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Nephrology in Rome began in the 1960s with the arrival of Ernico Fiaschi in the wake of Cataldo Cassano at the Institute of Medical Pathology (later on Clinica Medica II). A group of doctors interested in nephrology was set up, with among them Giulio A. Cinotti, who was to become full professor of nephrology at the University of Rome ''La Sapienza'' in 1980. By the end of the 1960s, the renal transplant activity had become an important asset at the Institute of Surgical Pathology (later on Clinica Chirurgica II) thanks to Paride Stefanini. A chair of surgical nephrology was instituted at the Urology Clinics of Ulrico Bracci; the chair was first held by Nicola Cerulli, who developed an intensive hemodialysis program. Around the same time, the Center for the Research and Treatment of Arterial Hypertension and Kidney Diseases became operational at the hospitals of Rome (under the responsibility of Vito Cagli at the Policlinico Umberto I), while a nephrology and dialysis unit, directed by Giancarlo Ruggieri, was set up at the San Giacomo Hospital. Many nephrology-related ''cultural'' activities started to be undertaken thanks to the ''Gruppo Laziale di Nefrologia Medica e Chirurgica'' founded by Drs Cagli, Cerulli, and Cinotti. Two national congresses were organized by Giulio Cinotti in 1979 (Fiuggi) and 1992 (Rome).

An 11-year old boy with acute lymphoid leukemia underwent umbilical cord stem cell infusion. This was followed at day 15 by the onset of asymptomatic hypotonic isovolemic hyponatremia. The disorder could be attributed to a syndrome of inappropriate ADH secretion (SIADH), most probably related to the massive i.v. induction treatment with cyclophosphamide. The major causes and clinical variants of SIADH are reviewed, with particular emphasis on the complications of chemotherapy in hematological diseases. Worsening of hyponatremia during routine parenteral feeding, as opposed to normalization of plasma Na+ by infusion of hypertonic saline, emphasize the importance of early accurate diagnosis and careful follow-up of these iatrogenic sequelae of stem cell allograft.

In patients with PG-dependent renal function, NSAID administration constantly reduces GFR and RBF in a dose-dependent fashion. In this situation, the risk of overt acute renal failure is high and should be taken into proper account. In contrast, the incidence of NSAID-related renal structural alterations appears to be very low, yet the absolute number of patients may be significant considering the wide use of such drugs. Concerning the antiproteinuric effect of NSAIDs, the unfavourable ratio risk/benefit does not seem to support their indication in proteinuric nephropathies. The development of PGHS-2 selective inhibitors is promising, and may open new therapeutical strategies in the treatment of the progression of renal disease.

Na+/Ca2+ exchange contributes to the control of cytosolic free Ca2+ levels ([Ca2+]i) in resting and activated cultured human mesangial cells. We have previously shown that activation of phospholipase C by vasoconstrictors enhances Ca2+ influx upon extracellular Na+ withdrawal. This effect is not mediated by concurrent activation of protein kinase (PK) C, since it occurs even after PKC inhibition, and phorbol esters actually blunt both basal and stimulated Na+/Ca2+ exchange. We now studied the effects of PKA and PKG activation by adenylate/guanylate cyclase stimuli or by permeant analogues of cyclic nucleotides in monolayer cultures loaded with the fluorescent Ca(2+)-sensitive probe, fura-2. The exchanger was inhibited by the stable prostaglandin I2 analogue, iloprost, which is transduced by cAMP (peak [Ca2+]i inhibition by 1 microM iloprost 35 +/- 3%). Similarly, non-receptor activation of adenylate cyclase by 10 microM forskolin inhibited basal and agonist-stimulated Na+/Ca2+ exchange by 52 +/- 4 and 66 +/- 4%, respectively. Dibutyryl-cAMP (0.1 mM) also inhibited stimulated Na(+)-dependent Ca2+ influx by 72 +/- 2%. The particulate guanylate cyclase agonist, atriopeptin III, and the soluble guanylate cyclase activator, glyceryltrinitrate, also inhibited both basal and angiotensin II-stimulated Na+Ca2+ exchange (to a maximum of 53 +/- 5 and 62 +/- 3%, respectively). Dibutyryl-cGMP (1 mM) mimicked the effects of cGMP stimuli, reducing stimulated Na+/Ca2+ exchange by 79 +/- 2%. Therefore, similar to PKC, cyclic nucleotide activation of PKA and PKG regulates Na+/Ca2+ exchange, providing a functional link between transmembrane signalling systems for vasoactive agents in cultured human mesangial cells.

