RESUMO
It is generally agreed that the kidneys are the only site of 1-hydroxylation of vitamin D and that the abnormal calcium metabolism in sarcoidosis is caused by increased production of 1,25-dihydroxyvitamin D (1,25-[OH]2D). We describe a patient with sarcoidosis with hypercalcemic nephropathy and end-stage renal disease undergoing long-term maintenance hemodialysis who was initially seen with hypercalcemia and elevated serum levels of 1,25-(OH)2D. Prednisone administration resulted in decreased serum calcium and 1,25-(OH)2D levels. These results confirm the recent evidence for extrarenal production of 1,25-(OH)2D in sarcoidosis and illustrate the importance of altered vitamin D metabolism in the development of hypercalcemia in sarcoidosis.
Assuntos
Calcitriol/sangue , Nefropatias/metabolismo , Sarcoidose/metabolismo , Adulto , Humanos , Hipercalcemia/tratamento farmacológico , Hipercalcemia/etiologia , Nefropatias/complicações , Nefropatias/tratamento farmacológico , Masculino , Prednisona/uso terapêutico , Sarcoidose/complicações , Sarcoidose/tratamento farmacológicoRESUMO
We performed prospective and retrospective studies of 96 consecutive patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) to determine the incidence, pathogenesis, and clinical significance of hyponatremia, defined as serum sodium levels less than or equal to 130 mmol/L on more than one occasion. Thirty (31.3%), six with ARC and 24 with AIDS, had hyponatremia, and it developed in 20 as outpatients. Age, gender, duration of illness, and weight loss did not differ between groups. The hyponatremic patient had more opportunistic illnesses, including Pneumocystis carinii pneumonia and cytomegalovirus infections, and had a mortality of 70% as compared to 36.4% of the patients without hyponatremia. The probability of 50% survival after diagnosis of human immunodeficiency virus (HIV) infection in the hyponatremic group was 11.5 months, as compared to 39 months for those without hyponatremia, p less than 0.001. The probability of 50% survival after development of hyponatremia was 4.5 months and the median length of time to development of hyponatremia was 12.5 months after diagnosis of HIV infection. Eighty-eight percent had hypovolemia and 12% normovolemia. Seventeen of 21 with hypovolemia had no evident source of fluid loss. Two had Addison's disease, and 15 had unexpectedly high urine sodium concentration without evidence of renal or adrenal insufficiency. Hyponatremia occurs commonly in ambulatory patients with ARC or AIDS, appears in patients with higher mortality and morbidity, and does not represent a terminal event. Most patients had hypovolemia and unexpectedly high urine sodium concentration, suggesting defective renal sodium conservation.
Assuntos
Complexo Relacionado com a AIDS/complicações , Síndrome da Imunodeficiência Adquirida/complicações , Hiponatremia/complicações , Complexo Relacionado com a AIDS/mortalidade , Síndrome da Imunodeficiência Adquirida/mortalidade , Adulto , Feminino , Seguimentos , Humanos , Hiponatremia/epidemiologia , Hiponatremia/mortalidade , Incidência , Masculino , Infecções Oportunistas/complicações , Infecções Oportunistas/epidemiologia , Probabilidade , Prognóstico , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Malignant disease is associated with a wide variety of derangements in renal function and electrolyte homeostasis. In many cases this leads to a clinically significant worsening of health status and rarely may lead to the patient's death. In this review we discuss several of the important abnormalities of renal structure and function associated with neoplastic disease.
