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1.
Pediatr Nephrol ; 14(8-9): 740-6, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10955918

ABSTRACT

Oxidative stress in unilateral ureteral obstruction (UUO) contributes to the development of glomerular and tubulointerstitial lesions. The present study investigated whether oxidized low-density lipoprotein (oLDL) contributes to the pathogenesis of kidney injury in UUO, and whether alpha-tocopherol modulates such cytotoxicity and promotes repair. Male Sprague-Dawley rats weighing 100-125 g were assigned to three groups of 6 animals each: (1) sham, regular chow; (2) UUO, regular chow; and (3) UUO, alpha-tocopherol supplementation. We found a significant increase in the level of oxidative stress in the UUO group as measured by malondialdehyde (MDA) content in both plasma and kidneys. The LDL isolated from this group was cytotoxic to rat mesangial cells. The level of oxidation and cytotoxicity was significantly reduced when animals were treated with alpha-tocopherol. Plasma cholesterol concentration, kidney MDA, and transforming growth factor beta1 mRNA expression were all significantly increased in the UUO animals, and partially reduced in alpha-tocopherol-treated animals. Our data suggest that oxidative modification of LDL is associated with the renal injury in UUO. Taken together, our data support the concept that alpha-tocopherol can modulate LDL oxidation and its cytotoxic effects on rat mesangial cells in vitro.


Subject(s)
Kidney/physiopathology , Lipoproteins, LDL/toxicity , Oxidative Stress/drug effects , Ureteral Obstruction/physiopathology , Vitamin E/pharmacology , Animals , Cell Survival/drug effects , Cholesterol/blood , Cytotoxins , Dietary Supplements , Glomerular Mesangium/drug effects , Glomerular Mesangium/pathology , Humans , Kidney/drug effects , Lipid Peroxidation , Lipoproteins, LDL/blood , Male , Malondialdehyde/analysis , Malondialdehyde/blood , Rats , Rats, Sprague-Dawley , Ureteral Obstruction/drug therapy , Ureteral Obstruction/pathology , Vitamin E/administration & dosage , Vitamin E/blood
3.
Kidney Int ; 56(3): 1094-100, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10469379

ABSTRACT

BACKGROUND: Transplantation (TX) has become an acceptable treatment for renal failure in primary hyperoxaluria (PH). We have analyzed data from three U.S. sources to estimate the success or failure of different modes of management in PH patients. METHODS: The United States Renal Data System (USRDS) tapes provided coded medical record data, with PH assigned to 235 patients from 1974 to 1996. Another 45 patients were found from USRDS hospitalization records. We limited patients to those developing end-stage renal disease at <55 years of age after 1984 (95 PH patients). The North American Pediatric Renal Transplantation Cooperative Study (NAPRTCS) identified 34 (11 new) PH patients, and the United Network for Organ Sharing (UNOS) database identified PH in 34 (16 new, 5 more in both UNOS and NAPRTCS) patients. These secondary sources were used to correct some data from the USRDS and to add 32 more patients, with a total of 128 PH patients. Considering kidney TX (KTX) prior to combined kidney/liver TX (K/LTX) as a separate record for some calculations, the total "cases" were 138. RESULTS: By life table analysis, the 94 total TX patient survival was better than for the 34 NoTX patients (P<0.001). The 52 KTX patients' survival was better than either the 32 primary K/LTX (P<0.001) or the 10 K/LTX that following KTX (P<0.001). The 62 KTX cases' survival was better than the 42 K/LTX cases (P<0.005), which did not differ from the 34 NoTX (P<0.67). The overall survival of these 62 KTX patients was 76%. The survival of 42 K/LTX was 69%, and the survival of 34 NoTX patients was 44%. Kidney graft life table projected survival curves for TX patients did not differ between K/LTX (56% at 6 years) and isolated KTX (51% at 6 years, 35% at 10 years, P<0.91). CONCLUSION: KTX offers better patient survival in the United States then either K/LTX or NoTX. Graft survival does not differ between KTX and K/LTX. Because K/LTX can still follow a failed KTX, isolated living related donor KTX is still a reasonable first option for PH type 1 if a strictly managed protocol is followed.


