Search

The onset of renal damage in diabetes mellitus may be influenced by several factors which largely result from genetic predisposition, hereditary factors and the early appearance of microalbuminuria and/or systemic hypertension. Most of these factors are also implicated in the progression of nephropathy from microalbuminuria to overt proteinuria and to end-stage renal failure (ESRF). Over the last few years, the role of hyperglycaemia has emerged as critical in mediating the progressive renal damage in diabetes. However, hyperglycaemia leads to increased formation of glycated proteins which may act as promoters of progression by localizing in renal tissue. In addition, hyperglycaemia may have a synergistic effect with some other risk factors, such as growth factors and the renin angiotensin system, in accelerating renal deterioration.

A multicentre, comparative, randomized study was performed to compare the efficacy and tolerability of two antibiotic regimens in the treatment of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients: teicoplanin plus tobramycin versus cephalothin plus tobramycin. After informed consent had been obtained, 68 patients were randomized prospectively to receive either teicoplanin plus tobramycin or cephalothin plus tobramycin. Patients were followed throughout the study and for up to 4 weeks after the end of treatment, when clinical and microbiological parameters were assessed again. The incidence of clinical failure was 4.6 times higher in the cephalothin plus tobramycin group than in the teicoplanin plus tobramycin group (7/28 versus 2/37; P < 0.05). There was no significant difference in bacterial eradication between the two groups. Local and systemic tolerability were good for both regimens. The study shows that teicoplanin plus tobramycin is more effective than cephalothin plus tobramycin and might become a 'first-line' treatment for peritonitis in CAPD patients.

Background: Renal biopsy procedure in patients with chronic renal failure (CRF) may represent a valid tool to help clinicians in clinical practice. However, the use of this invasive method in CRF is variable and it reflects the hospital biopsy policy. Methods: To better define the CRF-related histological patterns and to assess the clinical utility of this procedure in this extensive group, we analyzed biopsy records of 1,185 CRF patients living in a large area of north-east Italy from 1998 to 2010. Results: Data analysis showed that, although the biopsy incidence rate and the histological features were unchanged, the mean age of our CRF patients increased during the study period (R2 = 0.42, p < 0.01). Primary and secondary glomerulonephritis (SGNs) were the main histological presentations (53.9 and 23%, respectively). SGNs were over-diagnosed in females. Leading histological types were immunoglobulin A nephropathy (22%), focal segmental glomerulosclerosis (12.4%), membranous glomerulonephritis (MGN, 7.5%) and nephroangiosclerosis (7.3%). These forms were also highly frequent in CRF patients with elevated proteinuria and moderate/severe renal damage. Elderly patients were primarily affected by MGN. After biopsy, 49.5% of CRF patients with and 34.1% without nephrotic syndrome received immunosuppression therapy. Conclusions: This study demonstrated that renal biopsy in CRF patients, regardless of age and glomerular filtration rates, is safe and essential to achieve a correct diagnosis and to commence the correct therapy. Additionally, it revealed that, even in patients with severe renal damage, it is possible to perform an accurate histological diagnosis and, interestingly, end-stage kidney disease seems not to be the primary form.