Assuntos
Nefropatias , Síndromes Paraneoplásicas , Humanos , Nefropatias/diagnóstico , Nefropatias/etiologia , Nefropatias/fisiopatologia , Nefropatias/terapia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/fisiopatologia , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/fisiopatologia , Síndromes Paraneoplásicas/terapia , Desequilíbrio Hidroeletrolítico/diagnóstico , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/fisiopatologia , Desequilíbrio Hidroeletrolítico/terapiaRESUMO
Among eight subjects suspected of excessive occupational exposure to lead, detailed examination of renal function identified abnormalities in four. Glomerular filtration rate was less than 87 ml/mim/1.73 m2 in one subject with asymptomatic renal failure, and in three subjects with preclinical renal dysfunction. In the subject with asymptomatic renal failure, chelation therapy increased the glomerular filtration rate, p-aminohippurate (PAH) extraction, the maximal PAH secretion rate (TmPAH) and improved proximal tubule ultrastructure, despite decreased renal plasma flow. This improvement in PAH transport was associated with correction of a proximal tubule defect in tritiated PAH uptake detected by section freeze-dry autoradiography of renal biopsy specimens. In three subjects, the etiologic diagnosis of lead-induced nephropathy was established by exclusion, but tubular dysfunction did not obviously exceed the reduction in blomerular filtration. Proximal tubule abnormalities were seen in each of the three patients who underwent biopsy. These studies suggest that lead nephropathy may be an important occupational hazard in the United States lead industry.
Assuntos
Nefropatias/fisiopatologia , Rim/fisiopatologia , Intoxicação por Chumbo/fisiopatologia , Doenças Profissionais/fisiopatologia , Ácidos Aminoipúricos/metabolismo , Autorradiografia , Taxa de Filtração Glomerular , Humanos , Rim/patologia , Nefropatias/metabolismo , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/ultraestrutura , Intoxicação por Chumbo/metabolismo , Intoxicação por Chumbo/patologia , Microscopia Eletrônica , Doenças Profissionais/metabolismo , Doenças Profissionais/patologiaRESUMO
Uric acid metabolism is reviewed as it relates mainly to kidney and electrolyte disorders, with emphasis on the difficulties in understanding urate transport because of its bidirectional transport and the species differences in which animal data may not have relevance to the human condition. A critical review of the effects of pyrazinamide and extracellular volume expansion on urate transport raises questions about the current popular teachings that pyrazinamide exclusively blocks tubule urate secretion and extracellular volume expansion has a major role in controlling urate excretion. There appears to be a renal salt-wasting syndrome with overlapping clinical features that make it indistinguishable from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), except possibly for extracellular volume depletion. Hypouricemia and the elevation in the fractional excretion of urate (%E/Furate) are extensively reviewed with a proposal to use the persistence of hypouricemia and elevated %E/Furate after the correction of hyponatremia to differentiate these patients from those with SIADH. An algorithm is proposed to differentiate one group from the other. A plasma natriuretic factor has been shown in some with probable renal salt wasting, which includes patients with AIDS, cancer, and pulmonary and intracranial diseases. The natriuretic factor may have etiologic implications and diagnostic and therapeutic applications.
Assuntos
Rim/metabolismo , Ácido Úrico/urina , Algoritmos , Transporte Biológico/efeitos dos fármacos , Humanos , Nefropatias/diagnóstico , Nefropatias/metabolismo , Natriuréticos/sangue , Insuficiência Renal/diagnóstico , Insuficiência Renal/metabolismo , Ácido Úrico/sangueRESUMO
OBJECTIVE: To study tubular urate transport in Alzheimer's disease (AD) and measure sodium and lithium transport rates in rats exposed to AD plasma. DESIGN: Cross-sectional study in three comparison groups. SETTING: Referral private institution involving outpatient and hospitalized patients. PATIENTS: AD, multi-infarct dementia (MID) and non-demented controls (C) were selected and evaluated by a geriatrician and a psychiatrist according to availability and willingness to participate in the study. Demented patients had brain imaging, categorized according to NINCDS-DSM III criteria, and had Mini-mental status examination (MMSE) scores determined. INTERVENTIONS: Injection of 0.5 mL of plasma I.P. followed 120 minutes later by an IV plasma injection of 0.2 mL priming dose and infusion of 1.8 mL of plasma at 0.01 mL/min in Sprague Dawley rats. MEASUREMENTS: Renal clearance studies were performed in subjects and in rats exposed to the plasma of study subjects. We measured serum urate concentration and fractional excretion (FE) of urate in subjects and FE sodium and FE lithium in rats. RESULTS: Serum urate was lower and FE urate higher in 18 AD patients compared with six patients with MID, P < 0.05 and P < 0.005, and 11 C, P < 0.02 and P < 0.005, respectively. Higher FE sodium and FE lithium were noted in rats given plasma from 19 AD patients compared with 12 with MID, P < 0.005 and P < 0.0025, and 14 C, P < 0.0025 and P < 0.0005, respectively. FE sodium and FE lithium decreased progressively after serial dilutions of three AD plasmas and FE lithium was negatively correlated with MMSE scores only in AD, r = -0.71 and P < 0.0005. CONCLUSIONS: In AD there is defective tubular urate transport and a plasma natriuretic factor(s). FE sodium and/or FE lithium in rats exposed to plasma of demented patients may differentiate AD from MID and estimate the severity of AD.
