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

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. METHODS: This was a retrospective review of renal transplantation undertaken at a single teaching hospital in Johannesburg, part of the University of the Witwatersrand. Two hundred and eighty-two transplants were performed between 1984 and 2003. Demographic characteristics of the transplanted population, diagnosis, morbidity, graft survival, and mortality were recorded. RESULTS: Overall 1-, 5-, and 10-yr graft survival was 82, 44, and 23%. Overall 1-, 5-, and 10-yr patient survival was 97, 84, and 68%. The median graft survival for all transplantation episodes was 4.38 yr; 70% of patients survive 10 yr and 54% survive 20 yr or more. Although early graft survival was good, there was a more rapid rate of graft loss than when compared to results from developed centers with much poorer results at 5 and 10 yr. Causes of ESRF show marked variation between the races, and black patients have significantly worse outcomes than others. Compared with white patients, black recipients received fewer living donor kidneys (26 vs. 10%, p = 0.0019), a greater proportion of totally mismatched organs (56 vs. 36%, p = 0.015), less pre-emptive transplantation (7 vs. 35%, p = 0.0001) and experienced a higher rate of primary non-function (13 vs. 3%, p = 0.004). Surgical complications of transplantation occurred in 9% of recipients, but rarely led to graft loss. CONCLUSION: Pediatric renal transplantation in Johannesburg can be accomplished with low complication rates, but medium and long-term graft survival is poor when compared with contemporary results achieved in developed countries. The difficulties of undertaking such complex, multidisciplinary interventions in a developing nation are daunting, but we believe that renal transplantation should still be the treatment of choice for all children with ESRF. The poorer outcomes in black recipients can be addressed by increasing education in our communities and expanding the pool of appropriate donors. Better institutional support would allow for improved long-term patient care.

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.

Immunology, microbiology, and the recalcitrant wound.

Wounding of normal skin initiates an acute inflammatory response that ordinarily contributes to the healing process. The underlying process is orchestrated by the specific and nonspecific immune response. Inflammatory cells provide growth factors and stimulate the deposition of matrix proteins and phagocytose debris. However, the maturation and resolution of a wound may be complicated by micro-organisms. The effects of micro-organisms on oxygen consumption and pH, or toxin production, may interrupt the natural course of wound healing. Thus, a wound may not progress from the acute phase and heal, but may become a nonhealing chronic or recalcitrant wound as long as the antigens from micro-organisms or underlying pathology remain. Depending on the underlying disease pathology and the micro-organism's virulence, microbial growth in acute or chronic wounds may lead to invasive wound infection. Wound infection is a complex interaction involving the host as well as the numbers and types of micro-organisms present. The literature suggests that micro-organisms alter the course of acute wound healing, and a body of evidence exists that suggests that large numbers of organisms in chronic wounds delay the healing process. However, other evidence suggests that, despite bacteria, most chronic wounds progress toward healing, depending upon the wound care strategy employed. Current therapy seeks to alter the relationships between microbial colonization and host defenses by providing an environment that tips the balance in favor of healing. The role of bacteria in acute and chronic wounds may span the spectrum from initiation of inflammation and the healing process, to colonization, invasive infection, systemic sepsis, organ system failure, and death. Understanding the interaction of the wound, wound micro-organisms, and the immune response is central to understanding how best to develop therapeutic approaches.

Noninvasive respiratory monitoring.

Advances in technology now permit a variety of noninvasive respiratory monitoring options for clinicians. Perhaps a more complex issue is determining how much monitoring is needed as part of routine patient care. Often, practitioners take a "more is better" approach. This reasoning is justified in critical care, because, in theory, the more information clinicians have available to them, the more likely they are to make accurate assessments and proper therapeutic interventions. If one fails to properly understand the physiologic significance and clinical limitations of the numbers or waveforms from the monitor, however, patient care may not improve and, even worse, may be compromised. Therefore, proper training in all aspects of respiratory monitoring should be a basic and fundamental component of any critical care nurse training program. There are important cost considerations to be taken into account with continuous respiratory monitoring. The financial impact as it relates to care of the critically ill patient is often difficult to assess. Issues of cost-effectiveness are often justified because of the complex nature of caring for these patients and their need for intensive clinical observation and evaluation. The fact that many aspects of cardiopulmonary assessment can now be determined noninvasively is an important advantage over more invasive technologies and their associated risks. Clearly, monitoring techniques such as pulse oximetry and capnography do not eliminate the need for arterial blood gases and other invasive cardiopulmonary monitoring techniques. Rather, when appropriately applied, noninvasive monitoring has the potential to reduce the frequency of certain invasive procedures and still provide valuable information to nurses and other health care practitioners.