The abnormal proliferation of mesangial cells with IgA deposition in the glomeruli characterizes primitive mesangial glomerulonephritis (IgA nephropathy, IgAN); this disease reduces the normal renal parenchyma while renal function becomes progressively impaired. The possible role of selenium has never been considered in evaluating factors involved in the pathogenesis of IgAN. In this work we compared the Se status of 14 IgAN patients (8 with normal renal function, IgAN NRF; 6 with impaired renal function, IgAN IRF) to that of 14 normal individuals (CG NRF) before and after an oral supplementation with selenite (0.13 mol Se/kg b.w./day for 60 days). The following indices of Se status were measured: Se in plasma and urine samples by PIXE; glutathione peroxidase activity in the cytosol of platelets (PLTs-GSH-Px) and of erythrocytes (RBCs-GSH-Px). Both concentrations and activities of plasma glutathione peroxidase (pl-GPx), a selenoenzyme mainly synthesized in and secreted by the kidney, were measured in plasma samples and results compared among groups. IgAN patients showed lower pl-Se and lower activities of selenoenzymes than normal controls before Se supplementation (p < 0.001). These findings suggest that an impaired Se status coexisted with the proliferation of mesangial cells in patients. Selenite induced PLTs-GSH-Px activity in all individuals (p < 0.001), but no variation was observed in RBCs-GSH-Px activity or in the concentration of pl-GPx in the plasma. On the other hand, selenium induced pl-GPx activity in CG NRF (p < 0.001) and in IgAN NRF (p < 0.01), but poorly stimulated pl-GPx activity in IgAN IRF (p = n.s.). However, only 17% and 25% of the pl-GPx activity of normal controls was measured in the plasma of IgAN IRF and IgAN NRF patients, respectively (p < 0.001). In conclusion, selenite only partially restored a normal Se status in patients whose low pl-GPx activity probably reflects an impaired synthesis of this protein as a consequence of reduced normal functioning of the parenchyma in kidneys affected by IgA nephropathy.

Over a 10-year period, 1,990 end-stage renal disease patients in 30 centers were treated with continuous ambulatory peritoneal dialysis by the Italian Cooperative Peritoneal Dialysis Study Group. At the start of treatment, patients had an average age of 58.4 years, with a 66% prevalence of one or more clinical risk factors for premature death. Patient survival was 51 % and 33% at 4 and 8 years on continuous ambulatory peritoneal dialysis, respectively, and technique survival was 62% and 48%, respectively. Occurrences of peritonitis progressively reduced until they reached an incidence of 0.50 episodes/yr in the last 5 years (1985 to 1989). Hernias and catheter-related problems did not influence the dropout rates. These Italian Cooperative Peritoneal Dialysis Study Group results demonstrate that continuous ambulatory peritoneal dialysis is a viable dialysis technique for long-term treatment of chronic renal failure and that it is an effective alternative to hemodialysis, especially for older and high-risk patients.

CAPD outcomes were compared between a group of 301 diabetic patients (mean age +/- SD, 58.9 +/- 12.7 years, 55.8% males) and a group of 1689 non-diabetic patients (mean age +/- SD 57.8 +/- 14.8 years, 55.9% males) treated in 30 centres participating in the Italian Cooperative Peritoneal Dialysis Study Group from 1980 to 1989, with follow-up observation periods of 444 years (mean +/- SD, 1.48 +/- 1.24) and of 3502 years (mean +/- SD, 2.07 +/- 1.91) respectively. CAPD was the first modality for 87.2% of diabetics and 78.1% of non-diabetics (P < 0.001). The percentage of patients who needed a partner for CAPD was 45.9% in diabetics and 30.2% in non-diabetics (P < 0.001). In diabetics compared with non-diabetics, cardiovascular diseases and cachexia were nearly twice and infections other than peritonitis more than three times as frequent in causing death. In diabetics, survival was significantly worse (P < 0.0001) and the relative risk of death 2.13 times higher (P < 0.001). The technique survival and the relative risk of drop-out were not significantly different in the two groups. Clinical problems were the most important cause of drop-out among diabetics. The probability and relative risk of drop-out due to peritonitis, as well as of the first peritonitis episode, were not significantly different between the two groups and between diabetics using or not using intraperitoneal insulin. Days per patient year of hospitalization, excluding the first, were 18.4 in diabetics and 14.3 in non-diabetics. CAPD-related problems caused hospitalization in a similar way in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