Subject(s)
Hyperoxaluria, Primary/surgery , Kidney Transplantation , Liver Transplantation , Adolescent , Adult , Child , Child, Preschool , Databases, Factual , Graft Survival , Humans , Hyperoxaluria, Primary/mortality , Infant , Infant, Newborn , Kidney Transplantation/mortality , Life Tables , Liver Transplantation/mortality , Middle Aged , Survival Rate , United States/epidemiology
4.
Pediatr Nephrol ; 13(3): 195-8, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10353404

ABSTRACT

Previous studies have shown that reduction of renal mass in the rat remnant kidney model induces overproduction of transforming growth factor beta1 (TGFbeta1). We investigated whether an antioxidant, vitamin E, administered before the renal mass reduction, could prevent oxidative stress, reduce the overproduction of TGFbeta1, and mitigate against the subsequent glomerulosclerosis. Our results revealed that the oxidative stress, as measured by the change in plasma malondialdehyde, is significantly reduced by prior vitamin E dietary supplementation. Finally, our data show that dietary vitamin E supplementation ameliorates the rise in TGFbeta1 secondary to renal mass reduction and inhibits the glomerular sclerosis of the remnant kidney over the time course of this experiment.


Subject(s)
Glomerulonephritis/prevention & control , Oxidative Stress/drug effects , Vitamin E/pharmacology , Animals , Creatinine/blood , Food, Fortified , Glomerulonephritis/pathology , Kidney Cortex/metabolism , Kidney Glomerulus/drug effects , Kidney Glomerulus/pathology , Male , Malondialdehyde/blood , Malondialdehyde/metabolism , Nephrectomy , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta/metabolism , Vitamin E/blood
6.
J Am Soc Nephrol ; 9(11): 2089-95, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9808095

ABSTRACT

Glomerulosclerosis and tubulointerstitial injury are characteristic features seen in the subtotal (5/6) nephrectomy remnant kidney model in the rat. Oxidative stress from renal mass reduction contributes to the glomerular and tubular injury. Previous studies have clearly demonstrated the prevention or inhibition of such injury by an antioxidant such as alpha-tocopherol. However, few data are available on the ability of alpha-tocopherol to modulate or arrest progression of the established disease. This study examines whether alpha-tocopherol modulates glomerulosclerosis and tubulointerstitial injury when it is given 2 wk after renal damage has been established. The findings indicate that alpha-tocopherol has the capacity to modulate both tubulointerstitial injury and glomerulosclerosis, lower the elevated expression of transforming growth factor-beta1, and reduce plasma and kidney malondialdehyde concentration, the end product of lipid peroxidation. The results support the potential utility of alpha-tocopherol in reversing established glomerulosclerosis and tubulointerstitial injury in a remnant kidney model.


Subject(s)
Glomerulosclerosis, Focal Segmental/drug therapy , Glomerulosclerosis, Focal Segmental/pathology , Nephrectomy , Vitamin E/administration & dosage , Animals , Creatinine/blood , Diet , Glomerulosclerosis, Focal Segmental/metabolism , Kidney/metabolism , Kidney/pathology , Male , Malondialdehyde/blood , Malondialdehyde/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta/genetics , Vitamin E/blood , Vitamin E/therapeutic use
8.
Nephron ; 80(2): 134-48, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9736810

ABSTRACT

We present data on the costs and impact of chronic renal failure, the primary renal diseases leading to end-stage renal disease in children, and review the adaptive responses and the pathophysiology and complications of uremia in experimental animals and in man. A treatment strategy is summarized.


Subject(s)
Kidney Failure, Chronic/economics , Adaptation, Physiological , Animals , Child , Costs and Cost Analysis , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/physiopathology , Kidney Failure, Chronic/therapy , United States , Uremia/complications , Water-Electrolyte Imbalance/physiopathology
9.
Curr Opin Pediatr ; 10(2): 174-83, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9608896

ABSTRACT

Many genetic renal disease now have specific genetic definitions, allowing prognostication. Several glomerular basement membrane defects include Alport's syndrome and benign familial hematurias. Genetic tubular or interstitial structural defects likely include familial juvenile nephronophthisis, as well as the polycystic diseases. Hereditary metabolic diseases can result in storage processes and circulating lipid disorders, which result in progressive glomerular sclerosis. Hereditary metabolic errors result in products causing obstruction and interstitial damage. Other hereditary disorders cause hemodynamic process that result in renal damage. The vascular structural defects of Marfan syndrome, Alagille syndrome, neurofibromatosis, and Cockayne's syndrome can secondarily result in renal vascular destruction. An awareness of these hereditary disease pathways to renal disease is essential to primary care pediatrics.


