RESUMO
The relative contributions of Ca++, phosphorus, and parathyroid hormone (PTH) on insulin secretion were evaluated in three groups of dogs. Dogs were studied with glucose infusions (group I) or standard intravenous glucose tolerance tests (IVGTT) (group II) before and after the development of diet-induced hypophosphatemia. Mean serum phosphorus levels for both groups fell from 4.1 to 1.1 mg/100 ml. Animals in group I demonstrated a fall in glucose disappearance rates (Kg) from 5.3+/-0.6% min to 3.5+/-0.5% after induction of hypophosphatemia (P less than 0.001). Mean insulin response was significantly greater in the hypophosphatemic animals than in controls in this group. In group II animals, mean insulin areas obtained during the IVGTT increased from 1,426+/-223 to 2,561+/-141 muU/ml/60 min after induction of hypophosphatemia, and were unaffected by Ca++ or PTH administration. Ca++ administration, but not hypophosphatemia or PTH infusion, increased significantly the mean insulin response to tolbutamide. Secondary hyperparathyroidism was induced by dietary manipulation in four dogs (group III). Mean PTH values increased from 71.4+/-2.1 to 3,012+/-372 pg/ml (P less than 0.001). Mean insulin response to an IVGTT was similar to group III animals, but increased from 1,352+/-128 to 1,894+/-360 muU/ml/60 min after the excessive dietary phosphorus was reduced for 3 mo, and plasma phosphorus fell from 3.2+/-0.1 to 2.8+/-0.3 mg/100 ml. PTH values decreased to 647+/-53 pg/ml. The insulin response to tolbutamide was comparable to that in group II animals, but increased significantly after calcium administration. Immunoreactive insulin disappearance rates were unaffected by hypophosphatemia or diet-induced secondary hyperparathyroidism. These data demonstrate that hypophosphatemia is associated with an augmented glucose-stimulated insulin release, without any effect on tolbutamide-stimulated insulin release. Hypercalcemia produces an augmented tolbutamide-stimulated insulin release with no apparent effect on glucose-stimulated insulin release. Finally, PTH does not appear to be an insulin antagonist and has no apparent effect on either glucose- or tolbutamide-stimulated insulin release in animals with dietary-induced secondary hyperparathyroidism.
Assuntos
Cálcio/farmacologia , Insulina/metabolismo , Hormônio Paratireóideo/farmacologia , Fósforo/farmacologia , Tolbutamida/antagonistas & inibidores , Animais , Cães , Feminino , Teste de Tolerância a Glucose , Hiperparatireoidismo/metabolismo , Hipoglicemia/metabolismoRESUMO
The role of the kidney in the metabolism of parathyroid hormone (PTH) was examined in the dog. Studies were performed in awake normal and uremic dogs after administration of bovine parathyroid hormone (b-PTH) or synthetic amino terminal tetratricontapeptide of b-PTH (syn b-PTH 1-34). The renal clearance of immunoreactive PTH was determined from the product of renal plasma flow and the percent extraction of PTH immunoreactivity by the kidney. Blood levels of circulating immunoreactive PTH were determined by radioimmunoassay. The normal dog kidney extracted 20 plus or minus 1% of the immunoreactive b-PTH delivered to it, and renal clearance (RC) of immunoreactivity was 60 ml/min. When RC was compared to an estimate of total metabolic clearance (MCR) of immunoreactivity, it accounted for 61% of the total. Both MCR and RC were markedly decreased in dogs with chronic renal disease. However, the percent extraction of immunoreactive PTH was unchanged in chronic renal disease, and the observed decrease in RC was due to changes in renal plasma flow. The largest portion of the reduction in total MCR was accounted for by the decrease in RC, and there was no compensation for the decrease in RC by extrarenal sites of PTH metabolism.
