Sex-difference of multifactorial intervention on cardiovascular and mortality risk in DKD: post-hoc analysis of a randomised clinical trial.

OBJECTIVE: Women with type 2 diabetes experience higher cardiovascular and mortality risk than men possibly because of a sub-optimal cardio-protective treatment. We evaluated whether an intensive multifactorial therapy (MT) produces similar protective effect on development of adverse outcomes in women and men. RESEARCH DESIGN AND METHODS: Nephropathy in Diabetes type 2 study is an open-label cluster randomized trial comparing the effect of Usual Care (UC) or MT of main cardiovascular risk factors (blood pressure < 130/80 mmHg, HbA1c < 7%, LDL < 100 mg/dL, and total cholesterol < 175 mg/dL) on cardiovascular and mortality risk in patients with type 2 diabetes. In this post-hoc analysis, we stratified patients by sex to compare the occurrence of MACEs (primary endpoint) and all-cause death (secondary endpoint) between women (104 MT and 105 UC) and men (103 MT and 83 UC). RESULTS: Achievement of therapeutic goals was similar by sex, with 44% and 47% of women and men in MT achieving at least 3 targets vs. 16% and 20% of women and men in UC. During a median follow-up of 13.0 years, we recorded 262 MACE (48.5% in women) and 189 deaths (53.6% in women). Compared to the UC group, the risk of MACE in the MT group was reduced by 52% in women and by 44% in men (P = 0.11). Conversely, the reduction in mortality risk by MT was greater in women (44% versus 12%, P = 0.019). CONCLUSIONS: MT similarly reduces the risk of MACEs in either sex. This therapeutic approach is associated with a survival advantage in women as compared with men and it may represent an important rationale to motivate physicians in overcoming their therapeutic inertia often encountered in female patients as well as to encourage patients of both sexes at improving their adherence to multidrug therapy.

Relationship between albuminuric CKD and diabetic retinopathy in a real-world setting of type 2 diabetes: Findings from No blind study.

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.

Statins in patients with chronic kidney disease: new evidence.

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.

Intradialytic changes of plasma amino acid levels: effect of hemodiafiltration with endogenous reinfusion versus acetate-free biofiltration.

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.

[Treatment of HCV-associated cryoglobulinemic glomerulonephritis]. / Terapia della glomerulonefrite secondaria a crioglobulinemia HCV-correlata.

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.

[Resistant hypertension in non-dialysis chronic kidney disease]. / Ipertensione resistente nella malattia renale cronica non-dialitica.

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.

[Erythropoiesis-stimulating agents in chronic kidney disease: which route of administration?]. / Agenti stimolanti l'eritropoiesi nell'insufficienza renale cronica: quale via di somministrazione?

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.

[Hyponatremia secondary to inappropriate antidiuretic hormone secretion]. / Iposodiemia da inappropriata secrezione di ADH.

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.

[Diagnostic role of ambulatory blood pressure monitoring in non-dialysis CKD patients]. / Monitoraggio della pressione arteriosa per 24 ore: indicazioni e utilità nella IRC pre-dialitica.

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.

[Heart failure in chronic kidney disease: from epidemiology to therapy]. / Lo scompenso cardiaco nel paziente con insufficienza renale cronica: dall'epidemiologia alla terapia.

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.

Management of hypertension in chronic kidney disease: the Italian multicentric study.

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.

[Hypertension in patients on hemodialysis: the role of salt intake]. / L'ipertensione arteriosa nell'uremico in emodialisi: importanza dell'intake di sale.

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.

Effect of posture on sodium excretion and diuretic efficacy in nephrotic patients.

