Predictor factors for renal outcome in renal artery stenosis.

BACKGROUND: Atherosclerotic ischemic renal disease is a frequent cause of end-stage renal failure. Correction of renal artery stenosis (RAS) may fail to stabilize or improve renal function. AIMS OF THE STUDY: Carotid and aortic Intima media thickness (IMT), resistance renal resistance index (RI), arterial blood pressure (BP), serum creatinine (SCr), creatinine clearance (CrCl), proteinuria and uricemia were considered as possible predictive factors and measured before renal-artery stenosis correction and during 12 months follow-up. MATERIALS AND METHODS: we performed an observational study on a total of 55 patients to find predictive factors of the outcome of renal function after renal percutaneous transluminal angioplasty and stenting (RPTAs). RESULTS: We found that uricemia, proteinuria and IR were higher at baseline in patients who worsened renal function after revascularization. CONCLUSIONS: The identification of predictive factors (uricemia; proteinuria and RI) of chronic kidney disease (CKD) progression in patients with RAS undergone revascularization could be useful to predict renal long term outcome and to select patients that really could benefit of this.

Downregulation of cell survival signalling pathways and increased cell damage in hydrogen peroxide-treated human renal proximal tubular cells by alpha-erythropoietin.

OBJECTIVE: Erythropoietin has been shown to have a protective effect in certain models of ischaemia-reperfusion, and in some cases the protection has been correlated with activation of signalling pathways known to play a role in cell survival and proliferation. We have studied whether erythropoietin would overcome direct toxic effects of hydrogen peroxide (H(2)O(2)) treatment to human renal proximal tubular (HK-2) cells. MATERIALS AND METHODS: HK-2 cells were incubated with H(2)O(2) (2 mm) for 2 h with or without erythropoietin at concentrations of 100 and 400 U/ml, and cell viability/proliferation was assessed by chemical reduction of MTT. Changes in phosphorylation state of the kinases Akt, glycogen synthase kinase-3beta (GSK-3beta), mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase 1 and 2 (ERK1/ERK2) were also analysed. RESULTS: Cells incubated with H(2)O(2) alone showed a significant decrease in viability, which did not significantly change by addition of erythropoietin at concentration of 100 U/ml, but was further reduced when concentration of erythropoietin was increased to 400 U/ml. Phosphorylation state of the kinases Akt, GSK-3beta, mTOR and ERK1/ERK2 of H(2)O(2)-treated HK-2 cells was slightly altered in the presence of erythropoietin at concentration of 100 U/ml, but was significantly less in the presence of erythropoietin at a concentration of 400 U/ml. Phosphorylation of forkhead transcription factor FKHRL1 was diminished in cells incubated with H(2)O(2) and erythropoietin at a concentration of 400 U/ml. CONCLUSIONS: Erythropoietin, at high concentrations, may significantly increase cellular damage in HK-2 cells subjected to oxidative stress, which may be due in part to decrease in activation of important signalling pathways involved in cell survival and/or cell proliferation.

[Nephroangiosclerosis and ischemic nephropathy: two different entities or two renal manifestations of the same systemic cardiovascular disease?]. / La nefroangiosclerosi e la malattia ateromasica ischemica renale: due entita' nosologiche diverse o solo due espressioni renali di una stessa patologia sistemica cardiovascolare?