1. Selenium status was investigated in patients with chronic renal failure, with special regard to its relations to the dialysis treatments, dietary habits and clinical signs of atherosclerosis. 2. Serum selenium concentration and platelet glutathione peroxidase activity were measured in 45 patients with chronic renal failure subdivided into three groups according to the type of treatment: 15 non-dialysed, 15 on haemodialysis, 15 on continuous ambulatory peritoneal dialysis. A 7-day diet history was carried out in all patients. Seventeen of the patients with chronic renal failure had clinically overt cardiovascular disease. Forty-five age-matched healthy subjects were considered as controls. 3. Both serum selenium concentration and platelet glutathione peroxidase were significantly reduced in all patients with chronic renal failure compared with control subjects; a direct and significant correlation was found between the two parameters. No differences in selenium status were observed among the non-dialysed, haemodialysis and continuous ambulatory peritoneal dialysis groups. No correlation between total calorie or protein intakes and selenium indices were observed. The chronic renal failure patients with cardiovascular complications showed a further significant reduction in both serum selenium concentration and platelet glutathione peroxidase activity as compared with the patients without cardiovascular complications; these two groups were similar with respect to the other well-known cardiovascular risk factors (age, smoking, plasma lipids, hypertension, body mass index). 4. It is concluded that a low selenium concentration is present in chronic renal failure, which is independent of dialysis and is accompanied by biological repercussion in terms of reduced platelet glutathione peroxidase activity. It may represent a previously unrecognized cofactor favouring the ‘accelerated’ atherosclerosis of patients with chronic renal failure.

ObjectiveTo investigate the overall susceptibility of red blood cells (RBC) to lipid peroxidation from patients on continuous ambulatory peritoneal dialysis (CAPD).MethodsThe following parameters were measured: RBC malondialdehyde (MDA) production after oxidative stress with H2O2, RBC antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and RBC membrane lipid composition. The levels of plasma vitamin E and serum selenium were also as sayed.PatientsEleven patients on continuous ambulatory peritoneal dialysis. Twenty-one healthy blood donors of similar age were used as normal controls.ResultsThe MDA formation after H2O2 stimulation was normal in CAPD patients (0.79±0.1 μmol/gHb versus 0.78±0.1 in the control group). RBC from CAPD patients also showed a normal SOD activity, a more than adequate vitamin E status, and a peculiar pattern of membrane lipids, with reduced polyunsaturated fatty acids (pConclusionsThis study found a normal sensitivity to oxidant stress in RBC from a group of CAPD patients, despite an impaired GSH-Px activity. The peculiar lipid pattern of RBC membrane, characterized by reduced PUFA and increased MUFA content, may contribute, in addition to adequate SOD activity and vitamin E status, to normal RBC lipid peroxidation.

The effects of high doses of frusemide on plasma and muscle electrolyte composition were investigated in 20 patients with chronic renal failure (CRF), in 5 of them complicated by superimposed cardiac

The investigation of fibrinogen degradation products (FDP) in urine has been suggested as a reliable method to detect the glomerular deposition of fibrin. Urinary FDP were investigated in 246 patients with renal disease by means of a latex test in 100 of them (positive in 54%); in the remaining 146 patients the Merskey method was used which gave positive results in 26% of them. A significant correlation between urinary protein excretion and FDP was only observed in those patients examined with the latex test. In patients investigated with the Merskey method, the simultaneous determination of serum FDP showed no correlation between FDP values in serum and urine. In those patients studied by means of renal biopsy, a poor correlation was observed between immunofluorescence and electron microscopic evidence of fibrin deposition and urinary FDP. In conclusion, isolated urinary FDP detection is not an index of pathologic coagulation in the glomeruli.

In 28 patients with bilaterally recurring calcium – containing renal staghorn calculi, 14 with normal GFR and 14 with mild renal insufficiency, a metabolic investigation of calcium metabolism during i

In 196 adult patients with chronic renal disease or primary hypertension, the evaluation of glomerular filtration rate (GFR) by means of creatinine clearance, ‘predicted’ creatinine clearance and [

The occurrence of the nephrotic syndrome in 3 patients treated for 1–8 months with 2-mercapto-propionyl-glycine (Thiola) (at doses ranging from 0.750 to 2.000 g/day) is reported. The drug had been administered for chronic active hepatitis in 1 patient and for cystinuria in the remaining patients. Percutaneous renal biopsies, obtained in all patients and examined at light microscopy, immunofluorescence and electron microscopy, showed ‘minimal change’ nephropathy in 2 patients and membranous glomerulonephritis in the 3rd patient. In all patients, complete remission of the nephrotic syndrome and, eventually, disappearance of proteinuria were observed 15–120 days after discontinuation of Thiola. It is suggested that this drug may act either through an antigenie mechanism, akin to that of penicillamine, or through a sensitization mechanism, both of them being able to cause the nephrotic syndrome.

