RESUMO
Ureteral obstruction affects the kidney's ability to conserve water and sodium. Using the isolated perfused tubule technique, we studied cortical collecting tubules (CCT) taken from rabbits subjected to a sham operation or to 4 h of unilateral ureteral obstruction (UUO). Tubules were perfused in the presence of an osmotic gradient directed to promote water movement from lumen to bath, and volume flux (Jv), hydraulic water permeability (Lp), and transepithelial voltage (V1) were determined. In tubules from sham-operated and UUO animals, basal (before exposure to vasopressin) J, and Lp were not different from zero. After addition of 200 microU . ml-1 of arginine vasopressin (aVP) to the bath, Jv and Lp increased to 1.64 +/- 0.23 nl . mm-1 . min-1 and 127.9 +/- 19.8 cm . s-1 . atm-1 x 10(7), respectively, in tubules from sham-operated animals, but not only 0.27 +/- 0.09 nl . mm-1 . min-1 an 18.8 +/- 6.2 cm . s-1 . atm-1 . 10(7) in tubules from UUO animals. Pretreatment with desoxycorticosterone acetate (DOCA) or indomethacin in vivo did not prevent the blunted vasopressin response seen in tubules taken from UUO animals. The Jv and Lp responses to the cyclic AMP (cAMP) analogue, 8-Br-cAMP, were also diminished in tubules taken from UUO animals compared with shams. V1, measured during the basal period, was diminished in tubules from UUO kidneys (-5.0 +/- 2.1 mV) compared with shams (-21.9 +/- 4.1 mV), and pretreatment with DOCA did no prevent the effects of UUO on V1. In contrast, tubules taken from animals that received indomethacin prior to UUO developed voltages not different from voltages in tubules taken from sham-operated animals (-17.3 +/- 1.7 mV). We conclude that, although CCT from UUO animals can maintain osmotic gradients, their ability to respond to vasopressin by increasing Lp is impaired by an intrinsic defect located at a step beyond the generation of cAMP, and that prostaglandin inhibition or DOCA pretreatment do not reverse the decreased responsiveness of Lp to aVP. UUO also diminished V1, and this abnormality was prevented by previous treatment with indomethacin, suggesting that prostaglandins may mediate the effect of UUO on V1.
Assuntos
Túbulos Renais Coletores/fisiopatologia , Túbulos Renais/fisiopatologia , Obstrução Ureteral/fisiopatologia , Corticosteroides/farmacologia , Animais , Bucladesina/farmacologia , Condutividade Elétrica , Feminino , Pressão Osmótica , Prostaglandinas/farmacologia , Prostaglandinas/fisiologia , Coelhos , Vasopressinas/antagonistas & inibidores , Vasopressinas/farmacologia , Equilíbrio HidroeletrolíticoRESUMO
Arginine vasopressin (AVP) has been shown to stimulate prostaglandin (PG) production in renal medulla, while PGs have been implicated in the suppression of the antidiuretic activity of AVP. These findings have suggested a local negative feedback system involving PGs in the modulation of the antidiuretic activity of AVP. However, coupling of the antidiuretic activity of AVP to its action to increase medullary PG production is not established. In the present study of rat inner medullary slices, we concurrently examined in the same incubate the relationship between the actions of AVP to increase media immunoreactive PGE (iPGE) and tissue cAMP, the presumed first biochemical step in expression of the antidiuretic activity of the hormone. The synthetic AVP analogue [1, d(CH2)5Tyr(Me)AVP], which selectively blocks the pressor but not the antidiuretic activity of AVP, abolished the action of AVP to increase media iPGE in inner medullary incubates but did not alter AVP induced increases in tissue cAMP in slices from the same incubates. By contrast, the analogue [d(CH2)5Tyr(Et)VAVP], which blocks both the pressor and antidiuretic activity of AVP, inhibited both the cAMP and iPGE responses to AVP. The analogue 1-deamino-8-D-AVP (dD'AVP), which has potent antidiuretic activity but little if any pressor activity, markedly stimulated inner medullary cAMP accumulation without altering media iPGE. These results indicate that the acute actions of AVP to increase inner medullary cAMP and iPGE are separable and independent. The latter effect of AVP appears to be linked to the pressor rather than the antidiuretic activity of the hormone.U
Assuntos
Arginina Vasopressina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , AMP Cíclico/biossíntese , Medula Renal/metabolismo , Prostaglandinas E/biossíntese , Animais , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/antagonistas & inibidores , Feminino , Técnicas In Vitro , Medula Renal/efeitos dos fármacos , Ratos , Ratos EndogâmicosRESUMO
In this study we measured indices of T-lymphocyte activation in normal volunteers, chronic hemodialysis patients, CAPD patients and chronic renal failure patients not yet on dialysis. Serum IL-2 levels were elevated in patients compared to controls. Soluble IL-2 receptors were elevated in all three patient groups and were highest in CAPD patients. Clearance of IL-2 and soluble interleukin receptors was negligible in dialysis and renal failure patients. Hemodialysis patients had a significantly lower percentage of CD3-positive cells than all other groups. Hemodialysis with a variety of membrane/bath combinations did not significantly affect any of the parameters measured. This study provides some support for the hypothesis that chronic T-cell activation is present in renal failure.
