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.

[Guidelines: general principles and clinical application in nephrology]. / Linee guida: principi generali ed applicazione nella clinica nefrologica.

Clinical practice guidelines (GL) are multiplying and spreading throughout the scientific world. Nephrology is no exception and GL are more often recalled in the daily activity. Therefore, it can be useful to propose an excursus on the issue, to report the most important principles on the base of GL and moreover, to remember that GL are the synthesis between the scientific evidences published in literature and the critical analysis performed by an international committee of experts. Not all GL have the same clinical value. As a matter of fact, GL have a different strength of recommendation and grading according to the clinical evidences published. The number and methodological accuracy of the available studies on a specific subject are crucial to define the quality, the grading and the strength of GL. GL must also be shared with a wide number of specialists and other interested people such as patient organizations as well as health political institutions. Although the knowledge of GL is widespread, their practical use is still limited. The spreading of the knowledge regarding how GL are arranged, their appropriate reading about procedures and/or treatments to be done or not, it will convert GL into a reliable tool for daily clinical practice. Therefore it is not a confused and incomprehensible set of rules imposed by some scientific organizations.

[Hemodiafiltration with endogenous reinfusion in chronic inflammation: a possible therapeutic alternative?]. / L'impiego dell' Emodiafiltrazione con reinfusione endogena (HFR) nell'infiammazione cronica idiopatica: una possibile alternativa terapeutica?

The patients under maintenance haemodialysis (HD) continue to have an unacceptably excess of mortality compared to general population, that may be explained by high prevalence of inflammation that significantly influences the survival of these patients. Indeed, chronic inflammation is very common in HD and it may cause malnutrition and progression of atherosclerotic disease by several pathogenetic mechanisms triggered by pro-inflammatory cytokines. Currently no pharmacological intervention is specifically targeted the idiopathic chronic inflammation. Hemodiafiltration with endogenous reinfusion (HFR) is a dialysis technique, highly biocompatible, that combines three depurative mechanisms: diffusion, convection and absorption. The ultrafiltrate is obtained from convective section of dialyzer (convection). It is regenerated by passing through the adsorbent macro-porous synthetic resin cartridge (absorption) and then it is reinfused into the second section of the filter (diffusion). This resin cartridge is able to absorb cytokines and other uremic toxins, whereas allows to pass nutrients and antioxidants, as amino acids and vitamins, with a consequent decrement of inflammation and oxidative stress. These characteristics suggest the use of HFR in HD patients affected by overt and idiopathic chronic inflammation. In these patients, we observed that the switching from Bic-HD to HFR allowed an improvement of inflammatory as testified by a significant decrement of serum levels of CRP IL-6, IL-1 and TNF- and a significant increase of albumin and pre-albumin. Whether these favorable effects may modify the outcomes of these high-risk patients, needs to be confirmed by studies ad-hoc.

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.

Very low protein diet supplemented with ketoanalogs improves blood pressure control in chronic kidney disease.

Blood pressure (BP) is hardly controlled in chronic kidney disease (CKD). We compared the effect of very low protein diet (VLPD) supplemented with ketoanalogs of essential amino acids (0.35 g/kg/day), low protein diet (LPD, 0.60 g/kg/day), and free diet (FD) on BP in patients with CKD stages 4 and 5. Vegetable proteins were higher in VLPD (66%) than in LPD (48%). LPD was prescribed to 110 consecutive patients; after run-in, they were invited to start VLPD. Thirty subjects accepted; 57 decided to continue LPD; 23 refused either diet (FD group). At baseline, protein intake (g/kg/day) was 0.79+/-0.09 in VLPD, 0.78+/-0.11 in LPD, and 1.11+/-0.18 in FD (P<0.0001). After 6 months, protein intake was lower in VLPD than LPD and FD (0.54+/-0.11, 0.78+/-0.10, and 1.04+/-0.21 g/kg/day, respectively; P<0.0001). BP diminished only in VLPD, from 143+/-19/84+/-10 to 128+/-16/78+/-7 mm Hg (P<0.0001), despite reduction of antihypertensive drugs (from 2.6+/-1.1 to 1.8+/-1.2; P<0.001). Urinary urea excretion directly correlated with urinary sodium excretion, which diminished in VLPD (from 181+/-32 to 131+/-36 mEq/day; P<0.001). At multiple regression analysis (R2=0.270, P<0.0001), BP results independently related to urinary sodium excretion (P=0.023) and VLPD prescription (P=0.003), but not to the level of protein intake. Thus, in moderate to advanced CKD, VLPD has an antihypertensive effect likely due to reduction of salt intake, type of proteins, and ketoanalogs supplementation, independent of actual protein intake.

Mesangial hypercellularity predicts antiproteinuric response to dual blockade of RAS in primary glomerulonephritis.

