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Biomedical subjects

P D Yorgin

Publications and source records attributed to P D Yorgin.

At least 19 recordsLinked to original sources
PubMed2001

Promising early outcomes with a novel, complete steroid avoidance immunosuppression protocol in pediatric renal transplantation.

BACKGROUND: Corticosteroids have been a cornerstone of immunosuppression for four decades despite their adverse side effects. Past attempts at steroid withdrawal in pediatric renal transplantation have had little success. This study tests the hypothesis that a complete steroid-free immunosuppressive protocol avoids steroid dependency for suppression of the immune response with its accompanying risk of acute rejection on steroid withdrawal. METHODS: An open labeled prospective study of complete steroid avoidance immunosuppressive protocol was undertaken in 10 unsensitized pediatric recipients (ages 5-21 years; mean 14.4 years) of first renal allografts. Steroids were substituted with extended daclizumab use, in combination with tacrolimus and mycophenolate mofetil. Protocol biopsies were performed in the steroid-free group at 0, 1, 3, 6, and 12 months posttransplantation. Clinical outcomes were compared to a steroid-based group of 37 matched historical controls. RESULTS: Graft and patient survival was 100% in both groups. Clinical acute rejection was absent in the steroid-free group at a mean follow-up time of 9 months (range 3-13.7 months). Protocol biopsies in the steroid-free group (includes 10 patients at 3 months, 7 at 6 months, and 4 at 12 months) revealed only two instances of mild (Banff 1A) subclinical rejection (reversed by only a nominal increase in immunosuppression) and no chronic rejection. At 6 months the steroid-free group had no hypertension requiring treatment (P=0.003), no hypercholesterolemia (P=0.007), and essentially no body disfigurement (P=0.0001). Serum creatinines, Schwartz GFR, and mean delta height Z scores trended better in the steroid-free group. In the steroid-free group, one patient had cytomegalovirus disease at 1 month and three had easily treated herpes simplex stomatitis, but with no significant increase in bacterial infections or rehospitalizations over the steroid-based group. The steroid-free group was more anemic early posttransplantation (P=0.004), suggesting an early role of steroids in erythrogenesis; erythropoietin use normalized hematocrits by 6 months. CONCLUSIONS: Complete steroid-free immunosuppression is efficacious and safe in this selected group of children with no early clinical acute rejection episodes. This protocol avoids the morbid side effects of steroids without increasing infection, and may play a future critical role in avoiding noncompliance, although optimizing renal function and growth.

Adolescent↗
PubMed2001

Coccidioidomycosis in adolescents with lupus nephritis.

Coccidioidomycosis, a fungal infection endemic in the southwestern United States, can cause life-threatening infections in immunosuppressed patients. We report the contrasting cases of two adolescents with lupus nephritis, treated with intravenous pulse cyclophosphamide and daily oral corticosteroids, who developed pulmonary coccidioidomycosis. One patient developed a fatal form of fulminant disseminated coccidioidomycosis, while the other patient developed a solitary pulmonary Coccidioides immitis abscess which was responsive to intravenous liposomal amphotericin and fluconazole therapy. Because serologies and initial X-ray studies can be negative, definitive diagnostic studies including bronchoaveolar lavage and needle aspiration should be performed when there is clinical suspicion of coccidioidomycosis in an immunocompromised patient. Immunosuppressed patients with coccidioidomycosis should receive early intravenous amphotericin therapy and may benefit from long-term suppressive antifungal therapy to prevent relapse.

Abscess↗
PubMed2001

Pulse methylprednisolone treatment of idiopathic steroid-resistant nephrotic syndrome.

