[The CROFF pavilion at the Policlinico Hospital in Milan: the beginnings].

This article collects the personal stories of the young doctors who in the early sixties contributed to the birth and development of the Croff pavilion at the Policlinico Hospital in Milan. Inaugurated on October 19, 1964, this has been the first institute in Italy entirely devoted to patients with kidney diseases. Since its inception, it has significantly contributed to the progress of nephrology thanks to important and pioneering investigations in the main fields of our specialty, which still continue nowadays. The different stories reported here follow the chronological order in which the young doctors arrived at Croff, each story representing a personal narrative that interweaves and integrates that of others. This gives rise to a vivid many-voiced account, from which emerge not only the figures of these young doctors, but also those of patients, nurses, and laboratory technicians.

Maternal outcome in pregnant women with lupus nephritis. A prospective multicenter study.

Retrospective studies reported a high incidence of maternal complications in pregnant women with lupus. In this paper we prospectively assessed the rate of risk and the risk factors of maternal outcome in women with stable lupus nephritis who received pre-pregnancy counseling. This prospective multicenter study includes 71 pregnancies in 61 women with lupus nephritis who became pregnant between 2006 and 2013. Complete renal remission was present before pregnancy in 56 cases (78.9%) and mild active nephritis in 15 cases. All women underwent a screening visit before pregnancy and were closely monitored by a multidisciplinary team. Lupus anticoagulant, serum C3 and C4 complement fractions, anti-DNA antibodies, anti-C1q antibodies, anticardiolipin IgG and IgM antibodies, anti-beta2 IgG and IgM antibodies were tested at screening visit, at first, second, third trimester of pregnancy, and one year after delivery. Renal flares of lupus during or after pregnancy, pre-eclampsia, and HELLP syndrome were defined as adverse maternal outcomes. Fourteen flares (19.7%), six cases of pre-eclampsia (8.4%) and two cases of HELLP (2.8%) occurred during the study period. All flares responded to therapy and the manifestations of pre-eclampsia and HELLP were promptly reversible. Low C3, high anti-DNA antibodies and predicted all renal flares. High anti-C1q antibodies and low C4 predicted early flares. The body mass index (BMI) was associated with increased risk of late flares. History of previous renal flares and the presence of clinically active lupus nephritis at conception did not increase the risk of renal flares during pregnancy. History of renal flares before pregnancy, arterial hypertension, and longer disease predicted pre-eclampsia/HELLP. In pregnant women with lupus nephritis adverse maternal outcomes were relatively common but proved to be reversible when promptly diagnosed and treated. Immunological activity, arterial hypertension and BMI may predispose to maternal complications.

A regional survey of serum creatinine measurement methods and estimated glomerular filtration rate reporting.

BACKGROUND: Only limited data are available on the diffusion of isotope dilution mass spectrometry (IDMS)-traceable methods used for serum creatinine measurement and on estimated glomerular filtration rate (eGFR) reporting. METHODS: A questionnaire was addressed to accredited laboratories in Lombardy, Italy, including the following issues: method of creatinine measurement, instrument model, IDMS calibration traceability, reference intervals reported by sex and age, eGFR reporting, eGFR formula used and information about the eGFR value reported in patient records. A parallel questionnaire was addressed to nephrology centers and included the following: knowledge of methods for serum creatinine measurement in their center, usefulness of eGRF reporting and opinions on the need for educational initiatives. RESULTS: Seventy-two percent of 72 laboratories and 89% of 47 nephrology centers responded to the questionnaires. Among the methods used for serum creatinine measurement, 87% were IDMS traceable and 30% were enzymatic. Reference intervals were differentiated by sex and by age in 90% and 42%, respectively. Laboratories reported eGFR in 35% and only when requested in 13%. eGFR was calculated by the Modification of Diet in Renal Disease (MDRD) Study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in 88% and 12% of laboratories, respectively, and reporting was accompanied by information on the interpretation of values in 62%. Among nephrologists, 64% thought eGFR reporting useful, 29% were concerned with an excess of unnecessary requests for consultations and 95% expressed a favorable opinion of educational initiatives. CONCLUSION: Our survey highlights the need for further improvement in serum creatinine measurement and reporting, and for coordinated interventions involving all major stakeholders.

Pregnancy and progression of IgA nephropathy: results of an Italian multicenter study.