Assuntos
Doença de Alzheimer/complicações , Túbulos Renais/metabolismo , Natriuréticos/sangue , Ácido Úrico/sangue , Desequilíbrio Hidroeletrolítico/sangue , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Animais , Bioensaio , Estudos de Casos e Controles , Creatinina/sangue , Creatinina/farmacocinética , Creatinina/urina , Estudos Transversais , Demência por Múltiplos Infartos/complicações , Demência por Múltiplos Infartos/diagnóstico , Feminino , Humanos , Testes de Função Renal , Lítio/sangue , Lítio/farmacocinética , Lítio/urina , Masculino , Entrevista Psiquiátrica Padronizada , Taxa de Depuração Metabólica , Natriuréticos/metabolismo , Natriuréticos/farmacocinética , Fósforo/sangue , Fósforo/farmacocinética , Fósforo/urina , Potássio/sangue , Potássio/farmacocinética , Potássio/urina , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Sódio/sangue , Sódio/farmacocinética , Sódio/urina , Ácido Úrico/metabolismo , Ácido Úrico/farmacocinética , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/metabolismoRESUMO
Apoptosis of neuronal cells is a proposed cause of certain neurological disorders. Here, we report on a 5- to 6-fold increase in apoptosis by exposure to prostaglandin D2 synthase (PGD2S) in PC12 neuronal cells. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) assay, and appears to be mediated via caspase-3 activation. Neutralization with anti-PGD2S antibody or pre-treatment with selenium, which inhibits PGD2S enzymatic activity, both significantly inhibited the PGD2S-induced apoptosis, however, neither had any effect on the apoptosis induced by the known neuronal apoptotic inducer, glutamate. In addition, prostaglandins E1, E2, and F2alpha all inhibited the PGD2S-induced apoptosis while prostaglandin H2 had no significant effect. Furthermore, PGD2S isolated from human serum was more effective at inducing apoptosis then recombinantly expressed protein, presumably due to glycosylation. This novel role of PGD2S, as an inducer of apoptosis, may have implications in PC12 differentiation and possibly some neurological disorders.
Assuntos
Apoptose , Oxirredutases Intramoleculares/farmacologia , Neurônios/efeitos dos fármacos , Animais , Anticorpos/farmacologia , Caspase 3 , Inibidores de Caspase , Caspases/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Glicosilação , Humanos , Marcação In Situ das Extremidades Cortadas , Oxirredutases Intramoleculares/antagonistas & inibidores , Oxirredutases Intramoleculares/sangue , Isoenzimas/antagonistas & inibidores , Isoenzimas/sangue , Isoenzimas/farmacologia , Lipocalinas , Neurônios/citologia , Neurônios/metabolismo , Células PC12 , Prostaglandinas/farmacologia , Ratos , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/farmacologiaRESUMO
Iron deficiency is a common problem in patients treated with hemodialysis. If not detected and treated appropriately, the effectiveness of recombinant human erythropoietin therapy is compromised. Much has been learned in recent years with respect to iron therapy for hemodialysis patients. A series of studies have clearly defined the efficacy of intravenous iron compounds, and recently released clinical practice guidelines have set the appropriate clinical context for the use of these agents. The purpose of this article is to examine the beneficial effects of iron replacement therapy for hemodialysis patients.
