RESUMEN
BACKGROUND AND AIMS: Recently, the albuminocentric view of diabetic kidney disease (DKD) in type 2 diabetes (T2DM) has been changing. Therefore, the relationship between diabetic retinopathy (DR) and chronic kidney disease (CKD) has to be addressed according to this new clinical presentation of DKD. The aim of this study was to evaluate, in a real-world setting, the correlation DR-DKD in T2DM. METHODS AND RESULTS: A total of 2068 type 2 diabetic patients enrolled in a multicenter cross-sectional study were investigated. Albuminuric subjects were largely prevalent among subjects with DR (p = 0.019). In the whole study population, no difference in albumin excretion rate (AER) was observed between presence/absence of DR; instead, AER was significantly higher among patients with glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (CKD) (p = 0.009), above all in those with CKD and AER ≥0.03 g/24 h (p = 0.005). Multivariate analysis confirmed that eGFR (O.R. 0.976; 95% C.I.: 0.960-1.028; p < 0.001) and AER (O.R. 1.249; 95% C.I. 1.001-1.619; p = 0.004) were independently associated with DR and HDL-cholesterol (O.R.: 1.042; 95% C.I.: 1.011-1.120; p = 0.014). Additionally, among patients with eGFR <60 mL/min/1.73 m2 and albuminuria, both eGFR and AER significantly varied between those with/without DR (p = 0.012 and p = 0.005, respectively), and this finding was observed among only albuminuric patients. Analogous results were obtained considering DR classification. AER was significantly higher among subjects with either proliferative DR (PDR) or severe nonproliferative DR (NPDR), with regard to mild NPDR (0.498 and 0.938 g/die vs. 0.101 g/die; p < 0.001, respectively). Similar results were obtained in the specular subgroups. CONCLUSION: In T2DM with DKD, the AER seems to be related to the presence of DR. This association is confirmed above all in those with more severe DR.
Asunto(s)
Albuminuria/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Nefropatías Diabéticas/epidemiología , Retinopatía Diabética/epidemiología , Insuficiencia Renal Crónica/epidemiología , Anciano , Albuminuria/diagnóstico , Albuminuria/fisiopatología , Estudios Transversales , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/fisiopatología , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/fisiopatología , Femenino , Tasa de Filtración Glomerular , Humanos , Italia/epidemiología , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Eliminación Renal , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Factores de Riesgo , Índice de Severidad de la EnfermedadAsunto(s)
Endocrinología/normas , Hiponatremia/terapia , Oncología Médica/normas , Nefrología/normas , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Consenso , Endocrinología/métodos , Endocrinología/organización & administración , Humanos , Hiponatremia/diagnóstico , Hiponatremia/epidemiología , Hiponatremia/etiología , Italia , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/terapia , Oncología Médica/métodos , Oncología Médica/organización & administración , Nefrología/métodos , Nefrología/organización & administración , Neurología/métodos , Neurología/normas , Procedimientos Neuroquirúrgicos/métodos , Procedimientos Neuroquirúrgicos/normas , Prevalencia , Sociedades Médicas/organización & administración , Sociedades Médicas/normasRESUMEN
Dyslipidemia represents a common metabolic alteration in chronic kidney disease (CKD). Alterations can be different depending on the stage of the disease and the extent of proteinuria. Despite the high cardiovascular risk in patients with renal impairment, only a small percentage of patients receive adequate cholesterol-lowering therapy. The use of statins, inhibitors of the endogenous synthesis of cholesterol in patients with CKD, represents an efficient therapeutic instrument for reducing cardiovascular risk, at least in the early stage of the disease. Such evidence is currently lacking in dialysis, that is a setting where cardiovascular mortality is not consistently due to classical atherosclerosis. In addition to their efficacy, statins are proved as safe drugs with a high tolerability profile in CKD. In the case of intolerant patients, a new therapeutic perspective is represented by ezetimibe, inhibitor of intestinal absorption of cholesterol, whose effectiveness and tolerability allow its use throughout all stages of the renal disease.