Clinical and experimental studies have markedly expanded our understanding of the causes of renal disease. Although they have not resulted in comparable therapeutic advances, new lines of treatment have emerged which cannot be underestimated. The prognosis of lipoid nephrosis has been substantially modified. The treatment of membranous glomerulonephropathy with steroids and immunosuppressive drugs may modify the course of the disease, at least in a subset of patients with decreased and deteriorating renal function. Encouraging results have been reported after the use of inhibitors of platelet aggregation in mesangiocapillary glomerulonephritis. We have demonstrated that a receptor antagonist of thromboxane can significantly influence the renal functional parameters in patients with lupus nephritis. ACE-inhibitors, cyclosporine and NSAID's have proved useful in reducing nephrotic proteinuria. Lipid lowering agents are able to ameliorate the glomerular lesions in experimental models of renal injuries. Since systemic hypertension may initiate the development of renal disease or accelerate loss of function in the kidney in which parenchymal disease is already established, controlling hypertension by any effective means helps to slow the progression of renal failure. Preliminary reports have suggested that there may be advantages to using ACE-inhibitors and/or calcium entry blockers.

OBJECTIVE To compare the efficacy (maintenance of remission), safety and tolerability of cyclosporin (CsA) with those of cyclophosphamide in patients with steroid-dependent or frequently relapsing nephrotic syndrome (NS). DESIGN Open, prospective, randomized, multicentre, controlled study for parallel groups, stratified for adults and children. The setting was in nephrological departments in Italy. SUBJECTS AND INTERVENTIONS Seventy-three patients with steroid-sensitive idiopathic NS admitted to the study were randomly assigned to cyclophosphamide (2.5 mg/kg/day) for 8 weeks or CsA (5 mg/kg/day in adults, 6 mg/kg/day in children) for 9 months, tapered off by 25% every month until complete discontinuation at month 12. Seven patients lost to follow up were not considered in the analysis. The remaining 66 patients were followed up for 3-24 months after randomization. MAIN OUTCOME MEASURES Relapse-free survival; number of N.S. relapses/patient/year; cumulative dose of prednisone/patient; laboratory investigations (kidney and liver functions, haematological parameters); incidence of adverse events. RESULTS At month 9, 26 of 35 CsA-treated patients were still in complete remission and a further five patients were in partial remission; 18 of 28 cyclophosphamide-treated patients were in complete remission, and one in partial remission (P = NS). No difference between adults and children was seen with either treatment. The risk of relapse was similar between frequent relapsers (19 of 22) and steroid-dependent patients (8 of 14) given CsA, and those given cyclophosphamide (5 of 15 and 6 of 15). The mean number of relapses per year and the mean dose of prednisone per year were significantly less (P < 0.001) in both groups for the experimental year than for the year before randomization. At 2 years, 25% of the patients given CsA (50% adults and 20% children) and 63% of those given cyclophosphamide (40% adults and 68% children) had not had any relapse of NS. Tolerance to the two drugs was generally good. The CsA-related side-effects were mild and disappeared after drug discontinuation. CONCLUSIONS This study shows that both treatments are effective and well tolerated; more patients given cyclophosphamide had stable remissions.