Assuntos
Ferro/uso terapêutico , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Eritropoetina/uso terapêutico , Ferritinas/sangue , Humanos , Injeções Intravenosas , Ferro/administração & dosagem , Deficiências de Ferro , Ferro da Dieta/administração & dosagem , Falência Renal Crônica/sangue , Proteínas Recombinantes , Transferrina/metabolismoRESUMO
Sucralfate is used in the treatment and prophylaxis of peptic ulcer disease. One possible mechanism of action is the binding of bile acids. Because the absorption of dietary fat and cholesterol is dependent on the presence of bile acids in the small intestines, sucralfate therapy may produce changes in serum lipoprotein composition qualitatively similar to bile acid sequestrants, such as cholestyramine, which reduce serum cholesterol levels. Although changes in total serum cholesterol have not been reported in sucralfate efficacy studies, the effect of sucralfate on serum lipoprotein composition has not been specifically addressed. The purpose of this study was to prospectively examine the effect of sucralfate on serum lipids and lipoproteins in normal volunteers. Eight healthy volunteers (six men, two women) were recruited for this 10-week study. Drugs known to affect cholesterol levels were not permitted before or during the study. Diet composition during the study period was unaltered from before the study. Subjects took 1 g sucralfate orally 1 hour before meals and at bedtime (four times a day) for 8 weeks, followed by a 2-week washout period. Fasting blood samples were obtained at baseline and weekly, and were analyzed for serum total and HDL cholesterol and for triglycerides. Levels of LDL cholesterol were estimated. After eight weeks of sucralfate, HDL cholesterol increased from baseline by 2.5 mg/dL (6.6%, from 37.6 +/- 9.5 to 40.1 +/- 8.69 mg/dL), and LDL cholesterol decreased by 7.6 mg/dL (6.4%, from 134 +/- 28.1 to 125.4 +/- 34.1). Total cholesterol decreased by 3.5 mg/dL (1.8%, from 192.9 +/- 34.3 to 189.4 +/- 37.2 mg/dL.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Lipídeos/sangue , Lipoproteínas/sangue , Sucralfato/farmacologia , Adolescente , Adulto , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta , Feminino , Humanos , Masculino , Projetos Piloto , Triglicerídeos/sangueRESUMO
To test our hypothesis that a circulating factor(s) may be causing the renal salt and urate wasting in patients (pts) with intracranial diseases, we exposed rats to the plasma of these patients and studied sodium and lithium transport. We selected 21 neurosurgical pts, 13 of whom had increased fractional excretion (FE) of urate, and 14 age and sex-matched controls. Plasma from pts and controls were injected IP (0.5 mL) and infused, 0.2 ml prime and 1.8 mL at 0.01 mL/min, to Sprague Dawley rats anesthetized with Inactin. Renal transport of sodium (Na), lithium (Li) and potassium (K) was determined. There were higher mean +/- SEM for FENa, 0.59 +/- 0.07% vs 0.29 +/- 0.05%, P < 0.01, FELi, 36.6 +/- 1.9% vs 24.0 +/- 1.6%, P < 0.001 and K excretion rates, 1.69 +/- 0.13 vs 1.31 +/- 0.09 mumol/min, p < 0.02, in rats infused with plasma of pts as compared to controls, respectively. FENa decreased with increasing dilution of plasma of 2 pts with ICD. There was no difference in mean weight of rats, blood pressure, urine flow rate or insulin clearance between pts and controls. These data suggest that pts with ICD have a plasma factor(s) which decreases net Na, Li and K reabsorption.
