Robert S. Fennell

Sodium Thiosulfate Treatment for Calcific Uremic Arteriolopathy in Children and Young Adults

In adult patients with ESRD, calcific uremic arteriolopathy (CUA) is an uncommon but life-threatening complication. No effective therapy exists, although anecdotal case reports highlight the use of sodium thiosulfate (STS), a calcium-chelating agent with antioxidant properties. CUA is rare in children, and STS use has not been reported. The objective of this study was to determine the influence of STS treatment on three patients with CUA in a pediatric chronic dialysis unit. The patients were between 12 and 21 yr of age; two were male; and primary diagnoses were obstructive uropathy, renal dysplasia, and calcineurin nephrotoxicity. Time from ESRD to CUA diagnosis was 1, 9, and 20 yr. Diagnosis was made by tissue biopsy and three-phase bone scan. Pain was the presenting symptom. Initial treatment included discontinuation of calcitriol and use of non-calcium-based phosphate binders and low-calcium dialysate concentration. STS dosage was 25 g/1.73 m(2) per dose intravenously after each hemodialysis session. For optimization of removal of calcium deposits, patient three received a combination of STS and continuous venovenous hemofiltration for the first 10 d. All patients demonstrated rapid pain relief. Within weeks, skin induration and joint mobility of the extremities improved. Radiographic evidence of reduction in the calcium deposits occurred within 3 mo of initiation of STS. The only complication was prolonged QT interval in one patient as a result of hypocalcemia, who was resolved by use of a higher dialysate calcium concentration. STS seems well tolerated in children and young adults with CUA and has mild adverse effects. For determination of its efficacy, optimum dosage, duration of therapy, and dialysis modality, controlled trials are needed.

Transplantation in Children: A Longitudinal Assessment of Mothers’ Stress, Coping, and Perceptions of Family Functioning

This study examined the parenting stress, coping resources, and family functioning among 27 mothers of children undergoing bone marrow, liver, kidney, and heart transplantation. The mothers completed a comprehensive battery of psychological instruments at the pretransplant stage and at 1- and 6-month posttransplant stages. Increased parenting stress, financial strain, caregiver burden, and family stress were reported following transplantation and persisted for several months. The mothers reported using coping strategies characterized by attempts to maintain family integration and to understand the childs medical situation. Development and evaluation of intervention programs to enhance parents ability to cope with stress and maintain family stability are warranted.

Intermediate‐dose cidofovir without probenecid in the treatment of BK virus allograft nephropathy

Abstract:u2002 BK virus allograft nephropathy (BKVAN) is a rising complication in kidney transplant recipients. Reducing immunosuppression has been the initial form of therapy in most cases, but is not always associated with improvement in graft function. Anti‐viral therapy with low‐dose cidofovir (0.25–0.42u2003mg/kg/dose) has been used successfully in some patients, but dose‐related nephrotoxicity has limited its use. We present our experience with 3 kidney transplant recipients diagnosed with BKVAN who received intermediate‐dose cidofovir (0.75–1.0u2003mg/kg/dose) without probenecid, and without concomitant nephrotoxicity. Three female patients, ages 8, 19 and 20u2003yr, presented with elevated serum creatinine (SCr) values, BK virus stain positive on renal biopsy and high plasma BK viral loads. As a result of viral loads being >2u2003million copies/ml in two patients and a lack of response to reduction in immunosuppression in the third, we initiated therapy with low‐dose cidofovir. Because of persistent positive BK stain and positive plasma viral load, we then administered intermediate‐dose cidofovir, without probenecid, for several subsequent doses (seven to 15 infusions till date). All patients tolerated the intermediate‐dose cidofovir with no significant rise in SCr during the course of the infusions. The most recent SCr values in all three patients were improved from those at the initial diagnosis of BKVAN. All three patients showed a marked drop in BK viral loads when on intermediate‐dose cidofovir, with complete clearing of viremia in two patients. In our experience, intermediate‐dose cidofovir without probenecid, used judiciously, is not associated with additional nephrotoxicity and may provide an additional alternative for treatment.

Intermediate dose cidofovir does not cause additive nephrotoxicity in BK virus allograft nephropathy

Abstract:u2002 BKVAN has emerged as a major morbidity in kidney transplant recipients. Among treatment options is cidofovir, which can be nephrotoxic. We previously reported that intermediate dose cidofovir could be used without significant nephrotoxicity. We present extended results of the same treatment protocol in a larger cohort and with longer follow up. Diagnosis of BKVAN was based on detection of BK viral DNA from plasma and renal allograft biopsy tissue. All patients received cidofovir (0.25–1u2003mg/kg/dose) every 2–3u2003wk. Total number of cidofovir doses ranged from 1 to 18 (mean 8). This report includes eight patients, aged 5–21u2003yr, treated with intermediate dose cidofovir. Median follow‐up was 11u2003months (range 4–32). Mean fall in reciprocal of serum creatinine (1/sCr) from baseline at BKVAN diagnosis was 64% (range 28–120%). A time‐series plot of plasma BK virus PCR and 1/sCr showed marked reduction in viral loads without significant deterioration in 1/sCr from the initial value at BKVAN diagnosis. In this larger series with extended follow up, intermediate dose cidofovir without probenecid for the treatment of BKVAN continues to show stabilization of renal function without progression to renal failure.

