ABSTRACT
We have previously reported the one-year outcomes of 16 children with severe proliferative lupus nephritis (LN) who were treated using a multi-targeted induction protocol based on intravenous (IV) pulse methylprednisolone (MP), mycophenolate mofetil (MMF) and cyclosporine (CSA). This study examined the long-term renal outcomes of these 16 children, followed up for a median duration of 9.2 years (range 5.8-14.2 years). Primary treatment outcome was complete renal remission. Secondary outcomes included patient and renal survival as well as relapse-free and event-free survival. All patients achieved complete renal remission within 24 months (median 8.7 months, range 4.0-24.0 months). Comparing clinical and laboratory parameters at induction and last follow-up, respectively, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (25.4 ± 8.7 vs. 0.4 ± 0.8), serum complement C3 (47 ± 21 vs. 107 ± 27 mg/dL), estimated glomerular filtration rate (eGFR) (72 ± 57 vs. 109.7 ± 43 ml/min/1.73 m2) and urine protein (6.97 ± 7.09 vs. 0.2 ± 0.02 g/day/1.73 m2) improved significantly (p < 0.05). Kaplan-Meier survival analysis showed a cumulative ten-year renal relapse-free survival of 73.3% when considering relapses with severe proteinuria >1 g/day/1.73 m2. Cumulative probability that hospitalization would not be required was 93.8% at one year, and 71.4% at ten years. Our multi-targeted protocol for induction and maintenance therapy in Asian children with severe proliferative LN resulted in good long-term patient survival and renal preservation, with a good safety profile.
Subject(s)
Cyclosporine/administration & dosage , Immunosuppressive Agents/administration & dosage , Lupus Nephritis/drug therapy , Methylprednisolone/administration & dosage , Mycophenolic Acid/administration & dosage , Administration, Intravenous , Adolescent , Age Factors , Child , Child, Preschool , Disease-Free Survival , Drug Therapy, Combination , Female , Follow-Up Studies , Hospitalization , Humans , Kaplan-Meier Estimate , Logistic Models , Lupus Nephritis/diagnosis , Lupus Nephritis/immunology , Male , Pulse Therapy, Drug , Recurrence , Remission Induction , Risk Factors , Severity of Illness Index , Singapore , Time Factors , Treatment OutcomeABSTRACT
Individuals with TRPC6 mutations have variable phenotypes, ranging from healthy carrier to focal segmental glomerulosclerosis (FSGS) leading to renal failure. Here, we describe a family where six members had a novel TRPC6 p.R68W (c.202C>T) mutation, two of whom had renal failure from FSGS, and one had proteinuria. One healthy carrier donated a kidney to her sister. Both donor and recipient had no proteinuria at 20 years posttransplant. Two synonymous NPHS1 polymorphisms, rs2285450 (c.294C>T) and rs437168 (c.2289C>T) segregated with renal failure in this family. These variants had higher allele frequencies in 97 unrelated patients with nephrotic syndrome or FSGS compared to 224 controls. Using patch-clamp experiments in HEK293 and podocytes, we showed that the p.R68W mutation increased TRPC6 current amplitudes, which may be explained by enhanced TRPC6 surface expression. Additionally, while wild-type nephrin suppressed TRPC6 currents, this ability was lost in the presence of NPHS1 c.294C>T polymorphism. When cells were transfected according to combined TRPC6 and NPHS1 genotypes in the family, those representing the donor had lower TRPC6 currents than cells representing the recipient, suggesting that interactions between TRPC6 and NPHS1 variants could possibly account for the variable penetrance of TRPC6 mutations and the absence of recurrence in the graft.