Assuntos
Encefalopatias/metabolismo , Nefropatias/metabolismo , Natriuréticos/sangue , Sódio/metabolismo , Ácido Úrico/metabolismo , Adulto , Animais , Transporte Biológico , Encefalopatias/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Nefropatias/urina , Lítio/metabolismo , Masculino , Pessoa de Meia-Idade , Natriuréticos/metabolismo , Ratos , Sódio/urina , Ácido Úrico/urinaRESUMO
Effects of short-term (4-14 days) total parenteral nutrition on renal handling of water and electrolytes were studied retrospectively in 24 patients and prospectively in eight patients. There was 33% incidence of hyponatremia and significant reductions in serum creatinine (from 1.03 +/- 0.06 to 0.88 +/- 0.06 mg/dl, p less than 0.001), phosphorus (from 3.2 +/- 0.14 to 2.5 +/- 0.17 mg/dl, p less than 0.005) and uric acid (from 6.09 +/- 0.38 to 3.66 +/- 0.24 mg/dl, p less than 0.001) were observed. Hypouricemia correlated with increased fractional excretion of urate (r = 0.81, p less than 0.05). Hypophosphatemia was associated with increased tubular reabsorption of phosphate. Clearance studies in eight patients showed high urine flow rate (1.7 +/- 0.2 ml/min), osmolar clearance (3.2 +/- 0.7 ml/min), urinary nonelectrolyte, nonurea solute excretion (0.23 +/- 0.14 mmol/min), and negative free water clearance (TcH2O = 1.5 +/- 0.6 ml/min). These data suggest presence of compartmental shifts, expanded extracellular fluid volume, and possible direct effects on renal tubular transport functions during total parenteral nutrition.
Assuntos
Eletrólitos/urina , Rim/metabolismo , Nutrição Parenteral Total/efeitos adversos , Nutrição Parenteral/efeitos adversos , Equilíbrio Hidroeletrolítico , Idoso , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Creatinina/urina , Eletrólitos/sangue , Humanos , Hiponatremia/etiologia , Pessoa de Meia-Idade , Concentração Osmolar , Fosfatos/sangue , Estudos Prospectivos , Estudos Retrospectivos , Ácido Úrico/sangue , Ácido Úrico/urinaRESUMO
Hypouricemia in coexistence with hyponatremia often differentiates the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from most other causes of hyponatremia. We report clearance studies in 5 cases of hyponatremia and hypouricemia that were not due to SIADH. One had metastatic pancreatic carcinoma with ascites, edema, hypoalbuminemia and hypophosphatemia. Two had adenocarcinoma of the lung with metastasis to the brain in 1, 1 had disseminated cryptococcus and 1 had Hodgkin's disease. None received radiation or known nephrotoxins at least 4 months prior to study. None had serum creatinine greater than 106.1 mumol/l (1.2 mg/dl). Two had postural hypotension and hyponatremia that responded to saline therapy. Fluid restriction corrected the hyponatremia in all patients, but the hypouricemia, high fractional excretion (FE) of urate, and high urine sodium concentration persisted. In 2 patients studied, ADH was appropriately suppressed after volume repletion but there was a defect in free water clearance due to high renal solute excretion. In contrast to patients with SIADH who correct their defect in renal urate transport with correction of hyponatremia by water restriction, our patients appear to have a persistent renal urate transport defect and abnormality in sodium conservation. Elevated FE urate of greater than 10% after correction of hyponatremia can thus differentiate these patients from SIADH. The diametrically opposing goals of fluid therapy emphasize the importance of differentiating one group from the other.