Asunto(s)
Dislipidemias/tratamiento farmacológico , Dislipidemias/etiología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , HumanosRESUMEN
During hemodialysis, amino acids (AA) are lost in the ultrafiltrate with consequent modification of their plasma profile. The aim of this cross-sectional study was to evaluate intradialytic changes of plasma AA levels during a single session of hemodiafiltration with endogenous reinfusion (HFR) versus acetate-free biofiltration (AFB). 48 patients chronically treated with HFR or AFB were matched 1:1 for age, gender, Kt/V and diabetes. Blood samples were collected at the beginning and the end of dialysis. Baseline plasma levels (µmol/l) of total AA (3,176 ± 722), essential AA (889 ± 221), and branched chain AA (459 ± 140) levels in HFR were similar to those in AFB (3,399 ± 621, 938 ± 277, and 463 ± 71, respectively). Plasma intradialytic AA levels did not change in HFR, while in AFB there was a reduction by about 25%. In conclusion, as compared with AFB, HFR has a sparing effect on AA loss due to the lack of adsorption by cartridge and to their complete reinfusion in blood.
Asunto(s)
Aminoácidos/sangre , Hemodiafiltración , Diálisis Renal , Anciano , Estudios Transversales , Soluciones para Hemodiálisis/administración & dosificación , Humanos , Persona de Mediana EdadRESUMEN
HCV-related membranoproliferative glomerulonephritis is the most common cause of hepatitis C-associated renal disease. Its treatment is still under debate and based on scant experimental evidence. The recommended therapeutic strategy depends on the severity of the kidney disease. The first-line treatment for patients with mild to moderate clinical and histological kidney damage is antiviral therapy with pegylated interferon alpha and ribavirin for 48 weeks combined with symptomatic treatment (diuretics, angiotensin converting enzyme inhibitors and angiotensin receptor blockers). In case of severe renal involvement (nephrotic syndrome, nephritic syndrome and/or progressive renal failure, high activity score of glomerulonephritis on light microscopy), the initial treatment may consist of sequential administration of immunosuppressive therapies (plasmapheresis, corticosteroids and cyclophosphamide) and antiviral agents, although no definitive data are yet available from the literature. B-cell depleting agents such as rituximab may be an alternative to conventional therapy in refractory or intolerant patients. Large randomized and controlled clinical trials are needed to establish guidelines for the treatment of HCV-related cryoglobulinemic glomerulonephritis.
Asunto(s)
Crioglobulinemia/tratamiento farmacológico , Crioglobulinemia/virología , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/virología , Hepatitis C/complicaciones , Algoritmos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Antivirales/uso terapéutico , Humanos , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , RituximabRESUMEN
Resistant hypertension is defined as blood pressure that remains above the target of <140/90 mm Hg in the general population and <130/80 mm Hg in people with diabetes mellitus or chronic kidney disease (CKD) in spite of the use of at least three full-dose antihypertensive drugs including a diuretic, or as blood pressure that reaches the target by means of four or more drugs. Hypertension is a frequent complication in CKD and a determining factor in the progression of renal damage, especially in proteinuric and diabetic patients, as well as contributing to a high cardiovascular risk. Clinical practice guidelines recommend blood pressure levels below 130/80 mm Hg in all CKD patients, but the target is reached in only a small proportion (10-20%), both in nephrology and non-nephrology settings. The resistance to antihypertensive treatment may be considered one of the causes of the poor achievement of blood pressure targets in CKD patients.