Although much of the interest in pulse methylprednisolone therapy (PMT) has centered around its use in children with focal segmental glomerulosclerosis, PMT has also been shown to be effective in the treatment of other proteinuric renal diseases. We hypothesized that a PMT-based treatment protocol, derived from the Tune-Mendoza protocol, would effectively induce a more rapid remission in young children with idiopathic steroid-resistant nephrotic syndrome (SRNS). A retrospective analysis was conducted of 11 consecutive SRNS patients (mean age 3.6 +/- 1.5 years) that received PMT between 1 August 1992 and 1 May 1998. The initial mean urinary protein/urinary creatinine ratio (UP/UC, mg/mg) was 8.3 +/- 9.7 and mean estimated creatinine clearance (CCr) 137.7 +/- 47.0 ml/min per 1.73 m2. An average of 24.8 +/- 10.5 PMT doses were given. The mean duration of PMT therapy until remission was 23.4 +/- 29.9 days (median 12 days). Cyclosporine and cyclophosphamide were used to maintain and extend remissions in 5 and 4 patients, respectively. At the conclusion of the study, the mean UP/UC was 0.12 +/- 0.22 and mean CCr 151.8 +/- 39.8 ml/min per 1.73 m2 (no CCr < or = 100 ml/min per 1.73 m2). Of the 11 patients, 9 attained complete remission. Adverse effects were mild and infrequent. This PMT protocol appears to safely and effectively induce remission in young children with SRNS. A future prospective trial that evaluates the efficacy of PMT in young children with SRNS is warranted.

Anti-Inflammatory Agents↗
PubMed2001

Visual loss caused by pseudotumor cerebri in an infant on peritoneal dialysis.

Infants with chronic renal insufficiency have multiple risk factors for developing pseudotumor cerebri (PTC) and are at particular risk for being diagnosed with PTC late, because of their inability to express symptoms. We describe a 13-month-old infant dependent on peritoneal dialysis, without evidence of central nervous system infection or inflammation, who developed acute vision loss secondary to PTC. Signs of PTC in infants include torticollis, inattentiveness, inability to track, facial paresis, or new-onset strabismus. Physicians responsible for the care of children with renal failure should be aware of the potential for PTC, as the diagnosis should be made as early as possible to prevent permanent visual loss.

Brain↗
PubMed2001

Long-term plasmapheresis and protein A column treatment of recurrent FSGS.

Transient or intermittent plasmapheresis with concurrent immunosuppressive therapy is thought to be beneficial in the treatment of recurrent focal segmental glomerulosclerosis (FSGS) in the early post-transplant period. The results of long-term (6-year) plasmapheresis therapy, in a 9-year-old female with an immediate recurrence of FSGS [urinary protein/urinary creatinine (UP/UC)=17.7] after cadaveric renal transplant, are presented. A 4-week plasmapheresis course induced a decline in the proteinuria, but a relapse occurred after cessation of plasmapheresis. Addition of protein A column therapy led to a further decrease in the proteinuria, to a non-nephrotic range. Long-term control of the nephrotic syndrome was established using a chronic treatment regimen consisting of a single-volume plasmapheresis, followed by a protein A column treatment, performed on sequential days every 3-4 weeks. Mean UP/UC values decreased to 1.15+/-0.9. A course of cyclophosphamide was successfully used to control a worsening of proteinuria 4 years post transplant. Although sequential renal biopsies demonstrated progressive glomerular sclerosis, the patient's mean calculated creatinine clearance only modestly declined from 78.3 ml/min per 1.73 m2, at the time of transplantation, to 62.7 ml/min per 1.73 m2, 6 years later. This patient demonstrated dependence on plasmapheresis/protein A column therapy to maintain a clinical remission of her FSGS recurrence. While long-term plasmapheresis and protein A column therapy in combination with immunosuppressive therapy reversed the effects of uncontrolled nephrosis and possibly facilitated long-term renal allograft survival, the glomerular sclerosis continued to progress.

Child↗
PubMed2001

Pulse methylprednisolone, cyclosporine, and ace inhibitor therapy decreases proteinuria in two siblings with familial focal segmental glomerulosclerosis.