Subject(s)
Glomerulosclerosis, Focal Segmental/etiology , Kidney Transplantation/adverse effects , Membrane Proteins/genetics , Mutation/genetics , Polymorphism, Single Nucleotide/genetics , TRPC Cation Channels/genetics , Adolescent , Adult , Aged , Animals , Blotting, Western , Case-Control Studies , Child , Child, Preschool , Female , Follow-Up Studies , Gene Frequency , Genotype , Glomerular Filtration Rate , Glomerulosclerosis, Focal Segmental/pathology , Graft Rejection/etiology , Graft Rejection/pathology , Graft Survival , HEK293 Cells , Humans , Infant , Kidney Function Tests , Male , Mice , Mice, Knockout , Middle Aged , Pedigree , Phenotype , Podocytes , Postoperative Complications , Prognosis , Recurrence , Risk Factors , TRPC6 Cation Channel , Young AdultABSTRACT
The outcomes of children with severe proliferative lupus nephritis (LN) were examined using a new mycophenolate and cyclosporine-based (MMF-CSA) induction protocol. Sixteen children with LN (WHO class III and IV), 31.3% of whom required dialysis at induction, were retrospectively studied. Median MMF dose was 942 mg/m( 2)/day. Thirteen patients (81%) with persistent proteinuria received CSA. Clinical and laboratory parameters were compared at pre-induction, 6 and 12 months. Treatment outcome was defined by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), renal function, haematuria, proteinuria and serological markers (complements C3, C4 and anti-dsDNA). Comparing these parameters at induction, 6 months and 12 months, respectively, SLEDAI (25.4 +/- 8.7 versus 3.2 +/- 2.9 versus 2.9 +/- 2.8), serum C3 (47 +/- 21 versus 107 +/- 27 versus 111 +/- 38 mg/dl), C4 (12 +/- 14 versus 23 +/- 14 versus 22 +/- 11 mg/dl) and urine protein (6.97 +/- 7.09 versus 0.98 +/- 1.56 versus 0.21 +/- 0.13 g/ day/1. 73 m(2)) improved significantly (p < 0.05). Anti-dsDNA titres decreased in 73% by 6 and 12 months (p < 0.05). Complete renal remission was achieved in 7/16 (43.8%) at 6 months and 12/16 (75%) at 12 months, the rest achieving partial remission with no treatment failures. In conclusion, a combination MMF-CSA protocol is an effective therapeutic alternative for induction of children with severe proliferative LN, resulting in significant clinical and serological improvement with minimal adverse effects.
Subject(s)
Cyclosporine/therapeutic use , Immunosuppressive Agents/therapeutic use , Lupus Nephritis/drug therapy , Lupus Nephritis/pathology , Mycophenolic Acid/analogs & derivatives , Adolescent , Child , Child, Preschool , Disease Progression , Humans , Lupus Nephritis/physiopathology , Male , Mycophenolic Acid/therapeutic use , Remission Induction , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: This article reviews published literature on the usefulness of population-based urinary screening in the Asian paediatric population. METHODS: Articles were found in the Medline database using the key words "paediatrics", "urine screening", "proteinuria", "haematuria" and "population". The Asian countries which had carried out population-based urinary screening of the paediatric population included Taiwan, Japan and Korea. One study was found on urinary screening in a select population in Malaysia. Preliminary results of the urinary screening of school children in Singapore are presented and compared with the results found in the above-mentioned countries. RESULTS: Overall, the proportion of children found to have urinary abnormalities ranged from less than 0.1% of the population screened to almost 50% of a select cohort referred from the screening programmes for the evaluation of urinary abnormalities. In the pilot Singapore school screening programme, the prevalence of clinically significant proteinuria was 1.25 per 1000 children screened. Multivariate analysis showed that low body weight was associated with a 1.8-fold greater risk for proteinuria. The major cause of haematuria and proteinuria in those studies where renal biopsies were performed was glomerulonephritis. The Taiwanese experience also showed a reduction in the incidence of end-stage renal failure diagnosed in children after the onset of urine screening. CONCLUSION: These studies showed that urinary screening programmes in school children allow the early detection of disease. The cost-benefit ratio for specific populations should be determined before the implementation of such programmes.