Subject(s)
Kidney Diseases/genetics , Basement Membrane , Child , Fabry Disease/genetics , Glycogen Storage Disease Type I , Humans , Hyperoxaluria , Kidney Calculi/genetics , Kidney Diseases/complications , Kidney Glomerulus , Nail-Patella Syndrome/genetics , Nephritis, Hereditary/genetics
10.
Toxicon ; 36(2): 359-66, 1998 Feb.
Article in Spanish | MEDLINE | ID: mdl-9620583

ABSTRACT

A retrospective epidemiological analysis is presented of 80 snakebites in children admitted to the Pediatrics Service of Tony Facio Hospital in Limón, Costa Rica, between 1985 and 1995. An overall incidence rate of 20 snakebite accidents per 100,000 inhabitants per year was calculated for the region in that period. However, a higher incidence was described in some counties (36 and 30 cases per 100,000 inhabitants in Talamanca and Siquirres, respectively). Most of the cases occurred in February and November, between 16:00 and 19:00 hr. The mean age of the affected children was 8.67 +/- 2.66 years. No significant difference was found between genders. Thirty-three children affected (41.2%) were members of the local indigenous groups and 31 (38.8%) were residents of Talamanca County. The species of snake responsible were identified in 58.4% of cases, with Bothrops asper being the most important. The lower extremities were the most important primary site affected (86.3%). The most common clinical complications described in the study group were abscess formation (11.25%), necrosis (10%), renal failure (3.75%), compartmental syndrome (2.5%) and anaphylactic shock (1.25%). The overall mortality was 2.5%. Statistical analysis of the risk factors relating to the two most common complications showed that the condition of coming from Talamanca County (P = 0.02), damage in the proximal extremities (P = 0.02), a prothrombin time < 2% (P = 0.01) and serum fibrinogen levels < 100 g/dl (P = 0.01) were risk factors for the development of abscesses. The grade of severity of the snakebite (P = 0.018) and serum fibrinogen levels < 100 g/dl were associated with development of necrosis. All of the patients with necrosis and abscesses also experienced two or more of the risk factors that correlated with a sensitivity of 100% and a specificity of 67% for the development of abscess, and 87% sensitivity and 88% specificity for necrotic complications. According to these data, snakebite complications are a relevant health problem in Costa Rica.


Subject(s)
Abscess/etiology , Bothrops , Snake Bites/complications , Snake Bites/epidemiology , Adolescent , Analysis of Variance , Animals , Child , Child, Preschool , Costa Rica/epidemiology , Female , Humans , Incidence , Infant , Infant, Newborn , Length of Stay , Male , Necrosis , Risk Factors
11.
Article in English | MEDLINE | ID: mdl-9553288

ABSTRACT

Data concerning the transcription of growth hormone and the various interactions between growth hormone/insulin-like growth factor (IGF) axis in uremia, acidosis and nutrition are presented. The recent evidence of tissue resistance to growth hormone in uremia provided the medical rationale for the use of growth hormone in chronic renal failure. The growth hormone receptor resistance in uremia and the decreased IGF-I by acidosis are additional rationale for the use of growth hormone. New findings of how acidosis causes the reduction of IGF-I expression at the growth plate of the long bone and the significant proteolysis after even small changes in serum bicarbonate content are presented to provide the pediatrician with an overview of these recent advances.


Subject(s)
Growth Disorders/etiology , Kidney Failure, Chronic/complications , Acidosis/complications , Adrenal Cortex Hormones/physiology , Animals , Dietary Proteins/administration & dosage , Energy Intake , Growth Hormone/physiology , Humans , Somatomedins/physiology
12.
Mol Genet Metab ; 65(4): 303-10, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9889018