Besides its structural role as the main stalk of the capillary network, the mesanguim is responsible for the formation and reabsorption of the extracellular matrix, for sieving and processing of circulating macromolecules, and for regulating glomerular capillary flow and filtration through its contractiler characteristics

In order to verify the validity of the assumption that male urinary Prostaglandin (PG) E2 reflects its renal production, PGE2 and PGF2 alpha concentrations were measured by radioimmunoassay in the renal venous plasma (RVP) and urine (U) of 12 male and 4 female healthy volunteers. While women had a similar PGE2/PFG2 alpha ratio in RVP (0.59 +/- 0.18) and U (0.41 + 0.06), men and a significantly (P less than 0.05) higher ratio in U (1.43 +/- 1.72) as compared to RVP (0.54 +/- 0.16). This was largely due to considerably higher and more variable U-PGE1 concentrations (roughly 6 times higher than female values), despite almost identical RVP levels. The possibility of an increased U excretion of a cross-reacting member of the PG-system, as a cause of such apparently high PGE2-like immunoreactivity (LI), was ruled out by TLC characterization of PGE2-LI with three different anti-PGE1 sera. Thus, male U-PGE2 may variably reflect an extra-renal source, such as contamination with trace amounts of seminal fluid. It is concluded that, unless such a contamination can be monitored and corrected for, measurement of male U-PGE1 should be considered of questionable relevance to renal PG-synthesis.

One-hundred patients suffering from slight-moderate hypertension (53 m, 47 f, aged between 18 and 78, average 49.08) have been studied in order to assess the effectiveness and tolerance of lisinopril ("Zestril", ICI-Pharma), a new ACE inhibitor in a single daily administration at doses of between 10 and 80 mg in relation to pressure values. Monotherapy with Lisinopril proved effective in 84 patients (88.4%), in 74 of whom (7.9%) pressure values were returned to normal. 11 patients (11.6%) did not respond to treatment. In most cases, the result was obtained with a dose of 20 mg in a single administration (32.6%). The incidence of side-effects was limited and in no case required the withdrawal of the drug.

The effect of 1-alpha-OHD3 on the rate of decline of renal function was studied in 18 patients with predialytic chronic renal failure. 9 patients with serum creatinine 4.19 +/- 1.63 mg/dl, were treated with 1-alpha-OHD3 0.4 +/- 0.11 micrograms/day and a low phosphate diet and 9 patients, with serum creatinine 3.69 +/- 1.24 mg/dl, received the low phosphate diet alone. In the first group retrospectively in 8 patients up to 3-44 months and prospectively in all patients reciprocal values of serum creatinine levels fell linearly with time. Comparison of the slopes of the regression lines before and following the start of treatment did not show statistical differences in 6 cases, in 1 case the decline of renal function improved significantly and in 1 case it became positive. Serum calcium increased significantly (p less than 0.025), alkaline phosphatase decreased (p less than 0.005) and serum iPTH decreased in 6 of 8 cases. In the low phosphate diet group, serum calcium, alkaline phosphatase did not change while iPTH increased in 8 of 9 cases. The rate of decline of renal function before treatment in 3 cases did not improve after the institution of the diet. In conclusion improvement or prevention of secondary hyperparathyroidism in predialytic chronic renal failure can be achieved with daily doses of less than or equal to 0.5 micrograms 1-alpha OHD and a low phosphate diet. The small increment in serum calcium levels induced by the treatment did not accelerate the deterioration of renal function while showing a better control of alkaline phosphatase and serum iPTH than the low phosphate diet alone.

Antirheumatic drugs may cause a significant, although generally reversible, reduction of GFR, RPF, CNa and hyperkalemia in a wide range of extrarenal and renal disease states (severe liver disease, congestive heart failure, SLE, nephrotic syndrome, etc.); chronic ingestion has been associated with analgesic nephropathy. Recently cases have been reported of reversible acute renal failure with massive proteinuria and interstitial nephritis. The acute effects of a renal PG-inhibiting (ibuprofen) or a renal PG-sparing (sulindac) cyclo-oxygenase inhibitor on renal functional parameters (GFR, RPF, CNa, CK, urine volume) and proteinuria have been studied in 24 patients with clinically and biopsy proven chronic glomerular disease; in all patients ibuprofen significantly reduced GFR, RPF, CNa; these changes were fully reversible within a week of withdrawal of the drugs. A causal relationship exists between inhibited PG-synthesis and reduced renal function in these patients, since sulindac, which failed to reduce urinary PG excretion did not alter significantly the renal function. Moreover proteinuria is not reduced by ibuprofen at doses comparable, as far as concerns inhibition of PG-synthesis, to those of indomethacin.