Asunto(s)
Hipertensión/tratamiento farmacológico , Hipertensión/etiología , Enfermedades Renales/complicaciones , Enfermedad Crónica , Resistencia a Medicamentos , Humanos , Fallo Renal Crónico/complicacionesRESUMEN
In the last twenty years, erythropoiesis-stimulating agents (ESAs) have improved the management of renal anemia, with significant amelioration of quality of life in patients on hemodialysis. ESAs can be administered both intravenously and subcutaneously. In predialysis chronic kidney disease and in peritoneal dialysis, the administration route is necessarily subcutaneous. In hemodialysis the intravenous route was initially preferred because of the presence of ready vascular access for drug administration. Subsequent studies have demonstrated that the subcutaneous route allowed the achievement of optimal levels of hemoglobin with a reduction of mean administered dose, number of injections, and costs. A few years ago, the finding of a higher risk of pure red cell aplasia associated with subcutaneous administration of epoetin reopened the debate about the route of administration. We here review the studies on the preferable route of administration of epoetin and darbepoetin- alpha, in terms of efficacy and safety, and take a look at future perspectives.
Asunto(s)
Anemia/tratamiento farmacológico , Anemia/etiología , Hematínicos/administración & dosificación , Enfermedades Renales/complicaciones , Enfermedad Crónica , Humanos , Inyecciones Intravenosas , Inyecciones SubcutáneasRESUMEN
Low-protein diets were originally identified as a therapeutic tool to alleviate symptoms and signs of uremia. Their prescription, however, became common in the 1980s to reduce the rate of progression of chronic kidney disease. Since then, several studies of this nonpharmacological intervention have been published. In particular, the Modification of Diet in Renal Disease (MDRD) study, which is a cornerstone of the nephrology literature, was specifically aimed at verifying the effectiveness of low-protein diets; the results, however, were negative. Therefore, the diet issue progressively disappeared from scientific meetings and journals, and as a consequence also its use in clinical practice has diminished. The aim of this paper is to describe the state of the art of low-protein diets almost 15 years from the publication of the MDRD study.
Asunto(s)
Dieta con Restricción de Proteínas/estadística & datos numéricos , Enfermedades Renales/dietoterapia , Enfermedad Crónica , Dieta con Restricción de Proteínas/efectos adversos , Progresión de la Enfermedad , Humanos , Cooperación del PacienteRESUMEN
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a disorder of sodium and water balance characterized by hypotonic hyponatremia and impaired water excretion in the absence of renal insufficiency , adrenal insufficiency or any recognized stimulus for the antidiuretic hormone (ADH). An inappropriate increase in ADH release of any cause produces hyponatremia by interfering with urinary dilution, thereby preventing the excretion of ingested water. Despite being the most common cause of hyponatremia in hospitalized patients, SIADH remains a diagnosis of exclusion. SIADH should be suspected in any patient with hyponatremia, hyposmolarity, urine osmolality above 100 mosmol/hgH2O, urine sodium concentration usually above 40 mEq/L, and clinical euvolemia. a number of modalities can be used to correct hyponatremia in SIADH, with water restriction and salt administration being the most important. The rate of correction is dependent upon the degree of hyponatremia and the presence or absence of symptoms. Patients with severe neurological symptoms require prompt correction; however, excessively rapid correction should be avoided because it can lead to the late onset of neurological complications from osmotic demyelination.
Asunto(s)
Hiponatremia/etiología , Síndrome de Secreción Inadecuada de ADH/complicaciones , Anciano de 80 o más Años , Humanos , Hiponatremia/diagnóstico , Hiponatremia/terapia , Síndrome de Secreción Inadecuada de ADH/diagnóstico , Síndrome de Secreción Inadecuada de ADH/terapia , MasculinoRESUMEN
Nitric oxide (NO) has been proposed to modulate the renal response to protein as well as basal renal hemodynamics. We investigated whether NO and angiotensin II (AII) interact to control glomerular hemodynamics and absolute proximal tubular reabsorption (APR) during glycine infusion and in unstimulated conditions. In control rats, glycine increased single nephron GFR and plasma flow with no change in APR. The NO synthase blocker, NG-monomethyl L-arginine (LNMMA), abolished the vasodilatory response to glycine, possibly through activation of tubuloglomerular feedback due to a decrease in APR produced by LNMMA + glycine. Pretreatment with an AII receptor antagonist, DuP 753, normalized the response to glycine at both glomerular and tubular levels. In unstimulated conditions, LNMMA produced glomerular arteriolar vasoconstriction, decreased the glomerular ultrafiltration coefficient, and reduced single nephron GFR. These changes were associated with a striking decrease in APR. DuP 753 prevented both glomerular and tubular changes induced by LNMMA. In conclusion, NO represents a physiological antagonist of AII at both the glomerulus and tubule in both the basal state and during glycine infusion; and inhibition of NO apparently enhances or uncovers the inhibitory effect of AII on proximal reabsorption.
