RESUMO
Renal mass and glomerular filtration rate (GFR) were reduced from normal to approximately 15% of normal in two groups of dogs. One group received a constant salt intake (CSI) throughout the study. The second group was subjected to "proportional reduction" of sodium intake (PRS), a dietary regimen which involved the reduction of sodium intake in exact proportion to the decrement in GFR. In the CSI group, absolute sodium excretion rate (U(Na)V) remained essentially unchanged as GFR fell, while fractional sodium excretion (FE(Na)) increased progressively from a mean control value of 0.3% to a final value of 4.4%. In the PRS group, U(Na)V decreased with each reduction in GFR and salt intake, and FE(Na) remained constant throughout. In a second study, the fraction of serum that previously has been shown to possess natriuretic activity in studies of uremic patients was obtained from a group of uremic dogs on the CSI and from another group on the PRS regimen, and the effects of the fraction was measured on sodium excretion in rats. The serum fractions from the dogs on the CSI regimen produced a significant increase in both U(Na)V and FE(Na) in the assay rats. The same serum fraction from the dogs on the PRS regimen failed to produce a significant increase in either U(Na)V or FE(Na). The data are consistent with the view that (a) The increase in FE(Na) in chronically uremic dogs is dictated by the requirements for external sodium balance and may be prevented by prospective manipulation of salt intake: (b) a natriuretic factor, previously shown to exist in the serum of patients with chronic uremia, is also demonstrable in the serum of uremic dogs; and (c) with the present bioassay system, the factor is not detectable in the serum fraction of uremic dogs in which the requirements for an increased natriuresis per nephron have been obviated.
Assuntos
Adaptação Fisiológica , Dieta Hipossódica , Rim/fisiopatologia , Natriurese , Uremia/urina , Animais , Nitrogênio da Ureia Sanguínea , Radioisótopos de Carbono , Creatinina/metabolismo , Cães , Feminino , Taxa de Filtração Glomerular , Inulina/metabolismo , Néfrons/metabolismo , Ratos , Uremia/sangue , Uremia/terapia , Urina/fisiopatologiaRESUMO
A gel filtration fraction of urine from patients with chronic renal disease (natriuretic factor) has been shown previously to cause natriuresis in rats and to inhibit sodium transport in the isolated toad bladder. The effect of this fraction on transtubular potential difference and sodium transport was examined on the isolated perfused cortical collecting tubule of the rabbit. A rapid inhibition of potential difference from -22.5 mV to -12 mV (P less than 0.001) was observed when the fraction was applied to the peritubular surface. This effect was accompanied by a decrease in net sodium flux from 6.29 to 3.21 pmol/cm per s (P less than 0.001). Unidirectional fluxes using isotopic sodium revealed that the inhibition of net sodium transport was due to a decrease in flux from the lumen to the peritubular surface, i.e., an inhibition of active sodium transport. There was no change in sodium flux in the reverse direction. These changes were all rapidly reversed by removal of the fraction from the peritubular surface. The addition of the fraction to the lumen had no effect on potential difference or net sodium flux. Control studies using the same fraction from the urine of normal subjects had no effect on any of the parameters studies. Where both a uremic and a normal fraction were sequentially applied to the peritubular surface of the same tubule, inhibition of potential difference was obtained only with the former. In the light of evidence implicating the collecting duct fraction from normal animals, the data are consistent with the view that the natriuretic factor may be biologically important in the regulation of sodium balance via it's regulatory role in active sodium transport in the collecting tubule.