Bone histology and its relationship with calcium metabolism was evaluated in adult patients with nephrotic syndrome: 29 had normal renal function (GFR 103 +/- 4 ml/min/1.73 m2) (group 1) and 20 had renal insufficiency (GFR 31 +/- 4 ml/min/1.73 m2) (group 2). In group 1, serum PTH, 1.25-HCC and 24.25-HCC levels were normal, while 25-HCC values were reduced. Bone histology was normal in 76% of the patients, while 17% had isolated osteomalacia and 7% an associated bone resorption. Group 2 showed a higher incidence of bone resorption when compared with a matched group of patients with renal failure and no proteinuria (40% vs. 13%) and a comparable frequency of isolated mineralization defect (25% vs. 34%). PTH levels were definitely increased and serum total calcium and all the vitamin D metabolites were reduced. A significant correlation between the apparent duration of the disease and the severity of osteodystrophy was found only in group 2. In conclusion, no constant derangement of calcium metabolism and bone histology is evident in patients with nephrotic syndrome and normal renal function, while patients with persistent proteinuria are at high risk of osteodystrophy even in the early phases of renal failure.

The effects of a standard oral glucose tolerance test (OGTT) on the serum concentrations of glucose, insulin, growth hormone (GH) and cortisol were evaluated in 38 adult patients with primary nephrotic syndrome and with normal renal function, and in 10 normal subjects. 14 patients had a diabetic-like response and 24 were not different from controls. In both groups of patients an increase in insulin pool secretion, probably due to elevated serum GH levels, was observed. The increased GH values were not related to serum albumin nor to urinary protein losses. No significant difference in serum cortisol values was observed in patients with nephrotic syndrome as compared to controls. There was no strict correlation between the various histologic lesions and the metabolic abnormalities. However, patients with a diabetic-like response to OGTT had a higher frequency of membranous glomerulopathy or focal glomerular sclerosis.

32 polycystic kidney disease (PKD) patients, 16 with normal 16 with variably decreased renal function, were studied; 12 were normotensive, 20 were hypertensive. Mean arterial pressure (MAP) was 90 +/- 8 mm Hg in the normotensive group and 117 +/- 17 in hypertensive patients; plasma renin activity (PRA) was similar. The glomerular filtration rate (GFR) was lower, but not significantly, in the hypertensive group and plasma volume (PV) was higher in hypertensive patients (normotensive 40.25 +/- 3.47 ml/kg body weight; hypertensive 46.30 +/- 3.54). No correlation was found between MAP, and PRA or GFR but MAP correlated with PV. Cardiac output was higher in hypertensive patients (normotensive 3.48 +/- 0.70 l/min/m2; hypertensive 3.89 +/- 1.47), also total peripheral resistance was higher in the hypertensive group (normotensive 2,035 +/- 503 dyn/s/cm-5/m2; hypertensive 2,577 +/- 808). Cardiac output and PV showed a high degree of correlation, but no correlation was seen between total peripheral resistance and PV, or PRA. The hypertensive patients were divided into two groups: one with hypertension of less than 2 years duration and one with more than 2 years but with similar GFR, PRA, PV and hemodynamic pattern. Our data indicate that hypertension in PKD is volume-dependent; that the increase in PV was not related to the loss of GFR, and that the role of the renin-angiotensin system in maintaining the hypertensive state is not well defined. Hemodynamically hypertension is characterized by high cardiac output and total peripheral resistance independent of the duration of hypertension.

