The effect of pregnancy on renal disease is a controversial issue. Some investigators hold that it has no effect, whereas others report a worsening of the glomerular lesions and a deterioration of renal function during gestation. The present authors, in a combined prospective and retrospective study, have analyzed the influence of pregnancy on the renal function profiles of patients with primary glomerulonephrities.

PURPOSE:This report describes data collected by the Italian Registry of Renal Biopsies (IRRB) (E mail http://www.teseo.it/nephrology/irrb), which includes 15461 renal biopsies (RB) performed over a period of 7 years (1987-1993).METHODS:From 1987 to 1988, the Registry recorded only the histological diagnosis of 3686 RB, whereas beginning in 1989, additional records (sex, age, clinical symptoms and renal function) were obtained from 11,775 patients undergoing RB. This is the first report on such a large number of RB containing data from 96% of Italian renal units which routinely perform RB.RESULTS:In 13,835 RB performed in native kidneys, two groups of renal diseases, primary (59.9%) and secondary (25.4%) glomerulonephritis (gn), were more frequent than others. Among primary gn, the frequency of cases of IgAN, membranous gn, and focal and segmental glomerulosclerosis were 36.9, 21.7 and 10.4% respectively. Renal disease due to immune-mediated causes (51%) and dysgammaglobulinaemia (26.9%) were the most frequent among secondary gn. In the former group, the frequency of cases with lupus nephritis and vasculitis were 51.6 and 25.9% respectively. Renal amyloidosis (39.3%), essential mixed cryoglobulinaemia (30.9%), and multiple myeloma were the most frequent forms in the latter group. In 1993 the incidence of the following groups of renal disease was: primary gn (22.7 p.m.p.), secondary gn (11.1 p.m.p.) of which immune-mediated gn (5.8 p.m.p.), dysgammaglobulinaemias associated with nephritis (2.4 p.m.p.). IgAN and membranous gn, as primary gn, had an incidence of 8.4 and 4.9 p.m.p, respectively, while lupus nephritis (2.6 p.m.p.) and renal vasculitis (1.6 p.m.p.) were the most frequent forms of secondary gn. Clinical data regarding 10357 RB collected during 5 years (1989-1993), showed that the most common indications to perform RB were urinary abnormalities (30.8%) and nephrotic syndrome (27.1%), followed by recurrent episodes of macrohaematuria (8.7%) and nephritic syndrome (5.4%). Acute renal failure was present in 9.2% of patients and chronic renal insufficiency in 18.8% of cases. Membranous gn (32.9%), focal and segmental glomerulosclerosis (12.3%), and minimal-change disease (12.0%) were the most frequent diagnoses in patients with nephrotic syndrome, while post-streptococcal gn (16.1%) and IgAN (14.0%) were frequent in the nephritic syndrome. IgAN was frequently found in patients with urinary abnormalities (29.8%) and recurrent episodes of macrohematuria (71.4%). Twenty per cent of the acute renal insufficiency cases were secondary to necrotizing vasculitis, while chronic renal failure was present in 16.6% of the IgAN patients.FUTURE TRENDS:The IRRB is considering to extend its programme to include (i) paediatric section regarding RB from patients aged less than 18 years; (ii) annual review of clinical data concerning the kidney function of selected groups of patients recorded in IRRB, and (iii) the listing of IRRB records on the INTERNET, to facilitate the distribution of information throughout the scientific community.

This study presents the 10-yr follow-up results of a multicenter controlled trial on 108 recipients of cadaveric renal transplantation, randomized to receive cyclosporine (N = 55) or azathioprine (N = 53), both in combination with steroids. The 10-yr patient survival rate was 89% in the cyclosporine group and 83% in the azathioprine group (P = not significant [NS]); the 10-yr graft survival was 56% and 35%, respectively (log-rank test, P = 0.009). The half-life of grafts functioning after 1 yr was 15.4 +/- 3.9 versus 10.6 +/- 3.6, P = NS). The rate of early rejection in the cyclosporine group was significantly lower than that in the azathioprine group (0.30 versus 1.4, P < 0.01). Although the mean creatinine clearance rate was always higher in the azathioprine group, the decline in graft function from the first to the tenth yr was not significantly different between the two groups (-13.0 +/- 16.4 versus -12.3 +/- 19 mL/min, P = NS). In cadaveric renal transplantation, cyclosporine allows better graft survival than azathioprine, not only in the short term but also in the long term, with similar attrition of graft function for up to 10 yr.