Familial focal segmental glomerulosclerosis (FSGS) is a heterogeneous renal disease characterized by proteinuria and an unremitting deterioration of renal excretory function. Previous studies showed corticosteroid unresponsiveness and a variable response to cyclophosphamide therapy. We hypothesized that treatment with pulse methylprednisolone therapy (PMT), alternate-day corticosteroids, and cyclosphosphamide or cyclosporine would decrease proteinuria in patients with familial FSGS. Two adolescent brothers, 13 and 16 years old, presented with nephrotic range proteinuria, but with normal renal excretory function. Both brothers had renal biopsies that showed FSGS with mesangial hypercellularity and tubular atrophy. Intravenous PMT, at doses of 1 g, was initiated per the Tune-Mendoza protocol. Both patients received lisinopril therapy. One brother (case 1) was treated with PMT, alternate-day corticosteroids, and cyclophosphamide (total cumulative cyclophosphamide dose was 154.3 mg/kg). Urinary protein-to-urinary creatinine (UP/UC) ratios decreased from 6.79 to 3.79. Cyclosporine therapy decreased the UP/UC further from 2.48 to 0.76 at the end of PMT. The other brother (case 2), treated with PMT, alternate-day corticosteroids, and cyclosporine, experienced a decrease in UP/UC from 7.27 to 1.14. At the time of last evaluation, approximately 7 months after the last PMT dose, the UP/UC ratios were 0.27 (case 1) and 0.37 (case 2). PMT-attributable adverse effects were not severe. Both patients continued to receive oral cyclosporine and lisinopril after completion of PMT. PMT and cyclosporine therapy may reduce proteinuria, without decreasing renal excretory function, in some patients with familial FSGS. Further evaluation of cyclosporine therapy and PMT of patients with familial FSGS is warranted.

Adolescent↗
PubMed2001

The clinical efficacy of higher hematocrit levels in children with chronic renal insufficiency and those undergoing dialysis.

The optimal hematocrit target range in children with end-stage renal disease, who are receiving recombinant human erythropoietin, is ambiguous due to the lack of compelling, age-appropriate studies. There are a large number of adult and pediatric studies which show that physical performance as well as morbidity and mortality are positively influenced by partial normalization of the hematocrit to 30 vol% to 36 vol%. Cognition studies performed in adults similarly show improvement with partial correction of hematocrit. Normalization of hematocrit studies show lower mortality rates, incremental further improvement in cognition, and greater resolution of cardiac anomalies when compared with patients with partial correction of anemia. Conversely, cardiac death rates may increase in adult patients receiving hemodialysis with preexisting cardiac disease, and there are concerns about the effect of recombinant human erythropoietin on catheter/shunt/fistula patency and on blood pressure. The high cost of recombinant human erythropoietin and established Medicare and Dialysis Outcomes Quality Initiative target hematocrit ranges have also influenced pediatric nephrologists in their assessment of the risk-benefit ratios, despite new adult data suggesting that maintenance of higher hematocrits may be cost-effective. The rationale of using adult-derived hematocrits in children with end-stage renal disease needs to be re-examined in the context of the unique growth and developmental requirements of children. A prospective, multicenter study which determines the relative benefits and risks of age-adjusted hematocrit normalization in children with renal failure is warranted.

Anemia↗
PubMed2000

Effects of geldanamycin, a heat-shock protein 90-binding agent, on T cell function and T cell nonreceptor protein tyrosine kinases.

The benzoquinoid ansamycins geldanamycin (GA), herbimycin, and their derivatives are emerging as novel therapeutic agents that act by inhibiting the 90-kDa heat-shock protein hsp90. We report that GA inhibits the proliferation of mitogen-activated T cells. GA is actively toxic to both resting and activated T cells; activated T cells appear to be especially vulnerable. The mechanism by which GA acts is reflected by its effects on an essential hsp90-dependent protein, the T cell-specific nonreceptor tyrosine kinase lck. GA treatment depletes lck levels in cultured T cells by a kinetically slow dose-dependent process. Pulse-chase analyses indicate that GA induces the very rapid degradation of newly synthesized lck molecules. GA also induces a slower degradation of mature lck populations. These results correlate with global losses in protein tyrosine kinase activity and an inability to respond to TCR stimuli, but the activity of mature lck is not immediately compromised. Although the specific proteasome inhibitor lactacystin provides marginal protection against GA-induced lck depletion, proteasome inhibition also induces changes in lck detergent solubility independent of GA application. There is no other evidence for the involvement of the proteosome. Lysosome inhibition provides quantitatively superior protection against degradation. These results indicate that pharmacologic inhibition of hsp90 chaperone function may represent a novel immunosuppressant strategy, and elaborate on the appropriate context in which to interpret losses of lck as a reporter for the pharmacology of GA in whole organisms.

