[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.

[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.

[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.

Does the presence of ANCA in patients with ulcerative colitis necessarily imply renal involvement?

BACKGROUND: ANCA are thought to play a pathogenic role in renal vasculitis. ANCA may also be detected in patients with diseases not usually associated with renal pathology, such as ulcerative colitis. Our study was conducted to determine if the presence of ANCA in patients with ulcerative colitis is associated with renal pathology. METHODS: Eight ANCA-positive and five ANCA-negative patients with a histological and endoscopic diagnosis of active ulcerative colitis were investigated. Repeated complete urinalyses and determination of microalbuminuria and creatinine clearance were performed. Serum IgG and IgA ANCA were evaluated in all patients by indirect immunofluorescence and ELISA, and when detected the antibodies were further characterized by alpha granules preparation, myeloperoxidase, lactoferrin, and cathepsin G. RESULTS: In both ANCA-positive and ANCA-negative patients renal function was normal or near normal and urinalyses (including microalbuminuria) failed to disclose any abnormalities. ANCA exhibited a perinuclear pattern in all ANCA-positive patients. Interestingly, none of the ANCA-positive patients had antibodies to myeloperoxidase or to alpha granules which are usually found in the sera of patients with ANCA-associated vasculitis, and only one had antibodies to lactoferrin. The ANCA specificity remained undetermined in the remaining seven patients. At the end of the 1-year observation period, all ANCA-positive patients remained ANCA-positive without developing symptoms, signs or laboratory abnormalities consistent with renal involvement. CONCLUSIONS: Renal damage was not observed in ANCA-positive patients with ulcerative colitis even after 1 year of follow-up, suggesting that the ANCA found in these patients do not share the antigenic targets with the ANCA commonly found in renal vasculitis. Therefore the potential of ANCA of inducing renal lesions (if any) is dependent on their own antigenic specificity.

Extra-natriuretic effects of atrial peptide in humans.

To evaluate extra-natriuretic effects of atrial natriuretic peptide (ANP), plasma ANP (pANP) levels were assessed in seven healthy men on low-sodium diet (80 mEq NaCl/day), in basal conditions and during stepwise infusion of human ANP (2, 4, 8 and 16 ng/min/kg). To determine the individual physiological (PHY) pANP level, we measured pANP in the same subjects after a high-salt diet (400 mEq NaCl/day), that is, in a physiological stimulation of ANP. We then compared the effects of the PHY levels of ANP to the effects of pharmacological (PHA) pANP levels. Neither PHY nor PHA pANP levels modified creatinine clearance or blood pressure. The progressive rise in pANP levels was associated with increases in urinary excretion of Na+, K+ and urea. ANP alone respectively accounted for 41%, 30% and 92% of the increase in natriuresis, kaliuresis and urea excretion that occurred after changing salt intake from 80 to 400 mEq/day. Pharmacological ANP levels raised CH2O and reduced UOsm. Interestingly, PHA levels were associated with significant decrease in serum K+ (from 4.5 +/- .1 to 4.0 +/- .1 mEq/liter) and plasma urea (from 31.9 +/- 5 to 24.2 +/- 4 mg/dl). The mean cumulative urinary potassium and urea losses corresponded to the theoretical body losses of potassium and urea; moreover, the individual cumulative urinary losses of potassium and urea significantly correlated with the corresponding decrement in their plasma levels. In conclusion, ANP has both physiological and pharmacological significance in the control of potassium and urea metabolism by decreasing plasma levels of K+ and urea through effects on the renal excretory function.

Role of inhibition of atrial natriuretic factor release in the down-regulation of salt excretion.

UNLABELLED: We investigated the role of atrial natriuretic factor (ANF) in the down-regulation of sodium excretion (UNaV). Seven subjects were sequentially studied while ingesting a normal-salt diet (220 mmol NaCl/day, NSD), a very low-salt diet (20 mmol NaCl/day, VLSD) for six days, and again at NSD for nine days. After one day of VLSD, a negative salt balance of 85 mmol was achieved and plasma ANF decreased from 19.1 (SE 2.5) to 7.2 (SE 2.1) pg/ml, whereas plasma renin activity (PRA) and plasma aldosterone (ALD) increased after the third and second day, respectively. During restoration of volemia (NSD), ANF increased after the third day; in contrast, PRA and ALD decreased earlier. Seven other subjects kept at low-salt diet (50 mmol NaCl/day) were studied during ANF infusion (at 2, 4, 8 ng/min/kg body wt). Increases of ANF from 10.3 (SE 0.9) pg/ml (basal condition) to levels of 24.0 (SE 1.9) pg/ml (infusion study), occurring physiologically in the same subjects after NSD, evoked increases in UNa V that accounted for 62% of UNa V rise necessary to balance the NSD, whereas PRA or ALD did not change. Plasma ANF, unlike PRA or ALD, was directly correlated with UNa V. IN CONCLUSION: (a) ANF changes earlier than PRA and plasma aldosterone during VLSD; (b) PRA and ALD respond more promptly than ANF in the recovery from hypovolemia; (c) during ingestion of a low-salt diet, changes in plasma ANF by infusion account for more than half the increase in UNa V following the shift from low- to normal-salt diet independently of alterations in PRA and ALD.