A review of Takayasu's arteritis in children in Gauteng, South Africa.

We have reviewed 31 patients with Takayasu's arteritis followed at two pediatric nephrology units in Gauteng, South Africa over a 15-year period. There were 25 black patients, 4 white, and 2 of mixed race. The mean age at diagnosis was 8.42+/-3.59 (range 2.4-14.5, median 8) years. The most common presenting sign was hypertension, followed by cardiac failure, bruits, and absent pulses. The Mantoux test was strongly positive in 27 patients (90%, control population 5%). Markers of activity included a raised erythrocyte sedimentation rate (23 patients) or Gallium single photon emission tomography (positive in 12 of 16 patients). Angiography revealed type II (abdominal aorta) and III (arch plus abdominal aorta) lesions to be most common (11 in each group). All patients received antituberculous therapy and most low-dose aspirin for its antithromboxane effect. Corticosteroids and further immunosuppression were used to control disease activity. We added total lymphoid irradiation (TLI) or cyclophosphamide. Twenty-six patients in all received further immunosuppression, with 13 patients in each group. Results were similar in the two groups, with similar pre- and posttherapy systolic blood pressures and creatinine clearances. Two patients in each group relapsed, 3 died in the TLI group and 2 in the cyclophosphamide group. Surgical intervention, usually in the quiescent phase, consisted mainly of renal autotransplantation. Because of the problems with TLI and 2 patients with papillary carcinoma of the thyroid with long-term follow-up, we no longer use TLI. We have shown that with active medical and surgical intervention the aggressive course of this disease in children can be modified.

Variants of alpha 1-proteinase inhibitor in black and white South African patients with focal glomerulosclerosis and minimal change nephrotic syndrome.

OBJECTIVE: To determine the prevalence and biochemical characteristics of certain alleles of alpha 1-proteinase inhibitor in black and white South African patients with two common types of pathology causing the nephrotic syndrome. DESIGN: A cross sectional study of black and white patients with focal glomerulosclerosis (FGS) or minimal change disease (MCNS) and black and white controls. SETTING: The patients were drawn from the Paediatric Nephrology Units at the Johannesburg and Baragwanath Hospitals and the controls were drawn from the South African Blood Transfusion Service and the Paediatric Nephrology Clinic in Johannesburg. RESULTS: There was a significant increase in the prevalence of the V allele in black patients with FGS (12%) as compared to black controls (1%) (p = 0.01). None of the white patients with FGS had the V allele but two out the five coloured (mixed race) patients had the V allele (20%). An increase in the prevalence of the S allele of alpha 1PI was found in white patients with FGS and MCNS (10%) as compared to white controls (2%). The plasma elastase inhibitory capacity (EIC) associated with the phenotypes (PI) M1 (Ala213)S, M1 (Ala213) V, and M1 (Ala213) M1 (Ala213) was significantly decreased as compared to the EIC associated with PI M1 (Val213) M1 (Val213) (p = 0.006, p = 0.004, and p = 0.025, respectively). Twelve of 13 patients with FGS and infected with tuberculosis had either the M1 (Ala213) V or F alleles and required transplantation owing to the severity of the disease. All of these patients were either black or coloured. However, eight of 12 patients with FGS who had the M1 (Ala213) V or S alleles but were PPD negative did not require transplantation. CONCLUSION: It is possible that the combination of functionally less efficient alpha 1PI and an inflammatory challenge associated with an infection such as tuberculosis could predispose black and coloured nephrotic patients to more aggressive scarring in FGS.

Renal problems in black South African children.

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.

Noncompliance in children and adolescents after renal transplantation.