Assuntos
Túbulos Renais/efeitos dos fármacos , Natriurese , Sódio/metabolismo , Uremia/urina , Animais , Transporte Biológico/efeitos dos fármacos , Doença Crônica , Eletrofisiologia , Feminino , Humanos , Túbulos Renais/metabolismo , Túbulos Renais/fisiopatologia , Néfrons/efeitos dos fármacos , Néfrons/metabolismo , Néfrons/fisiopatologia , CoelhosRESUMO
A gel filtration fraction of serum from chronically uremic patients has been shown previously to produce natriuresis in the rat. In the present studies, the same fraction from urine of uremic patients and normal subjects was studied for its natriuretic activity. Urine samples were obtained from 17 chronically uremic patients (mean glomerular filtration rate [GFR], 8.7 ml/min; mean fractional sodium excretion [FE(Na)], 5.7%), and 14 normal subjects. The fraction from the uremic patients produced a significant increase in absolute sodium excretion (U(Na)V) and FE(Na); the fraction from normal subjects had no statistically significant effect on either U(Na)V or FE(Na); and the difference between the response to the uremic vs. normal fractions was highly significant for both parameters of sodium excretion. When a more concentrated urine fraction from uremic patients was administered, a striking natriuresis was observed with values for FE(Na) rising to levels as high as 12%. Studies also were performed on eight patients with far advanced chronic renal insufficiency and the nephrotic syndrome. The serum fraction was studied in each of these patients and the urine fraction in three. For the group, U(Na)V in the assay rats decreased by 0.87 mueq/min and FE(Na) decreased by 1.35% after infusion of the serum fraction. These results differ significantly from those of patients with chronic uremia without the nephrotic syndrome. The data are consistent with the view that the increased activity of the natriuretic factor in the serum of chronically uremic patients is not due to failure of excretion; rather it relates either to an increased rate of production and/or a decreased rate of degradation. The data also show that the inhibitor is detectable when FE(Na) is increased, but not when uremia is associated with a sodium-retaining state.
Assuntos
Falência Renal Crônica/urina , Natriurese , Síndrome Nefrótica/urina , Uremia/urina , Animais , Cromatografia em Gel , Relação Dose-Resposta a Droga , Edema/sangue , Edema/urina , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/metabolismo , Síndrome Nefrótica/sangue , Ratos , Uremia/metabolismo , Equilíbrio HidroeletrolíticoRESUMO
An in vitro approach to the study of single nephron function in uremia has been employed in evaluating the control of fluid reabsorption by the renal superficial proximal straight tubule (PST). Isolated segments of PSTs from the remnant kidneys of uremic rabbits (stage III) were perfused in vitro and their rate of fluid reabsorption compared with normal PSTs and with PSTs derived from the remnant kidneys of nonuremic rabbits (stage II). All segments were exposed to a peritubular bathing medium of both normal and uremic rabbit serum thereby permitting a differentiation to be made between adaptations in function which are intrinsic to the tubular epithelium and those which are dependent upon a uremic milieu.Compared with normal and stage II PSTs, there was significant hypertrophy of the stage III tubules as evidenced by an increase in length and internal diameter, and a twofold increase in the dry weight per unit length. Fluid reabsorption per unit length of tubule was 70% greater in stage III than in normal and stage II PSTs, and was closely correlated with the increase in dry weight. Substitutions between normal and uremic rabbit serum in the peritubular bathing medium did not affect fluid reabsorption significantly in any of the three groups of PSTs. Perfusion of the tubules with an ultrafiltrate of normal vs. uremic serum likewise failed to influence the rate of net fluid reabsorption. It has previously been observed that net fluid secretion may occur in nonperfused or stop-flow perfused normal rabbit PSTs exposed to human uremic serum. Additional studies were thus performed on normal and stage III PSTs to evaluate whether net secretion occurs in the presence of rabbit uremic serum. No evidence for net secretion was found. These studies demonstrate that fluid reabsorption is greatly increased in the superficial PST of the uremic remnant kidney and that this functional adaptation is closely correlated with compensatory hypertrophy of the segment. Humoral factors in the peritubular environment do not appear to be important mediators of the enhanced fluid reabsorption.
Assuntos
Túbulos Renais Proximais/metabolismo , Rim/metabolismo , Néfrons/metabolismo , Uremia/metabolismo , Absorção , Animais , Hipertrofia , Técnicas In Vitro , Túbulos Renais Proximais/patologia , Néfrons/patologia , Tamanho do Órgão , Perfusão , Coelhos , Uremia/patologiaRESUMO
The urine of patients with chronic uremia contains a gel filtration fraction that is natriuretic in the rat. The effects of this fraction on the isolated urinary bladder of the toad were examined in the present studies. When added to the serosal surface of the bladder, a significant and substantial fall in short-circuit current and potential difference was observed. The changes began after a lag period of at least 10 min and continued over a period of 60 min. The decrease in short-circuit current at the end of 1 h averaged 44%. The same fraction from the urine of normal subjects produced no significant change in either short-circuit current or potential difference. When the isolated epithelial cells from the toad bladder were incubated in the presence of the inhibitor, intracellular sodium content increased significantly. There was no change in intracellular water content; hence the intracellular concentration of sodium increased by a mean of 7 meq/liter. The changes in intracellular potassium content and concentration were not satistically significant. When the isolated epithelia were incubated with the uremic factor, there was also a significant decrease in pyruvate utilization in relation to cells from paired hemibladders incubated in the absence of the fraction. The fraction from normal subjects produced no change in either intracellular sodium content or pyruvate oxidation. The results suggest that the inhibitor acts from the serosal surface, inhibits sodium transport across the serosal barrier, and produces a decrease in substrate utilization in association with the change in transepithelial sodium transport.
