Sudden Death in End Stage Renal Disease: Comparing Hemodialysis versus Peritoneal Dialysis.

BACKGROUND/AIMS: This study aimed to evaluate total and sudden death (SD) in a cohort of dialysis patients, comparing hemodialysis (HD) vs. peritoneal dialysis (PD). METHODS: This is a multicenter retrospective cohort study. RESULTS: Deaths were 626 out of 1,823 in HD and 62 of 249 in PD patients. HD patients had a greater number of comorbidities (p < 0.05). PD patients had a lower risk of death than HD patients (p < 0.001); however, the advantage decreased with time (p < 0.001). Mortality predictors were left ventricular ejection fraction (LVEF) ≤35%, older age, ischemic heart disease, diabetes mellitus, previous stroke, and atrial fibrillation (p < 0.03). SDs were 84:71 in HD and 13 in PD population (12.1 and 22.8% of all causes of death, respectively). A non-significant risk of SD among PD compared to HD patients was detected. SD predictors were older age, ischemic heart disease, and LVEF ≤35% (p < 0.05). CONCLUSIONS: HD patients showed a greater presence of comorbidities and reduced survival compared to PD patients; however, the incidence of SD does not differ in the 2 populations. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=464347.

Pro: STOP immunosuppression in IgA nephropathy?

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest a 6-month course of corticosteroids (CS) for IgA nephropathy (IgAN) patients with persistent proteinuria ≥1 g/day despite 3-6 months of renin-angiotensin system (RAS) blockers and glomerular filtration rate (GFR) >50 mL/min/1.73 m2 In December 2015, Rauen et al. (N Engl J Med 2015; 373: 2225-2236) published an article entitled 'Intensive supportive care plus immunosuppression in IgA nephropathy' (STOP-IgAN), which presented results from 379 IgAN patients from 32 nephrology centres in Germany. During a run-in phase of 6 months, patients received supportive care therapy including RAS blockers, dietary counselling, advice to stop smoking and avoid nephrotoxic drugs, and statins if required. After 6 months, 177 patients with proteinuria >0.75 g/day (non-responder patients) were randomized to either receive continued supportive care or supportive care plus immunosuppression (monotherapy with CS or combined therapy with three immunosuppressants). The authors reported that, after 36 months of observation, the addition of immunosuppressants to ongoing comprehensive supportive care was not beneficial in IgAN patients with moderate proteinuria and chronic kidney disease stages 1-3. These conclusions are questionable for several reasons: (i) studies on time-average proteinuria have shown that beneficial effects on renal survival, not evident after 36 months, emerge over the course of longer observation periods; (ii) supportive care in the STOP-IgAN study resulted in a small loss of renal function during the 36 months of observation (annual decrease in the estimated GFR of 1.6 mL/min/1.73 m2), but was unable to reduce proteinuria below 1 g/day; in contrast, 6 months of steroid therapy lowered proteinuria below 1 g/day; and (iii) the lack of any assessment of the histological data does not allow the importance of the morphological lesions on renal survival and therapy effects to be monitored. Further evaluation with a longer follow-up period is needed to obtain more reliable answers than the weak evidence of this study.

Warfarin use, mortality, bleeding and stroke in haemodialysis patients with atrial fibrillation.