Progression of renal failure in patients with renal disease of diverse etiology on protein-restricted diet. The rate of progression of early renal failure was evaluated in three groups of adult patients with renal disease of diverse etiology on dietary protein and phosphorus restriction (about 0.6 g/kg of protein, 700mg of phosphorus) and in a control group of 22 patients with the same renal disease, retrospectively studied, on a free diet. Group 1 had 33 patients with chronic glomerulonephritis (CG), initial serum creatinine (Scr) of 1.4 to 4.3 mg/dl (mean, 2.20), followed for 5 to 94 months (mean, 44). Group 2 had 17 patients with polycystic kidney disease (PKD), Scr 1.3 to 4.7 mg/dl (mean, 2.40), followed for 8 to 81 months (mean, 42). Group 3 had 28 patients with primary chronic pyelonephritis (CP), Scr of 1.5 to 4.5 mg/dl (mean, 2.57), followed for 9 to 92 months (mean, 41). The control group had 22 patients (11 with CG, five with PKD, and six with CP), with Scr 1.7 to 4.1 mg/dl, followed for 6 to 72 months (mean, 24). In the regression analysis between reciprocal creatinine and time, the slopes were -0.0017, -0.0025, and -0.00016 dl/mg/month in the three patient groups on a protein-restricted diet, respectively. The difference between both groups 1 and 2 and group 3 was statistically significant (P < 0.05). The slopes in patients on a free diet were significantly greater than those found in patients on a protein-restricted diet. The actuarial survival probability at 72 months, assuming as “renal death” a Scr of 10 mg/dl, was 45% in patients with CG, 44% in those with PKD, and 67% in those with CP on a protein-restricted diet. Proteinuria and hypertension were the major factors affecting the progression of renal failure in all patient groups. With this dietary regimen, substantial percentages of patients (51% in group 1, 41% in group 2, and 68% in group 3) had no progression of functional deterioration during followup.Progression de l'insuffisance rénale chez des malades atteints de néphropathies de causes diverses en régime restreint en protides. La vitesse de progression d'une insuffisance rénale précoce a été évaluée dans trois groupes d'adultes atteints de néphropathies de causes diverses en restriction alimentaire en protides et phosphore (environ o,6g/kg de protides, 700mg de phosphore) et dans un groupe contrôle de 22 malades atteints des mêmes néphropathies, étudiés rétrospectivement en régime libre. Le groupe 1 comprenait 33 malades atteints de glomérulonéphrite chronique (CG), avec créatininémies initiales de 1,4 à 4,3 mg/dl (moyenne, 2,20), suivis pendant 5 à 94 mois (moyenne, 44). Le groupe 2 comprenait 17 malades atteints de polykystose rénale (PKD), avec Scr de 1,3 à 4,7 mg/dl (moyenne, 2,4) suivis pendant 8 à 81 mois (moyenne, 42). Le groupe 3 comprenait 28 malades atteints de pyélonéphrite chronique primitive (CP), Scr de 1,5 à 4,5 mg/dl (moyenne, 2,57) suivis de 9 à 92 mois (moyenne, 41). Le groupe contrôle comprenait 22 malades (11 avec CG, cinq avec PKD, et six avec CP), avec Scr 1, 7 à 4,1, suivis de 6 à 72 mois (moyenne, 24). Dans l'analyse de régression entre l'inverse de la créatinine et le temps, les pentes étaient de -0,0017, -0,0025, et -0,00016 dl/mg/mois dans les trois groupes de malades en régime restreint en protides, respectivement. La différence entre les groupes 1 et 2 et le groupe 3 était statistiquement significative (P < 0,05). Les pentes chez les malades en régime libre étaient significativement plus élevées que celles trouvées chez les malades en régime restreint en protides. La probabilité de survie actuarielle à 72 mois, en définissant la “mort rénale” pour Scr de 10 mg/dl, était de 45% chez les malades atteints de CG, 44% chez ceux atteints de PKD et 67% chez ceux atteints de CP, en régime restreint en protides. La protéinurie et l'hypertension étaient les facteurs principaux affectant la progression de l'insuffisance rénale dans tous les groupes de malades. Avec ce régime alimentaire, des pourcentages substantiels de malades (51% dans le groupe 1, 41% dans le groupe 2, et 68% dans le groupe 3) n'avaient pas de progression de la détérioration fonctionnelle pendant le suivi.