Assuntos
Falência Renal Crônica/metabolismo , Rim/metabolismo , Hormônio Paratireóideo/metabolismo , Animais , Antígenos , Cromatografia em Gel , Modelos Animais de Doenças , Cães , Feminino , Taxa de Filtração Glomerular , Soros Imunes , Radioisótopos do Iodo , Rim/irrigação sanguínea , Falência Renal Crônica/sangue , Falência Renal Crônica/etiologia , Taxa de Depuração Metabólica , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/imunologia , Peptídeos/metabolismo , Radioimunoensaio , Fluxo Sanguíneo RegionalRESUMO
Previous studies from this laboratory demonstrated that secondary hyperparathyroidism in dogs with chronic renal disease may occur, at least in part, as a consequence of the need for progressive adaptation in renal phosphorus (P) excretion that occurs as glomerular filtration rate falls. However, the studies were of relatively short duration. Moreover, no information emerged regarding a potential role of calcium malabsorption in the pathogenesis of secondary hyperparathyroidism. The short duration of the protocol did not lend itself to the study of the effect of P control or the administration of vitamin D in the pathogenesis of renal osteodystrophy. In the present studies, 14 dogs with experimental chronic renal disease were studied serially for a period of 2 yr. Each animal was studied first with two normal kidneys on an intake of P of 1,200 mg/day. Then, renal insufficiency was produced by 5/6 nephrectomy. The dogs then were divided into three groups. In group I, 1,200 mg/day P intake was administered for the full 2 yr. In group II, P intake was reduced from the initial 1,200 mg/day, in proportion to the measured fall in glomerular filtration rate, in an effort to obviate the renal adaptation in P excretion. In group III, "proportional reduction" of P intake also was employed; but in addition, 20 mug of 25(OH)D(3) were administered orally three times a week. In group I, parathyroid hormone (PTH) levels rose throughout the 2-yr period reaching a final concentration of 557+/-70 U (normal 10-60). In group II, values for PTH remained normal throughout the 1st yr, increased modestly between the 12th and the 18th mo, but then did not rise after the 18th mo. In group III, no elevation of PTH levels was observed at any time; however, these animals were hypercalcemic. Histomorphologic analyses of the ribs of these dogs were performed serially throughout the 2-yr period. A linear relationship was obtained between the osteoclastic resorption surface and the concentration of circulating immunoreactive PTH. The osteoid volume was greater in group I animals when compared to those in group II. None of the morphologic abnormalities associated with renal osteodystrophy were observed in the animals in the third group.
Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Hidroxicolecalciferóis/uso terapêutico , Fosfatos/uso terapêutico , Animais , Cálcio/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Modelos Animais de Doenças , Cães , Feminino , Taxa de Filtração Glomerular , Absorção Intestinal , Cinética , Hormônio Paratireóideo/sangue , Fosfatos/sangueRESUMO
This article chronicles the health care quality improvement efforts that relate to patients with end stage renal disease (ESRD). The emphasis is on quality improvement as a management system as opposed to the quality improvements that resulted from strictly technical dialysis-related issues. The government has exercised considerable oversight on the ESRD program because of its growth and cost. History has shown that quality assurance (QA) has had little effect on improving quality or decreasing cost. The philosophy, methods, and tools of continuous quality improvement (CQI) have been shown to work in health care. CQI is a management system that offers hope for higher quality affordable health care. Computer technology is at last sophisticated enough to permit the collection of large amounts of clinical data at the point of care. This will permit CQI methods and tools to be applied generally at reasonable costs. Physicians in general and nephrologists in particular are beginning to understand the managed care environment. They are beginning to understand the paradigm shift that is required to effect the changes necessary for physicians to assume their leadership role in health care. This article reviews the quality efforts of the past and present. It discusses the strengths and weaknesses of efforts to improve quality and lastly presents a vision for the future.
Assuntos
Atenção à Saúde/normas , Falência Renal Crônica/terapia , Controle de Qualidade , Diálise Renal/normas , Humanos , Diálise Renal/tendências , Estados UnidosRESUMO
The potential contribution of the splanchnic tissues to the carbohydrate intolerance of uremia was studied in fasted, partially nephrectomized rats. The livers of sham operated (C) and partially nephrectomized (Nx) rats were perfused with physiologic concentrations of potential gluconeogenic substrates using a nonrecirculating perfusion apparatus. Glucose release was slightly greater in the livers of Nx rats as compared to C rats. The portal vein concentrations of the potential gluconeogenic precursors were not different in the two groups. Moreover, there were no differences in the net hepatic extraction of alanine, glutamine or glutamate between the two groups of rats. There was also no difference in the production of glucose from U14C alanine. The livers of Nx rats, however, demonstrated less net extraction of lactate and released greater concentrations of betahydroxybutyrate. The increased release of glucose by livers of Nx rats may be at least partially due to their greater hepatic glycogen content.