BACKGROUND: Oral anticoagulation therapy (OAT) is the choice treatment for thromboembolism prevention in atrial fibrillation (AF), although data about OAT use in haemodialysis (HD) patients with AF are contradictory. METHODS: The effect of OAT on the risk of mortality, stroke and bleeding was prospectively evaluated in a population of HD patients with AF. All the patients of 10 HD Italian centres alive on 31 October 2010 with documented AF episode(s) were recruited and followed-up for 2 years. OAT and antiplatelet intake, age, dialytic age, comorbidities and percentage time in the target international normalized ratio (INR) range (target therapeutic range; TTR) were considered as predictors of hazard of death, thromboembolic and bleeding events. RESULTS: At recruitment, 134 patients out of 290 were taking OAT. During the follow-up, 115 patients died (4 strokes, 3 haemorrhagic and 1 thromboembolic). Antiplatelet therapy, but not OAT, was associated with increased mortality (HR 1.71, CI 1.10-2.64, P = 0.02). The estimated survival of patients always taking OAT tended to be higher than that of patients who stopped taking (68.6 versus 49.6%, P = 0.07). OAT was not correlated to a significant decreased risk of thromboembolic events (HR 0.12, CI 0.00-3.59, P = 0.20), while it was associated with an increased risk of bleeding (HR 3.96, CI 1.15-13.68, P = 0.03). Higher TTR was associated with a reduced bleeding risk (HR 0.09, CI 0.01-0.76, P = 0.03), while previous haemorrhagic events were associated with higher haemorrhagic risk (HR 2.17, CI 1.09-4.35, P = 0.03). CONCLUSIONS: In our population of HD patients with AF, the mortality is very high. OAT is not associated with increased mortality, while antiplatelet drugs are. OAT seems, on the contrary, associated with a better survival; however, it does not decrease the incidence of ischaemic stroke, whereas it increases the incidence of bleeding. Bleeding risk is lower in subjects in whom the INR is kept within the therapeutic range.

Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy.

The optimal treatment for IgA nephropathy (IgAN) remains unknown. Some patients respond to corticosteroids, suggesting that more aggressive treatment may provide additional benefit. We performed a randomized, multicenter, controlled trial to determine whether adding azathioprine to steroids improves renal outcome. We randomly assigned 207 IgAN patients with creatinine ≤2.0 mg/dl and proteinuria ≥1.0 g/d to either (1) a 3-day pulse of methylprednisolone in months 1, 3, and 5 in addition to both oral prednisone 0.5 mg/kg every other day and azathioprine 1.5 mg/kg per day for 6 months (n = 101, group 1) or (2) steroids alone on the same schedule (n = 106, group 2). The primary outcome was renal survival (time to 50% increase in plasma creatinine from baseline); secondary outcomes were changes in proteinuria over time and safety. After a median follow-up of 4.9 years, the primary endpoint occurred in 13 patients in group 1 (12.9%, 95% CI 7.5 to 20.9%) and 12 patients in group 2 (11.3%, CI 6.5 to 18.9%) (P = 0.83). Five-year cumulative renal survival was similar between groups (88 versus 89%; P = 0.83). Multivariate Cox regression analysis revealed that female gender, systolic BP, number of antihypertensive drugs, ACE inhibitor use, and proteinuria during follow-up predicted the risk of reaching the primary endpoint. Treatment significantly decreased proteinuria from 2.00 to 1.07 g/d during follow-up (P < 0.001) on average, with no difference between groups. Treatment-related adverse events were more frequent among those receiving azathioprine. In summary, adding low-dose azathioprine to corticosteroids for 6 months does not provide additional benefit to patients with IgAN and may increase the risk for adverse events.

[The ambiguous concept of predialysis: proposal for a model]. / L'ambiguita' del concetto di predialisi: proposta di un modello.

In 2009, 90% of nephrology centers in Lombardy declared to have a ''predialysis'' outpatient department, without, however, specifying its meaning. Research carried out in 2008 among nephrology centers in Piemonte showed how ambiguous this term was. According to the 2007 EDTA-ERA Registry, about 68% of European nephrology centers stated that they had an outpatient department for stage 4-5 CKD patients, but no information was available about the role of patients in the choice of dialysis. It is known that when the predialysis phase is poorly managed, the patient's rehabilitation will be more difficult. Dissatisfaction with dialysis often leads to withdrawal from dialysis, as several registries have shown. For this reason, we created a predialysis course at our center, involving a nephrologist, a nurse, and a dietician. The nephrologist helps the patient choose the most suitable therapeutic strategy, which means that doctor and patient share the responsibility for the treatment choice. The offered options are hemodialysis, peritoneal dialysis, preemptive kidney transplant, and a conservative dietary-pharmacological program. The nurse plans at least 4 meetings: 1) to talk with the patient in order to get to know him or her and his/her family; 2) to provide information about the dialysis procedure and establish the patient's preferences; 3) to clear any doubts about the treatment and deliver a booklet with information about the chosen dialysis procedure; 4) to explain the chosen dialysis procedure; 5) to meet the patient after their preparation for dialysis (vascular access or peritoneal catheter). The dietician manages the dietary programs both for patients who are close to starting dialysis and those on a longlasting conservative program. The predialysis course includes a meeting among all those involved with the patient (nephrologists, nurses, dieticians) to exchange information with the purpose of shared evaluation and decision-making.