Epithelial–mesenchymal transition (EMT) of tubular cells is one of the mechanisms which contribute to renal fibrosis and transforming growth factor-β (TGF-β) is one of the main triggers. Heparanase (HPSE) is an endo-β-D-glucuronidase that cleaves heparan-sulfate thus regulating the bioavailability of growth factors (FGF-2, TGF-β). HPSE controls FGF-2-induced EMT in tubular cells and is necessary for the development of diabetic nephropathy in mice. The aim of this study was to investigate whether HPSE can modulate the expression and the effects of TGF-β in tubular cells. First we proved that the lack of HPSE or its inhibition prevents the increased synthesis of TGF-β by tubular cells in response to pro-fibrotic stimuli such as FGF-2, advanced glycosylation end products (AGE) and albumin overload. Second, since TGF-β may derive from sources different from tubular cells, we investigated whether HPSE modulates tubular cell response to exogenous TGF-β. HPSE does not prevent EMT induced by TGF-β although it slows its onset; indeed in HPSE-silenced cells the acquisition of a mesenchymal phenotype does not develop as quickly as in wt cells. Additionally, TGF-β induces an autocrine loop to sustain its signal, whereas the lack of HPSE partially interferes with this autocrine loop. Overall these data confirm that HPSE is a key player in renal fibrosis since it interacts with the regulation and the effects of TGF-β. HPSE is needed for pathological TGF-β overexpression in response to pro-fibrotic factors. Furthermore, HPSE modulates TGF-β-induced EMT: the lack of HPSE delays tubular cell transdifferentiation, and impairs the TGF-β autocrine loop.

The introduction of radiological contrast media and intravenous (i.v.) urography in clinical diagnostics in the 1930s enabled the discovery of several diseases, including the medullary sponge kidney (MSK). MSK is a renal malformation characterized by cystic anomalies of precalyceal ducts, which is frequently associated with nephrocalcinosis and renal stones. Although it was first recognized by G Lenarduzzi in 1939, its thorough description was the result of the ante litteram multidisciplinary cooperation between a radiologist (Lenarduzzi), a urologist (Cacchi), and a pathologist (Ricci), all at the Padua University Hospital. These authors 'established' the paradigm for its diagnosis that is still used today. I.v. urography is the gold standard for the diagnosis of MSK, but as the technique is used less and less, there is a concrete possibility of this renal condition being forgotten in the future. Although the pathogenesis of MSK has yet to be elucidated, its association with different malformative conditions supports the idea that it is a developmental disorder. Recent findings suggest that MSK may be the consequence of a disruption of the ureteral-bud/metanephric-blastema interface.

The authors performed a metabolic and morphologic investigation of calcium metabolism in 22 patients on continuous ambulatory peritoneal dialysis (CAPD), selected as the first procedure. The patients were kept on a diet containing about 30 Kcal/ kg, 1 g/kg of protein, 950 mg of phosphate and 1500 mg of calcium per day. They showed normal mean values of serum calcium, phosphate, alkaline phosphatase, total protein and albumin at the start and after six, 12 and 21 months of CAPD. Serum PTH levels showed a progressive decrease over 21 months. Serum 25-OH-D3 were low at start and showed a further decrease after 12 months of CAPD. Before and during CAPD, serum 1,25 (OH)2D3 levels were undetectable. The bone mineral content was within normal range at start and showed a slight decrease after 12 months of CAPD. In 64% of the patients, bone biopsies, obtained from the iliac crest at the start showed osteomalacia, either isolated or associated with hyperparathyroidism. After 12 months, osteomalacia was still evident in 71% of this group. The authors concluded that dietary restriction of phosphate is important in preventing secondary hyperparathyroidism in patients on CAPD. However, prevalence of osteomalacia is due to defective vitamin D metabolism and its management requires administration of vitamin D metabolites. In its morphological aspects and clinical features, renal osteodystrophy (RO) may differ significantly between patients on CAPD and those on hemodialysis (1–3). In addition, workers have reported conflicting opinions concerning the incidence and severity of bone lesions in CAPD patients (4–6). We undertook this investigation in order to evaluate the evolution and clinical, biochemical and morphologic aspects of RO in 22 ESRD patients treated with CAPD after long-term restriction of dietary protein and phosphate.