Assuntos
Hiponatremia/diagnóstico , Síndrome de Secreção Inadequada de HAD/diagnóstico , Ácido Úrico/sangue , Xantina Oxidase/deficiência , Adulto , Diagnóstico Diferencial , Humanos , Síndrome de Secreção Inadequada de HAD/complicações , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sódio/metabolismo , Vasopressinas/metabolismoRESUMO
BACKGROUND: Accurate information on prevalence and status of blood pressure (BP) control in hemodialysis patients is lacking. Our Hemodialysis Quality Improvement Program, sought to determine: 1) The extent and control of hypertension (HTN), 2) whether Erythropoietin (EPO) dose or intradialytic fluid loss had any effect on BP and 3) a means to follow the severity of HTN. PATIENTS AND METHODS: The pre/post mid-week dialysis BP readings of 190 patients (64+/-14.1 years, 53% males, 77% whites) were evaluated over a 3 month period. HTN was defined as BP >150/90. Hypertension was further characterized according to whether the patients had normal or elevated pre-dialysis systolic, pre-dialysis diastolic, post-dialysis systolic or post-diastolic BP readings on more than 6 of the possible 13 recordings. The average EPO dose and weight loss during dialysis was correlated with BP. To better understand the extent of HTN, systolic and diastolic pressures were separately graded from 0 to 3 and a number designated as hypertension sensitivity index (HSI) was assigned to each patient. RESULTS: Of the 190 patients, 146 (76.8%) were hypertensive. 117 out of 146 hypertensive patients (80.1%) had persistent elevation of BP despite being on one or more antihypertensive medications. Most patients were on calcium channel blockers (39%) with 27% being on beta-blockers and 14% on Angiotensin converting enzyme inhibitors. There was no correlation between the number of medications used and the control of HTN. The dose of EPO also had no effect on the degree of HTN. 69.8% of all HTN was systolic. Of this, 64.7% was pre-dialysis and 35.3% post-dialysis. Multiple regression analysis demonstrated a significant correlation with loss of weight during dialysis and lowering of systolic BP (r = 0.33, p = 0.0001). The mean HSI for this population was 2.3+/-1.8. CONCLUSION: HTN was a frequent finding in our hemodialysis population and it was controlled in only 19.9% of hypertensive patients. Most of this HTN was pre-dialysis systolic. There was a significant correlation between fluid loss during dialysis and lowering of blood pressure. The use of the HSI has proven to be helpful in differentiating type and severity of HTN.
Assuntos
Eritropoetina/uso terapêutico , Hipertensão Renal/fisiopatologia , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Eritropoetina/farmacologia , Feminino , Humanos , Hipertensão Renal/tratamento farmacológico , Hipertensão Renal/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Redução de PesoAssuntos
Hiponatremia/metabolismo , Síndrome de Secreção Inadequada de HAD/metabolismo , Ácido Úrico/sangue , Humanos , Hiponatremia/diagnóstico , Hiponatremia/terapia , Síndrome de Secreção Inadequada de HAD/diagnóstico , Síndrome de Secreção Inadequada de HAD/terapia , Concentração Osmolar , Sódio/metabolismoRESUMO
One of the important components of successful anemia therapy in patients with end-stage renal disease (ESRD) treated with recombinant human erythropoietin is the maintenance of adequate available iron. To accomplish this task, iron status must be serially monitored and supplemental iron administered as required. Among nonuremic subjects, the body's iron supply is tightly conserved, and iron deficiency usually develops only when chronic blood loss occurs. In patients with ESRD, iron deficiency occurs more frequently, because of increased external losses of iron, decreased availability of the body's storage of iron, and perhaps a deficit in intestinal iron absorption. Detecting iron deficiency in these patients can be difficult because of the inaccuracy of available diagnostic tests. The goals of iron therapy in ESRD include the prevention of iron deficiency by chronically supplementing iron, and the prompt treatment of overt iron deficiency. Oral iron supplements are inexpensive and safe, but poor patient compliance and reduced intestinal absorption may limit their effectiveness. Intravenous iron supplements have a greater efficacy then oral iron, which must be weighed against the small risk of allergic reactions. We present strategies for using the various diagnostic tests and treatment modalities to effectively manage iron supply for predialysis, hemodialysis, and peritoneal dialysis patients.