Subject(s)
Kidney Diseases/prevention & control , Mass Screening/methods , Asia/epidemiology , Biopsy , Blood Pressure Monitoring, Ambulatory , Body Weight , Child , Chronic Disease , Humans , Kidney/pathology , Kidney Diseases/diagnosis , Kidney Diseases/epidemiology , Prevalence , Risk Factors , School Health Services , UrinalysisSubject(s)
Algorithms , Kidney Failure, Chronic/therapy , Peritoneal Dialysis , Treatment Refusal , Adolescent , Adult , Child , Child, Preschool , HumansABSTRACT
Interleukin-13 (IL-13) is a known modulator of monocyte function, down-regulating monocyte surface markers such as CD14 and proinflammatory cytokines. We have shown previously that lymphocyte IL-13 gene expression was up-regulated during relapses in children with steroid-responsive nephrotic syndrome (SRNS). In this study, we examined the monocyte mRNA expression and lipopolysaccharide (LPS)-stimulated intracellular production of tumour necrosis factor-alpha (TNF-alpha) and IL-8 in children with SRNS during relapse and remission. Additionally, we investigated CD14 mRNA levels, CD14 surface expression and its soluble component (sCD14) in serum. Our results showed that the percentages of TNF-alpha positive monocytes following LPS stimulation were significantly lower in nephrotic children in relapse (64.4 +/- 13.7%) compared to remission (81.6 +/- 9.0%, P < 0.005). This was associated with down-regulation of CD14 mRNA, as well as both membrane and sCD14 in patients with nephrotic relapse (82.9 +/- 10.1% and 1.23 +/- 0.30 micro g/ml, respectively) compared to remission (93.9 +/- 3.2% and 1.77 +/- 0.82 micro g/ml, respectively) (P < 0.003). Although we demonstrated a decrease in LPS-stimulated intracellular production of TNF-alpha in monocytes from patients with nephrotic relapse, we were unable to show a concomitant decrease in mRNA expression during relapses. This could be explained by down-regulation of gene expression at the translational rather than transcriptional level. In conclusion, it is conceivable that up-regulation of T-cell IL-13 production in children with active nephrotic relapse was associated with suppression of monocyte CD14 expression, down-regulating pro-inflammatory cytokine production, and could account for the increased susceptibility to bacterial sepsis seen in nephrotic children in active relapse.
Subject(s)
Lipopolysaccharide Receptors/immunology , Monocytes/immunology , Nephrotic Syndrome/immunology , Adolescent , Adult , Case-Control Studies , Cell Membrane/immunology , Cells, Cultured , Child , Child, Preschool , Cross-Sectional Studies , Female , Glucocorticoids/therapeutic use , Humans , Interleukin-13/immunology , Interleukin-8/immunology , Lipopolysaccharide Receptors/blood , Lipopolysaccharide Receptors/genetics , Lipopolysaccharides/pharmacology , Male , Nephrotic Syndrome/drug therapy , RNA, Messenger/analysis , Recurrence , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
The deletion polymorphism of the angiotensin-converting enzyme (ACE) gene has been considered as a risk factor for IgA nephropathy and for its progression to end-stage renal failure. However, results from various studies are conflicting. We had genotyped the ACE gene in 100 patients with IgA nephropathy, 32 of whom were in end-stage renal failure and in 90 normal adult subjects. All DD cases were subjected to confirmation with a second PCR, performed with the insert-specific forward primer. Similar genotype frequencies were obtained for the 90 normal control subjects (II: 47%, ID: 44%, DD: 9%); for the 68 patients not in end-stage renal failure (ESRF) (II: 47%, ID: 46%, DD: 7%) and for the 32 patients with ESRF (II: 53%, ID: 38%, DD: 9%). The genotype frequencies in all 3 series are in Hardy-Weinberg equilibrium. These results suggest that ACE gene polymorphism is not a risk factor for IgA nephropathy and is not a predictor for its progression. Definitive proof of association between ACE gene polymorphism and progression in IgA nephropathy will require a prospective study, controlled for important risk factors, with adequate patient numbers and facility for confirming DD genotypes.