Nephroangiosclerosis (NAS) is increasingly diagnosed in adult and elderly patients with slowly progressive chronic renal insufficiency. Since these patients usually present with arterial hypertension, this is considered the main cause of NAS (sometimes called, in fact, hypertensive NAS or hypertensive nephropathy). However, there is evidence that other factors such as aging, black race, smoking, and metabolic disturbances contribute to the development and progression of the disease. In some patients, these factors may be prominent while hypertension may be mild or even absent: this form has been denominated ischemic nephropathy (IN). Are NAS and IN really two different diseases or just different presentations of cardiovascular disease involving the kidney? The latter hypothesis is supported by evidence that (a) NAS and IN share a relative aspecificity in their clinical symptoms (low proteinuria, microhematuria, high blood pressure, dyslipidemia) and histopathological features (as determined in the few cases that undergo a kidney biopsy), and (b) there is a high likelihood that atheromatous and hypertensive lesions coexist in the same patient. In this ''Controversy in Nephrology'', Rosario Cianci and Alessandro Zuccala' analyze this issue and try to answer the following questions: 1 - Are NAS and IN two different diseases or two different expressions of the same disease? Rosario Cianci, ''They are two different diseases''. Alessandro Zuccala', ''They represent two different expressions of the same disease''. 2 - Is the pathogenesis different in nephroangiosclerosis and IN? Rosario Cianci, ''The pathogenesis is high blood pressure in NAS and renal ischemia in IN''. Alessandro Zuccala', ''NAS and IN share the same multifactorial pathogenesis: vascular metabolic alterations can cause chronic renal ischemia with or without hypertension''. 3 - Is a biopsy necessary for the diagnosis? Rosario Cianci, ''Yes, it is''. Alessandro Zuccala', ''No, it is not''. 4 - Is it possible to prevent or to slow the progression of the renal damage in this (these) disease(s)? Rosario Cianci, ''Yes it is, by reducing blood pressure''. Alessandro Zuccala', ''Normalization of blood pressure is not enough but all the other risk factors of vascular damage must be addressed, when possible''.

[Multiple peritrochanteric and pubic calcifications in a young woman on hemodialysis with severe renal osteodystrophy successfully treated with sevelamer+cinacalcet+paracalcitol combination therapy]. / Calcificazioni multiple peritrocanteriche e pubiche in giovane emodializzata con grave osteodistrofia renale risolte dall'associazione sevelamer+cinacalcet+paracalcitolo.

Secondary hyperparathyroidism is a frequent complication of chronic renal failure that can induce severe bone disease and negatively influence the cardiovascular outcome. Therefore, nephrologists should attempt to reach the targets recommended by national and international guidelines using all the available therapeutic strategies. We describe the case of a 37-year-old woman affected by spina bifida and myelomeningocele who had been on hemodialysis since 1993. In July 2006 she developed secondary hyperparathyroidism complicated by peritrochanteric calcifications which did not respond to standard therapy. Because it was impossible to perform a parathyroidectomy, we started medical therapy with a combination of sevelamer hydrochloride, paracalcitol and cinacalcet, which resulted in progressive improvement of laboratory data and osteodystrophy. A diagnosis of mixed secondarytertiary hyperparathyroidism was made, but a progressive increase in iPTH to very high levels suggested a rapid evolution toward a pure tertiary form.

The usefulness of the prognostic inflammatory and nutritional index (PINI) in a haemodialysis population.

BACKGROUND AND AIM: Protein-Energy Wasting and inflammation are the principal risk factors of haemodialysis complications. We evaluated the reliability of a simple and non expensive test, the Prognostic Inflammatory and Nutritional Index (PINI), for regular screening of maintenance haemodialysis (MHD) patients in order to detect early onset of inflammation and malnutrition. METHODS AND RESULTS: 121 adult patients on maintenance dialysis were followed up for 32 months and screened every 6 months for PINI, calculated as alpha1-Acid Glycoprotein (alpha1-AG)xC-Reactive Protein (CRP)/AlbuminxTransthyretin. PINI score < or =1 was considered normal. Patients were stratified according to their PINI score: 86 patients (71.66%) had a normal score, whereas 35 (28.33%) had PINI > or = 1. The latter also had higher CRP levels, despite no clinical evidence of inflammation at the time of enrolment. Survival in patients with normal PINI was similar to patients with normal CRP, while in patients with abnormal PINI it was significantly lower than in patients with low serum albumin (p<0.05) or elevated CRP (p<0.05). After follow-up, all surviving MHD patients with PINI > or = 1 had at least one cardiovascular event vs 2.5% of patients with PINI > or = 1. CONCLUSION: The assessment of PINI can reliably identify MHD patients at higher risk of mortality and morbidity even in the absence of overt Malnutrition-Inflammation Complex Syndrome (MICS). This simple test appears to be more sensitive and specific of the single components, and not expensive, so that it could be routinely used to identify patients with sub-clinical inflammation and/or malnutrition.

Monitoring chronic hemodialysis patients: a questionnaire-based survey.