Asunto(s)
Angiotensina II/fisiología , Glomérulos Renales/efectos de los fármacos , Túbulos Renales/efectos de los fármacos , Óxido Nítrico/metabolismo , Animales , Arginina/análogos & derivados , Arginina/farmacología , Compuestos de Bifenilo/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Glicina/farmacología , Imidazoles/farmacología , Glomérulos Renales/fisiología , Túbulos Renales/fisiología , Losartán , Masculino , Ratas , Ratas Endogámicas , Saralasina/farmacología , Tetrazoles/farmacología , omega-N-MetilargininaRESUMEN
Glycine (G) infusion causes renal vasodilation mediated by nitric oxide (NO). Cyclosporine A (CsA) nephrotoxicity is characterized by preglomerular vasoconstriction and decreased efferent arteriolar tone probably related to reduced NO and angiotensin II, respectively. L-Arginine (ARG) is a precursor to NO. To test the hypothesis that chronic CsA decreases renal NO activity, we compared the glomerular hemodynamic response to glycine infusion in rats after 8 d of CsA (30 mg/kg per d s.c.), CsA and ARG (1.6 g/kg per d p.o.) (A/CsA), and in two groups of pair-fed controls (CON, A/CON). Single nephron GFR (SNGFR), single nephron plasma flow (SNPF), glomerular capillary hydrostatic pressure gradient (delta P), proximal tubular reabsorption (APR), and kidney tissue angiotensin II (AIIk) were measured before and during G. CsA was associated with baseline decrements in SNGFR, SNPF, delta P, and AIIk, and with a blunted hemodynamic response to G. In CON, ARG did not affect baseline hemodynamics or modify the response to G. In CsA, ARG decreased baseline preglomerular resistance and restored the glomerular hemodynamic response to G. G was associated with a significant increase in AIIk in both CON and CsA. These findings suggest that (a) CsA is associated with decreased AIIk, and (b) CsA may diminish NO activity within the kidney, and that this capacity may be partially restored by arginine feeding.
Asunto(s)
Arginina/farmacología , Ciclosporina/toxicidad , Riñón/efectos de los fármacos , Administración Oral , Angiotensina II/metabolismo , Animales , Arginina/administración & dosificación , Arginina/análogos & derivados , Capilares/efectos de los fármacos , Capilares/fisiología , Tasa de Filtración Glomerular/efectos de los fármacos , Presión Hidrostática , Riñón/patología , Riñón/fisiología , Glomérulos Renales/irrigación sanguínea , Masculino , Nefronas/irrigación sanguínea , Óxido Nítrico/metabolismo , Ratas , Ratas Wistar , Flujo Sanguíneo Regional/efectos de los fármacos , Resistencia Vascular/efectos de los fármacos , omega-N-MetilargininaRESUMEN
In chronic kidney disease, blood pressure control is a major aim of therapy to slow down renal disease progression and reduce the cardiovascular risk. Ambulatory blood pressure monitoring is a valid tool to define the prognosis and indicated therapy for hypertension. It allows to detect blood pressure patterns such as the white-coat effect, resulting in a better definition of the cardiovascular risk profile. Description of the circadian pressure rhythm, moreover, may reveal the presence of physiological nocturnal loss (dipping status). Recently, it has been demonstrated that a non-dipping status is associated with a higher risk of end-stage renal disease and more rapid progression of kidney disease independent of blood pressure control. Furthermore, longitudinal studies have demonstrated that a non-dipping status is associated with increased cardiovascular morbidity and mortality in the general population and in hypertensive patients. We have less information on this issue in chronic kidney disease. In this high-risk subgroup of hypertensive patients, it remains ill-defined whether ambulatory blood pressure monitoring predicts cardiovascular outcomes better than in-office measurement.
Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Fallo Renal Crónico/fisiopatología , Progresión de la Enfermedad , HumanosRESUMEN
Many patients affected by chronic kidney disease (CKD) die before reaching endstage renal disease because of cardiovascular disease (CVD). Recent guidelines and position statements have therefore defined CKD as a cardiovascular risk equivalent, and patients in all stages of CKD are considered in the highest risk group for development of CVD. Heart failure (HF) is the main cardiovascular complication that occurs in renal patients and its incidence increases proportionally with the reduction of glomerular filtration rate. In fact, pressure and volume overload, that are inherent to the abnormalities of homeostasis typical of CKD, lead to concentric/eccentric left ventricular hypertrophy (LVH). Initially, LVH is adaptative because energy is spared by maintaining stable wall stress. However, in the long term, LVH becomes maladaptative, inducing systolic and/or diastolic dysfunction that, in turn, lead to symptomatic left ventricular failure. Nowadays, it is well established that several classes of drugs, including reninangiotensin system antagonists, beta blockers and aldosterone antagonists, improve survival in patients with HF. In fact, all major guidelines on HF recommend such drugs as standard therapy. The problem for nephrologists is that the general approach and recommendations for the management of HF in the general population may not be completely safe in renal patients with HF. This review is conducted with the purpose to provide more information on the efficacy and safety of HF therapy in renal patients.
Asunto(s)
Insuficiencia Cardíaca/etiología , Fallo Renal Crónico/complicaciones , Antagonistas Adrenérgicos beta/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Humanos , Fallo Renal Crónico/epidemiología , Antagonistas de Receptores de MineralocorticoidesRESUMEN
The role of renal functional reserve (RFR; increase in plasma flow and glomerular filtration rate in response to protein loading) as an indicator of increased glomerular hydrostatic pressure and flow was evaluated in recent-onset poorly controlled diabetic rats. Streptozocin-induced diabetic (STZ-D) rats were studied with micropuncture (MP) technique after 10-15 days of diabetes (daily blood glucose level 15.3-18 mmol). We also studied STZ-D rats treated with the converting-enzyme inhibitor (CEI) enalapril or the angiotensin II (ANG II) receptor antagonist DuP 753 (DuP) for 3 days before MP. Nondiabetic rats (NOR) served as controls. Glomerular hemodynamics and proximal tubular reabsorption were measured in the control period and during intravenous glycine infusion. In NOR rats, glycine increased single-nephron plasma flow (SNPF) and single-nephron glomerular filtration rate (SNGFR). Although STZ-D rats did not exhibit hyperfiltration, SNGFR and SNPF were not modified by glycine, defining loss of RFR. CEI rats responded to glycine with an increase in SNGFR due to a rise in SNPF and a rise in the ultrafiltration coefficient. Interestingly, loss of RFR in STZ-D rats was associated with a decrease in absolute proximal reabsorption. The decrease in absolute proximal reabsorption was corrected by both CEI and DuP, although glomerular vasodilation was restored only in the CEI group. In conclusion, at the early stage of diabetes mellitus, loss of RFR does not detect hyperfiltration, but rather the presence of a tubular alteration probably dependent on ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Riñón/fisiopatología , Antagonistas de Receptores de Angiotensina , Animales , Compuestos de Bifenilo/farmacología , Enalapril/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Glicina/farmacología , Presión Hidrostática , Imidazoles/farmacología , Riñón/fisiología , Glomérulos Renales/fisiología , Glomérulos Renales/fisiopatología , Túbulos Renales/efectos de los fármacos , Túbulos Renales/fisiología , Túbulos Renales/fisiopatología , Losartán , Masculino , Nefronas/efectos de los fármacos , Nefronas/fisiología , Nefronas/fisiopatología , Ratas , Ratas Endogámicas , Valores de Referencia , Circulación Renal/efectos de los fármacos , Tetrazoles/farmacologíaRESUMEN