Ramipril and Cardiovascular Outcomes in Patients on Maintenance Hemodialysis: The ARCADIA Multicenter Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Renin-angiotensin system (RAS) inhibitors reduce cardiovascular morbidity and mortality in patients with CKD. We evaluated the cardioprotective effects of the angiotensin-converting enzyme inhibitor ramipril in patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this phase 3, prospective, randomized, open-label, blinded end point, parallel, multicenter trial, we recruited patients on maintenance hemodialysis with hypertension and/or left ventricular hypertrophy from 28 Italian centers. Between July 2009 and February 2014, 140 participants were randomized to ramipril (1.25-10 mg/d) and 129 participants were allocated to non-RAS inhibition therapy, both titrated up to the maximally tolerated dose to achieve predefined target BP values. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the single components of the primary end point, new-onset or recurrence of atrial fibrillation, hospitalizations for symptomatic fluid overload, thrombosis or stenosis of the arteriovenous fistula, and changes in cardiac mass index. All outcomes were evaluated up to 42 months after randomization. RESULTS: At comparable BP control, 23 participants on ramipril (16%) and 24 on non-RAS inhibitor therapy (19%) reached the primary composite end point (hazard ratio, 0.93; 95% confidence interval, 0.52 to 1.64; P=0.80). Ramipril reduced cardiac mass index at 1 year of follow-up (between-group difference in change from baseline: -16.3 g/m2; 95% confidence interval, -29.4 to -3.1), but did not significantly affect the other secondary outcomes. Hypotensive episodes were more frequent in participants allocated to ramipril than controls (41% versus 12%). Twenty participants on ramipril and nine controls developed cancer, including six gastrointestinal malignancies on ramipril (four were fatal), compared with none in controls. CONCLUSIONS: Ramipril did not reduce the risk of major cardiovascular events in patients on maintenance hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ARCADIA, NCT00985322 and European Union Drug Regulating Authorities Clinical Trials Database number 2008-003529-17.

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

The low-protein diet for chronic kidney disease: 8 years of clinical experience in a nephrology ward.

BACKGROUND: Guidelines indicate that a low-protein diet (LPD) delays dialysis in severe chronic kidney disease (CKD). We assessed the value of these guidelines by performing a retrospective analysis in our renal clinical practice. METHODS: The analysis was performed from 1 January 2010 to 31 March 2018 in 299 CKD Stage 4 patients followed for 70 months in collaboration with a skilled nutritionist. The patients included 43 patients on a controlled protein diet (CPD) of 0.8 g/kg/day [estimated glomerular filtration rate (eGFR) 20-30 mL/min/1.73 m2 body surface (b.s.)], 171 patients on an LPD of 0.6 g/kg/day and 85 patients on an unrestricted protein diet (UPD) who were not followed by our nutritionist (LPD and UPD, eGFR <20 mL/min/1.73 m2 b.s.). RESULTS: eGFR was higher in CPD patients than in UPD and LPD patients (21.9 ± 7.4 mL/min/1.73 m2 versus 17.6 ± 8.00 mL/min/1.73 m2 and 17.1 ± 7.5 mL/min/1.73 m2; P = 0.008). The real daily protein intake was higher in UPD patients than in LPD and CDP patients (0.80 ± 0.1 g/kg/day versus 0.6 ± 0.2 and 0.63 ± 0.2 g/kg/day; P = 0.01). Body mass index (BMI) was stable in the LPD and CPD groups but decreased from 28.5 ± 4.52 to 25.4 ± 3.94 kg/m2 in the UPD group (P < 0.001). The renal survival of UPD, LPD and CPD patients was 47.1, 84.3 and 90.7%, respectively, at 30 months (P < 0.001), 42.4, 72.0 and 79.1%, respectively, at 50 months (P < 0.001) and 42.4, 64.1 and 74.4%, respectively, at 70 months (P < 0.001). The LPD patients started dialysis nearly 24 months later than the UPD patients. Diet was an independent predictor of dialysis [-67% of RR reduction (hazard ratio = 0.33; confidence interval 0.22-0.48)] together with a reduction in BMI. CONCLUSIONS: An LPD recommended by nephrologists in conjunction with skilled dietitians delays dialysis and preserves nutritional status in severe CKD.