Assuntos
Transporte Biológico , Natriurese , Piruvatos/metabolismo , Sódio/metabolismo , Uremia/urina , Bexiga Urinária/metabolismo , Urina/fisiologia , Equilíbrio Hidroeletrolítico , Cloreto de Amônio/farmacologia , Animais , Anuros , Bufo marinus , Cromatografia em Gel , Eletrofisiologia , Células Epiteliais , Epitélio/análise , Epitélio/metabolismo , Humanos , Falência Renal Crônica/urina , Mucosa , Oxirredução , Potássio/análise , Membrana Serosa , Sódio/análise , Bexiga Urinária/fisiologiaRESUMO
Sera from chronically uremic and normal individuals were subjected to gel filtration with Sephadex G-25 and the same fraction of both was infused into rats with a decreased nephron population to determine the effects on sodium excretion. Sodium excretion rate and fractional sodium excretion increased slightly with the normal fractions; but the increase in both functional parameters produced by the uremic fractions was substantially and significantly greater. The natriuresis could not be explained by associated changes in glomerular filtration rate (GFR), para-aminohippurate (PAH) clearance, filtration fraction, hematocrit, or blood pressure. The possibility thus exists that the inhibitor affected some component part of the transepithelial sodium transport system. The elution characteristics of the fraction plus certain of its physicochemical properties suggest that the inhibitor of sodium reabsorption by the rat nephron may be identical with the inhibitor of PAH uptake by kidney slices and the inhibitor of transepithelial sodium transport by the frog skin and toad bladder previously found in the serum of chronically uremic patients.
Assuntos
Sangue , Natriurese , Uremia/sangue , Adolescente , Adulto , Ácidos Aminoipúricos/sangue , Ácidos Aminoipúricos/urina , Animais , Anuros , Bioensaio , Doença Crônica , Quimotripsina/farmacologia , Feminino , Taxa de Filtração Glomerular , Humanos , Inulina/sangue , Inulina/urina , Túbulos Renais/fisiologia , Pessoa de Meia-Idade , Pronase/farmacologia , Ratos , Absorção Cutânea , Bexiga Urinária/fisiologiaRESUMO
24,25-dihydroxycholecalciferol [24,25-(OH)(2)D(3)], once considered a relatively inert metabolite of vitamin D(3), has been recently recognized as a metabolically active product in some species. In previous studies, we have shown that infusion of 24,25(OH)(2)D(3) into the thyroid artery of normal dogs results in prompt and complete suppression of parathyroid hormone (PTH) secretion. In this study, we have examined the metabolic consequences of oral administration of this metabolite in dogs with experimentally induced renal hyperparathyroidism. Dogs with comparable degrees of renal insufficiency (glomerular filtration rate, 10-15 ml/min) were treated for 3 wk with daily doses of either 2 mug of 24,25(OH)(2)D(3) or 50% ethanol, the vehicle in which the metabolite was suspended. After a 6-wk recovery period, treatments were reversed: dogs who had previously served as controls received the metabolite while dogs previously treated with metabolite received the vehicle. Administration of 24,25(OH)(2)D(3) resulted in a 40-60% decrease of immunoreactive PTH. This was associated with a small (0.1-0.2 mg/dl) but unequivocal decrease of serum ionized calcium. Calcium balance, which was slightly negative under control conditions, became slightly but definitively positive on treatment with 24,25(OH)(2)D(3). All other parameters measured, including total serum calcium, magnesium, phosphorus, creatinine, electrolytes, phosphorus excretion, and phosphorus balance, remained unchanged. The data support the hypothesis that 24,25(OH)(2)D(3) not only decreases PTH secretion but also functions as an anabolic hormone in bone under the conditions of this experiment.
Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Di-Hidroxicolecalciferóis/metabolismo , Hidroxicolecalciferóis/metabolismo , Administração Oral , Animais , Cálcio/sangue , Cálcio/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Di-Hidroxicolecalciferóis/administração & dosagem , Di-Hidroxicolecalciferóis/uso terapêutico , Cães , Feminino , Hormônio Paratireóideo/sangueRESUMO
The concentrating ability of the kidney was studied by clearance and micropuncture techniques and tissue slice analyses in normal rats with two intact kidneys (intact controls), normal rats with a solitary kidney (uninephrectomized controls), and uremic rats with a single pyelonephritic kidney. Urinary osmolality after water deprivation for 24 h and administration of antidiuretic hormone was 2,501+/-217 and 2,874+/-392 mosmol/kg H2O in intact and uninephrectomized control rats, respectively, and 929+/-130 mosmol/kg H2O in pyelonephritic rats (P less than 0.001 compared to each control group). Fractional water reabsorption and concentrating ability were significantly decreased in the pyelonephritic group, and, to achieve an equivalent fractional excretion of urea, a greater fractional excretion of water was required in the pyelonephritic rats than in the control rats. Whole animal glomerular filtration rate was 1.57+/-0.19 ml/min and 1.39+/-0.18 ml/min in intact and in uninephrectomized controls, respectively, and 0.30+/-0.07 ml/min in pyelonephritic rats (P less than 0.001 compared to each control group). Single nephron glomerular filtration rate was 35.6+/-3.8 nl/min in intact control rats and was significantly increased (P less than 0.05) in both uninephrectomized (88.0+/-10.8 nl/min) and pyelonephritic rats (71.5+/-14.4 nl/min). In all groups fractional water delivery and fractional sodium delivery were closely comparable at the end of the proximal convoluted tubule and at the beginning of the distal convoluted tubule. In contrast, fractional urea delivery out of the proximal tubule was greater in the intact control group (73+/-8%) than in either the uninephrectomized (52+/-2%) or the pyelonephritic group (53+/-3%) (P less than 0.005). Fractional urea delivery at the early part of the distal tubule increased significantly to 137+/-11% and 93+/-6% of the filtered load in intact control and uninephrectomized control rats, respectively (P less than 0.001 compared to the late proximal values of each group), but failed to increase significantly in pyelonephritic rats (65+/-13%), indicating interruption of the normal recycling of urea in the latter group. Analysis of tissue slices demonstrated a rising corticopapillary gradient for total tissue water solute concentration as well as for tissue water urea concentration in both groups of control rats. In contrast, the pyelonephritic animals exhibited no similar gradients from cortex to papilla. These data indicate that the pyelonephritic kidney fails to recycle urea and accumulate interstitial solute. The latter must inevitably lead to a concentrating defect.
Assuntos
Capacidade de Concentração Renal , Rim/fisiopatologia , Pielonefrite/fisiopatologia , Animais , Doença Crônica , Taxa de Filtração Glomerular , Rim/metabolismo , Túbulos Renais/metabolismo , Masculino , Ratos , Ureia/metabolismoRESUMO
The urine and serum of chronically uremic patients and dogs contain an inhibitor of sodium transport that reduces short-circuit current (SCC) in the toad bladder and produces natriuresis in the rat. The present studies represent an effort to determine whether the same inhibitor is detectable in urine of normal dogs maintained on a dosium intake varying from 3 to 258 meq/day. Observations were made with and without fludrocortisone. The same Sephadex G-25 gel filtration fraction previously shown to contain the "uremic" inhibitor was tested in both the isolated toad bladder and rat bioassay systems. The fraction from dogs maintained on 258 meq qodium plus 0.2 mg fludrocortisone/day consistently inhibited SCC in the toad bladder and induced a natriuresis in the rat (P less than 0.001). The fraction from dogs on the same sodium intake without fludrocortisone was also natriuretic (P less than 0.01) but did not inhibit SCC significantly. In contrast, the fraction from dogs fed 3 meq sodium with fludrocortisone or 91 meq sodium without fludrocortisone had no significant effect in either assay system. Thus, an inhibitor of sodium transport has been found in the urine of nonuremic dogs. Both the degree of natriuresis in the rat and the degree of inhibition of SCC in the toad bladder correlated with the state of sodium balance which ensued in the dog.
