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.

Ischemic steal syndrome in a hemodialysis patient: The roles of Doppler ultrasonography and dynamic Doppler studies in diagnosis and treatment selection.

Ischemic steal syndrome (ISS) is a complication that can occur after the construction of a vascular access for hemodialysis. It is characterized by ischemia of the hand caused by marked reduction or reversal of flow through the arterial segment distal to the arteriovenous fistula (AVF). The diagnosis of hand ischemia is based on physical examination, but imaging studies are very useful for detecting the true cause of ischemia and for selecting an appropriate therapeutic strategy. In this report, we describe an uncommon cause of ISS in a patient on hemodialysis. The ischemia was caused by the presence of undetected flow through an older AVF on the same arm as the AVF used for dialysis. The unsuspected "steal" was disclosed by color Doppler examination of the vascular bed of the patient's left arm. Dynamic Doppler studies then played a fundamental role in the decision to ligate the distal radio-cephalic AVF. The procedure led to the complete relief of ischemic symptoms.

[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.

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.

[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.

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.

[Clinical management of the patient affected with acute renal failure (ARF) secondary to volume depletion]. / Gestione clinica del paziente con insufficienza renale acuta (IRA)da ipovolemia.

Most cases of ARF are secondary to volume depletion. In the literature, very few scientific publications address the problem of what to do when confronted with such a patient. As regarding the diagnosis of hypovolemia, an accurate history and physical examination can help to determine both the presence and etiology of volume depletion; postural hypotension (decrement in systolic blood pressure of more than 20 mmHg after standing from the supine position), associated with a pulse increment of 30 beats/min or more and dizziness are specific symptoms of hypovolemia. Laboratory indices are useful to diagnose volume depletion, but their interpretation is not simple, and they may not be available in the non-nephrologic environment. Fluid replacement therapy in hypovolemia is largely dependent upon the type of fluid that has been lost and concurrent electrolytic and acid-base disorders. Patients with hypernatremia and volume depletion should receive mild hypotonic solutions, whereas those with hyponatremia and hypovolemia should receive mild hypertonic solutions. The entity of reinfusion depends on daily losses. Conversely, monitoring of body weight can be considered an adequate index of fluid balance. Concerning the treatment of ARF, the use of loop diuretics in the early phases of pre-renal ARF decrease oxygen consumption in the tubular cells by inhibiting transcellular sodium transport, therefore preventing or limiting ischemic cell injury. The use of loop diuretics should also be evaluated in intermediate syndrome and ischemic NTA where diuretics can, respectively, reduce renal ischemia and convert oliguric ARF into the non-oliguric form.

[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.