Long-term blood pressure behavior and progression to end-stage renal disease in patients with immunoglobulin A nephropathy: a single-center observational study in Italy.

BACKGROUND: Antihypertensive treatment by the use of RAAS inhibitors (RAAS-is) is of paramount importance in the management of slowly progressive IgA nephropathy (IgAN). With the aim of better understanding the relationship between BP behavior and progression, we looked at time-averaged SBP and time-averaged proteinuria and renal outcome in a single-center cohort of IgAN patients. METHODS: Among 248 consecutive patients referred to the Clinic of Nephrology of San Martino Hospital from 1996 to 2018 for native renal biopsy with a diagnosis of IgAN, we retrospectively analyzed 145 with available data at baseline and during follow-up. All patients received Supportive Care, 39% were on RAAS-is alone, 45% plus steroids, and 16% plus steroids and immunosuppressors. Renal replacing treatment (RRT) was the primary endpoint. RESULTS: During a mean follow-up of 67 ±â€Š6 months, 23% of study patients (n = 33) progressed to RRT and 6% (n = 9) died. Patients who reached the renal endpoint, had lower baseline eGFR and higher proteinuria and proteinuria indexed at baseline. Moreover, they had higher TA-SBP (139 ±â€Š17 vs. 130 ±â€Š13, P = 0.0016). The incidence of RRT was higher in IgAN patients in the highest time-averaged SBP tertile as compared with the others (32 vs. 23 vs. 9%, χ 6.8, P = 0.033). After adjusting for baseline SBP, baseline and time-averaged proteinuria indexed, MEST-C score, and treatment, the association between TA-SBP and RRT persisted. CONCLUSION: Time-averaged low BP values were independently associated to a decreased risk of renal progression in IgAN with no evidence of a J-curve relationship even at SBP levels below 125 mmHg.

Effect of oral anticoagulant therapy on mortality in end-stage renal disease patients with atrial fibrillation: a prospective study.

BACKGROUND: The aim of this study was to evaluate, in a cohort of haemodialysis patients with atrial fibrillation (AF), the relationship between oral anticoagulant therapy (OAT) and mortality, thromboembolic events and haemorrhage. METHODS: Two hundred and ninety patients with AF were prospectively followed for 4 years. Warfarin and antiplatelet intake, age, dialytic age, comorbidities, CHA2DS2-VASc and HAS-BLED scores were considered as predictors of risk of death, thromboembolism and bleeding events. In patients taking OAT, the international normalized ratio (INR) was assessed and the percentage time in the target therapeutic range (TTR) was calculated. RESULTS: At recruitment, 134/290 patients were taking warfarin. During follow-up there were 170 deaths, 28 thromboembolic events and 95 bleedings. After balancing for treatment propensity, intention-to-treat analysis on OAT intake at recruitment did not show differences in total mortality, thromboembolic events and bleedings, while the as-treated analysis, accounting for treatment switch, showed that patients taking OAT at recruitment had a significantly lower mortality than those not taking it [hazard ratio, HR 0.53 (95% confidence interval 0.28-0.90), p = 0.04], with a decrease of thromboembolic events [HR 0.36 (0.13-1.05), p = 0.06], and an increase of bleedings [HR 1.79 (0.72-4.39), p = 0.20], both non-significant. Among patients taking OAT at recruitment, those continuing to take warfarin had a significant reduction in the risk of total [HR 0.28 (0.14-0.53), p < 0.001] and cardiovascular [HR 0.21 (0.11-0.40), p < 0.001] mortality compared to patients stopping OAT. CONCLUSIONS: In haemodialysis patients with AF, continuously taking warfarin is associated with a reduction of the risk of total and cardiovascular mortality.