It is well known that posture affects natriuresis in cirrhosis and heart failure. This study evaluates the role of posture on spontaneous urinary salt excretion (U(Na)V) and diuretic-induced natriuresis in nephrotic patients with mild renal impairment. U(Na)V and plasma concentrations of the main hormones involved in sodium regulation were evaluated at baseline (Baseline) and after furosemide administration (20 mg intravenously at 8:00 AM [Diuretic]) in seven nephrotic patients with mild renal impairment (creatinine clearance, 68.5 +/- 7.6 mL/min) in either the supine or upright position for 6 hours (from 8:00 AM to 2:00 PM). At baseline, U(Na)V was greater in the supine than upright position (sodium, 51.8 +/- 6.2 versus 38.3 +/- 6.1 mEq/d; P: < 0.01). Similarly, furosemide was more effective in increasing U(Na)V in the supine (sodium, 51.8 +/- 6.2 to 87.4 +/- 9.1 mEq/d; P: < 0.005) than upright position (sodium, 38.3 +/- 6.1 to 59.0 +/- 6.8 mEq/d; P: = not significant). Consequently, body weight decreased in the supine but not the upright position (-0.73 +/- 0.15 versus -0.17 +/- 0.22 kg; P: < 0. 05). Peripheral renin activity (PRA) and plasma aldosterone (Aldo) concentrations were greater in the upright than supine position at both Baseline and Diuretic. A similar pattern was observed for hematocrit, used as an index of plasma volume. In addition, a positive correlation was detected between hematocrit and PRA (r = 0.89; P: < 0.001) in the upright position. Postural changes did not influence plasma concentrations of atrial natriuretic peptide. These data indicate that in nephrotic patients with mild impairment of glomerular filtration rate, the upright position causes a reduction in plasma volume; this hypovolemia activates the renin-Aldo system responsible for sodium retention in unstimulated conditions and a blunted natriuretic response to furosemide.

Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy.

Angiotensin-converting enzyme (ACE) inhibitors and AT1-receptor antagonists (ARAs) are widely administered to reduce urinary protein loss and slow the progression of proteinuric nephropathy to end-stage renal failure. Our group recently observed that the combination of ACE inhibitors and ARAs may have an additive antiproteinuric effect, which may occur because ACE inhibitors do not completely reduce angiotensin II (Ang II) production. Ang II is also produced by chymase. Thus, combination therapy better antagonizes the effects of Ang II. The purpose of this study is to ascertain whether the additive antiproteinuric effect of ACE inhibitors plus ARAs is dose dependent and related to the drug-induced reduction in systemic blood pressure. Therefore, enalapril (E; 10 mg/d) and losartan (LOS; 50 mg/d) were randomly administered alone and then in association; initial dosages were doubled when drugs were administered alone and in association. To determine the influence of the drug-dependent effect on reducing blood pressure and the reduction in urinary proteinuria, both ambulatory and office blood pressures were recorded. E and LOS administered alone reduced proteinuria by the same extent; no further reduction was observed when E and LOS alone were administered at a doubled dose. When E and LOS were coadministered, proteinuria decreased by a greater extent compared with E and LOS alone; an additional reduction in proteinuria was observed when combined therapy doses were doubled. The reduction in proteinuria was not correlated with clinical through blood pressure; however, reductions in diastolic and mean ambulatory blood pressures significantly correlated with the decrease in proteinuria, as well as with creatinine clearance. In conclusion, this study shows that combination therapy with E and LOS has an additive dose-dependent antiproteinuric effect that is likely induced by the drug-related reduction in systemic blood pressure. In normotensive proteinuric patients, it is likely that even a small reduction in systemic blood pressure may affect intraglomerular hemodynamics by a great extent because efferent arteriole regulation is hampered more completely by the coadministration of ACE inhibitors and ARAs.

Gross hematuria of uncommon origin: the nutcracker syndrome.