Animals↗
PubMed2000

Sodium ferric gluconate therapy in renal transplant and renal failure patients.

Intravenous infusion of sodium ferric gluconate (Ferrlecit) has been reported to be effective and safe in pediatric and adult hemodialysis patients with iron depletion. We sought to expand on the previous studies by treating 13 consecutive pediatric renal failure and renal transplant patients with sodium ferric gluconate doses that were higher than previously reported. Efficacy was defined as: (1) an increase in hematocrit of > or = 3 vol% with no change or a decrease in erythropoietin dose or (2) a stable hematocrit with a decrease of > or = 25% in the erythropoietin, 2 weeks to 2 months after sodium ferric gluconate infusion. Two dosing strategies were employed: (1) high dose, where single dose sodium ferric gluconate (mg) approximately calculated iron deficit, and (2) sodium ferric gluconate, 62.5 mg/dose for children < 40 kg, 125 mg/dose for children > 40 kg, infused on eight consecutive hemodialysis runs. There was only one self-limited adverse reaction in 60 doses. Three patients with previous adverse reactions to iron dextran tolerated sodium ferric gluconate without adverse effect. Sodium ferric gluconate was efficacious in eight out of ten patients that received a cumulative dose > 5 mg/kg. The mean hematocrit increased 30.3 +/- 7.8 to 36.4 +/- 4.4 vol% (P = 0.04) and the mean erythropoietin dose decreased 251.5 +/- 149.1 to 100.7 +/- 113.0 units/kg/week (P = 0.02). Although sodium ferric gluconate appears to be effective and safe at the doses used, multicenter, prospective pharmacokinetic and clinical trials of sodium ferric gluconate should be conducted in children.

Adolescent↗
PubMed2000

Concurrent centrifugation plasmapheresis and continuous venovenous hemodiafiltration.

Continuous venovenous hemofiltration/hemodiafiltration (CVVH/D) is commonly used to provide renal replacement therapy for critically ill patients who are hemodynamically unstable. Occasionally, the addition of plasmapheresis therapy is necessary for some conditions, including immune-mediated acute renal failure, sepsis, fulminant hepatic failure, and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Most tertiary care facilities provide centrifugation plasmapheresis instead of membrane plasmapheresis, because of the requirement for both therapeutic plasma exchange and pheresis of cellular blood products. We report a new technique where centrifugation plasmapheresis and CVVHD (P-CVVHD) are combined and used concurrently. Blood from the patient was concurrently filtered utilizing a Hospal BSM 22 machine with a Multiflow 60 hemofilter and a Cobe Spectra continuous cell separator in a parallel configuration. P-CVVHD is technically possible and can be used for long periods of time with limited risks. There may be advantages to P-CVVHD compared with discontinuous combined CVVH/D and plasmapheresis therapy.

Adolescent↗
PubMed1998

Renal manifestations of rheumatic diseases affecting adolescents.

Because of complex immunologic, renal, infectious, fertility, and psychological issues, renal disease secondary to rheumatic disease represents one of the most challenging medical problems for subspecialist and primary care physician alike. However, adolescents with renal disease respond better to treatment than do adults. This chapter addresses the renal manifestations of rheumatic diseases, current treatment options, and complications associated with treatment and long-term prognosis.

Adolescent↗
PubMed1997

Propylene glycol-induced proximal renal tubular cell injury.

Propylene glycol is a solvent that is used in many oral, injectable, and topical medications. Although uncommon, acute renal failure has been attributed to propylene glycol. The mechanism of propylene glycol-mediated renal injury is unknown. We report a case of acute renal failure in a 16-year-old boy given large doses of pentobarbital and phenobarbital, both of which are solubilized with propylene glycol. A renal biopsy showed proximal renal tubular cell swelling and vacuole formation. The data from this case suggest that the reversible acute renal failure caused by propylene glycol is attributable to proximal renal tubular cell injury.

Acute Kidney Injury↗
PubMed1994

Alteration in insulin-like growth factor-binding proteins (IGFBPs) and IGFBP-3 protease activity in serum and urine from acute and chronic renal failure.