BACKGROUND: The monitoring program for patients on regular hemodialysis treatment (RDT) is not well defined yet by current international guidelines (CIG). METHODS: To evaluate the extent to which CIG are implemented, we sent a questionnaire to 100 Italian hemodialysis units (DU) with questions concerning: (a) the frequency with which routine tests were performed for the follow-up of patients on RDT; (b) which other non-routine tests were performed. We analyzed the response data and compared them with the CIG. RESULTS: We received 37 replies. We found several differences between the monitoring program of our respondents and the CIG. CONCLUSION: Because of the small number of responses, this survey is only preliminary; however, it shows the difficulty nephrologists have in using the CIG to create a correct monitoring program in patients on RDT. Although our analysis is limited to 37 DUs, it suggests that specific guidelines are necessary to optimize the management of patients on RDT.

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.

[Resistant hypertension and paradox effect in patient with hemodialysis treatment]. / Ipertensione arteriosa resistente con effetto paradosso in corso di trattamento emodialitico sositutivo.

This is a case study of a 65-year-old female, on regular haemodialysis treatment, with resistant hypertension and paradoxical blood pressure (BP) elevation during dialysis. This phenomenon occurs in a small number of patients, since in most patients an acceptable BP is usually reached by adequate control of fluid and volume status with dialysis, sometimes associated with pharmacologic intervention. Since in our patient hypertension persisted despite apparent achievement of dry weight and maintenance of antihypertensive medications, we did some extensive investigations to disclose any secondary causes of hypertension (other than ESRD); we also evaluated whether the optimal dry weight was really achieved and maintained, and if the pharmacokinetics of the antihypertensive drugs was influenced by dialysis. We found no secondary cause of hypertension; by contrast, we detected the presence of a mild cardiac dilatation, and realized that some antihypertensive drugs, taken by our patient, were removed by dialysis. Since both these are known to precipitate the paradoxical BP rise during dialysis, we successfully modified once again our dialysis strategy and changed the antihypertensive therapy, adding a calcium antagonist to both losartan and low-dose minoxidil.

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.

[Guidelines on water and solutions for dialysis. Italian Society of Nephrology]. / Linee Guida su acque e soluzioni per dialisi.

The National Society of Nephrology has promoted the development of specific Italian Guidelines for dialysis fluids. Two previous national inquiries showed a wide variety in the type and frequency of both microbiological and chemical controls concerning dialysis water, reinforcing the need for specific standards and recommendations. An optimal water treatment system should include tap water pre-treatment and a double reverse osmosis process. Every component of the system, including the delivery of the treated water to the dialysis machines, should prevent microbiological contamination of the fluid. Regular chemical and microbiological tests and regular disinfection of the system are necessary. 1. Chemical quality (Table: see text). Treated tap water used to prepare dialysis fluid should be within European Pharmacopoeia limits at the water treatment system inlet and at the reverse osmosis outlet. In addition dialysate, concentrate and infusion fluids must comply with specific Pharmacopoeia limits. The physician in charge of the dialysis unit is advised to institute a multidisciplinary team to evaluate the requirement for added chemical controls in the presence of local hazards. 2. Microbiological quality (Table: see text). High microbiological purity of dialysis fluid--regularly verified--is a fundamental prerequisite for dialysis quality and every dialysis unit should aim as a matter of course to obtain "ultra-pure" dialysate (microbial count <0.1 UFC/mL, endotoxins <0.03 U/mL). On-line dialysate ultrafiltration and regular disinfection of dialysis machines greatly enhance microbiological purity. On-line dialysate reinfusion requires specific devices used according to corresponding instructions and to more frequent microbiological tests. Dialysis fluids for home dialysis should comply with the same chemical and bacteriological quality. The appendix reports the water treatment system's technical characteristics, sampling and analytical methods, monitoring time-tables, as well as the origin and effects of the main toxic substances. Suggestions and questions concerning these guidelines are welcome to nefrologia@sin-italy.org.

[Guidelines for dialysis. Replacement therapy for acute renal failure in critically ill patients]. / Linee Guida sulla Dialisi. Il trattamento sostitutivo della Insufficienza Renale Acuta nel paziente critico.