Assuntos
Bioensaio , Rim/metabolismo , Sódio/metabolismo , Urina/análise , Animais , Anuros , Cães , Fludrocortisona/farmacologia , Natriurese/efeitos dos fármacos , RatosRESUMO
Chronic cimetidine therapy has been shown to suppress circulating concentrations of immunoreactive parathyroid hormone (iPTH) in hemodialysis patients. To evaluate the long-term metabolic effects of cimetidine treatment, we studied seven chronically uremic dogs for 20 wk. The dogs were studied under metabolic conditions before, during, and after cimetidine therapy. iPTH fell progressively in the five treated dogs from 536+/-70 muleq/ml (mean+/-SE) (nl < 100 muleq/ml) before treatment to 291+/-25 muleq/ml at 12 wk (P < 0.001) and 157+/-32 muleq/ml at 20 wk (P < 0.001). The control dogs showed no consistent change in iPTH. The fall in iPTH was not associated with a change in serum ionized calcium. However, serum phosphorus decreased from 5.7+/-0.9 mg/dl to 3.4+/-0.2 mg/dl by the 20th wk (P < 0.05). By contrast, the serum concentration of 1,25-dihydroxycholecalciferol increased in all treated dogs from 33.4+/-4.3 pg/ml to 51.8+/-2.4 pg/ml during treatment (P < 0.01). Calcium balance was negative in all seven dogs before cimetidine (-347+/-84 mg/72 h) and remained so in the control dogs; it became positive in the five treated dogs after 12 wk (1,141+/-409 mg/72 h) (P < 0.05). Phosphorus balance, 24-h fractional phosphate excretion, and creatinine clearance remained unchanged. Pooled samples of serum obtained during the control and 20th wk of therapy were fractionated by gel filtration and the eluates assayed for immunoreactivity. The decrease in iPTH was associated with a decrease in all the immunoreactive species, indicating suppression of parathyroid gland secretion. These observations indicate that cimetidine suppressed circulating concentration of biologically active parathyroid hormone. A probable net decrease in the loss of phosphorus from bone to blood ensued, resulting in a fall in serum phosphorus. This may have stimulated synthesis of 1,25-dihydroxycholecalciferol and led to a positive calcium balance, thereby maintaining the serum ionized calcium concentration. The maintenance of phosphate balance, despite suppression of iPTH by cimetidine, indicates that factors other than hyperparathyroidism relate to phosphate homeostasis in chronically uremic dogs.
Assuntos
Cimetidina/uso terapêutico , Guanidinas/uso terapêutico , Hiperparatireoidismo Secundário/tratamento farmacológico , Uremia/metabolismo , Animais , Cálcio/metabolismo , Cães , Feminino , Homeostase , Hiperparatireoidismo Secundário/etiologia , Hormônio Paratireóideo/sangue , Fosfatos/metabolismo , Fatores de Tempo , Uremia/complicações , Vitamina D/metabolismoRESUMO
The purpose of this report is to alert the clinician that hyponatremic patients with CNS disease do not necessarily have a syndrome of inappropriate secretion of antidiuretic hormone. We describe a patient with hyponatremia and carcinomatous meningitis whose volume contraction resulted from striking urinary sodium losses. Although no longer even alluded to in reviews of hyponatremia, cerebral salt wasting appears to be a real clinical entity that warrants further investigation.