BACKGROUND: Guidelines have indicated the achievement of blood pressure target (BP <130/80 mmHg) as a priority in the conservative treatment of chronic kidney disease (CKD), but the current implementation of these recommendations in clinical practice is unknown. METHODS: We assessed control rates, treatment and clinical correlates of hypertension in 1201 adult non-dialyzed CKD patients followed up by a nephrologist for at least 6 months. RESULTS: Estimated glomerular filtration rate (GFR) was 32 (SD 15) mL/min/1.73 m2. BP target was not achieved in 88% of patients (95% confidence interval (95% CI): 86-90%). In 84% of patients, BP levels were also above the target at the first visit to the nephrology unit 4.5 yrs previously. The risk of not achieving BP target during the nephro-logy follow-up was associated with older age (odds ratio (OR): 1.24, 95% CI 1.06-1.45, p=0.008), diabetes (OR: 2.25, 95% CI 1.20-4.20, p=0.011), and the duration of hypertension (OR: 1.13, 95% CI 1.02-1.24, p=0.016). Among patients with uncontrolled BP, about 70% received multidrug antihypertensive therapy including renin-angiotensin system (RAS) inhibitors; conversely, diuretic treatment was prescribed in a minority of patients (37%), and at insufficient doses in half the cases, despite the insufficient implementation of a low salt diet (18%). CONCLUSIONS: BP target was not reached in most CKD patients routinely seen in the renal clinics. The main barrier to guideline implementation is possibly the inadequate treatment of extracellular volume expansion despite the large prevalence of factors, such as older age and diabetes, which further enhance the intrinsic BP salt sensitivity of CKD.
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Antihipertensivos/uso terapéutico , Diuréticos/uso terapéutico , Hipertensión/terapia , Fallo Renal Crónico/complicaciones , Anciano , Presión Sanguínea/fisiología , Dieta Hiposódica , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/fisiología , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Italia , Fallo Renal Crónico/fisiopatología , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
In the 1960s, about 10% of hemodialysis (HD) patients had hypertension; the current percentage of hypertensive patients has risen to 70-75%. The scarce implementation of low-salt diets and the increment of dialysate sodium concentration aimed at ameliorating treatment tolerability are the main causes of the currently poor hypertension control. Considerable sodium intake activates a vicious circle: an increase in serum osmolarity, greater thirst and greater water intake, high inter-dialytic weight gains, need for large ultrafiltration rates, more frequent episodes of intradialytic hypotension, failure to achieve dry weight, progressive extra-cellular volume (ECV) expansion, and finally, blood pressure (BP) increase. Therefore, many studies have pointed out the importance of a low-salt diet in HD; it has been proven that the normalization of BP and ECV overload with a low-salt diet is associated with left ventricular hypertrophy regression and diastolic dysfunction improvement. Preparing meals with fresh foods, using spices, avoiding salt when cooking, and drastically limiting salty foods reduce dietary sodium down to about 6 g/day. Sodium intake during inter-dialytic periods can easily be assessed by measuring the changes in serum sodium concentration and in body weight.