The greater antiproteinuric efficacy of converting enzyme inhibitor and angiotensin II receptor blocker combination (CEI+ARB), versus monotherapy with either drug, is not a consistent finding. We evaluated the clinicopathologic predictors of response to CEI+ARB in 43 patients with primary glomerulonephritis (GN), never treated with immunosuppressive drugs, and with persistent proteinuria after CEI alone. Main histological lesions were analyzed by obtaining on 557 glomeruli and 165 arteries formal score of mesangial cellularity, glomerulosclerosis, tubulointerstitial damage, mononuclear cell infiltration, arteriosclerosis, and arteriolar hyalinosis. Duration of CEI and CEI+ARB therapy was similar (4.7+/-2.4 and 5.0+/-1.5 months). Proteinuria (g/day) decreased from 3.5+/-2.9 to 2.4+/-2.3 after CEI, and to 1.5+/-1.3 after CEI+ARB (P<0.0001). Reduction of proteinuria after CEI+ARB was greater in proliferative versus non-proliferative GN (-63.3+/-23.4 versus 42.4+/-23.7%, respectively; P=0.006). When patients were categorized in responders and non-responders to CEI+ARB, no difference between the two groups was detected in any demographic or clinical variable, whereas histology showed in responders a greater prevalence of proliferative GN (71.4 versus 31.8%, P=0.009) and higher score of mesangial cellularity (1.76+/-0.53 versus 1.20+/-0.22, P<0.0001). At multiple regression analysis (r(2)=0.476, P=0.001), response to CEI+ARB resulted independently related only to mesangial cellularity (P<0.0001). In conclusion, the best independent predictor of antiproteinuric efficacy of CEI+ARB in patients with primary GN is the degree of mesangial cellularity. This finding supports the experimental evidence that high angiotensin II contributes to proliferation of mesangial cells.

Global approach to cardiovascular risk in chronic kidney disease: reality and opportunities for intervention.

The current implementation into nephrology clinical practice of guidelines on treatment of cardiovascular (CV) risk factors in chronic kidney disease (CKD) is unknown. We designed a cross-sectional analysis to evaluate the prevalence and treatment of eight modifiable CV risk factors in 1058 predialysis CKD patients (stage 3: n=486; stage 4: n=430, stage 5: n=142) followed for at least 1 year in 26 Italian renal clinics. The median nephrology follow-up was 37 months (range: 12-391 months). From stages 3 to 5, hypertension was the main complication (89, 87, and 87%), whereas smoking, high calcium-phosphate product and malnutrition were uncommon. The prevalence of proteinuria (25, 38, and 58%), anemia (16, 32, and 51%) and left ventricular hypertrophy (51, 55, and 64%) significantly increased, while hypercholesterolemia was less frequent in stage 5 (49%) than in stages 4 and 3 (59%). The vast majority of patients received multidrug antihypertensive therapy including inhibitors of renin-angiotensin system; conversely, diuretic treatment was consistently inadequate for both frequency and dose despite scarce implementation of low salt diet (19%). Statins were not prescribed in most hypercholesterolemics (78%), and epoietin treatment was largely overlooked in anemics (78%). The adjusted risk for having a higher number of uncontrolled risk factors rose in the presence of diabetes (odds ratio 1.29, 95% confidence interval 1.00-1.66), history of CV disease (odds ratio 1.48, 95% confidence interval 1.15-1.90) and CKD stages 4 and 5 (odds ratio 1.75, 95% confidence interval 1.37-2.22 and odds ratio 2.85, 95% confidence interval 2.01-4.04, respectively). In the tertiary care of CKD, treatment of hypertension is largely inadequate, whereas therapy of anemia and dyslipidemia is frequently omitted. The risk of not achieving therapeutic targets is higher in patients with diabetes, CV disease and more advanced 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.

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.

[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.

[Acute and chronic effects of standard hemodialysis and soft hemodiafiltration on interdialytic serum phosphate levels]. / Effetti acuti e cronici della emodialisi standard e dell'emodiafiltrazione-soft sui livelli interdialitici della fosforemia.

INTRODUCTION: The dialytic management of hyper-phosphoremia, which is inadequate because of insufficient intra-dialytic removal of phosphate (P), is further limited by PDR-P, i.e. the significant increase in serum P levels during the early postdialytic period. Patients and methods. To investigate the effects of enhanced P removal by haemodiafiltration on the inter-dialytic phosphoremia, we studied 12 uremic patients that were switched, with cross-over randomised modality, to a single session of standard hemodialysis (HD) and hemodiafiltration (HDF) (Acute Study). Blood samples were obtained before the treatment, at the end (T0), after 30, 60, 90 and 120 minutes, and at 24, 48 and 68 hours. During both dialytic treatments the whole effluent dialysate was collected to evaluate the intradialytic removal of P. Thereafter, patients were randomised to receive either HD or HDF for three months, in the presence of constantly similar Kt/V, food intake and dose of phosphate binder (Chronic Study). RESULTS: Acute Study. Compared to HD, P removal in HDF was about 44% greater in the presence of identical predialytic P levels (6.0+/-0.2 and 5.9+/-0.4 mg/dl) and Kt/V (1.35+/-0.06 and 1.34+/-0.05); however, the inter-dialytic decline of serum P levels did not differ (-50+/-3% versus -42+/-3%, p=0.098). In HDF, PDR-P was faster (30 min versus 90 min) and better (at T120: +69+/-6% versus +31+/-4%, p<0.001). The higher P levels were maintained throughout the inter-dialytic period whereas Ca x P changed in parallel. Chronic Study. During the three months, pre-dialytic serum P diminished in HDF (from 5.8+/-0.2 to 4.4+/-0.3 mg/dl, p<0.05), while it remained unchanged in HD. A similar pattern of changes was detected in Ca x P. CONCLUSIONS: Enhancement of P removal, acutely amplifies the extent of PDR-P, but allows better control of Ca-P homeostasis in the medium term. This effect is likely to be dependent on the enhanced mobilisation of phosphate from a deep compartment.

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.

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.