Antirheumatic drugs may cause a significant, although generally reversible, reduction of GFR, RPF, CNa and hyperkalemia in a wide range of extrarenal and renal disease states (severe liver disease, congestive heart failure, SLE, nephrotic syndrome, etc.); chronic ingestion has been associated with analgesic nephropathy. Recently cases have been reported of reversible acute renal failure with massive proteinuria and interstitial nephritis. The acute effects of a renal PG-inhibiting (ibuprofen) or a renal PG-sparing (sulindac) cyclo-oxygenase inhibitor on renal functional parameters (GFR, RPF, CNa, CK, urine volume) and proteinuria have been studied in 24 patients with clinically and biopsy proven chronic glomerular disease; in all patients ibuprofen significantly reduced GFR, RPF, CNa; these changes were fully reversible within a week of withdrawal of the drugs. A causal relationship exists between inhibited PG-synthesis and reduced renal function in these patients, since sulindac, which failed to reduce urinary PG excretion did not alter significanctly the renal function. Moreover proteinuria is not reduced by ibuprofen at doses comparable, as far as concerns inhibition of PG-synthesis, to those of indomethacin.

Intestinal absorption of calcium was evaluated in 6 uraemic patients and in 7 control subjects by a two isotope technique exploring absorption in the four hours following ingestion of the dose. In the first two hours, calcium absorption in the patients was markedly lower than normal and was corrected by 6-10 day administration of dihydrotachysterol, 0.66 mg per day. The administration of 0.33 mg per day proved less effective. The data indicate the existence of impaired intestinal calcium absorption in chronic renal failure and reversal of the defect after DHT administration. The method of investigation appears to be a valid procedure for the study of calcium malabsorption of CRF and in the evaluation of the effect of vitamin D metabolities and analogs.

Alterations in the pattern of renal PG have been reported in hypertensive animals and in human essential hypertension, reflecting a primary causative defect or changes which are secondary to hypertension. Furthermore, direct evidence for a primary role of AA metabolites in the long term control of blood pressure emerges from the interrelationship between angiotensin II, vasopressin, norepinephrine, and alfa-adrenergic stimuli. Since locally synthetized vasodilatory PG are known to modulate the effects of vasoconstrictor stimuli on renal vasculature and sodium excretion, it is suggested that an alteration of this interplay may be responsible for some forms of experimental and human hypertension.

Nel corso dello studio ultrastrutturale di una biopsia renale di un paziente con sindrome di Alport sono stati frequentemente osservati corpi nucleolari nelle cellule endoteliali glomerulari. Gli autori descrivono tale reperto e ne discutono il possibile significato.

The present study deals with the appropriate statistical approach to the histomorphometric technique carried out on bone tissue with the Merz and Schenk integrating eyepiece. Statistical analysis of the results obtained from ten bone biopsies of renal osteodystrophic patients enabled to calculate the values of standard errors for each histomorphometric parameter as a function of measured histological fields. The examination of 42 fields chosen at random on histological sections from different sites of the bone biopsy guarantees sufficiently low standard error values. This technique is of invaluable help in the study of metabolic bone diseases, and extremely useful in the evaluation of treatment trials in renal osteodystrophy.

Plasma renin activity may be affected by temperature during the processing of blood samples (loss of activity or cryoactivation). We measured plasma renin activity on samples maintained at room temperature up to 240 min. No significant change was found in comparison with samples maintained at 0 degrees C; similarly, no cryoactivation was observed when routine freezing procedures were employed instead of instant freezing.

