Enrico Imbasciati

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

BACKGROUNDnOnly 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.nnnMETHODSnIn 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.nnnRESULTSnRenal 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).nnnCONCLUSIONSnPregnancy 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.

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.

Pregnancy in women with chronic renal failure.

We describe 19 pregnancies in 18 women with chronic renal disease and plasma creatinine greater than or equal to 1.6 mg/dl before pregnancy. There were 2 spontaneous abortions (11th and 21st week), 2 therapeutic abortions (18th and 19th week), 1 stillbirth (30th week), 1 neonatal death (31st week) and 13 live births, 7 of them were preterm. Nine cesarean sections were done. Serial determinations of plasma creatinine during pregnancy showed a trend to decrease during the first half and to increase during the second half of pregnancy. The effect of pregnancy on the progression of renal failure was evaluated in 14 patients by comparing the linear regression lines of reciprocal plasma creatinine versus time before and after pregnancy. In 5 patients the rate of progression worsened after pregnancy. Our data indicate that women with chronic renal failure may have a successful pregnancy, but one third of them will have an accelerated rate of progression of the disease.

Collagen Type III Glomerulopathy: A New Idiopathic Glomerular Disease

A new type of idiopathic glomerular disease is reported in a 49-year-old Italian woman who presented with uncharacteristic renal symptoms, i.e., hypertension and slight proteinuria. Clinical investigation excluded a familial renal disease and more specifically nail-patella syndrome. Diagnostic renal biopsy by light microscopy showed a picture similar to membranoproliferative glomerulonephritis. The enlarged glomeruli were lobulated, the peripheral basement membranes were thickened by the deposition of light-microscopically undefined material, cell proliferation was lacking. By electron microscopy, the material was nonhomogenous, partly granular partly fibrillar, containing typical collagen fibers. The latter were identified as collagen type III, to a lesser extent collagen type I. Review of the literature resulted in 12 similar or identical cases reported from Japan and one additional case reported in a white American female. Evidence of systemic disease is lacking. Etiology and pathogenesis are elusive. A progressive deterioration of renal function must be expected. Collagen type III glomerulopathy is suggested as term of this new type of idiopathic glomerular disease.

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

BACKGROUNDnWhether 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.nnnSTUDY DESIGNnMulticenter longitudinal cohort study.nnnSETTING & PARTICIPANTSnWomen of childbearing age with biopsy-proven IgA nephropathy, serum creatinine level<or=1.2 mg/dL at diagnosis, and minimum follow-up of 5 years after biopsy recruited from 35 nephrology centers participating in a national collaborative study group of pregnancy and kidney disease sponsored by the Italian Society of Nephrology.nnnPREDICTORSnPregnancy, treated as a time-dependent variable; baseline proteinuria; hypertension; and kidney biopsy histologic characteristics.nnnOUTCOME & MEASURESnRate of change in estimated creatinine clearance, change in proteinuria, and new-onset hypertension.nnnRESULTSn245 patients were enrolled. Of these, 223 women (136 and 87 in the pregnancy and nonpregnancy groups, respectively) had serum creatinine levels<or=1.2 mg/dL at diagnosis. Baseline data (including age, estimated creatinine clearance, prevalence of hypertension, and histologic grade of kidney damage) were similar between groups with the exception of proteinuria (protein excretion, 1.33 vs 0.95 g/d in the pregnancy vs nonpregnancy groups, respectively; P=0.03). Kidney function decreased 1.31 mL/min/y (95% CI, 0.99-1.63) during a median follow-up of 10 years (range, 5-31 years) and did not differ between groups. Baseline proteinuria predicted a faster decrease, but did not modify the effect of pregnancy. Pregnancy did not affect changes in proteinuria over time or risk of new-onset hypertension.nnnLIMITATIONSnUnrecognized or unmeasured factors associated with the decision of becoming pregnant might have influenced results.nnnCONCLUSIONSnPregnancy does not seem to affect the long-term outcome of kidney disease in women with IgA nephropathy and preserved kidney function.