Subject(s)
Asian People/genetics , Glomerulonephritis, IGA/genetics , Glomerulonephritis, IGA/physiopathology , Peptidyl-Dipeptidase A/genetics , Polymorphism, Genetic , Adult , Disease Progression , Female , Genotype , Humans , Kidney Failure, Chronic , Male , Middle Aged , SingaporeABSTRACT
We report a rare presentation of mitochondrial disorder in a child with recurrent carpopedal spasms due to hypocalcemia and hypomagnesemia, secondary to renal proximal tubulopathy and possible hypoparathyroidism. At least two mutant mitochondrial DNA species were identified, and abnormal mitochondria were found in the muscle and renal biopsy specimens. The case illustrates the spectrum and diversity of mitochondrial presentations, arising because of heteroplasmy of mutations and the type of organs affected.
Subject(s)
Kidney Diseases/etiology , Kidney Tubules, Proximal/physiopathology , Mitochondrial Diseases/complications , Child, Preschool , DNA, Mitochondrial/genetics , Humans , MutationABSTRACT
This study reviewed the 18-year experience of acute dialysis in the pediatric intensive care unit, in order to identify factors that could predict outcome, and to determine whether newer modalities of acute dialysis have influenced this outcome. Sixty-six children (ages 1 day to 19 years) received acute dialysis from May 1980 to April 1998. Factors predicting outcome were analyzed using univariate and Cox regression analysis. Modality of dialysis in the first 15 years was exclusively peritoneal dialysis. with a mortality of 63.9%. However, in the last 3 years, with increasing patient numbers, continuous hemodiafiltration (CHDF) was the modality of choice (56.7%), with a mortality of 73.3%. Univariate analysis showed that age <1 year, coma, acute tubular necrosis, disseminated intravascular coagulopathy, assisted ventilation, and hypotension were associated significantly with poor outcome (P<0.05). Cox regression analysis revealed that mortality was significantly higher in patients on mechanical ventilation (RR 5.96, 95% CI 1.82-19.50), or with age <1 year (RR 2.00, 95% CI 1.08-3.73). In conclusion, despite the increasing use of CHDF over the last 3 years, there was no significant improvement in mortality, probably related to the fact that more critically ill patients were dialyzed.
Subject(s)
Kidney Diseases/therapy , Renal Dialysis , Acute Disease , Adolescent , Adult , Child , Child, Preschool , Critical Care , Female , Humans , Infant , Infant, Newborn , Kidney Diseases/mortality , Male , Peritoneal Dialysis , Prognosis , Prospective Studies , Risk Factors , Singapore/epidemiology , Treatment OutcomeABSTRACT
OBJECTIVE: Children with steroid-dependent nephrotic syndrome (SDNS), despite being in remission on glucocorticoids, continue to have growth retardation and short stature. The mechanism is uncertain as both chronic glucocorticosteroids and the nephrotic syndrome may independently affect growth. We investigated the changes in the IGFs and IGF-binding proteins (IGFBPs) in a group of short SDNS children, and studied the changes prospectively with 1 year's treatment with GH. DESIGN AND METHODS: Total and 'free' IGF-I, IGFBP-3 and acid-labile subunit (ALS) were studied in eight SDNS boys (mean age=12.6 years; mean bone age=9.1 years) on long term oral prednisolone (mean dose 0.46 mg/kg per day) before, during, and after, 1 year's treatment with GH (mean dose 0.32 mg/kg per week). Pretreatment comparisons were made with two control groups, one matched for bone age (CBA; mean bone age=9.2 years), and another for chronological age (CCA; mean chronological age=13 years). Subsequently, three monthly measurements of serum and urine IGFBPs were carried out in the GH-treated SDNS patients using Western ligand blot and Western immunoblot. RESULTS: Pre-treatment serum total IGF-I levels and the IGF-I/IGFBP-3 ratio were elevated significantly in SDNS compared with CBA, and were similar to CCA. Serum free IGF-I levels were elevated significantly compared with both control groups, but serum IGFBP-3 did not differ significantly. Urinary IGFBP-2, IGFBP-3 and ALS were detectable in the SDNS children only. With GH treatment, IGF-I and IGFBP-3, but not IGF-II, increased significantly compared with pre-treatment values, and returned to baseline after cessation of GH treatment. Urinary IGFBPs did not change significantly with GH treatment. CONCLUSIONS: There is persistent urinary loss of IGFBP-2, IGFBP-3 and ALS in children with SDNS in remission with growth retardation. However, the significant elevation in serum IGF-I suggests that glucocorticoid-induced resistance to IGF is the main factor responsible for the persistent growth retardation in these children. Exogenous GH was able to overcome this resistance by further increasing serum IGF-I.