A clinical study was performed in 2 groups of patients with solitary kidneys, followed for 11-146 months. Group 1 had 9 patients (7 males and 2 females, aged between 23 and 68 years) with unilateral renal agenesis. Group 2 had 13 patients (9 females and 4 males, aged between 27 and 70 years) who underwent unilateral nephrectomy for the following reasons: hydronephrosis secondary to ureteropelvic junction stenosis, 7 patients; renal trauma, 4 patients; benign neoplasia, 2 patients. During the follow up, urinary protein excretion of more than 300 mg/day was observed in 9 patients, 3 in group 1 and 6 in group 2. Eleven patients, 8 in group 1 and 3 in group 2, were hypertensive (diastolic blood pressure higher than 95 mm Hg). Hyperuricemia was observed in 14 patients, 10 in group 1 and 4 in group 2. Seven patients, 4 in group 1 and 3 in group 2, had a significant deterioration of renal function. Neither proteinuria nor renal failure were observed before at least 10 years had elapsed since the anatomic condition of solitary kidney had been established. A surgical renal biopsy was performed in 1 patient with unilateral renal agenesis and showed focal glomerular sclerosis. This study adds support to the view that the reduction of 50% of the renal tissue may be a risky situation in humans as well as in animals.

Fifteen patients aged 31-74 years (five male, ten female) on renal biopsy showed intense linear deposits of light chains along tubular basement membranes (TBM) by immunofluorescence, and/or granular dense deposits on electronmicroscopy. Multiple myeloma was diagnosed in ten patients. The onset of myeloma and nephropathy was simultaneous in six patients; nephropathy preceded or followed the diagnosis of myeloma in three and one patients respectively. The mode of onset of nephropathy was acute or rapidly progressive renal failure in five cases, chronic renal failure in seven, and heavy proteinuria in three. Only two patients had normal renal function at biopsy. Serum monoclonal component was kappa in five patients, IgG kappa in three, IgD kappa in one, IgG lambda in one, IgA lambda in one, absent in three, and not detected in one. On light microscopy eight cases had nodular glomerulosclerosis, three cast nephropathy and 14 TBM thickening. Immunofluorescence for monoclonal light chain(s) was positive in 11 of 13 cases. Electron microscopy showed finely granular deposits in the inner side of glomerular basement membranes (GBM) and the outer side of TBM in 11 of 11 tested cases. The evolution was towards chronic renal failure in 12 patients (six of whom required dialysis), death in two, unknown in one. Four patients died after a period of dialysis, from infections or cardiovascular complications.

The frequency of renal tubular acidosis was evaluated in 28 adult patients with recurrent calcium nephrolithiasis (19 with 'renal' hypercalciuria, 9 with normocalciuria and no metabolic abnormality) and no evidence of obstruction or infection of the urinary tract. Eight patients with hypercalciuria (42%) had a defective renal reabsorption of bicarbonate, based on a fractional excretion of bicarbonate higher than 7% and a TmHCO3/GFR lower than 2.2 mEq/dl; 2 of them had an associated distal defect of acidification, as judged by a U-B pCO2 lower than 18 mm Hg in maximally alkaline urine. One patient with hypercalciuria had distal tubular acidosis, based on a urine pH higher than 5.3 during acidosis. Only 1 patient with normocalciuria had associated proximal and distal acidification defects. The remaining 8 patients displayed a normal renal acidifying capacity. The bicarbonate wastage was independent of serum PTH levels, vitamin D status and hypercalciuria and was associated with a defective tubular reabsorption of phosphate, increased random urinary pH and more active nephrolithiasis, with a prevalence of mixed calcium oxalate and phosphate stones. Our study shows a high incidence of defective tubular reabsorption of bicarbonate in patients with calcium nephrolithiasis and 'renal' hypercalciuria and suggests that the proximal acidification defect plays a pathogenetic role in promoting calcium nephrolithiasis.