This study assesses the perceptions, knowledge, and attitudes of patients and parents attending the Pediatric Transplant Unit at the Johannesburg Hospital. Fifty-six children with renal transplants accompanied by their parents were assessed by means of a questionnaire. The children's ages were 2.53 to 20.85 years. Eleven of twelve in the noncompliant group were male and nine were Black. The ages of the two groups of patients and distance traveled to the transplant center were similar. The noncompliant group of patients more often missed clinic visits (50% vs. 14%), P=0.0201; forgot to take their medications (50% vs. 23%); and took more medications (10.3 +/- 3.0 vs. 7.5 +/- 2.0) and remembered fewer of their names (4.0 +/- 3.5 vs. 6.5 +/- 2.5), P=0.0001 than the compliant group. The noncompliant patients knew less about their disease (50% vs. 8.3%) P=0.0141, allograft (53% vs. 33%), and immunosuppression (66% vs. 200%) P=0.0217, than the compliant patients. A total of 9% of the patients (5/56) were concerned about immunosuppressive side-effects, and indicated that this affected their compliance. Families wanted additional information, both pretransplant (52%) and posttransplant (45.5%). In addition, 85% wanted ongoing in-house education concerning transplantation and medications. Pediatric renal transplant patients and their families require ongoing education, support, medication evaluation, and compliance surveillance. Patients at high risk of noncompliance require directed additional intervention.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Gallium scintigraphy in the diagnosis and total lymphoid irradiation of Takayasu's arteritis.

Takayasu's arteritis (TA) in children causes appreciable morbidity and mortality, predominantly as a result of the complication of renovascular hypertension (RVH). Ten children with TA, complicated by RVH, were treated at our centre over the past decade. An initial raised erythrocyte sedimentation rate (ESR) and a purified protein derivative greater than 15 mm were present in every case. More recently, gallium scintigraphy has been used to demonstrate sites of active inflammation in affected vessels (3/4 patients) which became negative after total lymphoid irradiation (TLI). The latter was used in the last 6 children, and appeared to be effective in controlling disease activity as evinced in the normalisation of their ESRs and negative findings on gallium scintigraphy (in all 3 patients with prior active inflammation). Because of vascular damage caused by the vasculitic process, surgical intervention is often required to improve organ perfusion, particularly of the kidney/s. Renal autografting (or allografting) seems preferable (6/11 kidneys functional) to renal bypass grafting (5/5 kidneys clotted). Patient survival improved when TLI was used in addition to standard surgical and medical therapy; this included steroids and antituberculous therapy with TLI, and steroids and cyclophosphamide in the two relapses. Five of 6 patients treated with TLI were alive after 32-54 months' follow-up, while 4 patients who received standard medical and surgical therapy but not TLI all died within 18 months of diagnosis. Gallium scintigraphy is a helpful diagnostic tool in assessing vasculitic activity in TA; TLI is an important mode of immunosuppression, but still needs to be compared with cyclophosphamide as the major immunosuppressive.

A prospective comparison of a new, synthetic donor site dressing versus an impregnated gauze dressing.

Three institutions enrolled 38 patients who required bilateral skin graft donor sites into a safety and efficacy study of a new synthetic donor site dressing. Bilateral donor sites were randomized to receive either a new, synthetic donor site dressing or an impregnated gauze dressing. Wounds were assessed by time to healing, pain, and patient preference. Synthetic dressing wounds were treated 7.9 days compared with 10.2 days for gauze dressing wounds (p < 0.001), and synthetic dressing wounds were more completely epithelialized. Visual analogue pain analysis revealed significantly less donor site pain with synthetic dressing (2.94) versus gauze dressing (4.64) (p < 0.001). Synthetic dressing had fewer treatment-related adverse experiences than gauze dressing (2 vs 7) and was judged by recipients to be superior to gauze dressing in comfort, pain relief, cosmetic appeal, ease of ambulation, and overall acceptance.

Burn wounds: infection and healing.

Early wound closure is the ultimate goal of burn care. While excisional therapy is necessary in the treatment of both large, full-thickness and deep, partial skin-thickness burns, the majority of burns are superficial partial skin-thickness injuries requiring a different clinical approach. In superficial wounds, cosmetic and functional restoration in conjunction with relief from pain and prevention of infection is as important as rapid wound closure. The moist wound healing associated with hydrocolloid dressings may provide an alternative treatment modality for certain partial-thickness injuries. In comparable wounds, these dressings produce good functional and cosmetic results, rapid reepithelialization, and improved patient comfort.

Donor site repair.