Assuntos
Gluconeogênese , Fígado/metabolismo , Uremia/metabolismo , Alanina/metabolismo , Animais , Glucose/metabolismo , Glutamatos/metabolismo , Ácido Glutâmico , Glutamina/metabolismo , Humanos , Cinética , Lactatos/metabolismo , Ácido Láctico , Glicogênio Hepático/metabolismo , Nefrectomia , Veia Porta , RatosRESUMO
Serum phosphorus concentrations are maintained within narrow limits in humans. In the extracellular fluid most of the phosphorus is present in the inorganic form and at the level of the glomerulus greater than 90% of PO4 is ultrafilterable. The kidney plays a key role in PO4 homeostasis. Micropuncture experiments have demonstrated that 60 to 70% of the filtered PO4 is reabsorbed in the proximal tubule; however, there is evidence that a significant amount of PO4 is reabsorbed in the distal tubule. Phosphate secretion probably plays a minor role in the overall renal regulation of phosphate. In normal individuals the amount of PO4 ingested plays a key role in the amount that ultimately will be excreted in the urine. The reabsorption of PO4 along the nephron is regulated by a series of factors of which parathyroid hormone is the most important one. Hyperphosphatemia is seen frequently in clinical medicine and by far, the most common cause is a decrease in urinary PO4 excretion secondary to renal failure. From the practical point of view, the most effective way to treat hyperphosphatemia is to decrease PO4 absorption in the GI tract by the use of PO4 binders.
Assuntos
Fosfatos/sangue , Acromegalia/metabolismo , Adulto , Compostos de Alúmen/uso terapêutico , Animais , Cães , Humanos , Hipoparatireoidismo/metabolismo , Recém-Nascido , Infecções/sangue , Falência Renal Crônica/metabolismo , Neoplasias/sangue , Hormônio Paratireóideo/sangue , Fosfatos/administração & dosagem , Fosfatos/metabolismo , Esforço Físico , Pseudo-Hipoparatireoidismo/metabolismo , Vitamina D/farmacologiaRESUMO
Northeast Louisiana Dialysis Center implemented continuous quality improvement (CQI) to improve the quality of care delivered to end stage renal disease (ESRD) patients treated by hemodialysis in their facility. The unit chose to address normalization of calcium and phosphorus and parathyroid hormone (PTH), anemia, nutrition, adequacy of dialysis and dialyzer reuse as well as performance benchmarks by the Health Care Financing Administration (HCFA) core indicators. This article presents the results obtained and the methodology used in this improvement effort. The article also presents nine principles the authors believe necessary for a successful CQI program.
Assuntos
Unidades Hospitalares de Hemodiálise/normas , Falência Renal Crônica/terapia , Diálise Renal/normas , Gestão da Qualidade Total/métodos , Algoritmos , Anemia/etiologia , Anemia/terapia , Benchmarking , Cálcio/sangue , Centers for Medicare and Medicaid Services, U.S. , Eritropoetina/uso terapêutico , Unidades Hospitalares de Hemodiálise/organização & administração , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/mortalidade , Louisiana/epidemiologia , Participação nas Decisões , Hormônio Paratireóideo/sangue , Fósforo/sangue , Avaliação de Processos em Cuidados de Saúde , Estados UnidosAssuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Fosfatos/metabolismo , Animais , Cálcio/sangue , Cães , Humanos , Hidroxicolecalciferóis/sangue , Hiperparatireoidismo Secundário/etiologia , Falência Renal Crônica/metabolismo , Hormônio Paratireóideo/fisiologia , Vitamina D/metabolismoAssuntos
Cálcio/metabolismo , Absorção Intestinal/efeitos dos fármacos , Nefropatias/metabolismo , Vitamina D/farmacologia , Adulto , Idoso , Radioisótopos de Cálcio , Doença Crônica , Humanos , Hipocalcemia/tratamento farmacológico , Hipocalcemia/etiologia , Nefropatias/complicações , Pessoa de Meia-Idade , Vitamina D/análise , Vitamina D/uso terapêuticoAssuntos
Hiperparatireoidismo Secundário/etiologia , Nefropatias/metabolismo , Hormônio Paratireóideo/metabolismo , Vitamina D/metabolismo , Sequência de Aminoácidos , Animais , Cálcio/metabolismo , Colecalciferol/metabolismo , Doença Crônica , Humanos , Hidroxicolecalciferóis/biossíntese , Hidroxilação , Nefropatias/complicações , Taxa de Depuração Metabólica , Peso MolecularAssuntos