A biochemical and bone biopsy investigation was made in 30 patients with chronic renal failure. Osteomalacia was the main pathological feature in 60% of the patients. Both optical and electron microsc

From use of 99mTc-Ca-Sn-gluconate in patients with various degrees of renal failure the following conclusions were drawn: 1. a good relationship exists between the parenchymal and vascular patterns in scintigraphy and the functional renal impairment; 2. the morphological definition is good, since in most cases a differential diagnosis can be made between diffuse parenchymal disease and space-occupying lesions even very low glomerular filtration rate values; 3. this technique is supplementary to i.v. pyelography in patients with relatively good glomerular filtration rate values and is a reliable alternative to i.v. pyelography in those with low creatinine clearance values.

Unilateral ureterosigmoidostomy (U.S.S.) was performed on 15 rabbits and then the animals were sacrificed after 3, 8 and 15 months. The gross appearance of the kidney and radiological investigations revealed enlargement of the pelvis and of the ureter on the operated side although the anastomosis was patent in all cases. In rabbits sacrificed 8 months after U.S.S. an adenomatous polyp was present at the site of anastomosis. Histological examination of the affected kidney showed pyelonephritis secondary to obstruction and immunopathological studies revealed in some rabbits glomerular and tubular deposition of immunoglobulins and complement. The contralateral kidney was always normal. Biochemical investigations showed only a moderate increase in blood urea nitrogen and plasma creatinine values.

To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy, we compared two regimens based on a 6-mo treatment, alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide. Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were randomized to be given methylprednisolone (1 g intravenously for 3 consecutive days followed by oral methylprednisolone, 0.4 mg/kg per d for 27 d) alternated every other month either with chlorambucil (0.2 mg/kg per d for 30 d) or cyclophosphamide (2.5 mg/kg per d for 30 d). The whole treatment lasted 6 mo; 3 mo with corticosteroids and 3 mo with one cytotoxic drug. Among 87 patients followed for at least 1 yr, 36 of 44 (82%; 95% confidence interval [CI], 67.3 to 91.8%) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome, versus 40 of 43 (93%; 95% CI, 80.9 to 98.5%) assigned to methylprednisolone and cyclophosphamide (P = 0.116). Of patients who attained remission of the nephrotic syndrome, 11 of 36 in the chlorambucil group (30.5%) and 10 of 40 in the cyclophosphamide group (25%) had a relapse of the nephrotic syndrome between 6 and 30 mo. The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups (P < 0.01) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr. Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects. Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster. One patient per group developed cancer. It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr.

Background: Immediately after renal transplantation, patients experience rapid and significant improvement of their clinical conditions and undergo considerable systemic and cellular modifications. However, some patients present a slow recovery of the renal function commonly defined as delayed graft function (DGF). Although clinically well characterized, the molecular mechanisms underlying this condition are not totally defined, thus, we are currently missing specific clinical markers to predict and to make early diagnosis of this event. Methods. We investigated, using a pathway analysis approach, the transcriptomic profile of peripheral blood mononuclear cells (PBMC) from renal transplant recipients with DGF and with early graft function (EGF), before (T0) and 24 hours (T24) after transplantation. Results: Bioinformatics/statistical analysis showed that 15 pathways (8 up-regulated and 7 down-regulated) and 11 pathways (5 up-regulated and 6 down-regulated) were able to identify DGF patients at T0 and T24, respectively. Interestingly, the most up-regulated pathway at both time points was NLS-bearing substrate import into nucleus, which includes genes encoding for several subtypes of karyopherins, a group of proteins involved in nucleocytoplasmic transport. Signal transducers and activators of transcription (STAT) utilize karyopherins-alpha (KPNA) for their passage from cytoplasm into the nucleus. In vitro functional analysis demonstrated that in PBMCs of DGF patients, there was a significant KPNA-mediated nuclear translocation of the phosphorylated form of STAT3 (pSTAT3) after short-time stimulation (2 and 5 minutes) with interleukin-6. Conclusions: Our study suggests the involvement, immediately before transplantation, of karyopherin-mediated nuclear transport in the onset and development of DGF. Additionally, it reveals that karyopherins could be good candidates as potential DGF predictive clinical biomarkers and targets for pharmacological interventions in renal transplantation. However, because of the low number of patients analyzed and some methodological limitations, additional studies are needed to validate and to better address these points. © 2014 Zaza et al.; licensee BioMed Central Ltd.