Asunto(s)
Hipertensión/etiología , Diálisis Renal , Sodio en la Dieta/efectos adversos , Uremia/complicaciones , Uremia/terapia , Dieta Hiposódica , Humanos , Hipertensión/dietoterapia , Hipertensión/prevención & controlRESUMEN
We have previously demonstrated that loss of renal functional reserve (renal response to protein loading) in two-kidney, one clip Goldblatt hypertension is characterized by no change in glomerular filtration rate or single nephron glomerular filtration rate and decreased absolute proximal tubular reabsorption during glycine administration. Captopril restores proximal reabsorption and renal functional reserve in this condition. Because captopril suppresses angiotensin II generation and increases bradykinin, prostaglandins, and potentially nitric oxide, we have investigated the role of angiotensin II blockade in restoring proximal reabsorption and renal functional reserve by comparing captopril with DuP 753, an angiotensin II receptor antagonist, in Goldblatt rats. One month after clipping, two period micropuncture studies (control and glycine) were performed on the unclipped kidney. Normal rats and three groups of clipped rats were studied: an untreated group (HYP), a group treated with captopril (CEI), and a group treated with DuP 753 (DuP) 5 days before micropuncture. Glycine increased glomerular filtration rate, nephron plasma flow, and single nephron glomerular filtration rate in normal rats. Systemic and glomerular hypertension in HYP rats was associated with loss of renal functional reserve and a decrease in absolute proximal reabsorption during glycine. Captopril and DuP 753 normalized systemic and glomerular capillary pressure and prevented the decrease in proximal reabsorption during glycine; however, only CEI rats increased single nephron glomerular filtration rate and glomerular filtration rate after glycine. In conclusion, abnormal responses of both glomerular and tubular function are responsible for the loss of renal functional reserve in Goldblatt rats. Inhibitory angiotensin II activity is responsible for decreasing proximal reabsorption during glycine; however, factors other than angiotensin II limit the glomerular response to glycine.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Angiotensina II/fisiología , Hipertensión Renovascular/fisiopatología , Riñón/fisiopatología , Animales , Antihipertensivos/farmacología , Compuestos de Bifenilo/farmacología , Captopril/farmacología , Glicina/farmacología , Hemodinámica/efectos de los fármacos , Imidazoles/farmacología , Inyecciones , Glomérulos Renales/irrigación sanguínea , Losartán , Masculino , Punciones , Ratas , Ratas Endogámicas , Tetrazoles/farmacologíaRESUMEN
Chromogranins A and B are major soluble proteins in chromaffin granules. Their adrenomedullary content is increased in the spontaneously (genetic) hypertensive rat. Is augmented catecholamine vesicular storage of the chromogranins a specific feature of genetic hypertension? To explore this question, we measured chromogranin A immunoreactivity, using a novel, synthetic peptide radioimmunoassay, in rat adrenal medullas 4-6 weeks after induction of the two-kidney, one clip Goldblatt model of renovascular hypertension and in unmanipulated control animals. We also measured messenger RNAs of chromogranins A and B and dopamine beta-hydroxylase by Northern blot. Immunoreactive adrenal chromogranin A was 3.3-fold higher (p < 0.01) in clipped rat adrenals. Adrenal catecholamine concentrations and phenylethanolamine-N-methyltransferase activity were also higher in clipped rats. Adrenal dopamine beta-hydroxylase activity (both membrane-bound and soluble forms) and corticosterone (glucocorticoid) concentration did not significantly differ between the groups. Adrenal medullary chromogranin A messenger RNA levels in clipped rats were 3.2-fold higher (p = 0.029) than those in the control group, and chromogranin B messenger RNA levels were 4.6-fold higher (p = 0.05). Dopamine beta-hydroxylase messenger RNA levels were 2.9-fold higher (p = 0.038). Thus, augmented synthesis and storage of adrenomedullary chromogranins A and B, catecholamines, and their biosynthetic enzymes appear to be characteristic of both acquired and genetic hypertension.