Acute renal failure (ARF) in patients admitted to the intensive care unit (ICU) is mostly caused by ischemic or toxic injury, with a higher incidence in the latest years due to the growing number of interventions in cardiac and vascular surgery and to the general enhancement of reanimation techniques, which allow a better outcome among ICU patients. In critically ill patients, the ARF incidence reported in the literature ranges between 1 and 25%. Among ICU patients with ARF the mortality is between 40 and 65%, much more than in patients without this complication. Higher mortality rates, longer hospitalisation times and higher therapy costs demand from us an early diagnosis and treatment of ARF. Due to the lack of controlled and randomized proofs, recommended criteria for starting renal replacement therapy (RRT) in critical ARF patients might overlap with those for ESRD therapy. Moreover, randomised and controlled trials, confirming the actual efficacy of early onset of RRT on the mortality rate, are not yet available. As for stable ESRD patients, a direct relationship between dialytic doses and mortality and morbidity has been established for ARF patients. For ARF patients, as well as for ESRD patients, a minimum Kt/V of 1.2 three times a week should be ensured, although higher doses for critical ARF patients may achieve better results. The choice between intermittent (IRRT) and continuous renal replacement therapy (CRRT) in these patients is still a controversial issue. In spite of the fact that most studies report a better outcome in patients treated with CRRT, a recent meta-analysis failed to demonstrate any difference on the relative risk (RR) of mortality and on the rate of renal recovery between patients treated with either IRRT or CRRT. Furthermore, the use of peritoneal dialysis for the treatment of ARF patients in ICU has not been dismissed yet; so far this is indeed considered to be the technique of choice in some specific clinical situations. The intrinsic urgency of dialysis in ARF patients entails the use of temporary central venous catheters. The internal right jugular vein is usually preferred for these catheters because of the easier insertion and the lower risk of stenosis and thrombosis. The anticoagulant procedure should be chosen on the basis of patient characteristics, treatment typology and the likelihood of effectively monitoring its action. The choice of buffers in the dialysate, mostly lactate or bicarbonate, should depend on patient characteristics; so far, however, controlled but not randomized studies do not show any significant difference in the correction of metabolic acidosis between lactate and bicarbonate.

Renal hemodynamic response to maximal vasodilating stimulus in healthy older subjects.

BACKGROUND: It is still unclear whether age per se is associated with preservation of renal functional reserve, that is, of the increase in glomerular filtration rate (GFR) induced by appropriate vasodilating stimulus. METHODS: To gain insights into this issue, we evaluated the renal response to a maximal vasodilating stimulus, represented by the combined infusion of mixed amino acid solution (AA) and dopamine at renal dose (D), in 10 young subjects (median age of 30 years, range of 19 to 32) and in 11 subjects of older age (median age of 67 years, range of 65 to 76). Two further age-matched groups of young (N = 15) and older (N = 11) living kidney donors underwent renal needle biopsy immediately before nephrectomy to perform semiquantitative scoring (0 to 3) of arteriosclerosis in intrarenal arteries. All of the study subjects were nonsmokers with healthy status proven by extensive diagnostic evaluation excluding any risk factor of renal dysfunction. RESULTS: Basal renal plasma flow (RPF) and GFR were proportionally lower in older subjects (RPF, 361 +/- 29 vs. 618 +/- 34 mL/min/1.73 m(2), P < 0.001; GFR, 79 +/- 4 vs. 127 +/- 5.8 mL/min/1.73 m(2), P < 0.001). After AA + D, a significant increase of RPF and GFR was observed in both groups, but the older subjects exhibited a smaller percentage increment (RPF, 25.5 +/- 4.8 vs. 42.4 +/- 5.8, P < 0.05; GFR, 19.6 +/- 5.7 vs. + 33.8 +/- 6.4, P < 0.05). Furthermore, the maximal vasodilating stimulus was not able to restore renal hemodynamics in older subjects to the level measured in young controls at baseline. Renal vascular resistances were higher (P < 0.05) in the older subjects both at baseline (0.19 +/- 0.02 vs. 0.09 +/- 0.004 mm Hg/mL/min) and after AA + D (0.14 +/- 0.01 vs. 0.06 +/- 0.004). Light microscopy examination detected the presence of a greater degree of arteriosclerosis at the level of interlobular and arcuate arteries (0.89 +/- 0.15 vs. 0.45 +/- 0.08) and interstitial fibrosis/tubular atrophy (1.18 +/- 0.13 vs. 0.53 +/- 0.13) in older than in young subjects. CONCLUSIONS: Therefore, aging has adverse effects on renal function despite the absence of any risk factor for renal disease, including chronic smoking: (1) GFR and RPF are lower, and (2) the renal response to maximal vasodilating stimulus is impaired. These aging-related alterations of renal hemodynamics are possibly due to organic lesions in renal vasculature.