The insulin-like growth factors, IGF-I and IGF-II, are proteins that promote cellular growth and differentiation of various organs, including the kidney. These peptides interact with high affinity cell surface receptors and bind to a family of IGF-binding proteins (IGFBPs). Altered serum and urinary IGFBP patterns in children with chronic renal failure have been previously described. In this study, we evaluated serum and urinary IGFBP profiles in acute renal failure patients (ARF; n = 10) and chronic renal failure patients (n = 10), using Western ligand blots. Most patients with acute or chronic renal failure showed decreased intact serum IGFBP-3 and increased serum IGFBP-2. Both groups displayed marked urinary IGFBP alterations, including increased urinary IGFBP-1 and totally absent urinary IGFBP-3, as detected by Western ligand blot. To evaluate altered IGFBP profiles, we performed IGFBP-3 protease assays with sera and urine from renal failure patients and normal controls. Although control urine had only minor protease activity (defined by the ability to degrade [125I]IGFBP-3), significant protease activity was found in urine from renal failure patients. The proteolytic pattern and susceptibility to protease inhibitors in most renal failure urine samples were the same as those seen in normal urine and with plasmin. Protease activity was completely inhibited by serine protease inhibitors. We speculate that urinary protease activity is mediated primarily by a serine protease(s), which may be involved in the modulation of renal IGF activity in health and disease.

Acute Kidney Injury↗
PubMed1993

Insulin-like growth factor binding protein-3 protease activity in the urine of children with chronic renal failure.

The insulin-like growth factors, IGF-1 and IGF-II, are polypeptides that potentiate cellular growth. In addition to binding to specific cell surface receptors, the IGFs bind with high affinity to a family of proteins, the insulin-like growth factor binding proteins (IGFBPs). Serum and urine IGFBP patterns are altered in individuals with chronic renal failure (CRF). We recently reported that the urinary IGFBP pattern of CRF patients is unique for increased insulin-like growth factor binding protein-1 (U-IGFBP-1) levels. In this study, we used western ligand blotting (WLB), western immunoblotting (WIB), and radioimmunoassay (RIA) to further evaluate serum and urine IGFBP profiles of children with CRF (n = 14). Five patients with CRF displayed decreased serum IGFBP-3 profiles by WLB. Serum IGFBP-3 WIB profiles were remarkable for 30- and 20-kDa fragments of IGFBP-3 not seen in control serum. Serum IGFBP-3 levels, as determined by RIA, were slightly elevated. Serum levels of IGFBP-2 also were increased, although not at a level reaching statistical significance. WLB of CRF urine revealed a large increase in U-IGFBP-1 and a complete absence of urinary IGFBP-3. Recent studies of serum from pregnant women and seminal plasma have demonstrated a similar absence of intact IGFBP-3, due to the presence of a specific IGFBP-3 protease. To evaluate whether an IGFBP-3 protease accounts for the absence of intact U-IGFBP-3 in children with CRF, urine and serum samples from individuals with CRF and controls were tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Continuous venovenous hemofiltration.

Continuous venovenous hemofiltration (CVVH) is a technique characterized by a venovenous circuit and a pump to perfuse the hemofilter. CVVH is suited to individualization of ultrafiltration and solute clearance in patients with acute renal failure and volume overload, specifically when there is impaired cardiovascular function or where arterial access is problematic. Examples, indications and relative advantages of this and other dialytic modalities are discussed.

Acute Kidney Injury↗
PubMed1990

Treatment of steroid-resistant focal segmental glomerulosclerosis with pulse methylprednisolone and alkylating agents.

In children, steroid-resistant nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) is frequently a progressive condition resulting in end-stage renal disease. There have been no reports of effective treatment for this condition. For the past several years, the Pediatric Nephrology services at the University of California, San Diego and Stanford University Schools of Medicine have treated these patients with a protocol involving infusions of high doses of methylprednisolone, often in combination with oral alkylating agents. Twenty-three children have been treated in this manner with a follow-up of 46 +/- 5 months. Twelve of these children are in complete remission. Six have minimal to moderate proteinuria. Four children remain nephrotic. Each of these children has a normal glomerular filtration rate. One child developed chronic renal failure and subsequently died while on dialysis. These results appear significantly better than previous series of children with FSGS. A controlled, multi-center trial of this protocol has been proposed.

Adolescent↗