Does pregnancy influence the course of IgA nephropathy? Proposal for an observational study.

Whether or not pregnancy adversely affects the course of IgA nephropathy (IgAN) remains a matter of debate. Studies have produced conflicting results to date, probably due to differences in patient selection, renal disease severity, grades of hypertension and proteinuria or the administration of different therapies. Since numerous variables can influence the long-term outcome, it is necessary to evaluate data from a large number of patients to minimize the effect of confounding factors. However, the number of patients considered in most studies is small, and long-term prognosis is not yet reported in the literature. In the case of a chronic disease with a slow course such as IgAN, a long observation period is needed to draw substantial conclusions about the prognostic value of pregnancy. We propose a multicenter, retrospective, observational study to clarify whether pregnancy negatively affects the long-term prognosis of women with IgAN. Data of women who became pregnant and of women who did not conceive during the follow-up will be collected at the time of renal biopsy and every 5 yrs to evaluate possible differences in the course of maternal renal disease between the two groups. In particular, the following endpoints will be compared: renal function and the onset of hypertension and proteinuria. Possible differences in therapy will be analyzed to investigate whether different treatment approaches in the two groups could have influenced the disease course.

ACE inhibitors and angiotensin II receptor blockers in IgA nephropathy with mild proteinuria: the ACEARB study.

Few studies have investigated IgA nephropathy patients presenting with 'favorable' clinical features at onset, such as normal renal function, proteinuria<1 g/24 hours and the absence of hypertension, and no controlled clinical trials have tested the effects of treatment in such patients who may nevertheless develop end-stage renal disease. It is therefore important to find a well-tolerated and economic therapy capable of decreasing their risk of high proteinuria and blood pressure levels. The aim of this multicenter open-label randomized clinical trial is to test whether blocking the renin-angiotensin system (RAS) decreases the risk of progression in patients aged 3-60 years with biopsy-proven benign IgA glomerulonephritis, proteinuria levels of 0.3-0.9 g/24 hours, and normal renal function and blood pressure. The RAS is blocked by first using a single drug class (angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker), and then combining the 2 classes as soon as the 1-drug blockade has become ineffective. We plan to enroll 378 patients over the next 3 years and randomize them to receive ramipril 5 mg/day (3 mg/m2 in children) (group A), irbesartan 300 mg/day (175 mg/m 2 in children) (group B) or supportive therapy (group C); if an increase in proteinuria of at least 50% from baseline is detected after 6 months of treatment, the other RAS inhibitor will be added. The observation period will be at least 5 years (except in the case of the development of the primary end point).

Treatment of IgA nephropathy.