ABSTRACT

Our previous studies noted the oxidative stress of unilateral ureteral obstruction (UUO). Now, we seek to explore whether UUO affects the intrinsic cellular antioxidants and triggers heat shock protein (HSP-70) and whether these are still highly expressed after reversal of the UUO (R-UUO). In addition, we designed the experiment to determine whether this expression of HSP-70 is a localized or a generalized response. Male Sprague-Dawley rats (125-150 g) were randomly assigned to sham operation, left UUO, or R-UUO procedures at six rats per group. The sham, UUO, and R-UUO animals were studied 10 days after UUO or 7 days after R-UUO. A clear increase in the left (obstructed) kidney's malondialdehyde (MDA), a marker of lipid peroxidation, was observed: a significant 2.6-fold of sham during UUO and a 1.7-fold of sham in R-UUO. The contralateral (unobstructed) right kidney showed a significant rise in MDA during UUO, but during R-UUO the MDA had fallen back to sham values. It is possibly the result of a systemic effect from the free radicals produced by the oxidative stress of the UUO. The antioxidant enzyme, manganese superoxide dismutase (MnSOD) of the left, obstructed kidney showed a significant reduction in UUO compared to that of the sham. Upon reversal of UUO (R-UUO), MnSOD was lower than that of the sham. The left kidney's HSP-70 increased during UUO and was 3.7-fold that of sham (P < 0.05) but, during R-UUO, was not different from sham (P, ns). The contralateral (intact) right kidneys' HSP-70 showed no change between sham, UUO, and R-UUO states. We conclude that UUO gives rise to oxidative stress which is generalized in both the obstructed and the contralateral unobstructed kidney, as indicated by the elevation in kidney MDA content in both kidneys. The intrinsic cellular antioxidant enzyme, manganese superoxide dismutase, showed a significant and generalized reduction in both UUO and R-UUO. In contrast, the HSP-70 was markedly elevated only in the obstructed kidney and not in the R-UUO or in the contralateral kidney, suggesting that the elevation of HSP-70 is a specific and localized response to oxidative injury of UUO.


Subject(s)
HSP70 Heat-Shock Proteins/metabolism , Kidney/metabolism , Kidney/pathology , Ureteral Obstruction/metabolism , Animals , Creatinine/blood , HSP70 Heat-Shock Proteins/analysis , Male , Malondialdehyde/analysis , Malondialdehyde/metabolism , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/analysis , Superoxide Dismutase/metabolism
14.
Saudi J Kidney Dis Transpl ; 8(3): 235-46, 1997.
Article in English | MEDLINE | ID: mdl-18417801
15.
Pediatr Nephrol ; 11(3): 296-301, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9203176

ABSTRACT

Bartter syndrome involves an overlapping set of closely related renal tubular disorders which can be subdivided into at least three clinical phenotypes: (1) classic Bartter syndrome (2) Gitelman syndrome, and (3) a neonatal variant of Bartter syndrome. In contrast to classic Bartter syndrome and Gitelman syndrome, the neonatal variant of Bartter syndrome has both the features of renal tubular hypokalemic alkalosis as well as profound systemic manifestations. Specifically, neonatal Bartter syndrome is characterized by intrauterine polyhydramnios, premature delivery, and life-threatening episodes of fever and dehydration. Most of these infants also have severe hypercalciuria with associated nephrocalcinosis and osteopenia. Over a 22-year period, 20 Costa Rican patients with a congenital syndrome that resembles neonatal Bartter syndrome have been identified and characterized. While these patients exhibit some of the clinical characteristics previously described for neonatal Bartter syndrome, this cohort also has a set of distinct features. They are predominantly female, have a later age of diagnosis, manifest a relatively unique set of physical traits, and appear to have milder clinical disease. Given these differences, it will be important to apply the emerging molecular tools to determine whether the phenotypic variability indicates genetic heterogeneity in neonatal-onset Bartter syndrome.


Subject(s)
Bartter Syndrome/epidemiology , Age of Onset , Bartter Syndrome/physiopathology , Child , Child, Preschool , Costa Rica/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , Phenotype , Sex Factors , Survival
16.
J Trop Med Hyg ; 98(5): 316-8, 1995 Oct.
Article in English | MEDLINE | ID: mdl-7563258

ABSTRACT

The cases of two Costa Rican children with pericarditis due to Paragonimus mexicanus are reported. Clinical, epidemiological and laboratory tests are consistent with the disease. Treatment with praziquantel and bitheonol was associated with clinical cure. A review of the literature and a suggested table of diagnostic criteria are included.


Subject(s)
Paragonimiasis , Pericarditis/parasitology , Antiplatyhelmintic Agents/therapeutic use , Bithionol/therapeutic use , Child, Preschool , Costa Rica , Eosinophilia , Female , Humans , Paragonimiasis/diagnosis , Paragonimiasis/drug therapy , Pericardial Effusion , Pericarditis/diagnosis , Pericarditis/drug therapy , Praziquantel/therapeutic use
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