Assuntos
Falência Renal Crônica/imunologia , Diálise Peritoneal Ambulatorial Contínua , Diálise Renal , Linfócitos T/imunologia , Adulto , Idoso , Análise de Variância , Anticorpos Monoclonais , Humanos , Interleucina-2/sangue , Falência Renal Crônica/terapia , Ativação Linfocitária , Pessoa de Meia-Idade , Receptores de Interleucina-2/análiseRESUMO
The purpose of this study was to evaluate the effects of oral base therapy on selected chemical parameters in chronic hemodialysis patients. Oral base supplements were administered to 20 acidotic chronic hemodialysis patients for one month. Serum bicarbonate levels rose from 18.6 +/- 2.9 to 22.5 +/- 4.0 mEq/L (p less than 0.0005) and pH rose from 7.35 +/- 0.03 to 7.39 +/- 0.04 (p less than 0.0005). Serum ionized calcium levels fell from 5.03 +/- 0.37 to 4.83 +/- 0.34 mg/dL (1.25 +/- 0.09 to 1.21 +/- 0.08 mmol/L) (p less than 0.01), while intact parathyroid hormone (PTH) levels rose from 547 +/- 697 to 619 +/- 776 pg/mL (p less than 0.05). Base therapy did not result in significant changes in serum levels of total calcium, phosphorus, alkaline phosphatase, urea nitrogen, creatinine, total protein, albumin or potassium. If empiric therapy with exogenous base is given to dialysis patients, ionized calcium levels should be closely monitored since changes in calcium supplement or vitamin D therapy may be required to maintain ionized calcium and parathyroid hormone values at the pre-treatment levels.
Assuntos
Acidose/tratamento farmacológico , Antiácidos/uso terapêutico , Cálcio/sangue , Hormônio Paratireóideo/sangue , Fósforo/sangue , Diálise Renal , Bicarbonatos/uso terapêutico , Citratos/uso terapêutico , Ácido Cítrico , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Sódio/uso terapêutico , Bicarbonato de SódioRESUMO
Atrial natriuretic peptide (ANP) is a hormone liberated from the heart during atrial stretch (volume overload). In order to determine if ANP levels are altered in patients on continuous ambulatory peritoneal dialysis (CAPD) or affected by the dialysis procedure itself, we measured plasma ANP in patients before and after peritoneal infusion of two liters of 1.5% Dianeal dialysate and in dialysate subsequently drained from these patients. Plasma ANP is elevated in CAPD patients, but is not affected by infusion of dialysate. ANP is cleared from plasma by peritoneal dialysis.
Assuntos
Fator Natriurético Atrial/sangue , Diálise Peritoneal Ambulatorial Contínua , Adulto , Idoso , Fator Natriurético Atrial/análise , Soluções para Diálise/análise , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Diálise RenalRESUMO
Phenazopyridine is a commonly used urinary tract analgesic. As illustrated by the case we have reported, its use may be complicated by the development of methemoglobinemia and hemolytic anemia, especially in patients with renal insufficiency.
Assuntos
Aminopiridinas/efeitos adversos , Anemia Hemolítica/induzido quimicamente , Falência Renal Crônica/terapia , Metemoglobinemia/induzido quimicamente , Fenazopiridina/efeitos adversos , Doença Aguda , Adulto , Hemólise/efeitos dos fármacos , Humanos , Masculino , Metemoglobinemia/tratamento farmacológico , Azul de Metileno/uso terapêuticoRESUMO
A 55-year-old man on chronic hemodialysis underwent a transurethral resection of the prostate (TURP), during which 3% sorbitol solution was used for urethral irrigation. Following the procedure, he developed symptomatic hyponatremia (serum sodium, 106 mEq/L), but had only mild hypoosmolality (serum osmolality, 269 mosm/kg). The "osmolal gap" was 47 mosm/kg, probably from sorbitol absorbed systemically during the TURP. Hemodialysis raised the serum sodium to 118 mEq/L, and the serum osmolality to 284 mosm/kg, while lowering the osmolal gap to 26 mosm/kg. The presence of severe hyponatremia with only modest hypoosmolality may occur in patients with renal failure following the systemic absorption of hypotonic fluids containing solutes such as sorbitol and mannitol. Hemodialysis offers the advantages of correcting the hyponatremia while removing the unmeasured solute, thus preventing rapid increases in the serum osmolality.