BACKGROUND: Whether pregnancy impacts on the long-term outcome of immunoglobulin A (IgA) nephropathy is unknown. This study aims to compare the long-term outcome of kidney disease in women with IgA nephropathy and preserved kidney function who did and did not become pregnant. STUDY DESIGN: Multicenter longitudinal cohort study. SETTING & PARTICIPANTS: Women of childbearing age with biopsy-proven IgA nephropathy, serum creatinine level

Severe reversible acute renal failure in idiopathic nephrotic syndrome.

BACKGROUND: Only few cases of acute renal failure (ARF) requiring dialysis have been reported in patients with idiopathic nephrotic syndrome (NS). This study aims to better define the clinical outcome and treatment of this condition. METHODS: A pilot enquiry regarding the occurrence of ARF requiring dialysis in patients with NS and biopsy proven minimal changes (MC) or focal segmental glomerulosclerosis (FSGS) was conducted among 5 nephrology centers. RESULTS: From 1996-2006, 6 patients with idiopathic NS (4 MC, 2 FSGS) developed ARF requiring dialysis early after onset of NS. At presentation all but 1 patient had elevated blood pressure. Patients were treated with dialysis from 7-40 days. All achieved complete or partial remission after 4-8 weeks of steroids. Recovery of renal function paralleled with the reduction of proteinuria. At renal biopsy proximal tubules showed a large amount of protein droplets, flattening of epithelial cells, and focal detachment of cells from the basal membrane. After a follow-up of 24-60 months, 5 patients had a relapse. Of these 4 were responsive to steroids, while one progressed to dialysis after an episode of hemolytic uremic syndrome related to cyclosporine treatment. ARF did not recur. CONCLUSION: ARF requiring dialysis is a rare and unexpected complication of idiopathic NS occurring in most cases early after presentation. These patients are sensitive to steroids that should be administered as promptly as possible in view of the potential noxious effect of protein overload on proximal tubular cells.

Pregnancy in women with pre-existing lupus nephritis: predictors of fetal and maternal outcome.

BACKGROUND: Only few data are available on pregnancy in patients with lupus nephritis (LN) diagnosed before conception. The aim of this study was to identify the risk factors for complicated pregnancy in women with pre-existing LN. METHODS: In a multicentre study, we collected data on 113 pregnancies occurring in 81 women with pre-existing biopsy-proven LN. Primary outcomes were fetal loss including perinatal death and renal flares during and 12 months after pregnancy. Univariate and logistic regression analyses were used to identify predictors of outcomes. RESULTS: Renal biopsy performed 7.2 +/- 4.9 years before pregnancy showed the following WHO classes: 6 patients in II, 8 in III, 48 in IV and 19 in V. At conception, most patients were in complete (49%) or partial (27%) remission. There were nine spontaneous abortions, one stillbirth and five neonatal deaths. Thirty-one deliveries were preterm. Birth weight was <2500 g in 34 newborns. During pregnancy or after delivery, there were 34 renal flares, most of which (20) were reversible. Three patients had a progressive decline of glomerular filtration rate (one on dialysis). At logistic regression analysis, the pregnancy outcome was predicted by hypocomplementaemia at conception (RR 19.02; 90% CI 4.58-78.96) and aspirin during pregnancy (RR 0.11; 90% CI 0.03-0.38). Renal flare was predicted by renal status (partial remission RR 3.0; 90% CI 1.23-7.34, nonremission RR 9.0; 90% CI 3.59-22.57). CONCLUSIONS: Pregnancy can be successful in most women with pre-existing LN, even for those with a severe renal involvement at onset. Renal flares during and after pregnancy are not uncommon and can be predicted by renal status assessed before pregnancy. Normocomplementaemia and low-dose aspirin therapy during pregnancy are independent predictors of a favourable fetal outcome.

Pilot study to assess increased dialysis efficiency in patients with limited blood flow rates due to vascular access problems.

In the last few years, the number of hemodialysis patients with inadequate blood flow (Qb) rates has increased due to vascular access problems. To avoid a clinical status of underdialysis, these patients need long-lasting dialysis sessions. However, other factors aimed to optimize the dialysis dose have to be considered. High-efficiency convective therapies, such as online hemodiafiltration (HDF), are claimed to be superior to high-flux hemodialysis (HF-HD) in improving the dialysis efficacy, but treatment efficacy is strongly related to blood flow rate and infusion volumes. Online mid-dilution (HDF-MD) with the Nephros OL-pure MD190 represents a new HDF concept to increase the removal of middle molecules. In a cross-over clinical trial, 8 patients, with Qb eff <300 mL/min, received either online HDF-MD or HF-HD; Qd was 700 mL/min, the time duration was 240 min, and the filtration volume in HDF-MD was 112+/-7 mL/min. No differences were found for Kt/V, urea, and creatinine clearances. Clearance of both small phosphate (P) large beta(2)-microglobulin (beta(2)m), and leptin (L) solutes was significantly greater for MD (P 217+/-32, beta(2)m 85.5+/-10, L 42.6+/-18 mL/min) than for HF-HD (P 178+/-32, beta(2)m 71.9+/-13, L 32.1+/-12 mL/min). The results of this study indicate that HDF remains the best means of providing increased removal of large-molecular weight solutes even in patients with vascular access problems.