Subject(s)
Dwarfism/metabolism , Glucocorticoids/pharmacology , Human Growth Hormone/pharmacology , Insulin-Like Growth Factor Binding Proteins/metabolism , Somatomedins/metabolism , Adolescent , Blotting, Western , Body Height/drug effects , Bone Development/drug effects , Carrier Proteins/blood , Carrier Proteins/metabolism , Carrier Proteins/urine , Child , Cholesterol/blood , Dwarfism/blood , Dwarfism/drug therapy , Dwarfism/urine , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Glycoproteins/blood , Glycoproteins/metabolism , Glycoproteins/urine , Human Growth Hormone/administration & dosage , Human Growth Hormone/therapeutic use , Humans , Insulin-Like Growth Factor Binding Protein 2/blood , Insulin-Like Growth Factor Binding Protein 2/metabolism , Insulin-Like Growth Factor Binding Protein 2/urine , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor Binding Protein 3/metabolism , Insulin-Like Growth Factor Binding Protein 3/urine , Insulin-Like Growth Factor Binding Proteins/blood , Insulin-Like Growth Factor Binding Proteins/urine , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor II/metabolism , Ligands , Male , Matched-Pair Analysis , Nephrosis/blood , Nephrosis/drug therapy , Nephrosis/metabolism , Nephrosis/urine , Prednisolone/administration & dosage , Prednisolone/pharmacology , Prednisolone/therapeutic use , SyndromeABSTRACT
Minimal change disease, the most common cause of idiopathic nephrotic syndrome (INS) in children, has a high relapse rate, with approximately half of patients developing steroid dependency. This study was aimed at determining the predictive risk factors for the development of steroid dependency in children diagnosed with INS. A retrospective study of 123 children with steroid-responsive INS, followed for at least 6 months between December 1974 and December 1999, was conducted. The following parameters were studied as predictors of steroid dependency: age at onset, gender, race, microscopic hematuria at onset, atopy, concomitant upper respiratory tract infections (URTI) during relapses, and days to remission with initial steroid therapy. Of the 91 children who fulfilled the inclusion criteria, 61.5% became steroid dependent. Both univariate and logistic regression analyses revealed that initial remission time of 9 or more days (P=0.02, OR=3.0, 95% CI=1.2-7.9) and concomitant URTI during relapses (P=0.01, OR=3.4, 95% CI=1.3-8.8) were significant predictors of steroid dependency. By identifying those children with predictive factors of steroid dependency, the clinician will be better able to plan the long-term management of these patients and reduce the morbidity seen with the frequent relapses and steroid treatment, in a disease that is otherwise associated with a favorable prognosis.