Mesangial expression of intercellular adhesion molecule-1 in primary glomerulosclerosis.

Frozen sections of renal biopsy specimens from eight patients with primary focal segmental glomerulosclerosis (FSGS) and 10 patients with membranous nephropathy (MN) were stained in immuno-peroxidase with the intercellular adhesion molecule-1 (ICAM-1) monoclonal antibody (MoAb), CL203.4. ICAM-1 was expressed by mesangial cells in six patients with FSGS. On the other hand, ICAM-1 was not detected in mesangial cells in patients with MN or in the non-affected portion of tumoral kidneys used to control normal renal expression of ICAM-1. De novo mesangial expression of ICAM-1 in FSGS suggests that sclerosis results from an inflammatory process, possibly associated with local release of cytokines.

Inhibition of urea tubular reabsorption by PGE1 infusion in man.

We have shown that the inhibition of prostaglandin (PG) synthesis in man decreases the fractional clearance of urea (FCurea). To understand the mechanism(s) by which PG affect the renal handling of urea, 6 normal volunteers were randomly studied in maximal antidiuresis (by water deprivation and by administering 1-desamino-8-D-arginine vasopressin) before and during PGE1 infusion, in two separate occasions: (A) after 7 days of normal protein (1 g/kg b.w./day) and water intake (10 ml/kg b.w./day), and (B) after 7 days of low protein intake (0.5 g/kg b.w./day) and high water intake (80 ml/kg b.w./day) to lower the corticomedullary osmotic gradient. During infusion of PGE1 at rates of 0.01, 0.05 and 0.1 micrograms/min/kg, randomly administered, the urinary fluid losses were replaced by infusing equal volumes of hypotonic NaCl (80 mmol/l). To evaluate the time effects of this protocol, control studies were performed in an other 8 subjects receiving vehicle infusion without PGE1. In study A, FCurea rose by 23% (p less than 0.01) at the lowest PGE1 infusion rate (0.01 micrograms/min/kg), in the absence of any simultaneous change in water and salt output, Uosm, PAH and inulin clearance. Higher PGE1 infusion rates (0.05 and 0.1 micrograms/min/kg) were associated with a progressive increase of FCurea (50%, p less than 0.001 and 91%, p less than 0.001, respectively), fractional clearance of water and salt output, inulin and PAH clearance and reduced Uosm from 1,005 (22 SEM; basal value) to 772 (38 SEM; minimum value) mosm/kg (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of atrial natriuretic factor in renal adaptation to variation of salt intake in humans.

This study was performed to define the extent to which atrial natriuretic factor (ANF) contributes to upregulate salt excretion in subjects eating a high-salt diet. Eight normal volunteers were first studied at low-salt diet (80 mmol NaCl/day); urinary sodium excretion (UNaV) and plasma ANF (PANF) were measured in the basal condition and during stepwise infusion of human alpha-ANF at 2, 4, 8, and 16 ng.min-1.kg-1. Then the same subjects were shifted to a high-salt diet (400 mmol/day), and UNaV and PANF were measured in the new balance condition. At low-salt diet, UNaV averaged 0.069 meq/min, and PANF averaged 21 pg/ml; infusion of human alpha-ANF raised stepwise both UNaV and PANF (means in meq/min and pg/ml, respectively, were 0.177 and 46, 0.218 and 76, 0.360 and 86, and 0.601 and 182). Infusion of ANF caused a progressive fall of plasma aldosterone and plasma renin activity. Mean UNaV and PANF at high-salt diet were 0.301 meq/min and 35 pg/ml. Thus, by increasing experimentally PANF in a low-salt diet condition to the levels occurring physiologically in a high-salt diet condition, a significant rise in UNaV is evoked, which accounts for approximately 50% of the rise of UNaV that is necessary to balance the increased salt intake.