Pregnancy in CKD stages 3 to 5: fetal and maternal outcomes.

BACKGROUND: Prognostic criteria to inform women with moderate to severe renal insufficiency who wish to bear children are not well established. STUDY DESIGN: Longitudinal multicenter cohort study. SETTINGS & PARTICIPANTS: Nondiabetic white women with pregnancies proceeded beyond the 20th week and estimated glomerular filtration rate (GFR) less than 60 mL/min/1.73 m(2) (<1 mL/s/1.73 m(2)) before conception. PREDICTORS: Baseline GFR and proteinuria (exposure); other clinical characteristics at conception (covariates). OUTCOMES & MEASUREMENTS: Difference in GFR decreases before conception versus after delivery (mixed linear models); low birth weight (<2,500 g), and maternal renal survival (logistic and Cox regressions). RESULTS: 49 women were studied. Mean serum creatinine and GFR at conception were 2.1 +/- 1 (SD) mg/dL (186 +/- 88 micromol/L) and 35 +/- 12 mL/min/1.73 m(2) (0.58 +/- 0.2 mL/s/1.73 m(2)), respectively. Overall mean GFR after delivery was less than before conception (30 +/- 13.8 versus 35 +/- 12.2 mL/min/1.73 m(2) [0.50 +/- 0.23 versus 0.58 +/- 0.20 mL/s/1.73 m(2)]; P < 0.001), but the rate of GFR decrease did not change (0.55 +/- 0.8 versus 0.50 +/- 0.3 mL/min/mo [0.0092 +/- 0.013 versus 0.0083 +/- 0.005 mL/s/mo]; P = 0.661). Independent of potential confounders, the combined presence of baseline GFR less than 40 mL/min/m(2) (<0.67 mL/s/m(2)) and proteinuria with protein greater than 1 g/d, but not either factor alone, predicted faster GFR loss after delivery compared with before conception (1.17 +/- 1.23 versus 0.55 +/- 0.39 mL/min/mo; difference, 0.62 mL/min/mo; 95% confidence interval [CI], 0.27 to 0.96 mL/min/mo [0.020 +/- 0.021 versus 0.0092 +/- 0.007 mL/s/mo; difference, 0.10 mL/s/mo; 95% CI, 0.005 to 0.016 mL/s/mo]). The presence of both risk factors, but not either alone, also predicted shorter time to dialysis therapy or GFR halving (N = 20; hazard ratio, 5.2; 95% CI, 1.7 to 15.9) and low birth weight (N = 29; odds ratio, 5.1; 95% CI, 1.03 to 25.6). LIMITATIONS: Generalizability to other settings; study power. CONCLUSION: In women with renal insufficiency, the presence of both GFR less than 40 mL/min/1.73 m(2) (<0.67 mL/s/m(2)) and proteinuria with protein greater than 1 g/d before conception predicts poor maternal and fetal outcomes.

Factors associated with unsuccessful utilization and early failure of the arterio-venous fistula for hemodialysis.

BACKGROUND: Arteriovenous fistulae survive longer than grafts and catheters. However, their short term outcomes may not be as good. We sought to determine whether fistulae created in patients referred to a nephrologist less than 3 months before dialysis start show higher risk of unsuccessful use and early failure. METHODS: All patients receiving a new vascular access over a six-year period at three centres were enrolled. Logistic and Cox's regression techniques were used to model late referral on successful utilization for <6 consecutive HD-sessions and time to failure within the first month from access creation, adjusting for demographics, comorbidities and surgical strategies. RESULTS: Among the 535 subjects enrolled, 513 received a fistula. Without considering revisions, 119 fistulae (23.2%) were not successfully used and 61 (11.9%) failed early. Independent predictors of unsuccessful utilization were late referral (Odds Ratio 2.15 [95% Confidence Interval 1.23, 3.75]), vascular diseases (1.86 [1.16, 2.97]), absence of treated hypertension (2.07 [1.17, 3.68]), and heart failure limited to late referrals (10.74 [4, 28.82]). Late referral (Hazard Ratio 1.72 [1.05, 2.81]), absence of treated hypertension (1.80 [1.02, 3.18]) and heart failure (2.34 [1.34, 4.08]) also predicted primary early failure. CONCLUSIONS: Late patient referral and presence of cardiovascular diseases, particularly heart failure, are potentially modifiable risk factors for short-term outcomes improvement of hemodialysis fistulae.