Subject(s)
Nephrotic Syndrome/drug therapy , Steroids/adverse effects , Steroids/therapeutic use , Substance-Related Disorders , Child, Preschool , Female , Humans , Incidence , Male , Nephrotic Syndrome/complications , Predictive Value of Tests , Recurrence , Regression Analysis , Respiratory Tract Infections/etiology , Retrospective Studies , Risk Factors , Substance-Related Disorders/epidemiologyABSTRACT
BACKGROUND: The potential of higher plants as sources for new immunosuppressive medications is well recognized. In our experiments we investigated the immunosuppressive effect of a highly refined and potent extract of a Chinese herbal preparation, CMX-13, on inhibiting acute allograft rejection (AR) in a highly histoincompatible rat lung transplant model, BN-->LEW, and on lymphocyte activation and cytokine gene expression in vitro. METHODS: Left lung transplants: the control group (group 1) received only dimethylsulfoxide (DMSO) which is the solvent for CMX-13. Group 2 received intramuscular cyclosporin A (CsA, 25 mg/kg) on day 2 posttransplant. Group 3 and 4 received i.p. CMX-13 (0.5 mg/day, low dose and 5 mg/day, high dose, respectively) on day 1, 2, and 3 posttransplant. All animals were killed on day 6 posttransplant. Several pathological categories of inflammation were examined. In vitro experiments: rat spleen cells were incubated with Con A or irradiated stimulator cells with/without serial dilutions of CMX-13 or CsA. Cell proliferation was measured by 3H-thymidine incorporation. mRNA expression of interleukin-2 and interferon-gamma was examined by reverse transcriptase-polymerase chain reaction. RESULTS: The severity of AR in animals receiving high dose CMX-13 was significantly reduced (stage II, P<0.05) compared with controls (stage IV). Significant differences were also seen when more specific parameters of inflammation were examined (necrosis, 0 vs. 1.7+/-1.0, P<0.05; interalveolar hemorrhage, 0 vs. 3.0+/-0.9, P<0.05). The responses seen in the animals treated with high dose CMX-13 were similar to those in the CsA group. CMX-13 inhibited T cell proliferative responses induced by Con A and alloantigen stimulation in a dose-dependent manner that were similar to CsA. Interleukin-2, and interferon-gamma mRNA expression in Con A-stimulated spleen cells was not inhibited by CMX-13 although CsA showed significant inhibition. CONCLUSIONS: 1) CMX-13 significantly reduces the stage of AR and parameters of inflammation in a highly histoincompatible rat lung transplant model. 2) CMX-13 has equal potency to CsA in the inhibition of Con A and alloantigen stimulated rat spleen cell proliferation. 3) CMX-13 showed no inhibitory effects on IL-2 and gamma-IFN mRNA expression, suggesting that its mechanism of action is different from CsA. 4) CMX-13 or derivatives may have potential utility as an immunosuppressive agent(s) in modulation of AR and management of other inflammatory and immunological disorders.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Lung Transplantation/immunology , Acute Disease , Animals , Cell Division , Cyclosporine/pharmacology , Gene Expression/drug effects , Histocompatibility , Interferon-gamma/genetics , Interleukin-2/genetics , Lung Transplantation/pathology , Lymphocyte Activation/drug effects , Male , RNA/isolation & purification , Rats , Rats, Inbred BN , Rats, Inbred Lew , Reverse Transcriptase Polymerase Chain Reaction , Spleen/cytology , Statistics as Topic , Transplantation, Homologous/pathologyABSTRACT
INTRODUCTION: Minimal change nephrotic syndrome (MCNS) is the most common primary nephrotic syndrome in childhood. While the pathogenesis of this disease is still unknown, there is considerable evidence that it is an immune disease. This role of genetic susceptibility in this disease is the subject of this review. METHODS: Reported studies addressing potential genetic factors in MCNS were reviewed. These factors included human leukocyte antigen (HLA) associations, genes involved in the renin-angiotensin system and cytokines. RESULTS: Several authors have reported the presence of familial clustering, human leukocyte antigen (HLA) associations, and association with asthma and atopy, suggesting a genetic susceptibility to the disease. Moreover, recent studies on the role of the renin angiotensin system, cytokines and their respective receptors on the severity and clinical course of the disease, have lent further support to the immunogenetic basis of this disease. CONCLUSION: Knowledge of the genetic basis of MCNS may have important therapeutic implications in this disease, in particular, the role of cytokines and their respective receptors, including the influence of environmental factors on their expression.