Asunto(s)
Aminas/metabolismo , Catecolaminas/metabolismo , Cromograninas/metabolismo , Hipertensión Renovascular/metabolismo , Médula Suprarrenal/metabolismo , Secuencia de Aminoácidos , Animales , Northern Blotting , Cromograninas/genética , Constricción , Dopamina beta-Hidroxilasa/metabolismo , Humanos , Masculino , Datos de Secuencia Molecular , Pruebas de Precipitina , ARN Mensajero/metabolismo , Radioinmunoensayo , Ratas , Ratas Endogámicas , Arteria RenalRESUMEN
The acute effects of cyclosporin (CsA, 20 mg(kg i.v.) and rapamycin (RAPA, 5 mg(kg i.v.) on glomerular dynamics were separately investigated by renal micropuncture in two groups of intact rats (group CsA and RAPA, respectively) and compared with vehicle-treated rats, used as controls (group CON). Left kidney glomerular filtration rate (GFR) was decreased by CSA (-35% vs. CON, P<0.05), but was not affected by RAPA (-14% vs. CON, NS), whereas the single-nephron GFR (SNGFR) was significantly decreased in both groups (-40% in CsA, P<0.01 and -26% in RAPA, P<0.05 vs. CON). In both groups glomerular plasma flow (GPF) was significantly reduced vs. CON (CsA: -48%, and RAPA: -25%) due to the increase in both afferent (Ra) and efferent (Re) glomerular resistances: group CSA showed a prevalent rise in Re (+98% vs. CON, P<0.001) than in Ra (+66%, P<0.001); in group RAPA the increment was modest and similar in Ra and Re (+33 and +32%, respectively, NS versus CON). A further group of rats was studied in which L-Arginine (ARG), the precursor of nitric oxide (NO), was administered (2.5 mg/Kg/min iv) with RAPA (group ARG). ARG limited the rise in Ra and Re, thereby preserving GPF; nevertheless, SNGFR remained low (-26% vs. CON, P<0.05) due to the decrease in the effective filtration pressure (-26% vs. CON). These data demonstrate that: (1) CsA is nephrotoxic at immunosuppressive doses; (2) RAPA, even at huge doses, has marginal effects on renal and glomerular dynamics; (3) the ARG-NO pathway is only partially involved in the vasoconstriction of superficial nephrons after RAPA administration.
Asunto(s)
Tasa de Filtración Glomerular/efectos de los fármacos , Inmunosupresores/toxicidad , Sirolimus/toxicidad , Animales , Arginina/farmacología , Ciclosporina/farmacología , Hemodinámica/efectos de los fármacos , Insulina/sangre , Masculino , Óxido Nítrico/fisiología , Punciones , RatasRESUMEN
Indications for renal biopsy are still ill defined. We recently sent a detailed questionnaire to 360 nephrologists in different areas of the world with the aim of providing information on this critical issue by evaluating the replies. The questionnaire was organized in four sections that included questions on renal biopsy indications in patients with normal renal function, renal insufficiency, and a transplanted kidney. In addition, the questions included methods applied to each renal biopsy procedure and to specimen processing. We received 166 replies; North Europe (50 replies), South Europe (47 replies), North America (31 replies), Australia and New Zealand (24 replies), and other countries (14 replies). In patients with normal renal function, primary indications for renal biopsy were microhematuria associated with proteinuria, particularly greater than 1 g/d of protein. In chronic renal insufficiency, kidney dimension was the major parameter considered before renal biopsy, whereas the presence of diabetes or serological abnormalities was not considered critical. In the course of acute renal failure (ARF) of unknown origin, 20% of the respondents would perform renal biopsy in the early stages, 26% after 1 week of nonrecovery, and 40% after 4 weeks. In a transplanted kidney, the majority of nephrologists would perform a renal biopsy in the case of graft failure after surgery, ARF after initial good function, slow progressive deterioration of renal function, and onset of nephrotic proteinuria. The last section provided comprehensive information on the technical aspects of renal biopsy. This survey represents the first attempt to provide a reliable consensus that can be used in developing guidelines on the use of kidney biopsy.