Cardiovascular comorbidity and late referral impact arteriovenous fistula survival: a prospective multicenter study.

Autologous arteriovenous fistulas (AVF) have the best 5-yr patency and the lowest complication rate among hemodialysis vascular accesses. However, maturation requirements to optimize survival are unknown. A longitudinal cohort study was conducted to ascertain risk factors for failure, maturation time, and survival of the first AVF. All patients who initiated hemodialysis between January 1, 1997, and December 31, 2002, in three centers were included in this study. Analysis was restricted to patients who received an AVF. Cox regression was used to estimate the association between predictors of interest and primary and secondary AVF survival. Of the 535 patients enrolled (mean age, 66.5 yr; 57.8% male; 26.7% diabetic), 513 (96%) received an AVF. Patients who initiated with catheters (47%) cannulated their AVF earlier (median maturation period, 0.78 versus 1.80 mo; P < 0.001). Median primary and secondary survivals were longer than 50 and 72 mo, respectively. After adjustment for confounding factors, cardiovascular disease (hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.26 to 2.67), utilization earlier than 1 mo after placement (HR, 1.94; 95% CI, 1.34 to 2.82), and referral within 3 mo of dialysis start (HR, 1.55; 95% CI, 1.04 to 2.32) were associated with a reduction in primary AVF survival. Presence of cardiovascular disease (HR, 2.21; 95% CI, 1.38 to 3.55), maturation time <15 d (HR, 2.12; 95% CI, 1.20 to 3.73), and presence of catheters at hemodialysis initiation (HR, 1.79; 95% CI, 1.13 to 2.84) were associated with lower secondary AVF survival. It is concluded that cardiovascular disease, late referral, temporary catheters, and early cannulation are associated with impaired AVF survival. It is recommended that AVF be allowed to mature at least 1 mo before cannulation.

Azathioprine hypersensitivity: report of two cases and review of the literature.

Azathioprine (AZA) is a widely-used drug in the treatment of different diseases such as vasculitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel diseases and in renal transplantation. Side effects of AZA can be classified as toxic, mainly dose related (myelosuppression and hepatotoxicity) and idiosyncratic, mainly dose independent. While the toxic effects are common and well documented, the hypersensitivity reactions are rare and it is not often easy to distinguish them from systemic sepsis or disease recurrence. We report two cases of AZA hypersensitivity occurring in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis each mimicking a vasculitis relapse or a septic complication of immunosuppression, as well as a review of the literature.

Blood volume controlled hemodialysis in hypotension-prone patients: a randomized, multicenter controlled trial.

BACKGROUND: Recently we have devised and tested a biofeedback system for controlling blood volume (BV) changes during hemodialysis (HD) along an ideal trajectory (blood volume tracking, BVT), continuously modifying the weight loss rate and dialysate conductivity. This multicenter, prospective, randomized, crossover study aimed to clarify whether BVT (treatment B) can improve hypotension-prone patients' treatment tolerance, compared with conventional hemodialysis (treatment A). METHODS: Thirty-six hypotension-prone patients enrolled from 10 hemodialysis (HD) centers were randomly assigned to either of the study sequences ABAB or BABA, each lasting four months. RESULTS: A 30% reduction in intradialytic hypotension (IDH) events was observed in treatment B as compared with A (23.5% vs. 33.5%, P = 0.004). The reduction was related to the number of IDH in treatment A (y = 0.54x + 5; r = 0.4; P < 0.001): the more IDH episodes in treatment A, the better the response in treatment B. The best responders to treatment B showed pre-dialysis systolic blood pressure values higher than the poor responders (P = 0.04). A 10% overall reduction in inter-dialysis symptoms was obtained also in treatment B compared to A (P < 0.001). Body weight gain, pre-dialysis blood pressure, intradialytic weight loss as well as Kt/V did not differ between the two treatments. CONCLUSIONS: An overall improvement in the treatment tolerance was observed with BVT, particularly intradialytic cardiovascular stability. Patients with the highest incidence of IDH during conventional HD and free from chronic pre-dialysis hypotension seem to respond better. Inter-dialysis symptoms also seem to improve with control of BV.