Assuntos
Encefalopatias/diagnóstico , Hiponatremia/diagnóstico , Meningite/diagnóstico , Idoso , Encefalopatias/complicações , Carcinoma/complicações , Carcinoma/diagnóstico , Humanos , Hiponatremia/complicações , Síndrome de Secreção Inadequada de HAD/diagnóstico , Masculino , Meningite/complicaçõesRESUMO
The Modification of Diet in Renal Disease Study showed a beneficial effect of a lower-than-usual blood pressure (BP) goal on the progression of renal disease in patients with proteinuria. The purpose of the present analyses was to examine the achieved BP, baseline characteristics that helped or hindered achievement of the BP goals, and safety of the BP interventions. Five hundred eighty-five patients with baseline glomerular filtration rate between 13 and 55 mL/min per 1.73 m2 (0.22 to 0.92 mL/s per 1.73 m2) were randomly assigned to either a usual or low BP goal (mean arterial pressure < or = 107 or < or = 92 mm Hg, respectively). Few patients had a history of cardiovascular disease. All antihypertensive agents were permitted, but angiotensin-converting enzyme inhibitors (with or without diuretics) followed by calcium channel blockers were preferred. The mean (+/- SD) of the mean arterial pressures during follow-up in the low and usual BP groups was 93.0 +/- 7.3 and 97.7 +/- 7.7 mm Hg, respectively. Follow-up BP was significantly higher in subgroups of patients with preexisting hypertension, baseline mean arterial pressure > 92 mm Hg, a diagnosis of polycystic kidney disease or glomerular diseases, baseline urinary protein excretion > 1 g/d, age > or = 61 years, and black race. The frequency of medication changes and incidence of symptoms of low BP were greater in the low BP group, but there were no significant differences between BP groups in stop points, hospitalizations, or death. When data from both groups were combined, each 1-mm Hg increase in follow-up systolic BP was associated with a 1.35-times greater risk of hospitalization for cardiovascular or cerebrovascular disease. Lower BP than usually recommended for the prevention of cardiovascular disease is achievable by several medication regimens without serious adverse effects in patients with chronic renal disease without cardiovascular disease. For patients with urinary protein excretion > 1 g/d, target BP should be a mean arterial pressure of < or = 92 mm Hg, equivalent to 125/75 mm Hg.
Assuntos
Pressão Sanguínea , Dieta com Restrição de Proteínas , Nefropatias/dietoterapia , Adolescente , Adulto , Idoso , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Doença Crônica , Dieta com Restrição de Proteínas/efeitos adversos , Feminino , Seguimentos , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Proteinúria/diagnóstico , SegurançaRESUMO
The prevalence of retroviral infection in renal transplantation remains poorly defined. We tested retrospectively sera from 224 of 331 patients undergoing renal transplantation between 1979 and 1985. Viral antigen based EIA was used for screening IgG antibodies to human immunodeficiency virus (HIV-I) and human T-cell leukemia virus type I (HTLV-I). Positive EIAs were confirmed by Western blot. Six patients (2.7%) were found to have retroviral infection, four with HIV-1 and two with HTLV-I. The four patients with HIV-1 infection were negative before and became EIA and Western blot positive following transplantation. All patients had transient HIV-1 antigenemia documented before antibody was detected. One patient died of Kaposi's sarcoma 2 years posttransplantion with a functioning graft. One is alive and asymptomatic 4 years posttransplant, and two rejected their grafts and are asymptomatic on maintenance hemodialysis. Six patients tested positive for HTLV-I by EIA. Only two patients, however, were also positive for HTLV-I by Western blot, RIPA, and p24 antigen RIA, one prior to and one after transplantation. Both had HTLV-I-positive lymphocyte cultures and remain asymptomatic of retroviral infection 3 years after renal transplantation. A third patient, positive for HTLV-I by EIA, had indeterminate Western blot and negative RIPA, RIA, and lymphocyte culture. Intravenous drug use was not a risk factor for retroviral infection in this patient population. It is likely that patients became infected peritransplantation from blood transfusions. Contamination by donor kidneys, however, cannot be excluded.
Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , HIV-1/isolamento & purificação , Infecções por HTLV-I/epidemiologia , Transplante de Rim , Síndrome da Imunodeficiência Adquirida/transmissão , Western Blotting , Ensaio de Imunoadsorção Enzimática , Florida , Infecções por HTLV-I/transmissão , Humanos , Técnicas Imunoenzimáticas , Prevalência , Estudos Retrospectivos , Reação TransfusionalRESUMO
PURPOSE: We have previously demonstrated the greater sensitivity of 131I-hippuran renography than 99mTC-DTPA scintigraphy to diagnose renovascular hypertension (RVH). This study assesses the predictive diagnostic value of furosemide-131I-hippuran renography after angiotensin-converting enzyme (ACE) inhibition in patients with and without RVH. PATIENTS AND METHODS: All patients were investigated at the University of Miami/Jackson Memorial Medical Center. Twenty-eight patients had RVH and 22 did not. Twenty-eight patients had normal or minimally decreased renal function (serum creatinine level 1.5 mg/dL or less) and 22 had renal insufficiency (serum creatinine level 1.8 mg/dL or more). Renography was performed 60 minutes after oral administration of 50 mg captopril or 10 minutes after intravenous injection of 40 micrograms/kg enalaprilat. Forty milligrams of furosemide were administered intravenously 2 minutes after injection of 131I-hippuran. The residual cortical activity (RCA) of 131I-hippuran was measured at 20 minutes. RESULTS: RVH was unlikely when RCA after ACE inhibition was less than 30% of peak cortical activity. Conversely, RVH was present when 131I-hippuran cortical activity steadily increased throughout the test to reach 100% at 20 minutes. In azotemic patients with RCA between 31% and 100%, RVH was differentiated from intrinsic renal disease by obtaining a baseline renogram without ACE inhibition and comparing RCA in that study and RCA after ACE inhibition. If RCA increased (indicating worsening renal function) after ACE inhibition, RVH was likely; whereas, intrinsic renal disease was more likely if RCA remained unchanged or decreased (indicating improved renal function) with ACE inhibition. The test had a specificity of 95% and a sensitivity of 96% in this population. There was a direct correlation between the results of angioplasty or surgery on high blood pressure and the changes in RCA before and after intervention (n = 20). CONCLUSION: Furosemide-131I-hippuran renography with ACE inhibition is highly predictive in identifying patients with RVH.
Assuntos
Inibidores da Enzima Conversora de Angiotensina , Furosemida , Hipertensão Renovascular/diagnóstico por imagem , Ácido Iodoipúrico , Rim/diagnóstico por imagem , Adulto , Idoso , Algoritmos , Angiografia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Cães , Feminino , Humanos , Hipertensão Renovascular/fisiopatologia , Radioisótopos do Iodo , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Renografia por Radioisótopo , Sensibilidade e EspecificidadeRESUMO
Factors influencing bone and mineral metabolism were evaluated in 16 children with active nephrotic syndrome and normal glomerular filtration rate. All patients were proteinuric and/or hypoalbuminemic and had elevated serum triglyceride and cholesterol levels. Seven patients had never received or had discontinued glucocorticoid treatment at least 6 months before the study; six patients were receiving prednisone at the time of study. Although all patients were hypocalcemic (serum total or ionized calcium), none was hypomagnesemic. Despite the low serum calcium levels, circulating immunoreactive parathyroid hormone was elevated in only nine of 16. Plasma 25-hydroxyvitamin D was low in all 16 patients, averaging 7.6 +/- 1.2 ng/mL for the group. In contrast, levels of 1,25-dihydroxyvitamin D were normal in 12 of 14 patients. Bone mineral content measured by photon absorptiometry averaged 83% and was less than 90% of normal in six of nine patients tested. The findings were not influenced by the recent or concurrent administration of glucocorticoid. The data demonstrate abnormalities of mineral and bone modulation in nephrotic children even in the absence of impaired glomerular filtration rate and irrespective of glucocorticoid therapy. The decrease in serum ionized calcium may be related to an absolute deficiency in 25-hydroxyvitamin D and/or a relative deficiency in 1,25-dihydroxyvitamin D. Undermineralization of bone may result from the low levels of vitamin D metabolites and, in some patients, from an increase in immunoreactive parathyroid hormone. Whether treatment with vitamin D metabolites and/or calcium supplementation will prevent the abnormalities remains to be demonstrated.
Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Taxa de Filtração Glomerular , Síndrome Nefrótica/sangue , Calcifediol/sangue , Calcitriol/sangue , Cálcio/sangue , Criança , Creatinina/sangue , Feminino , Humanos , Hipocalcemia/sangue , Magnésio/sangue , Masculino , Hormônio Paratireóideo/sangueRESUMO
Renal scintigraphy with [99mTc]diethylenetriaminepentaacetic acid (DTPA) and/or sodium-iodine-131-o-iodohippurate (HIP) was performed before and after an oral dose of captopril (50 mg) in 18 patients with renovascular hypertension (RVH) due to renal artery stenosis (RAS) and 18 controls. In every patient with RVH, captopril induced, enhanced or sustained abnormal findings on HIP scintigraphy depending on the degree of RAS. With DTPA scintigraphy, renal function decreased after captopril in ten kidneys with RVH-related RAS and adequate baseline renal function, but this phenomenon was not evident in 11 kidneys with RVH and poor renal function. Captopril did not influence HIP or DTPA studies of kidneys with patent renal arteries (patients after successful renal angioplasty, patients with essential hypertension, contralateral kidneys of patients with unilateral RVH) or ipsilateral kidneys with mild and subcritical (less than 60%) RAS in patients without hypertension and/or normal renal vein renin activity. When HIP and DTPA scintigraphy were compared in the same patients, HIP demonstrated greater sensitivity and specificity than DTPA, particularly in patients with poor renal function. HIP scintigraphy before and after a single dose of captopril may provide a rapid sensitive and minimally invasive test for screening patients with hypertension.