Subject(s)
Genetic Predisposition to Disease , Nephrosis, Lipoid/genetics , Cytokines/genetics , Gene Expression , Genes, MHC Class I/genetics , Genes, MHC Class II/genetics , Humans , Renin-Angiotensin System/geneticsABSTRACT
The association of membranous nephropathy with Fanconi syndrome and anti-tubular basement antibodies appears to be a distinct subset of familial membranous nephropathy. We studied two Chinese families with four affected boys to evaluate the mode of inheritance of disease. HLA haplotype analysis of the family members in these two pedigrees did not reveal any significant linkages. However, microsatellite analysis of both pedigrees using markers on the X chromosome suggested linkage to the long arm of the X chromosome between the microsatellite markers DXS1001 and DXS1227. Identification and analysis of additional pedigrees may allow more precise mapping of the disease gene for anti-tubular basement membrane antibody-associated membranous nephropathy.
Subject(s)
Autoantibodies/analysis , Glomerulonephritis, Membranous/genetics , Glomerulonephritis, Membranous/immunology , Kidney Tubules/immunology , X Chromosome , Basement Membrane/immunology , Basement Membrane/pathology , China , Chromosome Mapping , DNA Primers , Female , Genetic Markers , Glomerulonephritis, Membranous/pathology , HLA Antigens/genetics , Haplotypes , Humans , Infant , Kidney Glomerulus/pathology , Kidney Tubules/pathology , Kidney Tubules, Proximal/physiopathology , Male , Microsatellite Repeats , PedigreeABSTRACT
INTRODUCTION: Traditional Chinese Medicines (TCM) have been used for centuries in China to treat various immune-mediated disorders. METHODS: This review focuses on the clinical and experimental studies that have been performed with TCM as immunosuppressive agents for the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), atopic eczema and solid organ transplantation. RESULTS: The "thunder god" vine, Tripterygium wilfordii Hook F (TWHf), has been extensively used in China to treat SLE and RA. TWHf not only inhibited mitogen-stimulated lymphoproliferation, but its active derivatives have also been shown to inhibit production of proinflammatory cytokines by monocytes and lymphocytes, as well as prostaglandin E2 production via the cyclooxygenase, COX-2, pathway, a potential mechanism of action in patients with RA. Demethylzelasteral (TZ-93), a triterpenoid isolated from the root cortex of TWHf, the plant alkaloid berbamine, and the hydrophobic extract of a Chinese herbal decoction, CMX-13, were all shown to be active in prolonging allograft survival in experimental animal models of heart, skin and single lung transplants, respectively. There are few well-designed randomised placebo-controlled clinical trials demonstrating the efficacy of TCM in various diseases. Zemaphyte, a decoction of 10 herbs, has been shown to be efficacious in the treatment of atopic dermatitis in both children and adults in two randomised double-blind placebo-controlled trials. CONCLUSION: There is both laboratory and clinical evidence that the derivatives of many of these herbs may have significant beneficial immunosuppressive effects, however, concerns of toxicity must also be addressed, as exact dosing of the active derivatives is difficult to achieve with the current prescriptions of TCM.
Subject(s)
Arthritis, Rheumatoid/drug therapy , Dermatitis, Atopic/drug therapy , Drugs, Chinese Herbal/therapeutic use , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Plants, Medicinal , Humans , Triterpenes/therapeutic useABSTRACT
Cytomegalovirus (CMV) infection is a major concern following solid organ transplantation, especially in the pediatric population who remain at high risk of primary infection. CMV disease leads not only to increased patient and graft morbidity, but also to increased health care costs. This study describes the usefulness of a quantitative CMV polymerase chain reaction (PCR) technique for monitoring peripheral blood CMV DNA in pediatric recipients of kidney and liver allografts who had recurrent CMV retinitis. The incidence of CMV disease in 28 pediatric transplant recipients was 28.6%, one-half of whom developed retinitis. Two of these patients had recurrent retinitis on cessation of anti-viral treatment. A peripheral blood CMV DNA copy number of > or =500/microg of DNA was associated with recrudescence of the retinitis in these patients. We conclude that the measurement of peripheral blood CMV DNA by PCR is a useful tool for the surveillance of disease resolution and recurrence. This is particularly important in patients with CMV retinitis, who may remain asymptomatic for a period of time, despite recurrences.