The therapy of IgA nephropathy (IgAN) is cause for debate among nephrologists. Since the early 1980s, many therapeutic attempts have been proposed, but most of them did not prove efficacy. The recent KDIGO Clinical Practice Guideline for Glomerulonephritis recommend long-term ACE-I or ARB treatment when proteinuria is more than 1 g/day, with up-titration of the drug. For patients with GFR >50 ml/min and proteinuria persistently higher than 1 g/day, they suggest a 6-month course of corticosteroid therapy. Based on our experience and the results of the literature, we propose a progressive treatment, which takes into account the time the IgAN is recognized and the clinical conditions present at that time. The treatment can be summarize as follows: (1) in patients with macro-microscopic haematuria, in case with proteinuria less than 0.3 g/day, only annual controls; (2) in patients with proteinuria between 0.3 and 0.9 g/day, ACE-I and/or ARB, with titration of the drugs; (3) in patients with proteinuria higher than 1 g/day, in case with the presence of arterial hypertension and GFR up to 30 ml/min, 6 months course of corticosteroids, in addition to ACE-I and/or ARB; (4) in patients with GFR less than 30 ml/min, ACE-I/ARB, dialysis and kidney transplantation; corticosteroids should be in case considered for patients with persistently high or increasing proteinuria; (5) the immunosuppressants (cyclophosphamide and azathioprine) should be reserved for patients with progressive renal insufficiency or with vasculitic lesions on renal biopsy.

Treatment of IgA nephropathy with renal insufficiency.

IgA Nephropathy leads young people to dialysis more often than other glomerular diseases, because often diagnosis and therapy are made late. Nephrologists waive to treat IgAN pts with chronic renal insufficiency, believing that treatment may not be effective and safe. Moreover, studies in IgAN pts with reduced renal function are lacking. Small studies seem to indicate a possible utility of RAS blockers and corticosteroids in these patients. Recently, VALIGA study showed that corticosteroids and immunosuppressants were more frequently used in pts with eGFR <30 ml/min than in those with eGFR >30 ml/min (60 vs. 44 %, respectively; p = 0.004). The goal of treating IgAN pts is to obtain a time-average proteinuria <1 g/day, regardless of the degree of renal function and histological damage. RASB and corticosteroids seem to be able to obtain this result. However, it's important to pay attention to the appearance of adverse events of CS. In the literature, major side effects occurred in 29 of 463 (6.2 %) patients enrolled in RCTs. However, scarce informations are obtained about the safety of CS in patients with reduced renal function. To better evaluate this aspect, we considered three studies, that used similar schemes of therapy and included patients with different degrees of renal function (1: GFR 90 ml/min/1.73 m(2), 2: 81 ml/min/1.73 m(2), 3: 34 ml/min/1.73 m(2)). The occurrence of adverse events increased with the worsening of renal function (2.3, 5.7 and 15.4 % in studies 1, 2 and 3 respectively). The aim of the treatment for a patient with an eGFR <30 is to slow the progression and to delay the need for dialysis. Therefore, in stage CKD 2, 3 and 4 with a proteinuria >1 g/day a 6-month course of corticosteroids could be useful and safe.

Impact of European medicines agency recommendations for hypersensitivity reactions on intravenous iron prescription in haemodialysis centres of the Lombardy region.

BACKGROUND: The European Medicines Agency (EMA) has recommended measures to minimize the risk of hypersensitivity reactions (HSRs) to intravenous iron (IVFe). We analysed the effects of these recommendations on IVFe clinical management among haemodialysis centres (HDCs) in Lombardy, Italy. MATERIALS AND METHODS: A questionnaire was sent to all 117 HDCs to collect information on centre characteristics, e.g. HDC type [hospital centre (HC) vs. centre with limited assistance (CAL)], presence/absence of intensive care unit (ICU) and/or emergency trained staff, IVFe therapy regarding molecules, administration modalities, side effects, and percentage variations in iron prescription between 2014 and 2013 (outcome, Δ-IVFe%). A linear regression model was applied to evaluate the focus effect (ß) of HDC type on the outcome, controlling for possible confounding effects of the other characteristics. RESULTS: Response rate was 73.5 %. IVFe therapy was used in 69.1 % (HDC range 11-100) of patients. Following EMA recommendations, prescription was reduced by 12.6 %, with the largest reduction observed in CALs. No severe HSRs were reported. HCs had more frequently an ICU [97.2 vs. 20 %, odds ratio (OR) = 63.6 (95 % confidence interval 15.56; 537.47), p < 0.001], emergency trained staff [97.2 vs. 61.2 %, OR = 10.7 (2.68; 85.33), p < 0.001] and instrumental facilities (91.7 vs. 58 %, OR = 5.8 (2.03; 23.55), p < 0.001] than CALs. Linear regression demonstrated a significant raw effect of HDC type on Δ- IVFe% [ß =  19.6 (9.82; 30.63), p < 0.001]. No association was found when HDC type was adjusted for ICU-presence [ß = 6.7 (-2.32; 18.30), p = 0.199] or for all-confounding factors [ß = 5.6 (-5.50; 17.08), p = 0.337]. CONCLUSIONS: This survey shows a disparity in IVFe therapy prescription following EMA recommendations, which is largely influenced by the presence/absence of ICUs in HD centres.

Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA Nephropathy.

BACKGROUND AND OBJECTIVE: Time-average proteinuria (TAp) is the strongest predictor of renal survival in IgA nephropathy (IgAN). Little is known about the utility and safety of corticosteroids (CS) to obtain TAp<1 g/d in patients with advanced IgAN. This study sought to evaluate TAp at different degree of baseline renal function and histologic severity during CS use and to investigate treatment safety. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed one-stage individual-patient data meta-analysis among 325 patients with IgAN enrolled in three prospective, randomized clinical trials. Patients were divided into three groups according to treatment: no treatment (NT; supportive therapy), CS, and CS plus azathioprine (CS+A). Associations of TAp with histologic grading, treatment, and eGFR at baseline were performed with linear regression models for repeated measures. The median follow-up duration was 66.6 months (range, 12-144 months). RESULTS: In the first 6 months, proteinuria did not change in the NT group and decreased substantially in the other groups(CS: from a mean±SD of 2.20±1.0 to 0.8 [interquartile range, 0.4-1.2] g/d; CS+A: from 2.876±2.1 to 1.0 [interquartile range, 0.5-1.7] g/d), independent of the degree of histologic damage and baseline eGFR. The percentage of patients who maintained TAp<1 g/d was 30.2% in the NT, 67.3% in the CS, and 66.6% in the CS+A group. Thirty-four patients experienced adverse events: none in the NT, 11 (6.4%) in the CS, and 23 (20.7%) in the CS+A group. The risk of developing adverse events increased with decreasing levels of eGFR (from 2.3% to 15.4%). The addition of azathioprine to CS further increased the percentage of patients with adverse events (16.8% versus 5.7% in study 2 and 30.0% versus 15.4% in study 3; overall P<0.001). CONCLUSIONS: In patients with IgAN, CS can reduce proteinuria and increase the possibility of maintaining TAp<1 g/d, regardless of the stage of CKD and the histologic damage. The risk of major adverse events is low in patients with normal renal function but increases in those with impaired renal function and with the addition of azathioprine.

Corticosteroid Treatment Influences TA-Proteinuria and Renal Survival in IgA Nephropathy.

The clinical course of IgA nephropathy (IgAN) and its outcome are extremely variable. Proteinuria at baseline has been considered one of the most important risk factors. More recently, mean proteinuria of follow-up (time-average proteinuria: TAp) was described as a stronger marker of renal survival, suggesting to consider it as a marker of disease activity and response to treatment. We evaluated predictors of renal survival in IgAN patients with different degrees of renal dysfunction and histological lesions, focusing on the role of the therapy in influencing TAp. We performed a retrospective analysis of three prospective, randomized, clinical trials enrolling 325 IgAN patients from 1989 to 2005. Patients were divided into 5 categories according to TAp. The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16.6%) and renal survival was much better in groups having lower TAp. The median follow up was 66.6 months (range 12 to 144). The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16,6%) and renal survival was much better in groups having lower TA proteinuria. At univariate analysis plasma creatinine and 24h proteinuria, systolic (SBP) and diastolic (DBP) blood pressure during follow-up and treatment with either steroid (CS) or steroid plus azathioprine (CS+A) were the main factors associated with lower TAp and renal survival. At multivariate analysis, female gender, treatment with S or S+A, lower baseline proteinuria and SBP during follow-up remained as the only variables independently influencing TAp. In conclusion, TA-proteinuria is confirmed as one of the best outcome indicators, also in patients with a severe renal insufficiency. A 6-month course of corticosteroids seems the most effective therapy to reduce TAp.