Left renal vein hypertension, also called "nutcracker phenomenon" or "nutcracker syndrome," is a rare vascular abnormality responsible for gross hematuria. The phenomenon is attributable to the idiopathic decrease in the angle between the aorta and the superior mesenteric artery with consequent compression of the left renal vein. The entrapment of the left renal vein is not easily detectable by ordinary diagnostic procedures. We report two cases of gross hematuria (persistent in one patient and recurrent in the other) caused by "nutcracker phenomenon." In both cases, no remarkable findings were obtained from medical history, urinary red blood cells morphology, repeated urinalysis, pyelography, cystoscopy, or ureteroscopy. Left renal vein dilation in one case was found with a computed tomography (CT) scan performed on the venous tree of left kidney. The diagnosis of "nutcracker phenomenon" was confirmed by renal venography with measurement of pressure gradient between left renal vein and inferior vena cava in both cases. In one case, the diagnosis was complicated by the presence of Mycobacterium tuberculosis in urine. The "nutcracker phenomenon" is probably more common than thought. Early diagnosis is important to avoid unnecessary diagnostic procedures and complications such as the thrombosis of the left renal vein. Many procedures are available to correct the compression of the left renal vein entrapped between the aorta and the superior mesenteric artery: Gortex graft vein interposition, nephropexy, stenting, and kidney autotransplantation. After surgery, gross hematuria ceases in almost all patients.

Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy.

We tested the hypothesis that the combination of converting enzyme inhibitor (CEI) with losartan (LOS) produces a more profound antiproteinuric effect than either drug alone in normotensive patients with immunoglobulin A (IgA) nephropathy. Eight normotensive (mean blood pressure, 88.9 +/- 2.1 mm Hg) patients with biopsy-proven IgA nephropathy, nonnephrotic proteinuria (protein, 1 to 3 g/d), and normal or slightly reduced creatinine clearance (range, 69 to 119 mL/min) were studied. Clinical evaluations and laboratory tests were performed (1) before CEI treatment (basal) and after (2) CEI alone (CEI, 12 weeks); (3) the combination of CEI and LOS, the latter at a dosage of 50 mg/d (CEI + LOS, 4 weeks); (4) LOS alone (LOS; 50 mg/d; 12 weeks); (5) the combination of LOS and CEI (LOS + CEI, 4 weeks, at the same dosage as CEI + LOS); and (6) a doubled dose of either CEI alone or LOS alone for 4 weeks. CEI and LOS as monotherapy significantly reduced proteinuria by 38% and 30%, respectively. No further reduction of proteinuria was achieved by doubling the dose of CEI or LOS. Both combinations induced a more remarkable reduction of proteinuria (73%; P < 0.05 v other periods) than either drug administered alone. The antiproteinuric effect of CEI or LOS and the more remarkable effect achieved with both combinations was not dependent on the reduction of blood pressure and/or creatinine clearance. In conclusion, this study provides first-time evidence that the combination of CEI and LOS in normotensive patients with IgA nephropathy produces a more profound decrease in proteinuria than either drug. This additive antiproteinuric effect is not dependent on changes in systemic blood pressure and creatinine clearance. Nevertheless, a larger controlled study is required to confirm this novel observation.

Endothelin-1 released by vascular smooth muscle cells enhances vascular responsiveness of rat mesenteric arterial bed exposed to high perfusion flow.

Vasodilation of resistance vessels ensues in response to increased perfusion flow to maintain tissue perfusion. The flow-induced vasodilation is mainly dependent on nitric oxide (NO), which also regulates vascular responsiveness to vasoconstrictors. Besides NO, however; high flow increases endothelin-1 (ET-1) production from endothelial cells. It is likely, therefore, that the interaction between NO and ET-1 may play a critical role in the control of arterial vascular tone under high perfusion flow. In this study, the vascular responsiveness (VR) to high flow rate and the role of ET-1 released by vascular smooth muscle cells (VSMC) were evaluated in isolated and in vitro-perfused mesenteric arteries (MA). MA were perfused at constant (3.5 mL/min; CPF) and increased flow rate (4.5, 5.5, 6.5 mL/min; IPF). VR was evaluated by infusing norepinephrine (NE; 5 micromol/L) and potassium chloride (KCl; 80 mmol/L). Mesenteric vascular resistance (MVR), ET-1, and cGMP release were measured under different flow rates. The role of endothelium-derived ET-1 was evaluated by perfusing MA with phosphoramidon (endothelin converting enzyme inhibitor), whereas the role of other endothelium-derived vasoactive substances was excluded by measuring VR in MA without endothelium. Finally, ETA and ETB receptor antagonists were perfused in disendothelized MA. In the IPF group of intact MA, MVR dropped (P<.05) and both ET-1 and cGMP increased in the perfusate (P<.05). VR was enhanced by high flow after NE (101+/-9 v. 56+/-12 mm Hg in CPF, P<.005) and KCl (119+/-12 v. 51+/-10 mm Hg in CPF, P<.005) and it was unaffected by either phosphoramidon or endothelium removal. On the contrary, BQ-610 abolished the flow-dependent increase in VR. No further additive effect was achieved with BQ-788. In conclusion, in MA, high flow reduces MVR and concurrently enhances VR, likely through VSMC-derived ET-1.