Assuntos
Ferro/sangue , Falência Renal Crônica/sangue , Anemia Ferropriva/sangue , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/etiologia , Eritropoetina/uso terapêutico , Ferritinas/sangue , Humanos , Ferro/administração & dosagem , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Peritoneal , Proteínas Recombinantes , Diálise Renal , Transferrina/análiseRESUMO
Micropuncture and microinjection studies were performed in Sprague-Dawley rats 20 h after subcutaneous injection of buffered maleic acid (MA) or buffer alone in experimental and control rats, respectively. Collections were made from earliest and latest accessible portions of proximal tubule (PT). Lissamine green injections and microperfusion of PT demonstrated leakage of lissamine green from late PT sites in MA-treated rats, whereas inulin leakage occurred at a more distal site. Whole kidney GFR was 58% lower in MA-treated rats despite comparable single nephron GFR in PT of both groups. Microinjections of PT with [methoxy-3H]inulin resulted in injected inulin recovery from the contralateral kidney in MA-treated rats of 24.0 +/- 2.0 compared with 4.7 +/- 0.89% in controls, suggesting that tubular leakage of inulin accounted for the lower whole kidney GFR. Net sodium and phosphate transport in early PT was similar in both groups but was decreased in late PT segments in MA-treated rats. Sodium and phosphate excretion in final urine were, however, comparable in both groups. The significantly lower plasma phosphate concentration might account for the blunted phosphaturia in MA-treated rats. These studies demonstrate a segmental effect of MA on 1) tubular leakage to lissamine green from late PT and inulin beyond the late PT, and 2) decreased net sodium and phosphate transport in the PT.
Assuntos
Síndrome de Fanconi/metabolismo , Túbulos Renais/metabolismo , Maleatos/farmacologia , Fosfatos/metabolismo , Sódio/metabolismo , Animais , Taxa de Filtração Glomerular/efeitos dos fármacos , Inulina/metabolismo , Corantes Verde de Lissamina/metabolismo , Masculino , Permeabilidade , RatosRESUMO
Despite significant advances in our understanding or renal tubular cell function, the in vivo handling of E. coli by renal tubules has not been previously investigated. The present studies were, therefore, designed to study this aspect of nephron function. Live and dead E. coli and vehicle alone were microinjected into the proximal tubular lumen of a single nephron of rats, and the microinjected tubules were morphologically studied at one-half, two, four, and six hours after. The bacteria initially contacted the luminal cell membrane. The luminal cell membrane adjacent to the bacteria subsequently invaginated, and both live and dead E. coli eventually became internalized into the tubular epithelial cytoplasm. Since dead E. coli are unlikely to invade the cells, their intracytoplasmic localization is a result of tubular epithelial phagocytosis. Similar microinjections of dead E. coli together with rat erythrocytes revealed a preferential phagocytosis of dead E. coli. Examination of the microinjected nephron with dead E. coli 48 hours after also demonstrated a development of microscopic interstitial nephritis surrounding the microinjected tubule. In conclusion, the renal tubular epithelia of the proximal and distal segments of rat nephron have phagocytic potential for E. coli which are further capable of inducing an inflammatory reaction around the microinjected tubule.
Assuntos
Escherichia coli/imunologia , Túbulos Renais/imunologia , Fagocitose , Animais , Epitélio/imunologia , Epitélio/patologia , Eritrócitos/imunologia , Túbulos Renais/patologia , Túbulos Renais Distais/imunologia , Túbulos Renais Proximais/imunologia , Alça do Néfron/imunologia , Masculino , Ratos , Obstrução Ureteral/imunologia , Obstrução Ureteral/patologiaRESUMO
This paper describes a technique for identifying individual nephrons that have been subjected to micropuncture. The general location of the nephron is marked on the surface of the kidney by implanting two micropipette tips on opposite sides of it two or three tubule diameters away. The tubule itself is marked by the injection into the lumen of a tracer material, for purposes of this account, a suspension of E. coli. After perfusion fixation the kidneys are removed and a block of tissue containing the extrapapillary portion of the nephron is excised. This block is cut into thin slices parallel to the surface of the kidney; these are embedded in plastic for subsequent sectioning. On sectioning, the marker material makes the nephron in question readily discernible under the microscope. A major advantage of this technique is that it allows the tubule of interest to be located as much as 48 hours later.