Mortality, sudden death and indication for cardioverter defibrillator implantation in a dialysis population.

BACKGROUND: The incidence of sudden death among dialysis patients is high, but end stage renal disease was an exclusion criterion in the trials that demonstrated the benefit of implantable cardioverter defibrillator (ICD) for sudden death prevention. METHODS: Dialysis patients alive on January 2010 or starting dialysis between January 2010 and January 2013 were enrolled and retrospectively evaluated. Patients were divided into three groups: No-Indication, Indication-With ICD and Indication-Without ICD. Cox and Fine and Gray regression models were used to estimate the total and cause-specific (sudden or non-sudden) mortality hazard ratio (HR, HR(cpRisk)), respectively. Survival was defined as the time from start of dialysis to the time of death. RESULTS: 154/2072 patients (7.4%) had indication for ICD implantation and 52 (33.8%) of them received the device; 688 (33.2%) deaths were recorded. Mortality was different among groups [Indication-With ICD vs No-Indication: HR 1.59 (95% CI 1.06-2.38) and Indication-Without ICD vs No-Indication: HR 2.67 (95% CI 2.09-3.39, p < 0.001)]. 84/688 (12.2%) were sudden deaths. The cumulative incidence of sudden death was higher in patients with ICD indication [Indication-With ICD vs No-Indication HR(cpRisk) 3.21 (95% CI 1.38-7.40) and Indication-Without ICD vs No-Indication: HR(cpRisk) 4.19 (95% CI 2.38-7.39), p < 0.001], but also No-Indication patients showed a high rate of sudden death [8.5% (95% CI.6.5-10.9) at 8 years of follow-up]. CONCLUSIONS: Dialysis patients with ICD indication had a worse survival than No-Indication subjects and the prognosis was particularly poor for the Indication-Without ICD group. Sudden death incidence was much higher than in the general population, even among No-Indication subjects.

Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors.

BACKGROUND: Light chain deposition disease (LCDD) is characterized by the tissue deposition of monotypical immunoglobulin light chains (LCs). The aim of this study was to investigate its clinical characteristics and prognostic factors. METHODS: Multicenter study of LCDD with renal and patient survival analyses. RESULTS: Sixty-three cases were studied (age: 58 +/- 14.2; males: 63.5%; kappa/lambda deposition: 68/32%; underlying disorders: multiple myeloma [MM] 65%, lymphoproliferative disorders 3%, idiopathic 32%). Ninety-six percent presented with renal insufficiency (acute, 52%; chronic, 44%), and 84% with proteinuria >1 g/d. During the follow-up, 36 patients reached uremia (incidence rate: 23.7/100 patient-years) and 37 died (17.5/100 patient-years). The factors independently associated with a worse renal prognosis were age (relative risk [RR], 1.05; 95% confidence interval [CI], 1.009 to 1.086) and serum creatinine at presentation (RR, 1.24; 95% CI, 1.02 to 1.5). Those independently associated with a worse patient survival were age (RR, 1.06; 95% CI, 1.03 to 1.1), MM (RR, 2.75; 95% CI, 1.22 to 6.2), and extrarenal LC deposition (RR, 2.24; 95% CI, 1.15 to 4.35). While kappa-LC deposition was more frequently associated with nodular sclerosing glomerulopathy, histological parameters were not predictors of renal/patient prognosis. The survival of the uremic patients undergoing dialysis was similar to that of patients not reaching uremia. CONCLUSION: LCDD is characterized by renal insufficiency with proteinuria and has a severe prognosis. Apart from age, the prognostic factors identified were degree of renal insufficiency at presentation affecting the renal prognosis, underlying hematologic disorder and extrarenal LC deposition affecting the patient prognosis. Dialysis is worth performing in uremic LCDD patients.