Physiologic role and diuretic efficacy of atrial natriuretic peptide in health and chronic renal disease.

In recent years, different clinical studies have provided new information on the pathophysiological role and diuretic effectiveness of atrial natriuretic peptide (ANP) in subjects with normal renal function and patients with chronic renal disease. Plasma ANP (pANP) was increased by infusion at the lowest doses ever tested in humans who were on low salt diet to the levels that the same subjects gained when on a normal salt diet; ANP accounted for at least 40% of the increase of natriuresis. Similarly, ANP appeared to be mainly involved in the physiological down-regulation of salt excretion (that is, during the shift from a normal to low-sodium diet). Interestingly, data have been also attained on the efficacy of ANP as diuretic agent when administered at a low nonhypotensive dosage in normals as well as CRF patients. Indeed, low-dose ANP promoted a marked increase of sodium excretion in CRF patients to the same levels observed in normals, likely because the renal patients exhibited a more marked pANP increment secondary to the lower renal catabolism of the infused hormone. Moreover, aldosterone suppression was greater in CRF patients with respect to normals. Furthermore, the fractional urinary excretion of cGMP increased more in CRF patients than in normals. Finally, ANP infusion augmented the urinary losses of the main solutes retained in CRF (urea, potassium, phosphorous) with a significant decrease in the plasma levels. Hence, ANP per se not only plays a significant role in the up- and down-regulation of sodium excretion in healthy state and chronic renal disease, but it may also be considered to be a powerful and unique diuretic agent in CRF at nonhypotensive dosages.

Atrial natriuretic factor in amniotic fluid and in maternal venous blood of pregnancies with fetal cardiac malformations and chromosomal abnormalities.

OBJECTIVE: We evaluated the levels of atrial natriuretic factor (ANF) in amniotic fluid and in maternal venous blood in pregnancies with fetal cardiac malformations and chromosomal abnormalities. METHOD: Between the 16th and 18th week of pregnancy, 151 women were divided into three groups. Group A included patients at lowest risk, carrying a fetus with a normally developing heart and normal karyotype (control group). Group B included women with a fetus suffering from cardiac malformations, with or without associated chromosomal abnormalities. Group C included women carrying a fetus affected with chromosomal abnormalities without congenital cardiopathies. ANF was evaluated by radioimmunoassay. RESULTS: In maternal venous blood, the mean levels of ANF were 42.1, 53.1 and 38.7 pg/ml in groups A, B and C, respectively. In amniotic fluid, the mean levels of ANF were 34.2, 101.8 and 35.8 pg/ml in groups A, B and C, respectively. In group A (control group) there was no statistical difference in ANF levels across the gestational age range of 16-18 weeks, either in amniotic fluid or in maternal venous blood. A significant difference of ANF content in maternal venous blood was revealed in comparing group A with group B (p < 0.01), and group C with group B (p < 0.01). A statistically significant difference in ANF levels was also found in amniotic fluid between group A and group B (p < 0.01), and between group C and group B (p < 0.01). No statistically significant differences were found between group C and group A in comparing ANF levels in maternal venous blood and amniotic fluid. CONCLUSION: ANF levels in amniotic fluid and in maternal venous blood are increased early in the case of fetuses with cardiac malformations, with or without associated karyotype alteration. Chromosomally abnormal fetuses without heart malformations have normal ANF levels. These results could be useful for elucidating fetal pathophysiology mechanisms.