Role Of Regular And Leukocyte-free Blood Transfusions In The Generation Of Broad Sensitization

The factors associated with the development of humoral sensitization were studied prospectively in 30 previously transplanted patients immediately after graft rejection. Lymphocyte antibodies were measured both by conventional cytotoxicity in 30 panel cells and by flow cytometry in up to 10 target cells. Although lymphocyte antibodies induced by graft rejection alone were detected in 12 of 26 patients (46%), lymphocytotoxic antibodies were present in only 2 of 27 patients. Of the 25 patients without lymphocytotoxic antibodies, 13 developed them later. In all cases panel antibody reactivity developed after the patients received blood transfusions. No other factor was associated with the development of lymphocytotoxic antibodies, including transplant nephrectomy. There were 12 patients who remained negative for lymphocytotoxic antibodies even though 5 of them were transfused. The powerful role of blood transfusions in the generation of broad sensitization was further documented in 5 patients who received blood units completely depleted of leukocytes by cottonwool filtration and red cell washing. Four of these patients showed significant increases in the level of lymphocytotoxic antibodies, even when stored blood units were used. One additional patient became broadly sensitized by the transfusion of frozen blood. These results show (A) that broad sensitization may not develop if patients are not transfused after graft rejection; (B) that blood transfusions lead to broad sensitization in most (76%) pretransplanted patients; and (C) that transfusion of leukocyte-free blood may delay, but not avoid, the development of broad sensitization.

PERCEPTIONS OF PARENTING STRESS AND FAMILY RELATIONS BY FATHERS OF CHILDREN EVALUATED FOR ORGAN TRANSPLANTATION

18 fathers of children evaluated for solid organ or bone marrow transplantation completed measures of parenting stress and family functioning. Comparisons with normative data indicated that these fathers reported less parenting stress, less family conflict, more concern about family finances, and more limitations in family activities. These data highlight the need for family-based assessments in pediatric transplantation.

Planned random donor blood transfusion in preparation for transplantation. Sensitization and graft survival.

Random donor blood transfusions were used to prepare 183 prospective recipients for one-haplotype living-related donor (LRD) grafts or cadaver donor (CD) grafts. Five units of packed red blood cells were administered over a 7–10 day period, and weekly sera were monitored for six weeks. Sensitization was uncommon in men and nulliparous women (8/153), was of low reactivity, and was not a barrier to transplantation. Multiparous women had a 44% frequency of sensitization on presentation and 11/24 initially lacking cytotoxicity developed reactive serum following transfusion. Single-haplotype LRD recipients had 96% one-year graft survival. CD recipients had one-year graft survival of 72%. The rate of transplantation in surviving candidates exceeded 90%, and supports the hypothesis of a protective immune response.

Total parathyroidectomy and autotransplantation for tertiary hyperparathyroidism in children with chronic renal failure

An association between chronic renal failure and skeletal deformities in the adolescent patient was first documented by Lucas in 1883. Since then it has been established that the kidneys play a major role in the regulation of calcium, phosphate, and parathyroid hormone, and that chronic renal failure is characterized by profound alterations in the normal metabolic homeostasis of the human body. With the hyperphosphatemia of uremia, compensatory hyperparathyroidism is also a well known complication. Due to these factors, loss of normal renal function ultimately leads to derangement in mineral and bone metabolism resulting in severe skeletal deformities. Reports in the English literature suggest that the changes of renal osteodystrophy are much more pronounced in the pediatric patient, as compared to those in the adult. In the last two decades, renal transplantation has come to be recognized as a satisfactory modality for controlling renal failure and its complications. This procedure is often not available as an option, however, in small patients, especially those under three years of age. The pediatric nephrologist is often forced to manage these patients for long periods with conservative therapy, in an attempt to control the ravages of renal osteodystrophy. The problem becomes unmanageable when the compensatory hyperparathyroidism proceeds to autonomy. When this occurs, despite maintenance of normal serum calcium levels, the renal osteodystrophy progresses rapidly, producing pain, deformities and growth retardation. At this point, the condition is often refractory to medical management and resection of parathyroid tissue remains the only satisfactory modality for control.(ABSTRACT TRUNCATED AT 250 WORDS)

Technetium-99M sulfur colloid accumulation as a predictor of acute renal transplant rejection

Renal transplantation is the preferred treatment for end-stage renal disease in children. Most transplant failures are due to allograft rejection. To date, only histo-pathological findings on renal biopsy can establish this diagnosis. Prior to the availability of cyclosporine, technetium-99m sulfur colloid nuclear scans (TSC) were used in a limited number of institutions to detect rejection episodes. The purpose of this study was to determine whether TSC could predict acute rejection in the cyclosporine era. A prospective study involving 41 pediatrie renal transplant patients (M=25, F=16) was conducted from 6/1/89 to 10/31/91. Patients who received a TSC and biopsy (41 patients, 62 studies) within one week of clinical and laboratory evidence of acute rejection were included in the study. A qualitative method of determining sulfur colloid uptake was used by comparing allograft uptake with that of the fifth lumbar vertebrae (L5) marrow uptake: 3+—allograft with greater than L5 marrow uptake, 2+—same as, 1+—less than, and 0—no allograft uptake. Transplant accumulation of ≥2+ was considered consistent with acute rejection (P<0.001). Acute rejection was noted in 53 of 62 renal biopsies. Of those with biopsy-proved acute rejection, SC was positive (≥2+) in 46 of 53. SC of ≥2+ has proved to be a good predictor of acute rejection. This technique has a sensitivity of 98%, specificity of 53%, positive predictive value of 87%, and negative predictive value of 89%.

ANTIPHOSPHOLIPID ANTIBODIES AS A CAUSE OF RENAL ALLOGRAFT LOSS. • 2174

Antiphospholipid antibody syndrome is a thrombophilic disorder in which both venous and/or arterial thromboses may occur in the presence of antiphospholipid antibodies (aPL). Renal allograft thrombosis remains a leading cause of allograft loss in the pediatric transplant population. We assessed the prevalence of aPL in pediatric patients with a history of thrombotic events including allograft loss due to thrombosis.