Delayed healing of skin donor sites may be costly and life threatening, especially in patients with large body-surface area burns. A donor site dressing should maximize the ability of the wound to heal without increasing the risk of local infection, systemic infection, or both. Specifically, the possibility of a secondary infection may either slow the healing process or ultimately convert the donor site to a full-thickness wound. A number of materials, ranging from gauze to biological agents, have been investigated for use as donor site dressings. The use of hydrocolloids for donor sites has been studied extensively, and, compared with conventional dressings, improved healing rates are reported. Our recent study using a hydrocolloid dressing confirmed earlier research showing fewer infections and more rapid donor site healing.

What is infection?

Wound colonization by bacteria is not always the same as invasive infection. Furthermore, the classic definition of infection does not always aid the clinician in determining whether a patient is in the process of developing life-threatening sepsis. Although research efforts have focused on identification and quantification of organisms involved, the predictive value of this variable is limited. Other variables, such as the nature of the organism, nature of the wound, and nature of the host's defense mechanisms must also be considered. For instance, large acute wounds have been found to react differently to skin flora organisms than small, chronic, ulcerative wounds. Careful and frequent patient and wound assessment is still required to predict if and when offending organisms, their toxins, or both reach sufficient concentrations to overwhelm their local host defenses.

Impact of tuberculosis in children with idiopathic nephrotic syndrome.

Forty black South African children (mean age 4.7 +/- 2.6 years) with idiopathic nephrotic syndrome due to focal glomerulosclerosis (FSGS) were evaluated. Tuberculosis (TB) was found in 37.5% of children with FSGS (FSGS-TB) compared with 6% of a comparable group with minimal lesion nephrotic syndrome. No significant differences were found in the initial mean serum albumin, cholesterol, triglyceride and creatinine levels in FSGS-TB compared with children with glomerulosclerosis but without TB (FSGS-nonTB). The mean serum levels of C4, IgA and IgM were increased by 30%, 25% and 23%, respectively in children with FSGS-TB compared with FSGS-nonTB. Initial estimated creatinine clearance was similar in the two groups, but after a mean follow-up of 2.4 years, the mean estimated creatinine clearance of children with FSGS-TB was significantly reduced by 46% from the initial value, but remained stable in the FSGS-nonTB group. FSGS-TB children also had significantly increased requirements for renal replacement therapy compared with children with FSGS-nonTB. We conclude that TB infection is commonly associated with FSGS in black South African children; this may have deleterious effects on renal function.

Effect of triglycyl-lysine-vasopressin on skin blood flow and blood loss during wound excision in patients with burns.

Excisional therapy often results in large-volume blood loss. Triglycyl-lysine-vasopressin selectively decreases dermal blood flow and therefore was tested for efficacy in limiting intraoperative blood loss in a series of patients undergoing excisional therapy. Ten patients with symmetric injuries were treated with intravenous triglycyl-lysine-vasopressin after excision of half of their burn wound. Blood loss, which was quantified by weighing sponges used to absorb shed blood, was significantly decreased after treatment. Triglycyl-lysine-vasopressin treatment was safe and effective and should be considered in cases when large-volume blood loss is expected.

Control of hemorrhage during renal failure with triglycyl-lysine-vasopressin.

A 35-year-old man with chronic renal failure developed toxic epidermal necrolysis due to combination antibiotic therapy for a community acquired pneumonia. During wound care for his toxic epidermal necrolysis, he developed massive bleeding, a 4 to 6 unit blood loss at each dressing change, due to uremia-associated platelet dysfunction and thrombocytopenia. After failure of standard therapy, the man was treated with intravenous triglycyl-lysine-vasopressin, a selective peripheral vasoconstrictor. Transfusion requirements stopped during treatment. This man went on to full recovery with complete wound healing. Triglycyl-lysine-vasopressin effectively reduced skin blood loss in this man with toxic epidermal necrolysis and an intrinsic hemostatic defect, and may be useful in other patients with cutaneous blood loss.

Microbiology and healing of the occluded skin-graft donor site.

Delayed healing of skin-graft donor sites may be costly and life-threatening, especially in patients with large body surface area burns. A donor site dressing should maximize the ability of the wound to heal without increasing the risk of local infection, systemic infection, or both. Specifically, the possibility of a secondary infection may either slow the healing process or ultimately convert the donor site into a full-thickness skin loss. A number of materials ranging from gauze to biologicals have been investigated for use as donor site dressings. The use of hydrocolloids for donor sites has been widely studied and has shown improved healing rates over the rates reported for conventional dressings. Our recent study using hydrocolloids confirmed earlier research that showed fewer infections and more rapid donor site healing.