[Daily nutrient intake in hemodialysis]. / Variabilità dell'introito giornaliero di nutrienti nei pazienti emodializzati.

BACKGROUND: Although there is a higher nutrient requirement, food intake in haemodialysis patients is often inadequate. Protein nitrogen appearance (PNA) indirectly estimates the mean protein intake during the short interdialysis period, but it does not measure the daily nutrient intake, which is generally unknown. We carried out a longitudinal study aimed at estimating the daily nutrient intake and its relationship with the nutritional status of haemodialysis patients. METHODS: We selected 28 haemodialysis patients with adequate nutritional status and no evidence of risk-factor for malnutrition. Patients were treated with biocompatible membranes, low-flux and high bicarbonate dialysis, Kt/V > 1.2, PNA > 1.1 g/kg/day and erythropoietin. We measured every four months daily PNA, protein and calorie intake (DPI, DCI) as well as weight gain (WG) during an entire week for one-year. The nutritional status was assessed by biochemical and BIA markers. RESULTS: Twenty seven subjects (8 F, 19 M; age 57.1 +- 2.7 yeas; dialysis age 105 +- 13 months) completed the trial. The mean interdialytic PNA did not change in both long- and short-interdialysis periods, resulting in the "normal" range (> 1.1 g/kg/day); however, daily levels of protein and calorie intake were significantly reduced on the third day during the long interdialysis interval. Eight patients showed time-averaged values of DPI and DCI lower than 0.8 g/kg/day and 25 Kcal/kg/day, respectively, on the third day (LOW group), values that were associated with similar changes in WG. Such a highly reduced nutrient intake during the third interdialysis day was associated with a normal PNA value (1.23 +- 0.05 g/kg/day vs 1.30 +- 0.06 in CON, NS) when measured during the short interdialysis period (S), just as it is in clinical practice; in contrast, when the PNA value was measured during the long interdialysis period it was found to be significantly reduced (1.07 +- 0.08 g/kg/day vs 1.37 +- 0.06 in CON, p < 0.05 and vs S, p < 0.05). During the study, the body weight progressively decreased from 68.0 +- 5.5 to 65.8 +- 5.9 kg (p < 0.05) in the LOW group, due to the decrease in lean body mass, as suggested by the reduction in serum creatinine (9.2 +- 1.1 vs 8.1 +- 0.7 mg/dL, p < 0.05), creatinine generation (835 +- 155 vs 723 +- 106 mg/die, p < 0.05) and serum albumin (3.96 +- 0.07 vs 3.66 +- 0.06 g/dL, p < 0.05). Moreover, reactance and phase angle declined in the LOW group (from 54 +- 4 to 44 +- 3 ohms, p < 0.05 and 5.5 +- 0.3 to 4.5 +- 0.3 degrees, p < 0.05, respectively). At the end of the study the nutritional status in the LOW group was reduced as compared to the CON group. CONCLUSIONS: In stable, well-nourished haemodialysis patients, in absence of known risk factors for malnutrition, the daily nutrient intake is variable and progressively reduce during the interdialytic interval. The measurement of interdialytic PNA, as is done in clinical practice, does not enable the discovery of such abnormal eating behaviour; the low daily nutrient intake, on the contrary, can be evidenced by the daily measurement of either PNA or weight gain, and it can also be inferred by the reduced PNA during the long interdialytic period. Finally, the persistent reduction in nutrient intake below the threshold of 0.8 g/kg/day of proteins and 25 Kcal/kg/day one day a week, is capable of inducing body protein wasting and moderate impairment of the nutritional status.