We have evaluated intracellular pH (pH(i)) and Na+/H+ exchanger activity in peripheral lymphocytes from 16 patients on regular acetate hemodialysis. All the patients were taking oral NaHCO3 supplementation (30 mmol/day), to maintain predialysis arterial blood acid-base status within normal range (pH 7.36 +/- 0.02, P-HCO3- 23.3 +/- 1.2 mM, pCO(2) 40.9 +/- 1.4 mm Hg). pH(i) was measured, using the fluorescent probe BCECF (2',7'-bis-carboxyethyl-5,6-carboxy-fluorescein), both in nominal absence of bicarbonate (Hepes solution, pH 7.4; n = 10) and in the presence of HCO3-/CO2 buffer system (pH 7.4, [HCO3-] 25 mM, pCO(2) 40 mm Hg; n = 6). Predialysis pH(i) did not differ from controls when measured in the presence of HCO3-/CO2 (7.28 +/- 0.04 vs. 7.29 +/- 0.04, p = NS), but was lower in dialysis patients than in normal subjects (7.11 +/- 0.04 and 7.20 +/- 0.02, respectively; p < 0.05) when measured in Hepes solution. This suggested that bicarbonate-independent pH(i) regulation was abnormal in dialysis patients. To further characterize this abnormality of pH(i) regulation, lymphocytes were exposed to ethylisopropylamiloride, a specific Na+/H+ antiporter inhibitor, in Hepes solution; this maneuver induced a significantly lower decrement in pH(i) (0.04 +/- 0.04 vs. 0.15 +/- 0.03, p < 0.05) in dialysis patients than in controls, indicating reduced Na+/H+ exchanger activity in the patients. The rate of pHi recovery during the first 30 s after induction of various degrees of cell acidification (pH(i) range 6.2-7.0), which in the absence of HCO3-/CO2 is dependent on Na+/H(+)exchanger activity, was also reduced in the patients as compared to controls (p < 0.001). These findings demonstrate depressed Na+/H+ exchanger activity in lymphocytes from patients on chronic maintenance hemodialysis; accounting for the lower pH(i) in Hepes solution. However, this abnormality does not prevent pH(i) to be mainteined in the normal range in the presence of the physiological buffer HCO3-/CO2 and possibly in vivo.

A case of end-stage renal failure caused by renal amyloidosis of the AA type is reported. No chronic disease responsible for the deposition of reactive amyloid was detected until giant lymph node hyperplasia of the angiofollicular type was identified in a mediastinal mass. Amyloid was found within the tumour mass and was characterized by immunochemistry with monoclonal antibodies to be of the AA type. Castleman's disease should be added to the list of chronic diseases endangering renal function by inducing the production and tissue deposition of secondary (AA) amyloid.

We report the clinical outcome of 105 essential mixed cryoglobulinemia (EMC) patients with renal involvement collected throughout 25 years in three renal Units of Milan. The median follow-up was 72 months since renal biopsy and 131 months since the clinical onset of EMC. Patient survival was 49% at 10 years after renal biopsy. Forty-two patients died primarily from cardiovascular and liver disease or infection, whereas 15 patients developed chronic renal failure. Two patients had a complete remission of the disease while 15 had a remission only of renal signs. Thirty-one patients are alive with persistent renal and extrarenal manifestations. Anti-HCV antibodies were retrospectively detected in 34 patients and were present in 85% of them. This variable was not included in the statistical evaluation. At multivariate analysis, age older than 50 years, purpura, splenomegaly, cryocrit levels higher than 10%, C3 plasma levels lower than 54 mg/dl, and serum creatinine higher than 1.5 mg/dl were independent risk factors for death or dialysis. In conclusion, several factors may influence the outcome of patients with EMC nephritis. Markers of disease activity and an impaired renal function can herald a bad prognosis. It should be stressed, however, that only a minority of patients eventually develop renal failure, probably because in the most severe cases patients die earlier.

In 10 adult patients (5 females and 5 males, aged 13-57 years) with Gitelman's syndrome (GS, or hypocalciuric variant of Bartter's syndrome, characterized by chronic renal hypokalemia, metabolic alkalosis, hypomagnesemia and hypocalciuria), parameters of Ca metabolism and calciotropic hormone levels were evaluated. Hypocalciuria was associated with a marked reduction of fractional excretion of ionized Ca (as compared with 16 sex- and age-matched controls) and normal filtered Ca load, as indicated by serum ionized Ca; hypocalciuria was thus the result of increased tubular reapsorption of filtered Ca. Plasma levels of total Ca were increased in GS (p < 0.02) but ionized Ca was not different from controls; percent fraction of ionized to total Ca was reduced, indicating increased Ca complexation and/or protein binding, possibly related to a metabolic alkalosis-induced increase of plasma albumin affinity for Ca. Levels of plasma total protein and albumin were similar in GS and controls. Despite similar ionized Ca levels, pTH(1-84) was lower in GS than in controls, indicating abnormal ionized Ca-PTH relationship, possibly related to hypomagnesemia. Plasma 1,25(OH)(2)D levels were not different in GS and in controls, and intestinal fractional Ca absorption (evaluated with a simplified method using stable Sr as a tracer) was not reduced in 4 patients. However, in 5 patients bone mineral density in the forearm (3 patients) or lumbar spine (2 patient) was normal. Thus, despite chronic hypocalciuria and normal 1,25(OH)(2)D levels, Ca 'thesaurosis' does not occur in bones of GS patients; a likely explanation is that, despite normal 'fractional' intestinal Ca absorption, 'net' intestinal absorption is reduced, due to increased intestinal Ca secretion.