Assuntos
Captopril , Hipertensão Renovascular/diagnóstico por imagem , Renografia por Radioisótopo/métodos , Administração Oral , Captopril/administração & dosagem , Humanos , Ácido Iodoipúrico , Compostos Organometálicos , Ácido Pentético , Pentetato de Tecnécio Tc 99mRESUMO
Captopril renography is a powerful tool for evaluating renovascular hypertension. In this article we examine four different protocols: 99mTc-DTPA, [131I]hippuran with captopril, [131I]hippuran with enalaprilat, and 99mTc-mercaptoacetyltriglycine (MAG3). In our experience, [131I]hippuran renograms are a reliable and reproducible test in patients both with and without azotemia. Although our experience with the new 99mTc-MAG3 technique is somewhat limited, it appears that this will also be a valuable test, which additionally has several advantages over hippuran, namely, a smaller turnaround time between test and baseline study, a smaller dose of radioactivity, better images, and more accurate counts. We look forward to the future development of this technique.
Assuntos
Inibidores da Enzima Conversora de Angiotensina , Furosemida , Hipertensão Renovascular/diagnóstico por imagem , Renografia por Radioisótopo/métodos , Angioplastia com Balão , Protocolos Clínicos , Humanos , Hipertensão Renovascular/terapia , Radioisótopos do Iodo , Ácido Iodoipúrico , Oligopeptídeos , Compostos de Organotecnécio , Radiografia , Artéria Renal/diagnóstico por imagem , Tecnécio Tc 99m MertiatidaRESUMO
Captopril renography is a valuable test in the diagnosis of patients with renal artery stenosis. We examined the criteria for selecting patients for this procedure and the best methods for preparing the patient for renography.
Assuntos
Captopril , Hipertensão Renovascular/diagnóstico por imagem , Renografia por Radioisótopo/métodos , Obstrução da Artéria Renal/diagnóstico por imagem , HumanosRESUMO
The pathogenesis of progressive renal disease includes systemic hypertension and intrarenal factors that may be hemodynamic or metabolic in origin and involve mediators of inflammation. Most current information derives from experiments in rodents. In other species (rabbit, dog, baboon) subjected to renal mass reduction, a greater variety of pathologic changes is apparent than in rats. Clinical trials at controlling progression of renal disease are compounded by numerous factors; and it is not evident that extrapolation can safely be made from results of animal studies to human disease. The mechanism(s) of renal disease progression in humans, therefore, remain largely unknown. Current therapeutic recommendations in patients with chronic renal disease include limitation of phosphorus absorption, correction of lipid abnormalities and control of systemic blood pressure. The latter can be achieved with a variety of agents some of which, like angiotensin converting enzyme inhibitors and calcium antagonists, may be preferred because of specific intrarenal effects.
Assuntos
Falência Renal Crônica/etiologia , Animais , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Proteínas Alimentares/administração & dosagem , Humanos , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Néfrons/lesões , Fósforo na Dieta/administração & dosagem , Circulação RenalRESUMO
The nephropathology observed in patients with HIV infection is reviewed. A characteristic, though not specific, nephropathy associated with HIV infection can be encountered in HIV carriers, in patients with AIDS-related complex and in patients with AIDS. HIV-associated nephropathy typically exhibits the features of an aggressive form of focal and segmental glomerulosclerosis. Distinctive pathologic features include: 1) the "collapsing" and predominantly global pattern of glomerulosclerosis; 2) the severity of visceral epithelial cell hypertrophy and droplet formation; 3) the prominent tubular microcysts and cast formation; 4) the focal tubular degenerative features; and 5) the numerous tubuloreticular inclusions.