Alumínio , Antiácidos , Fosfatos , Animais , Ânions , Antiácidos/uso terapêutico , Fenômenos Químicos , Química , Géis , Humanos , Concentração de Íons de Hidrogênio , Ratos , Sulfatos , Uremia/tratamento farmacológicoAssuntos
Cálcio/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Hiperparatireoidismo Secundário/metabolismo , Falência Renal Crônica/metabolismo , Fosfatos/metabolismo , Osso e Ossos/patologia , Calcinose/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/patologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Humanos , Hidroxicolecalciferóis/deficiência , Hidroxicolecalciferóis/uso terapêutico , Rim/metabolismo , Síndromes de Malabsorção/metabolismo , Osteogênese , Hormônio Paratireóideo/metabolismo , Vitamina D/metabolismoRESUMO
A simplified method is described for the measurement of calcium absorption in the dog. This method uses 45Ca and takes less than 8 h to perform. Calcium absorption was measured in normal and uremic dogs on different intakes of calcium and phosphorus and compared to the results obtained in the same animal maintained on the same diet by another method using 47Ca and a double dilution procedure. The correlation coefficient between the two methods was 0.99 (P < 0.001). The advantages of the simplified method are discussed.
Assuntos
Cálcio/metabolismo , Absorção Intestinal , Uremia/metabolismo , Animais , Calcifediol , Radioisótopos de Cálcio , Cálcio da Dieta/farmacologia , Dieta , Cães , Feminino , Hidroxicolecalciferóis/farmacologia , Métodos , Fosfatos/deficiência , Fósforo/administração & dosagem , Técnica de Diluição de RadioisótoposRESUMO
A 30-year-old black male with end-stage renal disease of 8 years' duration had undergone 16 prior access operations and was still without an adequate access for dialysis. A spiral saphenous vein graft conduit was constructed from the left saphenous vein and used as a straight arterial conduit graft between the superficial femoral artery at Hunter's canal and the saphenofemoral vein junction in the groin. The spiral vein graft tube was used as the sole means of dialysis for the next consecutive 750 dialysis procedures over nearly 6 years without any complication.
Assuntos
Derivação Arteriovenosa Cirúrgica , Prótese Vascular/métodos , Falência Renal Crônica/terapia , Diálise Renal , Veia Safena/cirurgia , Adulto , Veia Femoral/cirurgia , Oclusão de Enxerto Vascular/cirurgia , Humanos , Masculino , Politetrafluoretileno , Reoperação , Infecção da Ferida Cirúrgica/cirurgiaRESUMO
The axillary artery-iliac vein graft using externally supported PTFE is a viable option for this difficult patient group. It is capable of functioning well for up to 12 months. Most importantly, despite numerous prior access procedures, the axillary artery and iliac vein in each case were amenable to the procedure. Critical technical points include the use of externally splinted PTFE grafts, avoidance of crossing joints, and angling of the graft in the direction of the iliac vein at that anastomosis. The lack of thrombosis or infection to date, coupled with successful dialysis in every patient, suggests that this is one more option that can be used in the difficult secondary access patient.
Assuntos
Artéria Axilar/cirurgia , Prótese Vascular , Veia Ilíaca/cirurgia , Adulto , Idoso , Artéria Axilar/diagnóstico por imagem , Seguimentos , Humanos , Veia Ilíaca/diagnóstico por imagem , Pessoa de Meia-Idade , RadiografiaRESUMO
We studied angiographically the access route 1-27 months after the insertion temporary dialysis catheters in 52 patients: 32 subclavian and 20 internal jugular. The two groups were statistically similar with respect to age, sex and race. The subclavian catheters were left in for a mean of 11.5 days (2-22) while the internal jugular ones were inserted for 15.8 days (5-25; p = 0.0015). One hundred percent of the internal jugular patients were free of any venogram abnormalities in their venous access return. In marked contrast, 50% of the subclavian sites had mild to severe stricutures with 90% having 70-100% occlusion of the subclavian vein. Six patients had bilateral severe strictures. The long-term stricture rate of subclavian catheters in the subclavian vein was unacceptably high compared to the internal jugular route.