Long-term effects of intravenous calcitriol therapy on the control of secondary hyperparathyroidism

Although high-dose intravenous calcitriol has been shown to be effective in suppressing parathyroid hormone (PTH) secretion in dialysis patients with secondary hyperparathyroidism, an increasing number of patients is refractory to treatment. Only a few studies have evaluated the factors that can predict a favorable response to calcitriol, but contrasting results have been reported. This study was performed to evaluate the effect of high-dose intravenous calcitriol on parathyroid function and to investigate the factors that can predict a favorable response to treatment. Thirty-five dialysis patients were selected for intravenous calcitriol treatment (2 microg after dialysis for 12 months) because of increased PTH levels (>325 pg/mL). Before starting the treatment, the set point of calcium and the PTH-ionized calcium (ICa) curve was evaluated in each patient by inducing hypocalcemia and, 1 week later, hypercalcemia to maximally stimulate or inhibit PTH secretion. Parathyroid glands were assessed by high-resolution color Doppler ultrasonography. Throughout the study, calcium carbonate or acetate dosage was modified to maintain serum phosphate less than 5.5 mg/dL. Hypercalcemia was managed by reducing dialysate calcium to 5 mg/dL and, if necessary, calcitriol dose. The therapeutic goal was to reduce PTH levels below 260 pg/mL while maintaining normocalcemia. The patients who achieved the therapeutic goal were considered responders. Taking the data from the 35 patients together, we observed a significant decrease (P < 0.01) in alkaline phosphatase (from 252 +/- 106 IU/L to 194 +/- 81 IU/L) and PTH (from 578 +/- 231 pg/mL to 408 +/- 291 pg/mL), and a significant increase in serum ICa (from 5.1 +/- 0.2 mg/dL to 5.3 +/- 0.2 mg/dL; P < 0.001) after calcitriol therapy. PTH changes after therapy were not correlated to serum ICa changes, serum phosphate levels during treatment, and calcitriol dose. The response to therapy was heterogeneous because PTH levels markedly decreased over the treatment period in 18 responsive patients, whereas they increased or remained unchanged in 14 of 17 nonresponders. In three additional refractory patients, there was a decline in PTH of 20% to 35%, but this decline was associated with hypercalcemia. Pretreatment parathyroid gland size, serum ICa, PTH, maximal PTH induced by hypocalcemia, minimal PTH induced by hypercalcemia, the set point of ICa, and the ICa levels at which maximal PTH secretion and inhibition occurred were higher in the 17 refractory patients than in the 18 responsive patients. However, logistic regression analysis showed that among these parathyroid function parameters, the only significant predictors of a favorable response to calcitriol therapy were the parathyroid gland size and the set point of ICa. Throughout the study, serum phosphate and calcitriol dose were comparable in the two groups. In conclusion, the response to intravenous calcitriol therapy in dialysis patients with secondary hyperparathyroidism is heterogeneous, consisting of patients who are either responsive or refractory to treatment; refractoriness can be predicted by parathyroid volume and calcium set point.

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.

Renal Lesions in Familial Lecithin-Cholesterol Acyltransferase Deficiency

Renal lesions of a new case of lecithin-cholesterol acyltransferase deficiency in an 18-year-old male are described. Large mesangial deposits and a sieve-like transformation of the peripheral basement membrane were the main glomerular lesions. Immunofluorescence identified C3 deposits in the mesangium. A heterogeneous pattern of ultrastructural findings was observed by electron microscopy. Thread-like structures with faint cross-striation and irregular tubular structures embedded in an amorphous material were found in mesangial and subepithelial sites. Mesangial areas and peripheral basement membranes showed irregular holes sometimes containing highly osmiophilic lamellar bodies. It is suggested that many mechanisms may be involved in the production of renal lesions induced by the lipoprotein abnormalities characteristic of the disease.

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 <300u2003mL/min, received either online HDF‐MD or HF‐HD; Qd was 700u2003mL/min, the time duration was 240u2003min, and the filtration volume in HDF‐MD was 112±7u2003mL/min. No differences were found for Kt/V, urea, and creatinine clearances. Clearance of both small phosphate (P) large β2‐microglobulin (β2m), and leptin (L) solutes was significantly greater for MD (P 217±32, β2m 85.5±10, L 42.6±18u2003mL/min) than for HF‐HD (P 178±32, β2m 71.9±13, L 32.1±12u2003mL/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.

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

BACKGROUNDnOnly 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.nnnMETHODSnA 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.nnnRESULTSnSeventy-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.nnnCONCLUSIONnOur survey highlights the need for further improvement in serum creatinine measurement and reporting, and for coordinated interventions involving all major stakeholders.