congestive cardiac failure. All had a strongly positive skin reactions to purified protein derivative of mycobacterium tuberculosis. Bilateral renal arterial bypass grafts performed in two children resulted in prolonged normalization of their blood pressures, but the grafts clotted 12–18 months later. Primary renal autotransplantation was unsuccessful in two children, one with bilateral renal arterial narrowing and iliac vessel involvement and one with a long coarctation. Secondary renal autotransplantation was successful in a third child with localized aortitis. A successful aortic patch graft was performed in one child with coarctation of the aorta. Angiotensin-converting-enzyme inhibitors should be used with caution in treating the hypertension caused by TA, since bilateral renal arterial narrowing is common and their administration may result in renal insufficiency. The long-term prognosis is guarded in severely hypertensive children with extensive vascular disease due to TA.

Demographics and presenting clinical features of childhood systemic lupus erythematosus

Objectives. To review the presentation and characteristics of children with systemic lupus erythematosus (SLE). Methods. The records of children with sufficient American College of Rheumatology (ACR) criteria for SLE treated by the renal units of the Johannesburg and Chris Hani Baragwanath hospitals, and the arthritis clinic of the Johannesburg Hospital between January 1974 and March 2000 were reviewed. The clinical presentation, age distribution and race were examined. Results. A total of 36 children met the criteria. There were 26 girls and 10 boys, with a mean age of 11.5 and 10.2 years respectively. The male-to-female ratio was 1:2.6 overall, with a ratio of 1:1.2 under 10 years and 1:4 over 10 years. There were 15 white, 2 Indian and 5 coloured patients. The 14 black patients all presented after 1986. Rashes were found to be the commonest clinical feature present at the time of diagnosis, followed by polyarthritis and renal pathology. Constitutional symptoms were common, as were generalised lymphadenopathy and hepatosplenomegaly, while neurological, pulmonary and cardiac signs and symptoms were less common. Renal disease was present in 58% of patients on presentation. Conclusion. There is a diverse array of presenting features in childhood SLE. There has been increased recognition of the disease in young black South Africans since 1986.

Skeletal manifestations of primary oxalosis

We describe the clinical, radiographic and histological features of skeletal involvement in four patients with end-stage renal failure due to primary oxalosis. The clinical features were unrelenting bone pain, and in two patients multiple fractures. Radiographic features were, in chronological order: (1) radiodense metaphyses and other red marrow bone; (2) cortical defects in metaphyses; (3) spontaneous fracture-separations of epiphyses of long limb bones which healed poorly. The fractures occurred through crystal deposits, and fracture displacement was associated with extrusion of crystalline material from bone. On histological examination crystals were found to replace metaphyseal bone. Pericrystalline giant cell granulomata replaced bone marrow. Erosion surfaces near granulomas were increased. Subperiosteal and intra-osseous tophi of calcium oxalate were seen. Calcium oxalate appears to precipitate with greater facility than does physiological mineral. Bone showed the features of mixed uraemic osteodystrophy in all four patients. We conclude that: (1) the fractures occurred through heavy crystal deposits; (2) ununited fractures and intra-osseous and subperiosteal tophi contributed to the pain; (3) spontaneous fractures are of poor prognostic significance. We recommend that unstable fractures be internally fixed.

Pediatric renal transplantation in a South African teaching hospital: A 20-year perspective

Abstract:  Introduction:  Renal transplantation is established as the standard of care for end‐stage renal failure (ESRF) in the developed world. In emerging nations, the appropriateness of such costly interventions has been questioned. We undertook an analysis of all renal transplants undertaken under the care of the pediatric nephrology service at the Johannesburg Hospital, South Africa, in order to establish the outcomes of a transplantation service in a resource‐constrained environment in a developing country.