Current indications for renal biopsy: a questionnaire-based survey.

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.

Diuretics in renal failure.

Fluid retention following reduction in the glomerular filtration rate causes extracellular fluid volume expansion that reduces tubular reabsorption by residual nephrons, thereby maintaining the external sodium balance. The price paid for this is salt-dependent hypertension. Thus, loop diuretics are the best treatment for uremic hypertension. Diuretics are also used in chronic renal failure to treat edema due to nephrotic syndrome and congestive heart failure (CHF). In nephrotics, edema is often refractory to diuretics because of low plasma protein, depletion of the intravascular compartment, decrease in the protein-bound fraction of the diuretic in peritubular blood, and increase in tubular fluid. Thus, higher doses are needed. In uremics with CHF the efficacy of diuretics may be hampered because of the reduced renal blood flow. The association of dopamine (1-1.5 microg/kg body weight/min) may overcome this resistance; improvement in cardiac function by dialysis ultrafiltration may also help. Diuretic resistance is sometimes observed; it may be overcome by the following procedures: in CHF by the use of digitalis and/or angiotensin-converting enzyme inhibitors; by substitution of an ineffective loop diuretic for another one; by using larger doses of diuretic; by intravenous infusion rather than bolus therapy, and by a combination of diuretics acting in different segments of the tubule: loop diuretic+thiazide+amiloride. Intravenous infusion of 20% albumin has also been suggested.

The impact of early normalization of haematocrit by erythropoietin on renal damage in the remnant kidney model.

BACKGROUND: Correction of anaemia in moderate to advanced renal failure is still a matter of debate because of postulated detrimental effects of erythropoietin on the progression of renal damage. METHODS: The renal effects of early normalization of haematocrit (Htc) by erythropoietin (rHuEpo) were investigated from the time of 5/6 nephrectomy up to 8 weeks post-intervention in three groups of remnant kidney model rats: untreated controls (CON), rats receiving 100 UI/kg body-wt of rHuEpo i.p. twice a week (EPO), and rats receiving rHuEpo in which periodic phlebotomies maintained Htc similar to the value of the control group (PHL). The latter group was included to evaluate the direct effects of rHuEpo on renal damage, i.e. independent from Htc correction. RESULTS: Two weeks after renal ablation (basal), Htc decreased in CON and PHL rats (from 49.3+/-1.4% to 43.2+/- 1.1, P < 0.05 and from 49.6+/-1.1 to 43.3+/-1.5%, P<0.05 respectively), while it remained consistently normal in EPO rats (48.9+/-1.2% to 48.9+/-1.50/%, P<0.05 vs other groups). Thereafter Htc did not change throughout the remaining period in all groups. At the end of the study, with respect to basal, resting blood pressure increased significantly by the same extent in CON (+ 13+/-2%) and EPO rats (+ 15+/-5%), while it remained constant in PHL rats. Notably, creatinine clearance significantly decreased in CON (-53+/-8% 8 vs basal) and EPO (-38+/-8% vs basal), while it did not change in PHL rats. Likewise the degree of proteinuria as well as renal morphologic alterations and glomerular hypertrophy/sclerosis was similar in CON and EPO rats, and was significantly more severe than in the phlebotomized group. The only difference detected between CON and EPO group was the greater mesangial hypercellularity in rHuEpo-treated rats. CONCLUSION: In uraemic rats, chronic treatment with rHuEpo aimed at normalization of Htc beginning the early stage of renal failure does not inevitably account for a rise in systemic blood pressure. In addition, neither erythropoietin per se nor the correction of haematocrit accelerates the progression of renal damage when blood pressure remains constant.

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.