Assuntos
Cateterismo Venoso Central/efeitos adversos , Diálise Renal/instrumentação , Cateteres de Demora/efeitos adversos , Feminino , Humanos , Veias Jugulares , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos , Estudos Retrospectivos , Veia Subclávia , Tromboflebite/etiologiaRESUMO
Elevated levels of fibrinogen/fibrin degradation products (FDP) occur in uremia, and have been thought to be in part related to intravascular coagulation in the kidney. More recent data indicated that delayed catabolism of fibrinogen fragment D occurred in anephric animals. To further evaluate FDP catabolism in the kidney, turnover studies of purified dog 131I-Fg-D and 125I-Fg-E were performed on dogs before and after acute subtotal nephrectomies, and later during chronic uremia. 131I-fibrinogen clearances were also perfomed. Slowed catabolism of Fg-D and Fg-E was observed in both the acute and chronic uremic stages. Altered urinary excretion was not a factor as only minimal amounts of Fg-D and Fg-E were excreted in the urine of the control animals. In the 131I-fibrinogen studies, there were significant changes in plasma volume, fibrinogen t 1/2, and intravascular/extravascular distribution, but not in fractional catabolic rate. To differentiate fully, the effects of uremia from those of loss of catabolic renal tissue, the Fg-D and Fg-E turnover studies were repeated on other animals with intact kidneys whose ureters were diverted into the peritoneum and compared to subsequent studies after total nephrectomy. The control and ureter-severed studies had the same clearance pattern, whereas decreased catabolism occurred in the nephrectomized dogs. The results demonstrate uremia per se does not have a major effect upon the catabolism of fibrinogen, Fg-D, and Fg-E. Loss of renal tissue does impair the clearance of Fg-D and Fg-E, indicating these proteins are normally catabolized in part by the kidneys. Thus elevated plasma FRA in uremic patients may reflect decreased Fg-D and Fg-E catabolism rather than increased FDP production from primary or secondary fibrinolysis.
Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Rim/metabolismo , Taxa de Depuração Metabólica , Uremia/metabolismo , Animais , Cães , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/urina , Fibrinogênio/urina , Meia-Vida , Radioisótopos do Iodo , Ligadura , Nefrectomia , Ligação Proteica , Artéria Renal/cirurgia , Uremia/urina , Ureter/cirurgiaRESUMO
The rate of change of the serum creatinine concentrations in 63 patients with chronic progressive renal disease of varied etiology was examined by linear regression analysis using the logarithm or the reciprocal of the serum creatinine concentration versus time. A single straight line was described by one or the other of these relationships in 53 patients. Six patients had an accelerated rate of nephron destruction terminally (two slopes) regardless of the mathematical analysis. The remaining four patients had course changes either due to apparent spontaneous remissions or temporally related to therapy. These data suggest that (functional) nephron loss in chronic progress disease is orderly and mathematically definable. The theoretical implications are that functional nephron loss is either exponential (log Cr) or constant (1/Cr).
Assuntos
Creatinina/sangue , Nefropatias/sangue , Doença Crônica , Taxa de Filtração Glomerular , Humanos , Modelos Biológicos , Análise de RegressãoRESUMO
Calcium absorption was measured in eight uremic patients before and after eight days of treatment with 100 or 500 mug of 25-hydroxycholecalciferol (25(OH)D3) per day. Fractional calcium absorption was estimated by administering 47Ca i.v. and orally on separate days and counting forearm radioactivity four hours later. Calcium absorption in four patients with residual renal function rose from 16.3 +/- 2.5 to 40.8 +/- 5.5% after treatment. In order to determine if the increased calcium absorption was mediated by an increase in the production of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) by virtue of increased substrate delivery to the 25-hydroxycholecalciferol-1-hydroxylase system present in the residual renal tissue, identical studies were performed in four anephric patients. Calcium absorption in these patients averaged 15.7 +/- 2.2% during the control period and rose to 46.0 +/- 11.1% after treatment. Increments in serum calcium after treatment were similar in both groups of patients; the mean concentration rose from 9.6 +/- 0.3 to 11.0 +/- 0.6 mg/100 ml. The results indicate that 25(OH)D3 can improve calcium absorption in the absence of renal tissue suggesting that its conversion to 1,25(OH)2D3 may not be necessary for its effect on the gastrointestinal tract in the uremic patient.