Assuntos
Técnicas Histológicas , Néfrons/ultraestrutura , Animais , Escherichia coli , Microinjeções , RatosRESUMO
We present four cases of proximal calciphylaxis in end-stage renal disease patients treated with hemodialysis. All patients were diabetic and developed lesions in areas that had previously served as sites of insulin injection. We review the presentation, pathogenesis, pathology, prognosis, and treatment of this devastating condition. Finally, we hypothesize that subcutaneous injection of insulin may play a pathogenic role in the development of proximal calciphylaxis.
Assuntos
Calciofilaxia/etiologia , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/complicações , Diálise Renal , Abdome , Nefropatias Diabéticas/terapia , Feminino , Humanos , Injeções Subcutâneas/efeitos adversos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Coxa da PernaRESUMO
It has been observed that while most hypertensive hemodialysis patients normalize their blood pressure with volume removal, there is a population of hemodialysis patients whose hypertension is refractory to volume removal. Our hypothesis is that such patients are still volume overloaded posthemodialysis and are not at a "true" dry weight. This study used atrial natriuretic peptide (ANP) assays (as a marker of hydration status) to study this hypothesis. Three groups of patients were studied: normotensive hemodialysis patients (n = 12; group 1), hypertensive hemodialysis patients who consistently normalize their blood pressure with fluid removal (n = 12; group 2), and hypertensive hemodialysis patients whose hypertension is refractory to fluid removal (n = 9; group 3). Plasma ANP levels were measured before and after hemodialysis by radioimmunoassay after extraction on Sep-Pac (Penninsula Laboratories, Belmont). On the day of study the predialysis mean arterial pressures in the three groups were 94.9 +/- 1.9 mm Hg in the normotensive group, 119.5 +/- 2.7 mm Hg in the dialysis-sensitive hypertension group, and 134.4 +/- 3.8 mm Hg in the dialysis-refractory hypertension group (P < 0.05 for comparisons between all groups). Mean arterial pressure did not change predialysis and postdialysis in the normotensive group (94.9 +/- 1.9 mm Hg to 93.1 +/- 1.8 mm Hg, respectively; P = 0.24), decreased in the dialysis-sensitive hypertension group (119.5 +/- 2.7 mm Hg to 100.8 +/- 3.7 mm Hg, respectively; P < 0.0001), and did not change in the dialysis-refractory hypertension group (134.4 +/- 3.8 mm Hg to 133.8 +/- 2.9 mm Hg, respectively; P = 0.77). Predialysis and postdialysis serum ANP levels were, respectively, 235.8 +/- 27.7 pg/mL and 237.8 +/- 36.2 pg/mL (P = 0.92) in the normotensive group, 809.2 +/- 295.5 pg/mL and 161.1 +/- 48.6 pg/mL (P = 0.03) in the dialysis-sensitive hypertension group, and 1,728.3 +/- 309.9 pg/mL and 1,936.1 +/- 359.1 pg/mL (P = 0.22) in the dialysis-refractory hypertension group. Mean predialysis ANP levels were higher in the dialysis-refractory hypertension group than in the dialysis-sensitive hypertension group (1,728.3 +/- 309.9 pg/mL v 809 +/- 359.1 pg/mL; P = 0.048). Mean prehemodialysis ANP in all hypertensive patients (n = 21) was higher (1,203.1 +/- 232.9) than in the normotensive patients (235.8 +/- 27.7) (P = 0.004). In conclusion, our findings are consistent with a hypothesis that inadequate removal of excess volume during hemodialysis plays a major role in dialysis-refractory hypertension.