Assuntos
Hiponatremia/etiologia , Falência Renal Crônica/complicações , Prostatectomia/efeitos adversos , Hiperplasia Prostática/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Hiperplasia Prostática/cirurgia , Diálise Renal , Irrigação Terapêutica/efeitos adversosRESUMO
Atrial natriuretic peptide (ANP) is released from the cardiac atria in response to acute volume loads; when infused acutely ANP causes diuresis and natriuresis. Cyclic GMP (cGMP) appears to be the second messenger for ANP in the kidney. The role that ANP plays in the long-term regulation of salt and water balance is unclear, however, since resistance to ANP's natriuretic and diuretic activity develops during prolonged administration. The purpose of the present study is to examine the relationship between the rate of cGMP excretion in response to ANP and the development of resistance to ANP's diuretic and natriuretic activity. Following a 30-min baseline period of infusion of Ringer's solution conscious rats received ANP at 15 micrograms/kg/hr (n = 6) or Ringer's alone (n = 5) for 240 min. ANP-infused rats had a significant diuresis and natriuresis during the first hour of infusion; urinary cGMP excretion also increased compared to baseline. By 120 min after initiating the infusion in ANP-rats urinary volume and sodium excretion had declined to values not significantly different from those of baseline or control. In contrast, urinary cGMP excretion remained elevated for the duration of the ANP infusion, whether compared to baseline values or the control group. Resistance to the diuretic and natriuretic activity of ANP is not a result of mechanisms that involve cGMP generation.
Assuntos
Fator Natriurético Atrial/administração & dosagem , GMP Cíclico/urina , Sódio/urina , Micção/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hematócrito , Infusões Intravenosas , Ratos , Ratos Endogâmicos , Circulação Renal/efeitos dos fármacosRESUMO
We measured fluoride flux (JF; pmol.min-1.mm-1) in the isolated rabbit cortical collecting duct (CCD) to investigate the determining factors of JF. The perfusate contained 100 microM fluoride and the bath was fluoride-free. Osmotically-induced lumen-to-bath water flux did not affect JF. When perfusate pH was reduced from 7.4 to 6.1 and from 6.1 to 5.0, JF increased from 0.008 +/- 0.002 to 0.027 +/- 0.007 (P less than 0.01) and from 0.018 +/- 0.003 to 0.040 +/- 0.005 (P less than 0.01), respectively. Acetazolamide at 10(-4) M in the bath reduced JF slightly though not statistically. The anion-transport inhibitor, 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS), at 10(-4) M in the perfusate did not affect JF. Substitution of luminal chloride with gluconate failed to affect JF in tubules from normal rabbits or from rabbits treated with deoxycorticosterone which stimulates chloride-bicarbonate exchange in the CCD. JF showed no correlation with transepithelial voltage which ranged from +4 to -104 mV. We conclude that the luminal pH represents the primary determining factor influencing JF in the rabbit CCD, and fluoride does not use a chloride-mediated or a DIDS-inhibitory transport pathway.
Assuntos
Fluoretos/metabolismo , Túbulos Renais Coletores/metabolismo , Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/análogos & derivados , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/farmacologia , Acetazolamida/farmacologia , Animais , Cloretos/farmacologia , Eletrofisiologia , Epitélio/metabolismo , Epitélio/fisiologia , Fluoretos/farmacologia , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Córtex Renal , Túbulos Renais Coletores/fisiologia , CoelhosRESUMO
The effects of fluid intake on basal and vasopressin-responsive urinary PGE excretion (UPGEV) were examined in conscious rats under conditions of 1) ad libitum water intake, 2) water deprivation, and 3) water diuresis induced by ad libitum intake of 5% dextrose in water. UPGEV fell progressively during 40 h of water deprivation. Water diuresis after water deprivation increased UPGEV transiently (8 h). Vasopressin (Pitressin tannate in oil, 5 U/kg subcutaneously) increased UPGEV and decreased urine volume (V) in rats on ad libitum water intake but did not alter UPGEV during water deprivation. Indomethacin suppressed UPGEV (70-90%), increased basal urine osmolality (Uosmol), and potentiated the antidiuretic response to Pitressin in rats on ad libitum water intake. Indomethacin accelerated by 8 h the onset of maximal antidiuresis in water-deprived rats but did not significantly alter water balance. During water diuresis, UPGEV declined in the first 8 h after Pitressin. Thereafter, UPGEV increased markedly, concurrent with early vasopressin escape. Indomethacin or meclofenamate inhibited the rise in UPGEV, the decline in Uosmol, and the increase in V of the escape phase. Indomethacin or meclofenamate also impaired the excretion of an acute water load (5% body wt) given during escape. The spontaneous decline in UPGEV during hydropenia may serve to maximize physiologic antidiuresis. Conversely, the marked increase in UPGEV induced by administration of vasopressin during water diuresis may serve to suppress the antidiuretic response and thus play a role in the mediation of escape from physiologically inappropriate antidiuresis.
Assuntos
Prostaglandinas E/urina , Vasopressinas/farmacologia , Animais , Arginina Vasopressina , Diurese , Feminino , Indometacina/farmacologia , Cinética , Ácido Meclofenâmico/farmacologia , Concentração Osmolar , Ratos , Ratos Endogâmicos , Urina , Privação de ÁguaRESUMO
Six patients with the intermediate form of cystinosis are described. Two have new mutations not previously described. The disease occurs due either to the combination of one mild mutation and one which is known to cause nephropathic cystinosis or to homozygosity for a predicted mild mutation. Partial phenotypic correction of cystinotic fibroblasts by transfection with normal cDNA or a cDNA derived from a mutation causing intermediate cystinosis is demonstrated.