Six adult patients (4 females and 2 males, age range 26-57 years) with Gitelman's syndrome (GS) were treated with spironolactone 200-300 mg/day (n = 5) and/or amiloride 10-30 mg/day (n = 3) for 1-18 months. The patients had hypokalemia, hyperreninemia, chloride-resistant metabolic alkalosis, renal hypomagnesemia (n = 5), and hypocalciuria (n = 5). Free water clearance studies during maximal water diuresis and furosemide administration were suggestive of a solute reabsorptive defect beyond the loop of Henle. Antialdosterone therapy induced a significant increase of PK (from 2.6 +/- 0.4 to 3.4 +/- 0.4 mM; p < 0.0001) and a decrease of CK (from 21.4 +/- 13.2 to 10.6 +/- 4.8 ml/min, p < 0.02) and FEK (from 21.0 +/- 13.6 to 13.4 +/- 5.7%; p < 0.03); PMg increased from 1.38 +/- 0.38 to 1.64 +/- 0.21 mg/dl (p < 0.03) with a parallel fall of CMg (from 5.5 +/- 2.3 to 2.9 +/- 1.5 ml/min; p < 0.02) and FEMg (from 5.7 +/- 2.6 to 2.9 +/- 0.6%; p < 0.05); arterial blood pH and HCO3- did not change (P = plasma, C = clearance, FE = fractional excretion). The creatinine clearance fell (from 90.5 +/- 16.8 to 65.8 +/- 20.9 ml/min; p < 0.05), and Prenin rose (from 16.6 +/- 8.9 to 35.3 +/- 25.3 ng/ml/h; p < 0.02, as did Paldo (from 26.1 +/- 12.3 to 109 +/- 82.6 ng/dl; p < 0.01), indicating extracellular fluid volume contraction; however no significant clinical symptoms of hypovolemia ensued.(ABSTRACT TRUNCATED AT 250 WORDS)

A clinical trial was performed in order to evaluate the safety and the variations of lymphocyte subpopulations induced by the intravenous administration of Deflazacort 21-hemisuccinate (DFZ-HS), the water-soluble derivative of the prednisolone analogue deflazacort acetate. DFZ-HS was tested at doses ranging from 1 to 10.55 mg/kg and was compared with methylprednisolone (MPR) administered at equipotent doses. Sixteen healthy volunteers were studied according to a double-blind, 4 period balanced, incomplete cross-over design. Both drugs were well tolerated. DFZ-HS dramatically, but transiently, reduced the number of total and CD4(+) T lymphocytes at all doses tested, the maximum decrease being observed at the 8(th) hour after injection. Similar effects were observed following MPR administration. The potency ratio between DFZ-HS and MPR, calculated on the basis of CD4(+) T cells decrease, was about 1:1, suggesting that both drugs exert comparable immunomodulatory activities. These data, toghether with the well known low impact of DFZ-HS on glucidic and calcium metabolisms, support its possible use when high glucocorticoid doses are required in immunosuppressive therapy.

In the interstitial cell infiltrates associated with primary glomerulonephritis, approximately the same cellular composition has been found, T cells being predominant, monocytes fewer, and B cells least. Cell composition did not seem to be related to the cell density; the lowest percentages of monocytes have been observed with either very high (FSGS) or very low (MGN) cell densities; and the highest percentages of T cells, with either the highest (FSGS) or the lowest (MGN) cell densities. On the other hand, some relationship seemed to exist with the cell distribution in the interstitium. The cell composition was nearly the same in diffuse and disseminated patterns, but was markedly different in nodular (focal) cell infiltrates; T cells were always in first place, but B cells instead of monocytes were in second place. Furthermore, IL2-receptor-presenting cells have been more often observed in nodular (focal) than in both diffuse and disseminated patterns, and more markedly in noniuxtaglomerular than in iuxtaglomerular noduli (foci). In conclusion, cell composition of intersitial infiltrates seems to reflect a cell-mediated immune reaction, leading to all interstitial cell infiltrates associated with primary glomerulonephritis. It is conceivable that the nodular (focal) pattern of distribution might correspond to a discrete mechanism and have a different meaning.