Techniques are described in detail for the radioimmunological measurement of prostaglandin (PG) E2 and F2alpha in human urine. 50 ml urine samples are extracted with an organic solvent system and then purified by silicic acid column chromatography. The overall recovery after extraction and purification, calculated with labeled as well as unlabeled compounds, is in the order of 70%. The column eluates are assayed at 1:12-1:60 dilution in the "standard diluent" of the assay: 8 pg PGE2 or PGF2 alpha/ml of whole urine represents the lowest measurable concentration. A urine blank and a solvent blank were evaluated separately, subjecting 50 ml of urine obtained from an indomethacin treated subject ("PG-free" urine) or 50 ml of distilled water, respectively, to the extraction-purification procedures. Both were found not to interfere with the antigen-antibody reaction. Urinary PG-like immunoreactivity (LI) was characterized in terms of immunochemical and thin-layer chromatographic (TLC) behavior. Both urinary PGE2-LI and PGF2 alpha-LI behaved as authentic PGE2 and PGF2 alpha, upon dilution and on TLC. In 33 healthy female subjects (aged 19-58 yr), urinary excretion rates averaged 178 +/- 80 (mean +/- SD) ng/day for PGE2 and 498 +/- 181 ng/day for PGF2 alpha. In a group of 8 healthy men, both PGE2 and PGF2 alpha excretion rates were higher and more scattered than the female values. When two healthy women were given indomethacin (200 mg/day), urinary PGE2 and PGF2 alpha dropped to undetectable levels during the 4th day of drug therapy. Intravenous injection of furosemide (50 mg) in a female volunteer was followed by an immediate rise of urinary sodium, PGE2, PGF2 alpha and PGE2/PGF2 alpha ratio and plasma renin activity. In a 10 year old girl with Bartter's syndrome, urinary PG excretion rate was elevated with a 3 times higher than normal PGE2/PGF2 alpha ratio. Indomethacin therapy resulted in a prompt drop of PG excretion rate and of plasma renin activity. These results show that a combination of adequate purification steps and antisera with optimal characteristics provides a reliable method for measuring PGE2 and PGF2 alpha in urine, and therefore a valuable tool to further our knowledge of the physiology and physiopathology of the renal PG-system.

Renal tissues from two groups of patients were studied with fluorescein-labeled (Fl-) antibodies (Abs) to immunoglobulins, complement, and antibodies prepared in rabbits against BSA conjugate of 5-methyluridine (T) and cytidine (C), the latter two of which react specifically with denatured DNA. The first group consisted of 13 SLE patients, and the second consisted of 53 patients with non-SLE nephropathies. The data obtained from the two groups of patients were used for comparison, and they showed the following:(a) Fl-Abs to immunoglobulins and complement were bound in the glomeruli of tissues from all patients with active SLE glomerulonephritis characterized by deposits of foreign material in glomerular capillary walls (GCW). The fluorescent pattern was granular, corresponding to the distribution of the glomerular deposits, as seen by electron microscopy. Fl-Abs reactive with thymine and cytosine were bound in the GCW of eight of the nine patients with active SLE glomerulonephritis and showed the same granular distribution. The capacity of these latter Fl-Abs to stain the GCW was removed by absorption with the homologous antigen or denatured DNA.(b) Fl-Abs to immunoglobulins, complement, and pyrimidine bases of DNA did not react with the GCW of two SLE patients without clinical and histologic evidence of glomerulonephritis or with the sclerotic glomeruli of two uremic patients with chronic "burned out" lupus nephritis.(c) The glomeruli of 47 of the 53 patients with other nephropathies bound Fl-Abs to immunoglobulins and complement to some extent, and in 26, the localization appeared as marked as in the patients with active SLE glomerulonephritis. Fl-Abs reactive with thymine and cytosine were bound in the GCW of only one of the renal tissues from the 53 non-SLE patients. In the remaining 52, no binding was seen.(d) The findings are consistent with the hypothesis that antigen-antibody complexes, formed by denatured DNA, specific antibody, and complement, are present in the deposits of foreign material accumulated in the GCW of patients with active SLE glomerulonephritis, and that they may contribute to the pathogenesis of this renal disease.